Do nocturnal asthma attacks influence sleep parameters and inflammatory markers? A cross-sectional population-based study.

PURPOSE: To evaluate the effects of nocturnal asthma on sleep parameters and inflammatory markers according to the severity of the condition in participants in the São Paulo Epidemiologic Sleep Study (EPISONO). METHODS: Data from the 2007 and 2018 editions of the EPISONO study were utilized. Subjects completed validated sleep and respiratory questionnaires, underwent nocturnal polysomnography and spirometry tests, and provided blood samples for the assessment of inflammatory parameters. RESULTS: Of 72 participants (67% women), 53% (n = 38) had intermittent nocturnal asthma symptoms and 47% (n = 34) had persistent asthma (mild, moderate, and severe). Individuals with persistent nocturnal symptoms had a higher body mass index (BMI), were more likely to have respiratory symptoms, and had worse lung function, a higher apnea-hypopnea index (AHI), and higher desaturation index than individuals with intermittent nocturnal symptoms. Positive associations were identified between nocturnal asthma and obstructive sleep apnea (OSA). A higher frequency of OSA was observed in participants with persistent asthma and participants with OSA were more likely to have persistent than intermittent asthma. However, there were no significant differences between the immunological parameters of those with intermittent or persistent asthma. CONCLUSIONS: This study highlights the relevance of nocturnal symptoms as a valuable indicator of asthma severity. The findings also add to the existing body of evidence linking nocturnal asthma and OSA.

The effects of sleep deprivation and obstructive sleep apnea syndrome on male reproductive function: a multi-arm randomised trial.

Sleep is essential for the maintenance of health and systemic homeostasis. Decreased sleep time and sleep quality have been associated with a wide range of diseases. To evaluate the effects of obstructive sleep apnea (OSA) and total or selective rapid eye movement (REM) sleep deprivation on male reproductive function, we performed a three-arm parallel study with one pre-defined OSA group and a group of healthy volunteers who were then randomised into total or REM sleep deprivation groups. Questionnaires were completed and overnight polysomnography was undertaken, and blood and sperm samples were collected at the Sleep Institute, São Paulo, Brazil. OSA was diagnosed using questionnaires and polysomnography. Male sexual function was assessed through the questionnaires, blood tests, and semen samples. Data showed an association between OSA and lower circulating levels of total and free testosterone and high-density lipoproteins, as well as a lower proportion of healthy sperm cells and decreased sperm concentration, in comparison to volunteers. Volunteers subjected to either total or REM sleep deprivation had increased circulating levels of thyroid-stimulating hormone, insulin, and higher homeostatic model assessment of insulin resistance (HOMA-IR) values. Both sleep-deprived groups also shown decreased cholesterol, and low-density lipoproteins when compared to their baseline levels, but had no alterations in their spermograms. We observed a reduction in total testosterone following total sleep deprivation, but no effect after REM sleep deprivation. OSA was associated with a hormonal imbalance, which is probably linked with impaired reproductive function and associated comorbidities, such as sleep fragmentation/loss and obesity.

Sleep restriction in Wistar rats impairs epididymal postnatal development and sperm motility in association with oxidative stress.

Good sleep quality has a direct effect on the activity of the neuroendocrine-reproductive control axis and oxidative stress. Thus, the aim of the present study was to evaluate whether sleep restriction (SR) during the peripubertal period impaired the postnatal development of the epididymis in Wistar rats. After 21 days SR (18h per day), epididymides were collected on Postnatal Day (PND) 62 for evaluation of oxidative stress markers, inflammatory profile, sperm count and histopathological and stereological analyses; in addition, the motility of spermatozoa from the vas deferens was examined. SR significantly increased lipid peroxidation and glutathione levels in the caput and cauda epididymidis, and increased levels of total radical-trapping antioxidant potential in the caput epididymidis only. Neutrophil migration to the caput or corpus epididymidis was decreased by SR, and the size of the luminal compartment in the 2A region and the epithelial compartment in the 5A/B region was also decreased. In these regions, there was an increase in the size of the interstitial compartment. The percentage of immotile spermatozoa was higher in the SR group. In conclusion, SR affects epididymal postnatal development, as well as sperm motility, in association with increased oxidative stress and a decrease in the size of the epithelial compartment in the cauda epididymidis.

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.

