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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 433 records · Page 24Linked to original sources

Modelling prey-predator cycles using hemipteran predators of mosquito larvae for reducing world-wide mosquito-borne disease incidence.

Diplonychus indicus is an aquatic hemipterous bug known to be a voracious predator of dipteran larvae, among others, and to show a selective predation for mosquito larvae when exposed to a mixed prey diet. A datum consisted of the percentage of the fourth instar of (25) culicine mosquitoes killed by the bug. Data around the clock, published earlier (from starved adult males of this bug), reanalyzed by single cosinor, reveal a circasemidian rhythm (p = 0.004). This result prompts the recommendation of studying the time structure of prey-predator cycles further to evaluate the merits or demerits of introducing the bug in the field with the aim of reducing worldwide mosquito-borne disease incidence.

Animals↗

Circannual bootstrapping complements pattern discrimination in the assessment of endocrine markers for an expansive personality (EP).

The bootstrap distribution of the difference in the circannual mesor of DHEA-S, TSH and LH between healthy adult women of a lowly or highly expansive personality, assessed by scale 9 of an abbreviated Minnesota Multiphasic Personality Inventory, validates the potential classifying role of these hormones, originally singled out by methods of pattern discrimination.

Adult↗

Sodium restriction amplifies and propranolol loading inhibits circadian rhythm of plasma renin-angiotensin and aldosterone.

Five male and 5 female clinically healthy volunteers, 17-37 years of age, gave systemic venous blood at 0600, 0800, 1200, 1800, 2000 and 0000 for RIA of (supine values) plasma renin-angiotensin (PRA) and aldosterone (PA) under 4 conditions: a. unrestricted sodium intake, no treatment; b. unrestricted sodium intake and 40 mg propranolol per os every 6 h; c. sodium restriction, no treatment; d. propranolol loading on sodium deprivation. Cosinor methods were used for data analysis. Sodium restriction amplifies the circadian rhythms of PRA and PA, whereas propranolol loading inhibits these same rhythms on a unrestricted sodium intake, but much less so under conditions of sodium deprivation. The propranolol-induced inhibition of the circadian rhythms investigated on a unrestricted sodium intake suggests that the beta-adrenergic system is an effective mechanism coordinating the circadian rhythmic functions investigated. The persistence of the rhythms in sodium-depleted subjects under pharmacological blockade of beta-adrenoreceptors is in keeping with the concept that a second mechanism of the circadian rhythms examined is located in the sodium-sensitive macula densa cells of the renal distal tubule.

Adolescent↗

Chronomodulatory infradian synchronization by placebo or ACTH 1-17 of Musca autumnalis mortality on shifted lighting regimens.

The face fly, Musca autumnalis, exposed to shifts of an LD16:8 lighting schedule at varying intervals, whether previously untreated or given placebo or ACTH 1-17 treatment, before the initiation of shifts, exhibits an infradian frequency response in mortality. At overall 50% mortality, a periodicity of approximately 4.5 days is found for flies exposed to placebo or ACTH 1-17 as a response to the shift interval. As compared to controls, the mortality of flies treated with placebo or ACTH 1-17 is delayed. Not all shift schedules are detrimental; some are actually beneficial.

Adrenocorticotropic Hormone↗

Cephalo-adrenal interactions in the broader context of pragmatic and theoretical rhythm models.

Some of the literature on modeling of biological rhythms with mathematical, physical, chemical, biochemical, in vivo and in vitro oscillations is succintly annotated. The need for biologic models that account for the interaction of 3 or more periodic entities is indicated, documented and illustrated, with emphasis on the cephalo-adrenal network of rodents. Patterns of interaction, in this context, involve attenuation, no-effect and/or amplification by a third entity, the modulator, of the effect of an actor upon the reactor. Such feedsidewards lead to chronomodulation, a phenomenon accounting for qualitatively as well as quantitatively different modulatory effects of the same drug or other stimulus. Controversies of long standing can thus be resolved and novel effects uncovered.

Adrenal Glands↗

Alsactide: ACTH-agonist for use in microdoses in brain-adrenal and other feedsidewards.

