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Biomedical subjects

A Reinberg

Publications and source records attributed to A Reinberg.

At least 55 records · Page 3Linked to original sources
PubMed1988

Circadian rhythms in circulating T lymphocyte subtypes and plasma testosterone, total and free cortisol in five healthy men.

Circadian variations of circulating T lymphocyte subtypes and their possible relations with those of endogenous cortisol or testosterone were investigated in five healthy young men. Venous blood (40 ml) was obtained every 4 h for 24 h from each subject in January, March, June, August and November. Leucocyte and differential counts were measured. Mononuclear cells were isolated on Ficoll-Paque gradient, and samples were incubated with OKT3, OKT4 or OKT8 monoclonal antibodies for characterizing all T, T helper and T suppressor-cytotoxic lymphocytes respectively. The proportion of labelled lymphocytes was determined under an epifluorescence microscope and the counts of circulating lymphocyte subsets (cells/mm3) computed. Total and free cortisol and testosterone were also determined in the corresponding plasma samples. Results from analysis of variance and cosinor indicated statistically significant differences (P less than 0.001) as a function of both individual subject and circadian sampling time for all variables. Circadian rhythms (with a period, tau = 24 h) were validated for total, T and T helper lymphocytes and for the T helper: T suppressor-cytotoxic ratio (P less than 0.001), with double amplitudes (2A, total extent of variation accounted for by the fitted cosine function) ranging from 25% up to 50% of the 24 h mean (M), and acrophases (phi, time of maximum) localized near 0100 h. A rhythm with tau = 12 h characterized circulating T suppressor-cytotoxic lymphocytes (P less than 0.001; 2A = 36% of M; phi = 0830 and 2030 h). Circadian rhythms were also found for plasma cortisol (either total or free) and testosterone (P less than 0.001). No correlation was found however between time-qualified data of these hormones and the immunological variables herein investigated (162 pairs of data) whether or not a 4 h or an 8 h lag time was considered to allow for hormonal actions to operate. This suggests that neither the circadian organization of the adrenal cortex nor that of the testis play a prominent role in the circadian time structure of the circulation of T lymphocytes.

Adult↗
PubMed1988

Persistence of circadian rhythms in gastric acid, gastrin, and pancreatic polypeptide secretions despite loss of cortisol and body temperature rhythms in man under stress.

During organic stress, severe dysfunctions of fundamental biological phenomena, such as modification of vagal tone, have been described. These dysfunctions could induce changes in the rhythm of acid secretion and/or its hormonal control. We therefore analyzed the effects of acute respiratory failure on the 24 h variations in intragastric pH, serum gastrin, and pancreatic polypeptide levels, taken as a marker of vagal tone. Body temperature and plasma cortisol circadian rhythms were used as marker rhythms. Twelve patients with chronic obstructive pulmonary disease complicated with acute respiratory failure were studied before and during continuous enteral nutrition; half of the patients received ranitidine, a H2 blocker. During the 3 days of the study, intragastric pH was below 2.5 for only one third of the time. No difference was observed between the placebo and the ranitidine groups. Plasma pancreatic polypeptide was within normal ranges despite increased cortisol levels. Gastrin levels reflected changes in intragastric pH over the 24 h time frame and were noted to increase during ranitidine and enteral nutrition. Despite the loss of cortisol and body temperature circadian rhythmicity all throughout the study, circadian rhythms were maintained or restored during the different therapeutic regimens for intragastric pH, serum gastrin, and pancreatic polypeptide levels. Moreover, an ultradian rhythm for gastrin before any treatment, a circadian rhythm for intragastric pH on enteral nutrition, a circadian rhythm for intragastric pH, plasma gastrin and plasma pancreatic polypeptide on ranitidine regimen were observed. Thus during acute respiratory failure, certain physiological circadian rhythms persisted despite the disappearance of "marker" rhythms. Furthermore, these rhythms for digestive secretions could be pharmacologically restored.

