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Biomedical subjects

Sergio Tufik

Publications and source records attributed to Sergio Tufik.

At least 37 records · Page 2Linked to original sources

Treatment of PTSD by eye movement desensitization reprocessing (EMDR) improves sleep quality, quality of life, and perception of stress.

The impact of posttraumatic stress disorder (PTSD) on the sleep of patients is widely reported. However, the parameters that can be altered are not the same for all patients. Some studies report an impairment of sleep maintenance and recurrent nightmares, while others failed to find such alterations. Among the many treatments, the eye movement desensitization reprocessing (EMDR) is a therapy used specifically to treat PTSD and general trauma. The purpose of this study was to examine whether EMDR treatment can improve PTSD symptoms, such as sleep, depression, anxiety, and poor quality of life.

Adult↗

[Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil].

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in Parkinsons disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean+/-SD) (0.38+/-0.12) compared to controls (BP=0.84+/-0.16; p<0.01). A 100% sensitivity and 100% specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho=-0.7, p<0.001) and motor scales (rho=-0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.

Adult↗

Does male sexual behavior require progesterone?

In this article, we provide a concise review of the past and current literature on the neglected influence of progesterone on male sexual behavior. Although there has been increased interest in all aspects of male sexual function, and the importance of androgens in the regulation of male copulatory behavior has long been well documented, knowledge of the role of progesterone on male sexual behavior is still patchy. Very little human data exist on this theme, and most of the literature concerns animal research, in particular reptiles and rodents. This review attempts to outline specific progesterone mechanisms involved in male sexual behavior, showing that this hormone plays a more relevant role in the control of male sexual behavior than commonly assumed. Exploring the neuroendocrine mechanisms of progesterone in the sexual behavior of males may provide insights into the regulation of sexuality in this gender.

Animals↗

The effects of paradoxical sleep deprivation on estrous cycles of the female rats.

The present purpose was to examine how sleep deprivation affects the estrous cycle of the female rat. Paradoxical sleep-deprived (PSD) adult female Wistar rats were compared to home-cage control (CTRL) on their estrous cyclicity. Forty-four PSD and forty-four CTRL female rats were distributed into 4 subgroups of 11 animals each according to the phase of estrous cycle and were subjected to sleep deprivation for 96 h by the multiple platform technique. After PSD period, vaginal estrous cycles were taken for an additional 9 days. Animals that were submitted to PSD in diestrus phase (PSD-diestrus) had their estrous cycles disrupted during the recovery period by showing a constant diestrus during the first week. As for hormone alterations, progesterone concentrations were statistically higher in PSD-diestrus compared to respective phase control and to PSD-proestrus and PSD-estrus rats while CTRL-metestrus had higher levels than CTRL-proestrus and estrus groups. Testosterone was significantly decreased in PSD-estrus in relation to PSD-proestrus and PSD-diestrus groups and was lower in CTRL-diestrus rats than in home-cage rats in proestrus. In addition, PSD-diestrus phase exhibited higher concentrations of corticosterone and lower estrogen than the respective control rats. These data indicate that PSD may modulate the ovarian hormone release through alterations in hormonal-neurochemical mechanisms.

Animals↗

Sleep disturbance induced by substance P in mice.

UNLABELLED: Substance P (SP) and neurokinins have been implicated in modulating pain and mood but little is known about their effect on sleep-wake behavior. The purpose of the present study was to examine the possible involvement of SP in sleep-wake mechanisms without activation of painful responses. Electrophysiological recordings of the sleep-wake cycle were conducted in C57BL/6J male mice that had intracerebral ventricular cannula inserted for drug administration. Initially, in order to determine the highest dose of SP that would not induce nociceptive response, 10 animals per group received administration of either SP doses or artificial cerebrospinal fluid (CSF-sham group) through the cannula and were assessed by the hot plate test. The sleep-wake cycle of two other groups of mice was recorded for 24 h before (baseline) and after receiving CSF (n=10) or SP-1 mM (n=11), dose that had been determined in the previous hot plate test. SP interfered with sleep, when compared to baseline and to sham group, by reducing sleep efficiency, increasing latency of sleep and the number of awakening bouts. To examine the reversal of SP effects, eight mice were administered with an NK1 receptor antagonist before SP administration. Prior administration of the NK1 antagonist prevented the disturbances in sleep. CONCLUSIONS: The results suggest that SP produces disturbances in sleep, likely mediated by the NK1 receptor.

