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Biomedical subjects

Sergio Tufik

Publications and source records attributed to Sergio Tufik.

At least 19 recordsLinked to original sources
PubMed2007

Cocaine-induced genital reflexes in paradoxical sleep deprived rats: Indications of mediation by serotonin receptors.

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.

Animals↗
PubMed2006

Suppression of adrenocorticotrophic hormone secretion by simultaneous antagonism of vasopressin 1b and CRH-1 receptors on three different stress models.

BACKGROUND/AIMS: Corticotrophin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH) and corticosterone are secreted during stress. These mediators may be involved in anxiety, depression and post-traumatic stress disorder, therefore antagonists have been developed to treat such conditions. METHODS: The non-peptide CRH receptor type 1 antagonist CP154,526 and the vasopressin receptor type 1b antagonist SSR149415 were used to suppress the secretion of ACTH induced by ether exposure, forced swimming and restraint in adult male Wistar rats. Doses ranged from 3 to 60 mg/kg s.c. (controls with vehicle) alone or in combination, in varying time schedules to assess the duration and effectiveness of treatments. RESULTS: Stressors increased plasma ACTH by 2.5- to 5-fold in control rats. SSR149415 at doses of 30 mg/kg was more effective at suppressing ACTH secretion after ether exposure and restraint but was ineffective against forced swimming. CP154,526 mildly affected ACTH rise after restraint at doses of 30 mg/kg. The combination of both antagonists at doses of 30 mg/kg effectively blocked the rise in plasma ACTH in all three stresses. The drug effects lasted less than 6 h. CONCLUSION: We demonstrated for the first time that simultaneous blockade of both vasopressin 1b and CRH-R1 receptors effectively abolish the ACTH response to physical and psychological stress modalities.

Adrenocorticotropic Hormone↗
PubMed2006

Rapid detection and identification of metallo-beta-lactamase-encoding genes by multiplex real-time PCR assay and melt curve analysis.

Metallo-beta-lactamase enzymes (MbetaL) are encoded by transferable genes, which appear to spread rapidly among gram-negative bacteria. The objective of this study was to develop a multiplex real-time PCR assay followed by a melt curve step for rapid detection and identification of genes encoding MbetaL-type enzymes based on the amplicon melting peak. The reference sequences of all genes encoding IMP and VIM types, SPM-1, GIM-1, and SIM-1 were downloaded from GenBank, and primers were designed to obtain amplicons showing different sizes and melting peak temperatures (Tm). The real-time PCR assay was able to detect all MbetaL-harboring clinical isolates, and the Tm-assigned genotypes were 100% coincident with previous sequencing results. This assay could be suitable for identification of MbetaL-producing gram-negative bacteria by molecular diagnostic laboratories.

Bacterial Typing Techniques↗
PubMed2006

Consequences of subchronic and chronic exposure to intermittent hypoxia and sleep deprivation on cardiovascular risk factors in rats.

Since studies suggest that both hypoxia and sleep fragmentation are related to cardiovascular alterations induced by obstructive sleep apnea, the present study was designed to evaluate the effects of hypoxia, sleep deprivation, and their combination on biochemical blood parameters in rats. In subchronic experiments (4 days), rats were exposed to intermittent hypoxia (IH) during the light period (2min room air-2min 10% O(2) for 12h/day) and/or paradoxical sleep deprivation (PSD, 24h/day). Consequences of chronic intermittent hypoxia (CIH) exposure were examined after 21 consecutive days of hypoxia protocol from 10:00 to 16:00 followed by a sleep restriction (SR) period of 18h (16:00-10:00). Rats were randomly assigned to seven treatment groups: (1) control (2) IH (3) PSD (4) IH-PSD (5) SR (6) CIH and (7) CIH-SR. PSD reduced triglycerides and very low-density lipoprotein (VLDL) cholesterol concentrations and increased total cholesterol and high-density lipoprotein (HDL) cholesterol. IH did not alter any of these parameters. The combination of IH-PSD did not modify the values of total cholesterol and HDL compared to control group. In the chronic experiment, the animals exposed to CIH displayed a reduction of Vitamin B(6) and an increase of triglycerides and VLDL. Our findings show a duration-dependent effect of hypoxia on triglycerides. Rats in the SR and CIH-SR groups showed a diminished concentration of triglycerides and VLDL. SR rats showed a reduction in the concentration of homocysteine but the animals in the CIH-SR treatment condition did not display any alterations in this parameter. In this latter group, an augmentation of cysteine concentration was observed. These results suggest that sleep deprivation and hypoxia modify biochemical blood parameters in distinct ways.

