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Biomedical subjects

Sergio Tufik

Publications and source records attributed to Sergio Tufik.

At least 73 records · Page 4Linked to original sources

Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component.

The effects of paradoxical sleep deprivation (PSD-48 h) on the conditioned and unconditioned components of behavioural sensitization to amphetamine (two injections of 2.0 mg/kg, separated by 7 days) were studied using locomotion frequency of mice observed in an open-field as experimental parameter. Behavioural sensitization only occurred in PS deprived mice that were exposed to the open-field after the first amphetamine injection. The possible involvement of PSD in the development of a Pavlovian association between the stimulant effect of amphetamine and environmental as well as interoceptive drug cues is discussed.

Amphetamine↗

Increased hypocretin-1 (orexin-a) levels in cerebrospinal fluid of rats after short-term forced activity.

The hypocretins (orexins) are recently discovered neuropeptides initially associated with feeding behavior and sleep regulation. However, the normal function of these peptides is unclear and a number of studies have reported a role in energy homeostasis and locomotor activity. Exercise (or physical activity) is the most powerful way of challenging the internal homeostatic process. This study examines the circadian differences in response to forced activity and homeostatic challenges on hypocretin-1 (Hcrt-1) levels in the cerebrospinal fluid (CSF) of rats. Hcrt-1 levels were decreased after long-term immobilization at the end of active phase (zeigeber time-0, ZT-0) and increased after short-term forced swimming in the rest phase (ZT-8). Nevertheless, no effects were observed after short-term immobilization, total sleep deprivation or cold exposure. We concluded that despite the relation between hypocretins, stress and sleep regulation reported in the literature, short-term total sleep deprivation, immobilization and cold exposure did not induce increases in CSF Hcrt-1 levels at ZT-0 and ZT-8. On the other hand, the relationship between hypocretinergic system activation and motor activation is reinforced by decrease in Hcr-1 levels after long-term immobilization at ZT-0 and its increased levels after short-term forced swimming at ZT-8 in CSF of rats.

Animals↗

Afferent pain pathways: a neuroanatomical review.

Painful experience is a complex entity made up of sensory, affective, motivational and cognitive dimensions. The neural mechanisms involved in pain perception acts in a serial and a parallel way, discriminating and locating the original stimulus and also integrating the affective feeling, involved in a special situation, with previous memories. This review examines the concepts of nociception, acute and chronic pain, and also describes the afferent pathways involved in reception, segmental processing and encephalic projection of pain stimulus. The interaction model of the cerebral cortex areas and their functional characteristics are also discussed.

Afferent Pathways↗

Behavioural and neurochemical effects of phosphatidylserine in MPTP lesion of the substantia nigra of rats.

The present study investigated the effects of intranigral MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) infusion on rats treated with phosphatidylserine and evaluated in two memory tasks and on striatal dopamine levels. The results indicated that MPTP produced a significant decrease in the avoidance number in comparison to sham-operated and non-operated rats submitted to a two-way avoidance task. MPTP-lesioned rats exhibited an increase in the latencies to find the platform in cued version of the water maze in comparison to sham-operated and non-operated animals. The tested toxin reduced striatal dopamine levels in comparison to sham-operated and non-operated groups. A final surprising result was that phosphatidylserine was unable to reverse the cognitive deficits produced by MPTP or the reduction of striatal dopamine levels. In conclusion, the data suggest that MPTP is a good model to study the early impairment associated with Parkinson's disease and phosphatidylserine did not improve the memory impairment induced by MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation.

Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or 96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8 after 24 h of REM sleep rebound. These results suggest that REM sleep deprivation activates and REM sleep rebound inhibits the hypocretin system. Increased hypocretin tone during REM deprivation may be important in mediating some of the effects of REM sleep deprivation such as antidepressant effects, hyperphagia and increased sympathetic activity.

Animals↗

Age-related effects on genital reflexes induced by paradoxical sleep deprivation and cocaine in rats.