Analysis of Variance↗

Influence of long-term food restriction on sleep pattern in male rats.

The present purpose was to determine the effects of different schedules of long-term food restriction (FR) applied to rats from weaning to the 8th week. Rats were distributed into FR and ad libitum groups at weaning and fed at 7 am, at 7 pm, and finally, restricted rats fed ad libitum. The restricted rats started with 6 g/day and the food was increased by 1 g per week until reaching 15 g/day by adulthood. The rats were implanted with electrodes to record electrocorticogram/eletromyogram signals. Their wake-sleep cycles were monitored over 3 consecutive days (72 h of recording). The FR group fed at 7 am showed an increase in awake time, and decrease in slow wave sleep (SWS) and paradoxical sleep (PS) during the three light periods compared with the control recordings whereas in the dark periods, these sleep parameters were the opposite. The restricted group fed in the evening showed no statistical significances at diurnal periods; however, a significant decrease was observed in the dark recordings for awake time, but the SWS and PS were increased in relation to controls. The analysis of the 24-h period demonstrated that both FR groups presented increase in SWS time. After being FR, the rats were fed ad libitum and their sleep was monitored for 3 additional days. During the first dark recording, the decrease in awake time and increase in SWS were still present; however, as ad libitum food continued, these sleep parameters returned to control values, reestablishing the normal sleep pattern. These results suggest that dietary restriction, regardless to the feeding schedule, caused increase in total sleep time, during the active period.

Activity Cycles↗

Clock gene polymorphisms and narcolepsy in positive and negative HLA-DQB1*0602 patients.

Narcolepsy is a chronic sleep disorder. It is linked to the HLA-DQB1*0602 allele. A recent report established a genetic linkage between narcolepsy and the chromosomal region 4p13-q21 that contains the Clock gene. We studied two SNPs in the Clock gene aiming to find any association with narcolepsy. We did not find differences in genetic frequencies in the patients group. We concluded that these two SNPs are not associated with narcolepsy.

Base Sequence↗

Effects of paradoxical sleep deprivation on the performance of rats in a model of visual attention.

In the present work we sought to evaluate the effects of paradoxical sleep deprivation (PSD) on the performance of rats in the five-choice serial reaction time task, a test designed to assess attentional function. Adult male Wistar rats were trained to detect a brief (1 s) light stimulus randomly presented in one of five locations in a box specially designed for the task. After achieving stable performance, the animals were submitted to 96 h of sleep deprivation by the platform technique, in which the rats are placed on top of small platforms in a tank filled with water. During sleep, particularly during the paradoxical stage, the loss of muscle tone make the animals fall into the water, thus awakening them and so depriving of sleep. Performance in the task was assessed daily during the 96 h deprivation period and also during seven recovery days afterwards. Paradoxical sleep deprivation reduced accuracy on the on the third (72 h) and fourth (96 h) days of sleep deprivation compared to home-cage controls, and this impairment reverted soon after the beginning of the recovery period. Sleep-deprived animals also showed an increase in omissions in the first day of PSD and a reduction on the number of trials started on the fourth day of sleep deprivation. No significant group differences were observed in premature and perseverative responses, correct response latency and reward latency. Our results thus indicate that paradoxical sleep deprivation impairs attentional function.

Animals↗

Effects of paradoxical sleep deprivation on genital reflexes in five rat strains.

This study examined the effects of cocaine on genital reflexes in paradoxical sleep-deprived (PSD) male rats of five strains since it has been demonstrated that this drug enhances genital reflexes in Wistar PSD rats. At the end of a 4-day period of PSD or at the equivalent time-point to control animals, cocaine or saline was acutely administered to the animals and penile erection (PE) and ejaculation (EJ) were quantified. Results indicated that PSD induced genital reflexes in all strains, and cocaine potentiated these behaviors in Wistar and Long-Evans rats. Wistar PSD rats injected with cocaine performed significantly more PE than all the other PSD + cocaine strains. The number of Wistar and Long-Evans PSD + cocaine ejaculating was significantly higher than the respective PSD + saline and control, whereas a tendency of increase was seen in relation to other groups. Wistar PSD + cocaine rats showed the highest EJ frequency compared to F344, Sprague-Dawley and Wistar-Kyoto strains, and the Long-Evans displayed more EJ than Sprague-Dawley and Wistar-Kyoto. Analysis of testosterone concentrations revealed that after sleep deprivation, Wistar, Long-Evans, and F344 rats showed significantly lower testosterone concentrations than control rats. In F344, Sprague-Dawley and Wistar-Kyoto controls rats, testosterone was significantly lower than in the control Wistar and Long-Evans. Progesterone concentrations were significantly higher in Wistar and Long-Evans PSD rats than in respective control groups. In the other strains, this hormone was significantly lower compared to the Wistar and Long-Evans PSD. This study demonstrates that genital reflexes are differently influenced by PSD associated to cocaine in five rat strains.

