Chronobiologia最新文献

A series of 274 attacks (256 of them recurring) of ulcerative colitis in 158 subjects, observed between January 1974 and December 1990 in Bratislava (48 degrees N, 17 degrees E), Slovakia, has been processed by R.A. Fisher's periodogram and F. Halberg's cosinor procedure. In spite of the long-term administration of sulfasalazin and/or corticosteroids, an unequivocal statistically significant (alpha = 0.01) annual (P = 0.0003) rhythmicity was identified. The amplitudes of both cycles were very similar, approximately 25% of the MESOR. The first estimated peak occurred in the second half of March and the first half of April, with an estimated increase of more than 50% over the average monthly incidence, resulting from coincident acrophases of both components. The second semiannual peak occurred at the end of September and early October. It is concluded that the long-term chemotherapy, applied in the majority of cases, failed to substantially influence the known circannual variations of the disease attacks. The issue has to be taken into account in planning prevention measures, treatment and its evaluation, as well as in organizing the regimen of management in endoscopic centers.

Parallaxes can originate from different sources, from bias towards proving a favored hypothesis, but also from bias against existing evidence in support of an unwanted hypothesis. One approach to avoiding either bias is to shift emphasis from hypothesis testing to parameter estimation. Complementary statistical approaches applied to replicates of given experiments can then serve to further a given field of science by providing converging or diverging results depending on whether the original hypothesis was true or false.

Reference standards were sought for use in the search of any indications of myocardial damage by an alteration of the time structure, or chronome, of creatine phosphokinase (CPK) "MB" isoenzyme activity in the heart of the male Holtzman rat. 144 rats were kept on 6 lighting regimens staggered by 4 hours, 24 rats per chamber. On 8 consecutive days, hearts from 3 animals from each chamber were harvested and weighed. The left ventricle was dissected, homogenized in a buffer solution at 4 degrees C and stored frozen at -20 degrees C until analysis. A supernatant aliquot of each sample was analyzed by a discontinuous gradient elution from DEAE-Shephadex A-50 columns. The CPK isoenzymes were quantified by the Rosalki method. Results of the CPK assay from each time point were analyzed by linear and nonlinear least-squares rhythmometry. Among other components, a 168h or circaseptan rhythm characterized CPK activity in the heart of Holtzman rats. This component and other ultradian and circadian aspects of the time structure of rhythms and trends, the chronome of a given variable, may serve, by any eventual alteration of their dynamic characteristics, as gauges of potential cardiac damage prior to the occurrence of an increase in the overall mean of the enzymatic activity.

Recently, assessment of T cell function has been refined by the ability to measure cytokines produced by activated T cells. We developed a whole blood assay to detect antigen-activated T cells that produce IFN-gamma. With this assay we have found a large circadian variation in tetanus- (acrophase 00(00) p < 0.001) and PPD- (acrophase 00(08) p < 0.001) stimulated IFN-gamma production. IFN-gamma production is inversely correlated with plasma cortisol (r = -0.5), suggesting that variation in IFN-gamma production may be secondary to circadian variation in plasma cortisol levels (acrophase 11(06)). The demonstration of circadian rhythmicity in antigen-stimulated IFN-gamma production is relevant to the diagnostic use of whole blood assays and, in addition, may have implications for the therapy of immuno-inflammatory diseases.

Whereas conventional time-unspecified single measurements of blood pressure and heart rate may mislead, influenced as they are, among other factors, by the individual's emotional state, position, diet and external stimuli generally, the chronobiologic evaluation of predictable variability in these physiologic variables assesses early cardiovascular disease risk in pregnancy by (a) the use of fully ambulatory devices and (b) the proper processing of the time series thus obtained. We have used this approach to quantify changes in 24-h synchronized circadian characteristics of cardiovascular variables in two consecutive pregnancies of a clinically healthy woman. The results were then compared with those obtained from data sampled after the second pregnancy. Blood pressure and heart rate were automatically monitored, at 1-h intervals, each time for at least 48 consecutive hours, and for a total of 76 days of monitoring in each pregnancy. Circadian parameters of those circulatory variables were computed for each 48-h profile of measurements by the least-squares fit of a 24-h cosine curve. Regression analysis of parameters thus obtained revealed patterns of variation of circadian rhythm-adjusted means and amplitudes with gestational age. In both pregnancies, the predictable variability of the circadian rhythm-adjusted mean of blood pressure can be approximated by a second-order polynomial model on gestational age: a steady linear decrease in systolic, mean arterial and diastolic blood pressures up to the 22nd week of pregnancy is followed by an increase up to the day of delivery. This pattern of variation is not found for data similarly sampled during non-pregnancy on the same woman. This longitudinal study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure and heart rate and also allows the establishment of prediction and confidence limits for cardiovascular parameters in a healthy pregnancy.

Several studies aimed at testing the effects of low-dose acetylsalicylic acid treatment (ASA, aspirin) in the prevention of preeclampsia conclude that beneficial effects of such treatment outweigh adverse ones. Since recent results suggest that desired effects upon lipoperoxides and beta-adrenergic receptors are dependent on the circadian timing of ASA administration, we aim to study if ASA therapy can be optimized by timing according to the rest-activity cycle. Accordingly, before conducting clinical trials on pregnant women, we have examined in clinically healthy subjects the possibility that effects of ASA upon blood pressure could indeed be time-dependent. We studied 55 healthy subjects (35 men and 20 women), 19-24 years of age (mean +/- SD: 20.9 +/- 1.8). Subjects were living on their usual diurnal waking (approximately 08:00 to approximately 24:00), nocturnal resting routine during sampling, following every-day life conditions without any restriction. The systolic, mean arterial and diastolic blood pressures and heart rates of each subject were automatically monitored every 30 min. for 48 hrs with an ABPM-630 Colin (Komaki, Japan) device before and after a one-week course of aspirin (500 mg/day). Subjects were randomly assigned to one of three groups, according to the circadian timing of administration of the daily dose of ASA: within two hours of awakening (R x 1), seven to nine hours after awakening (R x 2), or within two hours before bedtime (R x 3). The second blood pressure profile was obtained during the sixth and seventh days of treatment (to avoid differences in activity dependent on the day of the week). Results indicate a statistically significant blood pressure reduction (negative mean area between the blood pressure profiles obtained before and after aspirin administration) only when ASA was given seven to nine hours after awakening (R x 2; P = .012, .003, and .006 for systolic, mean arterial and diastolic blood pressure, respectively). These results were corroborated by a non-parametric (sign) test, also indicating the significant reduction in systolic and diastolic BP for R x 2 (P = .003 and .010, respectively). Non-invasive BP monitoring combined with the proper analysis of the time series thus obtained could then provide a cost-effective approach for testing the circadian optimization of long-term ASA administration for both cardiovascular disease prophylaxis and prevention of preeclampsia.