Animals↗
PubMed2006

Acute stressor-selective effects on homocysteine metabolism and oxidative stress parameters in female rats.

Homocysteine levels are affected by diet factors such as vitamin deficiencies, non-diet factors such as genetic disorders, and stress exposure. Hyperhomocysteinemia has been implicated in several disorders, including cardiovascular disease, depression, schizophrenia, Alzheimer's and Parkinson's disease. Since sex differences play a role both in stress responses and in susceptibility to various diseases, the objective of this study was to evaluate possible alterations in homocysteine metabolism including cysteine, folate, and vitamin B(6), and oxidative stress markers in female rats exposed to different types of acute stress. Female rats were randomly distributed into eight groups according to stress manipulation (restraint, swimming, cold and control) and estrous cycle (diestrus and estrus). In general no significant differences were seen between rats in estrus and diestrus. Restraint stress was the only type of stress that altered homocysteine concentrations (+33% relative to controls). An increase in levels of thiobarbituric acid reactive substances (TBARS) and a decrease in total glutathione (GSHt) concentration were also observed in animals subjected to restraint and swimming stress, suggesting the possibility of oxidative damage. Thus, both the homocysteine results and the oxidative stress data indicated that restraint stress was the most powerful stress manipulation in female rats, as previously observed in male rats. These findings indicate that hormonal and gonadal differences do not interfere with stress responses related to homocysteine metabolism and suggest that putative gender-related differences in homocysteine responses are probably not involved in the differential prevalence of some diseases in human males and females.

Animals↗
PubMed2006

A double-blind, placebo-controlled, crossover study of sildenafil in obstructive sleep apnea.

BACKGROUND: Sildenafil prolongs the action of cyclic guanosine monophosphate and nitric oxide by inhibiting cyclic guanosine monophosphate-specific phosphodiesterase 5. It is largely used for erectile dysfunction, a highly prevalent condition in obstructive sleep apnea. Because nitric oxide promotes upper airway congestion, muscle relaxation, and pulmonary vasodilation, the aim of this study was to establish the impact of a single 50-mg dose of sildenafil on the sleep of patients with severe obstructive sleep apnea. METHODS: Thirteen [corrected] middle-aged men with severe obstructive sleep apnea were consecutively selected for this double-blind, placebo-controlled, crossover study. Exclusion criteria were obesity, cardiovascular and/or respiratory disease, and conditions that interfere with sleep. All-night polysomnography was preceded by a single 50-mg dose of sildenafil or matching placebo randomly administered at bedtime, after a washout period of 1 week. RESULTS: In comparison to placebo, a single 50-mg dose of sildenafil significantly increased the percentage of total sleep time with an arterial oxygen saturation of less than 90% (mean +/- SD, 15.6% +/- 9.6% vs 7.9% +/- 3.3%, [corrected] P < .01), without a difference in the nadir of oxygen desaturation. The mean arterial oxygen saturation also decreased (92.1% +/- 1.9% vs 93.8% +/- 1.3%, P = .03), [corrected] and the desaturation index increased (30.3 +/- 14.5 [corrected] events per hour vs 18.5 +/- 9.1 [corrected] events per hour, P < .001). There was an increase in apnea-hypopnea index (48.1 +/- 20.8 [corrected] events per hour vs 32.3 +/- 11.3 [corrected] events per hour, P = .001), [corrected] involving mostly obstructive events. CONCLUSION: In patients with severe obstructive sleep apnea, a single 50-mg dose of sildenafil at bedtime worsens respiratory and desaturation events.

