Subject: Endocrinology and chronobiology

Research Notes on Avian Biology 1994: Selected Contributions from the 21st International Ornithological CongressMorphology and Physiology: Endocrinology

Subject: Endocrinology and chronobiology     

Contributions made to chronobiology by studies of fiddler crab rhythms.

One of the classic organisms used in chronobiological research is the fiddler crab (genus Uca), an animal unique in that it displays both circadian and tidal (i.e., circalunidian) rhythms. The pioneering work on this animal helped produce the early evidence for many of the standard properties now recognized for all circadian rhythms: near temperature independence of the period, phase lability and setability, the light and temperature sensitivity rhythms expressed by phase response curves, and the persistence of rhythms in organs isolated from a multicellular animal. Importantly, results arising from studies of this crab--and a few other organisms--resulted in the development of the exogenous timing hypothesis. While philosophically sound, the lack of supporting evidence for this hypothesis has resulted in it being discarded by most chronobiologists; but while still in its prime, it drew great interest, and therefore grant support, to the field in general, stimulated a great deal of research that otherwise might not have been performed, and resulted in the discovery of environmental stimuli previously unsuspected to influence organisms. As could be expected, continuing work with this crab, using modern approaches and statistical techniques, has modified earlier findings and interpretations, has revealed new properties, and has resulted in the creation of new hypotheses. The review and update is a synthesis of 45 years of this work.     

Perspectives in chronobiology of air pollution

In a series of experiments, male and female Sprague Dawley rats, kept in light (L) from 06(00) to 18(00) alternating with darkness (LD 12:12) inhaled different concentrations of carbon monoxide (50-1,700 ppm) at each of two test times, 12 h apart. A decrease in flow of CO2 (VCO2) resulting from CO inhalation was greater in the active dark (D) than resting light (L) span. Experimental hypoxic mortality of male and female mice also shows circadian variations, being greater in the D than in the L span. Moreover, a difference of mortality was observed betwen hypoxic exposures performed at 12(00) (in LD or DL) and hypoxic exposures performed at 00(00) (in LD or DL). Such results await tests of any extent to which they model responses of human beings to air pollution. In human beings any external environmental circadian, circaseptan and circannual variations in air pollution as such may serve to variable extent as socioeconomic synchronizers of innate rhythms with a corresponding frequency, rather than as solely generators of time patterns in any physiopathologic response to air pollution.     

Application of flow cytometry in chronobiology

A survey is given on flow cytometric techniques and their applications in chronobiology. Rapid automatic single cell measurements with a high rate (1,000-5,000 single cells/sec) enable the accumulation of large numbers of data at short intervals, thus obtaining important knowledge on circadian variations of cell proliferation in epidermis and other types of surface epithelium as well as hemopoiesis. In addition, the method has to some extent been used for monitoring cancer chemotherapy, and is thus available for the application in chronotherapy of malignancy. The introduction of rapid automatic techniques such as flow cytometry is a great advantage for any study on single cells and tissues where rhythmic variations in different functions have to be taken into consideration.     

The clinical application of chronobiology to oncology

The introduction to medical practice of chemical agents for fighting human cancer some 30 years ago brought hope to a field of medicine previously shrouded in despair and impeded by superstition. Gradually more and better agents have become available to the physician and to the patient suffering from cancer. The physician-scientist has, in turn, learned a great deal about normal and abnormal cellular biology by using these drugs as probes. The observations that certain tissues and certain tumors share patterns of drug toxicity have led to a broadening of biologic understanding and to the use of combinations of drugs with shared antitumor activity and unshared toxicities. This empiric art of cancer chemotherapy has resulted in great progress in the treatment of a large number of advanced cancers. As important, however, is that this experience has resulted in knowledge which is leading to the development of rationally designed therapeutic regimens; to drug analogues seeking greater therapeutic-toxic ratios; to the development of methods for chemically interfering with toxic drug effects while allowing or enhancing antitumor effect; and to work defining effects of drug timing. Drug timing research considers drug dosage in respect to the timing of a drug relative to the timing of other drugs (drug-time-drug interactions) or to other doses of that same drug (drug-drug interval); the order of drugs (drug-drug sequence); and the timing of drugs relative to an internal organismic time structure (time-drug interactions). Data in this brief review clearly show that drug timing needs to be considered when designing rational chemotherapy for a living organism suffering from a cancer. The beautiful spatiotemporal complexity of life is not to be ignored or avoided, but should be considered as a golden opportunity to use what few imprecise chemical weapons we have a little more effectively.     

