RESUMO
Tumor invasion is likely driven by the product of intrinsic and extrinsic stresses, reduced intercellular adhesion, and reciprocal interactions between the cancer cells and the extracellular matrix (ECM). The ECM is a dynamic material system that is continuously evolving with the tumor microenvironment. Although it is widely reported that cancer cells degrade the ECM to create paths for migration using membrane-bound and soluble enzymes, other nonenzymatic mechanisms of invasion are less studied and not clearly understood. To explore tumor invasion that is independent of enzymatic degradation, we have created an open three-dimensional (3D) microchannel network using a novel bioconjugated liquid-like solid (LLS) medium to mimic both the tortuosity and the permeability of a loose capillary-like network. The LLS is made from an ensemble of soft granular microgels, which provides an accessible platform to investigate the 3D invasion of glioblastoma (GBM) tumor spheroids using in situ scanning confocal microscopy. The surface conjugation of the LLS microgels with type 1 collagen (COL1-LLS) enables cell adhesion and migration. In this model, invasive fronts of the GBM microtumor protruded into the proximal interstitial space and may have locally reorganized the surrounding COL1-LLS. Characterization of the invasive paths revealed a super-diffusive behavior of these fronts. Numerical simulations suggest that the interstitial space guided tumor invasion by restricting available paths, and this physical restriction is responsible for the super-diffusive behavior. This study also presents evidence that cancer cells utilize anchorage-dependent migration to explore their surroundings, and geometrical cues guide 3D tumor invasion along the accessible paths independent of proteolytic ability.
Assuntos
Microgéis , Humanos , Movimento Celular , Invasividade Neoplásica/patologia , Matriz Extracelular/metabolismo , Colágeno Tipo I , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
BACKGROUND: Resting heart rate (HR) and HR variability (HRV) are known to predict mortality in patients after myocardial infarction (MI). OBJECTIVE: We assessed acute and chronic effects of high-intensity interval training (HIIT) versus moderate-intensity continuous exercise (MICE) on HR and HRV in individuals after acute ST-segment elevation MI (STEMI). METHODS: Participants within 7 weeks after MI were randomly assigned to HIIT or MICE groups for a 9-week intervention. HR and the power spectrum of HRV were measured pre- and post-intervention by using orthostatic challenge and during sleep to assess chronic effects. Sleep measurements were performed at night after HIIT, MICE or no training to assess acute effects. Mixed models assessed time*group interaction for differences in chronic and acute effects, adjusted for beta-blocker dose and number of training sessions. RESULTS: Overall, 34 of 37 and 35 of 36 participants in the HIIT and MICE groups completed the study. We found a trend for an acute increase in HR of 2.5 bpm (4%, P=0.023) during sleep after HIIT. We found a trend for a chronic decrease in HR during supine and standing position as well as during sleep in the MICE group but a trend for an increase in HR during supine and standing position in the HIIT group. Low- and high-frequency power (LF, HF) of the standing segment increased from pre- to post-intervention in the MICE group but decreased in the HIIT group (group*time interaction P=0.005 and P=0.026, respectively). CONCLUSION: HR during sleep tended to be increased acutely during the night after HIIT but not after MICE as compared with controls. Chronic effects on resting HR, HF and LF tended to be more beneficial after MICE than HIIT in individuals with recent STEMI.
