Intrathecal morphine and sleep apnoea severity in patients undergoing hip arthroplasty: a randomised, controlled, triple-blinded trial.

BACKGROUND: Intrathecal morphine prolongs analgesia after surgery, but has been implicated in postoperative respiratory depression or apnoeic episodes. However, this has not been investigated in a prospective trial using respiratory polygraphy. This randomised controlled triple-blinded trial tested the hypothesis that intrathecal morphine increases sleep apnoea severity, measured using respiratory polygraphy. METHODS: Sixty subjects undergoing hip arthroplasty under spinal anaesthesia received either 15 mg isobaric bupivacaine 0.5% with 0.5 ml normal saline 0.9% (control group) or 15 mg isobaric bupivacaine 0.5% with 0.5 ml intrathecal morphine 100 µg (intrathecal morphine group). Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the apnoea-hypopnoea index in the supine position (supine AHI) on the first postoperative night. Secondary outcomes included supine AHI on the third postoperative night, oxygen desaturation index (ODI), and ventilatory frequency during the first and third postoperative nights. RESULTS: On the first postoperative night, mean (95% confidence interval) values for supine AHI were 20.6 (13.9-27.3) and 21.2 (12.4-30.0) events h-1 in the control and intrathecal morphine groups, respectively (P=0.90). There were no significant between-group differences for any of the secondary outcomes, except for a significantly higher central and mixed apnoea index preoperatively and significantly lower mean SpO2 on the third postoperative night in the control group. CONCLUSIONS: Intrathecal morphine did not increase sleep apnoea severity when measured using respiratory polygraphy. Of note, all patients had an increased number of apnoeic episodes on the third postoperative night. CLINICAL TRIAL REGISTRATION: NCT02566226.

Health-related quality of life in patients with narcolepsy types 1 and 2 from a Sleep Center in Brazil / Qualidade de vida relacionada à saúde em pacientes com narcolepsia tipos 1 e 2 de um Centro de Sono no Brasil

ABSTRACT Introduction: Narcolepsy patients have higher prevalence of comorbidities, such as obesity, depression, and pain. Narcolepsy symptoms and concomitant medical conditions can impact the daily activities of patients. The objective of this study is to describe the quality of life in a sample of patients with narcolepsy, and the influence of the nutritional status in health domains. Methods: At Unifesp, two groups of 33 patients (narcolepsy types 1 and 2 meeting 2014 criteria, concerning hypocretin-1) and 33 controls without sleepiness, matched by age and sex, filled out the SF-36. Results: Narcolepsy groups, regardless of their nutritional status, had significantly lower scores in all domains, compared to controls, mainly in Role-physical, Role-emotional, and Energy/Fatigue. Role-physical score was lower in type 1 than in type 2 and controls (37.8±1.0 vs. 50.0±1.2 vs. 85.6±1.6; p<0.0001). Obese with type 2 narcolepsy scored lower than type 1 in physical scales. Conclusion: In a Sleep Center in São Paulo, Brazil, physical and mental health were impaired in narcolepsy types 1 and 2. The first report of the poor health status in Brazilians with narcolepsy type 2 suggests that obesity negatively affects physical domains.

RESUMO Introdução: Pacientes com narcolepsia têm maior prevalência de comorbidades, como obesidade, depressão e dor. Sintomas de narcolepsia e condições médicas concomitantes podem afetar as atividades diárias dos pacientes. O objetivo deste estudo é escrever a qualidade de vida em uma amostra de pacientes com narcolepsia e a influência do estado nutricional nos domínios de saúde. Métodos: Na Unifesp, dois grupos de 33 pacientes (narcolepsia tipos 1 e 2 compatível com os critérios de 2014, em relação a hipocretina-1) e 33 controles sem sonolência, pareados por idade e sexo, preencheram o SF-36. Resultados: Os grupos de narcolepsia, independentemente do estado nutricional, apresentaram pontuações significantemente menores em todos os domínios, comparados aos controles, principalmente nos quesitos físico, emocional e energia/fadiga. A pontuação do critério físico foi menor no tipo 1 do que no tipo 2 e nos controles (37,8±1,0 vs. 50,0±1,2 vs. 85,6±1,6; p<0,0001). Obesos com tipo 2 tiveram pontuação menor do que os com tipo 1 nas escalas físicas. Conclusão: Em um Centro de Sono de São Paulo, Brasil, as saúdes física e mental estavam comprometidas na narcolepsia tipos 1 e 2. O primeiro relato de estado de saúde ruim em brasileiros com narcolepsia tipo 2 sugere que a obesidade afeta negativamente os domínios físicos.

