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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
PubMed1986

Circadian characteristics of urinary epinephrine and norepinephrine from healthy young women in Japan and U.S.A.

Clinically healthy diurnally active young adult women were studied during the same season (March) at the Universities of Kyushu (Fukuoka City, Japan) and of Minnesota (Minneapolis, U.S.A.), under comparable conditions, except that the habitual diets were not changed. The subjects (20 Japanese and 16 Americans of mixed Caucasian background) were studied over a single 24-hr span. Urine was collected at 4-hr intervals. A circadian rhythm in total urinary norepinephrine excretion showed similar characteristics in Japanese and Americans. In epinephrine excretion, the Japanese women showed a statistically significantly higher amplitude with higher peak values, but no statistically significant difference in the rhythm-adjusted mean. This intergroup difference is strictly time dependent; it does not come to the fore in urine samples covering the nocturnal rest span of the subjects.

Adult↗
PubMed1986

Circadian rhythm in mammary cytoplasmic estrogen receptor content of Balb/C female mice with and without pituitary isografts.

Cytoplasmic estrogen receptors were determined by the dextran-coated charcoal method in inguinal breast tissue of three groups of Balb/C female mice 6-8 weeks following subcutaneous implantation into the intact animals of three pituitary glands and three pieces of skeletal muscle (group I), three pituitary glands and three segments of hypothalamic tissue (group II), or three pieces of skeletal muscle (group III) obtained from animals of the same inbred strain as control. A circadian rhythm in estrogen receptor content was statistically quantified by cosinor analysis in the muscle implanted control and the pituitary and hypothalamic implant groups. In the pituitary and muscle implant group the circadian rhythm is of borderline significance with a P-value between 0.05 and 0.10. The timing (acrophase) and extent of change (amplitude) are similar in all three treatment groups. The average receptor content (MESOR) in the two pituitary-implanted groups, which in previous studies were shown to have an increased breast cancer incidence is about twice that of the control group. The reduction in the pituitary induced breast cancer rate by hypothalamic tissue addition to a cancer incidence between the animals with pituitary and muscle isograft and the mice carrying no pituitary at all has also been shown previously in this strain of mice and is not reflected in receptor content.

Animals↗
PubMed1986

[Persistence of the circadian rhythm of dehydroepiandrosterone in the brain, but not in the plasma, of castrated and adrenalectomized rats].

In adrenalectomized and orchidectomized rats, the removal of the steroidogenic endocrine glands is associated with a near-disappearance of corticosterone (B) from plasma and brain; circadian variations of B and of plasma dehydroepiandrosterone (D), characteristic of the intact rat, are no more detected. By contrast, analyses of brain D measurements by the cosinor method demonstrate a persisting circadian rhythm of large amplitude.

Adrenalectomy↗
PubMed1985

Effect of an adrenocorticotropin analogue, ACTH 1-17, on DNA synthesis in murine metaphyseal bone.

The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six different timepoints, 4 hr apart, during a single 24-hr span with either a low (0.02 I.U./kg) or a high (20 I.U./kg) dose of ACTH 1-17. Control groups received injections of a placebo at corresponding timepoints. Subgroups of mice were injected with [3H]thymidine ([3H]Tdr) to follow the changes in DNA labeling in the proximal tibial metaphysis at 15 min and 2, 4, 8, 12 and 24 hr after ACTH 1-17 or placebo treatment. All mice were injected with the isotope 30 min before killing, except for those killed 15 min after Rx administration where the isotope had been injected 14 min before killing. The data were analyzed both by analysis of variance and by the cosinor method, the latter of which tests the fit of a 24-hr cosine curve to the data. The effect of ACTH 1-17 on the target cell population was dependent not only upon the dose but upon the time of administration. Both doses exerted time-dependent action, ranging from stimulation to inhibition of DNA labeling. Inhibition was noted when the ACTH 1-17 was administered at 2 hr after the beginning of the daily dark span when nocturnal animals become active. When administered at this circadian stage, the larger dose in particular was associated with an inhibition of DNA labeling lasting for 24 hr. The inhibitory effect was much shorter when the same dose was injected 4 hr earlier. Moreover, the large ACTH 1-17 dose had a stimulatory effect lasting for 24 hr when it was administered 2 hr after the onset of the daily light span, with a much shorter stimulation following administration of the large dose at 6 hr after the beginning of the daily dark span. A circadian stage-dependent stimulation or inhibition of DNA labeling at 2 or 14 hr after light onset, respectively, was thus complemented by an initial inhibition followed by stimulation and vice versa at 10 and 18 hr after light onset respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1985

Circadian toxicology of cyclosporin.

