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Short-term sleep deprivation reinstates memory retrieval in mice: The role of corticosterone secretion. | Autor: Takatsu-Coleman AL, Zanin KA, Patti CL, Zager A, Lopes-Silva LB, Longo BM, Tufik S, Andersen ML, Frussa-Filho R. | Revista: Psychoneuroendocrinologyresumo
While the effects of sleep deprivation (SD) on the acquisition and consolidation phases of memory have been extensively characterized, its effects on memory retrieval remain overlooked. SD alone is a stressor, and stress-activated glucocorticoids promote bimodal effects on memory. Because we have recently demonstrated that 72 h SD impairs memory retrieval in the plus-maze discriminative avoidance task (PM-DAT) in mice, this study investigated whether shorter SD periods would facilitate retrieval. In Experiment I, the temporal forgetting curve of the PM-DATwas determined and an interval between training/testing in which retrieval was no longer present was used in all subsequent experiments. In Experiments II and III, retrieval performance and corticosterone concentration, respectively, were quantified in mice that were sleep deprived for 12 or 24 h before testing. In Experiments IV and V, the effects of the corticosterone synthesis inhibitor metyrapone were evaluated on 12 h SD-induced retrieval reinstatement and corticosterone concentration enhancement, respectively. Experiment VI determined whether pre-test acute administration of exogenous corticosterone would mimic the facilitatory effects of 12 h SD on retrieval. Thirty days after training, mice presented poor performance of the task; however, SD for 12 h (but not for 24) before testing reinstated memory retrieval. This facilitatory effect was accompanied by increased corticosterone concentration, abolished by metyrapone, and mimicked by pre-test acute corticosterone administration. Collectively, short-term SD can facilitate memory retrieval by enhancing corticosterone secretion. This facilitatory effect is abolished by longer periods of SD.
Changes in gene expression of frontal cortex from pilocarpine-induced status epilepticus rats after sleep deprivation | Autor: Hirotsu C, Matos G, Tufik S, Andersen ML | Revista: Epilepsy & Behaviorresumo
Sleep and epilepsy present a bidirectional interaction. Sleep complaints are common in epilepsy, and sleep deprivation may provoke seizures. However, the mechanisms underlying this relationship are unknown. Thus, this study investigated the effects of paradoxical sleep deprivation (PSD24h) and total sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen species and nitric oxide production in the frontal cortex of a rodent model of temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2 expression and decreased SOD expression, independent of sleep. Higher NOX-2 expression was observed only in PILO rats subjected to the control condition and TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h. Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h was reduced compared to that of PILO rats that were not sleep-deprived. The molecular changes found in the frontal cortex of PILO rats following sleep deprivation suggest a mechanism via oxidative stress.
Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes | Autor: Lungato L, Marques MS, Pereira VG, Hix S, Gazarini ML, Tufik S, D'Almeida V | Revista: Scand J Immunolresumo
Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses.
Chitotriosidase as a marker of macrophage activation after paradoxical sleep deprivation. | Autor: Lungato L, Tamanaha P, Rodrigues MB, Visniauskas B, Chagas JR, Tufik S, D’Almeida V. | Revista: Sleep Sci.
Role of Corticosterone on sleep homeostasis induced by REM sleep deprivation in rats. | Autor: Machado RB, Tufik S, Suchecki D. | Revista: PLoS ONE
Sleep deprivation increases mortality in female mice bearing Ehrlich ascitic tumor. | Autor: Maragno-Correa JMR, Patti CL, Zanin KA, Wuo-Silva R, Ruiz FS, Zager A, Sá-Nunes A, Tufik S, Andersen ML, Frussa-Filho R | Revista: Neuroimmunomodulationresumo
OBJECTIVES: Sleep deprivation is a growing public health hazard, yet it is still under-recognized. Sleep disorders and disruption of sleep patterns may compromise the immune function and adversely affect host resistance to infectious diseases. This is a particular risk in cancer patients, who report a high frequency of sleep disturbances. The present study investigated the effects of sleep deprivation on the development of Ehrlich ascitic tumors (EAT) in female BALB/c mice. Our study also evaluated whether EAT would induce alterations in sleep pattern. Spleen lymphocyte cell populations and mortality were also quantified.
METHODS: Female BALB/c mice were intraperitoneally inoculated with EAT cells. Immediately after the inoculation procedure, animals were sleep deprived for 72 h. Ten or 15 days after inoculation, the number of tumoral cells was quantified and the lymphocytic cell population in the spleen was characterized by flow cytometry. In addition, the effect of sleep deprivation on EAT-induced mortality was quantified and the influence of EAT on sleep patterns was determined.
RESULTS: Sleep deprivation did not potentiate EAT growth, but it significantly increased mortality. Additionally, both EAT and sleep deprivation decreased frequencies of splenic CD4+, CD8+ and CD19+ cells. With respect to sleep patterns, EAT significantly enhanced paradoxical sleep time.
CONCLUSIONS: Although sleep deprivation did not potentiate EAT growth, it decreased the survival of female tumor-bearing mice.
More than hormones: sex differences in cardiovascular parameters after sleep loss in rats | Autor: Matos G, Tenório NM, Bergamaschi CT, Campos RR, Cintra F, Tufik S, Andersen ML | Revista: Progr Neuropsychopharmacol Biol Psychiatryresumo
Although the influence of sex on sleep pattern and cardiovascular parameters is well known, knowledge regarding the effects of sleep loss on heart responses in both sexes is scarce. The present study investigated the effects of paradoxical sleep deprivation (PSD) and chronic sleep restriction (SR) on cardiovascular parameters and adrenocorticotropic hormone (ACTH) levels in male and female rats. Both groups were randomly assigned to PSD for 96 h, SR for 21 days or home-cage control. Mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity (bradycardia and tachycardia responses) and ACTH levels were evaluated. The results showed that PSD induced a significant increase in HR and ACTH levels in both sexes, although male rats presented higher levels of ACTH hormone compared to females. In addition to sex-specific responses, PSD decreased the tachycardia only in male rats. SR, induced a significant increase in MAP and decrease in bradycardia in both sexes. Male rats were more affected by sleep deprivation protocols than females for MAP, bradycardia response, and ACTH levels. The results showed that the effects of sleep loss on cardiovascular parameters are associated with the protocol of sleep deprivation and that sex can modulate these effects. We suggested this experimental model as a suitable tool for further investigations of the relationship between cardiovascular parameters and sleep.
Sleep deprivation alters phosphorylated CREB levels in the amygdala: Relationship with performance in a fear conditioning task | Autor: Pinho N, Moreira KM, Hipolide DC, Sinigaglia-Coimbra R, Ferreira TL, Nobrega JN, Tufik S, Oliveira MG | Revista: Behav Brain Resresumo
We investigated the relationship between deficits in fear memory induced by sleep deprivation and pCREB expression in the basal and central nuclei of the amygdala. Sleep deprivation reduced pCREB expression in the central nucleus compared to control or sleep recovered groups, and in the basal nucleus only compared to sleep recovered group. Moreover, 24h of sleep recovery prior to training prevented changes in both pCREB expression and performance.
Grooming analysis algorithm: use in the relationship between sleep deprivation and anxiety-like behavior | Autor: Pires GN, Tufik S, Andersen ML | Revista: Progr Neuropsychopharmacol Biol Psychiatryresumo
Increased anxiety is a classic effect of sleep deprivation. However, results regarding sleep deprivation-induced anxiety-like behavior are contradictory in rodent models. The grooming analysis algorithm is a method developed to examine anxiety-like behavior and stress in rodents, based on grooming characteristics and microstructure. This study evaluated the applicability of the grooming analysis algorithm to distinguish sleep-deprived and control rats in comparison to traditional grooming analysis. Forty-six animals were distributed into three groups: control (n=22), paradoxical sleep-deprived (96 h, n=10) and total sleep deprived (6 h, n=14). Immediately after the sleep deprivation protocol, grooming was evaluated using both the grooming analysis algorithm and traditional measures (grooming latency, frequency and duration). Results showed that both paradoxical sleep-deprived and total sleep-deprived groups displayed grooming in a fragmented framework when compared to control animals. Variables from the grooming analysis algorithm were successful in distinguishing sleep-deprived and normal sleep animals regarding anxiety-like behavior. The grooming analysis algorithm and traditional measures were strongly correlated. In conclusion, the grooming analysis algorithm is a reliable method to assess the relationship between anxiety-like behavior and sleep deprivation.
Influence of sleep deprivation on cardiovascular parameters in female zucker obese and lean rats. | Autor: Tenório NM, Tufik S, Bergamaschi CT, Campos RR, Cintra F, Andersen ML | Revista: Obesityresumo
OBJECTIVE: There is a reciprocal relationship between sleep duration and weight gain. However, the consequences of this relationship on the cardiovascular system over an entire life span are still not fully elucidated. We examined the effect of acute sleep deprivation (SD) on baroreflex sensitivity and blood pressure in Zucker rats of different ages.
DESIGN AND METHODS: Female lean and obese Zucker rats at 3, 6 and 15 months of age were assigned to SD or control (CTRL) groups. After a 6 h period of the SD procedure (6 h of gentle handling) or CTRL procedure (an equivalent period without handling), the animals were anesthetized for surgical catheterization of the femoral artery and vein. To evaluate the baroreflex sensitivity index, bolus infusions of phenylephrine (bradycardia response) and sodium nitroprusside (tachycardia response) were administered.
RESULTS: Obesity resulted in dysfunctional tachycardia responses at 3 months of age. At 6 and 15 months of age, both bradycardia and tachycardia responses were significantly lower in obese animals than those in lean animals. At 15 months of age, interactions among obesity, SD and aging produced the most marked effects on the cardiovascular system (increased mean arterial pressure and heart rate and decreased baroreflex sensitivity).
CONCLUSIONS: Therefore, these results suggest that there is no direct relationship between baroreflex imbalance and an increase in arterial pressure.
Influence of sleep deprivation and obesity on DNA damage in female Zucker rats. | Autor: Tenorio NM, Ribeiro DA, Alvarenga TA, Fracalossi ACC, Carlin V, Hirotsu C, Tufik S, Andersen ML | Revista: Clinicsresumo
OBJECTIVE: The aim of this study was to evaluate overall genetic damage induced by total sleep deprivation in obese, female Zucker rats of differing ages.
METHOD: Lean and obese Zucker rats at 3, 6, and 15 months old were randomly distributed into two groups for each age group: home-cage control and sleep-deprived (N = 5/group). The sleep-deprived groups were deprived sleep by gentle handling for 6 hours, whereas the home-cage control group was allowed to remain undisturbed in their home-cage. At the end of the sleep deprivation period, or after an equivalent amount of time for the home-cage control groups, the rats were brought to an adjacent room and decapitated. The blood, brain, and liver tissue were collected and stored individually to evaluate DNA damage.
RESULTS: Significant genetic damage was observed only in 15-month-old rats. Genetic damage was present in the liver cells from sleep-deprived obese rats compared with lean rats in the same condition. Sleep deprivation was associated with genetic damage in brain cells regardless of obesity status. DNA damage was observed in the peripheral blood cells regardless of sleep condition or obesity status.
CONCLUSION: Taken together, these results suggest that obesity was associated with genetic damage in liver cells, whereas sleep deprivation was associated with DNA damage in brain cells. These results also indicate that there is no synergistic effect of these noxious conditions on the overall level of genetic damage. In addition, the level of DNA damage was significantly higher in 15-month-old rats compared to younger rats.
Sleep deprivation alters gene expression and antioxidant enzyme activity in mice splenocytes. | Autor: Lungato L, Marques MS, Pereira VG, Hix S, Gazarini ML, Tufik S, D'Almeida V. | Revista: Scand J Immunolresumo
Cellular defence against the formation of reactive oxygen species (ROS) involves a number of mechanisms in which antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) play an important role. The relation between sleep deprivation and oxidative stress has not yet been completely elucidated. Although some authors did not find evidence of this relationship, others found alterations in some oxidative stress markers in response to sleep deprivation. Thus, the objective of this study was to identify changes induced by sleep deprivation in the activity and gene expression of antioxidant enzymes in mice splenocytes, ideally corroborating a better understanding of the observed effects related to sleep deprivation, which could be triggered by oxidative imbalance. Splenocytes from mice sleep deprived for 72 h showed no significant difference in CAT and CuZnSOD gene expression compared with normal sleep mice. However, sleep-deprived mice did show higher MnSOD gene expression than the
control group. Concerning enzymatic activity, CuZnSOD and MnSOD significantly increased after sleep deprivation, despite the expression in CuZnSOD remained unchanged. Moreover, CAT activity was significantly lower after sleep deprivation. The data suggest that the antioxidant system is triggered by sleep deprivation, which in turn could influence the splenocytes homoeostasis, thus interfering in physiological responses.
Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation. | Autor: Hirotsu C, Matos G, Tufik S, Andersen ML. | Revista: Epilepsy Behav | Site: http://dx.doi.org/10.1016/j.yebeh.2013.02.024resumo
Sleep and epilepsy present a bidirectional interaction. Sleep complaints are common in epilepsy, and sleep deprivation may provoke seizures. However, the mechanisms underlying this relationship are unknown. Thus, this study investigated the effects of paradoxical sleep deprivation (PSD24h) and total sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen species and nitric oxide production in the frontal cortex of a rodent model of temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2 expression and decreased SOD expression, independent of sleep. Higher NOX-2 expression was observed only in PILO rats subjected to the control condition and TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h. Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h was reduced compared to that of PILO rats that were not sleep-deprived. The molecular changes found in the frontal cortex of PILO rats following sleep deprivation suggest a mechanism via oxidative stress.
Influence of food restriction on lipid profile and spontaneous glucose in male rats subjected to paradoxical sleep deprivation | Autor: Alvarenga TA, Tufik S, Pires GN, Andersen ML. | Revista: Clinics | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Influence+of+food+restriction+on+lipid+profile+and+spontaneous+glucose+in+male+rats+subjected+to+paradoxical+sleep+deprivationresumo
OBJECTIVES: The purpose of this study was to determine the paired consequences of food restriction and paradoxical sleep deprivation on lipid profile and spontaneous glucose levels in male rats.
METHOD: Food restriction began at weaning, with 6 g of food being provided per day, which was subsequently increased by 1 g per week until reaching 15 g per day by the eighth week. At adulthood, both rats subjected to food restriction and those fed ad libitum were exposed to paradoxical sleep deprivation for 96 h or were maintained in their home-cage groups.
RESULTS: Animals subjected to food restriction exhibited a significant increase in high-density lipoprotein levels compared to animals that were given free access to food. After the paradoxical sleep deprivation period, the food-restricted animals demonstrated reduced concentrations of high-density lipoprotein relative to their respective controls, although the values for the food-restricted animals after sleep deprivation were still higher than those for the ad libitum group. The concentration of low-density lipoproteins was significantly increased in sleep-deprived animals fed the ad libitum diet. The levels of triglycerides, very low-density lipoproteins, and glucose in food-restricted animals were each decreased compared to both ad libitum groups.
CONCLUSION: These results may help to illustrate the mechanisms underlying the relationship between sleep curtailment and metabolism and may suggest that, regardless of sleep deprivation, dietary restriction can minimize alterations in parameters related to cardiovascular risk.
Expression of ceruloplasmin in cavernosal tissue of paradoxically sleep deprived rats. | Autor: Andersen Ml, Lee KS, Alvarenga TAF, Guindalini C, Egydio F, Tufik S. | Revista: Sleep Science
Neverending science. | Autor: Andersen ML | Revista: Sleep Sci. 2012;5(2):iii.
Successful Combined Therapy with Tamoxifen and Lithium in a Paradoxical Sleep Deprivation-Induced Mania Model | Autor: Armani F, Andersen ML, Andreatini R, Frussa-Filho R, Tufik S, Galduroz JCF | Revista: CNS Neurosci Therapeutics | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Successful+Combined+Therapy+with+Tamoxifen+and+Lithium+in+a+Paradoxical+Sleep+Deprivation-Induced+Mania+Modelresumo
BACKGROUND: Previous studies have suggested that manic states and sleep deprivation could contribute to the pathophysiology of bipolar disorder (BD) through protein kinase C (PKC) signaling abnormalities. Moreover, adjunctive therapy has become a standard strategy in the management of BD patients who respond poorly to current pharmacological treatments.
AIM: Thus, the aim of this study was to investigate the possible involvement of PKC inhibition by tamoxifen both separately or in combination with lithium, in paradoxical sleep deprivation (PSD)-induced hyperactivity, one facet of mania-like behavior.
MATERIALS & METHODS: Adult male C57BL/6J mice were randomly distributed (n = 7/group) in 24-h PSD or control groups and injected intraperitoneally (i.p.) with vehicle, lithium (50, 100, or 150 mg/kg) or tamoxifen (0.5, 1.0, or 2.0 mg/kg - experiment 1). In a second experiment, mice were injected i.p. with vehicle or a combination of subeffective doses of lithium and tamoxifen. Animals were subjected to a protocol based on repetitive PSD conditions, followed by assessment of locomotion activity in the open-field task.
RESULTS: PSD significantly increased locomotor activity in both experiments. These behavioral changes were prevented by a treatment with lithium or tamoxifen, or a combined treatment with both lithium and tamoxifen.
DISCUSSION: Therefore, our findings suggest that lithium and tamoxifen exert reversal effects against PSD-induced hyperactivity in mice.
CONCLUSION: Furthermore, tamoxifen as an adjunct to lithium therapy provides support for an alternative treatment of individuals who either do not respond adequately or cannot tolerate the adverse effects associated with therapeutic doses of lithium.
DNA methylation and oxidative stress in sleep deprived rats. | Autor: Calegare BFA, Tufik S, D’Almeida V. | Revista: Sleep Sci.
Paradoxical sleep deprivation induces muscle atrophy | Autor: Dattilo M, Antunes HK, Medeiros A, Mônico-Neto M, Souza Hde S, Lee KS, Tufik S | Revista: Muscle and Nerveresumo
INTRODUCTION: Because paradoxical sleep deprivation (PSD) induces a catabolic hormone profile, we sought to evaluate the morphology of the tibialis anterior (TA) muscle and testosterone and corticosterone levels of paradoxical sleep-deprived rats.
METHODS: Three study groups of rats were established: the first group was sleep deprived for 96 h; the second group was also sleep deprived for 96 h, but then returned to their home-cage and allowed to sleep for the next 96 h; and the third group was the control group, with a normal sleep cycle.
RESULTS: PSD reduced the weight and fiber cross-sectional area of the TA muscle. Moreover, PSD enhanced plasma corticosterone and reduced serum testosterone levels. The 96 h of sleep after PSD was sufficient to restore partially the morphology of TA, while hormones returned to basal levels.
CONCLUSION: PSD induces hormonal alterations that may mediate muscle atrophy.
Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals | Autor: De Souza L, Smaili SS, Ureshino RP, Sinigaglia-Coimbra R, Andersen ML, Lopes GS, Tufik S | Revista: Progr Neuropsychopharmacol Biol Psychiatryresumo
Aging leads to progressive deterioration of physiological function and diminished responses to environmental stress. Organic and functional alterations are frequently observed in elderly subjects. Although chronic sleep loss is observed during senescence, little is known about the impact of insufficient sleep on cellular function in aging neurons. Disruption of neuronal calcium (Ca²⁺) signaling is related to impaired neuronal function and cell death. It has been hypothesized that sleep deprivation may compromise neuronal stability and induce cell death in young neurons; however, it is necessary to evaluate the impact of aging on this process. Therefore, the aim of this study was to evaluate the effects of chronic sleep restriction (CSR) on Ca²⁺ signaling and cell death in the hippocampus of young and aged animals. We found that glutamate and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) induced a greater elevation in cytosolic Ca²⁺ ([Ca²⁺](c)) in hippocampal slices from aged rats subjected to CSR compared to age-matched controls. Interestingly, aged-matched controls showed a reduced Ca²⁺ response to glutamate and FCCP, relative to both CSR and control young animals. Apoptotic nuclei were observed in aged rats from both treatment groups; however, the profile of apoptotic nuclei in aged CSR rats was highly variable. Bax and Bcl-2 protein expression did not change with aging in the CSR groups. Our study indicates that aging promotes changes in Ca²⁺ signaling, which may also be affected by CSR. These age-dependent changes in Ca²⁺ signaling may increase cellular vulnerability during CSR and contribute to Ca²⁺ signaling dysregulation, which may ultimately induce cell death.
Influence of sleep deprivation and morphine on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in skin of hairless mice | Autor: Egydio F, Ribeiro DA, Noguti J, Tufik S, Andersen ML | Revista: Toxicol Mech Methodsresumo
Skin performs a host of primordial functions that keep the body alive. Morphine is a drug with immunosuppressant properties whose chronic use may lead to increased infection and delayed wound healing. Sleep is a fundamental biological phenomenon that promotes the integrity of several bodily functions. Sleep deprivation adversely affects several systems, particularly the immune system. The aim of this study was to perform an immunohistochemical evaluation on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in skin of sleep-deprived mice and mice chronically treated with morphine. Adult hairless male mice were distributed into the following groups: Control, morphine, sleep-deprived, and morphine + SD. Morphine (10 mg/kg, subcutaneous) was injected every 12 h for 9 days. Morphine induced immunoexpression of cyclooxygenase-2 and nitric oxide synthase. Sleep deprivation did not modulate outcomes induced by morphine. Morphine, not sleep loss, induces cyclooxygenase-2 and nitric oxide synthase immunoexpression in the skin of hairless mice.
Sleep deprivation impairs memory retrieval in mice: influence of sex | Autor: Fernandes-Santos L, Patti CL, Zanin KA, Fernandes HA, Tufik S, Andersen ML, Frussa-Filho R | Revista: Progr Neuropsychopharmacol Biol Psychiatryresumo
The deleterious effects of paradoxical sleep deprivation on memory processes are well documented. However, non-selective sleep deprivation occurs more commonly in modern society and thus represents a better translational model. We have recently reported that acute total sleep deprivation (TSD) for 6 h immediately before testing impaired performance of male mice in the plus-maze discriminative avoidance task (PM-DAT) and in the passive avoidance task (PAT). In order to extend these findings to females, we examined the effect of (pre-test) TSD on the retrieval of different memory tasks in both male and female mice. Animals were tested using 3 distinct memory models: 1) conditioning fear context (CFC), 2) PAT and 3) PM-DAT. In all experiments, animals were totally sleep-deprived by the gentle interference method for 6h immediately before being tested. In the CFC task and the PAT, TSD induced memory impairment regardless of sex. In PM-DAT, the memory impairing effects of TSD were greater in females. Collectively, our results confirm the impairing effect of TSD on emotional memory retrieval and demonstrate that it can be higher in female mice depending on the memory task evaluated.
Bone marrow and peripheral white blood cells number is affected by sleep deprivation in a murine experimental model | Autor: Guariniello LD, Vicari P, Lee KS, Oliveira AC, Tufik S | Revista: J Cell Physiol.resumo
Sleep deficit and related disorders are becoming increasingly prevalent in modern life and an extensive literature has documented that acute or chronic sleep deprivation can lead to several physiological consequences. Here, we evaluated the effects of sleep deprivation on hematopoietic composition of either bone marrow or peripheral blood. Mice were subjected to paradoxical sleep deprivation (PSD) for 72 h by modified multiple platform method, with or without an additional sleep recovery (SR) period of 10 days. PSD decreased total cellularity of the bone marrow and peripheral blood concomitantly. Subsequent analysis of cell composition showed that absolute number of hematopoietic stem/progenitor cells and colony-forming units was decreased. Moreover, the absolute number of granulocytes and monocytes in bone marrow was reduced in PSD group. These alterations were paralleled by an accumulation of neutrophils and monocytes in peripheral blood. PSD also induced lymphopenia in the circulation. To the best of our knowledge, this is the first study that demonstrates the importance of sleep on the hematopoietic microenvironment and provides new insights into the relationship between sleep and the immune system.
Sleep deprivation impairs calcium signaling in mouse splenocytes and leads to a decreased immune response | Autor: Lungato L, Gazarini ML, Paredes-Gamero EJ, Tersariol IL, Tufik S, D'Almeida V | Revista: Biochim Biophys Acta General Subjectsresumo
BACKGROUND: Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca(2+)) plays a critical signaling role. We performed live cell measurements of cytosolic Ca(2+) mobilization to understand the changes in Ca(2+) signaling that occur in splenic immune cells after various periods of sleep deprivation (SD).
METHODS: Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72h) and Ca(2+) intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca(2+) mobilization in endoplasmic reticulum and mitochondria. Additionally, Ca(2+) channel gene expression was evaluated
RESULTS: Splenocytes showed a progressive loss of intracellular Ca(2+) maintenance from endoplasmic reticulum (ER) stores. Transient Ca(2+) buffering by the mitochondria was further compromised. These findings were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca(2+) channels.
CONCLUSIONS AND GENERAL SIGNIFICANCE: These novel data suggest that SD impairs Ca(2+) signaling, most likely as a result of ER stress, leading to an insufficient Ca(2+) supply for signaling events. Our results support the previously described immunosuppressive effects of sleep loss and provide additional information on the cellular and molecular mechanisms involved in sleep function.
Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus | Autor: Matos G, Ribeiro DA, Alvarenga TA, Hirotsu C, Scorza FA, Le-Suer-Maluf LA, Cavalheiro EA, Tufik S, Andersen ML. | Revista: Neurosci Lettresumo
The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE.
Inhibition of self-grooming induced by sleep restriction in dam rats. | Autor: Pires GN, Alvarenga TA, Maia LO, Mazaro-Costa R, Tufik S, Andersen ML | Revista: Indian J Med Resresumo
BACKGROUND & OBJECTIVES: Sleep restriction is a common feature of modern lifestyle and its effects can be extended to pregnancy. Several neurobehavioural consequences of sleep restriction during pregnancy have been reported, among which stand out perinatal depression and maternal fatigue, however, its effects over mother-infant relationship warrant further investigation. Thus, this study was aimed to evaluate the effects of sleep restriction during pregnancy over maternal behaviour and maternal aggression through animal models.
METHODS: Eighteen 90-day-old female Wistar rats were distributed in two groups: (i) Control - not submitted to any manipulation during pregnancy, and (ii) Sleep restriction - submitted to sleep restriction during the entire pregnancy (21 days) through the multiple platforms technique. In the postpartum day 5, resident-intruder paradigm and the latencies test were performed to assess both maternal behaviour and maternal aggression.
RESULTS: The sleep-restricted females displayed grooming in less frequency and duration, and with higher latency when compared to normal animals, while maternal aggression and maternal behaviour parameters remained equivalent between groups.
INTERPRETATION & CONCLUSIONS: Considering the maintenance of maternal behavioural parameters, the inhibition of grooming seems to exert an adaptive mechanism, enabling sleep-restricted rats to display maternal behaviour properly.
Immune alterations after selective REM or total sleep deprivation in healthy male volunteers | Autor: Ruiz FS, Andersen ML, Martins RCS, Zager A, Lopes JD, Tufik S. | Revista: Innate Immunity
Sleep deprivation alters rat ventral prostate morphology, leading to glandular atrophy: a microscopic study contrasted with the hormonal assays | Autor: Venancio D, Andersen ML, Vilamaior P, Santos F, Zager A, Tufik S, Taboga S, Mello MT. | Revista: J Biomed Biotechnolresumo
We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR.
Immune outcomes of paradoxical sleep deprivation on cellular distribution in naive and LPS-stimulated mice. | Autor: Zager A, Ruiz F, Tufik S, Andersen ML | Revista: Neuroimmunomodulationresumo
BACKGROUND/AIMS: Several lines of evidence indicate that sleep loss imposes significant consequences on the host defense system, including changes in cell number, activity and distribution. However, it is not clear whether cellular alterations after sleep deprivation are caused by redistribution to immune organs or by death of these cells or how the response to a nonspecific immune activator would be affected. Therefore, the aim of this study was to assess the leukocyte distribution after paradoxical sleep deprivation (PSD) in saline- and lipopolysaccharide-treated mice.
