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Biomedical subjects

S Tufik

Publications and source records attributed to S Tufik.

At least 37 records · Page 2Linked to original sources

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical 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 role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

Animals↗

Organization of single components of defensive behaviors within distinct columns of periaqueductal gray matter of the rat: role of N-methyl-D-aspartic acid glutamate receptors.

The periaqueductal gray matter (PAG) is functionally organized in longitudinal columns arranged along the aqueduct. Stimulation of lateral and dorsal columns produces a complex set of unconditioned behaviors named the 'defense reaction.' Overt responses in rats comprise a tense immobile display, fully opened eyes (herein named exophthalmus), trotting, galloping, jumping, micturition and defecation. Besides, the PAG is rich in glutamate and respective receptors, including the N-methyl-d-aspartic acid (NMDA) type. Therefore, the present study employed regression analysis to map out electrically and NMDA-induced single components of defensive behaviors produced by stepwise increasing stimulation of PAG. Data confirmed the defensive nature of PAG-evoked responses. Neither the appetitive, nor offensive, mouse-killing or male reproductive behaviors were produced by stimulation of PAG in presence of appropriate targets. Threshold and dose-response logistic analyses largely corroborated the columnar organization of PAG-evoked responses. Thus, whereas the defecation was restricted to PAG lateral column, exophthalmus, micturition and somatic defensive responses were similarly organized in dorsolateral and lateral, but not in the ventrolateral column. Moreover, thresholds of dorsolateral and lateral repertoires were strictly hierarchical, with exophthalmus, immobility, trotting, galloping and jumping appearing in this very order. However, the defensive responses of PAG dorsolateral column required NMDA doses significantly lower than those of lateral PAG. Accordingly, NMDA receptors within the dorsolateral PAG are likely to play a major role in the initiation of PAG-evoked defensive responses. In contrast, the present data do not support the organization of unconditioned defensive behaviors in ventrolateral PAG. The neuroanatomical substrate of each response and the role of PAG and NMDA receptors are discussed in relation to the present data. Further, this is the first report on PAG columnar organization of single components of defensive behaviors.

Animals↗

Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice.

The aim of the present study was to verify the effects of pre- or post-training paradoxical sleep (PS) deprivation in mice tested in the passive and the plus-maze discriminative avoidance tasks. Three-month-old Swiss male mice were placed in narrow platforms in a water tank for 72 h to prevent the occurrence of PS. Control animals were kept in the same room, but in their home cages. Before or after this period, the animals were submitted to the training session of one of the behavioral tasks. The test sessions were performed 3 and 10 days after the training. The animals that were PS-deprived before the training session showed retention deficits in the test sessions performed 3 days later in both tasks (decreased latency to enter the dark chamber of the passive avoidance apparatus or increased percent time spent in the aversive arm of the plus-maze discriminative avoidance apparatus). Animals that were PS deprived after the training session showed no differences from control animals in the test sessions performed 3 days after the training in any of the tasks, but showed passive and discriminative avoidance retention deficits in the test performed 10 days after the training. The results suggest that both pre- and post-training paradoxical sleep deprivation produce memory deficits in mice. However, these effects have different temporal characteristics.

Animals↗

Cholinergic mechanisms in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats.

In view of the fact that paradoxical sleep deprivation (PSD) modifies cocaine-induced genital reflexes (penile erection [PE] and ejaculation [EJ]), the aim of this study was to address the interaction of cholinergic agents with the action of cocaine on the genital reflexes of PSD male rats. After a 4-day period of PSD, each group was administered with cholinergic drugs 1 h prior to cocaine and was placed in observation cages. The administration of nicotine (0.12, 0.25, 0.5 and 1 mg/kg sc) reduced the frequency and number of animals displaying PE and increased PE latency. Pretreatment with mecamylamine (1.25, 5, 10 and 20 mg/kg sc) also significantly reduced PE frequency for all doses used. The percentage of rats showing EJ was significantly reduced in the group pretreated with 1 mg/kg of nicotine compared with the saline group. The administration of pilocarpine (1.25, 2.5, 5 and 10 mg/kg sc) and atropine (1.25, 5, 10 and 20 mg/kg sc) led to a reduction in the frequency of PE displayed by the rats. These data show that agonist and antagonist cholinergic drugs inhibit genital reflexes in PSD male rats injected with cocaine. The data also suggest that the stimulating action of cocaine in potentiating the sexual effects in PSD rats does not override the effects of the cholinergic mechanisms of sexual behavior.

