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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 163 records · Page 9Linked to original sources
PubMed1983

Circadian as well as circannual rhythms of circulating aldosterone have decreased amplitude in aging women.

Age differences in the characteristics of the circadian rhythm in circulating radioimmunoassayable aldosterone were studied on nine 20 to 26 year-old and ten 70 to 78 year-old women and ten 23 to 26 year old and ten 70 to 80 year old men in Würzburg, West Germany. These diurnally active-nocturnally resting subjects were sampled every 3 hours for 15 hours. A classical analysis of variance and a multivariate analysis of rhythm characteristics revealed major effects of age exerted on the circadian aldosterone amplitude in women (p = 0.003) but not in concomitantly sampled men. These observations complement the study of circadian and circannual rhythms in 8 young adults (15-21 years), 10 mature adults (29-36 years) and 10 post-menopausal (44-59 years) North American women, sampled at 100 minute intervals for 24 hours, once in each season, and document that the adrenocortical aldosterone-producing system remains rhythmic with at least two frequencies up to the late decades of human life, although in women it may be characterized by a reduction in the extent of spectral change after 70 years of age.

Adult↗
PubMed1983

Pineal modulation of ACTH 1-17 effect upon murine corticosterone production.

In tests of corticosterone production in vitro, aqueous pineal homogenate (APH) modulates the effect of a short-chain ACTH analogue, ACTH 1-17, added to adrenals from different circadian stages. Adrenal and pineal glands from female B6D2F1 mice, standardized on staggered LD 12:12 regimens, were obtained at the same clock-hour from each room, in order to cover 6 different circadian stages. Adrenals from each circadian stage were bisected and incubated with APH from the same circadian stage (isophasic incubation) or from one of the other 5 circadian stages (heterophasic incubation). ACTH 1-17 (0.05 IU) was added to each incubation medium. After 4 hours of incubation at 37 degrees C with 95% O2 and 5% CO2, the media were stored at -20 degrees C until corticosterone RIA were done. APH was found to have a statistically significant modulatory effect upon the stimulation by ACTH 1-17 of adrenal corticosterone production in vitro. This APH effect changed rhythmically as a function of circadian stage from amplification over no effect to attenuation, as a so-called feed-sideward.

Adrenal Glands↗
PubMed1983

Circadian pineal modulation of pituitary effect on murine corticosterone in vitro.

An old controversy is resolved as a novel effect: In a rhythmic fashion, aqueous pineal homogenate (APH) enhances, attenuates or leaves unaffected the production of corticosterone by mouse adrenals incubated with pituitary media. All glands stem from the same circadian stage in these (isophasic) studies on 72 female CD2F1 mice, standardized for two weeks in L 0600-1800 and D 1800-0600. Every 4 hours during a 24-hour span, 12 mice were killed. Pineals were removed for the preparation of APH and stored at 4 degrees C. Hypothalami, pituitaries and adrenals were removed, bisected and placed in wells containing 1 ml Krebs-Ringer buffer (K), at 4 degrees C, until incubation. At each circadian stage, bisected adrenals were incubated with 95% O2 and 5% CO2 at 37 +/- 1 degree C for 5 hours, with K only or with the addition of 0.05 IU ACTH 1-17 or APH or with isophasic pituitary or hypothalamic preincubation media with and without APH or muscle. Media were stored at -20 degrees C until corticosterone RIA. A circadian rhythm (p less than 0.05) characterized corticosterone production after stimulation by the pituitary alone or with APH. The overall modulatory effect of APH is an increased circadian amplitude of adrenal corticosterone production, in response to the isophasic pituitary.

Adrenal Glands↗
PubMed1983

Comparison of circadian rhythms of the renin-angiotensin-aldosterone system and electrolytes in clinically healthy young women in Fukuoka (Japan) and Minnesota (USA).

Circadian rhythms of the renin-angiotensin-aldosterone (R-A-A) system and electrolytes were evaluated in young healthy Fukuokan (Japan) and Minnesotan (USA) women. A similar protocol was used and each group remained on its usual diet. Blood was taken for 24 h at 4 h intervals from 8 a.m. during which time urine samples were also collected. The determinations in both groups were made in a laboratory in Japan. Plasma renin activity, plasma aldosterone concentration and aldosterone excretion rate showed similar circadian rhythms in both groups. However, those values at each sampling time and each span were always significantly higher in the Americans while the urinary Na and Cl excretions and blood pressure were higher in Japanese. The significant differences in the R-A-A system and blood pressure levels between these two groups may be due to the large amount of salt consumed by the Japanese.

Adult↗
PubMed1983

Lighting cycle and social isolation affect development of elevated blood pressure in spontaneously hypertensive rats.

Around-the-clock blood pressure measurements repeated from the 2nd to 6th month of life in spontaneously hypertensive rats (SHR) quantify circadian rhythmicity during the development of an elevated mean blood pressure. The rise in overall pressure is aggravated by social isolation in SHR maintained on a 12-hour white light/12-hour dim red light cycle, but not in SHR kept in continuous dim red light. The demonstration of this interaction is not possible with blood pressure measurements performed only at certain (convenient) times: failure to quantify the circadian rhythm in systolic blood pressure leads to conclusions which can vary with the circadian time at which measurements are made, even in comparisons at the same fixed clock-hour. Thus, in order to model and optimize multiple factors interacting in the genesis of overall mammalian pressure in SHR, rhythmometry is an indispensable tool as it is in other fields.