Associations between sleep conditions and body composition states: results of the EPISONO study.

BACKGROUND: Evidence suggests anthropometric indicators of obesity are associated with changes in sleep quality and quantity, and the presence of obstructive sleep apnoea (OSA). Investigations including diverse and objective evaluations of sleep and body composition are scarce. We aimed to evaluate the associations between indicators of sleep impairment and body composition states in a sample from a population-based study. METHODS: Participants of the first follow-up of the EPISONO (São Paulo, Brazil) >50 years were cross-sectionally evaluated. Sleep was assessed through questionnaires, actigraphy, and polysomnography. Body composition was evaluated by bioelectrical impedance analysis. Appendicular skeletal muscle mass adjusted for body mass index defined sarcopenia (men <0.789 and women <0.512). Total body fat defined obesity (men >30% and women >40%). The overlap between both conditions defined sarcopenic obesity (SO). Final results were obtained by multinomial logistic regression analysis. RESULTS: Three hundred fifty-nine adults [mean (standard deviation) age, 61 (8.8) years; 212 (59.1%) female] were enrolled. Obesity was detected in 22.6% of the sample, sarcopenia in 5.6%, and SO in 16.2%. After controlling for covariates, OSA was associated with SO [odds ratio = 3.14, 95% confidence interval (CI) = 1.49-6.61]. Additionally, nocturnal hypoxaemia was associated with both obesity (adjusted odds ratio = 2.59, 95% CI = 1.49-4.49) and SO (odds ratio = 2.92, 95% CI = 1.39-6.13). Other indicators of poor sleep/sleep disorders were not associated with body composition states. CONCLUSIONS: Sarcopenic obesity but not obesity alone was associated with OSA. Both obesity and SO but not sarcopenia were associated with nocturnal hypoxaemia. The findings suggest a complex pathophysiologic relationship between adverse body composition states and OSA. Upcoming research on risk factors and therapeutic interventions for OSA should target synchronically the lean and adipose body tissues.

Spirometry reference values for Black adults in Brazil / Valores de referência para espirometria forçada em adultos negros no Brasil

ABSTRACT Objective: To derive reference equations for spirometry in healthy Black adult never smokers in Brazil, comparing them with those published in 2007 for White adults in the country. Methods: The examinations followed the standards recommended by the Brazilian Thoracic Association, and the spirometers employed met the technical requirements set forth in the guidelines of the American Thoracic Society/European Respiratory Society. The lower limits were defined as the 5th percentile of the residuals. Results: Reference equations and limits were derived from a sample of 120 men and 124 women, inhabitants of eight Brazilian cities, all of whom were evaluated with a flow spirometer. The predicted values for FVC, FEV1, FEV1/FVC ratio, and PEF were better described by linear equations, whereas the flows were better described by logarithmic equations. The FEV1 and FVC reference values derived for Black adults were significantly lower than were those previously derived for White adults, regardless of gender. Conclusions: The fact that the predicted spirometry values derived for the population of Black adults in Brazil were lower than those previously derived for White adults in the country justifies the use of an equation specific to the former population.

