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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 235 records · Page 13Linked to original sources
PubMed1980

Chronopharmacology: a therapeutic frontier.

Chronopharmacology, the study of time-dependent physiological response to drugs, and its relationship to current drug therapy are discussed. The objective of chronotherapy is to apply chronobiologic principles to the treatment of human disease. The appropriate patients for chronotherapy are those who are receiving high-risk drugs, who have a high-risk disease (e.g., cancer) or who are receiving a high-cost drug. Although little is known of the chronobiologic characteristics of many drugs or diseases, researchers should take into account the possible relationship of chronobiology to drug effects when designing therapeutic trials. Drug therapy can be optimized by tailoring dosing schedules and distribution systems to chronobiologic patterns.

Animals↗
PubMed1980

Circadian variation of serum prolactin and TSH of women in health or with mammary carcinoma, fibroadenoma or fibrocystic mastopathy.

Prolactin and TSH were determined in serum samples obtained at 4-hourly intervals throughout a 24-hour span from healthy women and from women with fibrocystic mastopathy, fibroadenoma or carcinoma of the breast. Data were subjected to analysis by the population mean-cosinor method. Differences in circadian mesor of prolactin among the 4 groups were statistically significant (P < .01), with healthy women having the lowest value. Prolactin amplitude differences among the groups were of borderline statistical significance (P = .05), while no differences in circadian acrophase were apparent. No statistically significance differences in TSH circadian mesor, amplitude or acrophase could be demonstrated. Individual values from subjects with breast disease were compared with time-qualified tolerance intervals based on data from healthy subjects. If these results can be corroborated on larger populations, sampling about 3 hours after arising may best detect an abnormal serum prolactin elevation. Results from this and other studies indicate the need for multi-variable and multifrequency investigations of breast disease.

Adenofibroma↗
PubMed1980

Meal timing alters circadian rhythm of skin surface temperature in non-human primates.

Circadian rhythms of skin surface temperature were demonstrated in a group of African green vervets. Alteration of the timing of a single daily meal of fixed caloric content resulted in a shift of the skin surface temperature acrophase in 7 of the 8 series. The timing of the individual temperature acrophases in relation to the light-dark cycle and the extent of acrophase shift in response to alteration of meal timing showed considerable variation between the individual animals studied.

Animals↗
PubMed1980

Chronotherapy of mammary cancer in rats.

Two studies were performed on female Fischer rats, housed 2/cage with food and water ad libitum in rooms maintained at 24 degrees C and with lights on daily for 8 hours (LD 8:16). In each study 192 rats were innoculated subcutaneously with 13762 mammary adenocarcinoma. Of these, 168 received chemotherapy, separate groups being treated at 1 of 6 different circadian stages. As controls, 24 tumour-bearing rats received saline while 24 rats without tumours received therapy. Chemotherapy consisted of 0.8 mg/kg Adriamycin (ADR) i.p. daily from day 11 to day 19 post tumour inoculation (except for days 16 and 17) followed by 1.6 mg/kg phenylalanine mustard (PAM) p.o. 3 times weekly beginning on day 20. In study-I PAM treatment was continued until 50% of the treated tumour-bearing rats died. In Study-II a 50% overall reduction in mean tumour size was not achieved before regrowth, presumably due to differences in the source of the rats, tumour-heterogeneity and/or other factors. At 50% overall tumour size reduction in the first study there was a statistically significant effect of treatment-timing on tumour size and on percent remission. The greatest reduction in mean tumour size and the highest percentage remission was observed in rats treated at the onset of darkness (activity), a timing similar to that observed in previous studies for optimal tolerance of ADR and PAM by the host. No deaths were observed in treated rats without tumours. When the drug combination used was sufficiently active against the tumour, the therapeutic index (selective toxicity) was improved by timing therapy according to circadian rhythms in the tumour-host system. This effect was achieved with doses not lethal to the nontumourous host. The presumption by others that chronotherapy depends on the use of toxic doses does not here apply.

Adenocarcinoma↗
PubMed1979

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America.

Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.

Adult↗
PubMed1979

Circannual rhythms in progesterone receptor levels and functions.

Studies in this laboratory on the nuclear binding sites (acceptors) for progesterone receptor in the developed chick oviduct have resulted in the detection of seasonal variations in the levels and functions of the receptor. Cytosol preparations obtained from the chick oviducts during the winter/spring period between January and May display reduced receptor levels as well as a loss of the capacity of the receptor to bind to nuclear "acceptor" sites in vitro. The binding of [3H]P-R to whole chromatin or purified acceptor proteins reannealed to DNA display the same rhythm. No such rhythm is detected for the binding of P-R to pure DNA. Computer analysis of the data, using least squares method to fit the data to cosine curves, shows a significant fit indicating a circannual rhythm in P-R binding to the acceptor protein-DNA complex but not to pure DNA. The nuclear binding in vivo, achieved by injecting [3H]progesterone into the wing vein and analyzing the radioactivity localized in the oviduct nuclei, also displays a similar rhythm. These results support that native nuclear acceptor sites for progesterone in the chick oviduct represent protein-DNA complexes and not pure DNA. The failure of P-R to bind the nuclear acceptor sites in vivo and in vitro during this period can be explained by the two subunit hypothesis of Schrader and O'Malley, whereby one of the two subunits is absent or inactive during this period.

Animals↗