Animals↗
PubMed1982

Bimodal age-frequency distribution of epitheliosis in cancer mastectomies: relevance to preneoplasia.

A census of epitheliosis in 500 consecutive cancer mastectomies has been carried out. The probability of concurrence of this phenomenon with cancer has a bimodal age-frequency distribution. It is high in cancer mastectomies from women in their early 40s, low in the late 50s and high again in the elderly. Epitheliosis during the reproductive life span is regarded as a reversible ovary-dependent abnormality. It is greatly increased in the premenopausal cancerous breast and it is thought that it carries increased risk for cancer initiation. In contrast the probability of epitheliosis in the breast in the elderly cancer patient is only slightly greater than in "noncancerous" post mortem breasts of similar age. Much of this "epitheliosis" may represent, in fact, indolent autonomous cancer though a small proportion could be epitheliosis supported by extraovarian estrogen.

Adult↗
PubMed1982

Lethal nephrotoxicity and hematologic toxicity of cis-diamminedichloroplatinum ameliorated by optimal circadian timing and hydration.

Three hundred and forty-one female F344 (Fischer) rats were kept in light for 8 hr alternating with darkness for 16 hr; some were observed for survival for 21 days, while others were killed for blood sampling 4.5 days after a single intraperitoneal (i.p.) injection of 11 mg/kg cis-diamminedichloroplatinum (cis-DDP). cis-DDP was administered with or without concomitant i.p. saline load at one of six equispaced circadian stages. This high dose of cis-DDP resulted in marked lethal and renal toxicity, but in a moderate bone marrow suppression. Blood urea nitrogen (BUN), circulating total white blood cell counts (WBC) and survival times revealed statistically significant circadian rhythms of drug toxicity (P less than 0.03). Optimal tolerance for cis-DDP gauged by these three variables resulted from drug administration in the second half of the dark span. Renal tolerance for cis-DDP guaged by BUN was improved two-fold by appropriate drug timing. This benefit from drug timing alone was further improved two-fold if hydration and cis-DDP were given at the optimal circadian stage. Hydration-induced ameloriation of cis-DDP nephrotoxicity requires time qualification of both hydration and cis-DDP.

Animals↗
PubMed1982

Effect of ageing on circadian rhythms of plasma renin and aldosterone in mesor-hypertensive women.

This study investigated the changes in circadian rhythms of plasma renin activity (PRA) and plasma aldosterone (PA) which occur in essential mesor-hypertensive women, increasing in age. Systemic blood samples were taken throughout a 12 h period from both mesor-hypertensive women and clinically healthy women (control). The women in each group were either post-menopausal or had normal menstrual cycles. A cosinor method of temporal series was the analysis employed to compute the properties of PRA and PA circadian rhythms. The clearest effect of ageing, recorded in essential mesor-hypertensive women, is a decrease in circadian mesor of PRA cycle (P = 0.002). The age-related changes in clinically healthy women appear to be more extensive and involve a decrease for both mesor (P less than 0.001) and amplitude (P = 0.007) of PRA circadian rhythm. These disparities are convincing evidence for a non-physiological decline of the RAAS rhythmic function in the aged essential mesor-hypertensive women. The lack of an age-associated decrease in circadian PRA amplitude merits and pathophysiological and clinical investigation because it is a possible risk factor for post-menopausal, essential mesor-hypertensive women.

Adolescent↗
PubMed1982

Methodologically critical interactions of circadian rhythm, sex, and aging characterize serum aldosterone and the female adrenopause.

Nine 20- to 26-year-old and ten 70- to 78-year-old diurnally active, nocturnally resting women in Würzburg, Federal Republic of Germany, gave blood at 0700, 1000, 1300, 1600, 1900, and 2200 for radioimmunoassay of aldosterone. Single and population-mean cosinors were applied. A multivariate analysis of circadian rhythm characteristics revealed effects of age on the amplitude (p = .003) but not the mesor of aldosterone in women (i.e., the age effect could only be detected at certain circadian times but not at others). No change with age was found for concomitantly sampled men. Statistically significant interactions among circadian time, age, and sex (p = .001) establish the adrenocorticopause in women and suggest that it may occur earlier in women than in men, in keeping with similar results on serum cortisol in the same subjects. This phenomenon awaits scrutiny from the viewpoint of its bearing on longevity and life quality. These results also indicate the importance of assessing chronobiological characteristics.

Adult↗
PubMed1982

Circadian meal timing in relation to lighting schedule optimizes catfish body weight gain.