Animals↗

Opposite effects of sleep rebound on orexin OX1 and OX2 receptor expression in rat brain.

Orexins (hypocretins) have been implicated in the regulation of the normal sleep-wake cycle, in sensorimotor programming, and in other homeostatic and neuroregulatory processes. The present study examined the effects of sleep deprivation (SD) and sleep recovery on the expression of orexin 1 receptors (OX1R) and orexin 2 receptors (OX2R) throughout the brain. Rats were sacrificed either immediately after 96 h of sleep deprivation (SD group) or after SD followed by 24 h of sleep recovery (Rebound group). Prepro-orexin mRNA showed a non-significant increase in the SD group relative to controls, but a pronounced and significant increase in the Rebound group (+88%, P < 0.007). Similarly, sleep deprivation produced no effect on OX1R or OX2R mRNA levels. However, in the Rebound group, OX1R mRNA levels increased significantly, compared to either control or SD groups, in 37 of 92 brain regions analyzed, with particularly strong effects in the amygdala and hypothalamus. Changes in OX2R mRNA levels were also seen only in the sleep Rebound group, but they were fewer in number (10 out of 86 regions), were in the direction of decreased rather than increased expression, and were predominantly confined to cerebral cortical areas. These observations indicate that some factor associated with sleep recovery, possibly the compensatory increase in REM sleep, has strong effects on the orexin system at the mRNA level. They further indicate that,pOX1 and OX2 receptors are affected in opposite way and that the former are more vulnerable to these effects than the latter.

Animals↗

Physiological variation in plasma total homocysteine concentrations in rats.

Hyperhomocysteinemia was initially related to cardiovascular diseases; but homocysteine (Hcy) metabolism disturbances have more recently associated with a wide range of pathophysiological conditions including age-related diseases, disrupted circadian rhythms and gynaecological disorders. Since in many cases we do not know to what extent animal models are physiologically similar to human ones, this study aimed to track spontaneous variations in rat plasma Hcy concentrations during different physiological processes such as life cycle, 24 hours and estrous cycle. Plasma total Hcy concentrations were accessed by HPLC. Plasma Hcy concentration varied with age and newborns had the lowest values (2.94 +/- 0.47 micromol/L). Rats aged 10 days presented concentration similar to 3 month old animals (6.87 +/- 0.67 and 8.29 +/- 1.55 micromol/L respectively). Values decreased to 6.42 +/- 1.65 micromol/L at 6 months and 4.87 +/- 0.81 micromol/L at 28 months. Concerning circadian variations in Hcy concentration cosinor analysis showed acrophase in young rats at 1:09 pm, but no plasma Hcy circadian variations in aged rats. Female rats showed changes in Hcy concentration during the estrous cycle with higher values during the diestrous I (10.61 +/- 1.81 micromol/L) compared with the estrous (8.47 +/- 1.86 micromol/L) and diestrous II (7.68 +/- 1.58 micromol/L) phases. In conclusion, plasma Hcy concentration varied spontaneously with ontogenic development and during the estrous cycle and presented a circadian rhythm variation in young rats.

Aging↗

Learning deficits induced by sleep deprivation and recovery are not associated with altered [(3)H]muscimol and [(3)H]flunitrazepam binding.

Several studies have shown that sleep deprivation produces deficits in learning tasks, but mechanisms underlying these effects remain unclear. Other lines of evidence indicate an involvement of brain GABA systems in cognitive processes. Here, we investigated the possibility that alterations in GABA(A) or benzodiazepine (BDZ) receptor binding might underlie avoidance deficits induced by sleep deprivation. Rats were deprived of sleep for 96 h using the platform method and then trained in a step-through inhibitory avoidance task, or allowed to recover sleep for 24 h before training (sleep rebound group). Thirty minutes after training, animals were given a retention test. Both sleep-deprived and sleep-recovered animals showed a significant impairment in avoidance responding compared to cage controls, and the sleep-deprived group performed significant worse than the sleep-recovered group. A separate group of animals was sacrificed either immediately after 96 h of sleep deprivation or after 96 h of sleep deprivation followed by 24 h of sleep recovery. [(3)H]muscimol and [(3)H]flunitrazepam binding were examined by quantitative autoradiography in 42 brain regions, including areas involved in cognitive processes. No significant differences among groups were found in any brain region, except for a reduction in [(3)H]flunitrazepam binding in the frontal cortex of sleep-recovered animals. These results confirm the deleterious effects of sleep loss on inhibitory avoidance learning, but suggest that such deficits cannot be attributed to altered GABA(A) or BDZ binding in brain.