An increasing number of ACTH-related peptides have been isolated and/or chemically synthesized. In addition to the multiplicity of molecules, there is experimental evidence for multiple target cells and multiple receptors, and hence for different biological activities. The heptadecapeptide analogue alsactide (ACTH 1-17: Synchrodyn) has a C-terminal amide group (butylamide) and the substitution of beta-alanine for serine in position 1 and of lysine for arginine in position 17. These modifications account for enhanced biological activity and uniquely demonstrated chronopharmacological properties. In adult healthy men, the tailoring of dosage and timing of peptide administration was successful in a selective and transient stimulation of glucocorticoid secretion, without a change in the plasma concentrations of aldosterone and testosterone. The dose of 10 micrograms alsactide injected subcutaneously at awakening is proposed for clinical application with the aim of enhancing cortisol secretion in diurnally active subjects. It is noteworthy that injection of even much higher doses for several days at this particular circadian stage did not elicit detectable antibodies to the peptide in more than 200 patients. Restoring or reinforcing the circadian ordering of bioperiodicities correlated with the adrenocortical cycle can thus be achieved as a result of a time-specified therapy with an ACTH-agonist analogue. The results of studies in experimental animals and of preliminary trials in human beings have emphasized the value of alsactide as the first chronizer-peptide in clinical medicine. Its use in the dosage here proposed is expected to be beneficial for preventing deterioration of the circadian system in the elderly, for enhancing psycho-physical performances, and for gaining compliance with regard to chronic disease as well as tolerance to a number of potentially damaging xenobiotics.

Adrenal Glands↗

Antimicrobial agents as biological response modifiers (BRM) and chrono-immunomodulation: an emerging relationship.

Immune defense mechanisms play an essential protective role against infections caused by a wide array of pathogenic microorganisms. Although the growing number of the available antimicrobial agents has certainly improved the overall clinical outcome of such infections, antimicrobial therapy not rarely fails whenever the host's immune function is depressed. On the other hand, recently introduced therapeutic and diagnostic procedures (antineoplastic chemotherapy causing severe neutropenia and mucositis; organ transplantation requiring conditioning regimens; the widespread use of intravascular catheters and prosthetic devices; administration of adrenal corticosteroids and/or other immunosuppressive agents) have resulted in an unprecedented number of immunocompromised hosts. In addition, a variety of antibiotics have been found to display adverse effects on specific and non-specific immune functions, thus further impairing the already depressed immune system of the host. Antibiotic-mediated immunomodulation hence is explored with the introduction of a third-generation cephalosporin, namely cefodizime (CDZ), which has been shown to possess immunostimulating properties in preliminary in vitro and ex vivo studies as well as in a few experimental animal models. A chronoimmunopharmacological approach to CDZ-induced immunomodulation has been started by ourselves. The study, which is still in progress, includes patients with multiple myeloma (MM), selective IgA deficiency and chronic uremia, and matched healthy subjects. A number of immunological parameters are being assessed on blood samples drawn every 6h in the 24-h span prior to CDZ administration (a single 2 g daily dose i.v. for 6 days to the patients and for 4 days to healthy subjects), and in the 24h following the last CDZ injection. Healthy subjects and patients are randomly assigned to two groups, depending on whether they are given the antibiotic at 0800 or at 1800. Although a full evaluation of the results will be reported elsewhere, the group of MM now includes 24 patients. A circadian stage-dependent chronoimmunomodulating effect has been unequivocally shown for the monocytic chemotactic responsiveness to CDZ in MM. Immunostimulating 'side-effects' suggest that CDZ should possibly be regarded as a prototype antimicrobial agent for patients with impaired immune functions. Conceivably, a better knowledge of such properties will help synthesize new antibiotics with specific immunomodulating effects.

Adjuvants, Immunologic↗

Multifrequency rhythms of immunological functions.

Chrono-immunological functions are reviewed starting from the first studies on circadian variations in the count of circulating blood eosinophils to the most recent studies on lymphocyte subpopulation periodicities. Serum Ig levels, complement components, plaque forming cells, phagocytosis, autologous mixed lymphocyte reactions, have also been demonstrated to be circadian periodic. Transplant immunology is also known to show circadian and circa septan periodicities in the rejection of transplanted organs. Rhythms of susceptibility to a series of allergens and bronchial asthma symptoms characterize chronobiology in allergy. A periodic pattern is a common finding in the recurrence of the symptoms in rheumatoid arthritis. Finally, the beginnings of chrono-immunotherapy of experimental and human tumors are briefly reviewed. The conclusion that can be drawn from this short overview is that the demonstration of the periodicity in such a big number of variables in health and the modifications of the relevant parameters in disease, emphasize the importance of the predictable, since periodic, part of the variations that can be shown by the immunological findings.

Animals↗

Chronobiologic pattern discrimination of plasma hormones, notably DHEA-S and TSH, classifies an expansive personality.