METHODS: Adult inbred mice were paradoxical sleep deprived (72 h), whereas the controls were kept in their home cages. After PSD, both groups received an injection of either saline or lipopolysaccharide (LPS; 1 or 5 μg/animal, intraperitoneally), 2 h prior to the collection of blood, spleen, lymph nodes and peritoneal wash. Isolated cells were then designated to differential leukocyte count (blood) and flow cytometry analysis of immune cell subsets (immune sites).
RESULTS: The data revealed that PSD caused a significant reduction of circulating lymphocytes and a general decrease in all cellular subsets of spleen, mainly T and B cells. However, no alteration in response of PSD was found on other immune sites, such as lymph nodes and peritoneum. Of note, immune cell distribution in response to in vivo LPS stimulation remained unchanged after PSD.
CONCLUSIONS: Our study provided original evidence concerning the immune outcomes of PSD, indicating that cellular decrease caused by PSD is not restricted to circulation, but also to immune sites. Taken together, our results could help shed light on the physiological mechanisms of leukocyte trafficking.
Free recall of word lists under total sleep deprivation and after recovery sleep. | Autor: Zanini GAV, Tufik S, Andersen ML, Silva RCM, Bueno OFA, Rodrigues CC, Pompéia S. | Revista: Sleepresumo
STUDY OBJECTIVES: One task that has been used to assess memory effects of prior total sleep deprivation (TSD) is the immediate free recall of word lists; however, results have been mixed. A possible explanation for this is task impurity, since recall of words from different serial positions reflects use of distinct types of memory (last words: short-term memory; first and intermediate words: episodic memory). Here we studied the effects of 2 nights of TSD on immediate free recall of semantically unrelated word lists considering the serial position curve.
DESIGN: Random allocation to a 2-night TSD protocol followed by one night of recovery sleep or to a control group.
SETTING: Study conducted under continuous behavioral monitoring.
PARTICIPANTS: 24 young, healthy male volunteers.
INTERVENTION: 2 nights of total sleep deprivation (TSD) and one night of recovery sleep.
MEASUREMENTS AND RESULTS: Participants were shown five 15 unrelated word-lists at baseline, after one and 2 nights of TSD, and after one night of recovery sleep. We also investigated the development of recall strategies (learning) and susceptibility to interference from previous lists. No free recall impairment occurred during TSD, irrespective of serial position. Interference was unchanged. Both groups developed recall strategies, but task learning occurred earlier in controls and was evident in the TSD group only after sleep recovery.
CONCLUSION: Prior TSD spared episodic memory, short-term phonological memory, and interference, allowed the development of recall strategies, but may have decreased the advantage of using these strategies, which returned to normal after recovery sleep.
Successful combined therapy with Tamoxifen and Lithium in a paradoxical sleep deprivation-induced mania model | Autor: Armani F, Andersen ML, Andreatini R, Frussa-Filho R, Tufik S, Galduróz JC | Revista: CNS Neuroscience & Therapeuticsresumo
BACKGROUND: Previous studies have suggested that manic states and sleep deprivation could contribute to the pathophysiology of bipolar disorder (BD) through protein kinase C (PKC) signaling abnormalities. Moreover, adjunctive therapy has become a standard strategy in the management of BD patients who respond poorly to current pharmacological treatments. - AIM: Thus, the aim of this study was to investigate the possible involvement of PKC inhibition by tamoxifen both separately or in combination with lithium, in paradoxical sleep deprivation (PSD)-induced hyperactivity, one facet of mania-like behavior. - MATERIALS & METHODS: Adult male C57BL/6J mice were randomly distributed (n = 7/group) in 24-h PSD or control groups and injected intraperitoneally (i.p.) with vehicle, lithium (50, 100, or 150 mg/kg) or tamoxifen (0.5, 1.0, or 2.0 mg/kg - experiment 1). In a second experiment, mice were injected i.p. with vehicle or a combination of subeffective doses of lithium and tamoxifen. Animals were subjected to a protocol based on repetitive PSD conditions, followed by assessment of locomotion activity in the open-field task. - RESULTS: PSD significantly increased locomotor activity in both experiments. These behavioral changes were prevented by a treatment with lithium or tamoxifen, or a combined treatment with both lithium and tamoxifen. - DISCUSSION: Therefore, our findings suggest that lithium and tamoxifen exert reversal effects against PSD-induced hyperactivity in mice. - CONCLUSION: Furthermore, tamoxifen as an adjunct to lithium therapy provides support for an alternative treatment of individuals who either do not respond adequately or cannot tolerate the adverse effects associated with therapeutic doses of lithium.
Reciprocal interactions between MK-801, sleep deprivation and recovery in modulating rat behavior | Autor: Dubiela FP, Messias MF, Moreira KM, Zanlorenci LHF, Grassl C, Frussa Filho R, Nobrega JN, Tufik S, Hipólide DC | Revista: Behavioural Brain Researchresumo
Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.
Inflammatory markers are associated with inhibitory avoidance memory deficit induced by sleep deprivation in rats | Autor: Esumi LA, Palma BD, Gomes VL, Tufik S, Hipólide DC | Revista: Behavioural Brain Researchresumo
Sleep deprivation (SD) causes detrimental effects to the body, such as memory impairment and weight loss. SD also changes the concentration of inflammatory mediators such as cytokines, which, in turn, can affect cognitive functioning. Thus, the objective of this study was to investigate the involvement of these inflammatory mediators in inhibitory avoidance memory deficit in sleep-deprived rats. Male Wistar rats were deprived of sleep by the modified multiple platform method for 96 h, while their respective controls remained in their housing cages. To assess memory after SD, all animals underwent training, followed by the inhibitory avoidance task test 24h later. Also, the weight of each animal was recorded daily. In the first experiment, animals received an acute administration of lipopolysaccharide (LPS, 50 or 75 μg/kg i.p.) 3h before the inhibitory avoidance training. In the experiment 2, the animals received acute or chronic administration of anti-IL-6 antibody (Ab, 2 μg/kg i.p.). The acute administration was performed 3h before the inhibitory avoidance training, while the chronic treatment administrations were performed daily during the SD period. The 75 μg/kg dose of LPS, but not the 50 μg/kg dose, caused a significant attenuation of memory impairment in the sleep-deprived animals. Although the treatments with the anti-IL-6 Ab did not produce any significant changes in cognitive performance, the Ab attenuated weight loss in sleep-deprived animals. Taken together, these results suggest the involvement of inflammatory mediators in the modulation of memory deficit and weight loss that are observed in sleep-deprived rats.
Angiotensin I-converting enzyme (ACE) activity and expression in rat central nervous system after sleep deprivation | Autor: Visniauskas B, Oliveira V, Carmona AK, D’Almeida V, de Melo RL, Tufik S, Chagas JR | Revista: The Journal of Biological Chemistryresumo
Proteases are essential either for the release of neuropeptides from active or inactive proteins or for their inactivation. Neuropeptides have a fundamental role in sleep-wake cycle regulation and their actions are also likely to be regulated by proteolytic processing. Using fluorescence resonance energy transfer substrates, specific protease inhibitors and real-time PCR we demonstrate changes in angiotensin I-converting enzyme (ACE) expression and proteolytic activity in the central nervous system in an animal model of paradoxical sleep deprivation during 96 h (PSD). Male rats were distributed into five groups (PSD, 24 h, 48 h and 96 h of sleep recovery after PSD and control). ACE activity and mRNA levels were measured in hypothalamus, hippocampus, brainstem, cerebral cortex and striatum tissue extracts. In the hypothalamus, the significant decrease in activity and mRNA levels, after PSD, was only totally reversed after 96 h of sleep recovery. In the brainstem and hippocampus, although significant, changes in mRNA do not parallel changes in ACE specific activity. Changes in ACE activity could affect angiotensin II generation, angiotensin 1-7, bradykinin and opioid peptides metabolism. ACE expression and activity modifications are likely related to some of the physiological changes (cardiovascular, stress, cognition, metabolism function, water and energy balance) observed during and after sleep deprivation.
Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice | Autor: Andreazza AC, Andersen ML, Alvarenga TA, de-Oliveira MR, Armani F, Ruiz FS, Giglio L, Moreira JCF, Kapczinski F, Tufik S. | Revista: Journal of Psychiatric Researchresumo
It has been demonstrated that sleep deprivation is associated with altered expression of genes related to metabolic processes, response to stress and inflammation, circadian sleep/wake cycles, regulation of cell proliferation and various signaling pathways. However, the molecular mechanisms underlying these changes remain poorly understood. Thus, the present study aims to characterize the function of the mitochondrial electron transport chain in the brain using an animal model of paradoxical sleep deprivation (PSD). The question of whether sleep recovery (rebound) can reverse changes found after PSD is also addressed. Adult male inbred C57BL/6J mice were randomly distributed into three groups: home-cage control, PSD and sleep rebound groups. The PSD and rebound groups were subjected to PSD for 72 h. After this sleep deprivation period, the rebound group was returned to its home cage and allowed to sleep in an undisturbed and spontaneous fashion for 24h. The mitochondrial complex I-III, complex II, succinate dehydrogenase and complex II-III activities were then measured by spectrophotometric methods in sub-mitochondrial particles extracted from the prefrontal cortex, hippocampus, striatum and hypothalamus. Our results showed a significant decrease in the activity of complex I-III in the PSD and rebound groups as compared to the control group. The complex II and II-III activity were particularly decreased in the hypothalamus of the sleep rebound group. These results are consistent with the involvement of sleep in energy metabolism and corroborate previous experiments demonstrating the importance of the hypothalamus in sleep regulation.
Biochemical, biometrical and behavioral changes in male offspring of sleep-deprived mice | Autor: Calegare BFA, Fernandes L, Tufik S, D’Almeida V. | Revista: Psychoneuroendocrinology
Inverse benzodiazepine agonist beta-CCM does not reverse learning deficit induced by sleep deprivation | Autor: Dubiela FP, Oliveira MGM, Moreira KM, Nobrega JN, Tufik S, Hipólide DC. | Revista: Neuroscience Lettersresumo
Increasing evidence indicates that sleep deprivation (SD) alters responses to pharmacological agents by affecting specific transmitter systems. The present work addressed deficits in passive avoidance (PA) performance that are seen after SD, and investigated whether treatment with the inverse benzodiazepine agonist beta-CCM could prevent such deficits. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24h (SR group). Animals were treated with saline or 0.5mg/kg beta-CCM before PA training, and were tested 30 min or 24h later. A separate set of animals was sacrificed for [(3)H]Ro 15-4513 binding analysis. beta-CCM increased PA performance in control animals in both short and long term retention tests, whereas SD and SR animals were unaffected by the drug treatment. Interestingly, [(3)H]Ro 15-4513 binding was reduced in the entorhinal cortex in both SD and SR groups. These findings suggest that the lack of promnesic effects of beta-CCM after SD and SR may be associated with benzodiazepine receptor downregulation in specific brain regions related to memory formation.
Sleep loss induces differential response related to genotoxicity in multiple organs of three different mice strains | Autor: Kahan V, Ribeiro DA, Andersen ML, Alvarenga TA, Tufik S. | Revista: Basic & Clinical Pharmacology & Toxicologyresumo
The purpose of the present study was to determine the genetic damage induced by paradoxical sleep deprivation (PSD) in three different male mice strains in peripheral blood, heart, kidney and liver tissues by the single cell gel (comet) assay. Swiss, C57BL/6j and hairless (HRS/j) mice were submitted to PSD by the multiple platform technique for 72 hr, and DNA damage was evaluated. Statistically significant differences in DNA damage were found in blood cells of the Swiss mice strain when compared to negative controls. By contrast, no statistically significant differences were found in the C57BL/6j or hairless mice strains. With regard to the liver, extensive genotoxic effects were found in the Swiss strain. The hairless and C57BL/6j mice strains did not show any signs of genotoxocity in this organ. The same lack of effect was noted in kidney and heart cells of all strains evaluated. In conclusion, our results reveal that sleep deprivation exerted genetic damage in the form of DNA breakage in blood and liver cells of the Swiss mice strain only. This type of approach should be considered when studying noxious activities on genetic apparatus induced by sleep deprivation in mice since the Swiss strain is more suitable for this purpose.
Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats? | Autor: Andersen ML, Ribeiro DA, Alvarenga TA, Silva A, Araujo P, Zager A, Tenorio NM, Tufik S. | Revista: Hormones and Behaviorresumo
The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones.
Dopaminergic and noradrenergic drugs revert cocaine-induced erection in paradoxical sleep-deprived rats | Autor: Andersen ML, Perry JC, Bignotto M, Tufik S. | Revista: Sleep Scienceresumo
Objectives: Evidence suggests that paradoxical sleep deprivation induces dopaminergic supersensitivity and noradrenergic subsensitivity. Previous studies have demonstrated that 96 hours of paradoxical sleep deprivation enhance cocaine-induced penile erection and ejaculation. The present study investigated the influence of the dopaminergic agonist apomorphine and noradrenergic antagonist propranolol in reverting genital reflexes potentiated by cocaine. Methods: Rats were exposed to 96 hours of paradoxical sleep deprivation and received acute and chronic intraperitoneally injections of apomorphine (120, 240 and 480 μg/kg) or propranolol (2, 4 and 8 mg/kg) before being challenged with cocaine (7 mg/kg). Acute or chronic apomorphine (240 and 480 μg/kg) administration reduced the proportion of animals that displayed erection. Results: acute propranolol administration induced a decrease in the proportion of animals displaying penile erection only at the lowest dose. Penile erection frequency decreased after acute and chronic propranolol treatment. Conclusions: This study indicates that dopaminergic supersensitivity and noradrenergic subsensitivity have critical roles in the regulation of sexual reflexes.
Sleep deprivation increases seizures induced by cocaine in rats | Autor: Andersen ML, Matos G, Martins RCS, Tufik S. | Revista: Sleep Scienceresumo
Objective: Medical emergency units have increasingly to deal with seizures associated with cocaine abuse, which are seen as a determinant of cocaine-related lethality in humans. Cocaine is an excitatory drug that inhibits catecholamine reuptake and induces sleep deprivation. In view of the fact that stress plays an important role in modulating drug action, the aim of this study was to compare whether paradoxical sleep deprivation and other modalities of chronic stress influence the proportion of cocaine-induced seizures in male rats. Methods: The incidence of seizures was measured for 60 minutes after acute administration of cocaine to rats (40, 45, 50 and 70 mg/kg) that have been submitted to different modalities of stress (paradoxical sleep deprivation, footshock, swimming and immobilization), applied repeatedly for 4 days, and then compared with non-stressed rats. Results: Cocaine induced seizures in 10% of control rats, and among stressful events this effect was potentiated only by paradoxical sleep deprivation, since 90% of the rats had seizures. Conclusion: Our data show that selective sleep loss triggers a marked increase in the number of cocaine-induced seizures, suggesting that the absence of sleep per se has a relevant effect in modulating such events.
Modulation of sleep homeostasis by corticotropin releasing hormone in REM sleep-deprived rats | Autor: Machado RB, Tufik S, Suchecki D. | Revista: International Journal of Endocrinology | Site: http://www.hindawi.com/journals/ije/2010/326151/resumo
Studies have shown that sleep recovery following different protocols of forced waking varies according to the level of stress inherent to each method. Sleep deprivation activates the hypothalamic-pituitary-adrenal axis and increased corticotropin-releasing hormone (CRH) impairs sleep. The purpose of the present study was to evaluate how manipulations of the CRH system during the sleep deprivation period interferes with subsequent sleep rebound. Throughout 96 hours of sleep deprivation, separate groups of rats were treated i.c.v. with vehicle, CRH or with alphahelical CRH(9-41), a CRH receptor blocker, twice/day, at 07:00 h and 19:00 h. Both treatments impaired sleep homeostasis, especially in regards to length of rapid eye movement sleep (REM) and theta/delta ratio and induced a later decrease in NREM and REM sleep and increased waking bouts. These changes suggest that activation of the CRH system impact negatively on the homeostatic sleep response to prolonged forced waking. These results indicate that indeed, activation of the HPA axis-at least at the hypothalamic level-is capable to reduce the sleep rebound induced by sleep deprivation.
Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation | Autor: Martins PJF, Marques MS, Tufik S, D’Almeida V. | Revista: American Journal of Physiology - Endocrinology and Metabolism | Site: http://ajpendo.physiology.org/content/298/3/E726.full?sid=121f5056-6f00-49cd-b63c-1a4e1094c336resumo
Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.
Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans | Autor: Martins RCS, Andersen ML, Garbuio SA, Bittencourt LR, Guindalini C, Shih MC, Hoexter MQ, Bressan RA, Castiglioni MLV, Tufik S. | Revista: Sleep | Site: http://www.journalsleep.org/ViewAbstract.aspx?pid=27699resumo
OBJECTIVES: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers. - DESIGN: Prospective study. - SETTING: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity. - PATIENTS OR PARTICIPANTS: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived). - MEASUREMENTS AND RESULTS: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation. - CONCLUSION: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.
Modafinil prevents inhibitory avoidance memory deficit induced by sleep deprivation in rats | Autor: Moreira KM, Ferreira TL, Hipolide DC, Fornari RV, Tufik S, Oliveira MGM. | Revista: Sleep | Site: http://www.journalsleep.org/ViewAbstract.aspx?pid=27852
Effects of sleep deprivation on memory in mice: role of state-dependent learning | Autor: Patti CL, Zanin KA, Sanday L, Kameda SR, Fernandes-Santos L, Fernandes HA, Andersen ML, Tufik S, Frussa-Filho R. | Revista: Sleepresumo
STUDY OBJECTIVES: A considerable amount of experimental evidence suggests that sleep plays a critical role in learning/memory processes. In addition to paradoxical sleep, slow wave sleep is also reported to be involved in the consolidation process of memories. Additionally, sleep deprivation can induce other behavioral modifications, such as emotionality and alternations in locomotor activity in rodents. These sleep deprivation-induced alterations in the behavioral state of animals could produce state-dependent learning and contribute, at least in part, to the amnestic effects of sleep deprivation. The aim of the present study was to examine the participation of state-dependent learning during memory impairment induced by either paradoxical sleep deprivation (PSD) or total sleep deprivation (TSD) in mice submitted to the plus-maze discriminative avoidance or to the passive avoidance task. - DESIGN: Paradoxical sleep deprivation (by the multiple platform method) and total sleep deprivation (by the gentle handling method) were applied to animals before training and/or testing. - CONCLUSIONS: Whereas pre-training or pre-test PSD impaired retrieval in both memory models, pre-training plus pre-test PSD counteracted this impairment. For TSD, pre-training, pre-test, and pre-training plus pre-test TSD impaired retrieval in both models. Our data demonstrate that PSD- (but not TSD-) memory deficits are critically related to state-dependent learning.
Sleep deprivation affects inflammatory marker expression in adipose tissue | Autor: 13. Rosa Neto JC, Lira FS, Venancio DP, Cunha CA, Oyama LM, Pimentel GD, Tufik S, do Nascimento CM, Santos RV, de Mello MT. | Revista: Lipids in Health and Diseaseresumo
Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. - METHODS: The study consisted of two groups: a control (C) group and a paradoxical sleep deprivation by 96 h (PSD) group. Ten rats were randomly assigned to either the control group (C) or the PSD. Mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL)-6, interleukin (IL)-10 and tumour necrosis factor (TNF)-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. - RESULTS: IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG), VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. - CONCLUSION: PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.
Age-related changes during a paradigm of chronic sleep restriction | Autor: Souza L, Andersen ML, Smaili SS, Lopes GS, Ho PS, Papale LA, Tufik S. | Revista: Behavioural Brain Researchresumo
Fragmented and restricted sleep is a common problem for the human elderly. There is evidence that aging impairs sleep in animals as well. After sleep deprivation, older animals have less sleep rebound. Despite increasing complaints of reduced time for sleep in contemporary society, few studies have examined chronic sleep restriction protocols in animals. Therefore, the aim of the present study was to evaluate the effects of chronic sleep restriction on the sleep patterns of aged rats. Using the single platform method, 22-month-old male rats were submitted to 18 h of sleep restriction followed by 6 h of total sleep opportunity. The sleep-wake cycles of these rats were recorded for 6h/day throughout the 12-day procedure. The results showed that total sleep time and NREM sleep were reduced during the 12-day sleep restriction period. However, rebound REM sleep was only significant on day 6. A negative rebound was also seen, particularly during the last days of the chronic sleep restriction period. Furthermore, sleep latency and mean wake bout length progressively increased during the protocol. These findings indicate that older rats have an inability to restore their sleep patterns during extended sleep deprivation.
Food restriction or sleep deprivation: Which exerts a greater influence on the sexual behaviour of male rats? | Autor: 1. Alvarenga TA, Andersen ML, Velázquez-Moctezuma J, Tufik S. | Revista: Behavioural Brain Researchresumo
The purpose of this study was to determine the effects of food restriction (FR) and paradoxical sleep deprivation (PSD), either alone or in combination, on sexual behaviours (mount, intromission and ejaculation) in adult male rats. Diet restriction began at weaning with 6g/day of food, and the amount of food was increased by 1g/week until it reached 15g/day amount (in adulthood). During adulthood, rats under FR and those fed ad libitum were either subjected to PSD for 96h or maintained in home-cage groups. The results indicated that both FR and ad libitum sleep-deprived groups showed a significant decrease in performance and motivation to initiate sexual behaviour, reflected by the increase in mount and intromission latencies and decreased copulatory rate. FR associated with PSD reversed the adverse effects of sleep deprivation on the number of ejaculations and inter-copulatory interval. Testosterone concentrations decreased after sleep deprivation, regardless of food availability; while progesterone was significantly higher in the FR-PSD group only. In light of the limited understanding of the link between secretion patterns and neural-hormonal control of food availability related to sexual behaviour, our data indicate that sleep loss affects sexual responses, and FR was able to restore some of the sexual parameters investigated.
Distinct effects of acute and chronic sleep loss on DNA damage in rats | Autor: Andersen ML, Ribeiro DA, Bergamaschi CT, Alvarenga TA, Silva A, Zager A, Campos RR, Tufik S. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatryresumo
The aim of this investigation was to evaluate genetic damage induced in male rats by experimental sleep loss for short-term (24 and 96 h) and long-term (21 days) intervals, as well as their respective recovery periods in peripheral blood, brain, liver and heart tissue by the single cell gel (comet) assay. Rats were paradoxically deprived of sleep (PSD) by the platform technique for 24 or 96 h, or chronically sleep-restricted (SR) for 21 days. We also sought to verify the time course of their recovery after 24 h of rebound sleep. The results showed DNA damage in blood cells of rats submitted to PSD for 96 h. Brain tissue showed extensive genotoxic damage in PSD rats (both 24 and 96 h), though the effect was more pronounced in the 96 h group. Rats allowed to recover from the PSD-96 h and SR-21 days treatments showed DNA damage as compared to negative controls. Liver and heart did not display any genotoxicity activity. Corticosterone concentrations were increased after PSD (24 and 96 h) relative to control rats, whereas these levels were unaffected in the SR group. Collectively, these findings reveal that sleep loss was able to induce genetic damage in blood and brain cells, especially following acute exposure. Since DNA damage is an important step in events leading to genomic instability, this study represents a relevant contribution to the understanding of the potential health risks associated with sleep deprivation.
The effects of sleep deprivation and sleep recovery on pain thresholds of rats with chronic pain | Autor: Andersen ML, Silva A, Kawakami R, Tufik S. | Revista: Sleep Scienceresumo
Background and objective: The aim of this study was to compare the effects of different paradoxical sleep deprivation methods on the pain threshold in rats submitted to inflammatory and neuropathic pain models. We also investigated whether changes in pain threshold could be reverted by sleep recovery period. - Methods: Wistar rats were randomly assigned in arthritis-induced by adjuvant (AIA), chronic constrictive injury (CCI) of sciatic nerve and non-handled control group. Paradoxical sleep deprivation was performed using small or large platforms in the water tank technique. Grid and home-cage groups were also evaluated. Pain threshold was determined in dry environment using the hot plate test, before, during and after (recovery) paradoxical sleep deprivation. - Results and conclusion: The data showed that AIA and CCI differ from control groups from the second day on after pain inducing procedures and lasted until the third day of sleep recovery. Paradoxical sleep deprivation reduced the pain threshold in all groups studied, independently the method used. Sleep recovery did not restore the baseline pain threshold in arthritis-induced animals, but it was restored in CCI group submitted to both paradoxical sleep deprivation methods.
Increased susceptibility to development of anhedonia in rats with chronic peripheral nerve injury: Involvement of sleep deprivation? | Autor: Andersen ML, Hoshino K, Tufik S. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatryresumo
The main purpose of the present study was to evaluate whether REM sleep deprivation (RSD) influences the development of anhedonia in rats in a peripheral neuropathy model induced by sciatic nerve constriction injury (CCI). Anhedonia was measured by assessing daily water/sucrose intake. Four groups were assessed: control (CTRL), CCI, RSD, and CCI+RSD (n=8/group). Intake data were collected at baseline (mean of 3 days), on the 1st and 2nd days after a CCI or SHAM procedure, during 4 days of RSD, and during an additional 10 days (rebound period or equivalent in home-cage rats). Control rats spontaneously and progressively increased sucrose intake, reaching final daily volumes significantly greater than respective initial baseline amounts. RSD promoted an additional and immediate significant increase in sucrose intake during sleep deprivation days. The CCI group did not display a spontaneous, progressive increase in sucrose intake. When CCI was combined with RSD, the increase in sucrose intake induced by RSD was significantly lower than in animals submitted to RSD alone; the (CCI+RSD) group also failed to show a spontaneous and progressive increase in sucrose intake. The present findings indicate that animal model of chronic neuropathy exhibits reduced sucrose ingestion. Accordingly, this anhedonic condition that constitutes to the core manifestation of depressive states did not occur in response to a single episode of total RSD.
Paradoxical sleep deprivation influences sexual behavior in female rats. | Autor: Andersen ML, Alvarenga TAF, Guindalini C, Perry JC, Silva A, Zager A, Tufik S. | Revista: The Journal of Sexual Medicineresumo
INTRODUCTION: Sleep disturbances are a frequent complaint in women and are often attributed to hormonal fluctuations during the menstrual cycle. Rodents have been used as models to examine the effects of sleep deprivation on hormonal and behavioral changes. Among the many comorbidities common to sleep disorders, sexual behavior remains the least well studied. - AIM: To determine whether paradoxical sleep deprivation (PSD) can affect sexual receptivity (male acceptance) and proceptivity (male solicitation) behaviors in female rats. - METHODS: Female Wistar rats were subjected to PSD or were maintained as controls. After this period, the estrous cycle (proestrus, estrus, and diestrus) was determined, and all females were placed with a sexually experienced male. In order to investigate the role of hormones in sexual behavior, we included additional groups that were artificially induced to be sexually receptive via administration of a combination of estradiol and progesterone. - MAIN OUTCOME MEASUREMENTS: Receptivity and proceptivity behaviors, as well as progesterone and corticosterone concentrations were monitored. - RESULTS: Selective sleep loss caused a significant increase in proceptivity and receptivity behaviors in females exclusively during the proestrus phase. The rejection response was increased in PSD rats during the estrus and diestrus phases, as compared with PSD-receptive and proestrus females. PSD reduced progesterone levels during the proestrus phase relative to the respective control group during the same phase of the estrous cycle. The PSD-proestrus females that displayed the most robust sexual response exhibited greater concentrations of corticosterone than PSD-diestrus females, with an absence of sexual solicitation behaviors. - CONCLUSIONS: PSD produced a distinct response in the hormonal profile that was consistent with the phase of the estrous cycle. These results show that sleep loss can affect sexual motivation and might lead to important clinical implications, including alterations in female physiology and reproductive abnormalities.