RESUMO Objetivo: Derivar equações de referência para a espirometria forçada em adultos brasileiros negros, saudáveis, que nunca fumaram, e comparar os resultados com os valores previstos para a raça branca publicados em 2007. Métodos: Os exames seguiram as normas recomendadas pela Sociedade Brasileira de Pneumologia e Tisiologia, e os espirômetros preencheram os requisitos técnicos exigidos pelas diretrizes da American Thoracic Society/European Respiratory Society. Os limites inferiores foram derivados pela análise do 5º percentil dos resíduos. Resultados: Equações e limites de referência foram derivados de uma amostra com 120 homens e 124 mulheres, habitantes de oito cidades brasileiras, utilizando-se um espirômetro de fluxo. Os valores previstos para CVF, VEF1, relação VEF1/CVF e PFE foram mais bem ajustados por regressões lineares, enquanto os fluxos, por equações logarítmicas. Os valores de referência de VEF1 e CVF para ambos os sexos foram significativamente menores quando comparados aos previstos para adultos da raça branca no Brasil. Conclusões: O fato de que os valores previstos da espirometria forçada derivados para a população negra no Brasil tenham sido inferiores aos previstos para a raça branca no país justifica a utilização de uma equação específica para adultos negros.

Nicotine and sleep deprivation: impact on pain sensitivity and immune modulation in rats.

Repeated nicotine administration has been associated with increased paradoxical sleep in rats and antinociceptive properties, whereas paradoxical sleep deprivation (PSD) elicits pronociceptive and inflammatory responses. Thus, we aimed to evaluate the effect of repeated nicotine administration and its withdrawal combined with PSD on pain sensitivity and inflammatory markers. Sixty adult male Wistar rats were subjected to repeated injections of saline (SAL) or nicotine (NIC) for 12 days or 7 days of nicotine followed by acute mecamylamine administration on day 8 to precipitate nicotine abstinence (ABST). On day 9, the animals were submitted to PSD for 72 h or remained in control condition (CTRL); on day 12, thermal pain threshold was assessed by the hot plate test. PSD significantly decreased the latency to paw withdrawal in all groups compared to their respective controls. ABST-PSD animals presented higher levels of interleukin (IL)-6 compared to all groups, except ABST-CTRL. After adjustment for weight loss, IL-6, IL-4 and tumor necrosis factor alpha, ABST-PSD was associated with the lowest pain threshold. Nicotine and IL-4 levels were predictors of higher pain threshold. Hyperalgesia induced by PSD prevailed over the antinociceptive action of nicotine, while the association between PSD and ABST synergistically increased IL-6 concentrations and decreased pain threshold.

Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness.

INTRODUCTION: Sleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D). METHODS: Adults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m2, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea-Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed. RESULTS: We observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002]. CONCLUSION: We present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.

Obstructive sleep apnea and objective short sleep duration are independently associated with the risk of serum vitamin D deficiency.

BACKGROUND: Studies demonstrate an association between vitamin D (25(OH)D) deficiency and sleep disturbances, such as obstructive sleep apnea (OSA) and short sleep duration. However, to date, no studies have concurrently and objectively evaluated the effect of these factors on 25(OH)D. OBJECTIVES: To evaluate whether OSA and objective short sleep duration are independently associated with reduced 25(OH)D in an adult population sample. METHODS: A cross-sectional study included 657 individuals from the city of Sao Paulo, Brazil, as part of the ERA project. Participants fulfilled questionnaires and underwent clinical evaluation, polysomnography and blood sample collection for 25(OH)D quantification. OSA was classified into three categories (mild, moderate and severe). The risk of 25(OH)D deficiency was considered as levels<30 ng/mL. Short sleep duration was defined as total sleep time<6 hours. RESULTS: The risk of 25(OH)D deficiency was observed in 59.5% of the sample, affecting more individuals of the female gender, obese, with African American ethnicity, and those that were smokers, sedentary and presented hypertension and diabetes. In the final logistic model adjusted for age, gender, ethnicity, obesity, smoking, hypertension, diabetes, sedentary lifestyle, seasonality and creatinine serum levels, both OSA and short sleep duration showed significant independent associations with the risk of 25(OH)D deficiency (moderate OSA: OR for 25(OH)D<30 = 2.21, 95% CI: 1.35-3.64, p<0.01; severe OSA: OR for 25(OH)D<30 = 1.78, 95% CI: 1.06-3.00, p = 0.03; short sleep duration: OR for 25(OH)D<30 = 1.61, 95% CI: 1.15-2.26, p = 0.01). After a subgroup analysis, similar results were observed only in participants ≥50 years. CONCLUSION: OSA and short sleep duration are independently associated with the risk of 25(OH)D deficiency in an adult population. Age-related changes in vitamin D metabolism and the frequency of sleep disorders may be involved in these associations. Future studies exploring whether 25(OH)D levels may modulate OSA and sleep curtailment-related outcomes are needed.