The influence of sleep restriction on expression of apoptosis regulatory proteins p53, Bcl-2 and Bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

PURPOSE: The aim of this study was to evaluate whether sleep restriction (SR) could affect the mechanisms and pathways' essentials for cancer cells in tongue cancer induced by 4-nitroquinoline 1-oxide in Wistar rats. METHODS: The animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to sleep restriction for 21 days using the modified multiple platform method, which consisted of placing 5 rats in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. RESULTS: Although no histopathologic abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplastic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53, and for bcl-2. Following 12 weeks of 4NQO administration, we found significant differences between SR and control groups in p53, bax, and bcl-2 immunoexpression. CONCLUSION: Our results reveal that sleep restriction exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.

Effects of sleep deprivation during pregnancy on the reproductive capability of the offspring.

OBJECTIVE: To investigate the effects of sleep deprivation during pregnancy on the reproductive capability of the offspring. DESIGN: Using a sleep loss model or control home-cage group (male and females rats) to evaluate sexual behavior and hormonal profile in males and females F1 offspring. SETTING: Laboratory. ANIMALS(S): First experiment: Pregnant females were exposed to sleep restriction (SR) protocol and the F1 generation was evaluated. Second experiment: male rats were submitted to SR or paradoxical sleep deprivation (PSD) protocol and the F1 generation was evaluated. INTERVENTION(S): Male and female rats were subjected to sleep restriction (SR) for 21 days or paradoxal sleep-deprived (PSD) for 96 hours. MAIN OUTCOME MEASURE(S): Sexual behavior and hormonal levels during the adult phase were analyzed in F1 offspring of female and male rats submitted to sleep loss. RESULT(S): F1 male offspring of SR females had lower motivation for sex and reduced progesterone concentrations. In contrast, F1 female offspring displayed significantly enhanced proceptivity compared with control offspring. F1 female offspring also demonstrated hypersexuality by mounting the males in the absence of any significant hormonal alterations. F1 male offspring of SR or paradoxically sleep-deprived (PSD) males presented a decline in the sexual response, accompanied by a reduction in testosterone concentrations. Proceptivity was significantly increased among F1 female offspring of PSD and SR males compared with control offspring. CONCLUSION(S): SR in progenitors may alter sexual behavior of the F1 offspring in adulthood. These findings reveal far-reaching consequences of sleep deprivation, and suggest that parental sleep influences the reproductive capability of subsequent generations.

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.

Sexual response in female rats with status epilepticus.

PURPOSE: Female sexual function is complex and may be disrupted by disease, in particular epilepsy. Chronic seizures in women can have adverse effects on reproductive function, but it has been difficult to dissociate the effects of epilepsy from those related to anticonvulsant medications. The purpose of this study was to evaluate sexual behavior in female rats submitted to pilocarpine-induced status epilepticus (SE). METHODS: Adult female Wistar rats were given saline or pilocarpine (350 mg/kg, i.p.) to induce SE. The groups were distributed according to the treatment or response to pilocarpine: CTRL (control rats maintained in the home-cage after saline administration); NSE (non-status epilepticus, rats that did not display convulsive and intermittent seizures after pilocarpine injection) and SE (status epilepticus, rats that displayed convulsive and intermittent seizures after pilocarpine injection). After 50 days, sexual receptivity in the female rats was artificially induced via administration of a combination of estradiol and progesterone. Sexual behavior was evaluated during three sessions in the presence of a sexually experienced male rat. Receptivity and proceptivity behaviors, as well as hormones concentrations, were monitored. KEY FINDINGS: Significant decreases in proceptivity and receptivity behaviors during the three tests were observed in SE female rats. The rejection response was significantly increased in SE rats compared with CTRL or NSE groups. Progesterone, testosterone, and corticosterone were unchanged between the groups. SIGNIFICANCE: The SE female rats showed lower sexual motivation and performance regardless of their steroid hormones levels.

Influence of acute sleep deprivation on cardiovascular parameters in female Zucker obese and lean rats.

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.

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.

Impairment of sexual function in rats with epilepsy.