Acute Disease↗
PubMed1987

Circadian time dependence of murine tolerance for the alkylating agent peptichemio.

Since the extent of host toxicity of cytostatics is considerably affected by dosing time, a chronopharmacologic approach was undertaken for optimizing the therapeutic index of the alkylating agent, peptichemio (PTC). In 4 studies involving a total of 463 male B6D2F1 mice, a highly statistically significant circadian rhythm characterized murine tolerance for PTC (8 or 10 mg/kg/day i.v. X 3 days). Six circadian stages were explored (3, 7, 11, 15, 19 and 23 Hours After Light Onset--HALO). Day-40 survival rate varied between 20% (PTC at 3 HALO) and 55% (PTC at 15 HALO) (chi 2 = 16.7; P less than 0.01). In each study, body weight loss was maximal in mice injected with PTC at 3 HALO and minimal in those treated at 15 HALO (P less than 0.01). In a further study involving 96 male B6D2F1 mice, the toxicity of PTC on several target tissues (bone marrow, spleen, small bowel, colon, liver, kidney and lungs) was investigated by histology and leukocyte count as a function of drug dosing time. A circadian rhythm in the susceptibility of the bone marrow, the spleen and the intestinal tract was demonstrated. Optimal murine tolerance for PTC resulted from dosing it at 15 HALO, e.g. in the first half of the activity span.

Animals↗
PubMed1987

Circannual and circa-hemiannual rhythms of basal and stimulated gastric secretion in conscious cats.

Conscious cats equipped with a gastric fistula and a denervated Heidenhain pouch were submitted to weekly measurements of the basal and pentagastrin-stimulated gastric secretion for 1 to 14 years. Rhythms of basal secretion were documented in 37 cats for the group studies, in 25 cats only for the individual studies which required at least whole year data. Twelve-month or 6-month rhythms were detected for each variable studied, i.e. volume, acid, pepsin, fucose and uronic acid outputs in the group studies, with peaks for volume, acid and pepsin in Winter, peaks for uronic acid in Spring and Fall indicating different rhythms for oxyntic, chief and mucous cells. Individual studies detected rhythms in 25% of the analyses, and demonstrated male and female and cat to cat differences. Spectral analysis in 3 cats confirmed the differences in the individual rhythms with prominent peaks differing from 365 days in 50% of the cases. Chronopharmacological responses to pentagastrin were documented for volume, acid and pepsin outputs in 5 male and 6 female cats. Group analysis detected a Winter acrophase for volume and acid secretion and a Summer acrophase for pepsin secretion. Analysis of the stimulated response data showed interindividual variation but a higher percentage of detection for rhythms, i.e. 38% for all variables and 50% for pepsin secretion. Different rhythms in acid and pepsin secretion documented in individual studies could provide the basis of a better understanding of the discrepancies reported in the literature concerning the seasonal incidence of peptic ulcer disease.

Animals↗
PubMed1987

Circadian changes in the pharmacokinetics of oral ketoprofen.