The interfaces between vitamin D, sleep and pain.

The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep-wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in the prevention and treatment of chronic pain conditions.

The association between caffeine consumption and objective sleep variables is dependent on ADORA2A c.1083T>C genotypes.

OBJECTIVE: To verify the association between c.1083T>C polymorphism in the adenosine receptor A2A gene (ADORA2A) and objective sleep, as well as the correlation between caffeine consumption, sleep parameters, and electroencephalographic spectral power in a large, population-based sample from São Paulo, Brazil. METHODS: This study was conducted in participants of the São Paulo Epidemiologic Sleep Study (EPISONO), a large, population-based survey consisting of a representative sample of the inhabitants of the city from São Paulo, Brazil, according to sex, age (20-80 years), and socioeconomic status in the year 2007. Questionnaires, polysomnography, spectral analysis of sleep electroencephalogram, and c.1083T>C polymorphism genotyping were performed in this study. RESULTS: We found that caffeine consumption was positively correlated with sleep latency and α spectral power, as well as negatively correlated with percentage of N3 stage and δ spectral power in this stage. However, this association was identified only in T allele carriers and not in CC genotype. CONCLUSION: Our data support an important aspect of this polymorphism in ADORA2A gene, showing that the variant affects the association between caffeine consumption and objective sleep parameters in a large population-based cohort. CLINICAL TRIAL INFORMATION: Name: Epidemiology of sleep disturbances among adult population of the Sao Paulo City. URL: http://www.clinicaltrials.gov/ct2/show/NCT00596713?term = NCT00596713&rank = 1. Number: NCT00596713.

The relationship between sleep apnea, metabolic dysfunction and inflammation: The gender influence.

Obstructive sleep apnea (OSA) has been associated with increased risk of cardiovascular morbidity and mortality. Although inflammatory markers may mediate this association, it is unknown the influence of gender in this mechanism. Thus, we aimed to evaluate the interaction effects between OSA and gender on metabolic and inflammatory profile in a population sample. This study is part of EPISONO cohort, in which 1042 participants underwent polysomnography, answered questionnaires, and had their blood collected for analysis of fasting glucose, total cholesterol and fractions, leptin, ghrelin, liver transaminases, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C-reactive protein. The results showed that men with OSA had higher leptin levels, shorter sleep latency and lower N3 sleep stage compared to men control (CTRL). They also presented higher apnea index and number of central apneas compared to both CTRL men and OSA women. In women, OSA was related to longer REM sleep latency, higher apnea-hypopnea index (AHI) during REM sleep and increased TNF-α levels compared to CTRL women. A multivariate model showed that male gender, ghrelin and total cholesterol were negatively associated with TNF-α, while IL-6, triglycerides and hypopnea index were positively associated (R2=0.21). Additionally, gender (men), body mass index, ghrelin, apnea index and smoking were positive predictors of leptin levels (R2=0.55). Of note, postmenopause was associated with changes observed in both TNF-α and AHI during REM sleep in women with OSA. Taken together, our study suggests that OSA consequences may differ between genders and this could indicate a need for different OSA management in women according to their reproductive life's stage.

The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study.