Animals↗

Sleep homeostasis in rats assessed by a long-term intermittent paradoxical sleep deprivation protocol.

Numerous studies have evaluated the sleep homeostasis of rats after short- or long-periods of sleep deprivation, but none has assessed the effects of prolonged sleep restriction on the rat's sleep pattern. The purpose of the present study, therefore, was to evaluate the sleep homeostasis of rats under a protocol of chronic sleep restriction. Male Wistar rats were implanted with electrodes for EEG and EMG recordings. Using the single platform method, the animals were submitted to 18 h of sleep restriction, beginning at 16:00 h (lights on at 07:00 h), followed by a 6 h sleep window (from 10:00 h to 16:00 h) for 21 days. Immediately after this period, rats were allowed to sleep freely for 4 days (recovery period). The sleep-wake cycle was recorded throughout the entire experiment and the results showed that during the 6h sleep window there was an increase on the percentage of sleep time, reflected by augmented time in high amplitude slow wave sleep and in paradoxical sleep, when compared to baseline sleep, whereas bouts of awakening longer than 1.5 min were greatly reduced, with the animals exhibiting a monophasic-type sleep pattern. During the deprivation period, paradoxical sleep was abolished. High amplitude slow wave sleep was also greatly affected by the protocol. Nonetheless, one day of recovery was sufficient to restore the normal sleep pattern. These findings indicate that this protocol was capable to induce many changes in the rat's sleep patterns, suggesting that during the 6h sleep window there is a sleep adaptive homeostatic process.

Activity Cycles↗

Acoustic arousal responses in children with obstructive sleep apnea.

Our objectives were to study the arousal responses to nonrespiratory (acoustic) stimuli in children with obstructive sleep apnea syndrome (OSAS). The acoustic arousal response was studied in children with OSAS due to adenotonsillar hypertrophy compared to normal, age-matched children. Acoustic stimuli were delivered incrementally from 30-100 dB during stage 2, slow wave sleep, and rapid eye movement (REM) sleep. The percentage of children who aroused in response to acoustic stimuli, and the arousal threshold (i.e., sound level at which arousal occurred), were compared between groups and sleep stages. The percentage of children who aroused was similar between children with OSAS and controls. The percentage of children who aroused was lower during slow wave sleep than REM sleep and stage 2 in both OSAS and controls. There were no statistically significant differences in acoustic arousal threshold between OSAS and control children. There was no difference in arousal response to moderate acoustic stimulation between children with OSAS and controls. These results contrast with previous data showing blunted arousal responses to hypercapnia and upper airway loading during sleep in children with OSAS, suggesting that children with OSAS have an arousal deficit specific to respiratory stimuli. However, further studies evaluating arousal to both respiratory and nonrespiratory stimuli in the same subjects are needed.

Acoustic Stimulation↗

Intra-nigral MPTP lesion in rats: behavioral and autoradiography studies.

The present study investigated the motor response and possible changes in binding to D1 and D2 receptors after intra-nigral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) infusion on rats. The results indicated that MPTP-lesioned rats exhibited a significant reduction in locomotion and rearing frequencies observed in an open field 24 h after surgery. However, at 7 and 14 days after surgery the MPTP-lesioned rats showed a significant increase in locomotion in comparison to the control groups, as well as a decrease in immobility time. In addition, 21 days after surgery the behavioral measurements were unaltered by these procedures. Moreover, latency in initiating movement and catalepsy were unchanged by this neurotoxin on the same days of observation. An autoradiography approach indicated that there was a reduction in [3H]SCH 23390 binding in substantia nigra pars compacta (SNpc), substantia nigra pars reticulata (SNpr) and ventrolateral striatum in MPTP-treated rats 21 days after the surgery. [3H]raclopride binding remained unaltered by the MPTP treatment. These results suggest that compensatory plastic changes occur in D1 dopamine receptors after partial lesion of nigral dopaminergic neurons. These alterations might be related to the occurrence and recovery of motor impairment observed in MPTP-lesioned rats.