Assuntos
Treinamento Intervalado de Alta Intensidade , Infarto do Miocárdio , Exercício Físico , Frequência Cardíaca , HumanosRESUMO
OBJECTIVES: Athletes performing sports on high level are at increased risk for sudden cardiac death. This includes paediatric athletes, even though data on screening strategies in this age group remain scarce. This study aimed to assess electrocardiogram interpretation criteria in paediatric athletes and to evaluate the cost of screening. METHODS: National, multicentre, retrospective, observational study on 891 athletes of paediatric age (<18â¯years) evaluated by history, physical examination and 12-lead electrocardiogram. The primary outcome measure was abnormal electrocardiogram findings according to the International Recommendations for Electrographic Interpretation in Athletes. The secondary outcome measure was cost of screening. RESULTS: 19 athletes (2.1%) presented abnormal electrocardiogram findings requiring further investigations, mainly abnormal T-wave inversion. These 19 athletes were predominantly males, performing endurance sports with a mean volume of 10 weekly hours for a mean duration of 6â¯years of training. Further investigations did not identify any relevant pathology. All athletes were cleared for competition with regular follow-up. Total costs of the screening were 108,860 USD (122 USD per athlete). CONCLUSIONS: Our study using the International Recommendations for Electrographic Interpretation in Athletes identified a low count of abnormal findings in paediatric athletes, yet raising substantially the cost of screening. Hence, the utility of electrocardiogram-inclusive screening of paediatric athletes remains to be elucidated by longitudinal data.
Assuntos
Cardiopatias , Adolescente , Atletas , Criança , Custos e Análise de Custo , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Cardiopatias/diagnóstico , Humanos , Masculino , Estudos Retrospectivos , SuíçaRESUMO
BACKGROUND: Many studies found increased central arterial stiffness and poor endothelial function in patients with coronary artery disease (CAD). Acute exercise has been shown to decrease peripheral pulse wave velocity (pPWV) in young healthy volunteers. We hypothesized the response to acute exercise to be diminished in CAD patients compared to healthy young (HY) and age-matched (HAM) controls. METHODS: In 21 patients after recent myocardial infarction (CAD), 11 HAM and 10 HY pPWV was measured by applanation tonometry at the proximal femoral artery and the posterior tibial artery at rest and from 5 to 15 min after cessation of exhaustive exercise. Heart rate (HR) and blood pressure (BP) were monitored continuously. Resting central PWV (cPWV) was measured between the carotid and femoral arteries. Resting values and reponses to acute exercise were compared between the three groups and predictors for pPWV response were sought. RESULTS: The response in pPWV to acute exercise seen in HY (lowering in pPWV by 17%) was absent in both CAD and HAM. Resting pPWV was not statistically different between the three groups, while cPWV was comparable in CAD and HAM but 17% lower in HY. Predictors for response in pPWV to exercise were age (Spearman r = 0.48), cPWV (r = 0.34) and response in diastolic BP (r = 0.32). CONCLUSION: The response in pPWV to acute exercise observed in HY was absent in CAD and HAM. In dilated peripheral arteries, PWV may reflect stiffness of passive vessel structures, which are likely to increase with age in healthy persons and CAD alike.
Assuntos
Exercício Físico/fisiologia , Infarto do Miocárdio/fisiopatologia , Adulto , Fatores Etários , Idoso , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Artéria Femoral/fisiopatologia , Voluntários Saudáveis , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Artérias da Tíbia/fisiopatologia , Rigidez Vascular/fisiologia , Adulto JovemRESUMO
INTRODUCTION: International criteria for the interpretation of the athlete's electrocardiogram (ECG) have been proposed. We aimed to evaluate the inter-observer agreement among observers with different levels of expertise. METHODS: Consecutive ECGs of Swiss elite athletes (≥14 years), recorded during routine pre-participation screening between 2013 and 2016 at the Swiss Federal Institute of Sports were analysed. A medical student (A), a cardiology fellow (B) and an electrophysiologist (C) interpreted the ECG's independently according to the most recent criteria. The frequencies and percentages for each observer were calculated. An inter-observer reliability analysis using Cohen Kappa (κ) statistics was used to determine consistency among observers. RESULTS: A total of 287 ECGs (64.1% males) were analysed. Mean age of the athletes was 20.4±4.9 years. The prevalence of abnormal ECG findings was 1.4%. Both, normal and borderline findings in athletes showed moderate to good agreement between all observers. κ scores for abnormal findings resulted in excellent agreement (κ 0.855 in observer A vs C and B vs C to κ 1.000 in observer A vs B). Overall agreement ranged from moderate (κ 0.539; 0.419-0.685 95% CI) between observer B vs C to good agreement (κ 0.720; 0.681-0.821 95% CI) between observer A vs B. CONCLUSIONS: Our cohort of elite athletes had a low prevalence of abnormal ECGs. Agreement in abnormal ECG findings with the use of the recently published International recommendations for ECG interpretation in athletes among observers with different levels of expertise was excellent. ECG interpretation resulted in moderate to good overall agreement.