Although sexual function often decreases with age, a recent study demonstrated that paradoxical sleep deprivation (PSD) was effective in inducing penile erection (PE) in 60% of 22-month-old PSD rats after acute cocaine injection, whereas this behavior was absent in non-PSD control rats. The present study sought to compare alterations in genital reflexes (PE and ejaculation-EJ) induced by PSD followed by acute cocaine or saline at different points in the life span of male rats. Rats of different ages (3, 6, 10, 12, 18, 22 and 28 months), were given a single injection of either saline or cocaine (7 mg/kg, i.p.) after a 4-day period of PSD, and then evaluated for genital reflexes. Results indicated that genital reflexes in PSD rats given saline become less frequent with age and disappear after the age of 18 months. However, cocaine potentiated and prolonged these behaviors until the age of 22 months. Although a number of factors are involved in such a complex phenomenon as PE, we suggest that the previously documented dopamine receptor supersensitivity induced by PSD may be an important contributor to the potentiation by cocaine of genital reflexes after sleep deprivation.

Aging↗

Evaluation of acute and chronic treatments with Harpagophytum procumbens on Freund's adjuvant-induced arthritis in rats.

The extract of Harpagophytum procumbens, widely utilized in Europe and, more recently, in other countries, is traditionally indicated to treat inflammatory processes. Harpagophytum procumbens acts by way of interleukins and leukocyte migration to the painful and inflamed joint area. Chemically, its secondary tuberous roots contains iridoid glycosides, harpagogide, procumbide, and harpagoside, as the active principle. The purpose of the present study was evaluate the therapeutic potential as anti-inflammatory and analgesic agent in rat model of Freund's adjuvant-induced arthritis both in the acute and chronic phases. The animals were injected with Freund's adjuvant in sub-plantar tissue of the right posterior paw and randomly assigned in acute (25, 50, or 100 mg/kg) or chronic (100 mg/kg) treatments with Harpagophytum procumbens solution test or vehicle. Then, submitted to behavioral test and assessment of body weight and right paw's measurements. The results show that Harpagophytum procumbens extract increased the animals 'latency of paws' withdrawal, indicating a protective effect against the pain induced by the thermal stimulus, both in acute and chronic treatments. In addition to reduction in the right paw edema in the experimental groups when compared to control group. Thus, the data showed anti-inflammatory and peripheral analgesic properties of Harpagophytum procumbens extract with all doses tested, thus confirming its indication for inflammatory processes.

Analgesics↗

Comparison between the effects of soy milk and non-fat cow milk on lipid profile and lipid peroxidation in patients with primary hypercholesterolemia.

OBJECTIVE: This study assessed whether the consumption of soy milk could add significantly to the lipid profile and lipid peroxidation in comparison with non-fat milk. METHODS: A double-blind, randomized, crossover study was conducted on 60 outpatients with primary hypercholesterolemia following a lipid-lowering diet for at least 6 wk. Lipid profile was obtained at baseline and at 6 and 12 wk, with the patients randomly assigned to receive initially 1 L/d of soy milk or non-fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric reactive substances. Apolipoprotein E genotypes were examined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: The soy milk diet was associated with low-density lipoprotein cholesterol reduction (baseline = 157 +/- 5 mg/dL; soy milk = 148 +/- 4 mg/dL; non-fat cow milk = 158 +/- 4 mg/dL; P < 0.05, soy milk versus other treatments) and with high-density lipoprotein cholesterol increase (baseline = 58 +/- 2 mg/dL; soy milk = 62 +/- 2 mg/dL; non-fat cow milk = 57 +/- 2 mg/dL; P < 0.05, soy milk versus other treatments). In addition, plasma thiobarbituric reactive substances were reduced by the soy milk diet (baseline = 1.82 +/- 0.12 nM/L; soy milk = 1.49 +/- 0.09 nM/L; non-fat cow milk = 1.91 +/- 0.11 nM/mL; P < 0.05, soy milk versus non-fat cow milk). Changes in lipid profile were not influenced by APOE genotypes. CONCLUSIONS: These results indicate that soy milk as part of a lipid-lowering diet has beneficial effects in improving lipid profile and reducing lipid peroxidation.

Adult↗

Sleep and sleepiness among Brazilian shift-working bus drivers.