Animals↗

Inhibitory effect of GABAergic drugs in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats.

The aim of this study was to seek whether GABAergic drugs were involved in the action of cocaine on spontaneous genital reflexes (penile erection-PE, and ejaculation-EJ) of paradoxical sleep-deprived (PSD) male rats. After a 4-day period of PSD, each group was administered with GABAergic drugs 1 h prior to cocaine and placed in observation cages. The administration of gamma-aminobutyric acid (GABA)-A agonist (muscimol, 2 and 3 mg/kg sc) reduced the number of animals displaying PE, whereas all doses tested of muscimol and bicuculline significantly reduced the frequency of PE. Pretreatment with the lower doses of GABA-B antagonist, phaclofen (1 and 2 mg/kg sc), also significantly reduced the percentage of rats showing PE; however, after the higher dose injection, the proportion of animals with PE was similar to those seen after vehicle pretreatment. Both GABA-B agonist and antagonist significantly reduced the PE frequency for all doses used compared with the vehicle group. There were no significant differences between control and GABA-A drugs in EJ behavior, whereas phaclofen 2 mg/kg pretreatment increased the ejaculatory latency. These data show that GABAergic compounds inhibited PE in male PSD rats suggesting that this inhibition points to a differential role of GABA receptor subtypes.

Animals↗

Effects of morphine or naloxone on cocaine-induced genital reflexes in paradoxical sleep-deprived rats.

The involvement of opioidergic neurotransmission in the modulation of genital reflexes induced by paradoxical sleep deprivation (PSD) and cocaine in rats was the aim of the present study. Morphine (0, 1, 5 and 10 mg/kg) and naloxone (0, 0.3, 3 and 30 mg/kg) were administered prior to saline or cocaine to rats that had been deprived of sleep and the incidence of penile erections (PE) and ejaculations (EJ) was measured. PSD alone induced PE in 50% and EJ in 20% of the rats, but these behaviors were not influenced by morphine or naloxone. Cocaine potentiated the incidence of genital reflexes in PSD rats to 90% (PE) and 70% (EJ). Morphine and not naloxone significantly reduced the percentage of rats displaying this response at the highest doses. Morphine also significantly reduced PE and EJ frequencies at 10 mg/kg. Furthermore, this inhibitory effect of morphine on genital reflexes was prevented by the prior injection of naloxone. Although a number of factors are involved in such a complex phenomenon as PE and EJ, our data show that activation of the opioidergic systems by the agonist morphine reduces genital reflexes-induced by cocaine in PSD males while the antagonist, naloxone, did not have any significant effect. The findings suggest that the stimulating effects of cocaine in potentiating genital reflexes in PSD rats can be unidirectionally modified by opioidergic systems.

Animals↗

Monosialoganglioside (GM1) attenuates the behavioural effects of long-term haloperidol administration in supersensitive rats.

In the present study we investigated the effects of co-administration of GM(1) (15.0 mg/kg, twice daily, for 30 days) and haloperidol (1.0 mg/kg, twice daily, for 30 days), as well as the effects of a 5-day treatment with this dose of GM(1) after withdrawal from haloperidol in rats. The animals were evaluated in the open-field test and apomorphine-induced stereotyped behaviour. The results show that GM(1) was able to attenuate dopaminergic supersensitivity evaluated by the locomotion frequency at 24 and 48 h after the withdrawal from haloperidol. On the other hand, rearing frequency was changed neither by haloperidol nor by GM(1.) In haloperidol-treated rats immobility time differs from 30 min observation session in comparison with the following sessions after the withdrawal from neuroleptic. Apomorphine-induced stereotyped behaviour produced a significant increase in scores of haloperidol-withdrawn rats. GM(1) did not modify the haloperidol effects and did not change the dopamine receptor affinity to apomorphine 100 h from abrupt neuroleptic withdrawal.

Analysis of Variance↗

Comparison between dopaminergic agents and physical exercise as treatment for periodic limb movements in patients with spinal cord injury.