Assuntos
Atletas , Eletrocardiografia , Diretrizes para o Planejamento em Saúde , Internacionalidade , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Adulto JovemRESUMO
Sleep initiation and sleep intensity in humans show a dissimilar time course. The propensity of sleep initiation (PSI), as measured by the multiple sleep latency test, remains at a relatively constant level throughout the habitual period of waking or exhibits a midafternoon peak. When waking is extended into the sleep period, PSI rises rapidly within a few hours. In contrast, sleep intensity, as measured by electroencephalographic slow-wave activity during naps, shows a gradual increase during the period of habitual waking. In the two-process model of sleep regulation, it corresponds to the rising limb of the homeostatic Process S. We propose that PSI is determined by the difference between Process S and the threshold H defining sleep onset, which is modulated by the circadian process C. In contrast to a previous version of the model, the parameters of H (amplitude, phase, skewness) differ from those of threshold L, which defines sleep termination. The present model is able to simulate the time course of PSI under baseline conditions as well as following recovery sleep after extended sleep deprivation. The simulations suggest that during the regular period of waking, a circadian process counteracts the increasing sleep propensity induced by a homeostatic process. Data obtained in the rat indicate that during the circadian period of predominant waking, a circadian process prevents a major intrusion of sleep.
Assuntos
Ritmo Circadiano , Homeostase , Fases do Sono , Sono/fisiologia , Animais , Humanos , Modelos Psicológicos , Tempo de Reação , Privação do Sono/fisiologia , Fatores de TempoRESUMO
Midazolam (15 mg), a benzodiazepine (BDZ) hypnotic, and zopiclone (7.5 mg), a non-BDZ hypnotic, were administered to young, healthy subjects prior to bedtime. They went to bed at 2300 hours after taking placebo (PL-23), and then on three occasions at 1900 hour after taking placebo (PL-19) or one of the hypnotics. Advancing bedtime by 4 hour increased the combined value of waking, stage 1, and movement time. Compared to PL-19, both drugs reduced sleep latency and stage 3, and increased stage 2. Spectral analysis of the EEG in non-rapid-eye-movement sleep revealed a declining trend of power density in the low-frequency range in the course of the night. Activity in the 1 to 10 Hz range was markedly depressed by the two hypnotics, whereas activity in the spindle range (11 to 14 Hz) was augmented. The former changes persisted throughout the 12-hour recording period. The fact that both hypnotics bind to BDZ receptors could be responsible for the similar effects on the EEG spectra.
Assuntos
Encéfalo/fisiologia , Hipnóticos e Sedativos/farmacologia , Midazolam/farmacologia , Piperazinas/farmacologia , Sono/efeitos dos fármacos , Adulto , Compostos Azabicíclicos , Encéfalo/efeitos dos fármacos , Eletroencefalografia , Humanos , Masculino , Fases do Sono/efeitos dos fármacos , Sono REM/efeitos dos fármacos , Vigília/efeitos dos fármacosRESUMO
Electroencephalographic slow-wave activity (SWA; power density in the 0.75 to 4.5 Hz band) and spindle frequency activity (SFA; 11.25 to 15.0 Hz) exhibit a typical time course and a distinct mutual relationship during sleep. Because benzodiazepines (BDZ) suppress SWA and enhance SFA, we investigated the effect of two BDZ-receptor agonists on the dynamics of these EEG parameters. A single dose of midazolam (15 mg), zopiclone (7.5 mg), or placebo was administered before bedtime to healthy young men. Although the two drugs reduced SWA and enhanced SFA, their time course across and within sleep cycles as well as their mutual relationship were little affected. The results constitute further evidence that hypnotics acting as BDZ-receptor agonists do not substantially interfere with the homeostatic aspect of sleep regulation.