Paradoxical sleep deprivation activates hypothalamic nuclei that regulate food intake and stress response. | Autor: Galvão MOL, Sinigaglia-Coimbra R, Kawakami SE, Tufik S, Suchecki D. | Revista: Psychoneuroendocrinologyresumo
A large body of evidence has shown that prolonged paradoxical sleep deprivation (PSD) results in hypothalamic-pituitary-adrenal (HPA) axis activation, and in loss of body weight despite an apparent increase of food intake, reflecting increased energy expenditure. The flowerpot technique for PSD is an efficient paradigm for investigating the relationships among metabolic regulation and stress response. The purpose of the present study was to examine the mechanisms involved in the effects of 96 h of PSD on metabolism regulation, feeding behaviour and stress response by studying corticotrophin-releasing hormone (CRH) and orexin (ORX) immunoreactivity in specific hypothalamic nuclei. Once-daily assessments of body weight, twice-daily measurements of (spillage-corrected) food intake, and once-daily determinations of plasma adrenocorticotropic hormone (ACTH) and corticosterone were made throughout PSD or at corresponding times in control rats (CTL). Immunoreactivity for CRH in the paraventricular nucleus of the hypothalamus and for ORX in the hypothalamic lateral area was evaluated at the end of the experimental period. PSD resulted in increased diurnal, but not nocturnal, food intake, producing no significant changes in global food intake. PSD augmented the immunoreactivity for CRH and plasma ACTH and corticosterone levels, characterizing activation of the HPA axis. PSD also markedly increased the ORX immunoreactivity. The average plasma level of corticosterone correlated negatively with body weight gain throughout PSD. These results indicate that augmented ORX and CRH immunoreactivity in specific hypothalamic nuclei may underlie some of the metabolic changes consistently described in PSD.
To what extent is sleep rebound effective in reversing the effects of paradoxical sleep deprivation on gene expression in the brain? | Autor: Guindalini C, Andersen ML, Alvarenga T, Lee L, Tufik S. | Revista: Behavioural Brain Researchresumo
Sleep is essential to maintaining health and well-being. It has been demonstrated that some of the biological alterations caused by paradoxical sleep deprivation (PSD) are not completely reversed after a period of sleep rebound (SR). The purpose of this study was to determine to what extent the specific molecular changes that occur in the rat cerebral cortex after 96 h of PSD can effectively be reversed during 24h of recovery. Total RNA from the right cerebral cortex of Wistar male rats and GeneChip Rat Genome 230 2.0 arrays were used to perform comprehensive microarray analysis of gene expression in control, PSD and SR groups. Microarray data were validated by Real Time qPCR. A total of 78 unique transcripts were differently expressed after PSD relative to control levels. These include genes related to metabolic processes, the circadian sleep-wake cycle, response to stimuli, regulation of cell proliferation and signaling pathways. After 24h of sleep rebound, approximately 62% of the sleep deprivation transcripts were again detected as differently expressed in the SR relative to the PSD group, although in the opposite direction. On the other hand, the expression of the remaining transcripts showed intermediate values between control and sleep-deprived animals. In summary, our results provide a unique set of transcripts that might be specific related to regulation of paradoxical sleep phase and sleep homeostasis processes, as well as to the biological basis of sleep disorders.
Prostaglandin involvement in hyperthermia induced by sleep deprivation: a pharmacological and autoradiographic study | Autor: Palma BD, Nóbrega JN, Gomes VL, Esumi LA, Seabra MLV, Tufik S, Hipolide DC. | Revista: Life Sciencesresumo
AIMS: Hyperthermia is a characteristic functional effect of sleep deprivation (SD). We hypothesize here that prostaglandin E2 (PGE2) could be involved in hyperthermia induced by sleep deprivation. - MAIN METHODS: To address this issue we examined the effects of a selective cyclo-oxygenase-2 inhibitor (COX-2) agent on hyperthermia induced by SD in rats. We also investigated binding to PGE2 receptors in hypothalamic brain areas of sleep-deprived rats using in vitro autoradiography. Male Wistar rats were deprived of sleep for 96 h using the platform technique. Sleep deprived and control groups received saline or Celecoxib (20, 30 and 40 mg/kg; p.o.) daily during the SD period. Colonic temperature was measured daily. - KEY FINDINGS: Results indicated that core temperature of sleep-deprived rats that receiving saline increased from the first to the fourth day of SD compared to baseline and to the respective control group. However, the hyperthermia induced by SD was not blocked by COX-2 inhibitor at any dose. [(3)H]PGE2 binding did not differ significantly among the groups in any of a number of hypothalamic areas examined. - SIGNIFICANCE: Although SD rats showed no response to the COX-2 inhibitor and no alterations in [(3)H]PGE2 binding, the possibility remains that other prostaglandin system and/or receptor subtypes may be altered by SD.
Effects on prolactin secretion and binding to dopaminergic receptors in sleep-deprived lupus-prone mice | Autor: Palma BD, Hipolide DC, Tufik S. | Revista: Brazilian Journal of Medical and Biological Researchresumo
Sleep disturbances have far-reaching effects on the neuroendocrine and immune systems and may be linked to disease manifestation. Sleep deprivation can accelerate the onset of lupus in NZB/NZWF(1) mice, an animal model of severe systemic lupus erythematosus. High prolactin (PRL) concentrations are involved in the pathogenesis of systemic lupus erythematosus in human beings, as well as in NZB/NZWF(1) mice. We hypothesized that PRL could be involved in the earlier onset of the disease in sleep-deprived NZB/NZWF(1) mice. We also investigated its binding to dopaminergic receptors, since PRL secretion is mainly controlled by dopamine. Female NZB/NZWF(1) mice aged 9 weeks were deprived of sleep using the multiple platform method. Blood samples were taken for the determination of PRL concentrations and quantitative receptor autoradiography was used to map binding of the tritiated dopaminergic receptor ligands [3H]-SCH23390, [3H]-raclopride and [3H]-WIN35,428 to D(1) and D(2) dopaminergic receptors and dopamine transporter sites throughout the brain, respectively. Sleep deprivation induced a significant decrease in plasma PRL secretion (2.58 +/- 0.95 ng/mL) compared with the control group (25.25 +/- 9.18 ng/mL). The binding to D(1) and D(2) binding sites was not significantly affected by sleep deprivation; however, dopamine transporter binding was significantly increased in subdivisions of the caudate-putamen--posterior (16.52 +/- 0.5 vs 14.44 +/- 0.6), dorsolateral (18.84 +/- 0.7 vs 15.97 +/- 0.7) and ventrolateral (24.99 +/- 0.5 vs 22.54 +/- 0.7 microCi/g), in the sleep-deprived mice when compared to the control group. These results suggest that PRL is not the main mechanism involved in the earlier onset of the disease observed in sleep-deprived NZB/NZWF(1) mice and the reduction of PRL concentrations after sleep deprivation may be mediated by modifications in the dopamine transporter sites of the caudate-putamen.
The effects of REM sleep deprivation and REM sleep rebound on hypocretin levels in mice brains | Autor: Pedrazzoli M, Hipólide D, D’Almeida V, Tufik S. | Revista: Sleep Scienceresumo
Background and objective: Hypocretins (orexins) are recently discovered neuropeptides that are produced in a very restricted area of the lateral hypothalamus. These peptides were originally associated with feeding behavior, but have come to be viewed as essential in causing narcolepsy and regulating sleep. Narcolepsy is a sleep disorder associated with REM sleep abnormalities, and it is likely that hypocretins play a major role in regulation of this sleep stage. - Methods: To verify the potential effects of REM sleep deprivation on the levels of hypocretins in the brain, we deprived mice of REM sleep for 96 h and measured the levels of hypocretins in whole brain preparations using an enzyme immunoassay. - Results: Our results showed no difference in the levels of hypocretin 1 and 2 (orexin A and B) in REM sleep-deprived animals or in animals that had a sleep rebound after sleep deprivation. - Conclusions: These results corroborate data in the literature that show that sleep deprivation does not produce significant alteration in hypocretin levels in the mouse brain just after an active period.
Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research | Autor: Tufik S, Andersen ML, Bittencourt LRA, Mello MT. | Revista: Anais da Academia Brasileira de Ciências
Paradoxical sleep deprivation impairs acquisition, consolidation, and retrieval of a discriminative avoidance task in rats | Autor: Alvarenga TA, Patti CL, Andersen ML, Silva RH , Calzavara MB, Lopez GB, Frussa-Filho R , Tufik S. | Revista: Neurobiology of Learning and Memoryresumo
The aim of the present study was to investigate the effects of paradoxical sleep deprivation (PSD) for 96 h on the learning/memory processes in rats submitted to the plus-maze discriminative avoidance task (PM-DAT), which simultaneously evaluates learning, memory, anxiety and motor function. Four experiments were performed in which rats were submitted to: (1) post-training and pre-test PSD; (2) post-training or pre-test PSD; (3) pre-training PSD or pre-training paradoxical sleep (PS) rebound (24 h) and (4) pre-test PSD rebound. Concerning Experiment I, post-training and pre-test PSD induced memory deficits, an anxiolytic-like behavior and an increase in locomotor activity. In Experiment II, both post-training PS-deprived and pre-test PS-deprived groups showed memory deficits per se. However, only the pre-test PS-deprived animals presented anxiolytic-like behavior and increased locomotor activity. In Experiment III, pre-training PS-deprived rats showed learning and memory deficits, anxiolytic-like behavior and increased locomotor activity. A 24h-sleep recovery period after the PSD abolished the learning and memory deficits but not anxiety and locomotor alterations. Finally, sleep rebound did not modify acquisition (Experiment III) and retrieval (Experiment IV). This study strengthened the critical role of paradoxical sleep (but not sleep rebound) in all the phases of learning and memory formation. In addition, it suggests that PSD effects on acquisition and consolidation do not seem to be related to other behavioral alterations induced by this procedure.
Effects of sleep loss on sleep architecture in Wistar rats: Gender-specific rebound sleep | Autor: Andersen ML, Antunes IB, Silva A, Alvarenga TAF, Baracat EC, Tufik S. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatryresumo
This study was designed to examine the influence of gender on sleep rebound architecture after a 4-day paradoxical sleep deprivation period. After a 5-day baseline sleep recording, both male and female rats in different phases of the estrus cycle were submitted to paradoxical sleep deprivation for 96 h. After this period, the sleep rebound recording was evaluated for 5 days (one estrus cycle). The findings revealed that after paradoxical sleep deprivation, sleep efficiency and paradoxical sleep returned to baseline values on the second day of the light period, for all except the proestrus group. During the dark rebound period, only the female groups presented increased sleep efficiency on the first day. Paradoxical sleep returned to baseline values on the third day, except for males and the cycling females submitted to paradoxical sleep deprivation in the diestrus phase, whose baseline values returned to normal on the second day of rebound period. Thus, the females and males displayed distinct patterns as a result of sleep disruption.
Sleep rebound attenuates context-dependent behavioural sensitization induced by amphetamine | Autor: Calzavara MB, Andersen ML, Fukushiro DF, Lopez GB, Abílio VC, Tufik S, Frussa-Filho R. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatryresumo
We have recently demonstrated that paradoxical sleep deprivation (PSD) potentiates the induction of amphetamine (AMPH)-induced behavioural sensitization by increasing its conditioned component. In the present study, the effects of sleep rebound (induced by 24 h recovery period from PSD) were studied on AMPH-induced behavioural sensitization. Sleep rebound attenuated the acute locomotor-stimulating effect of AMPH. AMPH-induced behavioural sensitization was context-specific and was also attenuated by sleep rebound. These results strengthen the notion that sleep conditions can influence AMPH-induced behavioural sensitization.
Sleep deprivation reduces rat hyperhomocysteinemia induced by a hyperlipidic diet | Autor: D’Almeida V, Andersen ML, Martins PJF, Tufik S. | Revista: Sleep Scienceresumo
Objective: Several clinical and experimental studies have shown an association between hyperhomocysteinemia and cardiovascular diseases (CVD). Long-term exposure to a hyperlipidic diet induces tissue fatty acid accumulation and increases circulating lipid concentrations, which raises the risk for CVD. Sleep debt is also considered to be an important factor enhancing cardiovascular risk. Since no information concerning homocysteine (Hcy) levels resulting from a hyperlipidic diet is currently available, our objective was to investigate changes in Hcy concentrations in sleep deprived rats fed a hyperlipidic diet. Subjects and Methods: Rats were maintained for 65 days on a high-fat diet, whereas control animals received regular food ad libitum. After this period, a sub-group of these animals was submitted to sleep deprivation (SD). Homocysteine, thiobarbituric acid reactive substances (TBARS), vitamin B6, folate, and the lipid profile were measured. Results: Hcy concentrations were significantly higher in hyperlipidic fed rats. Sleep deprivation reduces high levels of this amino acid as well as triacylglicerols and TBARS levels. Conclusions: The present study shows for the first time that plasma Hcy concentrations in rats increase as a result of a hyperlipidic diet consumption. Metabolic changes induced by SD interfered in CVD-related factors even after the use of a hyperlipidic diet.
Blockage of dopaminergic D2 receptors produces decrease of REM but not of slow wave sleep in rats after REM sleep deprivation | Autor: Lima MMS, Andersen ML, Reksidler AB, Silva A, Zager A, Zanata SM, Vital MABF, Tufik S. | Revista: Behavioural Brain Scienceresumo
Dopamine (DA) has, as of late, become singled out from the profusion of other neurotransmitters as what could be called a key substance, in the regulation of the sleep-wake states. We have hypothesized that dopaminergic D(2) receptor blockage induced by haloperidol could generate a reduction or even an ablation of rapid eye movement (REM) sleep. Otherwise, the use of the selective D(2) agonist, piribedil, could potentiate REM sleep. Electrophysiological findings demonstrate that D(2) blockage produced a dramatic reduction of REM sleep during the rebound (REB) period after 96 h of REM sleep deprivation (RSD). This reduction of REM sleep was accompanied by an increment in SWS, which is possibly accounted for the observed increase in the sleep efficiency. Conversely, our findings also demonstrate that the administration of piribedil did not generate additional increase of REM sleep. Additionally, D(2) receptors were found down-regulated, in the haloperidol group, after RSD, and subsequently up-regulated after REB group, contrasting to the D(1) down-regulation at the same period. In this sense, the current data indicate a participation of the D(2) receptor for REM sleep regulation and consequently in the REM sleep/SWS balance. Herein, we propose that the mechanism underlying the striatal D(2) up-regulation is due to an effect as consequence of RSD which originally produces selective D(2) supersensitivity, and after its period probably generates a surge in D(2) expression. In conclusion we report a particular action of the dopaminergic neurotransmission in REM sleep relying on D(2) activation.
Chronic stress during paradoxical sleep deprivation increases paradoxical sleep rebound: Association with prolactin plasma levels and brain serotonin content | Autor: Machado RB, Tufik S, Suchecki D. | Revista: Psychoneuroendocrinologyresumo
Previous studies suggest that stress associated to sleep deprivation methods can affect the expression of sleep rebound. In order to examine this association and possible mechanisms, rats were exposed to footshock stress during or immediately after a 96-h period of paradoxical sleep deprivation (PSD) and their sleep and heart rate were recorded. Control rats (maintained in individual home cages) and paradoxical sleep-deprived (PS-deprived) rats were distributed in three conditions (1) no footshock--NF; (2) single footshock--SFS: one single footshock session at the end of the PSD period (6-8 shocks per minute; 100 ms; 2 mA; for 40 min); and (3) multiple footshock--MFS: footshock sessions with the same characteristics as described above, twice a day throughout PSD (at 7:00 h and 19:00 h) and one extra session before the recovery period. After PSD, animals were allowed to sleep freely for 72 h. Additional groups were sacrificed at the end of the sleep deprivation period for blood sampling (ACTH, corticosterone, prolactin and catecholamine levels) and brain harvesting (monoamines and metabolites). Neither SFS nor MFS produced significant alterations in the sleep patterns of control rats. All PS-deprived groups exhibited increased heart rate which could be explained by increased dopaminergic activity in the medulla. As expected, PS deprivation induced rebound of paradoxical sleep in the first day of recovery; however, PSD+MFS group showed the highest rebound (327.3% above the baseline). This group also showed intermediate levels of corticosterone and the highest levels of prolactin, which were positively correlated with the length of PS episodes. Moreover, paradoxical sleep deprivation resulted in elevation of the serotonergic turnover in the hypothalamus, which partly explained the hormonal results, and in the hippocampus, which appears to be related to adaptive responses to stress. The data are discussed in the realm of a prospective importance of paradoxical sleep for processing of traumatic events.
Sleep deprivation-induced gnawing—relationship to changes in feeding behavior in rats | Autor: Martins PJF, Nobrega JN, Tufik S, D'Almeida V. | Revista: Physiology & Behavior
Effects of cocaine, metamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats | Autor: Martins RC, Andersen ML, Shih MC, Tufik S. | Revista: Brazilian Journal of Medical and Biological Research
Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression | Autor: Mattos ABM, Pinto MJS, Oliveira C, Biz C, Ribeiro EB, Nascimento CMO, Andersen ML, Tufik S, Oyama LM | Revista: Lipids in Health and Disease
Distinct behavioral and neurochemical alterations induced by intermittent hypoxia or paradoxical sleep deprivation in rats | Autor: Perry JC, D’Almeida V, Antunes IB, Tufik S. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatry
Glucocorticoids are not responsible for paradoxical sleep deprivation-induced memory impairments | Autor: Tiba PA, Menezes Oliveira MG, Rossi VC, Tufik S, Suchecki D. | Revista: Sleep
Cocaine-induced genital reflexes in paradoxical sleep deprived rats: Indications of mediation by serotonin receptors | Autor: Andersen ML, Antunes IB, Tufik S. | Revista: Progress in Neuro-Psychopharmacology & Biological Psychiatryresumo
As paradoxical sleep deprivation (PSD) modifies cocaine-induced genital reflexes (penile erection [PE] and ejaculation [EJ]) and since cocaine is a serotonin (5-HT) reuptake inhibitor, we hypothesized that 5-HT also plays a role in these genital reflexes in PSD male rats. After a 4-day period of PSD each group was administered with serotonergic drugs prior to cocaine and placed in observation cages. The selective 5-HT(1) agonist (8-OH-DPAT) completely abolished PE events whereas the antagonist (pindolol) did not produce significant effects in the number of animals displaying PE. It was found that both drugs reduce the frequency of PE. There were no significant effects on the number of animals that ejaculated or in its frequency after pindolol although both parameters were reduced by the agonist at the highest doses (2 and 4 mg/kg, SC). Pretreatment with the 5-HT(2) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.12; 0.5 and 1 mg/kg, SC) significantly reduced the number of rats displaying PE and all doses reduced both PE and EJ frequencies. The number of animals displaying PE after 5-HT(2) antagonist (ketanserin) pretreatment at 1 and 2.5 mg/kg doses was significantly decreased in relation to vehicle rats and all doses reduced PE frequency. 5-HT(2) compounds at any dose did not affect the number of animals ejaculating, but the frequency was significantly reduced by all doses of DOI and by 1 to 5 mg/kg doses of ketanserin. Taken together, the results suggest that serotonergic receptors play an important role in genital reflexes induced by cocaine in sleep deprived males.
Cocaine-induced genital reflexes in paradoxical sleep deprived rats: Indications of mediation by serotonin receptors | Autor: Andersen ML, Antunes IB, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Involvement of nitric oxide in cocaine-induced erections and ejaculations after paradoxical sleep deprivation | Autor: Andersen ML, Perry JC, Antunes IB, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats | Autor: Andersen ML, Martins RCS, Alvarenga TAF, Antunes IB, Papale LA, Tufik S. | Revista: Reproductive Biology and Endocrinology
Effects of different substance misuse in genital reflexes of paradoxical sleep deprived male rats | Autor: Andersen ML, Perry JC, Papale LA, Tufik S. | Revista: Scandinavian Journal of Psychology
Influence of chronic cocaine treatment and sleep deprivation on sexual behavior and neurogenesis of the male rat | Autor: Andersen ML, Perry JC, Bignotto M, Perez-Mendes P, Cinini SM, Mello LEA, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Effect of Sildenafil (Viagra) on the genital reflexes of paradoxical sleep-deprived male rats | Autor: Andersen ML, Bignotto M, Tufik S. | Revista: Brazilian Journal of Medical and Biological Research
Participation of D3 and D4 dopaminergic receptors on genital reflexes-induced by cocaine in paradoxical sleep deprived male rats | Autor: Andersen ML, Perry JC, Tufik S. | Revista: Scandinavian Journal of Psychology
Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in intact and ovariectomized rats compared with male rats | Autor: Antunes IB, Andersen ML, Alvarenga TAF, Tufik S. | Revista: Behavioural Brain Research
Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice | Autor: Fukushiro DF, Calzavara MB, Trombin TF, Lopez GB, Abílio VC, Andersen ML, Tufik S, Frussa-Filho R. | Revista: Physiology & Behavior
Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain opioid receptors | Autor: Nascimento DC, Andersen ML, Hipolide DC, Nobrega JN, Tufik S. | Revista: Behavioural Brain Science
Effect of sleep deprivation on the corticosterone secretion in na experimental model of autoimmune disease | Autor: Palma BD, Suchecki D, Catallani B, Tufik S. | Revista: Neuroimmunomodulation
Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats | Autor: Perry JC, D'Almeida V, Souza FG, Schoorlemmer GH, Colombari E, Tufik S. | Revista: Respiratory Physiology & Neurobiology
Sleep deprivation reduces lymphocytes in non-obese diabetic (NOD) mouse model of Type 1 Diabetes Mellitus | Autor: Ruiz FS, Andersen ML, Zager A, Martins RCS, Tufik S. | Revista: Brazilian Journal of Medical and Biological Research
Effects of 3-nitropropionic acid administration on memory and hippocampal lipid peroxidation in sleep-deprived mice | Autor: Silva RH, Abilio VC, Kameda SR, Takatsu-Coleman AL, Carvalho RC, Ribeiro RA, Tufik S, Frussa-Filho R. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Sleep deprivation abolishes the locomotor stimulant effect of ethanol in mice | Autor: Araujo NP, Andersen ML, Abílio VC, Gomes DC, Carvalho RC, Silva RH, Ribeiro RA, Tufik S, Frussa-Filho R. | Revista: Brain Research Bulletin
Effects of long-term food restriction on genital reflexes in paradoxically sleep-deprived male rats | Autor: Alvarenga TA, Andersen ML, Papale LA, Tufik S. | Revista: Brain Research
Effect of paradoxical sleep deprivation on genital reflexes in five rat strains | Autor: Andersen Ml, Antunes IB, Tufik S. | Revista: Hormones and Behavior
Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital reflexes in male rats | Autor: Andersen ML, Perry JC, Battisti MC, Calzavara MB, Costa JL, Neto ON, Frussa-Filho R, Tufik S. | Revista: Behavioural Brain Research
The effects of paradoxical sleep deprivation on estrous cycles of the female rats | Autor: Antunes IB, Andersen ML, Baracat EC, Tufik S. | Revista: Hormones and Behavior
Paradoxical sleep deprivation and sleep recovery: effects on the hypothalamic–pituitary–adrenal axis activity, energy balance and body composition of rats | Autor: Hipólide DC, Suchecki D, Carvalho Pinto AP, Chiconelli Faria E, Tufik S, Luz J. | Revista: Journal of Neuroendocrinology
Sleep deprivation and sleepiness caused by sleep loss | Autor: Leibowitz SM, Lopes MC, Andersen ML, Kushida CA. | Revista: Sleep Medicine Clinics
Comparison of the sleep pattern throughout a protocol of chronic sleep restriction induced by two methods of paradoxical sleep deprivation | Autor: Machado RB, Suchecki D, Tufik S. | Revista: Brain Research Bulletin
A reassessment of the hyperphagia/weight-loss paradox during sleep deprivation | Autor: Martins PJF, D’Almeida V, Nobrega JN, Tufik S. | Revista: Sleep
Effects of sleep deprivation on the development of autoimmune disease in an experimental model of systemic lupus erythematosus | Autor: Palma BD, Gabriel A Jr, Colugnati FA, Tufik S. | Revista: American Journal os Physiology - Regulatory, Integrative and Comparative Physiology
Acute cocaine effects in paradoxical sleep deprived male rats | Autor: Andersen ML, Perry JC, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
The effects of dopaminergic agonists on genital reflexes in paradoxical sleep deprived male rats | Autor: Andersen ML, Tufik S. | Revista: Physiology & Behavior
Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats | Autor: Andersen ML, Martins PJF, D’Almeida V, Bignotto M, Tufik S. | Revista: Journal of Sleep Research
Effects of progesterone blockade over cocaine-induced genital reflexes of paradoxical sleep deprived male rats | Autor: Andersen ML, Tufik S. | Revista: Hormones and Behavior
Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation | Autor: Andersen ML, Papale LA, Hipolide DC, Nobrega JN, Tufik S. | Revista: Behavioural Brain Research
Noradrenergic system interacts with genital reflexes induced by cocaine in paradoxical sleep-deprived male rats | Autor: Andersen ML, Antunes IB, Tufik S. | Revista: Behavioral Neuroscience
Effects of paradoxical sleep deprivation and cocaine on genital reflexes in hyperlipidic-fed rats | Autor: Andersen ML, D'Almeida V, Martins PJF, Antunes HKM, Tufik S. | Revista: Pharmacology Biochemistry and Behavior
Does sleep deprivation interfere with sexual behavior in male rats? | Autor: Andersen ML, Tufik S. | Revista: World Federation of Sleep Research & Sleep Medicine Societies
Opposite effects of sleep rebound on orexin OX1R and OX2R receptor expression in rat brain | Autor: D'Almeida V, Hipólide DC, Raymond R, Barlow KB, Parkes JH, Pedrazzoli M, Tufik S, Nobrega J. | Revista: Molecular Brain Research
Learning deficits induced by sleep deprivation and recovery are not associated with altered [3H]muscimol and [3H]flunitrazepam binding | Autor: Dubiela FP, Oliveira MGM, Moreira KM, Nobrega JN, Tufik S, Hipolide DC. | Revista: Brain Research
Effects of paradoxical sleep deprivation on the performance of rats in a model of visual attention | Autor: Godoi FRL, Oliveira MGM, Tufik S. | Revista: Behavioural Brain Research
Distinct effects of sleep deprivation on binding to repinephrine and serotonin transporter in rat brain | Autor: Hipolide DC, Moreira KM, Barlow K, Wilson A, Nobrega JN, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Sleep homeostasis in rats assessed by a long-term intermittent paradoxical sleep deprivation protocol | Autor: Machado RB, Suchecki D, Tufik S. | Revista: Behavioural Brain Research
Age-related effects on genital reflexes induced by paradoxical sleep deprivation and cocaine in rats | Autor: Andersen ML, Bignotto M, Papale LA, Tufik S. | Revista: Experimental Gerontology
Hormone treatment facilitates penile erection in castrated rats after sleep deprivation and cocaine | Autor: Andersen ML, Bignotto M, Tufik S. | Revista: Journal of Neuroendocrinology
Cholinergic mechanisms in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats | Autor: Andersen ML, Papale LA, Tufik S. | Revista: Pharmacology Biochemistry and Behavior
Effects of paradoxical sleep deprivation on blood parameters associated with cardiovascular risk in aged rats | Autor: Andersen ML, Martins PJF, D’Almeida V, Santos RF, Bignotto M, Tufik S. | Revista: Experimental Gerontology
Inhibitory effect of GABAergic drugs in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats | Autor: Andersen ML, Tufik S. | Revista: Pharmacology Biochemistry and Behavior
Diurnal variation in the genital reflexes and hormone levels induced by paradoxical sleep deprivation and cocaine in male rats | Autor: Andersen ML, Papale LA, Tufik S. | Revista: Brain Research Bulletin
The effects of sleep deprivation and sleep recovery on pain thresholds of rats with chronic pain | Autor: Andersen ML, Kawakami R, Tufik S. | Revista: Hypnos
Effects of morphine or naloxone on cocaine-induced genital reflexes in paradoxical sleep deprived rats | Autor: Andersen ML, Frussa-Filho R, Tufik S | Revista: Pharmacology Biochemistry and Behavior
Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component | Autor: Frussa-Filho R, Gonçalves MTM, Andersen ML, Araujo NP, Chinen CC, Tufik S. | Revista: Brain Research
Sleep deprivation induced by the modified multiple platform technique: quantification of sleep loss and recovery | Autor: Machado RB, Hipolide DC, Benedito-Silva AA, Tufik S. | Revista: Brain Research
Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation | Autor: Pedrazzoli M, D’Almeida V, Martins PJF, Machado RB, Ling L, Nishino S, Tufik S, Mignot E. | Revista: Brain Research
Rapid eye movement sleep deprivation-induced down-regulation of beta-adrenergic receptors in the rat brainstem and hippocampus | Autor: Pedrazzoli M, Benedito MAC. | Revista: Pharmacology Biochemistry and Behavior
Rapid eye movement (REM) sleep deprivation induces a decrease in neuronal nuclear volume in the locus coeruleus, hippocampus and cingulated cortex of the rat | Autor: Pedrazzoli M, Benedito MAC | Revista: Hypnos
Role of hippocampal oxidative stress im memory déficits induced by sleep deprivation in mice | Autor: Silva RH, Abílio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, Medrano WA, Calzavara MB, Registro S, Andersen ML, Machado RB, Carvalho RC, Ribeiro RA, Tufik S, Frussa-Filho R. | Revista: Neuropharmacology
Anxiogenic effect of sleep deprivation in the elevated plus-maze test in mice | Autor: Silva RH, Kameda SR, Carvalho RC, Takatsu-Coleman AL, Niigaki ST, Abílio VC, Tufik S, Frussa-Filho R. | Revista: Psychopharmacology
Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice | Autor: Silva RH, Chehin A, Kameda S, Takatsu-Coleman A, Abílio VC, Tufik S, Frussa-Filho R. | Revista: Neurobiology of Learning and Memory
Effects of maternal separation on baseline sleep and cold stress-induced sleep rebound in adult Wistar rats | Autor: Tiba PA, Tufik S, Suchecki D. | Revista: Sleep
Selective serotonin 2A receptor antagonism attenuates the effects of amphetamine on arousal and dopamine overflow in non-human primates. | Autor: Murnane KS, Andersen ML, Rice KC, Howell LL. | Revista: J Sleep Resresumo
The objective of the present study was to further elucidate the mechanisms involved in the wake-promoting effects of psychomotorstimulants. Many previous studies have tightly linked the effects of stimulants to dopamine neurotransmission, and some studies indicate that serotonin 2A receptors modulate these effects. However, the role of dopamine in arousal is controversial, most notably because dopamine neurons do not change firing rates across arousal states. In the present study, we examined the wake-promoting effects of the dopaminereleaser amphetamine using non-invasive telemetric monitoring. These effects were evaluated in rhesus monkeys as a laboratory animal model with high translational relevance for human disorders of sleep and arousal. To evaluate the role of dopamine in the wake-promoting effects of amphetamine, we used in vivo microdialysis targeting the caudate nucleus, as this approach provides clearly interpretable measures of
presynaptic dopamine release. This is beneficial in the present context because some of the inconsistencies between previous studies examining the role of dopamine in arousal may be related to differences between postsynaptic dopamine receptors. We found that amphetamine significantly and dose-dependently increased arousal at doses that engendered higher extracellular dopamine levels. Moreover, antagonism of serotonin 2A receptors attenuated the effects of amphetamine on both wakefulness and dopamine overflow. These findings further elucidate the role of dopamine and serotonin 2A receptors in arousal, and they suggest that increased dopamine neurotransmission may be necessary for the wake-promoting effects of amphetamine, and possibly other stimulants.