Cross-Over Studies↗
PubMed2006

Effects of long-term food restriction on genital reflexes in paradoxically sleep-deprived male rats.

The purpose was to ascertain whether the different schedules of long-term food restriction (FR) exert influence on genital reflexes (penile erection-PE and ejaculation-EJ) induced by paradoxical sleep deprivation (PSD) in male rats. Diet restriction began at weaning with 6 g/day and food was increased by 1 g per week until reaching 15 g/day by adulthood. Rats submitted to FR and those fed ad libitum were distributed into PSD or maintained as control groups and challenged with saline or cocaine. The results indicated that PSD+saline induced PE and EJ in both ad libitum and FR groups, but cocaine only potentiated reflexes in ad libitum group. In an attempt to revert the effects of FR on genital reflexes, we provided food ad libitum to the restricted group during the PSD period (4 days). When compared to FR rats, an increase in the frequency of PE was observed in the FR group fed ad libitum during PSD (both groups were challenged with cocaine). Further, we sought to investigate motivational behavior by placing food within the behavioral cage during the evaluation of genital reflexes. The FR PSD+saline group challenged with food did not display genital reflexes but when injected with cocaine the responses were similar to those observed in FR PSD+cocaine rats not challenged with food. Our data suggest that the facilitatory effect of PSD on genital reflexes did not override the inhibitory effect of FR on erectile function, but different schedules of FR produce distinct effects on genital reflexes. Further studies are warranted to dissect the effect of food restriction on sexual behavior.

Animals↗
PubMed2006

Effects of 3-nitropropionic acid administration on memory and hippocampal lipid peroxidation in sleep-deprived mice.

Numerous studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the effects of a pro-oxidant agent--3-nitropropionic acid (3-NP)--on hippocampal oxidative stress and passive avoidance performance of sleep-deprived mice. Mice were repeatedly treated i.p. with saline or 5 or 15 mg/kg 3-NP and sleep-deprived for 24 h by the multiple platform method--groups of 4-5 animals placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface or kept in their home cage (control groups). The results showed that: (1) neither a 24 h sleep deprivation period nor 3-NP repeated treatment alone were able to induce memory deficits and increased hippocampal lipid peroxidation; (2) this same protocol of sleep deprivation, combined with 15 mg/kg 3-NP repeated treatment, induced memory deficits and an increase in hippocampal lipid peroxidation. The results support the involvement of hippocampal oxidative stress in the memory deficits induced by sleep deprivation and the hypothesis that normal sleep would prevent oxidative stress.

Animals↗
PubMed2006

Effects of sleep deprivation on the development of autoimmune disease in an experimental model of systemic lupus erythematosus.

Sleep is hypothesized to play a restorative role on immune system. In addition, disturbed sleep is thought to impair host defense mechanisms. Chronic sleep deprivation is a common occurrence in modern society and has been observed in a number of chronic inflammatory conditions, such as systemic lupus erythematosus (SLE). New Zealand Black/New Zealand White (NZB/NZW) F1 mice develop an autoimmune disease that strongly resembles SLE in humans, exhibiting high titers of antinuclear antibodies associated with the development of rapidly progressive and lethal glomerulonephritis. On the basis of this evidence, the present study examined the onset and progress of lupus in as-yet healthy female mice submitted to sleep deprivation. Sleep deprivation was accomplished by two 96-h periods in the multiple-platform method when mice were 10 wk old, and they were observed until 28 wk of age. Blood samples were collected from the orbital plexus fortnightly to evaluate serum antinuclear antibodies and anti-double-stranded DNA. Proteinuria and longevity as well as body weight were also assessed. The results indicated that mice submitted to sleep deprivation exhibited an earlier onset of the disease, as reflected by the increased number of antinuclear antibodies. However, no statistical difference was found in the other parameters analyzed. According to these results, sleep deprivation could be considered as a risk factor for the onset but not for the evolution of the disease.