The aim of this study was to evaluate daytime and nighttime sleep, as well as daytime and nighttime sleepiness of professional shift-working bus drivers. Thirty-two licensed bus drivers were assessed by nocturnal and diurnal polysomnography (PSG) recording and multiple sleep latency testing (MSLT) sessions. Sleep length was shorter and sleep efficiency reduced during daytime sleep compared with nighttime sleep. Thirty-eight percent of the drivers had indices of obstructive apnea and hypopnea syndrome (>5/h sleep) during nighttime and daytime sleep; more drivers snored during daytime than nighttime sleep (50% vs. 35%, p < 0.05), and 38% of the drivers evidenced periodic leg movements. The MSLT revealed that 42 and 38% of the bus drivers met the criteria for sleepiness when the test was conducted during the day and night, respectively. The daytime as compared to nighttime sleep of shift-working bus drivers was shorter and more fragmented and was associated in many with evidence of excessive sleepiness. Respiratory disorder was a common finding among the professional shift-working bus drivers. All these sleep deficiencies may adversely affect on the job driving performance.

Adult↗

Sleep parameters among offshore workers: an initial assessment in the Campos Basin, Rio De Janeiro, Brazil.

Shift work has potentially adverse effects on health, particularly on sleep. The purpose of the present study was to assess sleep parameters among personnel working in oil and gas offshore installations in the Campos Basin, Rio de Janeiro, Brazil. One hundred and seventy-nine subjects were asked to complete a sleep questionnaire with multiple-choice answers. Offshore workers were divided into two groups according to their work schedule: (1) fixed daytime workers (n = 86; age: 35.8+/-9.6 yrs) and (2) shift (n = 87) or night (n = 6) workers (total n = 93; age: 37.7+/-9.7 yrs). Shift/night workers reported poor sleep more frequently than the daytime workers (20.4% vs. 1.2%, p < 0.01), as well as habitual difficulty in falling asleep (15.1% vs. 4.7%, p<0.01), long latency of sleep onset (28% vs. 7%, p<0.01), fragmented sleep (45.2% vs. 16.3%, p<0.01), short sleep episodes (44.1% vs. 16.3%, p < 0.01), irregular bedtimes (29.0% vs. 12.8%, p < 0.01), and feeling tired upon awakening (15.1% vs. 3.5%, p < 0.01). Habitual napping and loud snoring were reported twice as often in shift/night than in day workers (p < 0.01). Nightmares, somnambulism, and unpleasant feeling in the legs were equality reported by both groups (p > 0.05). Few offshore workers had sought medical help for their sleep problems. A higher number of shift/night workers reported feelings of sadness compared with day workers (26.9% vs. 9.3%, p < 0.01). The findings of this study show that subjective reports of sleep-related problems are quite common among Brazilian offshore shift workers. Reliance on self-reported sleep problems and a cross-sectional design are the main limitations of our study.

Adult↗

Sleep patterns over 21-day period in rats with chronic constriction of sciatic nerve.

The main purpose of the present study was to examine sleep patterns over 21-day periods of rats in a peripheral neuropathy model induced by sciatic nerve constriction. Evaluation of the recordings showed that chronic constrictive injury (CCI) induced sleep alterations such as reduced sleep efficiency and increased number of arousals, especially during the light period. Among these alterations, sleep patterns were most affected between day 2 and day 10. The rats took longer to get to sleep from day 2 to 7 days after the CCI in the light period. Additionally, latency to the first paradoxical sleep episode was reduced in the second to fourth day after CCI in both light and dark period recordings. In conclusion, sciatic nerve constriction induced poor sleep quality with disrupted sleep in rats, particularly during the first week of that condition.

Animals↗

Facilitation of ejaculation after methamphetamine administration in paradoxical sleep deprived rats.

This study investigated the effects of methamphetamine (MA) on genital reflexes in paradoxical sleep deprived (PSD) rats. Different doses of MA (0, 4, 16 and 64 mg/kg) were acutely given after PSD or the equivalent time to control animals. We observed enhancement of spontaneous ejaculation in PSD rats with larger doses of MA, the highest of which induced ejaculation in 100% of the PSD rats. This was significantly higher than the 30% in the control. Although testosterone exerts motivational effects on male sexual behavior, our data shows that testosterone levels were lower after the PSD period in saline and in the 64 mg/kg MA groups, which present ejaculation at different rates (20% and 100%, respectively). Progesterone levels were significantly higher in PSD-saline in relation to control group and in the 16 and 64 mg/kg of MA groups compared to the other doses. Since PSD induces dopaminergic alterations and dopamine (DA) has a key role in male sexual behavior, plasma DA was also measured. The DA concentration was enhanced in all PSD groups compared with their control group. The mechanism that activates steroid hormones may represent an important physiological effect through which neurotransmitters can affect behavioral events. These data show that MA facilitates ejaculation in PSD rats, however, further studies need to be carried out in order to clarify the hormonal-neurochemical mechanisms involved.