Assuntos
Eletroencefalografia/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Midazolam/farmacologia , Piperazinas/farmacologia , Fases do Sono/efeitos dos fármacos , Adulto , Compostos Azabicíclicos , Humanos , Masculino , Fases do Sono/fisiologiaRESUMO
In vivo studies reported that cholinergic agents affect mammalian circadian rhythmicity. To study phase resetting properties of cholinergic compounds more directly, we carried out experiments in rat suprachiasmatic nuclei slices. Compounds were added to the perfusate for 1 h at specific phases of the circadian cycle. On the following day, the time of peak neuronal activity, a measure of the phase of the endogenous circadian pacemaker, was assessed by means of extracellular recording in the suprachiasmatic nuclei. The peak of neuronal activity occurred at circadian time 5.8 +/- 0.7 (mean +/- 95% confidence limits) in the control slice (circadian time 0: lights-on). Ten-micromolar carbachol had no effect on the phase of the circadian rhythm when given at circadian times 6 and 15, while at circadian time 21 a phase advance of one hour was observed. By contrast, 10 microM nicotine significantly phase advanced (> 1 h) the neuronal circadian rhythm at all but one experimental circadian phase. The circadian times of maximal nicotinic phase advances were 15 (+2.6 h) and 21 (+2.8 h). A concentration response curve for nicotine was generated and pharmacological blocking experiments were performed at circadian time 15. The estimated maximum response of nicotine was 3.4 h, and the estimated concentration for half maximal response was 5 microM. The Hill coefficient (= 1.08) indicated that the effects of nicotine may be explained by a single receptor occupancy model. Mecamylamine (20 microM) almost completely antagonized the nicotinic phase-advances, whereas tetrodotoxin (1 microM) or high Mg2+ (10 mM) did not significantly attenuate the nicotinic phase-advances.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ritmo Circadiano/efeitos dos fármacos , Nicotina/farmacologia , Núcleo Supraquiasmático/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Magnésio/farmacologia , Masculino , Mecamilamina/farmacologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Frequency specific power obtained from time and frequency domain analyses are explored in simulated signals and all-night electroencephalogram (EEG). Signals were subjected to a fast Hartley transformation (FHT) and to digital sixth-order Bessel bandpass filters (BDF) of the infinite impulse response type. Numeric values of FHT, BDF and, if suited, authentic frequency specific power were subjected to a Pearson correlation. Frequency bins at 1.6-2.4 Hz (delta), 4.75-5.9 Hz (theta), 9.3-11.5 Hz (alpha), 12.5-14.9 Hz (sigma) and 16.6-19.5 Hz (beta) were investigated. When compared with true power of single frequency oscillators (256-sample windows), frequency specific power of the FHT correlated functionally (1.0) and BDF correlated highly (0.85, delta; 0.99, other bins). For analyses of "white noise", a multiple frequency oscillator and all-night EEG, four rectangular window sizes were applied (256, 512, 1,024 or 2,048 samples). The FHT power correlated better with authentic frequency specific power of "white noise" (256-sample windows) (0.61-0.98) than BDF power (0.67-0.89). With 512-sample windows of "white noise", the estimate of both the FHT (0.69-0.99) and BDF (0.71-0.93) improved. Direct comparison between FHT and BDF frequency specific power obtained from "white noise" or all-night EEG revealed a high degree of compliance between methods for all frequency bins (up to 0.99). For delta, the accord was relatively low for the 256-sample window (EEG, 0.68; "white noise", 0.72), but increased with lengthening window size (2,048-sample: 0.97; 0.99). Averaging of multiple EEG 256-sample windows also increased the agreement between methods.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Encéfalo/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Neurônios/fisiologia , Ruído , Sono REM/fisiologiaRESUMO