Animals↗
PubMed2006

Different parkinsonism models produce a time-dependent induction of COX-2 in the substantia nigra of rats.

The present study investigated the effects on general activity, COX-2 and TH protein expression of intranigral neurotoxins LPS, MPTP or 6-OHDA infusion in rats. Results indicate that LPS produced an increase in locomotion frequency (3 and 7 days after surgery) and a strong up-regulation of COX-2 protein 16 and 24 h after surgery, as observed in the substantia nigra (SN). The MPTP model generated impairment in locomotion frequency 24 h after surgery. Besides, MPTP caused a marked up-regulation in COX-2 protein observed in the SN 16 h after surgery. Moreover, the 6-OHDA model produced severe motor impairment indicated by the decrease in locomotion (24 h) and rearing (24 h, 3 and 7 days) frequencies and also an increase in latency (24 h, 3 and 7 days) and immobility (24 h and 3 days) times. We also demonstrated an up-regulation of COX-2, which occurred in the SN 4-24 h after surgery. TH protein did not appear to be reduced in the striatum in the groups lesioned with the neurotoxins. In contrast, the TH content of SN was significantly reduced in the groups lesioned with the very same neurotoxins. For all the models analyzed, we observed no statistical differences in the expression of COX-2 in the striatum along the time-points. The results of the present study suggest that COX-2 induction patterns differ in function of the neurotoxin tested. Such time-dependent induction has been found to be relatively constant, a fact of great significance considering the importance of the neuroinflammatory process in Parkinson's disease.

Analysis of Variance↗
PubMed2006

Comparison of the sleep pattern throughout a protocol of chronic sleep restriction induced by two methods of paradoxical sleep deprivation.

The purpose of the present study was to evaluate the sleep homeostasis of rats submitted to a protocol of chronic sleep restriction by two methods and to evaluate the sleep characteristics during the recovery period. The sleep restriction protocol was accomplished by sleep depriving rats for 18 h everyday for 21 days, using the single platform method (SPM) or the modified multiple platform method (MMPM) of paradoxical sleep (PS) deprivation. Rats were allowed to sleep for 6 h (from 10:00 to 16:00; starting 3 h after lights on) in their individual home-cages, during which their sleep was recorded. At the end of the sleep restriction protocol, rats were recorded in their home-cages for 4 days, where they could sleep freely. Both methods used to induce chronic sleep restriction were effective, in sofar as they resulted in augmented sleep time during the 6h-sleep period, with very few bouts of wakening. Although comparison between the methods did not reveal differences, sleep restriction under MMPM produced a more consistent daily rebound, mainly of paradoxical sleep, with longer episodes. These results showed distinct sleep recovery patterns, suggesting a possible role of the waking experiences (i.e. immobilization stress, social interaction) acting on sleep consolidation.

Animals↗
PubMed2006

A case-control sleep study in children with polyarticular juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between clinical manifestations and sleep abnormalities in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-one patients with active polyarticular JRA and 20 healthy controls were enrolled consecutively. Pain and functional impairment were assessed with standardized, validated Brazilian questionnaires. Sleep evaluation was based on parent reporting of their child's sleep habits and polysomnography; subjects underwent an adaptation night in the sleep laboratory. Sleep architecture was analyzed and spectral analysis of non-rapid eye movement (REM) sleep was carried out by electroencephalography. RESULTS: Patients with JRA exhibited higher indexes of periodic leg movements (PLM; p = 0.02), isolated leg movements (LM), and arousals, as well as increases in alpha activity in non-REM sleep (all p < 0.01), in spite of similar frequency of sleep complaints in comparison to controls. Among JRA patients, greater alpha activity in non-REM sleep was observed in the participants with greater joint involvement assessed by the Escola Paulista de Medicina-Pediatric Range of Motion Scale (p = 0.03) or joint count (p = 0.02). Correlation was observed between morning stiffness and PLM and/or LM (rS = 0.75, Sr = 0.74, p < 0.001 for both), and between self-rating scores of pain and alpha activity in non-REM sleep (rS = 0.74, p < 0.001). CONCLUSION: Pain symptoms and disability are related to sleep fragmentation in patients with active polyarticular JRA.