Analysis of Variance↗

Deficits in avoidance responding after paradoxical sleep deprivation are not associated with altered [3H]pirenzepine binding to M1 muscarinic receptors in rat brain.

Previous work had indicated that animals that were sleep-deprived and then trained on a passive avoidance task show poor retention of the task 24 h later after being allowed to sleep freely again. Cholinergic involvement is suggested by the fact that this effect is prevented by treatment with the muscarinic agonist pilocarpine during sleep deprivation. The observation that similar deficits are observed in non-deprived rats after treatment with M1-selective antagonist compounds such as dicyclomine or pirenzepine cause similar impairments, and gave rise to the hypothesis that sleep deprivation might induce significant reductions in M1 binding in brain areas involved in learning and memory processes. Rats were deprived of sleep for 96 h and then either immediately killed, or allowed to recover sleep for 24 h before being killed. [3H]pirenzepine binding to M1 sites was examined by quantitative autoradiography in 39 different brain areas in cage controls, sleep-deprived and sleep-recovered animals (N=8 per group). No significant differences among groups were found in any brain region. A separate group of animals was subjected to the sleep deprivation procedure and then trained in a simple avoidance task. Animals were then allowed to sleep and retested 24 h later. This group showed a significant impairment in the avoidance task compared to cage controls, in agreement with previous observations. These data suggest that proactive learning/memory deficits induced by sleep deprivation cannot be attributed to altered M1 binding either immediately after deprivation (when avoidance training occurs) or after sleep has recovered (when acquisition/retention are tested). The possibility remains that alterations in M1 function occur at post-membrane second messenger systems.

Analysis of Variance↗

Effects of early handling on basal and stress-induced sleep parameters in rats.

Exposure of humans and animals to stressful events early in life leads to significant and often permanent behavioural, neuroendocrine and central alterations. Early handling consists of removing the litter from the nest for 15 min/day, from post-natal days 2 to 14 and results in lowered ACTH and corticosterone stress response and reduced anxiety-like and fear behaviours. Stress-induced sleep alterations usually consists of increased sleep time, known as sleep rebound. In the present study, basal and stress-induced sleep pattern of control non-manipulated (CTL) and early handled (EH) adult male rats was investigated. Sleep was evaluated by 21-h polysomnographic recordings (from 10:00 to 07:00 h of the next day) before and after a 1-h session of restraint stress. The results showed that in the first 3 h following stress, both CTL and EH animals exhibited an impairment of sleep, with a reduction of sleep efficiency, duration of slow wave sleep and of paradoxical sleep. On the contrary, time awake and awakening bouts were augmented in this period. Sleep rebound was observed mainly in the dark period of the light-dark cycle. Stress-induced sleep changes were similar between CTL and EH animals for most sleep parameters. However, EH animals exhibited more bouts of paradoxical sleep on the night following stress exposure and longer bouts of paradoxical sleep in the light period that followed restraint stress. These data indicate that stress-induced alterations of sleep in early handled animals are similar to that observed in control animals, except for some parameters related to paradoxical sleep.

Animals↗

Influence of paradoxical sleep deprivation and cocaine on development of spontaneous penile reflexes in rats of different ages.

Recent studies have established that paradoxical sleep deprivation (PSD) and cocaine administration induce genital reflexes (penile erection and ejaculation) in adult and old rats. To determine whether the same effects would induce spontaneous genital reflexes in rats of different ages (30-90 days old), we administered with cocaine (7 mg/kg) or saline to rats after a 4-day period of PSD, or at the equivalent time-point in control animals, and penile erection and ejaculation were then evaluated. In PSD rats administered cocaine, erection was observed from 30 days old to 90 days old, when both genital reflexes reached a peak. Animals submitted to PSD and saline injection showed erection from 60 to 90 days old. None of the control (saline and cocaine) groups of any age displayed these behaviors. The effects of PSD on steroid hormone levels showed that, although testosterone levels increased with age, PSD caused a marked decrease in testosterone at all ages evaluated. Progesterone and corticosterone levels were higher in PSD groups than in the respective control groups. These findings suggest that the interaction of PSD and cocaine probably enhances dopaminergic transmission in the brain and may accelerate the development of genital reflexes in male rats.

