Cardiovascular and respiratory changes during slow-wave sleep in rats are associated with electrocorticogram desynchronization

In awake rats a single recurrent larger tidal volume (deep breaths) occurs at regular intervals, followed by oscillations in arterial pressure and heart rate. In the present study we recorded the changes in blood pressure, heart rate and ventilation during the wakefulness-sleep cycle identified by electrocorticographic records in order to determine whether the deep breaths and cardiovascular oscillations were associated with changes in the electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats the deep breaths and oscillations in arterial pressure and heart rate were preceded by SWS desynchronization. The interval between deep breaths during SWS was 71 ± 4 s, the period between initial desynchronization and the generation of deep breaths was 3.98 ± 0.45 s and the duration of SWS desynchronization was 11 ± 0.65 s. Hypotension (-16 ± 1 mmHg) and tachycardia (+15 ± 5 bpm) were observed during deep breaths in the SWS state. These data indicate that the oscillations in arterial pressure and heart rate during SWS are associated with deep breaths, which in turn are preceded by desynchronization of the electrocorticogram in this state of sleep

Behavioral correlates of the activity of serotonergic and non-serotonergic neurons in caudal raphe nuclei

We investigated the behavioral correlates of the activity of serotonergic and non-serotonergic neurons in the nucleus raphe pallidus (NRP) and nucleus raphe obscurus (NRO) of unanesthetized and unrestrained cats. The animals were implanted with electrodes for recording single unit activity, parietal oscillographic activity, and splenius, digastric and masseter electromyographic activities. They were tested along the waking-sleep cycle, during sensory stimulation and during drinking behavior. The discharge of the serotonergic neurons decreased progressively from quiet waking to slow wave sleep and to fast wave sleep. Ten different patterns of relative discharge across the three states were observed for the non-serotonergic neurons. Several non-serotonergic neurons showed cyclic discharge fluctuations related to respiration during one, two or all three states. While serotonergic neurons were usually unresponsive to the sensory stimuli used, many non-serotonergic neurons responded to these stimuli. Several non-serotonergic neurons showed a phasic relationship with splenius muscle activity during auditory stimulation. One serotonergic neuron showed a tonic relationship with digastric muscle activity during drinking behavior. A few non-serotonergic neurons exhibited a tonic relationship with digastric and/or masseter muscle activity during this behavior. Many non-serotonergic neurons exhibited a phasic relationship with these muscle activities, also during this behavior. These results suggest that the serotonergic neurons in the NRP and NRO constitute a relatively homogeneous population from a functional point of view, while the non-serotonergic neurons form groups with considerable functional specificity. The data support the idea that the NRP and NRO are implicated in the control of somatic motor output.

Effects of the length and timing of nighttime naps on task performance and physiological function

OBJECTIVE: To examine the effects of the length and timing of nighttime naps on performance and physiological functions, an experimental study was carried out under simulated night shift schedules. METHODS: Six students were recruited for this study that was composed of 5 experiments. Each experiment involved 3 consecutive days with one night shift (22:00-8:00) followed by daytime sleep and night sleep. The experiments had 5 conditions in which the length and timing of naps were manipulated: 0:00-1:00 (E60), 0:00-2:00 (E120), 4:00-5:00 (L60), 4:00-6:00 (L120), and no nap (No-nap). During the night shifts, participants underwent performance tests. A questionnaire on subjective fatigue and a critical flicker fusion frequency test were administered after the performance tests. Heart rate variability and rectal temperature were recorded continuously during the experiments. Polysomnography was also recorded during the nap. RESULTS: Sleep latency was shorter and sleep efficiency was higher in the nap in L60 and L120 than that in E60 and E120. Slow wave sleep in the naps in E120 and L120 was longer than that in E60 and L60. The mean reaction time in L60 became longer after the nap, and faster in E60 and E120. Earlier naps serve to counteract the decrement in performance and physiological functions during night shifts. Performance was somewhat improved by taking a 2-hour nap later in the shift, but deteriorated after a one-hour nap. CONCLUSIONS: Naps in the latter half of the night shift were superior to earlier naps in terms of sleep quality. However performance declined after a 1-hour nap taken later in the night shift due to sleep inertia. This study suggests that appropriate timing of a short nap must be carefully considered, such as a 60-min nap during the night shift.

