Effects of endothelin on spontaneous contractions in lymph vessels.
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A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10(-10) and 10(-9) M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ET(A)-receptor antagonist BQ-123 (5 x 10(-7) M) caused a significant inhibition of the ET-1-induced positive chronotropic effect in the ring preparations with and without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10(-8)-10(-7) M), a selective ET(B)-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) (10(-5) M) but unaffected by aspirin (10(-5) M). Additional treatment with L-arginine (10(-4) M) completely reversed the L-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ET(A) receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ET(B) receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics. (+info)
Morningness/eveningness and the need for sleep.
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The purpose of this study was to determine, in a large sample of adults of all ages (17-80 years), the effect of morningness/eveningness on sleep/wake schedules, sleep needs, sleep hygiene and subjective daytime somnolence. A total of 617 subjects (219 subjects per chronotype group) matched for age, sex and employment status, completed an abridged morningness/eveningness questionnaire, a questionnaire on sleep habits and the quality of sleep, and the Epworth Sleepiness Scale. Eveningness was associated with a greater need for sleep, less time in bed during the week compared to ideal sleep needs, more time in bed at the weekend, a later bedtime and waking-up time especially at the weekend, more irregular sleep/wake habits and greater caffeine consumption. These subjects built up a sleep debt during the week and extended their duration of sleep at the weekend. They did not, however, rate themselves more sleepy than other types, despite the fact that our results showed a clear link between subjectively evaluated daytime somnolence and sleep debt. Why they were less affected by sleep deprivation is not clear. This raises the question of individual susceptibility to the modification of sleep parameters. (+info)
Is the secretion of atrial natriuretic peptide in man under neural control?
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AIMS: Previous work has described short-term variation in the circulating plasma level of atrial natriuretic peptide (ANP), but the mechanism remains unknown. Our aim was to investigate the role of cardiac innervation in this variability. METHODS AND RESULTS: Blood samples were obtained from the right atrium via a pulmonary artery flotation catheter every 2 min over a 90 min period. Seven patients who underwent cardiac transplantation by the standard biatrial technique (partial innervation) and ten patients who underwent transplantation by the bicaval technique (total denervation) were studied. ANP levels were measured by radioimmunoassay. The median ANP levels were somewhat higher in the biatrial group compared to the bicaval group [470 (150-1095) vs. 216 (100-605) pg. ml(-1); median (range); P = ns], and both were much higher than normal levels in the pulmonary artery (40 (24, 56) pg ml(-1); median and interquartile range). In both transplant groups circulating plasma ANP levels showed considerable variability. The median number of 'peaks' and 'troughs', as counted by visual inspection, were not significantly different between the two groups. Computer analysis identified 12-16 and 6-15 'pulses' in the biatrial and bicaval group, respectively. Further analysis revealed that pulse amplitude, height and area were significantly higher in the biatrial compared to the bicaval group. CONCLUSION: It would appear that variability of circulating plasma levels of ANP is preserved despite complete or partial cardiac denervation, and so a neural mechanism does not appear to account for such variation. (+info)
Basis for dosing time-dependent changes in the antiviral activity of interferon-alpha in mice.
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The influence of dosing time on the pharmacological effect (antiviral activity) of interferon-alpha (IFN-alpha), and the pharmacological and pharmacokinetic mechanisms, were investigated in ICR male mice under a 12-h light/dark cycle (lights on from 7:00 AM to 7:00 PM). 2'-5'Oligoadenylate synthetase activity in plasma at 24 h after IFN-alpha (10 MI.U./kg, i.v.) injection, as an index of antiviral activity, was significantly higher for injections given at 9:00 AM than for injections given at 9:00 PM (P <.05). The uptake of [(3)H]thymidine by lymphocytes after 24-h incubation with IFN-alpha, as an index of lymphocyte-stimulating effect, was significantly higher in cells obtained at 9:00 AM than in the cells obtained at 9:00 PM (P <.01). The number of receptors per cell and the expression of interferon-stimulated gene factor in lymphocytes after 24-h incubation with IFN-alpha were significantly higher in the cells obtained at 9:00 AM than at 9:00 PM (P <.05). A significant dosing time-dependent difference was demonstrated for the pharmacokinetic parameters of IFN-alpha, which showed higher clearance for injections given at 9:00 PM than for those at 9:00 AM (P <.05). The metabolism of IFN-alpha was significantly higher in kidney obtained at 9:00 PM than at 9:00 AM (P <.05). These findings support that choosing the most appropriate time of day for administration of IFN-alpha, associated with the rhythmicity of IFN-alpha receptor function and IFN-alpha pharmacokinetics, may increase the antiviral activity in experimental and clinical situations. (+info)
Biological time and in vivo research: a field guide to pitfalls.