Several investigations which have taken treatment time into account have shown that the pharmacokinetic parameters, the therapeutic efficacy and even the toxicity of a large number of products may vary according to the administration schedule. The present study was carried out in order to evaluate any circadian changes in pharmacokinetic parameters of ketoprofen, a new non-steroidal anti-inflammatory drug (NSAID). This randomised crossover study consisted of a single oral dose of ketoprofen 100mg administered to 8 healthy male volunteers, mean age 27.2 years, at 07.00 hours, 13.00 hours, 19.00 hours or 01.00 hours in 4 study periods during the first 3 months of the year. The order of administration was randomised, with each subject acting as his own control. A total of 14 blood and 4 urine samples were taken over a 12-hour period. The peak plasma concentration was twice as high after drug administration at 07.00 hours (13.4 +/- 1 mg/L) than after other administration times (13.00 hours: 6.9 +/- 1; 19.00 hours: 7.2 +/- 0.7; 01.00 hours: 6.3 +/- 0.5 mg/L) [p less than 0.001]. The time to reach peak concentration was much longer after drug administration at 01.00 hours (135 +/- 16.7 min) than at 07.00 (73.1 +/- 14.1 min), 13.00 (75 +/- 16.5 min) or 19.00 hours (82.5 +/- 12.7 min) [p less than 0.05]. The lag time was significantly longer at 01.00 hours than at 13.00 hours (p less than 0.01). The absorption rate constant after treatment at 01.00 hours was less than at the other times of administration (p less than 0.05). The bodyweight-corrected area under the curve (AUC0-12) was greater after 07.00 hours than after 13.00 (p less than 0.01) or 19.00 hours (p less than 0.05) and greater after 01.00 hours than after 13.00 hours (p less than 0.05). The elimination half-life was significantly longer after administration at 01.00 hours than after 19.00 hours (p less than 0.05), while the total clearance was lowest at 07.00 hours. Cosinor analysis demonstrated statistically significant circadian rhythms for all pharmacokinetic parameters described above. The amount of ketoprofen eliminated in the urine was delayed, and was significantly greater after the administration at 01.00 hours than 07.00 hours or 19.00 hours (p less than 0.01). The relationship between absorption, diffusion and/or elimination mechanisms of the drug are discussed.

Administration, Oral↗
PubMed1987

Chronobiology and asthma. II. Body-time-dependent differences in the kinetics and effects of bronchodilator medications.

Several bronchodilator medications exhibit body-time (i.e., biological rhythm)-dependent changes in their pharmacokinetics and effects. Epinephrine (Adrenalin), metaproterenol (orciprenaline), aminophylline, and ipratropium bromide all have a better effect on the tone of the airways during the night and/or morning, when bronchial patency is low, than during the day, when it is high. The pharmacokinetics of sustained-release theophyllines (SRTs) exhibit administration-time differences. Day-night dosing-time differences in the kinetics of theophylline are especially prominent in children. Generally, in day-active asthmatic children the absorption of SRT is more rapid after a morning than an evening dosing. The administration-time effect on the kinetics of SRTs also is apparent in adult patients, but the magnitude of difference between the day versus evening administrations apparently is more moderate. Initial findings from studies of unequal (morning versus evening) BID dosing schedules--more theophylline or terbutaline before bed-time than arising--reveal a better therapeutic advantage relative to equal BID dosing schedules for those patients with predominantly nocturnal symptoms. Once-daily (OD) SRTs intended for delivery of the entire daily dose at a single time also differ quantitatively in their chronokinetics. Since asthma is mainly a nocturnal disease in many patients, it has been recommended by many that ODSRTs be taken in the evening. If taken in the morning, as is the current practice in the United States, they may not ensure therapeutic theophylline blood levels during the night when most needed. Moreover, not all ODSRTs appear suitable for once-nightly administration because of unacceptable kinetics.

Adult↗
PubMed1987

Clinical chronopharmacology with special reference to NSAIDs.

Both drug disposition and effects vary as a function of dosing time. A chronotherapeutic study was therefore undertaken with sustained-release indomethacin (ISR) to quantitate any potential therapeutic gain from an optimal time of administration. Four studies were performed on a total of 517 patients with osteoarthritis of the hip or knee. Each patient took the same dose of ISR at 8:00 am for one week, 12:00 noon for one week and 8:00 pm for one week. In addition to conventional evaluation criteria, patients performed self-rating of pain on visual analogue scales. Overall, there were 44 withdrawals (29 associated with morning ingestion). At group level, time-dependent differences in drug effectiveness were small, although large inter-individual differences were documented. Evening ingestion was most effective in patients with predominant nocturnal or morning pain; conversely, morning or noon ingestion was most effective in patients with maximum afternoon or evening pain. A four-fold improvement in tolerance and a doubling of analgesic effectiveness resulted from varying the ingestion time. Chronotherapeutic studies should therefore include careful longitudinal documentation of pertinent marker rhythms such as self-rating of pain.