Cyclosporin (Cs), a cyclic nonpolar undecapeptide of fungal origin, has potent immunosuppressive and antiparasitic activities, and renal and hepatic toxicities, the mechanisms of which are not worked out. Many nephrotoxins and hepatotoxins are predictably more or less harmful, depending upon the circadian stage at which they are administered. In order to find treatment schedules that might damage the animal least, the toxicity of 20 mg kg-1 day-1 of Cs given intraperitoneally was studied at six different circadian stages in adult male Lewis rats. Cs toxicity was gauged by body temperature decline, body weight loss, and survival time. Rectal temperatures over a 24-hr span during the 2 days prior to the first death revealed that rats treated during darkness were 1.6 +/- 0.3 degree C cooler than vehicle-treated controls, whereas rats treated during the light span were only 0.4 +/- 0.2 degree C cooler than controls (p less than 0.01). Rats treated in darkness lost twice as much weight compared to those treated in light (20 +/- 2 versus 10 +/- 2%, p less than 0.01). Rats receiving daily Cs in the dark span lived an average of 28 +/- 5 days compared with 44 +/- 4 days for animals getting Cs during the light span (p less than 0.05). Three separate nonspecific measures of drug toxicity confirmed that there was substantial circadian stage dependence to Cs toxicity. The safest time for the drug in rats was 2 to 10 hr after lighting onset, a time when rats are usually beginning their diurnal rest and/or sleep span.

Animals↗
PubMed1985

Temporal correlation of some endocrine circadian rhythms in elderly subjects.

The aim of this chronobiological study was to investigate temporal correlations in the circadian patterns of 6 hormones, namely somatotrophic hormone (STH), prolactin (PRL), cortisol (F), aldosterone (ALD), insulin (IRI) and C-peptide (CP), assayed in systemic blood serum drawn at 07:00, 10:00, 13:00, 16:00, 19:00 and 22:00 h from an antecubital vein in 19 young subjects (aged 20-29 yr, comprising 10 males and 9 females; and 20 elderly subjects (aged 70-81 yr, comprising 10 males and 10 females). All subjects were sampled on a normal dietary sodium intake (120-140 mEq/24h) while following a social routine of diurnal activity (07:00-23:00) and nocturnal rest (23:00-07:00). Time-qualified data were analyzed by lead-lag correlation and by cosinor analysis. According to the lead-lag correlation findings, it would appear that the correlation which exists between several time-qualified series in young subjects is no longer present in elderly subjects. The circadian rhythms which were found to have lost their temporal correlations with advancing age were those between STH and IRI, STH and ALD, PRL and IRI, PRL and CP, and ALD and CP. It should be noted that the correlation between hormonal rhythms breaks down mainly on account of a peculiar age-related change in the magnitude of the circadian fluctuation. This chronological decline in amplitude led to the conclusion that the senescence of endocrine rhythmic functions is a biological phenomenon characterized by altered circadian variability.

Adult↗
PubMed1985

Circadian rhythms of plasma renin activity and aldosterone: changes related to age, sex, recumbency and sodium restriction. Chronobiologic specification for reference values.

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

Adult↗
PubMed1985

[Circadian course of delta 5,3 beta-hydroxysteroids and glucocorticosteroids in the plasma and brain of rats].

Corticosterone (B), pregnenolone (P) and dehydroepiandrosterone (D) undergo circadian variations in the rat plasma and brain. When the data are interpreted by the Cosinor method, the acrophases of P in brain and of D in plasma significantly precede the acrophase of B. The asynchrony of delta 5-3 beta-hydroxysteroid and glucocorticosteroid rhythms brings an additional argument in favor of separate regulatory mechanisms.

Animals↗
PubMed1984

Toward a chronophysiology of circulating aldosterone.