Two groups of 4- to 5-month-old catfish, Heteropneustes fossilis, were studied 2 years apart, in each case after standardization in light for 12 hours, alternating with darkness for 12 hours. The two studies involved 5 groups of 10 catfish each and 10 groups of 17 catfish each, respectively. In each study some fish were allowed access to food only during certain times in the circadian cycle: early dark, late dark, early light and late light for 45 or 50 days. On the average, in both studies, the catfish on restricted feeding schedules gained in body weight but more so when fed at certain times in the circadian cycle as compared to others. A circadian rhythm in weight response was demonstrated by a zero-amplitude test associated with the fit of a 24-hour cosine curve to the data (P less than 0.03). The acrophase (time of high values) for body weight gain occurred consistently either near the middle or in the second half of the daily dark span. That is, body weight gain in the presumably dark-active catfish seems to be maximal when food is made available in the middle or later part of the daily dark span. In catfish, as in human beings and mice, the timing of food intake can serve to optimize the utilization of ingested calories, by mechanisms yet to be elucidated.

Animals↗
PubMed1982

Chronopsies assess the within-day variability of blood pressure and pulse.

Blood pressure and pulse were monitored throughout 24 hours in 13 middle-aged men using a sphygmomanometer with an automatically inflatable cuff. These volunteers were in part mistakenly believed to have a "mildly elevated blood pressure" (in the light of a conventional non-chronobiologic approach, involving time-unspecified spot checks of blood pressure). Within about 24 hours, blood pressures and pulse varied remarkably: the coefficient of variation extended from 6.9 to 14.9% for systolic blood pressure (SBP), from 8.5 to 15.4% for diastolic blood pressure (DBP) and from 8.0 to 17.9% for pulse. By applying the single cosinor method (involving the least-squares fit of a 24-hour cosine curve), statistically significant circadian rhythms were observed in SBP, DBP, and pulse in all but 2 cases. In most cases, the timing of peak values was estimated to be in the evening for all 3 variables. Circadian rhythmicity accounted for up to 46, 30, and 42% of the total variability of SBP, DBP, and pulse, respectively. This marked circadian rhythmic variability is an important aspect of cardiovascular function.

Adult↗
PubMed1982

Toward chronobiologic pattern discrimination of the risk of developing breast cancer and other diseases.

With a view of the prevention as well as treatment of cancer and other diseases, it is important to quantify health positively and on an individual basis by chronobiologic methods. These include the assessment of the characteristics of certain circadian, circannual and other endocrine rhythms and trends, for the recognition of risk (prior to the occurrence of a given disease) by an alteration of the same rhythm characteristics and even by a time-specified single sample. With this aim in mind, a small number of selected (rather than randomly picked) women of 3 age groups was extensively sampled for 12 plasma hormones around the clock and the calendar, in 2 geographic locations. Such data revealed correlations of the familial risk of developing breast cancer with the circannual amplitudes of circulating prolactin and TSH. The risk of several other conditions was also correlated with hormonal rhythm characteristics; for example, the risk of developing diseases associated with a high blood pressure was correlated with the circannual amplitude of plasma aldosterone. The mapping of circannual characteristics, however, is time-consuming and costly and may not be warranted as a first step, for example when a physician is not in a position to wait for a year to make a diagnosis. With the possibility in mind that sampling requirements may be reduced to one or at most two samples, a chronobiologic pattern discrimination analysis was undertaken on the original data from young adults. The results are presented to indicate the method and to suggest the singling-out of certain variables for further testing on a larger, properly stratified and randomized sample, rather than as definitive results. Different classifiers and different corresponding reference values from variables that undergo circadian and circannual rhythms may perhaps withstand the test (and, with Vergil, the tooth) of time. If so, reference values that are time-specified may well prove to be a sine qua non in the assessment of certain neuroendocrine aspects of developing certain diseases, including breast cancer.

Adolescent↗
PubMed1982

Cisplatin urinary pharmacokinetics and nephrotoxicity: a common circadian mechanism.

Renal toxicity and urinary pharmacokinetics following a nonlethal dose (5 mg/kg) of cisplatin were investigated in female F344 (Fischer) rats that were on a standardized light-dark schedule, with water freely available. Circadian timing of drug administration had a major effect on the BUN increase (P less than 0.01), the urine volume increase (P less than 0.025), and the urinary concentration of cisplatin following drug administration (P less than 0.01). Renal toxicity was positively correlated with the peak urinary concentration of cisplatin and with the area under the curve of urinary concentration over the first 20 hours after drug administration (P less than 0.01). Drug administration near the normal circadian maximum of urinary volume prior to treatment resulted in the least renal toxicity, lowest peak, and smallest area of urinary concentration of cisplatin.

Animals↗
PubMed1982

[Circadian rhythm of temperature, heart rate and blood pressure in normal rats and hypothyroid rats].

We explored the circadian variation of core temperature, heart rate and blood pressure in hypothyroid and euthyroid male Sprague-Dawley rats. A circadian rhythm was quantified by the population mean-cosinor method for the core temperature of both hypothyroid and intact rats, whereas for the blood pressure and heart rate values a circadian rhythm was validated by rejection of the zero-amplitude assumption only in the hypothyroid rats. Whether hypothyroid rats adjust to new schedules at a rate different from euthyroid animals is an inference from these studies awaiting scrutiny.

Animals↗