Methods of chronobiologic pattern discrimination, a "monotest' involving the leave-one-out technique and a "maximin distance' algorithm for cluster analysis, along with stepwise discriminant analysis procedures and correlation techniques are used in the search for classifiers of personality. By these methods, chronoendocrine relations of an expansive personality are explored in data sampled around the clock in 4 seasons on 10 North American and 3 Japanese women. Of 12 plasma hormones determined in each season, DHEA-S shows a time-dependent relation to an expansive, egocentric personality assessed by an abbreviated version of the Minnesota Multiphasic Personality Inventory; time-dependent co-classifiers are TSH, LH, prolactin and cortisol. Cost-effective recommendations for sampling are thus proposed for further tests of endocrine factors classifying for an expansive personality and, perhaps, classifying also for any associated vulnerability or risk state.

Adolescent↗

Toward a chronoimmunomodulation by cefodizime in multiple myeloma and chronic uremia.

Nine healthy subjects, 19 patients with multiple myeloma (MM) and 21 patients with chronic uremia were given cefodizime (2 g i.v.) at 2 different timepoints either in the morning or in the evening for 5 to 7 consecutive days. The following immunological parameters were comparatively evaluated before and after cefodizime administration: rosette-forming cells (RFC%), T lymphocyte subpopulations, monocyte chemotaxis index (MCI) and granulocyte chemotaxis index (GCI). Independently of the time of drug administration, a circadian rhythm was clearly detected (90% CI) as regards RFC%, CD3, CD4, CD8, CD4/CD8 before and RFC%, CD3, CD4, CD8, GCI after therapy. In addition, in patients treated at 0800 cefodizime increased the MESOR of the MCI and, to a lesser extent, of the GCI. The chronoimmunomodulatory effects of cefodizime in patients with MM and chronic uremia are discussed.

Adjuvants, Immunologic↗

Rhythm scrambling: good, bad or indifferent?

The scrambling of rhythms, i.e. their mixing-up or throwing into disorder, on a variety of schedules of lighting and feeding, left the average overall life span of several groups of mice unaffected. One particularly scrambled schedule prolonged 10th-decile survival time. The phase-shifting of rhythms, in a mammalian simulation of shift-work schedules, need not be harmful and can be indifferent or even beneficial. Such findings have important implications for health, performance and safety in human shift-work by both sexes and for the choice of other schedules, such as those for drug treatments or exercise.

Animals↗

Chronosynergistic effects of lighting schedule-shift and cefodizime on plasmacytoma growth and host survival time.

Lighting regimen shifts can modify the effects of cefodizime, for the purpose of a chronoimmunomodulation. Two experiments were carried out on male and female LOU rats inoculated subcutaneously with plasmacytoma cells. Some rats were kept on their original LD12:12 regimen, whereas others, after tumor implantation, were subjected every second day to 6-h shifts, instituted, in alternation, as advance or delay. Daily treatment with cefodizime or placebo started when, overall, about 50% of the animals had developed a palpable tumor. A subgroup of animals contributed daily smears for the determination of the estrus cycle and further provided core temperature and activity data by telemetry. In Experiment I, the repeated shifting of the LD regimen was associated with survival time prolongation (p less than 0.05), irrespective of drug administration. Moreover, in those (female) rats repeatedly exposed to shifts of the lighting schedule, cefodizime was found to prolong survival time (p less than 0.05). The effects of cefodizime vs placebo on survival time were found to be circadian stage-dependent. In Experiment II, differing from Experiment I in the initial conditions before the institution of the shifts, cefodizime treatment was associated with a prolongation of survival time of the female rats kept on a fixed LD12:12 regimen. Both male and female rats again showed a circadian stage-dependence of the cefodizime effect. These results suggest that interactions between synchronizers of rhythms (such as shifts of the lighting regimen, the latter simulating the daily routine) and immunomodulating agents such as cefodizime may be optimized to improve treatment strategies against cancer and other diseases.

Animals↗

Experimental models for the study of chronoimmunomodulation (rhythms of the springtail Folsomia candida, Collembola: Isotomidae).

A third-generation cephalosporine, cefodizime, was tested in two experiments on the springtail, Folsomia candida, used as a model of infradian rhythmicity. Any effect on ecdysis (molt), oviposition and oviproduction was sought for 6, 20 or 60 ng of cefodizime administered with brewer's yeast every other day, as compared to controls given only the yeast. Results indicate that a 20-ng dose of cefodizime on alternate days may shorten an infradian period (of molt) in the springtail.

Adjuvants, Immunologic↗

Circadian rhythm of melatonin in the brain of the face fly, Musca autumnalis De Geer.

Melatonin was radioimmunoassayed in extracts from brains of Musca autumnalis De Geer, the face fly, obtained 4h apart during 24h in 3 series pools of over 2 dozen brains at each of 6 or 7 circadian times. A circadian rhythm in the data expressed as percent of mean was demonstrated by the population-mean cosinor method. Face flies thus offer themselves for studies of melatonin-mediated chronomodulation by feedsideward mechanisms.

Animals↗