BACKGROUND: Diagnosis of sleep-disordered breathing requires overnight recordings, such as polygraphy or polysomnography. Considering the cost and low availability of these procedures, preselection of patients at high risk is recommended. We aimed to develop a screening tool allowing identification of individuals at risk of sleep-disordered breathing. METHODS: We used the participants from the population-based HypnoLaus cohort in Lausanne, Switzerland, who had a clinical assessment and polysomnography at home, to build a clinical score (the NoSAS score) using multiple factor analysis and logistic regression to identify people likely to have clinically significant sleep-disordered breathing. The NoSAS score was externally validated in an independent sleep cohort (EPISONO). We compared its performance to existing screening scores (STOP-Bang and Berlin scores). FINDINGS: We used the 2121 participants from the HypnoLaus cohort who were assessed between Sept 1, 2009, and June 30, 2013. The NoSAS score, which ranges from 0 to 17, allocates 4 points for having a neck circumference of more than 40 cm, 3 points for having a body-mass index of 25 kg/m(2) to less than 30 kg/m(2) or 5 points for having a body-mass index of 30 kg/m(2) or more, 2 points for snoring, 4 points for being older than 55 years of age, and 2 points for being male. Using a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0·74 (95% CI 0·72-0·76). It showed an even higher performance in the EPISONO cohort, with an AUC of 0·81 (0·77-0·85). The NoSAS score performed significantly better than did the STOP-Bang (AUC 0·67 [95% CI 0·65-0·69]; p<0·0001) and Berlin (0·63 [0·61-0·66]; p<0·0001) scores. INTERPRETATION: The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Because of its high discrimination power, the NoSAS score can help clinicians to decide which patients to further investigate with a nocturnal recording. FUNDING: Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.

A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients.

Several studies have reported an increase in the prevalence of adult female acne. This subtype of acne presents particular characteristics, and can be triggered by several factors such as smoking, stress, the use of oily cosmetics and even by poor sleep. Sleep quality is related to well-being and the maintenance of body homeostasis. In addition, several skin diseases present a bidirectional relationship with sleep, demonstrating an important connection between skin and the central nervous system. With this in mind, we aimed to compare the effect of two types of treatment for adult female acne (azelaic acid or a combined oral contraceptive) on sleep quality and on concentrations of stress hormones. Also, we proposed to assess the correlation of sleep and hormonal parameters with acne severity. In order to do this, 32 women underwent a clinical evaluation, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and had their blood collected for hormone assays. These procedures were performed at baseline and after 6 months of treatment. At baseline there were no differences between the groups in terms of body mass index, age, acne severity and hormone concentrations. Results showed that both treatments demonstrated effectiveness but that women treated with azelaic acid presented a better sleep quality after the treatment compared to baseline and to the group treated with the combined oral contraceptive. The combined oral contraceptive group presented an increase in cortisol and a decrease in free testosterone concentration in relation to baseline. These data suggest that both azelaic acid and combined oral contraceptive are effective in the treatment of adult female acne but, azelaic acid seems to be a more suitable option for those women who may benefit from a better subjective sleep quality.

Impairment of male reproductive function after sleep deprivation.

OBJECTIVE: To evaluate the influence of sleep loss on sexual behavior, hormone levels, sperm parameters, and testis-specific gene expression in male rats. DESIGN: Experimental research. SETTING: Animal laboratory. ANIMAL(S): Male adult Wistar-Hannover rats. INTERVENTION(S): Sexually experienced rats were subjected to paradoxic sleep deprivation (PSD) for 96 hours or sleep restriction (SR) for 21 days or kept in their home cage as control (CTRL). MAIN OUTCOME MEASURE(S): Sexual behavior, hormone levels, sperm parameters and expression of stress and nitric oxide-related genes were evaluated. RESULT(S): PSD significantly decreased sexual behavior compared with the CTRL group, whereas SR had no effect. The PSD group had significantly lower testosterone levels than the CTRL group. Both PSD and SR groups had lower sperm viabilities than the CTRL group. The decrease in the number of live sperm compared with the CTRL group was larger in the PSD group than in the SR group. Regarding testicular gene expression, both PSD and SR led to an increase of iNOS and hydroxysteroid 11ß-dehydrogenase 1 expressions compared with the CTRL group. These changes were more pronounced in the PSD group. A significant increase in endothelial nitric oxide synthase expression was observed in the PSD groups compared with the CTRL group. No changes were observed in dimethylarginine dimethylaminohydrolase 1 and casein kinase 2ß-polypeptide expressions. CONCLUSION(S): Sleep loss can promote marked changes in the male reproductive system of rats, particularly affecting spermatic function in part by interfering in the testicular nitric oxide pathway.

Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

BACKGROUND: Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. METHODS: Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. RESULTS: Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. CONCLUSIONS: SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target.

Fibromyalgia and sleep in animal models: a current overview and future directions.

Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of the daytime symptoms, such as chronic pain and fatigue, may be related to the non-restorative sleep patterns associated with the disease. Pain influences the sleep process and sleep disturbances decrease the pain threshold in a reciprocal framework. Thus, understanding the link between sleep and FM has become an important research topic in basic science. Therefore, in the current review we connect these topics and provide some insights into the cyclic relationship between sleep and pain, which has been addressed mainly in animal models. Additionally, we highlight the urgent need for sleep studies in FM animal models, which might improve the knowledge base and accelerate advances in this field.

Association between uric acid levels and obstructive sleep apnea syndrome in a large epidemiological sample.

INTRODUCTION: Recurrent hypoxia, which is associated with obstructive sleep apnea syndrome (OSAS), leads to an increase in the degradation of adenosine triphosphatase into xanthine, which in turn increases uric acid concentrations. OBJECTIVE: The current study aimed to determine whether an association exists between OSAS and uric acid levels in the peripheral blood from a representative population of Sao Paulo (Brazil). METHODS: A population-based survey adopting a probabilistic 3-stage cluster sample of Sao Paulo was used to represent the population according to gender, age, and socioeconomic class. A total of 1,042 volunteers underwent polysomnography recordings for OSAS diagnosis, blood pressure assessment, and biochemical blood analysis, and answered questionnaires. RESULTS: Uric acid levels were correlated with most important risk factors for OSAS, such as AHI, desaturation time and index, minimum oxyhemoglobin saturation (SpO2), blood pressure, cholesterol, BMI, triglycerides and arousal, and with OSAS itself. Also, uric acid was increased in OSAS volunteers even after controlling for all confounders. Hyperuricemic volunteers presented lower mean and minimum SpO2 and increased desaturation index. Importantly, minimum SpO2 was a significant predictor of uric acid levels, which in turn was considered an independent predictor for OSAS in the binary logistic model. However, a ROC curve analysis for establishing cut-off points for uric acid levels as a biomarker of OSAS revealed moderate sensitivity and specificity. CONCLUSION: A strong association was found between uric acid levels and OSAS in a representative sample of the population of Sao Paulo. Although they do not qualify for a biomarker alone, uric acid levels may be involved in OSAS severity and should be considered in sleep apnea management in the future.

Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation.

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.

The influence of sleep deprivation and obesity on DNA damage in female Zucker rats

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.

Genomic damage in the progression of chronic kidney disease in rats.

Patients with chronic renal failure exhibit massive oxidative genome damage and an elevated risk of cancer. Previous studies have demonstrated the relationship between DNA damage and carcinogenesis. The current study aimed to investigate whether the progression of chronic kidney disease induces genomic damage in an animal model. Adult Wistar rats were assigned to either the control or chronic kidney disease groups. The chronic kidney disease group was subdistributed into five groups with progressively longer durations of disease (30, 60, 90, 120 and 150 days). The results showed that chronic kidney disease induced genomic damage in the blood, liver and kidney cells during all periods evaluated, as indicated by the mean tail moment measured in the comet assay. In brain cells, no genetic damage was induced at early/intermediate disease durations; however, positive genotoxicity was found at 120 and 150 days. Blood pressure and pro-inflammatory cytokine levels (IL-1α, IL-1ß, IL-6 and TNFα) were increased after chronic kidney disease induction, while blood iron concentration was significantly reduced in these animals. The results suggest that chronic kidney disease progression contributes to DNA damage in blood, liver, kidney and brain and that such damage can be mediated by hypertension, an inflammatory status and iron deficiency. Additionally, the brain was sensitive to genotoxic insult after extended chronic kidney disease, suggesting a potentially important role of genetic damage in the neurological disorders of end-stage renal patients.