Insects as novel models for research in chronobiology

A need exists for novel models for chronopharmacological research. Insects could serve in this capacity since they are relatively inexpensive, short-lived and acceptable to the public. With the cooperation of Franz Halberg, tests which demonstrated that this was feasible were undertaken over an about 10 year span. Specifically, life span was shown to be different in different photoperiodic regimens for the codling moth and the face fly. Evidence was also found for a circaseptan rhythm as well as an about 3-day rhythm in the response to the photoperiodic shifts. These results are consistent with those reported by F. Halberg and others in mammals and a unicellular plant. The finding, in collaboration with F. Halberg and others, of a rhythm in melatonin in the heads of face flies suggests that biochemical as well as behavioural analogies between insects and other animals can be drawn when insects are used as models for research in chronopharmacology.     

Hormones and blood pressure: clues from chronobiology

Results relating to the study of several hormones homeostatically related to blood pressure (renin-angiotensins, mineralocorticoids, glucocorticoids, atrial natriuretic factor) are reviewed. Most experimental data and clinical observations concerning 'hypertension' are specified neither as to circadian stage nor do they assess rhythm parameters. Such homeostatic data suggest that several groupings of hormones play a major role in coordinating blood pressure. The majority of hormones involved have multiple actions and the diversity of effects is often unexplained in homeostatic terms. In chronobiology, opposite effects are seen in response to the same stimulus depending upon the stage of the organism's multifrequency rhythms and their intermodulation. The periodic pattern exhibited by some of the hormones coordinating blood pressure in health and the capability of these hormones to modify temporal structure, either inducing a change in timing (circadian blood pressure ecphasia) or in amplitude (amplitude-hypertension) or in mean level of the values (MESOR-hypertension) are reviewed as well.     

中西医观解读时间生物学

时间生物学是一门研究生命活动节律的科学.在西方医学中,研究时间生物学是利用分子生物学实验来阐释其机制,以西医的思维方法解释时间生物学的生理及病理过程;中医对时间生物学的记载有两千多年的历史,阴阳理论、子午流注学说以及五运六气学说一直以来都在指导中医的诊断和治疗.中西医观的不同对时间生物学的研究提供了新的研究思路,同时时间生物学也为研究中西医结合提供了广阔的前景.     

Time is ripe: maturation of metabolomics in chronobiology

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The birth of chronobiology: Julien Joseph Virey 1814

Julien-Joseph Virey (1775-1846) held the position of pharmacist-in-chief at the Val-de-Grace, a military hospital. He was an innovative pharmacist, naturalist, anthropologist, and philosopher and a prolific author. His writings encompassed a wide range of topics, although many of his ideas were sometimes harshly questioned. Interest in Virey's work today stems from renewed appreciation of his doctoral thesis in medicine, which was completed in 1814 in Paris and was the first devoted to biological rhythms. Virey envisioned biological rhythms to be innate in origin and controlled by living clocks entrained by periodic environmental changes, such as the day-night alternation in light and darkness. He also reported that the effects of drugs vary according to their administration time. But, above all, he collected and published quantified time series that demonstrated human circadian and annual mortality rhythms. Statistical analysis of Virey's data using modern time series methods confirms his deduction that human mortality exhibits rhythmicity. Comparison of his findings with those derived from analyses of more recent human mortality time series shows the characteristics of these rhythms have changed little since 1807 despite differences in environmental conditions. Virey deserves credit for establishing the field of chronobiology based on his insights and writings.