O conhecimento da higiene do sono na menopausa. | Autor: Vigeta SMG, Ribeiro FMN, Hachul H, Tufik S, Haidar MA. | Revista: Rev APSresumo
Identificar o conhecimento sobre a Higiene do Sono em mulheres que frequentavam um ambulatório de climatério. Método: Os dados foram obtidos pelo preen¬chimento de questionário sobre a higiene do sono, por 72 mulheres na perimenopausa/pós-menopausa, sendo que 30 eram atendidas pelo ambulatório geral do climatério e 42 pelo ambulatório de “distúrbios do sono”. Foram realizadas análises estatísticas por frequência simples, diferenciando entre o conhecimento ou não da higiene do sono e com¬paração entre os subgrupos pelo qui-quadrado. Resultados: No grupo total de mulheres, foi identificado que 79,2% delas não conheciam a expressão higiene do sono, apesar de, muitas vezes, reconhecerem as medidas que induzem a um sono adequado. Conclusão: O artigo sugere a impor¬tância da assistência dos profissionais de saúde durante a fase de transição menopáusica e pós-menopausa no que se refere à promoção de conhecimento sobre a importância da qualidade do sono.
Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients? | Autor: Alves ES, Ackel-D'Elia C, Luz GP, Cunha TCA, Carneiro G, Tufik S, Bittencourt LRA, De Mello MT | Revista: Sleep Breath. | Site: http://www.ncbi.nlm.nih.gov/pubmed/22760814resumo
INTRODUCTION Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic–pituitary–adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which
predispose an individual to vascular damage.
DISCUSSION Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6,which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, andmood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.
Effects of methamphetamine self-administration on actigraphy-based sleep parameters in monkeys. | Autor: Andersen ML, Diaz MP, Murnane KS, Howell LL. | Revista: Psychopharmacologyresumo
RATIONALE: Sleep disorders and substance abuse are highly comorbid. Although methamphetamine is a very commonly abused drug, to the best of our knowledge, no study has evaluated its effects on sleep during drug use and abstinence under well-controlled conditions in laboratory animals.
OBJECTIVES: The objective of this study was to examine the effects of methamphetamine self-administration on sleep-like measures in nonhuman primates.
METHODS: Adult male rhesus monkeys (Macaca mulatta; n = 4) self-administered methamphetamine (0.01 and 0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week) for 5 weeks. Sleep-like measures were evaluated with Actiwatch monitors before, during, and after each period of drug self-administration.
RESULTS: Both doses of methamphetamine reliably maintained self-administration. Methamphetamine (0.03 mg/kg) increased derived measures of latency to sleep onset and sleep fragmentation, and decreased sleep efficiency compared to abstinence, and higher methamphetamine intake predicted worse sleep quality. However, sleep normalized immediately after the discontinuation of methamphetamine self-administration.
CONCLUSIONS: Methamphetamine markedly disrupted sleep-like measures; however, methamphetamine self-administration did not disrupt sleep quality during subsequent periods of drug abstinence.
Short sleep and obesity: other factors to be considered | Autor: Barros LMA, Kim LJ, Tufik S, Andersen ML | Revista: Sleep Med
Microinjection of Melanin Concentrating Hormone into the lateral preoptic area promotes non-REM sleep in the rat | Autor: Benedetto L, Rodriguez-Servetti Z,Lagos P, D'Almeida V, Monti JM, Torterolo P | Revista: Peptides.resumo
The ventrolateral preoptic area (VLPO) has been recognized as one of the key structures responsible for the generation of non-REM (NREM) sleep. The melanin-concentrating hormone (MCH)-containing neurons, which are located in the lateral hypothalamus and incerto-hypothalamic area, project widely throughout the central nervous system and include projections to the VLPO. The MCH has been associated with the central regulation of feeding and energy homeostasis. In addition, recent findings strongly suggest that the MCHergic system promotes sleep. The aim of the present study was to determine if MCH generates sleep by regulating VLPO neuronal activity. To this purpose, we characterized the effect of unilateral and bilateral microinjections of MCH into the VLPO on sleep and wakefulness in the rat. Unilateral administration of MCH into the VLPO and adjacent dorsal preoptic area did not modify sleep. On the contrary, bilateral microinjections of MCH (100 ng) into these areas significantly increased light sleep (LS, 39.2±4.8 vs. 21.6±2.5 min, P<0.05) and total NREM sleep (142.4±23.2 vs. 86.5±10.5 min, P<0.05) compared to control (saline) microinjections. No effect was observed on REM sleep. We conclude that MCH administration into the VLPO and adjacent dorsal lateral preoptic area promotes the generation of NREM sleep.
Expanding investigations on the relationship between sleep restriction and energy balance | Autor: Bennedsen L, Tufik S, Andersen ML | Revista: Am J Clin Nutrition
Effects of acute systemic administration of cannabidiol on sleep-wake cycle in rats. | Autor: Chagas MHN, Crippa JAS, Zuardi AW, Hallak JEC, Machado-de-Sousa JP, Hirotsu C, Maia L, Tufik S, Andersen ML | Revista: J Psychopharmacolresumo
Cannabidiol (CBD) is one of the main components of Cannabis sativa and has a wide spectrum of action, including effects in the sleep-wake cycle.
OBJECTIVE: The objective of this paper is to assess the effects on sleep of acute systemic administration of CBD.
METHOD: Adult male Wistar rats were randomly distributed into four groups that received intraperitoneal injections of CBD 2.5 mg/kg, CBD 10 mg/kg, CBD 40 mg/kg or vehicle (n=seven animals/group). Sleep recordings were made during light and dark periods for four days: two days of baseline recording, one day of drug administration (test), and one day after drug (post-test).
RESULTS: During the light period of the test day, the total percentage of sleep significantly increased in the groups treated with 10 and 40 mg/kg of CBD compared to placebo. REM sleep latency increased in the group injected with CBD 40 mg/kg and was significantly decreased with the dose of 10 mg/kg on the post-test day. There was an increase in the time of SWS in the group treated with CBD 40 mg/kg, although this result did not reach statistical significance.
CONCLUSION: The systemic acute administration of CBD appears to increase total sleep time, in addition to increasing sleep latency in the light period of the day of administration.
Short sleep time increases lipid intake in obese adolescents. | Autor: Corgosinho FC, Dâmaso AR, Ganen AP, Campos RMS, Silva PL, Sanchez PL, Ackel-D’Elia C, Carnier J, Tock L, Andersen ML, Tufik S, De Mello MT. | Revista: Sleep Sci.
Drug-induced sleepiness and insomnia: an update. | Autor: Gonçalves R, Togeiro SMG. | Revista: Sleep Sci.
A population-based survey on the influence of the menstrual cycle and the use of hormonal contraceptives on sleep patterns in São Paulo, Brazil | Autor: Hachul H, Andersen ML, Bittencourt LR, Santos-Silva R, Tufik S | Revista: Int J Gynecol Obstetrresumo
OBJECTIVE: To investigate the effects of the phases of the menstrual cycle and the use of hormonal contraception on sleep patterns in a population-based study.
METHODS: In a prospective study carried out among premenopausal women between July and December 2007, a 3-stage cluster sampling was used to ensure accurate representation of the general population of São Paulo, Brazil. Questionnaires were administered, hormonal assays were performed, and full-night polysomnography was recorded.
RESULTS: The study sample included 297 premenopausal women. Women in the follicular phase complained of fatigue more than those in the luteal phase and those using hormonal contraceptive treatment. Premenopausal women using hormonal contraceptives had a significantly lower apnea-hypopnea index (1.1 ± 2.0) compared with women in both the follicular (2.2 ± 4.5) and the luteal (2.9 ± 5.4) phases (P=0.01). Women taking hormonal contraceptives tended to have increased sleep efficiency compared with women in either the follicular or luteal phases.
CONCLUSION: The use of hormonal contraceptives was associated with a lower apnea-hypopnea index and a trend toward improved sleep efficiency. The current findings suggest that the use of hormonal contraceptives has a stronger association with sleep duration compared with menstrual cycle phase.
Clinical and Polysomnographic Findings of Patients with Large Goiters | Autor: Haddad L, Haddad FLM, Bittencourt LRA, Gregorio LC, Tufik S, Abrahão M. | Revista: Sleep Breath.resumo
INTRODUCTION: Goiters cause a series of compressive symptoms, including dyspnea and dysphagia. There have been reports of the coexistence of this syndrome with obstructive sleep apnea (OSA). The objective of this study was to evaluate the prevalence of OSA in a group of patients with goiters.
METHODS: Twenty-four patients with a mean age of 52.7 ± 12.7 years, including five males (20.8 %) and 19 (79.2 %) females, who were diagnosed with euthyroid goiters with volumes exceeding 100 ml were consecutively selected. The protocol consisted of sleep questionnaires, physical examinations, and baseline polysomnography measurements. Patients were divided into two groups, OSA and NOSA (no OSA), and all findings were compared between the two groups.
RESULTS: Of the studied patients, 70.8 % had OSA (p = 0.004). Regarding clinical parameters, age (p = 0.001), Epworth Sleepiness Scale scores (p = 0.039) and complaints of habitual snoring (p < 0.001) had higher values in the OSA group. Regarding physical examination parameters, body mass index (p = 0.012), neck circumference (p = 0.009) and the presence of tracheal compression (p = 0.021) had higher values in the OSA group. The polysomnographic parameters that were significantly different between the two groups were the greater apnea and hypopnea index per hour of sleep (p < 0.001) and the lower minimum oxyhemoglobin saturation in the OSA group (p = 0.011).
CONCLUSIONS: There is a high prevalence of OSA in patients with goiters. The main findings that were associated with the presence of OSA are known clinical predictors of OSA and the presence of tracheal compression.
Another view of phenotypic evaluation in obstructive sleep apnea | Autor: Kim L, Barros LA, Tufik S, Andersen ML | Revista: J Appl Physiol
Can high altitude influence cytokines and sleep? | Autor: Lemos VA, Santos RVT, Lira FS, Rodrigues B, Tufik S, De Mello MT. | Revista: Mediators Inflammresumo
The number of persons who relocate to regions of high altitude for work, pleasure, sport, or residence increases every year. It is known that the reduced supply of oxygen (O2) induced by acute or chronic increases in altitude stimulates the body to adapt to new metabolic challenges imposed by hypoxia. Sleep can suffer partial fragmentation because of the exposure to high altitudes, and these changes have been described as one of the responsible factors for the many consequences at high altitudes. We conducted a review of the literature during the period from 1987 to 2012. This work explored the relationships among inflammation, hypoxia and sleep in the period of adaptation and examined a novel mechanism that might explain the harmful effects of altitude on sleep, involving increased Interleukin-1 beta (IL-1 β ), Interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF- α ) production from several tissues and cells, such as leukocytes and cells from skeletal muscle and brain.
Does menopause influence nocturnal awakening with headache? | Autor: Lucchesi LM, Hachul H, Yagihara F, Santos-Silva R, Tufik S, Bittencourt L | Revista: Climactericresumo
OBJECTIVE: The aim of the present study was to assess whether menopausal status influences the occurrence of nocturnal awakening with headache (NAH) in the female population of Sao Paulo, Brazil. We also examined the relationship of this complaint to sociodemographic determinants, hot flushes, sleep quality and parameters, anxiety and depressive symptoms, somnolence and fatigue according to menopausal status.
METHODS: The female population of the Sao Paulo Epidemiologic Sleep Study (EPISONO) (n = 576) was divided according to menopausal status (pre-, peri-, early and late menopause) based on questionnaires and hormonal blood measures. The complaint of waking up because of a headache at least once a week was assessed by the UNIFESP Sleep questionnaire. Additionally, hot flushes, sleep complaints, anxiety and depressive symptoms, somnolence and fatigue were assessed by specific questionnaires. A full-night polysomnography assessed sleep parameters.
RESULTS: The prevalence of NAH in women in the Sao Paulo population was 13.3%. Perimenopause was associated with a higher risk of having NAH (odds ratio 13.9; 95% confidence interval 4.3-45.2). More complaints of NAH were observed in obese women. All the groups with NAH showed more hot flushes, worse subjective sleep quality, more complaints of insomnia, anxiety symptoms and fatigue.
CONCLUSIONS: We observed a constellation of symptoms in women according to menopausal status and NAH that included hot flushes, sleep complaints, more anxiety symptoms and fatigue. Moreover, some of these symptoms were more frequent in perimenopausal women with NAH. Therefore, we concluded that menopausal status influences NAH and the women in perimenopause presented a high risk of having this complaint.
Agreement in the scoring of respiratory events and sleep among international sleep centers. | Autor: Magalang UJ, Chen NH, Cistulli PA, Fedson AC, Gíslason T, Hillman D, Penzel T, Tamisier R, Tufik S, Phillips G, Pack AI; SAGIC Investigators. | Revista: Sleep.resumo
STUDY OBJECTIVES: The American Academy of Sleep Medicine (AASM) guidelines for polysomnography (PSG) scoring are increasingly being adopted worldwide, but the agreement among international centers in scoring respiratory events and sleep stages using these guidelines is unknown. We sought to determine the interrater agreement of PSG scoring among international sleep centers.
DESIGN: Prospective study of interrater agreement of PSG scoring.
SETTING: Nine center-members of the Sleep Apnea Genetics International Consortium (SAGIC).
MEASUREMENTS AND RESULTS: Fifteen previously recorded deidentified PSGs, in European Data Format, were scored by an experienced technologist at each site after they were imported into the locally used analysis software. Each 30-sec epoch was manually scored for sleep stage, arousals, apneas, and hypopneas using the AASM recommended criteria. The computer-derived oxygen desaturation index (ODI) was also recorded. The primary outcome for analysis was the intraclass correlation coefficient (ICC) of the apnea-hypopnea index (AHI). The ICCs of the respiratory variables were: AHI = 0.95 (95% confidence interval: 0.91-0.98), total apneas = 0.77 (0.56-0.87), total hypopneas = 0.80 (0.66-0.91), and ODI = 0.97 (0.93-0.99). The kappa statistics for sleep stages were: wake = 0.78 (0.77-0.79), nonrapid eye movement = 0.77 (0.76-0.78), N1 = 0.31 (0.30-0.32), N2 = 0.60 (0.59-0.61), N3 = 0.67 (0.65-0.69), and rapid eye movement = 0.78 (0.77-0.79). The ICC of the arousal index was 0.68 (0.50-0.85).
CONCLUSION: There is strong agreement in the scoring of respiratory events among the SAGIC centers. There is also substantial epoch-by-epoch agreement in scoring sleep variables. Our results suggest that centralized scoring of PSGs may not be necessary in future research collaboration among international sites where experienced, well-trained scorers are involved.
The human leucocyte antigen DQB1*0602 allele is associated with electroencephelograph differences in individuals with obstructive sleep apnoea syndrome | Autor: Manzotte T, Guindalini C, Mazzotti DR, Palombini L, de Souza AL, Poyares D, Bittencourt LR, Tufik S | Revista: J Sleep Res.resumo
Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety-four individuals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602 allele-positive and -negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele-positive individuals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with individuals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in individuals without OSAS. The data highlight the HLA-DQB1*0602 as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS.
Sleep and epilepsy: exploring an intriguing relationship with a translational approach | Autor: Matos G, Tufik S, Scorza F, Cavalheiro EA, Andersen ML. | Revista: Epilepsy & Behaviorresumo
The relationship between sleep and epilepsy has been well established. There is a high prevalence of sleep disturbances in epilepsy, which are associated with a decreased quality of life of individuals with epilepsy. In view of this fact, preclinical research is necessary to address many gaps in knowledge. For instance, it is well known that sleep deprivation can trigger seizures; however, this is a complex pathophysiological event. In this context, there are many valuable animal models of epilepsy that reproduce clinical symptoms and can be used. Investigations using animal models that simulate clinical epilepsy are imperative. Furthermore, preclinical studies that reveal mechanisms related to sleep-epilepsy interactions are very important. Results of such studies can, in turn, improve the understanding of epilepsy itself and can be useful in developing new antiepileptic drugs and preventive measures to control seizures. Preclinical research should be performed using a translational framework with experimental designs that can lead to advances in the quality of life of individuals with epilepsy. In view of the fact that more than 50 million of people are affected by epilepsy around the world, understanding the relationship between sleep and epilepsy is imperative.
Doctors, have you ever heard about sleep disturbance, erectile dysfunction and epilepsy? | Autor: Matos G, Tufik S, Scorza FA, Cavalheiro EA, Andersen ML | Revista: Epilepsy & Behavior
Association between body mass index and sleep duration assessed by objective methods in a representative sample of the adult population | Autor: Moraes W, Poyares D, Zalcman I, de Mello MT, Bittencourt LR, Santos-Silva R, Tufik S | Revista: Sleep Medresumo
INTRODUCTION: Sleep duration has been associated with overweight individuals in many epidemiological studies; however, few studies have assessed sleep using objective methods. Our study was designed to evaluate the association between body mass index (BMI) and sleep duration measured by actigraphy (Acti), polysomnography (PSG) and the Pittsburgh sleep quality index questionnaire (PSQIO). Furthermore, we evaluated other biochemical and polysomnographic parameters.
METHODS: A representative sample of 1042 individuals from Sao Paulo, Brazil, including both genders (20-80 yrs), participated in our protocol. Weight and other anthropometric parameters were measured at the onset of the study. Sleep duration was calculated by Acti, PSG, and the PSQIQ. The population was sorted by sleep duration, body, slow wave sleep (SWS) and REM sleep (REMS) duration subsets. In addition, other biochemical and polysomnographic parameters were analyzed. Differences between population subsets were analyzed by one-way analysis of variance (ANOVA). Linear regression analysis was performed between sleep and anthropometric parameters.
RESULTS: Shorter sleep duration was associated with higher BMI and waist and neck circumference when measured by Acti and PSG (p<0.05). Lower leptin levels were associated with short sleep in normal-weight (BMI>18 and ⩽25) individuals (p<0.01). The association between short sleep duration Acti and higher BMI was present when apnea-hypopnea index (AHI) was less than 15 (p=0.049). Shorter REMS and SWS also were associated with higher BMI (p<0.01). Normal-weight individuals tended to sleep longer, have higher sleep efficiency and longer SWS and REMS than obese individuals (Acti, PSG; p=0.05). Sleep duration was negatively correlated with BMI (Acti, PSG; p<0.05). Short SWS and REMS were associated with higher cardiovascular risk factors (p<0.05).
CONCLUSION: Shorter sleep, SWS, and REMS duration were associated with higher BMI, central adiposity measurements, and cardiovascular risk factors when measured by objective methods.
Altered sleep regulation in a mouse model of SCN1A-derived genetic epilepsy with febrile seizures plus (GEFS+) | Autor: Papale LA, Makinson CD, Christopher Ehlen J, Tufik S, Decker MJ, Paul KN, Escayg A | Revista: Epilepsia.resumo
PURPOSE: Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A are responsible for a number of epilepsy disorders, including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. In addition to seizures, patients with SCN1A mutations often experience sleep abnormalities, suggesting that SCN1A may also play a role in the neuronal pathways involved in the regulation of sleep. However, to date, a role for SCN1A in the regulation of sleep architecture has not been directly examined. To fill this gap, we tested the hypothesis that SCN1A contributes to the regulation of sleep architecture, and by extension, that SCN1A dysfunction contributes to the sleep abnormalities observed in patients with SCN1A mutations.
METHODS: Using immunohistochemistry we first examined the expression of mouse Scn1a in regions of the mouse brain that are known to be involved in seizure generation and sleep regulation. Next, we performed detailed analysis of sleep and wake electroencephalography (EEG) patterns during 48 continuous hours of baseline recordings in a knock-in mouse line that expresses the human SCN1A GEFS+ mutation R1648H (RH mutants). We also characterized the sleep-wake pattern following 6 h of sleep deprivation.
KEY FINDINGS: Immunohistochemistry revealed broad expression of Scn1a in the neocortex, hippocampus, hypothalamus, thalamic reticular nuclei, dorsal raphe nuclei, pedunculopontine, and laterodorsal tegmental nuclei. Co-localization between Scn1a immunoreactivity and critical cell types within these regions was also observed. EEG analysis under baseline conditions revealed increased wakefulness and reduced non-rapid eye movement (NREM) and rapid eye movement (REM) sleep amounts during the dark phase in the RH mutants, suggesting a sleep deficit. Nevertheless, the mutants exhibited levels of NREM and REM sleep that were generally similar to wild-type littermates during the recovery period following 6 h of sleep deprivation.
SIGNIFICANCE: These results establish a direct role for SCN1A in the regulation of sleep and suggest that patients with SCN1A mutations may experience chronic alterations in sleep, potentially leading to negative outcomes over time. In addition, the expression of Scn1a in specific cell types/brain regions that are known to play critical roles in seizure generation and sleep now provides a mechanistic basis for the clinical features (seizures and sleep abnormalities) associated with human SCN1A mutations.
Is portable monitoring for diagnosing obstructive sleep apnea syndrome suitable in elderly population? | Autor: Polese JF, Santos-Silva R, de Oliveira Ferrari PM, Sartori DE, Tufik S, Bittencourt L | Revista: Sleep Breath.resumo
PURPOSE: Obstructive sleep apnea syndrome (OSAS) is highly prevalent in the elderly. Unattended, at-home portable monitoring (PM) is a diagnostic alternative to polysomnography in adults with high clinical probability of OSAS. However, no studies have evaluated the diagnostic accuracy of PM in elderly population. The aim of our study was to evaluate the effectiveness of PM in elderly patients.
METHODS: We selected patients aged over 65 years with suspected OSAS. Two-order randomized evaluations were performed: one night of at-home PM (PMhome) and one night of simultaneous PM and polysomnography (PSG) in the sleep lab (PSG+PM). We obtained three different apnea-hypopnea index (AHI): AHI from PSG (AHI PSG), AHI from at-home PM (AHI PMhome), and AHI from PM+PSG (AHI PM+PSG). Two technicians, blinded to the recording order, scored each sleep study.
RESULTS: We studied a total of 43 patients. No difference between the AHI values for each of the different recordings was found (p > 0.05). There was good correlation between AHI PSG and AHI PMhome (r = 0.67) and AHI PSG+PM (r = 0.84). The area under the receiver operator curve was above 0.83, indicating good sensitivity and a positive predictive value for AHI with cutoffs of 5, 15, and 30 and good specificity and negative predictive value for AHI values above 15. Correlation, accuracy, and agreement were greater when the recordings were made simultaneously.
CONCLUSIONS: PM was effective for diagnosing OSAS in the elderly and can be used as an alternative to PSG in elderly patients with a high clinical probability of OSAS.
Obesity, dyslipidemia and sleep disorders: complexity requires complementary analysis | Autor: Polesel D, Nozoe K, Decleva D, Tufik S, Andersen ML | Revista: Chest
The impact of sleep duration in obstructive sleep apnea patients. | Autor: Risso TT, Poyares D, Rizzi CF, Pulz C, Guilleminault C, Tufik S, de Paola AA, Cintra F | Revista: Sleep Breath.
Does obstructive sleep apnea impair the cardiopulmonary response to exercise? | Autor: Rizzi CF, Cintra F, Mello-Fujita L, Rios LF, Mendonça ET, Feres MC, Tufik S,Poyares D. | Revista: Sleepresumo
STUDY OBJECTIVES: The aim of this study was to evaluate cardiopulmonary exercise performance in lean and obese patients with obstructive sleep apnea (OSA) compared with controls.