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Biological rhythmicity is a fundamental characteristic of all life forms, from primitive bacteria to man. The molecular biology, genetics, and the neurobiology of the biological clock(s) are being elucidated. Daily (circadian) statistically significant fluctuations occur in all of the normal biological variables studied in the experimental animal and the human. Many researchers, however, are not aware of the negative impact biological rhythmicity can have on experimental design and/or data interpretation. This article serves not as a review, but as a "field guide" to the pitfalls that can occur when research is performed in the absence of an understanding of biological rhythmicity. The major topics discussed are: 1) data transfer from the diurnally in-active/resting/sleeping lab animal to the diurnally active human, 2) frequency of sampling, 3) free-running vs. synchronization, 4) alternating periods of resistance and susceptibility, 5) phase shifting of a rhythm, 6) the assumption that one mean +/- S.E. from control animals can be "stretched" across an experimental time span, and 7) plotting data on an "hours after treatment" format vs. a "time of day" format. The hope is that by avoiding the pitfalls, biological time will become an ally in the endeavor to understand human biology. (+info)
The temporal organization of life: the impact of multi-frequency non-linear biologic time structure upon the host-cancer balance.
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The current scientific paradigm, based upon an erroneous assumption of linear biologic reality and simple cause and effect relationships, has outlived its usefulness. In order to begin to turn the voluminous data the reductive process provides us with daily into meaningful understanding of life, it is essential to integrate these data within a complex, multi-frequency temporo-spatial framework. This rhythmic chronobiology more accurately depicts the life process, as well as its evolutionary and ongoing vital interaction with the pulsating cosmic resonance structure. Examples of the kinds of thinking and experiments necessary to exploit this new paradigm are provided. (+info)
Diurnal variations of post-exercise parasympathetic nervous reactivation in different chronotypes.
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The purpose of this study was to investigate the diurnal variation and chronotype differences, i.e., in morning-types and evening-types, in post-exercise vagal reactivation. Twelve healthy male college students who were classified as morning-type (6) and evening-type (6), based on responses to a questionnaire, participated in this study. Postexercise vagal reactivation was assessed as the time constant of the beat-by-beat heart rate decrease for the first 30 sec after exercise (T30) at an intensity lower than the ventilatory threshold. The subjects performed 3-min cycle ergometer exercise at an intensity corresponding to 80% of the ventilatory threshold after a 1 min warm-up exercise in the morning (7:00 - 8:00) and evening (17:00 - 18:00) to obtain the T30. A significant interaction (chronotype-by-time) effect was found for T30. The morning value of the T30 in evening-type subjects was significantly larger than their evening value and the morning value in morning-type subjects. There was no significant interaction effect for heart rate and oxygen uptake during exercise. These results suggest that diurnal variation in post-exercise vagal reactivation is different between morning-type and evening-type, and post-exercise vagal reactivation in evening-type individuals is sluggish in the morning. (+info)
The brain decade in debate: IV. Chronobiology.
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The present article is the adapted version of an electronic symposium organized by the Brazilian Society of Neuroscience and Behavior (SBNeC) which took place on June 14, 2000. The text is divided into three sections: I. The main issues, II. Chronodrugs, and III. Methods. The first section is dedicated to the perspectives of chronobiology for the next decade, with opinions about the trends of future research being emitted and discussed. The second section deals mostly with drugs acting or potentially acting on the organism's timing systems. In the third section there are considerations about relevant methodological issues concerning data analysis. (+info)