Endotoxin, a lipopolysaccharide (0.4 or 0.8 ng/kg body weight), was injected at 1900 hours in 17 healthy men in a single-blind, placebo-controlled experiment. The administration was followed by a 4-hour period of quiet wakefulness in bed (light intensity < 200 lux). Unlimited sleep was allowed after 2300 hours (lights off) until the next morning. The electroencephalogram (EEG), electromyogram, electrooculogram, electrocardiogram and rectal temperature were recorded throughout the experimental session. Standard sleep stages were assessed, and the EEG was submitted to a state-specific, serial spectral analysis. Endotoxin administration induced a rise of body temperature and heart rate, which started approximately 2 hours after the injection and persisted through most of the sleep period. Sleep latency remained unchanged, whereas rapid eye movement (REM) sleep latency increased from 60.3 to 89.0 minutes (paired t test; p = 0.06) compared to control values. Stage 2 sleep was elevated from 45.5 to 49.0% of time in bed (p < 0.05), and total nonrapid eye movement (NREM) sleep from 64.2 to 69.1% (p < 0.05). No significant change could be observed in slow-wave sleep (SWS, stages 3 and 4). During the first 4 hours of the sleep period, NREM sleep EEG spectral power was distinctly and markedly increased between 8 and 12 Hz (alpha) and 15 and 20 Hz (beta) (p < 0.05), whereas at the same time EEG power between 1 and 8 Hz (delta, theta) was not significantly changed. We conclude that in humans the primary host response induced by endotoxin initially suppresses REM sleep and increases stage 2 NREM sleep, but does not affect SWS. No clear modification of sleep EEG delta activity could be observed after endotoxin injection, despite marked endocrinological and physiological changes such as the elevation of body temperature. Numerous factors related to the human primary host response may be responsible for the EEG intensification of the alpha and beta range.
Assuntos
Eletroencefalografia/efeitos dos fármacos , Endotoxinas/farmacologia , Sono/efeitos dos fármacos , Adulto , Ritmo alfa/efeitos dos fármacos , Ritmo beta/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Método Simples-Cego , Sono/fisiologiaRESUMO
Evidence from electroencephalographic, thermoregulatory and cellular neurophysiological studies suggests that sleep and hibernation may be homologous adaptations for energy conservation. However, despite the similarities between non-rapid eye movement (NREM) sleep and hibernation, the restorative function normally associated with slow wave sleep appears not to occur during hibernation, perhaps because of the low body temperature (Tb). Cellular neurophysiological studies also suggest that a bout of hibernation is not exclusively NREM sleep but is punctuated by periods of wakefulness. The entrance to hibernation involves both an inhibition of cortical activity and activation of hypothalamic regions, whereas the arousal from hibernation is primarily a hypothalamic function. Multiple neurochemical systems are affected by the arousal state change that occurs in hibernation, and a serotonergic-opiatergic interaction, in particular, may be important in regulating these events. Among regulated physiological systems affected by arousal state changes, the episodic respiration evident in hibernation shows striking similarities to the apneas observed during sleep in both humans and other mammals. Although the slight down-regulation of Tb and metabolism that accompanies the transition from wakefulness to NREM sleep may have served as a preadaptation for the evolution of hibernation among the mammals, increasing consideration must be given to the possibility that hibernation represents an arousal state distinct from any known normothermic arousal state.
Assuntos
Hibernação/fisiologia , Mamíferos/fisiologia , Sono/fisiologia , Animais , Nível de Alerta/fisiologia , Comportamento Animal/fisiologia , Tronco Encefálico/fisiologia , Eletrocardiografia , Eletroencefalografia , Eletromiografia , Endorfinas/fisiologia , Humanos , Hipotálamo/fisiologia , Respiração/fisiologia , Serotonina/fisiologiaRESUMO
Preclinical data suggest that the imidazodiazepinone derivative bretazenil (Ro 16-6028) has anxiolytic and anticonvulsant properties with only weak sedative effects. We examined the influence of oral administration of 1 mg bretazenil on the sleep EEG and the concomitant nocturnal secretion of cortisol, growth hormone and prolactin in ten healthy young men. After bretazenil we found a significant increase in stage 2 sleep and a significant reduction in stage 3 sleep. REM latency was prolonged. Spectral analysis of sleep-EEG power revealed a decrease in delta and in theta power and an increase in sigma power. We found no significant influence on sleep onset latency or on intermittent wakefulness. Bretazenil prompted a significant decrease in cortisol secretion and a significant increase in prolactin release. It had no major influence on growth hormone secretion.