DESIGN: Case-control study.
SETTING: The study was carried out in Sao Paulo Sleep Institute, Sao Paulo, Brazil.
PATIENTS AND PARTICIPANTS:
INDIVIDUALS WITH SIMILAR AGES WERE ALLOCATED INTO GROUPS: 22 to the lean OSA group, 36 to the lean control group, 31 to the obese OSA group, and 26 to the obese control group.
INTERVENTIONS: The participants underwent a clinical evaluation, polysomnography, a maximum limited symptom cardiopulmonary exercise test, two-dimensional transthoracic echocardiography, and spirometry.
MEASUREMENTS AND RESULTS: The apnea-hypopnea index, arousal index, lowest arterial oxygen saturation (SaO2) and time of SaO2 < 90% were different among the groups. There were differences in functional capacity based on the following variables: maximal oxygen uptake (VO2max), P < 0.01 and maximal carbon dioxide production (VCO2max), P < 0.01. The obese patients with OSA and obese controls presented significantly lower VO2max and VCO2max values. However, the respiratory exchange ratio (RER) and anaerobic threshold (AT) did not differ between groups. Peak diastolic blood pressure (BP) was higher among the obese patients with OSA but was not accompanied by changes in peak systolic BP and heart rate (HR). When multiple regression was performed, body mass index (P < 0.001) and male sex in conjunction with diabetes (P < 0.001) independently predicted VO2max (mL/kg/min).
CONCLUSIONS: The results of this study suggest that obesity alone and sex, when associated with diabetes but not OSA, influenced exercise cardiorespiratory function.
Cognition and biomarkers of oxidative stress in obstructive sleep apnea. | Autor: Sales LV, De Bruin VMS, D’Almeida V, Pompéia S, Bueno OF, Tufik S, Bittencourt LR. | Revista: Clinicsresumo
OBJECTIVES: The aim of this study was to investigate neuropsychological performance and biomarkers of oxidative stress in patients with obstructive sleep apnea and the relationships between these factors.
METHODS: This was an observational, cross-sectional study of 14 patients (36.0±6.5 years old) with obstructive sleep apnea and 13 controls (37.3±6.9 years old). All of the participants were clinically evaluated and underwent full-night polysomnography as well as neuropsychological tests. Blood samples were used to assay superoxide dismutase, catalase, glutathione and homocysteine, as well as vitamins E, C, B11 and B12.
RESULTS: The patients performed poorly relative to the controls on several neuropsychological tests, such as the attention test and tests of long-term memory and working memory/executive function. They also had lower levels of vitamin E (p<0.006), superoxide dismutase (p<0.001) and vitamin B11 (p<0.001), as well as higher concentrations of homocysteine (p<0.02). Serum concentrations of vitamin C, catalase, glutathione and vitamin B12 were unaltered. Vitamin E levels were related to performance in the backward digit span task (F = 15.9; p = 0.002) and this correlation remained after controlling for age and body mass index (F = 6.3, p = 0.01). A relationship between superoxide dismutase concentrations and executive non-perseveration errors in the Wisconsin Card Sorting Test (F = 7.9; p = 0.01) was also observed.
CONCLUSIONS: Decreased levels of antioxidants and lower performance on the neuropsychological tasks were observed in patients with obstructive sleep apnea. This study suggests that an imbalance between antioxidants and pro-oxidants may contribute to neuropsychological alterations in this patient population.
Passive body heating improves the sleep pattern in women patients with fibromyalgia. | Autor: Silva A, Queiroz SS, Andersen ML, Mônico-Neto M, Campos RMS, Roizenblatt S, Tufik S, Mello MT | Revista: Clinicsresumo
OBJECTIVE: To assess the effect of passive body heating on the sleep patterns of patients with fibromyalgia.
METHODS: Six menopausal women diagnosed with fibromyalgia according to the criteria determined by the American College of Rheumatology were included. All women underwent passive immersion in a warm bath at a temperature of 36 ±1 °C for 15 sessions of 30 minutes each over a period of three weeks. Their sleep patterns were assessed by polysomnography at the following time-points: pre-intervention (baseline), the first day of the intervention (acute), the last day of the intervention (chronic), and three weeks after the end of the intervention (follow-up). Core body temperature was evaluated by a thermistor pill during the baseline, acute, chronic, and follow-up periods. The impact of this treatment on fibromyalgia was assessed via a specific questionnaire termed the Fibromyalgia Impact Questionnaire.
RESULTS: Sleep latency, rapid eye movement sleep latency and slow wave sleep were significantly reduced in the chronic and acute conditions compared with baseline. Sleep efficiency was significantly increased during the chronic condition, and the awakening index was reduced at the chronic and follow-up time points relative to the baseline values. No significant differences were observed in total sleep time, time in sleep stages 1 or 2 or rapid eye movement sleep percentage. The core body temperature and Fibromyalgia Impact Questionnaire responses did not significantly change over the course of the study.
CONCLUSION: Passive body heating had a positive effect on the sleep patterns of women with fibromyalgia.
Consequences of Obstructive Sleep Apnea on metabolic profile: a population-based survey | Autor: Togeiro SM, Carneiro G, Filho FF, Zanella MT, Santos-Silva R, Taddei JA, Bittencourt LR, Tufik S | Revista: Obesityresumo
OBJECTIVE: Epidemiologic studies that control for potential confounders are needed to assess the independent associations of obstructive sleep apnea (OSA) with metabolic abnormalities. The aim of our study was to evaluate the associations of OSA with metabolic abnormalities among the adult population of Sao Paulo, Brazil.
DESIGN AND METHODS: Questionnaires were applied face-to-face, full night polysomnography (PSG) was performed, and blood samples were collected in a population-based survey in Sao Paulo, Brazil, adopting a probabilistic three-stage cluster sample method. The metabolic profile included fasting glucose, insulin, and lipid levels. The hepatic insulin resistance index was assessed by the homeostasis model assessment-estimated insulin resistance (HOMAIR ).
RESULTS: A total of 1,042 volunteers underwent PSG. Mild OSA and moderate to severe OSA comprised 21.2% and 16.7% of the population, respectively. Subjects with severe to moderate OSA were older, more obese, had higher fasting glucose, HOMAIR , and triglycerides (TG) levels than did the mild and non-OSA group (P < 0.001). Multivariate regression analyses showed that an apnea-hypopnea index (AHI) ≥ 15 and a time of oxy-hemoglobin saturation <90% were independently associated with impaired fasting glucose, elevated TG, and HOMAIR .
CONCLUSIONS: The results of this large cross-sectional epidemiological study showed that the associations of OSA and metabolic abnormalities were independent of other risk factors.
Potential role of sleep in bipolar disorder | Autor: Tufik SB, Bennedsen L, Andersen ML, Tufik S | Revista: J Psychiatr Res
The interaction of Sjögren's syndrome, gastroesophagel reflux and sleep | Autor: Tufik SB, Bennedsen L, Andersen ML, Tufik S | Revista: Sleep Med
Subjective, anatomical and functional nasal evaluation of patients with Obstructive Sleep Apnea Syndrome | Autor: Vidigal TA, Haddad FM, Gregório LC, Poyares D, Tufik S, Bittencourt LRA | Revista: Sleep Breath.resumo
BACKGROUND: Studies have shown a high occurrence of nasal alterations in patients with obstructive sleep apnea syndrome (OSAS), but no studies have used different methods to evaluate the nose of patients with OSAS. The objective of this study was to evaluate the nose of patients with OSAS, compare them to controls, and correlate the different methods used to evaluate the nose.
METHODS: Forty-seven patients with moderate/severe OSAS and 20 controls who were matched for gender, age, and body mass index were included. Questionnaires regarding sleep and nasal symptoms, physical examination, rhinoscopy, nasofibroscopy, nasal inspiratory peak flow (NIPF), and acoustic rhinometry (AR) measurements were performed.
RESULTS: In the OSAS group, 33 (70.2%) were male, with a mean age of 53.2 ± 9.1 years. In the control group, 13 (65%) were male, with a mean age of 53.7 ± 9.7 years. The OSAS group had a higher score on the nasal symptoms scale (p < 0.01) and a higher frequency of nasal alterations [presence of septal deviation, clinical complaints (p = 0.01) and hypertrophy of the inferior nasal turbinate (p < 0.01)]. The NIPF and AR parameters could not differentiate between the OSAS and control groups. There were no significant correlations among the different methods used to evaluate the nose. Lower NIPF values were capable of predicting higher apnea-hypopnea index scores (p = 0.007).
CONCLUSION: Clinical complaints and nasal alterations as measured by rhinoscopy and nasofibroscopy were associated with the presence of OSAS, which was not the case for the NIPF and AR parameters. The results of different evaluation methods were not correlated with each other.
Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task | Autor: Zanin K, Patti C, Sanday L, Fernandes-Santos L, Oliveira L, Poyares D, Tufik S, Frussa-Filho R | Revista: Psychopharmacologyresumo
RATIONALE: Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent.
OBJECTIVES: We examined the effects of acute doses of Zolp (2, 5, or 10 mg/kg, i.p.) on memory formation (learning, consolidation, and retrieval) using the plus-maze discriminative avoidance task.
METHODS: Mice were acutely treated with Zolp 30 min before training or testing. In addition, the effects of Zolp and midazolam (Mid; a classic benzodiazepine) on consolidation at different time points were examined. The possible role of state dependency was investigated using combined pre-training and pre-test treatments.
RESULTS: Zolp produced a dose-dependent sedative effect, without modifying anxiety-like behavior. The pre-training administration of 5 or 10 mg/kg resulted in retention deficits. When administered immediately after training or before testing, memory was preserved. Zolp post-training administration (2 or 3 h) impaired subsequent memory. There was no participation of state dependency phenomenon in the amnestic effects of Zolp. Similar to Zolp, Mid impaired memory consolidation when administered 1 h after training.
CONCLUSIONS: Amnestic effects occurred when Zolp was administered either before or 2-3 h after training. These memory deficits are not related to state dependency. Moreover, Zolp did not impair memory retrieval. Notably, the memory-impairing effects of Zolp are similar to those of Mid, with the exception of the time point at which the drug can modify consolidation. Finally, the memory effects were unrelated to sedation or anxiolysis.
Sleep and epilepsy: Exploring an intriguing relationship with a translational approach. | Autor: Matos G, Tufik S, Scorza FA, Cavalheiro EA, Andersen ML. | Revista: Epilepsy Behav | Site: http://dx.doi.org/10.1016/j.yebeh.2012.12.003resumo
The relationship between sleep and epilepsy has been well established. There is a high prevalence of sleep disturbances in epilepsy, which are associated with a decreased quality of life of individuals with epilepsy. In view of this fact, preclinical research is necessary to address many gaps in knowledge. For instance, it is well known that sleep deprivation can trigger seizures; however, this is a complex pathophysiological event. In this context, there are many valuable animal models of epilepsy that reproduce clinical symptoms and can be used. Investigations using animal models that simulate clinical epilepsy are imperative. Furthermore, preclinical studies that reveal mechanisms related to sleep–epilepsy interactions are very important. Results of such studies can, in turn, improve the understanding of epilepsy itself and can be useful in developing new antiepileptic drugs and preventive measures to control seizures. Preclinical research should be performed using a translational framework with experimental designs that can lead to advances in the quality of life of individuals with epilepsy. In view of the fact that more than 50 million of people are affected by epilepsy around the world, understanding the relationship between sleep and epilepsy is imperative.
Passive body heating improves sleep patterns in female patients with fibromyalgia. | Autor: Silva A, Queiroz SS, Andersen ML, Mônico-Neto M, Campos RMS, Roizenblatt S, Tufik S, De Mello MT. | Revista: Clinicsresumo
OBJECTIVE: To assess the effect of passive body heating on the sleep patterns of patients with fibromyalgia. METHODS: Six menopausal women diagnosed with fibromyalgia according to the criteria determined by the American College of Rheumatology were included. All women underwent passive immersion in a warm bath at a temperature of 36¡1°C for 15 sessions of 30 minutes each over a period of three weeks. Their sleep patterns were assessed by polysomnography at the following time-points: pre-intervention (baseline), the first day of the intervention (acute), the last day of the intervention (chronic), and three weeks after the end of the intervention (follow-up). Core body temperature was evaluated by a thermistor pill during the baseline, acute, chronic, and follow-up periods. The impact of this treatment on fibromyalgia was assessed via a specific questionnaire termed the Fibromyalgia Impact Questionnaire.
RESULTS: Sleep latency, rapid eye movement sleep latency and slow wave sleep were significantly reduced in the chronic and acute conditions compared with baseline. Sleep efficiency was significantly increased during the chronic condition, and the awakening index was reduced at the chronic and follow-up time points relative to the baseline values. No significant differences were observed in total sleep time, time in sleep stages 1 or 2 or rapid eye movement sleep percentage. The core body temperature and Fibromyalgia Impact Questionnaire responses did not significantly change over the course of the study.
CONCLUSION: Passive body heating had a positive effect on the sleep patterns of women with fibromyalgia.
Association between body mass index and sleep duration assessed by objective methods in a representative sample of the adult population. | Autor: Moraes W, Poyares D, Zalcman I, De Mello MT, Bittencourt LR, Santos-Silva R, Tufik S. | Revista: Sleep Medresumo
Introduction: Sleep duration has been associated with overweight individuals in many epidemiological studies; however, few studies have assessed sleep using objective methods. Our study was designed to evaluate the association between body mass index (BMI) and sleep duration measured by actigraphy (Acti), polysomnography (PSG) and the Pittsburgh Sleep Quality Index questionnaire (PSQIO). Furthermore, we evaluated other biochemical and polysomnographic parameters.
Methods: A representative sample of 1042 individuals from Sao Paulo, Brazil, including both genders (20–80 yrs), participated in our protocol. Weight and other anthropometric parameters were measured at the onset of the study. Sleep duration was calculated by Acti, PSG, and the PSQIQ. The population was sorted by sleep duration, body, slow wave sleep (SWS) and REM sleep (REMS) duration subsets. In addition, other biochemical and polysomnographic parameters were analyzed. Differences between population subsets were analyzed by one-way analysis of variance (ANOVA). Linear regression analysis was performed between sleep and anthropometric parameters.
Results: Shorter sleep duration was associated with higher BMI and waist and neck circumference when measured by Acti and PSG (p < 0.05). Lower leptin levels were associated with short sleep in normalweight (BMI > 18 and 625) individuals (p < 0.01). The association between short sleep duration Acti and higher BMI was present when apnea-hypopnea index (AHI) was less than 15 (p = 0.049). Shorter REMS and SWS also were associated with higher BMI (p < 0.01). Normal-weight individuals tended to sleep longer, have higher sleep efficiency and longer SWS and REMS than obese individuals (Acti, PSG; p = 0.05). Sleep duration was negatively correlated with BMI (Acti, PSG; p < 0.05). Short SWS and REMS were associated with higher cardiovascular risk factors (p < 0.05).
Conclusion: Shorter sleep, SWS, and REMS duration were associated with higher BMI, central adiposity measurements, and cardiovascular risk factors when measured by objective methods.
Effects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndrome | Autor: Ackel-D'Elia C, da Silva AC, Silva RS, Truksinas E, Sousa BS, Tufik S, de Mello MT, Bittencourt LR | Revista: Sleep Breath | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+exercise+training+associated+with+continuous+positive+airway+pressure+treatment+in+patients+with+obstructive+sleep+apnea+syndromeresumo
PURPOSE: The aim of this study was to evaluate the effects of a 2-month exercise training associated with continuous positive airway pressure (CPAP) treatment on the subjective and objective sleep measurements, quality of life, and mood in moderate to severe obstructive sleep apnea syndrome (OSAS) patients.
METHODS: Male patients were randomized into two treatment groups: CPAP (n = 19) and CPAP + exercise (n = 13). All patients completed 1 month of sleep hygiene, 2 months of treatment (CPAP or CPAP + exercise), and 1 week of washout (no treatment). Fletcher and Luckett sleep questionnaire, Epworth sleepiness scale, sleep diaries, polysomnography, SF-36 inventory of quality of life, Profile of Mood States (POMS) questionnaire, neck circumference, and body composition were evaluated. CPAP + exercise group also underwent cardiopulmonary exercise test before and after treatment.
RESULTS: Both treatments were effective in improving subjective sleepiness but CPAP + exercise treatment was more effective in maintaining this improvement after washout. No significant differences were found in most of the sleep parameters studied in both groups. CPAP + exercise group showed lower values of tension and fatigue on POMS and higher values of physical functioning, general health perception, and vitality on SF-36 after treatment.
CONCLUSIONS: A 2-month exercise training associated with CPAP treatment for OSAS patients has a positive impact on subjective daytime sleepiness, quality of life (physical functioning and general health perception), and mood state (tension and fatigue).
Yoga decreases insomnia in postmenopausal women: a randomized clinical trial | Autor: Afonso RF, Hachul H, Kozasa EH, de Souza Oliveira D, Goto V, Rodrigues D, Tufik S, Leite JR | Revista: Menopause | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Yoga+decreases+insomnia+in+postmenopausal+women%3A+a+randomized+clinical+trialresumo
OBJECTIVE: The practice of yoga has been proven to have positive effects on reducing insomnia. Studies have also shown its effects on reducing climacteric symptoms. To date, however, no studies that evaluate the effects of yoga on postmenopausal women with a diagnosis of insomnia in a randomized clinical trial have been conducted. The aim of this study was to evaluate the effect of yoga practice on the physical and mental health and climacteric symptoms of postmenopausal women with a diagnosis of insomnia.
METHODS: Postmenopausal women not undergoing hormone therapy, who were 50 to 65 years old, who had an apnea-hypopnea index less than 15, and who had a diagnosis of insomnia were randomly assigned to one of three groups, as follows: control, passive stretching, and yoga. Questionnaires were administered before and 4 months after the intervention to evaluate quality of life, anxiety and depression symptoms, climacteric symptoms, insomnia severity, daytime sleepiness, and stress. The volunteers also underwent polysomnography. The study lasted 4 months.
RESULTS: There were 44 volunteers at the end of the study. When compared with the control group, the yoga group had significantly lower posttreatment scores for climacteric symptoms and insomnia severity and higher scores for quality of life and resistance phase of stress. The reduction in insomnia severity in the yoga group was significantly higher than that in the control and passive-stretching groups.
CONCLUSIONS: This study showed that a specific sequence of yoga might be effective in reducing insomnia and menopausal symptoms as well as improving quality of life in postmenopausal women with insomnia.
Complete denture wear during sleep in elderly sleep apnea patients - a preliminary study | Autor: Almeida FR, Furuyama RJ, Chaccur DC, Lowe AA, Chen H, Bittencourt LR, Frigeiro ML, Tsuda H | Revista: Sleep Breath. | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Complete+denture+wear+during+sleep+in+elderly+sleep+apnea+patients+-+a+preliminary+studyresumo
OBJECTIVES: There is no consensus in the literature about the impact of complete denture wear on obstructive sleep apnea (OSA). The goal of this randomized clinical study was to assess if complete denture wear during sleep interferes with the quality of sleep.
MATERIALS AND METHODS: Elderly edentulous OSA patients from a complete denture clinic were enrolled and received new complete dentures. An objective sleep analysis was determined with polysomnography performed at the sleep laboratory for all patients who slept either with or without their dentures.
RESULTS: Twenty-three patients (74% females) completed the study with a mean age of 69.6 years and a mean body mass index of 26.7 kg/m(2). The apnea and hypopnea index (AHI) was significantly higher when patients slept with dentures compared to without (25.9 ± 14.8/h vs. 19.9 ± 10.2/h; p > 0.005). In the mild OSA group, the AHI was significantly higher when patients slept with the dentures (16.6 ± 6.9 vs. 8.9 ± 2.4; p < 0.05), while in moderate to severe OSA patients, the AHI was not significantly different when sleeping with dentures (.30.8 ± 15.6 vs. 25.7 ± 7.5; p = 0.2). The supine AHI in mild patients was related to a higher increase in AHI while wearing dentures (12.7 ± 8.4/h vs. 51.9 ± 28.6/h; p < 0.001). A limitation of the study is that the mild OSA patients had a higher BMI when compared to the moderate to severe OSA patients. Ten out of 14 patients who preferred to sleep with their upper and lower dentures showed an increase in their AHI while wearing dentures to sleep.
CONCLUSIONS: Contrary to previous studies, we found that OSA patients may experience more apneic events if they sleep with their dentures in place. Specifically, in mild OSAS patients, the use of dentures substantially increases the AHI especially when in the supine position.
Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep and hormone levels in rhesus monkeys. | Autor: Andersen ML, Sawyer EK, Carroll FI, Howell LL | Revista: Exp Clin Psychopharmacol | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Influence+of+chronic+dopamine+transporter+inhibition+by+RTI-336+on+motor+behavior%2C+sleep+and+hormone+levels+in+rhesus+monkeys.resumo
Dopamine transporter (DAT) inhibitors have been developed as a promising treatment approach for cocaine dependence. However, the stimulant effects of DAT inhibitors have the potential to disrupt sleep patterns, and the influence of long-term treatment on dopamine neurochemistry is still unknown. The objectives of this study were to (1) explore the stimulant-related effects of chronic DAT inhibitor (RTI-336) treatment on motor activity and sleep-like measures in male rhesus monkeys (Macaca mulatta; n = 4) and (2) to determine the effect of drug treatment on prolactin and cortisol levels. Subjects were fitted with a collar-mounted activity monitor to evaluate their motor activity, with 4 days of baseline recording preceding 21 days of daily saline or RTI-336 (1 mg/kg/day; intramuscular) injections. Blood samples were collected immediately prior to and following chronic treatment to assess hormone levels. RTI-336 produced a significant increase in locomotor activity at the end of the daytime period compared to saline administration. During the 3-week treatment period, sleep efficiency was decreased and the fragmentation index and latency to sleep onset were significantly increased. Hormone levels were not changed throughout the study. Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures.
Lights out! It's time for bed. Warning: obstructive sleep apnea increases risk of sudden death in people with epilepsy | Autor: Andersen ML, Tufik S, Cavalheiro EA, Arida RM, de Albuquerque M, Matos G, Scorza FA | Revista: Epilepsy & Behavior | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Lights+out!+It's+time+for+bed.+Warning%3A+obstructive+sleep+apnea+increases+risk+of+sudden+death+in+people+with+epilepsy
Is thyroid screening of sleep clinic patients essential? | Autor: Andersen ML, Tufik S | Revista: Sleep Med | Site: http://www.ncbi.nlm.nih.gov/pubmed/23146746
Vitamin D as an Underlying Factor in Sleep-Related Issues | Autor: Andersen ML, Tufik S | Revista: J Clin Sleep Med | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Vitamin+D+as+an+Underlying+Factor+in+Sleep-Related+Issues
Is acupuncture a real alternative treatment for mild apnea? | Autor: Bezerra AG, Andersen ML, Tufik S, Hachul H. | Revista: Sleep Sci.
Late-onset, insidious course and invasive treatment of congenital central hypoventilation syndrome in a case with the Phox2B mutation: case report | Autor: Bittencourt LR, Pedrazzoli M, Yagihara F, Luz GP, Garbuio S, Moreira GA, Perfeito JA, Tufik S | Revista: Sleep Breath. | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Late-onset%2C+insidious+course+and+invasive+treatment+of+congenital+central+hypoventilation+syndrome+in+a+case+with+the+Phox2B+mutation%3A+case+report
Is mandatory screening for obstructive sleep apnea with polysomnography in all severe obese patients indicated? | Autor: Carneiro G, Florio RTB, Zanella MT, Pradella-Hallinan M, Ribeiro Filho FF, Tufik S, Togeiro SM. | Revista: Sleep Breath | Site: http://www.ncbi.nlm.nih.gov/pubmed/?term=Is+mandatory+screening+for+obstructive+sleep+apnea+with+polysomnography+in+all+severe+obese+patients+indicated%3Fresumo
PURPOSE: The study aims to assess the risk factors for the presence and severity of obstructive sleep apnea (OSA) among severely obese patients evaluated for bariatric surgery.
PATIENTS AND METHODS: Polysomnography recordings were performed in consecutive patients undergoing Roux-en-Y gastric bypass from January 2004 to January 2007. Sleep apnea was noted as present or absent and graded from mild to severe according to the apnea/hypopnea index. Patient gender, age, weight, height, body mass index, neck circumference, and waist circumference were recorded.
RESULTS: A total of 132 patients were included in the study group, and 85 patients had a confirmed diagnosis of OSA (64.4%). The prevalence of OSA was 55.7% in female and 77.4% in male. The prevalence of moderate or severe sleep apnea was higher in males (71.6%) than in females (31.6%). In OSA patients, body mass index (p = 0.020), neck circumference (p < 0.001), and age (p = 0.003) were higher as compared with obese patients without OSA, whereas no differences were found in waist circumference between groups. After multiple regression analysis, body mass index, age, and male gender were independent predictors of sleep apnea. In the female group, age greater than 49 years was the only significant predictor of moderate or severe OSA (odds ratio 5.42 (95% confidence interval 1.61-18.1); p = 0.006).
CONCLUSION: Males and females with age greater than 49 years are at greatest risk for OSA. Preoperative sleep studies should be mandatory in this group of severely obese patients.
Assessment of the impact of vertical dimension alterations on the quality of sleep in elderly patients wearing upper and lower full dentures. | Autor: Chaccur DC, Bittencourt LRA, Lucchesi L, Almeida FR, Fróes TC, Furuyama RJ, Frigerio MLMA. | Revista: Sleep Sci.
The association between the Framingham risk score and sleep: a São Paulo Epidemiological Sleep Study | Autor: Cintra F, Bittencourt LR, Santos-Silva R, Andersen M, Paola AD, Poyares D, Tufik S | Revista: Sleep Medresumo
BACKGROUND: Sleep is an important factor in the maintenance of cardiovascular integrity. It seems that cardiovascular injury and sleep impairment is another chicken or egg puzzle and we hypothesized that the higher the cardiovascular risk factors the higher the sleep impairment. Therefore, the goal of this study is to analyze the sleep profile of a general population based on cardiovascular risk stratification.
METHODS: This population-based survey used a probabilistic three-stage cluster sample of Sao Paulo inhabitants to represent the population. A sample size of 1056 volunteers was defined in order to allow for prevalence estimates with 3% precision. From the 1101 selected and interviewed participants, a complete full-night polysomnogram (PSG) was performed in 1042 participants as well as clinical evaluation and blood samples analyses to assess Framingham risk score.
RESULTS: Nine hundred four subjects were classified according the Framingham score and were included in the analyses. A total of 91.7% were classified as a low risk, 5.8% in the intermediate, and 2.4% in the high risk groups according to Framingham score. All polisomnographic parameters were different between groups, except those related to REM sleep parameters. AHI were greater in the high risk compared to the intermediate and low risk groups (23.9 ± 2.8; 17.7 ± 1.8; 7.2 ± 0.5, respectively, p<0.001), as well as a lower total sleep time in minutes (295.3 ± 16.2; 338.4 ± 10.2; 347.4 ± 2.6, respectively, p=0.01). Sleep efficiency in percentage also exhibits a reduction between groups (67.6 ± 2.5; 78.4 ± 1.6; 82.9 ± 0.4, respectively, p<0.001). After adjustment for confounder factors age (p<0.001) and sleep efficiency (p=0.06) remained strongly associated with high risk population.
CONCLUSION: High Framingham risk score was associated with poor sleep efficiency and aging.