Electrophysiological measurements of spectral sensitivities: a review

Spectral sensitivities of visual systems are specified as the reciprocals of the intensities of light (quantum fluxes) needed at each wavelength to elicit the same criterion amplitude of responses. This review primarily considers the methods that have been developed for electrophysiological determinations of criterion amplitudes of slow-wave responses from single retinal cells. Traditional flash methods can require tedious dark adaptations and may yield erroneous spectral sensitivity curves which are not seen in such modifications as ramp methods. Linear response methods involve interferometry, while constant response methods involve manual or automatic adjustments of continuous illumination to keep response amplitudes constant during spectral scans. In DC or AC computerized constant response methods, feedback to determine intensities at each wavelength is derived from the response amplitudes themselves. Although all but traditional flash methods have greater or lesser abilities to provide on-line determinations of spectral sensitivities, computerized constant response methods are the most satisfactory due to flexibility, speed and maintenance of a constant adaptation level

Effect of SX-3228, a selective ligand for the BZ1 receptor, on sleep and waking during the light-dark cycle in the rat

The effects of the benzodiazepine1 (BZ1) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning of the light phase of the light-dark cycle induced a significant reduction of rapid-eye-movement sleep (REMS) during the third recording hour. Moreover, slow wave sleep (SWS) was increased during the fourth recording hour after the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the light-dark cycle caused a significant and maintained (6-h recording period) reduction of waking (W), whereas SWS and light sleep (LS) were increased. REMS values tended to increase during the entire recording period; however, the increase was statistically significant only for the 1.0 mg/kg dose during the first recording hour. In addition, a significant and dose-related increase of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX-3228 is a potent hypnotic when given to the rat during the dark period of the light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Delta sleep instability in children with chronic arthritis

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 ± 6.7 vs 95.8 ± 4.0), sleep stage in minutes: stage 1 (16.8 ± 8.5 vs 17.8 ± 4.0), stage 2 (251.9 ± 41 vs 262.8 ± 38.1), stage 3 (17.0 ± 6.0 vs 15.1 ± 5.7), stage 4 (61.0 ± 21.7 vs 77.1 ± 20.4), and rapid eye movement sleep (82.0 ± 27.6 vs 99.0 ± 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Sleep, ageing and night work

Studies have shown that the frequency or worsening of sleep disorders tends to increase with age and that the ability to perform circadian adjustments tends to decrease in individuals who work the night shift. This condition can cause consequences such as excessive sleepiness, which are often a factor in accidents that occur at work. The present study investigated the effects of age on the daytime and nighttime sleep patterns using polysomnography (PSG) of long-haul bus drivers working fixed night or day shifts. A total of 124 drivers, free of sleep disorders and grouped according to age (<45 years, N = 85, and ≥45 years, N = 39) and PSG timing (daytime (D) PSG, N = 60; nighttime (N) PSG, N = 64) participated in the study. We observed a significant effect of bedtime (D vs N) and found that the length of daytime sleep was shorter [D: <45 years (336.10 ± 73.75 min) vs N: <45 years (398 ± 78.79 min) and D: ≥45 years (346.57 ± 43.17 min) vs N: ≥45 years (386.44 ± 52.92 min); P ≤ 0.05]. Daytime sleep was less efficient compared to nighttime sleep [D: <45 years (78.86 ± 13.30%) vs N: <45 years (86.45 ± 9.77%) and D: ≥45 years (79.89 ± 9.45%) and N: ≥45 years (83.13 ± 9.13%); P ≤ 0.05]. An effect of age was observed for rapid eye movement sleep [D: <45 years (18.05 ± 6.12%) vs D: ≥45 years (15.48 ± 7.11%) and N: <45 years (23.88 ± 6.75%) vs N: ≥45 years (20.77 ± 5.64%); P ≤ 0.05], which was greater in younger drivers. These findings are inconsistent with the notion that older night workers are more adversely affected than younger night workers by the challenge of attempting to rest during the day.

