Piernatale Lucia

Circadian Rhythms of Plasma Renin Activity and Aldosterone: Changes Related to Age, Sex, Recumbency and Sodium Restriction. Chronobiologic Specification for Reference Values

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

Twenty-four-hour pattern of atrial natriuretic peptide in heart transplantation: evidence for lack of circadian rhythm. Temporal inter-relationships with plasma renin activity, aldosterone and cortisol

We have investigated the circadian rhythm of plasma atrial natriuretic peptide in 13 stable output heart transplanted patients, all without evidence of histological rejection and cardiac impairment, following antirejection therapy with Cyclosporine, Azathioprine and Prednisone. The 24-h pattern of plasma renin activity, plasma aldosterone and plasma cortisol has been studied as well. All the investigated variables were assayed six times over the 24-h span. The circadian time-qualified data were analyzed by ANOVA and Cosinor method. The 24-h mean levels of atrial natriuretic peptide, plasma renin activity and plasma aldosterone are significantly increased, while the concentrations of plasma cortisol are reduced in the heart transplanted recipients. ANOVA detected a significant within-day variability of all these humoral variables only in healthy subjects. A statistically significant circadian rhythm was validated by Cosinor procedure for all the investigated molecules in healthy subjects but not in heart transplanted patients. In our opinion, the increase of atrial natriuretic peptide is a counterregulatory mechanism aimed to compensate the cyclosporine-mediated activation of the renin-angiotensin-aldosterone system. The disappearance of the plasma renin activity, aldosterone and atrial natriuretic peptide circadian rhythm can be ascribed to the constant activation of the renin-angiotensin-aldosterone system. The hypocortisolism is due, in our opinion, both to glucocorticoid therapy and increase of plasma ANP concentration.

Circadian Rhythm of Cardiac Output, Peripheral Vascular Resistance, and Related Variables by a Beat-to-Beat Monitoring

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomanometric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.

Vasoactive intestinal peptide fluctuates in human blood with a circadian rhythm

The vasoactive intestinal peptide (VIP) may be radioimmunoassayed in systemic venous blood. The plasma concentrations of VIP were investigated in human blood according to a chronobiological design. The study documented a circadian rhythmicity in time-qualified concentrations of VIP. Accordingly, VIP may be ascribed to biological variables characterized by periodicity in their physiological attributes. The rhythmic physiology of VIP is, however, highly disturbed in its tonic and phasic properties during senescence.

MULTIPLE CATECHOLAMINE-SECRETING PARAGANGLIOMAS: DIAGNOSIS AFTER HEMORRHAGIC STROKE IN A YOUNG WOMAN

OBJECTIVE To describe a case of multiple catecholamine-secreting paragangliomas, with a hemorrhagic stroke as the main clinical manifestation. METHODS We present a case report with clinical, laboratory, histologic, and genetic details. RESULTS A 23-year-old woman with a history of hypertension treated with orally administered medications presented to our emergency department because of sudden onset of hemiplegia of the left side of the body. A computed tomographic scan of the brain showed a right frontoparietal hematoma, and her blood pressure was 185/115 mm Hg. She was admitted to the Department of Neurosurgery, and an external drain was inserted to evacuate the hematoma. She was then referred to the Department of Clinical Sciences, where a search for possible secondary causes of hypertension was undertaken. Substantially elevated urinary levels of vanillylmandelic acid and metanephrines were found, and a pheochromocytoma was suspected. Abdominal computed tomographic scans revealed a large retroperitoneal mass (3.6 by 4 cm) and similar smaller lesions in the right adrenal gland, between the aorta and the vena cava, and in the left paraaortic area. Iodine I 123 metaiodobenzylguanidine scintigraphy showed high uptake in those same areas, consistent with the diagnosis of multiple catecholamine-secreting paragangliomas. After adequate control of the patients hypertension was achieved with an alpha1-adrenergic receptor blocker, a Ca2+ antagonist, and a beta-adrenergic blocking agent, the tumors were excised in the Department of Surgery. The histopathologic findings confirmed the diagnosis of multiple paragangliomas. The genetic analysis demonstrated an exon 4 mutation in codon 109 (CAA>TAA, Gln>Stop) of the SDHD gene. CONCLUSION Although cerebral hemorrhage is an unusual complication of pheochromocytomas or paragangliomas, early recognition of the characteristic symptoms of headache, palpitations, and diaphoresis in a patient with hypertension and prompt appropriate intervention can minimize the morbidity associated with such tumors and prevent a potentially fatal outcome.

Vasoactive intestinal peptide (VIP): a new neuroendocrine marker of clinical progression in chronic heart failure?

objective  Vasoactive intestinal peptide (VIP) is a powerful vasodilatory neuropeptide with positive inotropic and chronotropic properties. The aim of the study was to investigate the pathophysiological role of VIP in heart failure.

Lack of circadian rhythm of plasma concentrations of vasoactive intestinal peptide in patients with orthotopic heart transplants.

OBJECTIVE--To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. PATIENTS AND METHODS--13 patients with orthotopic heart transplants were studied 12-53 months (mean 31.8 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Students t test for unpaired data and Binghams test for cosinor-derived parameters were used for statistical comparisons. RESULTS--Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants. DISCUSSION--The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural function and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be further investigated.

Increased serum aldosterone in diabetic pregnancy

SummarySerum levels of aldosterone and cortisol were measured by radioimmunoassay in 15 patients with gestational diabetes, in 18 patients with Type 1 (insulin-dependent) diabetes, in 36 pregnant control women and in 10 non-pregnant control women. All subjects, on habitual sodium and potassium intake, were sampled in a supine position at 09.00 hours. Pregnant women were examined twice, during gestational week 32–34 and at delivery. Serum levels of aldosterone and cortisol were also measured in the umbilical cord blood of newborn babies of these diabetic and non-diabetic mothers. Serum levels of aldosterone in both gestational and Type 1 pregnant diabetic women were found to be consistently above the reference values of non-diabetic pregnant women. Abnormal serum levels of aldosterone were also observed in newborn infants of diabetic mothers. In contrast, serum levels of cortisol were not increased.

The relevance of continuous blood pressure monitoring in examining the relationship of memory efficiency with blood pressure characteristics

The study of the relationship between hypertension and cognitive decline is characterized by various difficulties of realization and, as a consequence, by incongruent results. One of the reasons for these difficulties may be explained by the occasional method of measurement of blood pressure (once a day). This study presents the results obtained in 27 normotensive and mild hypertensive subjects of both sexes (ages between 20 and 77 years) with a continuous blood pressure monitoring for 24 h. A noninvasive sphygmomanometric technique was used employing a portable recorder programmed to take a measure every 30 min. Both objective and subjective measures of memory, measures of attention efficiency, and IQ were correlated to the blood pressure measures. Continuous monitoring data of blood pressure were analyzed according to a model that included a macroscopic descriptive analysis, a microscopic rhythmometric analysis, and a microscopic integrative analyses where the effects of the interaction between level and duration of excess and the time of the day when the excess eventually appeared were considered. Results evidenced no differences in cognitive efficiency between those subjects identified with the traditional occasional measurement of blood pressure as hypertensives of mild severity and the normal subjects. Cognitive efficiency of our subjects was found correlated, independently from the clinical diagnosis, with the time of peak and with the duration of excess of their blood pressure when the results of the analyses on the continuous monitoring of blood pressure were considered.

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.