STUDY DESIGN: Randomized controlled trial of physical exercise and dopaminergic agonist in persons with spinal cord injury and periodic leg movement (PLM). OBJECTIVE: The objective of the present study was to compare the effectiveness of physical exercise and of a dopaminergic agonist in reducing the frequency of PLM. SETTING: Centro de Estudos em Psicobiologia e Exercício. Universidade Federal de São Paulo, Brazil. METHODS: A total of 13 volunteers (mean age: 31.6+/-8.3 years) received L-DOPA (200 mg) and benserazide (50 mg) 1 h before sleeping time for 30 days and were then submitted to a physical exercise program on a manual bicycle ergometer for 45 days (3 times a week). RESULTS: Both L-DOPA administration (35.11-19.87 PLM/h, P<0.03) and physical exercise (35.11-18.53 PLM/h, P<0.012) significantly reduced PLM; however, no significant difference was observed between the two types of treatment. CONCLUSIONS: The two types of treatment were found to be effective in the reduction of PLM; however, physical exercise is indicated as the first treatment approach, while dopaminergic agonists or other drugs should only be recommended for patients who do not respond to this type of treatment.

Adult↗

Hormone treatment facilitates penile erection in castrated rats after sleep deprivation and cocaine.

Sleep deprivation is associated with cocaine-enhanced genital reflexes in male rats, and castration of the male rat causes a decline in sexual behaviour, which can be reversed by hormone administration. We conducted two experiments to determine whether sleep deprivation and cocaine administration could also induce spontaneous penile erection in castrated rats after hormonal treatment (testosterone, progesterone and oestradiol). Different doses of hormones or vehicle were administered to rats during the 4-day period of sleep deprivation, and in home-cage control rats. Testosterone did not restore penile erection in castrated sleep-deprived rats. Progesterone triggered penile erection, and 100 mg/day of progesterone induced the highest proportion of rats displaying penile erection, and restored the frequency of penile erection observed in noncastrated sleep deprived rats. Penile erection was absent in vehicle as well as oestradiol-treated sleep-deprived castrated rats. Whereas sleep deprivation increased progesterone concentrations in noncastrated rats, sleep deprivation decreased progesterone concentrations in castrated rats. Corticosterone concentrations were lower in the castrated sleep-deprived rats than in respective control group. These data show that progesterone treatment facilitates penile erection in sleep deprived-cocaine castrated rats.

Animals↗

Influence of temporomandibular joint pain on sleep patterns: role of nitric oxide.

Since nitric oxide is related to nociception and the sleep-wake cycle, this study sought to determine its involvement in the altered sleep pattern in a temporomandibular joint pain model by investigating the effect of the inhibitor of nitric oxide synthase (L-NAME) and that of its precursor (L-arginine). The temporomandibular joints of test animals were injected with Freund's adjuvant or saline, and their sleep was recorded. The procedure was repeated after the administration of L-NAME and L-arginine. L-NAME increased rapid eye movement (REM) sleep in the control group. The orofacial pain group showed a reduction in total sleep time and an increase in sleep latency compared with the SHAM group. L-NAME increased sleep time, non-rapid eye movement (NREM), and REM sleep and reduced sleep latency in the orofacial pain group. L-arginine did not alter sleep parameters. Thus, L-NAME improved sleep efficiency, whereas L-arginine did not modify it, suggesting the involvement of nitric oxide in painful temporomandibular joint conditions.

Animals↗

A comparison of public and private obstructive sleep apnea clinics.