The STOP-BANG questionnaire was a useful tool to identify OSA during epidemiological study in São Paulo (Brazil). | Autor: Coelho FMS, Pradella-Hallinan M, Palombini L, Tufik S, Bittencourt LRA. | Revista: Sleep Med
Narcolepsy in childhood and adolescence | Autor: Coelho FMS, Aloe F, Moreira G, Sander HH, Roitman I, Prado LF, Pradella-Hallinan M, Fernandes RMF, Alves RSC. | Revista: Sleep Sci.
Rats with different thresholds for DMCM-induced clonic convulsions differ in the sleep-time of diazepam and [(3)H]-Ro15-4513 binding | Autor: Contó MB, Hipólide DC, de Carvalho JG, Venditti MA | Revista: Epilepsy Resresumo
The current study investigated the possible inherent relationship between convulsions and sleep involving the GABA(A)/benzodiazepine site complex. The aim of this study was to determine if rats with high (HTR) and low (LTR) thresholds for clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ in the following aspects: (1) sensitivity to the hypnotic effects of the GABA(A) positive allosteric modulators diazepam, pentobarbital and ethanol and (2) in the binding of [(3)H]-flunitrazepam, a benzodiazepine agonist, measured by autoradiography, and [(3)H]-Ro 15-4513, a benzodiazepine partial inverse agonist, to membranes from discrete brain regions. The LTR subgroup presented a shorter diazepam-induced sleeping time compared to that of the HTR subgroup. Biochemical assays revealed that the LTR subgroup did not differ in [(3)H]-flunitrazepam binding compared to the HTR subgroup. With respect to the binding of [(3)H]-Ro 15-4513, the LTR subgroup had higher binding in the brainstem and lower binding in the striatum compared to the HTR subgroup. These results suggest that differences in the benzodiazepine site on the GABA(A) receptor may underlie the susceptibility to DMCM-induced convulsions and sensitivity to the hypnotic effect of diazepam.
Can morphine interfere in the healing process during chronic stress? | Autor: Egydio F, Ruiz FS, Tomimori J, Tufik S, Andersen ML | Revista: Arch Dermatol Resresumo
Technological advances, constant pressure, increased qualified demand, and other daily activities present in modern society result in increasingly stressful living conditions for the population. In the short term, the release of stress-related hormones can play a key role in the survival of an organism. However, it is well known that chronic exposure to cortisol can lead to many adverse effects. Several findings show immunological changes in response to chronic exposure to cortisol, in particular in skin integrity, which may interfere with the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. The importance of opiates as analgesics in the medical setting is indisputable. However, there are a limited number of studies in this field. These investigations can provide further understanding of the mechanisms involved in the healing process in morphine-dependent individuals under chronic stress, which is a common condition in modern society. Furthermore, medical prescriptions of opiates are common among terminal patients, who frequently develop decubitus ulcers and bacterial infections. This review is aimed to provide a concise analysis of effects of morphine and stress on the healing process.
Wound-healing and benzodiazepines: Does sleep play a role in this relationship? | Autor: Egydio F, Pires GN, Tufik S, Andersen ML | Revista: Clinicsresumo
Patients who have suffered burns frequently experience psychological consequences, among which anxiety disorders are prominent. Benzodiazepines are commonly administered to treat these symptoms. The effects of benzodiazepines on healing may not be direct but rather are modulated by alterations of the sleep architecture. This hypothesis is supported by studies that demonstrate the effects of benzodiazepines on the immune system and the inflammatory profile under both normal sleep conditions and during sleep deprivation, particularly rapid eye movement sleep deprivation.
Characteristics of muscle fibers in rats with limb movements during sleep after spinal cord injury | Autor: Esteves AM, Squarcini CFR, Lancellotti CLP, Tufik S, Mello MT | Revista: Eur Neurolresumo
BACKGROUND/AIMS: Previous studies have demonstrated that spinal cord injury (SCI) results in changes in sleep patterns through increased arousals and limb movements during sleep. Dramatic changes in muscle myosin heavy-chain isoforms have also been reported. The aim of this study was to investigate the characteristics of muscle fibers after SCI in rats with limb movements during sleep.
METHODS: Forty male Wistar rats were divided into four groups: SHAM, SCI 3, 7 and 15 days. Animals were subjected to electrode insertion surgery, 24-hour baseline sleep recording, SCI, and subsequent sleep recording for 3, 7, or 15 consecutive days. In addition, the gastrocnemius muscle and spinal cord were collected for histopathological/histochemical analyses.
RESULTS: Our results indicate a rapid and progressive decrease in the cross-sectional area of type I fibers in the gastrocnemius muscle (35.76-24.74 μm(2)) after SCI. Additionally, we found SCI-induced changes in sleep patterns. Following SCI, we also observed limb movements in sleeping rats, as well as significant negative moderate correlations between type I fibers and limb movement.
CONCLUSION: Our study strengthened the hypothesis by correlation between changes in types of muscle fiber (decline in type I fibers) and an increase in limb movements during sleep after SCI.
Distúrbios respiratórios do sono na gravidez. | Autor: Fontes AHM, Lopes EM, Togeiro SMGP. | Revista: Pneumol Paulista
Nocturia X disturbed sleep: a review. | Autor: Furtado D, Hachul H, Andersen ML, Castro RA, Girão MB, Tufik S | Revista: Int Urogynecology Jresumo
In this article, we provide a concise review of the literature on nocturia and its interference with sleep and, consequently, on quality of life. There are few studies addressing the possible influences of nocturia on sleep disruption. Nocturia is a potential contributor to sleep disorders because affected individuals experience nonrestorative sleep due to frequent interruptions. We also attempted to determine whether individuals with nocturia wake to urinate or, alternately, urinate because they are awake. This review attempts to outline this specific association by examining the possible interactions with other medical conditions and the pathophysiology and prevalence. Most studies have observed a higher prevalence among women; however, the impact on quality of life is higher in men. Nocturia is not necessarily associated with natural aging. The exploration of these topics provides information to clarify the implications of nocturia on sleep, sleep disruption, and other related consequences. Additional evidence is still required to address the question of whether nocturia leads to disordered sleep or whether disordered sleep leads to nocturia.
Quality of life in children with sleep-disordered breathing. | Autor: Gomes AM, Santos OM, Pimentel K, Marambaia PP, Gomes LM, Pradella-Hallinan M, Lima MG. | Revista: Braz J Otorhinolaryngol.
Genetic aspects of sleep in humans. | Autor: Guindalini C, Tufik S. | Revista: Sleep Sci.
Letter to the editor: Soy germ isoflavones improve menopausal symptoms. | Autor: Hachul H, Bennedsen L, Tufik S, Andersen ML. | Revista: Menopause
Sleep loss and cytokines levels in an experimental model of psoriasis | Autor: Hirotsu C, Rydlewski M, Araújo MS, Tufik S, Andersen ML | Revista: PLoS Oneresumo
Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD). Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1β, IL-6 and IL-12) and decreases in the anti-inflammatory cytokine (IL-10) after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis.
High Altitude Exposure Impairs Sleep Patterns, Mood and Cognitive Functions | Autor: Lemos VA, Antunes HKM, Santos RVT, Lira FS, Tufik S, De Mello MT | Revista: Psychophysiologyresumo
This work evaluated the importance of sleep on mood and cognition after 24 h of exposure to hypoxia. Ten males, aged 23-30 years, were placed in a normobaric chamber simulating an altitude of 4,500 m. Sleep assessments were conducted from 22:00-6:00; all mood and cognitive assessments were performed 20 min after awakening. The assessments were conducted in normoxic conditions and after 24 h of hypoxia. Sleep was reevaluated 14 h after the start of exposure to hypoxic conditions, and mood state and cognitive functions were reevaluated 24 h after the start of exposure to hypoxic conditions. Hypoxia reduced total sleep time, sleep efficiency, slow-wave sleep, and rapid eye movement. Depressive mood, anger, and fatigue increased under hypoxic conditions. Vigor, attention, visual and working memory, concentration, executive functions, inhibitory control, and speed of mental processing worsened. Changes in sleep patterns can modulate mood and cognition after 24 h.
Evaluation of Periodic Limb Movements in a Putative Animal Model of Restless Leg Syndrome | Autor: Lopes C, Esteves AM, Frussa-Filho R, Tufik S, de Mello MT | Revista: Movement Disordersresumo
Restless leg syndrome (RLS) is a major healthcare burden with increasing prevalence. It has been demonstrated that periodic limb movements (PLM) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. The aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of RLS induced by lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6-OHDA). Rats were implanted with electrodes for electrocorticography and electromyography. Sleep recordings were monitored during light/dark periods lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of the drug or phosphate-buffered saline (PBS). A control group that did not receive any injection was also included. Wakefulness percentages were generated for 4-hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM, 11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of wakefulness during the last block of the dark period, as would be expected for an animal model of this syndrome. In addition, at all time points after lesioning, these animals presented increased frequencies of limb movement during both the light and the dark periods. These alterations were reversed by the acute administration of the dopaminergic agonist pramipexole. This animal model strengthens the notion that 6-OHDA-induced A11 lesions can be a valid animal model for RLS and PLM.
The role of the nose in obstructive sleep apnea. | Autor: Machado CC, Haddad FLM. | Revista: Sleep Sci.
Overview of sleep disordered breathing management in 12 latin american sleep centers. | Autor: Maldonado AC, Poyares D, Chada DP, Silveira FM, Lorenzi-Filho G, Castro JR, Nogueira JF, Serra L, Bittencourt L, Oliveira LR, Bazurto MA, Varela MVL, Flores MV, Garcia RAL. | Revista: Sleep Sci.
A possible role of cyclooxygenase-2 in the relationship between sleep and sudden unexpected death in epilepsy. | Autor: Matos G, Bennedsen L, Garcia VA, Scorza FA, Cavalheiro EA, Tufik S, Andersen ML. | Revista: Epilepsia
Encouraging pre-clinical findings regarding the relationship between sleep and epilepsy | Autor: Matos G, Bennedsen L, Tufik S, Andersen ML | Revista: Sleep.
Prevalence and correlates for sleep complaints in older adults in Low and Middle Income Countries: A 10/66 Dementia Research Group study. | Autor: Mazzotti DR, Guindalini C, Ferri CP, Sosa AL, Tufik S | Revista: Sleep Medresumo
BACKGROUND: Although it is well recognized that the prevalence of sleep complaints increases with age, estimates in developing countries are still unknown. The present study aims to estimate the prevalence and prevalence ratios of the correlates of sleep complaints in a large population of older adults from low and middle income countries (LAMICs).
METHODS: A cross-sectional survey was performed in 16,680 65 year-old or older residents in catchment areas of Cuba, the Dominican Republic, Peru, Venezuela, Mexico, China, India, and Puerto Rico (10/66 Dementia Research Group study). Information about socio-demographic factors, lifestyle, health, and sleep complaints was obtained. Results were standardized by age, sex, household clustering, and residence site (urban or rural). Prevalence ratios were derived for each country and fixed effects meta-analyses were used to combine them.
RESULTS: The standardized prevalence of sleep complaints varied from 9.1% (China) to 37.7% (India). The meta-analysis showed that female gender, urban residence, low educational level, low physical activity status, high pain scores, poor health, higher memory impairment score, presence of major depression, mild cognitive impairment, and high number of co-morbidities were associated with sleep complaints.
CONCLUSIONS: This study robustly characterized the prevalence of sleep complaints in large samples of the elderly in LAMICs and identified potential risk factors that may be specific to these populations. This approach can help to direct health-care efforts related to sleep disturbances in these countries.
Adenosine Deaminase Polymorphism Affects Sleep EEG Spectral Power in a Large Epidemiological Sample | Autor: Mazzotti DR, Guindalini C, de Souza AA, Sato JR, Santos-Silva R, Bittencourt LR, Tufik S | Revista: PLoS Oneresumo
Slow wave oscillations in the electroencephalogram (EEG) during sleep may reflect both sleep need and intensity, which are implied in homeostatic regulation. Adenosine is strongly implicated in sleep homeostasis, and a single nucleotide polymorphism in the adenosine deaminase gene (ADA G22A) has been associated with deeper and more efficient sleep. The present study verified the association between the ADA G22A polymorphism and changes in sleep EEG spectral power (from C3-A2, C4-A1, O1-A2, and O2-A1 derivations) in the Epidemiologic Sleep Study (EPISONO) sample from São Paulo, Brazil. Eight-hundred individuals were subjected to full-night polysomnography and ADA G22A genotyping. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the signals from each EEG electrode. The genotype groups were compared in the whole sample and in a subsample of 120 individuals matched according to ADA genotype for age, gender, body mass index, caffeine intake status, presence of sleep disturbance, and sleep-disturbing medication. When compared with homozygous GG genotype carriers, A allele carriers showed higher delta spectral power in Stage 1 and Stages 3+4 of sleep, and increased theta spectral power in Stages 1, 2 and REM sleep. These changes were seen both in the whole sample and in the matched subset. The higher EEG spectral power indicates that the sleep of individuals carrying the A allele may be more intense. Therefore, this polymorphism may be an important source of variation in sleep homeostasis in humans, through modulation of specific components of the sleep EEG.
Is sleep related to cancer in murine model of obstructive sleep disorder? | Autor: Nozoe KT, Tufik S, Andersen ML | Revista: Eur Respir J
Is portable monitoring accurate in the diagnosis of Obstructive Sleep Apnea Syndrome in Chronic Pulmonary Obstructive disease? | Autor: Oliveira MG, Nery LE, Santos-Silva R, Sartori DE, Alonso FF, Togeiro SM, Tufik S, Bittencourt L | Revista: Sleep Medresumo
BACKGROUND: No scientific evidence supports the use of portable devices to diagnose obstructive sleep apnea syndrome (OSAS) in patients with co-morbities. Our aim was to evaluate the accuracy of a portable monitoring device (Stardust - STD) in the detection of patients with chronic obstructive pulmonary disease (COPD).
METHODS: Patients with COPD and clinical suspicion of OSAS were recruited for a prospective randomized study. The STD was used on two different nights: (1) at home (STDHome) and (2) at the sleep laboratory simultaneous with polysomnography (PSG-STDLab).
RESULTS: A total of 72 patients underwent the proposed recordings. Forty-six volunteers were excluded due to recording problems, and data from 26 subjects were analyzed. The mean age was (mean±SD) 62.8±8.5 years, 50% were male, and the mean forced expiratory volume in the first second was 55±11%. Significant intraclass correlation was observed between apnea-hypopnea index (AHI)-PSG vs. AHI-STDLab (r=0.61, p<0.0001) and AHI-STDHome (r=0.47, p<0.007). Kappa analysis also showed a significant agreement for severe group.
CONCLUSION: Despite the agreement found in a small number of patients between AHI, a large number of failures in the recording limits the use of this portable device for the diagnosis of OSAS in patients with COPD.
Is exercise an alternative treatment for chronic insomnia? | Autor: Passos GS, Poyares DLR, Santana MG, Tufik S, De Mello MT. | Revista: Clinicsresumo
The purposes of this systematic/critical review are: 1) to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2) to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary.
Relação entre privação de sono e ansiedade na pesquisa básica. | Autor: Pires GN, Tufik S, Andersen ML. | Revista: Einstein
Demand for multi-centric climatic research to investigate the relationship between sleep apnea and other disorders and seasonality | Autor: Ramos-Xavier F, Bennedsen L, Hachul H, Andersen M, Tufik S | Revista: CHEST
Pain-related diseases and sleep disorders | Autor: Roizenblatt M, Rosa Neto NS, Tufik S, Roizenblatt S | Revista: Braz J Med Biol Res.
Priapism is associated with sleep hypoxemia in sickle cell disease | Autor: Roizenblatt M, Figueiredo MS, Cançado RD, Pollack-Filho F, Arruda MMAS, Vicari P, Sato JR, Tufik S, Roizenblatt S | Revista: J Urolresumo
PURPOSE: We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease.
MATERIALS AND METHODS: This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations.
RESULTS: The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index.
CONCLUSIONS: Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.
Chronobiology: Relevance for tuberculosis | Autor: Santos LG, Pires GN, Bittencourt LRA, Tufik S, Andersen ML | Revista: Tuberculosisresumo
Despite the knowledge concerning the pathogenesis of tuberculosis, this disease remains one of the most important causes of mortality worldwide. Several risk factors are well-known, such poverty, HIV infection, and poor nutrition, among others. However, some issues that may influence tuberculosis warrant further investigation. In particular, the chronobiological aspects related to tuberculosis have garnered limited attention. In general, the interface between tuberculosis and chronobiology is manifested in four ways: variations in vitamin D bioavailability, winter conditions, associated infections, and circannual oscillations of lymphocytes activity. Moreover, tuberculosis is related to the following chronobiological factors: seasonality, latitude, photoperiod and radiation. Despite the relevance of these topics, the relationship between them has been weakly reviewed. This review aims to synthesize the studies regarding the association between tuberculosis and chronobiology, as well as urge critical discussion and highlight its applicability to health policies for tuberculosis.
Sleep disorders and demand for medical services: evidence from a population-based longitudinal study. | Autor: Santos-Silva R, Castro LS, Taddei JA, Tufik S, Bittencourt LR. | Revista: PLoS Oneresumo
BACKGROUND: The aim of this study was to investigate whether insomnia and obstructive sleep apnea (OSA) were predictors of hospitalizations or emergency department visits during two years following the Sao Paulo Epidemiologic Sleep Study (EPISONO) sample.
METHODS AND FINDINGS: All participants (n = 1,101) who underwent a baseline evaluation between July and December 2007 were contacted in December 2009 and asked to fill out a questionnaire about body weight changes, number of hospitalizations and visits to the emergency department. Participants lost during the follow-up period represented 3.2% (n = 35) and 7 subjects had died. Hospitalizations were reported by 116 volunteers (10.5%) and emergency department visits were reported by 136 participants (12.4%). The average body mass index (BMI) did not vary significantly between the first and the second assessment [26.7(95%CI:26.3-27.1) vs. 26.9(26.5-27.4) kg/m2]. After adjusting for confounders, a multiple logistic regression model revealed that female gender [1.4(1.0-1.9)], age ≥ 40 years, insomnia diagnosed according to the DSM-IV criteria [1.6(1.0-2.6)], and apnea-hypopnea index ≥ 15 [1.5(1.0-2.2)] were predictors of hospitalizations and/or demand for emergency services.
CONCLUSION: Our study of a probabilistic sample of the Sao Paulo inhabitants shows that over a period of two years, insomnia and OSA were both associated with health impairment. Considering the high prevalence and public health burden of sleep disorders, the consequences of untreated disease for both the individual and society are undeniable and should be addressed.
Comparing the clinical profile of non obese children with sleep apnea and snoring. | Autor: Stefanini DOS, Barros EL, Stefanini R, Pradella-Hallinan MLC, Pignatari SSN, Fujita RR | Revista: Braz J Otorhinolaryngol.resumo
Few studies in the literature have looked into the cardiovascular and metabolic effects of Obstructive Sleep Apnea Syndrome (OSAS) in children.
OBJECTIVE: This study aims to evaluate the metabolic profile of non-obese children with OSAS.
METHODS: Fifty-two children were enrolled in this study, 21 girls and 31 boys. Patients were divided into two groups: OSAS (28 children) and Snore (22 children) according to polysomnographic evaluation. All children were submitted to ENT examination, measurements of weight, height and blood pressure. Blood samples were tested for hemoglobin, hematocrit, fasting glucose, fasting insulin, triglycerides, total cholesterol, HDL, LDL, VLDL, TSH and T4. The gathered data sets were compared between groups and also within the OSAS group according to the severity of the syndrome.
RESULTS: The children from both groups had no alterations in blood pressure levels. The results of the blood tests were normal for both groups. Results of hemoglobin, hematocrit, and HDL were all significantly higher in the Snore group when compared to the OSAS group; by their turn, VLDL levels were higher in the OSAS group. There was no statistical difference between the groups based on OSAS severity.
CONCLUSION: Non-obese children with OSAS present no significant alterations in metabolic tests or blood pressure levels.
Systematic Evaluation of the Upper Airway in the Adult Population of Sao Paulo, Brazil | Autor: Stefanini R, Tufik S, Soares MC, Haddad FL, Bittencourt LR, Santos-Silva R, Gregorio LC | Revista: Otolaryngol Head Neck Surgresumo
OBJECTIVES: To study the prevalence of otorhinolaryngologic symptoms and findings of physical examination of the upper airway (UA) of a representative sample of the adult population of São Paulo, Brazil, and the association between these findings.
STUDY DESIGN: Cross-sectional survey.
SETTING: Population sample.
METHODS: A total of 1101 randomly selected volunteers representing the adult population of São Paulo according to sex, age, and socioeconomic class were included in this study. Otorhinolaryngological evaluation included investigation of nasal complaints, physical examination of the UA, and a facial inspection.
RESULTS: A total of 993 volunteers (53.9% women), with a mean age of 41.8 ± 0.89 years, underwent otorhinolaryngologic examination. The most prevalent symptoms were the following: symptoms suggestive of rhinitis (44.9%), snoring (42.8%), mouth breathing (39.3%), and nasal obstruction (33.3%). In physical examination, the most common findings were a web palate (redundant posterior pillar; 62.9%), septum deviation (56.9%), and inferior turbinate hypertrophy (37.7%). Significant associations were found between nasal obstruction and septum deviations, inferior turbinate hypertrophy, high-arched palate, and class II dental occlusion; between symptoms of rhinitis and inferior turbinate hypertrophy; and between snoring and obstructive deviated septum, modified Mallampatti grades III and IV, increased neck circumference, and age greater than or equal to 50 years.
CONCLUSIONS: The prevalence of otorhinolaryngologic symptoms and alterations in physical examination of the UA were high in the adult population of São Paulo, Brazil. The snoring and nasal symptoms were significantly associated with findings from UA physical examination and inspection of the facial skeleton.
REM sleep rebound as an adaptive response to stressful situations. | Autor: Suchecki D, Tiba PA, Machado RB. | Revista: Front Neurol.resumo
Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior.
Assessment of biological components associated with sleepiness in young working college students. | Autor: Teixeira LR, Pedrazzoli M, Luz AA, Turte SL, De Paula LP, Valente D, Tufik S, Fischer FM. | Revista: Sleep Sci.
The effects of a session of resistance training on sleep patterns in the elderly | Autor: Viana VA, Esteves AM, Boscolo RA, Grassmann V, Santana MG, Tufik S, de Mello MT | Revista: Eur J Appl Physiol.resumo
The purpose of this study was to evaluate the influence of a session of resistance training on the sleep patterns of elderly people. Forty men aged 65-80 years who were sedentary and clinically healthy were divided into two groups: the control group (n = 18) and the resistance group (n = 22). Both groups underwent two polysomnography tests, one at baseline and another after either a resistance training session (the resistance group) or no physical exercise (the control group). The resistance training session was based on 60% of one repetition maximum (a test that assesses the maximum force). We observed that the frequency with which the control group awoke (arousal index) increased from 16.29 ± 6.06 events/h to 20.09 ± 6.9 events/h, and in the resistance group, it decreased from 22.27 ± 11 events/h to 20.41 ± 8.57 events/h (t = 2.10 and p = 0.04). For stage-1 sleep, there was an increase from 4.96% at baseline to 5.40% in the control group, and there was a decrease in the resistance group from 8.32 to 6.21% after the exercise session (t = 2.12 and p = 0.04). A session of resistance training at 60% of one repetition maximum was able to modify the sleep pattern in men aged 65-80 years, suggesting that physical exercise has a modest influence on sleep consolidation.
Sleep in Postmenopausal Women | Autor: Vigeta SM, Hachul H, Tufik S, de Oliveira EM | Revista: Qualitative Health Research
Sleep, neuropeptides and proteases. | Autor: Visniauskas B, Julian GS, Oliveira RW, Tufik S, Chagas JR | Revista: Sleep Sci.
Oxidative stress and quality of life in obstructive sleep apnea syndrome elderly patients: are there differences after six months of continuous positive airway pressure treatment? | Autor: Yagihara F, Lucchesi LM, D’Almeida V, De Mello MT, Tufik S, Bittencourt LRA. | Revista: Clinicsresumo
OBJECTIVES: This study evaluated the effect of Continuous Positive Airway Pressure treatment on oxidative stress parameters and the quality of life of elderly patients with obstructive sleep apnea syndrome.
METHODS: In total, 30 obstructive sleep apnea syndrome patients and 27 subjects without obstructive sleep apnea syndrome were included in this study. Both groups underwent quality of life and oxidative stress evaluations at baseline and after six months. Polysomnography was performed in both groups at baseline and a second time in the obstructive sleep apnea syndrome group after six months of Continuous Positive Airway Pressure treatment. All of the variables were compared between the control and obstructive sleep apnea syndrome groups in this prospective case-control study.
RESULTS: The baseline concentrations of the antioxidant enzyme catalase were higher in the obstructive sleep apnea syndrome group than the control group. After Continuous Positive Airway Pressure treatment, the obstructive sleep apnea syndrome group exhibited a reduction in the level of oxidative stress, as indicated by a decrease in the level of lipid peroxidation measured by the malondialdehyde (MDA) concentration [pre: 2.7 nmol malondialdehyde/mL (95% 1.6-3.7) vs. post: 1.3 nmol MDA/mL (0.7-1.9), p<0.01]. Additionally, improvements were observed in two domains covered by the SF-36 questionnaire: functional capacity [pre: 77.4 (69.2-85.5) vs. post: 83.4 (76.9-89.9), p = 0.002] and pain [pre: 65.4 (52.8-78.1) vs. post: 77.8 (67.2-88.3), p = 0.004].
CONCLUSION: Our study demonstrated that the use of Continuous Positive Airway Pressure to treat obstructive sleep apnea syndrome in elderly patients reduced oxidative stress and improved the quality of life.
Primary headaches and their relationship with sleep. | Autor: Yagihara F, Lucchesi LM, Smith AKA, Speciali JG. | Revista: Sleep Sci.
Short sleep duration and obesity: mechanisms and future perspectives | Autor: Zimberg IZ, Dâmaso A, Del Re M, Carneiro AM, Souza HS, Lira FS, Tufik S, De Mello MT. | Revista: Cell Biochem Functionresumo
A reduction of sleep time has become common over the last century, and growing evidence from both epidemiological and laboratory-based studies suggests sleep curtailment is a new risk factor for the development of obesity. On this basis, the present review examines the role of sleep curtailment in the metabolic and endocrine alterations, including decreased glucose tolerance and insulin sensitivity, increased evening concentrations of cortisol, increased levels of ghrelin, decreased levels of leptin and increased hunger and appetite. It will be discussed how sleep restriction may lead to increase in food intake and result in greater fatigue, which may favour decreased energy expenditure. Altogether, evidences point to a possible role of decreased sleep duration in the current epidemic of obesity and therefore present literature highlights the importance of getting enough good sleep for metabolic health. Many aspects still need to be clarified and intervention studies also need to be conducted.
