Chronobiologia最新文献

Thyroid-stimulating hormone (TSH) regulates thyroid growth and differentiated function by binding to the TSH-receptor (TSH-R). In Graves' disease, hyperthyroidism and goiter growth are thought to be mediated by prolonged, continued activation of the TSH-R by TSH receptor-stimulating antibodies (TSAb). However, continuous experimental stimulation of the TSH-R with TSH or TSAb leads to a desensitization of the thyrocyte with a decrease of thyroid function in vitro and in vivo. In order to clarify this discrepancy we determined serum levels of TSH-binding-inhibiting immunoglobulins (TBII) in 10 patients with GD every 10 minutes over 6h (patients 1 to 5, group A) and over 24h (patients 6 to 10, group B) using a commercially available radio ligand receptor assay (TRAK, Henning Berlin, FRG). Visual and computer analysis revealed some variation of TBII serum levels but no obvious pattern indicative of circadian variation nor major secretory peaks could be distinguished. Variation of TBII serum levels were within or only slightly above intraassay CV. Data were tested in order to decide whether the observed fluctuations are of chaotic (deterministic) or of stochastic (random) origin. In none of these tests did we find evidence for chaos in the data suggesting that the observed fluctuations reflect other sources of noise such as sampling errors or intraassay variation. We conclude that in Graves' disease, patients are rendered hyperthyroid by continued, non-pulsatile and non-chaotic binding of stimulatory antibodies to the TSH binding site of the TSH-R.

Changes in central neurotransmission and in hypothalamo-pituitary function occur in both ethanol (ETOH) intake and withdrawal. Melatonin (MLT) secretion is regulated by the noradrenergic system, which is activated upon ETOH withdrawal. Experimental evidence exist that pineal gland may have a role in ETOH intake and preference in rats. Twenty-four hour urinary excretion of MLT was found to be increased during ETOH intake in chronic alcoholics. In this study we have determined 24h plasma levels of MLT and cortisol in 8 chronic alcoholic males hospitalized for a detoxication program and in 8 healthy controls. The study was performed just after admission, on the first day of ETOH withdrawal and after 14 days of controlled abstinence. Circadian periodicity has been evaluated by the cosinor method. The initial determinations corresponded to the acute withdrawal phase. Twenty-four hour plasma MLT mean levels on acute withdrawal were higher than after 14 days abstinence and than those found in controls. Large interindividual differences prevented the detection of statistical significance. The cosinor analysis disclosed the loss of circadian periodicity in the acute withdrawal. Significant 24h periodicity was restored after 14 days abstinence. Cortisol levels were significantly higher than those found on day 14 and in healthy controls. Twenty-four hour periodicity was maintained in both alcoholics series. A delay in cortisol acrophase occurred in acute withdrawal. The effects of Corticotropin Releasing Hormone infusion on cortisol secretion were significantly enhanced in the acute withdrawal phase in comparison with those occurring when patients were retested and with healthy controls.

Increasing evidence indicates that the application of stressor paradigms in experimental animals affects tumor incidence and progression. However, a high heterogeneity appears both for the animal-tumor system used and for the characteristics of the stressor employed. A high variability was observed also with the application of rotational stress, a carefully and widely characterized mild psychological stressor, to mice bearing Lewis lung carcinoma. The aim of this work has been therefore to examine the possible seasonal dependency of the effects of experimental stressors (rotational stress, forced immobilization and electric foot shock) on spontaneous lung metastasis formation in mice bearing Lewis lung carcinoma. The possible participation of pineal gland and of melatonin have also been examined including in the experimental protocol the measurement of melatonin urinary excretion. The stressor paradigms used significantly increased metastasis weight in spring, in comparison with non-stressed animals. When examined in winter, rotational stress and foot shock significantly decreased metastasis formation, in comparison with non-stressed mice. The effects of forced immobilization were not season-dependent. The melatonin urinary excretion has been measured in relation to the seasonal effects of rotational stress. Nocturnal melatonin excretion is markedly increased by rotational stress in spring and is remarkably decreased in winter. These variations in endogenous melatonin levels caused by rotational stress appear to directly correlate with the effects of the stressor or metastasis. These results lend support to the view that the mechanisms underlying the tumor enhancing action of stressors involve the psychoneuroendocrine network, and indicate the relevance of chronobiology in experimental cancer research and neuro-immuno-modulation.

Background: Results from unpublished data on the incidence of adverse vascular events and from several published studies are reevaluated chronobiologically.

Methods and results: Cosinor methods indicate 1. a circadian variation in the incidence of paroxysmal supraventricular tachycardia (PST), of broadly classified ventricular arrhythmia (VAr), and of atrial fibrillation (AF); 2. a statistically significant difference in the timing of the circadian rhythm of PST and VAr versus that of AF; and 3. a further difference in the timing of these rhythms from that in the incidence of myocardial infarctions (MI). Electrocardiographic records for spans longer than 24h show the extent of day-to-day variability in circadian characteristics of the given patient and indicate the presence of even lower-frequency components, notably along the scale of a week, that may underlie weekly and half-weekly patterns of morbidity and mortality.

Conclusion: Beyond alterations in the about 1-Hz periodicity of the heart, predictable changes along the scales of the day and the week may constitute a clue to the etiopathology of a given condition and provide a basis for treatment timing. The assessment of unfavorable changes in the lower frequency components may provide a lead time long enough to prompt the institution of preventive, rather than curative, intervention.

Suprachiasmatic nuclei (SCN) contain a circadian oscillator that is normally synchronized by the light/dark cycle. Embryonic SCN grafted into the brain of an SCN-lesioned arrhythmic host define the period of the restored circadian locomotor rhythm. Gene expression of immediate-early genes, such as c-fos and jun-B, in the ventrolateral SCN is associated with circadian synchronization by light pulses and subjected to circadian control. Vasopressin and somatostatin gene expression in dorsomedial SCN show distinct circadian rhythms with higher peptide levels occurring during the day. It is currently unknown whether the circadian oscillator in SCN resides in a single cell or is a property of cellular network. Briefly presented are some model views about the circadian oscillator in SCN and the molecular and cellular approaches to the circadian function of the nucleus.

The time of maturation of the circadian periodicity in humans has been differently considered. The present study aimed to investigate the existence of rhythmic variations in the body temperature of healthy full-term infants just after birth. We studied 19 healthy term newborns, nursed in their cribs at environment temperature of 25 degrees C and moderately dimmed artificial lighting during the night. Continuous recording of body temperature was performed with a solid memory recorder (Fiamarker) connected to a disposable rectal probe, during the first three days of life. Data were analyzed by means of single and mean cosinor methods and spectral analysis. All the newborns, except two, demonstrated a statistically significant circadian periodicity of temperature (p < .001). Acrophases were distributed along the 24h since the synchronization to environment was not yet completed. A clear ultradian fluctuation of body temperature was observed in all 19 newborns with an unexpected fall of temperature every three-four hours. Our data show that the maturation of the circadian system is probably almost complete in newborns, but the adjustment to the new environment can be expected in the subsequent weeks of life.