Animals↗
PubMed1987

Circadian and circahemidian rhythms in plasma prolactin of the ram: seasonal changes.

The existence of a circadian rhythm in plasma prolactin of the ram is controversial. Differences among authors can be related to both data sampling (e.g. interindividual changes, time of day, time of year, sampling interval among others) and statistical analyses. To test this hypothesis six adult "Préalpes du Sud" rams were studied individually during 72 hr in January (8 hr of light-16 hr of darkness), April (13L-11D), June (16L-8D) and September (13L-11D). Blood was sampled (vacutainer) from a jugular vein every hour, centrifuged and plasma samples stored at -20 degrees C until prolactin determinations (radioimmunoassay) were made. Individual time series were analysed according to three complementary methods: display of raw data (chronogram), best fitting cosine functions with different period tau (iterative cosinors) and power spectra. Seasonal changes in the 24 hr mean (peak time in June) were confirmed. A circahemidian rhythm (tau = 12 hr) and a circadian rhythm (tau = 24 hr) were validated, respectively in January and April while time series documented in June and September exhibited no rhythmic organization. It seems, therefore, that animals adjusted their rhythmic patterns of prolactin secretion to the increasing (January, April) rather than decreasing (June, September) photofraction (duration of the light span/24 hr).

Activity Cycles↗
PubMed1987

Comparison of once-daily evening versus morning sustained-release theophylline dosing for nocturnal asthma.

Eight diurnally active (approximately 0730-1100 hr) adults (41-61 yr) suffering from nocturnal asthma volunteered for a double-blind, cross-over randomized study of a once-daily dosing (600-900 mg/24 hr) of Armophylline (Rorer s.a., France), a sustained-release theophylline given either at 0800 hr or 2000 hr for 8-day durations. Study variables monitored daily were: (a) self-measured peak expiratory flow (PEF), heart rate, oral temperature and self-rated fatigue checked every 2 hr during the waking span as well as upon spontaneous nocturnal awakenings and (b) duration and subjective characteristics of sleep rated every morning. In addition, serum theophylline concentration (STC) plus the variables in (a) were sampled every 2 hr during the 24 hr of the eighth day of each timed treatment span. Rx at 0800 hr was associated with a nocturnal dip in PEF of 20 +/- 2.8% (X +/- S.E.M.) from the level achieved at the time of the diurnal crest; Rx at 2000 hr moderated the nocturnal fall; it was only 10 +/- 2.1% and within the physiologic limits of non-asthmatic persons. The STC peak height (Cmax) was greater (P less than 0.05) and time-to-peak (Tmax) shorter (P less than 0.005) with Rx at 0800 hr than at 2000 hr. With Rx at 2000 hr an STC plateau of approximately 12 hr resulted. A statistically significant correlation (r = 0.86; P less than 0.01) between PEF and the corresponding-in-time STC was observed with Rx at 2000 hr but not with Rx at 0800 hr. A small, but statistically significant, higher heart rate resulted from 2000 hr dosings in five out of eight subjects relative to the 0800 hr dosing. There were no differences in the sleep characteristics nor in oral temperature between dosing times. Once-daily (600-900 mg) SRT dosing at 2000 hr controlled the nocturnal dip of bronchial patency with no major side-effects in diurnally active adult patients with nocturnal allergic asthma.

Adult↗
PubMed1987

[Chronobiology and chronopharmacology. Concepts and definitions].