Analysis of Variance↗

Effects of paradoxical sleep deprivation and cocaine on genital reflexes in hyperlipidic-fed rats.

The present study was designed to investigate the effects of a hyperlipidic diet (HD) on penile erection (PE) and ejaculation (EJ) induced by cocaine in paradoxical sleep deprived (PSD) rats. Secondly, we aimed to verify the influence of HD cafeteria diet on steroid hormone levels. Twenty-one day-old male Wistar rats were randomly assigned into two groups: rats fed with commercial chow diet and rats fed with a palatable HD containing chow mixed with peanuts, milk chocolate and sweet cookies in the proportion of 3:2:2:1. After nine weeks of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h and challenged with cocaine (7 mg/kg, i.p.). Results showed that the HD led to a reduction in the frequency of erection in the PSD+cocaine group when compared to the PSD+cocaine fed with standard diet. Regardless of the diet, testosterone concentrations were significantly lower and progesterone was higher in the PSD rats than in the respective home-cage control rats. Although there were no hormonal alterations, the findings showed that a long-term HD might modify the stimulating effects of cocaine in potentiating genital reflexes in PSD rats.

Analysis of Variance↗

Acute neurophysiological effects of the hypnotic zolpidem in healthy volunteers.

INTRODUCTION: The imidazopyridine zolpidem is a hypnotic drug with relative selectivity for the benzodiazepine (BZP) type 1 receptor subtypes displaying a different biochemical structure to that of BZPs. Little is known of its electrophysiological effects. PURPOSE: The aim of the present study was to investigate the acute neurophysiological effects of clinical oral doses of zolpidem. METHODS: This was a double blind, independent group design study. Thirty-six young, healthy volunteers were randomly allocated to one of three groups--zolpidem (5 mg and 10 mg) and placebo. In addition to ERPs, behavioural measures were used to examine sedative effects of the drug. RESULTS: ERPs were affected in a similar way to that described after sedative/hypnotic drug ingestion: increased N2 and P3 latencies and decreased N2 and P3 amplitudes. However, contrary to what is expected of a hypnotic drug, there was no change with N1 while P2 amplitude increased after the highest dose. CONCLUSIONS: Because zolpidem showed different effects in different components, it seems to first enhance or preserve initial orienting (no change in N1), after an increase of P2 and then drastically diminish resource allocation (affecting N2 and P3 latencies and amplitudes). The study with ERPs, therefore, allows a more direct "moment to moment" investigation of finer mechanisms of changes in cerebral processes underlying the acute ingestion of the drug in question. The effects on N2 and P3 amplitudes and latencies were similar to those of other sedative/hypnotic drugs. However, zolpidem led to an unexpected increase in P2 amplitude; this effect may be related to its selective receptor binding profile and warrants further research.

Adult↗

Effects of progesterone blockade over cocaine-induced genital reflexes of paradoxical sleep-deprived male rats.

Paradoxical sleep deprivation (PSD) enhances cocaine-induced genital reflexes (penile erection [PE] and ejaculation [EJ]) in male rats and induces a significant increase in progesterone concentration. As progesterone treatment facilitates PE in PSD castrated rats, we may speculate that progesterone appears to be a relevant hormonal factor eliciting genital reflexes in PSD males. In order to expand the latter finding, different doses of antiprogestin mifepristone (vehicle, 2.5, 5, 10, and 20 mg/kg, s.c.) were administered to PSD rats at the end of a 4-day period of PSD 1 h prior to cocaine administration (7 mg/kg, i.p.) and placed in observation cages for the evaluation of genital reflexes. Pretreatment with vehicle induced PE in all rats and this effect was significantly reduced by mifepristone at 5 to 20 mg/kg doses that lowered the proportion to 40% of the rats. The frequency of PE was also significantly reduced for all doses used. There were no significant differences between vehicle and mifepristone in EJ behavior. As for hormone concentrations, mifepristone reduced progesterone concentrations at the 5-20 mg/kg doses compared to vehicle group. At 20 mg/kg, it also elevated testosterone concentrations. In addition, mifepristone administration induced a significant decrease in the duration of PS episodes at all doses. These data suggest that progesterone exerts an essential role in erectile response induced by cocaine in PSD male rats.

Analysis of Variance↗