Sleep pattern and learning in knockdown mice with reduced cholinergic neurotransmission

Impaired cholinergic neurotransmission can affect memory formation and influence sleep-wake cycles (SWC). In the present study, we describe the SWC in mice with a deficient vesicular acetylcholine transporter (VAChT) system, previously characterized as presenting reduced acetylcholine release and cognitive and behavioral dysfunctions. Continuous, chronic ECoG and EMG recordings were used to evaluate the SWC pattern during light and dark phases in VAChT knockdown heterozygous (VAChT-KDHET, n=7) and wild-type (WT, n=7) mice. SWC were evaluated for sleep efficiency, total amount and mean duration of slow-wave, intermediate and paradoxical sleep, as well as the number of awakenings from sleep. After recording SWC, contextual fear-conditioning tests were used as an acetylcholine-dependent learning paradigm. The results showed that sleep efficiency in VAChT-KDHET animals was similar to that of WT mice, but that the SWC was more fragmented. Fragmentation was characterized by an increase in the number of awakenings, mainly during intermediate sleep. VAChT-KDHET animals performed poorly in the contextual fear-conditioning paradigm (mean freezing time: 34.4±3.1 and 44.5±3.3 s for WT and VAChT-KDHET animals, respectively), which was followed by a 45% reduction in the number of paradoxical sleep episodes after the training session. Taken together, the results show that reduced cholinergic transmission led to sleep fragmentation and learning impairment. We discuss the results on the basis of cholinergic plasticity and its relevance to sleep homeostasis. We suggest that VAChT-KDHET mice could be a useful model to test cholinergic drugs used to treat sleep dysfunction in neurodegenerative disorders.

Radiometric detection of metabolic activity of Paracoccidioides brasiliensis and its susceptibility to amphotericin B and diethylstilbestrol

Paracoccidioidomycosis (South American blastomycosis) is a systemic disease, strikingly more frequent in males, caused by the dimorphic fungus Paracoccidioides brasiliensis. A radiometric assay system has been applied to study the metabolic activity and the effect of drugs on this fungus "in vitro". The Y form of the yeast, grown in liquid Sabouraud medium was inoculated into sterile reaction vials containing the 6B aerobic medium along with 2.0 μCi of 14C-substrates. Control vials, prepared in the same way, contained autoclaved fungi. To study the effects of amphotericin B (AB) (0.1 and 10 μg/ml) and diethylstilbestrol (DSB) (1.0, 5.0 and 10 μg/ml) extra controls with live fungi and no drug were used. All vials were incubated at 35°C and metabolism measured daily with a Bactec instrument. 14CO2 production by P. brasiliensis was slow and could be followed for as long as 50 days. AB at 10mg/ml and DSB at 5 μg/ml inhibited the metabolism and had a cidal effect on this fungus. The results with DSB might explain the low incidence of the disease in females. This technique shows promise for studying metabolic pathways, investi gating more convenient 14C-substrates to expedite radiometric detection and for monitoring the effects of other drugs and factors on the metabolism of P. brasiliensis "in vitro".

Antitumor activity of chemical modified natural compounds

Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1). Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

Serotonergic neurons in the caudal raphe nuclei discharge in association with activity of masticatory muscles

There is a dense serotonergic projection from nucleus raphe pallidus and nucleus raphe obscurus to the trigeminal motor nucleus and serotonin exerts a strong facilitatory action on the trigeminal motoneurons. Some serotonergic neurons in these caudal raphe nuclei increase their discharge during feeding. The objective of the present study was to investigate the possibility that the activity of these serotonergic neurons is related to activity of masticatory muscles. Cats were implanted with microelectrodes and gross electrodes. Caudal raphe single neuron activity, electrocorticographic activity, and splenius, digastric and masseter electromyographic activities were recorded during active behaviors (feeding and grooming), during quiet waking and during sleep. Seven presumed serotonergic neurons were identified. These neurons showed a long duration action potential (>2.0 ms), and discharged slowly (2-7 Hz) and very regularly (interspike interval coefficient of variation <0.3) during quiet waking. The activity of these neurons decreased remarkably during fast wave sleep (78-100%). Six of these neurons showed tonic changes in their activity positively related to digastric and/or masseter muscle activity but not to splenius muscle activity during waking. These data are consistent with the hypothesis that serotonergic neurons in the caudal raphe nuclei play an important role in the control of jaw movements