Adolescent↗
PubMed2006

Sleep deprivation abolishes the locomotor stimulant effect of ethanol in mice.

The present study aimed to investigate the effects of sleep deprivation (SD) on the dose-dependent stimulant effect of ethanol (ETOH) on the open-field behavior of female and male mice. Sleep-deprived (48 h, multiple platforms method) or home-cage control female mice were treated with saline (SAL) or 1.4, 1.8 or 2.2g/kg ETOH 5 min before behavioral testing. ETOH produced a dose-dependent increase in open-field locomotor behavior. This locomotor stimulant effect did not reflect a general stimulation in motor activity, since it was accompanied by a simultaneous decrease in rearing frequency as well as by no modification in immobility duration. The effects of ETOH on these three behavioral parameters were specifically modified by SD: the locomotor stimulant effect was abolished, the rearing inhibitory effect was potentiated and the lack of effect on immobility was changed to increase in immobility. Similar results were obtained for male mice although the effects of SD had a lower magnitude. The present findings demonstrate that the acute effect of ETOH on mice's motor activity are behaviorally complex and can be specifically modulated by SD.

Analysis of Variance↗
PubMed2006

Upper airway surgery: the effect on nasal continuous positive airway pressure titration on obstructive sleep apnea patients.

The objective of this study was to observe the change in CPAP pressure after nasal and/or tonsil surgery in a retrospective study involving 17 patients unable to tolerate CPAP titration. All patients had two polysomnography studies for titration: one before and another subsequent to upper airway surgical treatment. The results showed a mean age of 49 +/- 9 years, a body mass index of 30 +/- 4 kg/m(2) and an apnea-hypopnea index of 38 +/- 19. Surgical procedures were radiofrequency reduction of the inferior turbinate (eight patients), septoplasty (one patient), septoplasty with inferior turbinectomy (two patients), septoplasty with inferior turbinate submucosal diathermy (two patients), septoplasty with tonsillectomy (two patients), septoplasty with inferior turbinate submucosal diathermy and tonsillectomy (one patient) and tonsillectomy (one patient). CPAP titration before and after surgery had respectively a mean pressure of 12.4 +/- 2.5 and 10.2 +/- 2.2 cmH(2)O ( P = 0.001). Maximum CPAP pressure was 16.4 cmH(2)O before and 13 cmH(2)O after surgery. A pressure reduction > or =1 cmH(2)O occurred in 76.5% of the patients and > or =3 cmH(2)O in 41.1%. Upper airway surgical treatment appears to have some benefit by reducing nasal CPAP pressure levels. The effect seems to be greater when the prior pressure was > or =14 cmH(2)O.

Adult↗
PubMed2006

Obstructive sleep apnea in patients undergoing supracricoid horizontal or frontolateral vertical partial laryngectomy.

OBJECTIVE: To assess obstructive sleep apnea (OSA) in patients undergoing supracricoid horizontal partial laryngectomy (SCPL) or frontolateral vertical partial laryngectomy (VPL) for the treatment of laryngeal carcinoma and correlate it with age, body mass index, physical examination, and upper airway evaluation. STUDY DESIGN AND SETTING: A prospective study was carried out involving 22 patients between 50 and 80 years of age divided into 2 equal groups. The patients underwent SCPL and VPL, and were evaluated by anamnesis, otolaryngologic examinations, nasopharyngolaryngoscopy, and polysomnography. RESULTS: A significant direct correlation was observed between the apnea/hypopnea index (AHI) and age of the patients. An inversely proportional relation was found between glottic opening and AHI. The presence of OSA was 81% in SCPL and 91% in VPL. CONCLUSION: We observed a high incidence of OSA in patients undergoing SCPL and VPL.