The aim of the present study was to compare the clinical findings and polysomnography results obtained at public and private clinics in Brazil, the follow-up after diagnosis, and the therapeutic aspects related to continuous positive airway pressure. Patients who snore and who have obstructive sleep apnea were retrospectively divided into two groups, i.e., public clinic (N=307) and private clinic (N=317). Data concerning age, sex, body mass index (BMI), neck circumference, medical history, sleepiness scale, follow-up after diagnosis, and acceptance of continuous positive airway pressure therapy were collected. Mean age was 50 +/- 12 (range: 15-80) for public patients and 48 +/- 12 years (range: 19-91) for private patients. Mean BMI was 30 +/- 6 (range: 19-67) for public patients and 31 +/- 6 kg/m (range: 21-59) for private patients. The public clinic had a significantly higher frequency of women than the private clinic (M:F ratio of 2.0:1 and 6.9:1, respectively). The condition of private patients (apnea-hypopnea index=31 +/- 25) was more severe than that of public patients (apnea-hypopnea index=25 +/- 24 events/h; P=0.0004). In the public and private clinics, 19 and 15% of patients were snorers, respectively, and 81 and 85% of them had sleep apnea. After diagnosis, follow-up was longer in the private group. The continuous positive airway pressure acceptance was similar for both groups (32 vs 35%), but patients from the public clinic abandoned treatment more than private ones (65 vs 13%). Social status was significant in terms of the severity of obstructive sleep apnea age and gender distribution. Private patients look for a diagnosis earlier in the course of the disease than public patients, adhere more to follow-up, and abandon continuous positive airway pressure treatment less than public patients do.

Adult↗

Sleep alterations in an experimental orofacial pain model in rats.

This study sought to assess sleep patterns in rats injected with Freund's adjuvant (FA) in the temporomandibular joint (TMJ) as a potential experimental orofacial pain model. Pain response to indomethacin was also assessed. Rats were implanted with electrodes to record electrocorticogram and eletromyogram signals. After a baseline (B) recording, they were injected with Freund's adjuvant (orofacial pain group, n=8) or saline (sham group, n=8) in the temporomandibular joint, and their sleep was monitored over two 12-h light periods. In the second phase of the study, after injecting Freund's adjuvant, indomethacin was administered (1 mg/kg p.o.) at 12- intervals, and sleep patterns were recorded for two additional light periods. The orofacial pain group showed a reduction in sleep efficiency during the two light periods compared with the baseline recording and with the sham group (p<0.001). Increases in sleep and paradoxical sleep (PS) latencies of approximately 200% and 420%, respectively, were observed, as well as an increase in the number of awakenings during both periods (p<0.001). Treatment with indomethacin increased sleep efficiency (p<0.001) and paradoxical sleep time (p<0.001). The number of awakenings (p<0.001) and sleep (p<0.001) and paradoxical sleep latencies (p<0.001) were reduced reestablishing the normal sleep pattern. The results showed the reliability and usefulness of the temporomandibular joint pain model to characterize sleep disturbances related to pain and its response to indomethacin.

Analysis of Variance↗

Stem-completion tasks (indirect, direct inclusion and exclusion) are differently affected by equipotent doses of lorazepam and flunitrazepam.

This study was designed to explore the effects on performance in stem-completion tasks of two benzodiazepines (BZ) in equipotent doses: lorazepam, a drug that atypically disrupts perceptual priming, and flunitrazepam, a compound with standard BZ effects. The study followed a placebo-controlled, double-blind, parallel-group design. Thirty-six young and healthy subjects carried out three completion tasks at theoretical peak-plasma concentrations of drugs: (a) indirect tasks, in which the subjects were instructed to complete stems with the first word that came to mind; (b) direct inclusion tasks/cued recall, in which the participants had to try to use words seen at study as completions; and (c) direct exclusion tasks, in which words seen at study were to be avoided. The PDP was applied to the results in the inclusion and exclusion tasks, to obtain indices of explicit/controlled (C) and implicit/automatic (A) memory. The C index was lowered by both BZs and A was equivalent in all treatments, confirming the general amnestic action of BZs. However, lorazepam led to decreases in completions in the indirect and inclusion tasks, while flunitrazepam impaired performance in the exclusion task. The qualitative differences between the drugs in their effects on performance suggest that these BZs may lead to differences in response bias.

Administration, Oral↗

Palatable solutions during paradoxical sleep deprivation: reduction of hypothalamic-pituitary-adrenal axis activity and lack of effect on energy imbalance.