Age Factors↗

Further validation of actigraphy for sleep studies.

STUDY OBJECTIVES: Actigraphy is generally compared to polysomnography (PSG), which has been considered the gold standard for sleep studies. The objective of the present study was to evaluate the concordance between PSG and two previously proposed algorithms (Cole et al, 1992; Sadeh et al, 1994) to analyze actigraphic recordings. The minute-by-minute agreement rate was evaluated through calculation of sensitivity, specificity, and accuracy. Regarding the sleep parameters, the concordance was performed through the Bland and Altman technique. DESIGN: A night of adaptation to the sleep laboratory followed by simultaneous polysomnographic and actigraphic recordings throughout the night. PARTICIPANTS: 21 healthy volunteers. SETTING: A sleep laboratory INTERVENTIONS: None. RESULTS: Ninety-one percent of all PSG epochs were correctly identified by both algorithms, and this accuracy is reasonably satisfactory. The actigraphy was a sensitive method, with values of 99% and 97% for Cole's and Sadeh's algorithms, respectively. However, actigraphy had a low specificity: 34% and 44% for Cole's and Sadeh's algorithms, respectively. The Bland and Altman technique showed that actigraphy systematically overestimated Sleep Latency, Total Sleep Time and Sleep Efficiency while it underestimated Intermittent Awakenings. CONCLUSIONS: The results of this study show the utility of actigraphy as a useful method for assessment of sleep, despite its limitations regarding identification of waking epochs during sleep. The Bland and Altman concordance technique was revealed to be a powerful tool to evaluate how well actigraphy agreed with polysomnography. This technique, combined with calculations of sensitivity and specificity, appears to be the most adequate procedure for the assessment of concordance.

Adolescent↗

The effect of apomorphine on genital reflexes in male rats deprived of paradoxical sleep.

Drugs that stimulate dopamine (DA) systems can stimulate sexual arousal in male rats and humans, and previous work has shown that cocaine enhances genital reflexes [penile erection (PE) and ejaculation (EJ)] in rats deprived of paradoxical sleep (PS). The present study sought to expand the latter finding by assessing the effects of DA receptor agonist apomorphine in sleep-deprived rats. Apomorphine in doses ranging from 10 to 240 microg/kg was administered intraperitoneally to rats that had been deprived of sleep for 4 days and to normal controls, and the incidence of PEs and EJs was measured for 60 min. Sleep deprivation alone induced PE and this effect was potentiated by apomorphine, with maximal effects occurring with the 120 microg/kg dose; results for this dose group differed from those of PSD groups treated with 0, 10, 20, 40, 80, and 240 microg/kg of apomorphine. Sleep deprivation alone also induced spontaneous EJ, but this response was not potentiated by apomorphine in the dose range tested. We suggest that the potentiating effects of apomorphine on PE are likely due to PSD-induced DA receptor supersensitivity.

Analysis of Variance↗

Cocaine-induced genital reflexes during paradoxical sleep deprivation and recovery.

Paradoxical sleep deprivation (PSD) for 96 h together with cocaine administration elicits genital reflexes (penile erection [PE] and ejaculation [EJ]) in rats. Our objective was to examine genital reflexes after periods of 24, 48, 72, 96, 120, and 144 h of PSD and during a 4-day recovery period in acute cocaine-administered rats. After 24 h of PSD followed by cocaine administration, animals started to display PE and EJ, peaking in the 96th h of PSD, whereas PE and EJ were absent in control animals. The effects of more than 96 h of PSD decrease genital reflexes as observed after 120 and 144 h. Genital reflexes were present in the recovery periods but diminished gradually during the period evaluated. Even short periods of PSD probably cause supersensitivity of dopamine (DA) receptors and exacerbate the effects of cocaine on dopaminergic pathways to induce frequent PE and EJ.

Animals↗