Assuntos
Anticonvulsivantes/farmacologia , Benzodiazepinonas/farmacologia , Eletroencefalografia/efeitos dos fármacos , Hormônios/sangue , Sono/efeitos dos fármacos , Adulto , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Masculino , Prolactina/sangue , Sono/fisiologiaRESUMO
The effects of flumazenil, a benzodiazepine antagonist, on the sleep electroencephalogram (EEG) and neuroendocrine secretion in early morning recovery sleep (0500-0800 hours) following sleep deprivation (SD; 2300-0500 hours) were studied in seven healthy men. SD induced an increase in slow wave sleep (SWS), a decrease in sleep onset latency (SOL), an enhancement of EEG delta and theta power in non-rapid-eye-movement sleep, an increase in plasma human growth hormone (GH) concentration, and a decrease in plasma cortisol levels in recovery sleep (0500-0800 hours). Plasma GH, but neither plasma cortisol nor adrenocorticotrophic hormone (ACTH) concentration was attenuated during SD as compared to sleep (2300-0445 hours). The administration of flumazenil (3 x 1 mg intravenously) during recovery sleep resulted in an inhibition in SWS, an increase in stage 2 sleep, a selective reduction in delta and theta power, and a tendency to prolongation of SOL. Plasma GH concentration was decreased but plasma cortisol and ACTH remained unaffected. Since the SD-induced changes in sleep EEG and plasma GH secretion were antagonized by flumazenil, it is suggested that electrophysiological and hormonal effects of SD are mediated at least in part through GABAergic mechanisms.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Flumazenil/farmacologia , Hormônio do Crescimento/sangue , Hidrocortisona/sangue , Privação do Sono/fisiologia , Sono/efeitos dos fármacos , Adulto , Eletroencefalografia , Humanos , Masculino , Fatores de TempoRESUMO
Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.
Assuntos
Ritmo Circadiano/fisiologia , Peptídeo Indutor do Sono Delta/sangue , Sono/fisiologia , Adulto , Eletroencefalografia , Hormônio do Crescimento/sangue , Homeostase , Humanos , Hidrocortisona/sangue , Masculino , Fases do Sono/fisiologiaRESUMO
The electroencephalogram (EEG) and electromyogram of rats with lesions in the suprachiasmatic nuclei (SCNx) were recorded during two series of 24-h baseline, 6-h sleep deprivation (SD), and 24-h recovery. At recovery onset, rats were injected i.p. with vehicle (VEH) control solution or 0.4 mg/kg triazolam (TRZ) in a balanced crossover design. Consecutive 10-s epochs were scored for vigilance states and EEG power spectra were computed. Arousal states were uniformly distributed during 24-h baseline (wake 47% of recording time, non-rapid-eye movement sleep (nonREMS) 47%, REMS 7%), and EEG spectra (0-25 Hz) were devoid of significant trends. State-specific EEG power spectra profiles in SCNx rats were similar to those of intact animals reported previously. However, EEG delta power (0.5-3.5 Hz) of nonREMS was markedly lower in SCNx rats. Recovery from 6-h SD was characterised by a short-lasting reduction of REMS, and a long-lasting increase of nonREMS time at the cost of wakefulness. EEG delta power rebounded during the first 8 h in recovery, and fell below baseline level after 12 h in recovery. During 0-2 h TRZ recovery, rats spent more time in nonREMS with higher EEG slow wave activity as compared to the corresponding VEH recovery period. EEG slow wave activity fell below baseline levels 10 h after TRZ injection and termination of SD. We conclude that major features of homeostatic sleep EEG regulation are present in SCNx rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Homeostase/fisiologia , Privação do Sono/fisiologia , Sono/fisiologia , Núcleo Supraquiasmático/fisiologia , Triazolam/farmacologia , Animais , Nível de Alerta/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Eletromiografia/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Núcleo Supraquiasmático/efeitos dos fármacosRESUMO