The physiology of aldosterone secretion has been prominently investigated by homeostatic studies on the levels of the steroid in plasma and/or urine. Aldosterone secretion is, however, arranged in a rhythmic fashion along the 24-hr cycle. The dynamics of aldosterone should thus be reanalyzed chronobiologically in order to gain further insight into the physiology of the hormone. Such a revisitation has been performed in the present study on four groups of clinically healthy volunteers categorized according to sex and age. Aldosterone has been assayed in the plasma of systemic venous blood six times a day (0600, 0800, 1200, 1800, 2000, 0000) in different conditions of physical activity and sodium intake. Time-qualified data have been analyzed by the single-cosinor method and then summarized by the population-mean cosinor procedure to quantify the circadian rhythms in their properties (mesor, amplitude, acrophase). Differences in rhythmometric parameters have been tested by a multivariate analysis for vectorial units. (Hotelling's T2 test). Cosinor analysis indicates that the dynamics of circulating aldosterone substantially changes in relation to posture. The habit of having a routine of diurnal activity leads the circadian rhythm of aldosterone to delay its acrophase from morning to afternoon. The postural shift of acrophase is essentially accompanied by an elevation in the 24-hr mean level. The restriction of salt intake is associated with an increase in mesor; the temporal localization of the circadian crest shows, however, a very high stability. Sex is not characterized by significant differences in the 24-hr patterns of aldosterone in the sense that young males and females show substantially identical time-qualified curves and circadian parameters. Increasing age until the seventh decade in life is responsible for changes mainly in 24-hr mean levels with a slight modification in amplitude. Such a chronophysiology for circulating aldosterone related to the motor-rest schedule, sodium intake, sex, and age, is of interest not only to heuristic but also to practical approaches in clinical medicine.

Adolescent↗
PubMed1984

Circadian rhythm of serum cortisol in Cushing's disease.

Two women with typical clinical and biochemical features of pituitary-dependent Cushing's disease each underwent hourly blood sampling for 24 h on two separate occasions for measurement of serum cortisol. The 24-h mean serum cortisol concentrations (17.7 and 15.4 micrograms/dl in patient 1; 19.0 and 15.8 micrograms/dl in patient 2) were elevated (normal level, less than 12.5 micrograms/dl), as expected. Cosinor analysis of the patients' serum cortisol patterns revealed statistically significant circadian rhythms on all four profiles. The amplitude of the rhythm on both occasions in patient 1 (5.8 and 6.6 micrograms/dl) and on one of two occasions in patient 2 (7.2 and 10.5 micrograms/dl) fell in the range for the amplitude of the cortisol circadian rhythm in normal subjects (2.2-8.6 micrograms/dl). In contrast to commonly held belief, some patients with Cushing's disease may exhibit circadian variation of serum cortisol.

Adult↗
PubMed1984

Circadian breast skin temperature rhythms: overt and occult benign and occult primary malignant breast disease.

Circadian variations of breast surface temperature have been measured in patients with overt or occult benign breast disease, or in those with occult breast cancer. Subjects were studied in a hospital ward environment well-controlled with respect to ambient temperature. Using manual techniques temperatures were recorded half-hourly for 96 hr from replicate sensors placed on quadrants of the left and right breasts inclusive of tumour areas and similar sites on the contralateral breast. Application of time series analysis failed to consistently demonstrate differences in values for the rhythm parameters for the tumour area and contralateral site. It was apparent, however, that the tumour area was generally associated with a reduced initial variance of the series in addition to a reduced percentage variance explained by a time series model with two rhythmic components when compared to the control site. These data suggest that efforts to identify early breast disease from signals of breast temperature should, at least, be directed to studies of temperature variance.

Adult↗
PubMed1984

Circadian-stage dependent ACTH 1-17 effect on DNA synthesis in murine duodenum, colon and rectum.

The objective was to determine the effect of adrenocorticotropin (ACTH 1-17) on the incorporation of [3H]TdR into DNA (DNA synthesis) in the duodenum, colon and rectum of CD2F1 mice standardised to 12 hr of light alternating with 12 hr of darkness. A question asked was whether the difference in times of administration along the 24-hr time scale influenced any response found. The response was complex as ACTH 1-17 was capable of bringing about statistically significant increases in the incorporation of [3H]TdR into DNA at certain times, decreases at other times, or no response at still another time. A generalization that can be made from all these tissues is that ACTH 1-17 had a greater influence in bringing about a decrease in DNA synthesis when it was administered around the time of transition from dark to light. A similar finding was made earlier for the ACTH 1-17 effect upon the tongue, esophagus and stomach. A 2- and 3-way analysis of variance supports our conclusion that the kind-of-treatment, time-of-treatment and the interval-to-kill (Sampling time) as well as their interactions are important factors when determining any response of ACTH 1-17 or placebo.

