Circannual versus seasonal variations of longitudinally sampled 25-hydroxycholecalciferol serum levels

Seasonal variations in human serum levels of 25-hydroxycholecalciferol (25OHD) have been largely documented in transverse studies of population. But seasonality is not per se a demonstration that 25OHD serum levels fluctuate along the course of year according to a waveform profile with a periodic rhythm. Because of this, we attempted to investigate the possible occurrence of a circannual rhythm for 25OHD serum levels in a longitudinal design, by fitting a 365.25-day cosine curve to temporal biodata recorded in 10 clinically healthy subjects, monthly sampled for RIA determinations of 25OHD. Cosinor procedure statistically validated the occurrence of a circannual rhythm for 25OHD serum concentrations at a highly significant level of probability (P = 0.0015) for null hypothesis amplitude = 0. With 95% of probability, amplitude ranges from 5.0 to 16.5 ng/ml (mean value of oscillation = 10 ng/ml), while acrophase is temporally located from September 14 to December 3 (mean timing = October 21). Yearly, mean values for 25OHD serum concentrations is of 40.3 +/- 5.4 ng/ml as quantified by the line which transversely divides the cosine curve interpolating original biodata. By calculating the band of a complete 12 months variability which includes 90% of the distribution with 90% confidence limits, the circannual chronodesm of 25OHD serum levels has been obtained. Such a chronodesmic sinusoid has been compared to the circannual chronogram. By this comparison, a dissociation between the crest (October) and the peak (August) has been detected. The finding suggests that seasonal variations are superimposed to the circannual rhythm. Seasonal but also circannual changes, thus, characterize the yearly variability of 25OHD serum levels in man.     

The circadian rhythm of serum angiotensin-converting enzyme is disrupted in ascitic liver cirrhosis

An increase in morning fasting levels of plasma (P) renin activity (RA), aldosterone (A) and serum (S) angiotensin-converting enzyme (ACE) activity has been demonstrated in ascitic cirrhotic patients (ACP). Since both PRA and PA change biorhythmically in their time structure, the relationship of SACE activity with the components of the renin-angiotensin-aldosterone system (RAAS) was investigated in clinically healthy subjects (CHS) and ACP. Time-qualified data were chronobiologically analysed by means of the cosinor procedure to resolve and quantify the circadian rhythm (CR). The 24-hour mean levels of PRA, PA and SACE activity were found to be elevated in ACP as compared to CHS. The temporal variability of these analytes was found to be of periodic type along the 24-hour span in CHS, but not in ACP. The well-organized cyclicity in CHS is of relevant interest. PRA and PA cycles were found to phase in a clear antiparallelism with the SACE activity CR. The phase opposition may be, speculatively, related to the physiologic nature of ACE, whose activity is devoted to generate angiotensin II. The disappearance of SACE activity CR in ACP is in accordance with the abolition of PRA and PA cyclicity and suggests a role of liver in regulating the periodic time function of the RAAS and related components.