The steroid pregnenolone (P) and its sulfate (PS) can accumulate in the central nervous system independent of peripheral sources. Pharmacologically, the sulphated form of P interacts with the GABAA receptor complex, and functional assays show that this steroid behaves as an allosteric GABAA receptor antagonist. The present study explored the effect of a single dose of P upon the sleep-EEG and concurrent secretion of growth hormone and cortisol in male volunteers. P increased the amount of time spent in slow wave sleep and depressed EEG sigma power. Sleep-associated nocturnal cortisol and growth hormone secretion remained unchanged, ruling out the possibility that P exerted its effect via altered regulation of these hormones. Furthermore, results from in vitro studies on the potency of P to activate gene transcription via corticosteroid receptors made a genomic action of P via hormone receptor-sensitive DNA sequences unlikely. We conclude that P acts in a non-genomic fashion at or in the vicinity of the benzodiazepine binding site, modulating allosterically the GABAA receptor like a partial inverse.
Assuntos
Eletroencefalografia , Pregnenolona/farmacologia , Receptores de GABA-A/fisiologia , Sono/efeitos dos fármacos , Adulto , Androstanóis/farmacologia , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , MasculinoRESUMO
The process of the human non-rapid eye movement (non-REM) sleep period has not been clarified. Time-based analysis on sleep EEG may provide an explanation. We focused on chronological aspects of initiation and termination of non-REM episodes, using spectral analysis of sleep EEG. The subjects were healthy male volunteers (n14 Hz) and longer in lower frequency ranges (<14 Hz). There were significant differences in the rise and decay latencies between low and high sigma ranges, indicating that the whole frequency ranges were clearly separated at the middle of the sigma range (14 Hz). The rise and decay latencies were significantly different in lower frequency ranges. The clock time of the night significantly affected only the rise latencies of the delta (0.78-3.9 Hz), alpha (8.2-11.7 Hz) and low sigma (12.1-13.7 Hz) ranges. In conclusion, initiation and termination of non-REM sleep was represented by higher frequency ranges, whereas further evolution and devolution of non-REM sleep was represented by lower frequency ranges, and only the evolution process was affected by the clock time of the night.
Assuntos
Eletroencefalografia , Sono/fisiologia , Adulto , Análise de Variância , Humanos , MasculinoRESUMO
Ritanserin (1.0 and 2.5 mg/kg i.p.) was administered to rats before the start, of the light period, and sleep was recorded during the subsequent 12 h. The higher dose reduced sleep in the first 3 h. Both doses caused a more prolonged suppression of REM sleep. Spectral analysis of the EEG in non-REM sleep showed an increase of power density in the low frequency range (1.5-6 Hz) and a depression in the high frequency range (8-25 Hz). Since these changes differ from those previously observed after sleep deprivation, it is premature to conclude that the drug induces a physiological sleep intensification.
Assuntos
Piperidinas/administração & dosagem , Fases do Sono/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Eletroencefalografia , Masculino , Ratos , Ratos Endogâmicos , RitanserinaRESUMO
A brief overview of models on the regulation of sleep/waking or rest/activity is provided. Applications of the two-process model are illustrated in two species: The homeostatic facet of the model (Process S) was used to quantitatively simulate sleep in the rat and guinea pig. The model parameters were estimated for rat sleep by an optimization procedure. A close correspondence between the time course of slow-wave activity and Process S was obtained for both species under baseline conditions. Whereas in the rat a close fit was obtained also for the recovery period from sleep deprivation, some discrepancies were present in the guinea pig. It is concluded that the concept of sleep homeostasis that has been elaborated and formalized in the two-process model for human sleep, can also be applied to simulate sleep in other mammals.