Topographic abnormality of slow cortical potentials in schizophrenia

A recent study from our laboratory has provided evidence for the generation of slow potentials occurring in anticipation to task-performance feedback stimuli, in multiple association cortical areas, consistently including two prefrontal areas. In the present study, we intended to determine whether these slow potentials would indicate some abnormality (topographic) in schizophrenic patients, and thus serve as an indication of abnormal association cortex activity. We recorded slow potentials while subjects performed a paired-associates memory task. A 123-channel EEG montage and common average reference were used for 20 unmedicated schizophrenic (mean duration of illness: 11.3 ± 9.2 years; mean number of previous hospitalizations: 1.2 ± 1.9) and 22 healthy control subjects during a visual paired-associates matching task. For the topographic analysis, we used a simple index of individual topographic deviation from normality, corrected for absolute potential intensities. Slow potentials were observed in all subjects. Control subjects showed a simple spatial pattern of voltage extrema (left central positive and right prefrontal negative), whereas schizophrenic patients presented a more complex, fragmented pattern. Topographic deviation was significantly different between groups (P < 0.001). The increased topographic complexity in schizophrenics could be visualized in grand averages computed across subjects. Increased topographic complexity could also be seen when grand averages were computed for subgroups of patients assembled either according to task-performance (high versus low) or by their scores on psychopathological scales. There was no significant correlation between topographic deviation and psychopathology scores. We conclude that the slow potential topographic abnormalities of schizophrenia indicate an abnormality in the configuration of large-scale electrical activity in association cortices.

A spectral analysis of the myoelectric activity of the left colon in patients with schistosomiasis mansoni

The objective of the present study was to perform a spectral analysis of the electrical activity of the left colon of patients with hepatosplenic schistosomiasis. Thirty patients were studied, divided into 2 groups: group A was composed of 14 patients (9 males and 5 females) with hepatosplenic schistosomiasis and group B was composed of 16 female patients without schistosomiasis mansoni. Three pairs of electrodes were implanted in the left colon at the moment of the surgical treatment. The signals of the electric activity of the colon were captured after postoperative recovery from the ileus and fed into a computer by means of a DATAQ data collection system which identified and captured frequencies between 0.02 and 10 Hz. Data were recorded, stored and analyzed using the WINDAQ 200 software. For electrical analysis, the average voltage of the electrical wave in the three electrodes of all patients, expressed as millivolts (mV), was considered, together with the maximum and minimum values, the root mean square (RMS), the skewness, and the results of the fast Fourier transforms. The average RMS of the schistosomiasis mansoni patients was 284.007 mV. During a long period of contraction, the RMS increased in a statistically significant manner from 127.455 mV during a resting period to 748.959 mV in patients with schistosomiasis mansoni. We conclude that there were no statistically significant differences in RMS values between patients with schistosomiasis mansoni and patients without the disease during the rest period or during a long period of contraction.

In vitro and in vivo antioxidant activity of the pulp of Jatobá-do-cerrado

Abstract Oxygen metabolism in cells causes the production of free radicals, which produce damage, including changes in cell structure and function. Antioxidants are substances that, at low concentrations, slow down or prevent oxidation. Fruits and vegetables contribute to the dietary supply of these compounds. The flora of the Cerrado in Brazil has shown to have high levels of bioactive compounds. This study aimed to characterize the antioxidant activity of the pulp of jatobá-do-cerrado in vitro and in vivo.In vitro antioxidant activity of the aqueous, ethanol and aqueous acetone extracts was evaluated by the DPPH method. We determined total phenols by the Folin-Ciocalteu assay and tannins by the Folin-Denis method.In vivo antioxidant potential of the aqueous acetone extract was evaluated by the TBARS technique. The aqueous acetone extract had the highest antioxidant capacity, followed by the aqueous and ethanol extracts. The same pattern occurred in the extraction of phenols and in the extraction of tannins. In vivo administration of the aqueous acetone extract inhibited lipid peroxidation compared to the control group. The inhibition of peroxidation has increased by elevating the dosage concentration of the extracts, demonstrating a significant antioxidant potential in vivo as well as in vitro.