Aged↗
PubMed2006

The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study.

STUDY OBJECTIVE: Examine the effects of donepezil on sleep and rapid eye movement (REM) sleep electroencephalogram (EEG) in patients with Alzheimer disease, using polysomnography, and the correlation between REM sleep EEG parameters and cognitive scores. DESIGN: Randomized, double-blind, placebo-controlled design. SETTINGS: Two sleep research centers, University Hospital. PARTICIPANTS: Thirty-five patients with mild to moderate Alzheimer disease, allocated to 2 groups: donepezil treated (n=17) and placebo treated (n=18). INTERVENTION: Patients were administered donepezil or placebo. OUTCOME MEASURES: Polysomnography with REM sleep EEG spectral analysis and cognitive evaluation using the Alzheimer Disease Assessment Scale, cognitive subscale, were performed at baseline and after 3 and 6 months. Slowing ratio was the ratio between slow and fast EEG frequency bands. Cognitive and sleep data were analyzed using analysis of variance. Correlations between cognitive improvement and REM sleep EEG were also calculated. RESULTS: REM sleep increased significantly after 3 and 6 months of donepezil treatment compared with baseline and placebo (p < .01). Overall theta (p = .04), frontal theta (p < .01) and frontal delta (p = .03) absolute power during REM sleep decreased after 6 months of donepezil treatment. The occipital slowing ratio decreased during treatment (p = .04). REM sleep overall and frontal and centroparietal alpha absolute power significantly correlated with the cognitive improvement rate on the Alzheimer Disease Assessment Scale, cognitive subscale (r = 0.75, r = 0.71, r = 0.78); p < .01). CONCLUSIONS: Donepezil treatment enhanced REM sleep and reduced slow frequencies of REM sleep EEG, suggesting a possible action upon REM sleep-related cholinergic neurons in patients with Alzheimer disease. Furthermore, REM sleep alpha power may predict the cognitive response to donepezil.

Aged↗
PubMed2006

A reassessment of the hyperphagia/weight-loss paradox during sleep deprivation.

STUDY OBJECTIVES: Sleep deprivation is a well-known paradigm to investigate the deleterious effects of prolonged wakefulness. Previous studies have shown that, during sleep deprivation, rats are hyperphagic but, paradoxically, lose body weight. This phenomenon has been attributed to increased metabolism. However, most previous studies have failed to account for food spillage, which may be considerable during sleep deprivation. DESIGN: In the present study, we revisited the issue of feeding changes in sleep-deprived rats and introduced different procedures to allow accurate estimation of food spillage prior to, during, and after 120 hours of sleep deprivation by a single platform technique. SETTING: Animal Sleep Research Laboratory, Psychobiology Department, Universidade Federal de São Paulo, Brazil. MEASUREMENTS AND RESULTS: The main finding was that, once corrected for spillage, food intake was not significantly increased during sleep deprivation. Increases in food removed from feeders were accompanied by proportional increases in food spillage, resulting in no net changes in food intake. Further, weight loss did occur during the sleep-deprivation period, especially in the first 24 hours, and it was actually explained by a reduction in food intake. CONCLUSION: The hyperphagia/weight-loss paradox previously seen during prolonged sleep deprivation does not necessarily occur with shorter periods of deprivation. Although we found no evidence of hyperphagia for up to 5 days of sleep deprivation in chow-fed rats, our data suggest that an impairment in the ability to increase food intake in response to increased energy expenditure contributes to the energy deficit during sleep deprivation in rats.

Animals↗