Paradoxical sleep deprivation (PSD) induces increased energy expenditure in rats, insofar as rats eat more but loose weight throughout the deprivation period. In the present study, rats were offered water, saccharin or sucrose to drink during the deprivation period, since it has been proposed that carbohydrates reduce the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Rats were submitted to the flower pot technique for 96 h. During the PSD period, they were weighed daily and food and fluid intake was assessed twice a day. At the end of the PSD period, rats were killed and plasma concentrations of glucose, adrenocorticotropic hormone (ACTH) and corticosterone were assayed. Compared to their control counterparts, all paradoxical sleep-deprived rats consumed more food, but lost weight. Paradoxical sleep-deprived rats given sucrose drank more than their control counterparts (especially in the light phase of the light/dark cycle). Paradoxical sleep-deprived rats showed increased food intake during all periods throughout the experiment, with peak intake during the dark phase and nadir during the light phase of the light/dark cycle. All paradoxical sleep-deprived rats showed lower glucose plasma levels than control rats and increased relative adrenal weight. However, when given saccharin or sucrose, paradoxical sleep-deprived rats showed lower concentrations of ACTH and corticosterone than their water-provided counterparts, indicating that palatable fluids were capable of lowering HPA axis activation produced by PSD. The fact that PSD induced energy imbalance regardless of the relative attenuation of the HPA axis activity produced by saccharin or sucrose suggests that the HPA axis may play only a secondary role in this phenomenon, and that other mechanisms may account for this effect. The data also suggest that supply of palatable fluids can be an additional modification to reduce the stress of the flower pot method.

Adrenal Glands↗

Hydrochlorothiazide abolishes the anti-atherosclerotic effect of quinapril.

1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.

Animals↗

Increased plasma homocysteine levels in shift working bus drivers.

BACKGROUND: Previous studies have indicated an association between shift work and cardiovascular disease. There is also considerable epidemiological evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular disorders. AIMS: To analyse plasma homocysteine levels in shift work bus drivers, and to investigate possible relations with sleep parameters and other biochemical factors. METHODS: Blood samples were collected from 30 male shift working long-haul bus drivers in a Brazilian sample and analysed for plasma levels of homocysteine, folic acid, vitamin B(12), and serum lipids. A group of 22 daytime workers, matched for age and body mass index served as controls. The incidence of mutations in the gene coding for methylene tetrahydrofolate, an enzyme which is related to hyperhomocysteinemia, was also assessed. Polysomnographic recordings were obtained from the target group. RESULTS: Bus drivers showed significantly higher levels of plasma homocysteine than the control group (18.57 v 9.43 micro M). Most of the other biochemical, behavioural, and molecular parameters did not differ between groups. Likewise, sleep parameters appeared to be within the normal range. CONCLUSIONS: The significantly increased plasma homocysteine levels in long-haul bus drivers did not appear to be secondary to other biochemical or behavioural problems in this group. These results suggest that hyperhomocysteinemia may be involved in the increased incidence of cardiovascular diseases observed in shift workers.

Adult↗

Lorazepam induces an atypical dissociation of visual and auditory event-related potentials.

Lorazepam has been reported to atypically disrupt visual processing compared to other benzodiazepines (BZs), but it is not known to what extent this effect extends to impairment in other modalities. Our objective was to compare the effects of lorazepam with those of flunitrazepam, a BZ with standard effects, on visual and auditory event-related potentials (ERPs) using the same paradigm. The study followed a placebo-controlled, double-blind, parallel group-design and involved single oral doses of lorazepam (2.0 mg), flunitrazepam (1.2 mg) and placebo. Thirty-six young, healthy subjects completed a test battery before and after treatment including classic behavioural tests, visual and auditory ERPs. Both drugs led to comparable alterations on behavioural tests and double-dissociations were found, indicating that the doses used were equipotent: lorazepam was more deleterious than flunitrazepam and placebo in fragmented shape identification, while simple reaction times were prolonged for flunitrazepam in comparison to lorazepam and placebo. Effects on P3 latencies were also distinct: alterations in both modalities for flunitrazepam were equivalent and greater than placebo's. In contrast, lorazepam at the frontal and central electrode sites led to greater changes in visual than in auditory latency, and also to longer visual latencies than flunitrazepam and placebo, but lorazepam's auditory latency effects were only different to placebo's at the parietal electrode site. Peripheral visual changes were not responsible for these effects. Differences in the impairment profile between equipotent doses of lorazepam and flunitrazepam suggests that lorazepam induces atypical central visual processing changes.

Adolescent↗