Consenso brasileiro de ronco e apneia do sono: aspectos de interesse aos ortodontistas | Autor: Chaves Junior CM, Dal-Fabbro C, de Bruin VMS, Tufik S, Bittencourt LRA. | Revista: Dental Press Journal of Orthodontics
Cysteine: a potential biomarker for obstructive sleep apnea | Autor: Cintra F, Tufik S, D’Almeida V, Calegare BFA, de Paola A, Oliveira W, Rizzi C, Roizenblatt S, Poyares D. | Revista: Chest
Perfil cardiovascular em pacientes com apnéia obstrutiva do sono | Autor: Cintra F, Tufik S, de Paola A, Feres MC, Mello-Fujita L, Oliveira W, Rizzi C, Poyares D. | Revista: Arquivos Brasileiros de Cardiologia
Psychological treatment for sleepwalking: two case reports | Autor: Conway SG, Castro L, Lopes-Conceição MC, Hachul H, Tufik S. | Revista: Clinics
Isoflavones decrease insomnia in postmenopause | Autor: Hachul H, Brandão LC, D’Almeida V, Bittencourt LRA, Baracat EC, Tufik S. | Revista: Menopause
Effect of massage in postmenopausal women with insomnia: a pilot study | Autor: Hachul H, Oliveira D, Tufik S, Bittencourt L. | Revista: Clinics
Sedative antidepressants and insomnia | Autor: Moraes WAS, Burke PR, Coutinho PL, Guilleminault C, Bittencourt AG, Tufik S, Poyares D. | Revista: Revista Brasileira de Psiquiatria
Nocturnal awakening with headache and its relationship with sleep disorders in a population-based sample of adult inhabitants of São Paulo City, Brazil | Autor: Lucchesi LM, Speciali JG, Santos-Silva R et al. | Revista: Cephalalgiaresumo
Our aim was to estimate the prevalence of nocturnal awakening with headache (NAH) in the population of São Paulo City according to gender, age (20-80 years old) and socioeconomic classes and its relationship to sleep disorders, sleep parameters, anxiety, depression, fatigue, life quality and obesity. We used a population-based survey with a representative three-stage cluster sample. Questionnaires and scales were applied face-to-face, and polysomnography was performed in 1101 volunteers, aged 42 ± 14 years, 55% women. The complaint of NAH occurring at least once a week had a prevalence of 8.4%, mostly in women, obese subjects and those aged 50-59 years-old. We observed associations of NAH with insomnia, restless leg syndrome (RLS), nightmares and bruxism, but not obstructive sleep apnea syndrome. In a logistics regression model, risk factors for NAH were female gender, odds ratio (OR) (95% confidence interval [CI]) 4.5 (2.8-7.3); obesity, OR 1.9 (1.1-3.3); age between 50 and 59 years, OR 2.4 (1.2-4.7); severe anxiety, OR 8.1 (3.6-18.1); RLS, 2.7 (1.2-5.6); and nightmares, 2.2 (1.3-3.7). Our study shows that NAH was highly prevalent in the population of São Paulo and suggests that this phenomenon has specific characteristics with specific risk factors: obesity, RLS and nightmares.
Obstructive Sleep Apnea Syndrome in the São Paulo Epidemiologic Sleep Study | Autor: Tufik S, Santos-Silva R, Taddei J, Bittencourt LA | Revista: Sleep Medresumo
OBJECTIVE: To estimate the prevalence of Obstructive Sleep Apnea Syndrome (OSAS), using current clinical and epidemiological techniques, among the adult population of Sao Paulo, Brazil. - METHODS: This population-based survey used a probabilistic three-stage cluster sample of Sao Paulo inhabitants to represent the population according to gender, age (20-80 years), and socio-economic status. Face-to-face interviews and in-lab full-night polysomnographies using a nasal cannula were performed. The prevalence of OSAS was determined according to the criteria of the most recent International Classification of Sleep Disorders (ICDS-2) from American Academy of Sleep Medicine (2005). - RESULTS: A total of 1042 volunteers underwent polysomnography (refusal rate=5.4%). The mean age+/-SD was 42+/-14 years; 55% were women and 60% had a body mass index>25 kg/m(2). OSAS was observed in 32.8% of the participants (95% CI, 29.6-36.3). A multivariate logistic regression model identified several independent and strong associations for the presence of OSAS: men had greater association than women (OR=4.1; 95% CI, 2.9-5.8; P<0.001) and obese individuals (OR=10.5; 95% CI, 7.1-15.7; P<0.001) than individuals of normal weight. The adjusted association factor increased with age, reaching OR=34.5 (95% CI, 18.5-64.2; P<0.001) for 60-80 year olds when compared to the 20-29 year old group. Low socio-economic status was a protective factor for men (OR=0.4), but was an associated factor for women (OR=2.4). Self-reported menopause explained this increased association (age adjusted OR=2.1; 95% CI, 1.4-3.9; P<0.001), and it was more frequent in the lowest class (43.1%) than either middle class (26.1%) or upper class (27.8%) women. - CONCLUSIONS: This study is the first apnea survey of a large metropolitan area in South America identifying a higher prevalence of OSAS than found in other epidemiological studies. This can be explained by the use of the probabilistic sampling process achieving a very low polysomnography refusal rate, the use of current techniques and clinical criteria, inclusion of older groups, and the higher prevalence of obesity in the studied population.
The influence of sleep apnea and obesity on expression of glycerol-3-phosphate dehydrogenase 1 gene | Autor: Guindalini C, Lee KS, Andersen ML, Santos-Silva R, Bittencourt LRA, Tufik S | Revista: Exp Biol Medresumo
Glycerol-3-phosphate dehydrogenase 1 (GPD1) is considered to be a key enzyme that connects carbohydrate and lipid metabolism. This gene is induced in response to sleep deprivation, suggesting a potential role for this enzyme in the manifestation of obstructive sleep apnea (OSA). This study aims to examine the effects of sleep apnea, obesity and other relevant clinical parameters on GPD1 expression in the peripheral blood of a rigorously selected sample population in order to identify a biological marker that would allow for early intervention and prevention of the disorder. Clinical and sleep parameters were assessed by a complete full-night polysomnography and the expression of GPD1 at the mRNA level was determined. The results were compared among 20 OSA patients and 20 controls, further classified into two subgroups according to their body mass index. The expression levels of the GPD1 gene did not differ between patients with OSA and their matched controls. The results were not affected by the clinical and biochemical measurements, the sleep parameters or the severity of nocturnal hypoxemia. On the other hand, individuals with OSA had higher levels of fasting glucose when compared with weight-matched controls (P = 0.01). Moreover, higher very low-density lipoprotein (VLDL) was found in the over-weight OSA patient group, and higher cholesterol levels were found in the eutrophic OSA group when compared with their respective controls (P < 0.05). Based on logistic regression analyses, fasting glucose levels emerged as an independent factor for OSA in both the eutrophic (odds ratio [OR] = 1.27; 95% confidence interval [CI] = 1.00-1.59) and over-weight groups (OR = 1.29; 95% CI = 1.04-1.59). Although the results from the current study corroborate the growing body of data connecting OSA to altered glucose metabolism, it does not provide evidence for the modulation of GPD1 transcription by either OSA or its related phenotypes. This suggests that GPD1 may not play a major role in the OSA manifestation.
Diretrizes brasileiras para o diagnóstico da narcolepsia | Autor: Alóe F, Alves RC, Araújo JF, Azevedo A, Bacelar A, Bezerra M, Bittencourt LRA, Bustamante G, Cardoso TA, Eckeli AL, Fernandes RM, Goulart L, Pradella-Hallinan M, Hasan R, Sander HH, Pinto Jr LR, Lopes MC, Minhoto GR, Moraes W, Moreira GA, Pachito D, Pedra | Revista: Revista Brasileira de Psiquiatria
Diretrizes brasileiras para o tratamento da narcolepsia | Autor: Alóe F, Alves RC, Araújo JF, Azevedo A, Bacelar A, Bezerra M, Bittencourt LRA, Bustamante G, Cardoso TA, Eckeli AL, Fernandes RM, Goulart L, Pradella-Hallinan M, Hasan R, Sander HH, Pinto Jr LR, Lopes MC, Minhoto GR, Moraes W, Moreira GA, Pachito D, Pedra | Revista: Revista Brasileira de Psiquiatria
Prevalence of erectile dysfunction complaints associated with sleep disturbances in Sao Paulo, Brazil: a population-based survey | Autor: Andersen ML, Santos-Silva R, Bittencourt LRA, Tufik S. | Revista: Sleep Medicine
Sleep disorders frequency in post-polio syndrome patients caused by periodic limb movements | Autor: Araújo MAP, Silva TM, Moreira GA, Pradella-Hallinan M, Tufik S, Oliveira ASB. | Revista: Arquivos de Neuropsiquiatria
Critérios diagnósticos e tratamento dos distúrbios respiratórios do sono: SAOS | Autor: Bittencourt LRA, Caixeta EC. | Revista: Jornal Brasileiro de Pneumologia
The effects of posterior fossa decompressive surgery in adult patients with Chiari malformation and sleep apnea | Autor: Botelho RV, Bittencourt LRA, Rotta JM, Tufik S. | Revista: Journal of Neurosurgery
Carneiro G, Fontes FH, Togeiro SMGP | Autor: Carneiro G, Fontes FH, Togeiro SMGP | Revista: Jornal Brasileiro de Pneumologia
Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre | Autor: Coelho FMS, Pradella-Hallinan M, Pedrazzoli M, Soares CAS, Fernandes GBP, Gonçalves AL, Tufik S, Bittencourt LRA. | Revista: Arquivos de Neuropsiquiatria
Avaliação clínica e polissonográfica do aparelho BRD no tratamento da Síndrome da Apnéia Obstrutiva do Sono | Autor: Dal-Fabbro C, Chaves Jr CM, Bittencourt LRA, Tufik S. | Revista: Dental Press Journal of Orthodontics
Immediate effect of acupuncture on the sleep pattern of patients with obstructive sleep apnoea | Autor: Freire AO, Sugai GCM, Togeiro SM, Mello LE, Tufik S. | Revista: Acupuncture in Medicine
The influence of obstructive sleep apnea on the expression of glycerol-3-phosphate dehydrogenase1 gene | Autor: Guindalini C, Lee KS, Andersen ML, Santos-Silva R, Bittencourt LRA, Tufik S. | Revista: Experimental Biology and Medicine
Influence of genetic ancestry on the risk of obstructive sleep apnoea syndrome | Autor: Guindalini C, Colugnati FAB, Pellegrino R, Santos-Silva R, Bittencourt LRA, Tufik S. | Revista: European Respiratory Journal
Hachul H, Andersen ML, Bittencourt LRA, Santos-Silva R, Conway SG, Tufik S. | Autor: Hachul H, Andersen ML, Bittencourt LRA, Santos-Silva R, Conway SG, Tufik S. | Revista: Climacteric
Integrative therapy for postmenopausal insomnia | Autor: Hachul H. | Revista: Alternative and Complementary Therapies
Obstructive sleep apnea syndrome (OSAS) in mouth breathing children | Autor: Alternative and Complementary Therapies | Issue List | Revista: Brazilian Journal of Otorhinolaryngology
Mind-body interventions for the treatment of insomnia: a review | Autor: Kozasa EH, Hachul H, Monson C, Pinto Jr L, Garcia MC, Mello LEAM, Tufik S. | Revista: Revista Brasileira de Psiquiatria
Nocturnal awakening with headache and its relationship with sleep disorders in a population-based sample of adult inhabitants of Sao Paulo City, Brazil | Autor: Lucchesi LM, Speciali JG, Santos-Silva R, Taddei JA, Tufik S, Bittencourt LR. | Revista: Cephalalgia
The relationship between sleep and epilepsy: Evidence from clinical trials and animal models | Autor: Matos G, Andersen ML, do Valle AC, Tufik S. | Revista: Journal of the Neurological Sciences
Sudden unexpected death in epilepsy: The obscure role of sleep | Autor: Matos G, Andersen ML, Tufik S. | Revista: Journal of the Neurological Sciences
Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea | Autor: Neves C, Tufik S, Chediek F, Poyares D, Cintra F, Roizenblatt M, Abrantes F, Monteiro MA, Roizenblatt S. | Revista: Clinics
The effect of sildenafil on sleep respiratory parameters and heart rate variability in obstructive sleep apnea | Autor: Neves C, Tufik S, Monteiro MA, Chediek F, Jose FF, Roizenblatt S. | Revista: Sleep Medicine
Fisiopatologia dos distúrbios respiratórios do sono | Autor: Palombini LO. | Revista: Jornal Brasileiro de Pneumologia
Critérios diagnósticos e tratamento dos distúrbios respiratórios do sono: RERA | Autor: Palombini LO. | Revista: Jornal Brasileiro de Pneumologia
Effect of acute physical exercise on patients with chronic primary insomnia | Autor: Passos GS, Poyares D, Santana MG, Garbuio SA, Tufik S, Mello MT. | Revista: Journal of Clinical Sleep Medicine
Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis | Autor: Pereira Jr. JC, Pradella-Hallinan M, Pessoa HL. | Revista: Clinics
New guidelines for diagnosis and treatment of insomnia | Autor: Pinto Jr LR, Alves RC, Caixeta E, Fontenelle JA, Bacellar A, Poyares D, Aloe F, Rizzo G, Minhoto G, Bittencourt LR, Ataíde Jr L, Assis M, Pradella-Hallinan M, Pinto MCR, Rodrigues RND, Hasan R, Fonseca R, Tavares S | Revista: Arquivos de Neuropsiquiatria
Monitorização portátil no diagnóstico da apneia obstrutiva do sono: situação atual, vantagens e limitações | Autor: Polese JF, Santos-Silva R, Kobayashi RF, Pinto INP, Tufik S, Bittencourt LRA. | Revista: Jornal Brasileiro de Pneumologia
Sleep-disordered breathing changes after kidney transplantation: a polysomnographic study | Autor: Rodrigues CJO, Marson O, Togeiro SMGP, Tufik S, Ribeiro AB, Tavares A. | Revista: Nephrology Dialysis Transplantation
Neonatal arthritis disturbs sleep and behaviour of adult rat offspring and their dams | Autor: Roizenblatt S, Andersen ML, Bignotto M, D’Almeida V, Martins PJF, Tufik S. | Revista: European Journal of Pain
Clinical and polysomnographic profile of sleep-disordered breathing patients according to the treatment indicated | Autor: Silva CAP, Prescinotto R, Haddad FLM, Lopes PR, Torres MA, Rapoport PB. | Revista: Sleep Science
Evaluation of the upper airway in obstructive sleep apnoea | Autor: Togeiro SMGP, Chaves Jr CM, Palombini L, Tufik S, Hora F, Nery LE. | Revista: Indian Journal of Medical Research
Hipoventilação relacionada ao sono | Autor: Togeiro SMGP, Fontes FH. | Revista: Jornal Brasileiro de Pneumologia
Electrophysiological correlates of sleep disturbance induced by acute and chronic administration of D-amphetamine | Autor: Andersen ML, Margis R, Frey BN, Giglio LMF, Kapczinski F, Tufik S. | Revista: Brain Research
Differential effects of sleep loss and chronic stressors on lipid metabolism | Autor: Andersen ML, Perry JC, Bignotto M, Tufik S. | Revista: Sleep Science | Site: http://www.sleepscience.com.br/pdf/articles/vol2/SleepScience_vol2_issue03_art03.pdf
Abordagem geral do paciente com síndrome da apneia obstrutiva do sono | Autor: Bittencourt LRA, Haddad FM, Dal Fabbro C, Cintra FD, Rios L. | Revista: Revista Brasileira de Hipertensão
Sleep-disordered breathing and chronic atrial fibrillation | Autor: Braga B, Poyares D, Cintra F, Guilleminault C, Cirenza C, Horbach S, Macedo D, Silva R, Tufik S, De Paola AAV. | Revista: Sleep Medicine
Effects of isoflavone on oxidative stress parameters and homocysteine in postmenopausal women complaining of insomnia | Autor: Brandão LC, Hachul H, Bittencourt LR, Baracat EC, Tufik S, D’Almeida V. | Revista: Biological Research | Site: http://www.scielo.cl/scielo.php?pid=S0716-97602009000300002&script=sci_arttext
Continuous positive airway pressure therapy improves hypoadiponectinemia in severe obese men with obstructive sleep apnea without changes in insulin resistance | Autor: Carneiro G, Togeiro SM, Ribeiro-Filho FF, Truksinas E, Ribeiro AB, MT Zanella, Tufik S. | Revista: Metabolic Syndrome and Related Disorders
Nocturnal hypoxia and sleep disturbances in cystic fibrosis | Autor: Castro-Silva C, de Bruin VMS, Cavalcante AGM, Bittencourt LRA, de Bruin PFC | Revista: Pediatric Pulmonology
Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in São Paulo | Autor: Coelho FMS, Pradella-Hallinan M, Predazzoli Neto M, Bittencourt LRA, Tufik S. | Revista: Revista Brasileira de Psiquiatria
Prevalence of temporomandibular disorders in Obstructive Sleep Apnea | Autor: Cunali P, Almeida FR, Santos CD, Valdrighi NY, Nascimento LS, Dal Fabbro C, Tufik S, Bittencourt LRA | Revista: Journal of Orofacial Pain
Long term PSG in a bruxist patient: the role of daily anxiety | Autor: Dal’Fabro C, Siqueira JTT, Tufik S. | Revista: Sleep Medicine
. Study of metabolic changes in patients with Obstructive Sleep Apnea Syndrome before and after use of continuous positive airway pressure | Autor: Garbuio S, Salles LV, D’Almeida V, Tufik S, Bittencourt LRA. | Revista: Sleep Science
Clinical profile of menopausal insomniac women referred to sleep laboratory | Autor: Hachul H, Brandão LC, Bittencourt LRA, D’Almeida V, Andersen ML, Baracat EC, Tufik S. | Revista: Acta Obstetricia et Gynecologica Scandinavica
Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males | Autor: Koyama RG, Drager LF, Lorenzi-Filho G, Cintra FD, Pereira AC, Poyares D, Krieger JE, Castro RMRPS, Tufik S, Mello MT, Pedrazzoli M. | Revista: Sleep Medicine
Is there a connection between long airplane flight, venous thromboembolism, and sleep-disordered breathing? | Autor: Lopes MC, Silva HS, Bittencourt LRA, Chervin RD, Tufik S. | Revista: Sleep Medicine
Impact of continuous positive airway pressure treatment on left atrial volume and function in patients with obstructive sleep apnoea assessed by real-time three-dimensional echocardiography | Autor: Oliveira W, Campos O, Cintra F, Matos L, Vieira ML, Rollim B, Fujita L, Tufik S, Poyares D. | Revista: Heart
Sleep perception in insomniacs, sleep-disordered breathing patients, and healthy volunteers – an important biologic parameter of sleep | Autor: Pinto Jr. LR, Pinto MCR, Goulart LI, Truksinas E, Rossi MV, Morin CM, Tufik S. | Revista: Sleep Medicine
Refractory cluster headache in a patient with bruxism and obstructive sleep apnea: a case report | Autor: Ranieri ALP, Tufik S, Siqueira JTT. | Revista: Sleep Breath
Improving CPAP compliance by a basic educational program with nurse support for Obstructive Sleep Apnea Syndrome patients | Autor: Rueda AD, Santos-Silva R, Togeiro SM, Tufik S, Bittencourt LRA. | Revista: Sleep Science | Site: http://www.sleepscience.com.br/pdf/articles/vol2/SleepScience_vol2_issue01_art01.pdf
Validation of a portable monitoring system for the diagnosis of Obstructive Sleep Apnea Syndrome | Autor: Santos-Silva R, Sartori DE, Truksinas V, Truksinas E, Alonso FFD, Tufik S, Bittencourt LRA. | Revista: Sleep
Distinct gender-related sleep pattern in an acute model of TMJ pain | Autor: Schütz TCB, Andersen ML, Silva A, Tufik S. | Revista: Journal of Dental Research
The influence of orofacial pain on sleep pattern: a review of theory, animal models and future directions | Autor: Schütz TCB, Andersen ML, Tufik S. | Revista: Sleep Medicine
Effects of the use of MIG3 bioceramics fabrics use - long infrared emitter – in pain, intolerance to cold and periodic limb movements in post-polio syndrome | Autor: Silva TM, Moreira GA, Quadros AAJ, Pradella-Hallinan M, Tufik S, Oliveira ASB. | Revista: Arquivos de Neuropsiquiatria
The prevalence and significance of periodic leg movements during sleep in patients with congestive heart failure | Autor: Skomro R, Silva R, Alves R, Figueiredo A, Lorenzi-Filho G. | Revista: Sleep Breath
Disturbed sleep and musculoskeletal pain in the bed partner of patients with obstructive sleep apnea | Autor: Smith AKA, Togeiro SMG, Tufik S, Roizenblatt S. | Revista: Sleep Medicine
Stress-induced sleep rebound: adaptive behavior and possible mechanisms. | Autor: Suchecki D, Machado RB, Tiba PA. | Revista: Sleep Science | Site: http://www.sleepscience.com.br/pdf/articles/vol2/SleepScience_vol2_issue03_art06.pdf
Almeida CMO, Poyares D, Tufik S. | Autor: Almeida CMO, Poyares D, Tufik S. | Revista: Reviews in the Neurosciences
The effects of testosterone on sleep and sleepdisordered breathing in men: its bidirectional interaction with erectile function | Autor: Andersen ML, Tufik S. | Revista: Sleep Medicine
Type of dental occlusion in children and adolescents presenting sleep disorders | Autor: Anselmo MRG, Siqueira JTT, Dal’Fabbro C, Tufik S. | Revista: Sleep Science
Placebo and modafinil effect on sleepiness in obstructive sleep apnea | Autor: Bittencourt LRA, Lucchesi LM, Rueda AD, Garbuio SA, Palombini LO, Guilleminault C, Tufik S. | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Distúrbios respiratórios relacionados ao sono: classificação e diagnóstico | Autor: Bittencourt LRA, Garbuio SA. | Revista: Pneumologia Paulista
Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome | Autor: Carneiro G, Togeiro SM, Hayashi LF, Ribeiro-Filho FF, Ribeiro AB, Tufik S, Zanella MT. | Revista: American Journal of Physiology - Endocrinology and Metabolism
Casein kinase I epsilon (CKIepsilon) N408 allele is very rare in the Brazilian population and is not involved in susceptibility to circadian rhythm sleep disorders | Autor: Castro RMRPS, Barbosa AA, Pedrazzoli M, Tufik S. | Revista: Behavioural Brain Research
Fisiopatologia da hipertensão arterial sistêmica na síndrome da apnéia e hipopnéia obstrutiva do sono | Autor: Cintra FD, Bittencourt LRA, Poyares D, Tufik S. | Revista: Hipertensão
Narcolepsia | Autor: Coelho FMS, Elias RM, Pradella-Hallinan M, Bittencourt LRA, Tufik S. | Revista: Revista Brasileira de Medicina
Physical therapy reduces insomnia symptoms in postmenopausal women | Autor: Llanas AC, Hachul H, Bittencourt LRA, Tufik S. | Revista: Maturitas
Relationship between the quality of life and the severity of obstructive sleep apnea syndrome | Autor: Lopes C, Esteves AM, Bittencourt LRA, Tufik S, Mello MT. | Revista: Brazilian Journal of Medical and Biological Research
Systematic head and neck physical examination as a predictor of obstructive sleep apnea in class III obese patients | Autor: Martinho FL, Tangerina RP, Moura SMGT, Gregório LC, Tufik S, Bittencourt LRA. | Revista: Brazilian Journal of Medical and Biological Research
Donepezil improves obstructive sleep apnea in Alzheimer’s disease: a double-blind placebo-controlled study | Autor: Moraes WAS, Poyares DLR, Sukys-Claudino L, Guilleminault C, Tufik S. | Revista: Chest
Left atrial colume and function in patients with obstructive sleep apnea assessed by real-time three-dimensional echocardiography | Autor: Oliveira W, Campos O, Lira-Filho EB, Cintra FD, Vieira M, Ponchirolli A, de Paola A, Tufik S, Poyares D. | Revista: Journal of the American Society of Echocardiography
Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health | Autor: Stucki A, Cieza A, Michel F, Stucki G, Bentley A, Culebras A, Tufik S, Kotchabhakdi N, Tachibana N, Ustun B, Partinen M | Revista: Sleep Medicine
Achados clínicos e polissonográficos em pacientes com obesidade classe III | Autor: Tangerina RP, Martinho FL, Togeiro SM, Gregório LC, Tufik S, Bittencourt LR. | Revista: Revista Brasileira de Otorrinolaringologia
Avaliação peri-operatória da apnéia obstrutiva do sono no obeso | Autor: Togeiro SMGP. | Revista: Pneumologia Paulista
Interações entre Síndrome da Apnéia Obstrutiva do Sono e resistência à insulina | Autor: Carneiro G, Ribeiro Filho FF, Togeiro SM, Tufik S, Zanella MT. | Revista: Arquivos Brasileiros de Endocrinologia e Metabologia
A study of T CD4, CD8 and B lymphocytes in narcoleptic patients | Autor: Coelho FMS, Pradella-Hallinan M, Alves GR, Bittencourt LRA, Pedrazzoli Neto M, Moreira F, Tufik S. | Revista: Arquivos de Neuropsiquiatria
Narcolepsia | Autor: Coelho FMS, Elias RM, Pradella-Hallinan M, Bittencourt LRA, Tufik S. | Revista: Revista de Psiquiatria Clínica
Relação entre sono e obesidade: uma revisão da literatura | Autor: Crispim CA, Zalcman I, Dattilo M, Padilha HG, Tufik S, Mello MT. | Revista: Arquivos Brasileiros de Endocrinologia e Metabologia
Treatment of moderate obstructive sleep apnea syndrome with acupuncture: a randomised, placebo-controlled pilot trial | Autor: Freire AO, Sugai GCM, Chrispin FS, Togeiro SM, Yamamura Y, Mello LE, Tufik S. | Revista: Sleep Medicine
Tratamento da respiração de Cheyne-Stokes em pacientes com insuficiência cardíaca congestiva | Autor: Freitas IGA, Togeiro SMGP, Tufik S. | Revista: Arquivos Brasileiros de Cardiologia
Estrogen therapy reduces nocturnal periodic limb movements | Autor: Hachul H, Baracat EC, Soares Jr. JM, Haidar MA, Mello MT, Tufik S, Bittencourt LRA. | Revista: Maturitas
Clinical, anthropometric and upper airway anatomic characteristics of obese patients with obstructive sleep apnea syndrome | Autor: Hora F, Nápolis LM, Daltro C, Kodaira SK, Tufik S, Togeiro SM, Nery LE. | Revista: Respiration
Síndrome da apnéia-hipopnéia obstrutiva do sono | Autor: Martins AB, Tufik S, Moura SMGPT. | Revista: Jornal Brasileiro de Pneumologia
Repercussões imunológicas dos distúrbios do sono: o eixo hipotálamo-pituitária-adrenal como fator modulador | Autor: Palma BD, Tiba PA, Machado RB, Tufik S, Suchecki D. | Revista: Revista Brasileira de Psiquiatria
Tratamento não farmacológico para a insônia crônica | Autor: Passos GS, Tufik S, Santana MG, Poyares D, Mello MT. | Revista: Revista Brasileira de Psiquiatria
HLA-DQB1 genotyping in a family with narcolepsy-cataplexy | Autor: Pedrazzoli M, Pontes JC, Peirano P, Tufik S. | Revista: Brain Research
Obesidade e distúrbio respiratório do sono, uma associação de fatores de risco | Autor: Poyares D, Moraes W. | Revista: Arquivos Brasileiros de Endocrinologia e Metabologia
Sleep bruxism and temporomandibular disorder: Clinical and polysomnographic evaluation | Autor: Camparis CM, Formigoni G, Teixeira MJ, Bittencourt LRA, Tufik S, Siqueira JTT. | Revista: Archives of Oral Biology
Sleep disturbance induced by substance P in mice | Autor: Andersen ML, Nascimento DC, Machado RB, Roizenblatt S, Moldofsky H, Tufik S. | Revista: Behavioural Brain Research
Effects of progesterone on sleep: a possible pharmacological treatment for sleep-breathing disorders? | Autor: Andersen ML, Bittencourt LRA, Antunes IB, Tufik S. | Revista: Current Medicinal Chemistry
Alterações cardiovasculares na síndrome da apnéia obstrutiva do sono | Autor: Cintra FD, Poyares D, Guilleminault C, Carvalho AC, Tufik S, De Paola AAV. | Revista: Arquivos Brasileiros de Cardiologia
TNF and IL-6 levels in narcoleptic patients | Autor: Coelho FMS, Sousa HP, Rodrigues Alves G, Bittencourt LRA, Pradella-Hallinan M, Moreira F, Pedrazzoli Neto M, Tufik S. | Revista: Einstein
Repercussions of a sleep medicine outreach program. | Autor: Conway SG, Tufik S, Frussa Filho R, Bittencourt LRA. | Revista: Brazilian Journal of Medical and Biological Research
Upper airway resistance syndrome: a long-term outcome study | Autor: Guilleminault C, Kirisoglu C, Poyares D, Palombini L, Leger D, Farid-Moayer M, Ohayon MM. | Revista: Journal of Psychiatric Research
Sleep disturbances, oxidative stress and cardiovascular risk parameters in postmenopausal women complaining of insomnia | Autor: Hachul de Campos H, Brandão LC, D'Almeida V, Grego BHC, Bittencourt LR, Tufik S, Baracat EC. | Revista: Climacteric
Obstructive sleep apnea in patients undergoing supracricoid horizontal or frontolateral vertical partial laryngectomy | Autor: Israel Y, Cervantes O, Abrahão M, Ceccon FP, Marques Filho MF, Nascimento LA, Zonato AI, Tufik S. | Revista: Otolaryngology - Head and Neck Surgery
Anestesia e apnéia obstrutiva do sono | Autor: Machado C, Yamashita AM, Poyares D, Tufik S, Togeiro S. | Revista: Revista Brasileira de Anestesiologia
Obese obstructive sleep apnea patients with tonsil hypertrophy submitted to tonsillectomy | Autor: Martinho FL, Zonato AI, Bittencourt LRA, Soares MCM, Silva RFN, Gregório LC, Tufik S. | Revista: Brazilian Journal of Medical and Biological Research
Sleep disorders, sleepiness and traffic safety: a public health menace | Autor: Pandi-Perumal SR, Verster JC, Kayumov L, Lowe AD, Santana MG, Pires MLN, Tufik S, Mello MT. | Revista: Brazilian Journal of Medical and Biological Research