Circadian (congruent to 24 h), circannual (congruent to 1 year) and other biological rhythms of endogenous origin, detectable at all levels of organization, constitute a temporal structure in all animal species, including man. Circadian, circannual and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical as well as chemical agents including medications and foods are rather common phenomena. Modern chronopharmacology investigates drug effects: a) as a function of biological timing and b) upon parameters characterizing the endogenous bioperiodicities. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts: the chronokinetics of a drug (rhythmic changes in its pharmacokinetics); the chronesthesy (rhythmic changes in susceptibility of target biosystem to this drug), and the chronergy (the drug-integrated overall effects). One of the aims of chronopharmacology is solving problems of drug optimization. Knowledge of those administration times coinciding with best effectiveness or tolerance is required to optimize both timing(s) and dosage(s) of a medication.

Animals↗
PubMed1987

[Chronotherapy and allergic diseases].

The author presents a study synthesizing chronobiological data on allergic diseases and their treatment. It is referred to circannual and circadian chronobiological progress in the field of neurovegetative and immunological respiratory functions. Optimization of treatment is described for inhaled medication, adrenergic and anticholinergic bronchodilators, anti-inflammatory corticoids and cromoglycate derivatives. Importance of ingestion of corticoids at the beginning of activity and of long acting theophylline when diurnal activity ceases is described at endocrinian and pharmacodynamic level. It is finally followed by a presentation of optimization of rhinitis treatment with non sedative antihistaminics, mequitazine, terfenadine, which when taken in the evening are more efficient and better tolerated.

Asthma↗
PubMed1987

Aspects of chronopharmacology and chronotherapy in pediatrics.

Pediatric chronopharmacological findings until now have been limited to circadian changes in children from ages 6 to 15 years. This means that data in newborns and even in infants of 1 year are not available and other bioperiodicities with periods of about-1-year (infradian rhythms) have not been explored in older children. Biologic time-related changes have been documented for phenytoin and theophylline with regard to pharmacokinetics, for orciprenaline with regard to bronchodilation, and for corticosteroids as well as anticancer agents with regard to their effectiveness. Despite the limited number of experiments performed to date, it is already possible to state that a chronopharmacological approach provides better precision in pharmacologic study than the conventional approach not using time-related data and better therapeutics can be achieved with the help of chronopharmacological facts since appropriate timing in administration of medicine usually enhances its desired and/or reduces its undesired effects.

Adrenal Cortex Hormones↗
PubMed1987

Circadian rhythm of serum total immunoglobin E (IgE) in asthmatic children.

Time of day related changes in serum total IgE (and cortisol as marker rhythm) were documented in 6 non-allergic children (2 girls, 4 boys, 6 to 10 years old) and 3 boys (10 to 14 years) with allergic asthma but symptom free at the time of the study. Subjects were synchronized with a diurnal activity from 07.00 to 21.00 and a nocturnal rest. Venous blood was sampled at fixed times (07.30, 11.30, 16.30 and 22.30) during a 24 hours span for the healthy children and during a 48 hours span for the asthmatics. Radioimmunoassay methods were used for the determinations. Time series were analyzed according to conventional (t tested differences, ANOVA) and Cosinor methods. No IgE circadian rhythm was validated in healthy children while a large amplitude (approximately equal to 30% of the 24 hours mean) circadian rhythm with 2 diurnal peaks and a nocturnal trough was demonstrated (P less than 0.0023) in the asthmatics. Therefore, time qualified references are needed for the interpretation of total IgE as they are for many biological variables. Circadian rhythm of IgE is presumably related to those of lymphocyte subpopulations such as B, T and T-suppressor cells.

Adolescent↗
PubMed1986

Age-related changes in both circadian and seasonal rhythms of rectal temperature with special reference to senile dementia of Alzheimer type.

The biological rhythms of rectal temperature were documented in young (circadian variations) and elderly (circadian and seasonal variations) human subjects either in apparent good health or suffering from senile dementia of Alzheimer type (SDAT). All the subjects were synchronized. Data obtained showed a decrease of the body core temperature rhythm amplitude in the healthy elderly for each documented season but not in patients with SDAT. Seasonal variations in these rhythms were observed in these elderly groups of persons.

Aged↗