INTRODUCTION: Epilepsy is a chronic disease that affects men and women of all ages, with different levels of severity. Many individuals with epilepsy also suffer from impairments in sexual function. However, it is difficult to differentiate between the impact of the disease and the impact of antiepileptic drugs on sexual function in human subjects. AIMS: To evaluate sexual behavior in adult male rats submitted to chronic pilocarpine-induced epilepsy. METHODS: First, non-epileptic rats were exposed to nine training sessions to acquire sexual experience, and their baseline sexual performance was evaluated. Then, the same rats were given pilocarpine to induce status epilepticus followed by chronic epilepsy. Once the animals had developed spontaneous recurrent seizures, their sexual behavior was evaluated during three sessions. MAIN OUTCOME MEASURES: Examine changes in latencies to first mount, intromission, and ejaculation, and the total number of mounts, intromissions, and ejaculations. RESULTS: All outcome measures related to sexual motivation and sexual performance were markedly impaired during chronic epilepsy compared with the baseline and the control group. CONCLUSION: These findings will aid in understanding the interaction between sexual behavior and epilepsy, as well as encouraging further experimental studies in human patients with epilepsy suffering from sexual dysfunction.

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

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.

Hormonal profile, the PROGINS polymorphism, and erectile dysfunction complaints: data from a population-based survey.

OBJECTIVE: To evaluate a potential association among the hormonal profile, PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large population-based sample in Sao Paulo, Brazil. DESIGN: Population-based questionnaire study. SETTING: Interviews, sleep recording, and blood sample were conducted in a sleep institute. PATIENT(S): The total study participants included 467 men. INTERVENTION(S): General information was obtained through interviews, and a blood sample was collected for hormone levels, DNA extraction, and PROGINS genotyping. MAIN OUTCOME MEASURE(S): The effect of progesterone and the PROGINS polymorphism on the risk of developing ED were measured by questionnaire and blood sample. RESULT(S): Progesterone, prolactin, testosterone, and estradiol levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No significant genotypic or allelic differences were found between individuals with ED complaints and controls. Multivariate logistic regression analyses including age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of association between the T2 allele carriers and the risk of ED (odds ratio = 0.80; 95% confidence interval = 0.40-1.62). CONCLUSION(S): This is the first study to demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in a large population-based sample of men. The results do not support a direct role for the PROGINS polymorphism in the risk of developing ED; however, further examination of other variants within PR gene will be necessary to completely rule out an effect.

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.

Influence of progesterone on sexual performance in male rats.

INTRODUCTION: It has been documented that copulatory experience can alter or improve sexual performance in male rats. However, the hormonal basis and the number of sexual encounters needed for a rat to acquire sufficient performance remains unclear. AIM: The aim of this study was to examine whether levels of testosterone and progesterone are associated with sexual performance in male rats. METHODS: Adult male Wistar Hannover rats were exposed to a receptive female for 15 minutes every other day for 9 days for acquiring sexual experience. MAIN OUTCOME MEASURES: After training protocol, rats were scored as low or high sexual performers. Hormonal levels (testosterone and progesterone) were evaluated in both trained and non-trained control groups. RESULTS: Our results showed that a 9-day training period was not sufficient for some male rats to acquire a good level of sexual performance. While 42.5% of the rats displayed excellent sexual performance during the training sessions, 17.5% showed adequate performance, 7.5% had low sexual activity, and 32.5% of the rats did not display any sexual behaviors whatsoever. Additionally, after 4 days of training, rats with excellent/adequate performance showed a significant decrease in ejaculation latency relative to the first day of training. The rats with low or no sexual activity had lower progesterone levels relative to those displaying the highest sexual performance after 9 days of training. Testosterone, in turn, was also significantly reduced in animals with low/no sexual performance compared with excellent/adequate rats. CONCLUSION: In conclusion, progesterone may be a limiting factor to promoting sexual performance in male rats.

Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice.

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.

Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of mice.

We evaluated the overall genetic damage induced by different doses of cocaine and MDMA (3,4-Methylenedioxymethamphetamine) in several organs. One hour after intraperitoneal drug administration, mice were euthanized; peripheral blood, liver and brain were collected, and the cellular suspensions were used for the single cell gel (comet) assay. We determined that all doses of cocaine and MDMA tested were able to induce DNA damage in blood cells. Extensive genotoxic damage was induced by cocaine or MDMA at the highest doses used in liver cells. Brain cells were affected by all doses administrated. These findings demonstrate that cocaine and MDMA are potent genotoxins.

Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

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.

WITHDRAWN: Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice.

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