A double-blind, placebo-controlled, crossover study of sildenafil in obstructive sleep apnea | Autor: Roizenblatt S, Guilleminault C, Poyares D, Cintra F, Kauati A, Tufik S. | Revista: Archives of Internal Medicine
Transtornos respiratórios do sono e fibromialgia | Autor: Roizenblatt S. | Revista: Jornal Brasileiro de Pneumologia
Visual and automatic cyclic alternating pattern (CAP) scoring | Autor: Rosa A, Alves GR, Brito M, Lopes MC, Tufik S. | Revista: Arquivos de Neuropsiquiatria
Aplicação do modelo morfométrico de Kushida em pacientes com distúrbios respiratórios do sono | Autor: Soares MCM, Bittencourt LRA, Zonato AI, Gregório LC. | Revista: Revista Brasileira de Otorribolaringologia
Upper airway surgery: the effect on nasal continuous positive airway pressure titration on obstructive sleep apnea patients | Autor: Zonato AI, Martinho FL, Bittencourt LR, Gregório LC, Tufik S | Revista: European Archives of Oto-Rhino-Laryngology
Sonolência excessiva | Autor: Bittencourt LRA, Silva RS, Santos RF, Pires MLN, Mello MT. | Revista: Revista Brasileira de Psiquiatria
Adult Chiari malformation and sleep apnoea | Autor: Botelho RV, Bittencourt LR, Rotta JM, Tufik S. | Revista: Neurosurgical Review
Prevalência de distúrbios do sono na pós-menopausa | Autor: Campos HH, Bittencourt LRA, Haidar MA, Tufik S, Baracat EC. | Revista: Revista Brasileira de Ginecologia e Obstetrícia
Distúrbios do sono no climatério | Autor: Campos HH, Bittencourt LRA, Tufik S, Baracat EC. | Revista: Femina
Heart rate variability, sympathetic and vagal balance and EEG arousals in upper airway resistance and mild obstructive sleep apnea syndromes | Autor: Guilleminault C, Poyares D, Rosa A, Huang YS. | Revista: Sleep Medicine
Distinct effects of sleep deprivation on binding to repinephrine and serotonin transporter in rat brain | Autor: Hipolide DC, Moreira KM, Barlow K, Wilson A, Nobrega JN, Tufik S | Revista: Progress in Neuropsychopharmacology & Biological Psychiatry
Poyares D, Pinto Jr LR, Tavares S, Barros-Vieira S. | Autor: Poyares D, Pinto Jr LR, Tavares S, Barros-Vieira S. | Revista: Revista Brasileira de Psiquiatria
Violência durante o sono | Autor: Poyares D, Almeida CMO, Silva RS, Rosa A, Guilleminault C. | Revista: Revista Brasileira de Psiquiatria
Relationship among end-stage renal disease, hypertension, and sleep apnea in nondiabetic dialysis patients | Autor: Rodrigues CJO, Marson O, Tufik S, Kohlmann Jr O, Togeiro SMGP, Ribeiro AB, Tavares A. | Revista: American Journal of Hypertension
Métodos diagnósticos nos distúrbios do sono | Autor: Togeiro SMGP, Smith AK. | Revista: Revista Brasileira de Psiquiatria
Síndrome da apnéia obstrutiva do sono: abordagem clínica | Autor: Togeiro SMGP, Martins AB, Tufik S. | Revista: Revista Brasileira de Hipertensão
Sono, transtornos do sono e uso de hipnoindutores em psiquiatria | Autor: Tufik S, Poyares D. | Revista: Revista Brasileira de Psiquiatria
Head and neck physical examination: comparison between nonapneic and obstructive sleep apnea patients | Autor: Zonato AI, Martinho FL, Bittencourt LR, de Oliveira Campones Brasil O, Gregorio LC, Tufik S. | Revista: Laryngoscope
A malformação de Chiari do adulto e a apnéia do sono | Autor: Botelho RV, Bittencourt LRA, Rotta JM, Tufik S. | Revista: Arquivos brasileiros de neurocirurgia
Challenges to orexins in the maintenance of homeostasis – their participation in wake-sleep cycle and motor activity | Autor: D'Almeida V, Pedrazzoli M, Martins PJF, Hipólide D, Lin L, Mignot E, Raymond R, Barlow K, Parkes J, Nobrega JN, Tufik S. | Revista: Hypnos
Occurrence of limb movement during sleep in rats with spinal cord injury | Autor: Esteves AM, Mello MT, Lancellotti CLP, Natal CL, Tufik S. | Revista: Brain Research
Indicação cirúrgica otorrinolaringológica em um ambulatório para pacientes com síndrome da apnéia e hipopnéia obstrutiva do sono | Autor: Martinho FL, Zonato AI, Bittencourt LRA, Gregório CL, Gregório LC, Tufik S. | Revista: Revista Brasileira de Otorrinolaringologia
Comparison between dopaminergic agents and physical exercise as treatment for periodic limb movements in patients with spinal cord injury | Autor: Mello MT, Esteves AM, Tufik S. | Revista: Spinal Cord
Different criteria of sleep latency and the effect of melatonin on sleep consolidation | Autor: Pinto Jr LR, Seabra ML, Tufik S. | Revista: Sleep
Repercussions of sleep apnea syndrome on the patient’s spouse and family | Autor: Pinto MCR, Roizenblatt S, Smith AK, Pinto Jr. LR, Tufik S. | Revista: Hypnos
Chronic benzodiazepine usage and withdrawal in insomnia patients | Autor: Poyares D, Guilleminault C, Ohayon MM, Tufik S. | Revista: Journal of Psychiatric Research
Influence of temporomandibular joint pain on sleep patterns: role of nitric oxide | Autor: Schutz TC, Andersen ML, Tufik S. | Revista: Journal of Dental Research
A comparison of public and private obstructive sleep apnea clinics | Autor: Zonato AI, Bittencourt LR, Martinho FL, Baiard P, Togeiro SM, Benedito-Silva AA, Tufik S. | Revista: Brazilian Journal of Medical and Biological Research
Sleep Disorders as a Cause of Motor Vehicle Collisions | Autor: De Mello MT, Narciso FV, Tufik S, Paiva T, Spence DW, BaHammam AS, Verster JC, Pandi-Perumal SR | Revista: Int J Preventive Medresumo
Studies have shown that a large proportion of traffic accidents around the world are related to inadequate or disordered sleep. Recent surveys have linked driver fatigue to 16% to 20% of serious highway accidents in the UK, Australia, and Brazil. Fatigue as a result of sleep disorders (especially obstructive sleep apnea), excessive workload and lack of physical and mental rest, have been shown to be major contributing factors in motor vehicle accidents. A number of behavioral, physiological, and psychometric tests are being used increasingly to evaluate the impact of fatigue on driver performance. These include the oculography, polysomnography, actigraphy, the maintenance of wakefulness test, and others. Various strategies have been proposed for preventing or reducing the impact of fatigue on motor vehicle accidents. These have included: Educational programs emphasizing the importance of restorative sleep and the need for drivers to recognize the presence of fatigue symptoms, and to determine when to stop to sleep; The use of exercise to increase alertness and to promote restorative sleep; The use of substances or drugs to promote sleep or alertness (i.e. caffeine, modafinil, melatonin and others), as well as specific sleep disorders treatment; The use of CPAP therapy for reducing excessive sleepiness among drivers who have been diagnosed with obstructive sleep apnea. The evidence cited in this review justifies the call for all efforts to be undertaken that may increase awareness of inadequate sleep as a cause of traffic accidents. It is strongly recommended that, for the purpose of promoting highway safety and saving lives, all disorders that cause excessive sleepiness should be investigated and monitored.
The impact of shift work on Brazilian train drivers with different chronotypes. A comparative analysis through objective and subjective criteria. | Autor: Fernandes-Junior SA, Antonietti LS, Saba A, Faria AP, Esteves AM, Tufik S, De Mello MT | Revista: Med Principles Practiceresumo
OBJECTIVE: The aim of this study was to compare sleep pattern, tiredness sensation and quality of life between different chronotypes in train drivers from a Brazilian transportation company.
SUBJECTS AND METHODS: Ninety-one train drivers, working a rotary work schedule including night shift, were divided into three groups according to their chronotype (morning types, intermediate or evening types) and were assessed for their sleep and quality of life, as characterized by a subjective questionnaire and the Psychomotor Vigilance Task (PVT), applied before and immediately after the night shift. The pattern of activity and rest was measured for 10 days by actigraphy, and the chronotype was determined through the Morningness-Eveningness Questionnaire.
RESULTS: Forty-one (45.1%) individuals were classified as morning type, 44 (48.4%) were classified as intermediate and 6 (6.6%) as evening type. The evening types had a tendency to remain awake for a longer period of time before the night shift (p = 0.05) and scored worse overall for quality of life compared to morning types (p = 0.11). There was no significant difference between the groups regarding variability in the PVT performance, even when covaried by the period of waking time before the test. There was no significant difference either in feelings of fatigue before and after starting the shift.
CONCLUSION: Although the evening type number was small, evening type individuals scored worse relative to sleep and quality of life than morning type individuals.
Shift work disorders: implications and proposed management. | Autor: Burke PR, Rios LF, Mendonça ET, Bittencourt AG, Tufik S, De Mello MT, Poyares D. | Revista: Sleep Sci.
Adipokine levels are altered by shiftwork: a preliminary study | Autor: Crispim CA, Padilha HG, Zimberg IZ, Waterhouse J, Dattilo M, Tufik S, de Mello MT | Revista: Chronobiol Intresumo
Shiftwork is often associated with metabolic diseases, and in the past few years, several cytokines have been postulated to contribute to various diseases, including insulin resistance. The aim of this study was to compare the concentrations of adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in samples of young adult men exposed to a fixed (i) night shift (n = 9), working from 22:00 to 06:00 h; (ii) early morning shift (n = 6), working from 06:00 to 14:00 h; and (iii) day shift (n = 7), working from 08:00 to 17:00 h. The fixed night-shift and early-morning-shift samples were considered collectively as a shiftworker group given their work times. Blood samples were collected during the regular working day at 4-h intervals over the course of 24 h, thus totaling six samples. Morphological and physical activity parameters did not differ between the three groups. Total energy intake was lowest on the early morning shifts (p < .03). Both shiftworker groups ingested a significantly higher percentage of fat (p < .003) and a lower percentage of carbohydrate (p < .0005) than the day group. The early morning group had a lower mean 24-h level of adiponectin than the other two groups (p = .016), and both the early morning and night groups exhibited higher mean 24-h levels of TNF-α than the day group (p = .0001). The 24-h mean levels of IL-6 did not differ significantly between the groups (p = .147). None of the groups exhibited a significant circadian effect on adiponectin (p = .829), TNF-α (p = .779), or IL-6 (p = .979) levels. These results indicate that individuals who are enrolled in shiftwork are susceptible to alterations in the secretion of cytokines that are involved in insulin resistance and cardiovascular disease, both of which are known to affect this population.
Prevalence of and risk factors for obstructive sleep apnea syndrome in Brazilian railroad workers | Autor: Koyama RG, Esteves AM, Oliveira E Silva L, Lira FS, Bittencourt LR, Tufik S, de Mello MT | Revista: Sleep Medresumo
OBJECTIVE: This study evaluated the prevalence of, and the risk factors for, obstructive sleep apnea syndrome (OSAS) among Brazilian railroad workers.
METHODS: Male railroad workers (745) from a railway company in Brazil were analyzed after responding to questionnaires about their demographics, sleep habits, excessive daytime sleepiness (Epworth), and the likelihood of having apnea (Berlin). We also performed polysomnography and measured anthropometric data for all of the railroad workers.
RESULTS: The results showed that 261 (35.03%) of the railroad workers presented with OSAS. These railroad workers were older (OSAS: 38.53±10.08 versus non-OSAS: 33.99±8.92 years), more obese according to body mass index (27.70±4.38 versus 26.22±3.92 kg/m(2)), and employed for a longer period of time (14.32±9.13 years) compared with those without OSAS (10.96±7.66 years). Among those with OSAS, 9.5% were smokers and 54.7% reported alcohol use. The associated risk factors were age (OR=2.51, 95% CI=1.76-3.57), BMI (OR=1.56, 95% CI=1.04-2.34), alcohol use (OR=1.28, 95% CI=0.90-1.81), and a high chance of having sleep apnea, as assessed by the Berlin questionnaire (OR=2.19, 95% CI=1.49-3.21).
CONCLUSION: The prevalence of OSAS in Brazilian railroad workers was higher than that observed in the general population but similar to that found in the population of the city of São Paulo, Brazil. These results suggest that age, BMI, a high risk of developing apnea through subjective self-reporting (Berlin), and alcohol use are associated with a higher risk of developing OSAS. These data reinforce the need to be more attentive to this population because they have a higher propensity for accidents.
Mood, sleep patterns and the effect of physical activity on the life quality of brazilian train operators. | Autor: Silva LO, Esteves AM, Alves NNL, Carvalho ANS, Narciso FV, Bittencourt LRA, Tufik S, De Mello MT. | Revista: Sleep Sci.
Metabolic impact of shift work. | Autor: Zimberg IZ, Fernandes Jr SA, Crispim CA, Tufik S, De Mello MT. | Revista: Work.
Sono, trabalho e estudo: duração do sono em estudantes trabalhadores e não trabalhadores | Autor: Pereira EF, Bernardo MPSL, D’Almeida V, Louzada FM. | Revista: Cadernos de Saúde Pública | Site: http://www.scielo.br/pdf/csp/v27n5/15.pdf
Metabolic responses on the early shift | Autor: Padilha HG, Crispim CA, Zimberg IZ, Folkard S, Tufik S, de Mello MT. | Revista: Chronobiology International
O piloto comercial e a jornada de trabalho: o tempo de jornada, o descanso e os acidentes, aspectos relacionados ao fator humano: uma revisão de literatura | Autor: De Mello MT, Noce F, Kouyomdjian C, Tufik S. | Revista: Revista Conexão SIPAER
Sleep and transit in Brazil: new legislation | Autor: Mello MT, Bittencourt LRA, Cunha RCF, Esteves AM, Tufik S. | Revista: Journal of Clinical Sleep Medicine
Trabalho em turnos e aspectos nutricionais: uma revisão | Autor: Crispim CA, Zimberg IZ, Dattilo M, Padilha HG, Tufik S, Mello MT. | Revista: Nutrire - Sociedade Brasileira de Alimentação e Nutrição
Sleep, ageing and night work | Autor: Pires MLN, Teixeira CW, Esteves AM, Bittencourt LRA, Silva RS, Santos RF, Tufik S, Mello MT. | Revista: Brazilian Journal of Medical and Biological Research
Professional drivers and working time: journey span, rest, and accidents | Autor: Noce F, Tufik S, Mello MT. | Revista: Sleep Science
Sleep complaints and polysomnographic findings: a study of nuclear power plant shift workers | Autor: Paim SL, Pires ML, Bittencourt LR, Silva RS, Santos RF, Esteves AM, Barreto AT, Tufik S, de Mello MT. | Revista: Chronobiology International
Hypersomnolence and accidents in truck drivers: a cross sectional study | Autor: Pinho RSN, Silva Jr. FP, Bastos JPC, Maia WS, Mello MT, de Bruin VMS, de Bruin PFC. | Revista: Chronobiology International
Sleep and sleepiness among Brazilian shift-working bus drivers | Autor: Santos EHR, Mello MT, Pradella-Hallinan M, Lucchesi L, Pires MLN, Tufik S. | Revista: Chronobiology International
Dopamine transporter shown by SPECT in PLM patients after acute physical exercise | Autor: Cavagnolli DA, Esteves AM, Castiglione ML, Batista IR, Bressan RA, Tufik S, De Mello MT. | Revista: Med Sci Sports Exerciseresumo
PURPOSE: This study aimed to evaluate dopamine transporter (DAT) density in patients with periodic leg movement (PLM) shown by [(99mt)Tc]TRODAT-1 single-photon emission computed tomography (SPECT) imaging and to determine the influence of acute physical exercise (maximal exercise test [MET]) on DAT densities.
METHODS: Sixteen healthy male volunteers between 45 and 65 yr of age were selected to participate in the study. Each subject (eight subjects in the control group and eight subjects in the patients with PLM experimental group) underwent baseline polysomnography (PSG) to evaluate sleep patterns and PLM index values. After obtaining PSG baselines, SPECT baselines were determined using [(99mt)Tc]TRODAT-1, a selective DAT imaging ligand. Subsequently, the volunteers performed the MET in the morning, followed by a SPECT 2 h later and PSG that night to assess the effect of acute physical exercise on DAT and sleep patterns.
RESULTS: The baseline SPECT results showed marginally significantly lower DAT densities in the striatal region of the experimental group. After the MET, no significant differences were observed between groups. The results also showed a significant reduction in the PLM index in the experimental group and a significantly increased percentage of stage 1 non-REM sleep in both groups after MET.
CONCLUSIONS: Our results show that patients with PLM had a marginally lower DAT density in the left putamen region compared with the control group. Although the effect of acute physical exercise (MET) reduced PLM symptoms, the results suggest that this improvement was not due to DAT availability.
Resistance exercise: a non-pharmacological strategy to minimize or reverse sleep deprivation-induced muscle atrophy | Autor: Mônico-Neto M, Antunes HKM, Dattilo M, Medeiros A, Souza HS, Lee KS, Melo CM, Tufik S, De Mello MT | Revista: Med Hypothesesresumo
Sleep is important for maintenance of skeletal muscle health. Sleep debt can induce muscle atrophy by increasing glucocorticoids and decreasing testosterone, growth hormone and insulin-like growth factor-I. These hormonal alterations result in a highly proteolytic environment characterized by decreased protein synthesis and increased degradation. Given that sleep deprivation is increasingly prevalent in modern society, strategies to minimize or reverse its adverse effects need to be investigated. Resistance exercise has been suggested as an intervention that would benefit the muscle health. The practice of this type of exercise can increase the concentration of testosterone, growth hormone and insulin-like growth factor I and stimulate the protein synthesis through a key signaling molecule, mammalian target of rapamycin. Thus, we hypothesized that resistance exercise is an important non-pharmacological strategy to counteract deleterious effects of sleep debt on skeletal muscle.
Free-running circadian rhythms of muscle strength, reaction time, and body temperature in totally blind people | Autor: Squarcini CF, Pires ML, Lopes C, Benedito-Silva AA, Esteves AM, Cornelissen-Guillaume G, Matarazzo C, Garcia D, Silva MS, Tufik S, de Mello MT | Revista: Eur J Appl Physiol.resumo
Light is the major synchronizer of circadian rhythms. In the absence of light, as for totally blind people, some variables, such as body temperature, have an endogenous period that is longer than 24 h and tend to be free running. However, the circadian rhythm of muscle strength and reaction time in totally blind people has not been defined in the literature. The objective of this study was to determine the period of the endogenous circadian rhythm of the isometric and isokinetic contraction strength and simple reaction time of totally blind people. The study included six totally blind people with free-running circadian rhythms and four sighted people (control group). Although the control group required only a single session to determine the circadian rhythm, the blind people required three sessions to determine the endogenous period. In each session, isometric strength, isokinetic strength, reaction time, and body temperature were collected six different times a day with an interval of at least 8 h. The control group had better performance for strength and reaction time in the afternoon. For the blind, this performance became delayed throughout the day. Therefore, we conclude that the circadian rhythms of strength and simple reaction time of totally blind people are within their free-running periods. For some professionals, like the blind paralympic athletes, activities that require large physiological capacities in which the maximum stimulus should match the ideal time of competition may result in the blind athletes falling short of their expected performance under this free-running condition.
Heavy episodic drinking and soccer practice among high school students in Brazil: the contextual aspects of this relationship. | Autor: Bedendo A, Opaleye ES, Andrade ALM, Noto AR. | Revista: BMC Public Health | Site: http://www.biomedcentral.com/1471-2458/13/247resumo
Heavy episodic drinking (HED) (consumption of five or more drinks on the same occasion) among adolescents is related to several problems and partaking in sport or physical activities has been suggested as an option to prevent or reduce alcohol consumption among this population. The aim of this study was to investigate the relationship between soccer practice and heavy episodic drinking among high school students from Brazil.
Data were obtained from a cross-sectional study among a representative sample of public and private high school students from all Brazilian state capitals (N=19,132). Only students aged from 14 to 18 who reported having taken part in soccer practice, other team sports or non-practicing sports in the last month were included. Characteristics of sport practice (frequency and motivation) and HED in the last month (type of drink; where and with whom they drank; frequency of HED) were also considered. Regression models were controlled for sociodemographic variables.
For all groups studied most of the students reported drinking beer, with friends and at nightclubs or bars. Soccer practice was associated to HED when compared to non-practicing sports and to other team sports. Compared to other team sports, playing soccer for pleasure or profession, but not for keep fit or health reasons, were more associated to HED. Frequency of soccer practice from 1 to 5 days per month and 20 or more days per month, but not from 6 to 19 days per month, were also more associated to HED.
The relationship between soccer and HED appears to be particularly stronger than in other team sports among adolescents in Brazil. Induced sociability of team sports practice cannot be assumed as the main reason for HED among soccer players. Possibly these results reflect the importance of a strong cultural association between soccer and beer in Brazil and these findings should be integrated to future prevention or intervention programs.
Physical exercise performed before bedtime improves the sleep pattern of healthy young good sleepers | Autor: Flausino NH, Prado JMS, Queiroz SS, Tufik S, De Mello MT | Revista: Psychophysiologyresumo
To investigate the influence of different intensities and durations of exercise before bedtime on the sleep pattern and core body temperature of individuals considered good sleepers, we selected 17 healthy males and all underwent 5 nonconsecutive days of study. Measurements of polysomnographic parameters and core body temperature were taken at baseline and after each experimental protocol, performed at night. We found increased sleep efficiency (p = .016) among all protocols compared with baseline data and increase in REM sleep latency (p = .047) between two experiments; there was decrease in the percentage of stage 1 sleep (p = .046) and wake after sleep onset (p = .003). Core body temperature did not change significantly during the nights following exercise. Exercise performed before sleep does not impair sleep quality; rather, its practice improves sleep in good sleepers who are nonathletes, and may be considered to improve sleep pattern.
Whole-blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery. | Autor: Pellegrino R, Sunaga DY, Guindalini C, Martins RCS, Mazzotti DR, Weiz Z, Daye J, Andersen ML, Tufik S | Revista: Physiological Genomicsresumo
Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.
Moderate exercise training modulates cytokine profile and sleep in elderly people | Autor: Santos RVT, Viana V, Boscolo R, Marques V, Santana M, Lira F, Tufik S, Mello M | Revista: Cytokine.resumo
Aging causes several physiological alterations, including alterations in sleep. It is possible that difficulty sleeping can be exacerbated by increased inflammation in older individuals. Moderate exercise training may be a modality of non-pharmacological treatment for sleep disorders and inflammation. We aimed to assess the effects of moderate exercise training on sleep in elderly people as well as their cytokine profiles. Additionally, we examined the effect of exercise training on quality of life parameters using a SF-36 questionnaire. Twenty-two male, sedentary, healthy, elderly volunteers performed moderate training for 60 min/day, 3 days/week for 24 week at a work rate equivalent to their ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2°C, with a humidity of 60 ± 5%. Blood and polysomnograph were collected twice: at baseline (1 week before training began) and after 6 months of training. Training increased aerobic capacity parameters (p<0.0001), decreased REM latency (p<0.02), and decreased time awake (p<0.05). After training, the levels of IL-6 (p<0.0001) and TNF-α (p<0.0001) and the ratio of TNF-α/IL-10 (p<0.0001) were decreased, whereas IL-10 levels were increased after training (p<0.001). Furthermore, exercise training was shown to improve quality of life parameters. Our results suggest that 6 months of training can improve sleep in the elderly and is related to the anti-inflammatory effect of moderate training, which modifies cytokine profiles.
Effects of Home-Based Exercise Training for Patients with Chronic Heart Failure and Sleep Apnea: Comparison of Two Different Programmes | Autor: Servantes DM, Mello MT | Revista: Clin Rehabresumo
OBJECTIVE: To evaluate the effects of home-based exercise for patients with chronic heart failure and sleep apnoea and to compare two different training programmes.
DESIGN: A randomized, prospective controlled trial.
SETTING: Department of Cardiology, University Hospital, Brazil.
SUBJECTS: Fifty chronic heart failure patients with sleep apnoea were randomized in three groups: Group 1 (aerobic training, n = 18), Group 2 (aerobic with strength training, n = 18), and Group 3 (untrained, n = 14).
INTERVENTIONS: The training programme for Groups 1 and 2 began with three supervised exercise sessions, after they underwent three months of home-based exercise. Patients were followed by weekly telephone call and were reviewed monthly. Group 3 had the status of physical activity evaluated weekly by interview to make sure they remained untrained.
MAIN OUTCOME MEASURES: At baseline and after three months: cardiopulmonary exercise testing, isokinetic strength and endurance, Minnesota living with heart failure questionnaire and polysomnography. Adherence was evaluated weekly.
RESULTS: Of the 50 patients enrolled in the study, 45 completed the programme. Clinical events: Group 1 (one death), Group 2 (one myocardial infarction), Group 3 (one death and two strokes). None were training related. Training groups showed improvement in all outcomes evaluated and the adherence was an important factor (Group 1 = 98.5% and Group 2 = 100.2%, P = 0.743). Untrained Group 3 demonstrated significant decrease or no change on measurements after three months without training.
CONCLUSION: Home-based exercise training is an important therapeutic strategy in chronic heart failure patients with sleep apnoea, and strength training resulted in a higher increase in muscle strength and endurance.