Adrenocorticotropic Hormone↗
PubMed1984

Circadian temperature rhythm and circadian-circaseptan (about 7-day) aspects of murine death from malaria.

About-7-day (circaseptan) and circadian rhythms were sought and found in host-parasite relations of mice infected with Plasmodium berghei. Five inbred male DBA mice, about 18 weeks of age, were implanted with transsensors for temperature telemetry. Core temperature, monitored every 10 min for 3 days before the intravenous or intraperitoneal inoculation of 10(5) infected erythrocytes and thereafter until death, was analyzed by cosinor. A statistically highly significant circadian rhythm exhibited similarly synchronized acrophases. Core temperatures on the days immediately after malarial infection were mostly within the range of temperatures observed before injection. A mesor-hypothermic stage preceded death by several days. In a second study, 24 male BALB/c and 42 male DBA mice, 12 weeks of age, housed in three rooms on different regimens of light and darkness (alternating at 12-hr intervals), staggered by 8 hr, were inoculated ip with 10(4) infected erythrocytes, one-half at noon, the other half at midnight, within 0.5 hr of blood withdrawal. Thus, one endeavored to cover six circadian host stages (02, 06, 10, 14, 18, and 22 hr after light-on). At 54 and 51% overall mortality (irrespective of inoculation time), a circadian rhythm in susceptibility to malaria was demonstrated in these mice by the single cosinor fit of a 24-hr period (P less than 0.003 and less than 0.020, respectively). The single cosinor fit of a 7-day period further demonstrated a circaseptan rhythm (P = 0.014) in the mortality of both strains following the inoculation of P. berghei. The acrophase (360 degrees = 168 hr) was at -325 degrees from the inoculation time with 95% confidence limits extending from -276 to -378 degrees. Such predictable time relations of P. berghei to its murine host await the exploration of mechanisms underlying the circadian and infradian (7-day) rhythmicities here demonstrated and quantified with their uncertainties. Irrespective of mechanisms, information on such periodicities may also guide attempts to optimize treatment by timing according to the interactions of plasmodial virulence and host resistance that remain to be quantified separately.

Animals↗
PubMed1983

Qualitative and quantitative assessment of the circadian rhythm of cortisol in pregnancy.

The effect of pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol and urinary free corticoids was examined in a sequential study during the second and third trimester and 6 to 12 weeks post partum. Hourly blood samples from six subjects and 8-hour urine collections from eight subjects were obtained around the clock. While the circadian rhythm was maintained during gestation, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased. The relative excursion of plasma cortisol (expressed as the percentage of deviation from the 24-hour mean) exhibited remarkable blunting compared with postpartum values. This pregnancy-associated blunting of plasma cortisol excursion was indicated by a significant reduction in the: (1) mean peak and nadir excursion, (2) integrated area between the percent deviation curve and the 24-hour mean, and (3) mean slope of the major incremental and decremental segments of the percent deviation curve. The circadian rhythm and diurnal excursion of plasma cortisol were reflected in urinary free corticoid values. Mean 24-hour urinary free corticoid concentrations increased 180% during gestation over nonpregnant levels. Nadir concentrations of urinary free corticoids in pregnancy exceeded peak nonpregnant levels. The gestational rise of metabolically active free cortisol and adrenocorticotropin (ACTH), and the pregnancy-associated blunting of the excursion of plasma cortisol may be explained by an autonomous source of ACTH during gestation.

Adolescent↗
PubMed1983

Circadian variation in the urinary excretion of electrolytes and trace elements in men.

Three-hour urine specimens were collected over a period of 27 hours from 11 healthy adult male subjects. Each specimen was analyzed for Na, K, Ca, Mg, and Zn using atomic absorption spectrophotometry. Each sample was also dialyzed, pH 7.35, and subsequently analyzed for Na, K, P, Ca, Mg, Zn, Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn using a multielemental argon-plasma emission system. The data were evaluated on conventional time plots (chronograms) and as computer-determined "cosinor" plots. A population circadian rhythm with a statistical significance was detected for total Na, K, Ca, and Mg, and for nondialyzable Na, K, P, Ca, Zn, and Mo. For almost every element studied the increase from lowest to highest 3-hour group mean along the 24-hour time scale was more than 100%. The 24-hour excretion of Na, K, Ca, Mg, and Zn appeared in good agreement with the so-called "normals." The nondialyzable levels of Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn were similar to the total urinary excretions reported in the literature.

Adult↗