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Biomedical subjects

F Portaluppi

Publications and source records attributed to F Portaluppi.

At least 55 records · Page 3Linked to original sources

Dissociated 24-hour patterns of somatotropin and prolactin in fatal familial insomnia.

To assess the changes in the 24-hour profiles of serum somatotropin and prolactin levels during total disruption of the sleep/wake cycle sustained over several months, we studied 2 subjects affected by fatal familial insomnia, a rare disease characterized by selective thalamic degeneration that causes chronic sleep loss. Under standardized conditions and polysomnographic control, the patients underwent repeated 24-hour study sessions covering the entire clinical course of the disease. Hormones were assayed at 30-min intervals. Four healthy volunteers were used as controls. A sleep/wake cycle was always absent in fatal familial insomnia. Serum somatotropin and prolactin concentrations never exceeded the normal range of variation. The nocturnal elevation of somatotropin disappeared simultaneously with sleep loss, whereas a significant 24-hour component of variations in serum prolactin levels was present for months after total disruption of the sleep/wake cycle, with normally placed nocturnal acrophases. Complete obliteration of the 24-hour component was achieved for prolactin only in the advanced stages, through a progressive decrease in 24-hour amplitude of variation. Selective and progressive degeneration of the mediodorsal and anterior ventral nuclei of the thalamus causes an early obliteration of the 24-hour rhythm of somatotropin and a later disappearance of circadian prolactin rhythmicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian variation in the occurrence of paroxysmal supraventricular tachycardia in clinically healthy subjects.

The purpose of this study was to assess prospectively the circadian distribution of spontaneous paroxysmal supraventricular tachycardia (PSVT) in drug-free subjects with no previous history or symptoms and signs of concomitant heart or lung disease. Of 112,424 presumably diurnally active patients admitted to the Emergency Department of a city hospital during a 2-year period (1990-1991), a total of 185 patients were screened with these characteristics. Time of symptom onset was exactly recordable in 177 (75 men and 102 women). Analysis of variance documented a higher incidence in the morning-afternoon hours. Cosinor analysis, although not a perfect method for the time series analysis, verified circadian rhythmicity with afternoon peak times. Our findings suggest that a circadian pattern in intrinsic electrical instability of the heart conduction system exists irrespective of the circadian fluctuations in the pathophysiologic mechanisms of the cardiovascular or lung diseases most frequently associated with PSVT itself.

Adult↗

Diurnal blood pressure variation and hormonal correlates in fatal familial insomnia.

Fatal familial insomnia is a prion disease in which a selective thalamic degeneration leads to total sleep deprivation, hypertension, dysautonomia, adrenal overactivity, and impaired motor functions. With patients under continuous recumbency and polysomnographic control, we assessed the changes in the 24-hour patterns of blood pressure, heart rate, plasma catecholamines, corticotropin, and serum cortisol in three patients at different stages of the disease. Six healthy volunteers were used as control subjects. A dominant 24-hour component was detected at rhythm analysis of all variables, both in patients and control subjects. In the patients, the amplitudes gradually decreased as the disease progressed, leading to the obliteration of any significant dirunal variation only in the preterminal stage. A shift in phase corresponded to the loss of the nocturnal fall in blood pressure in an early stage of the disease, when nocturnal bradycardia was still preserved. Plasma cortisol was high and became increasingly elevated, whereas corticotropin remained within normal levels; abnormal nocturnal peaks appeared in their circadian patterns. The disrupted patterns of cortisol and blood pressure preceded the development of hypertension and severe dysautonomia, which in turn were paralleled by increasing catecholamine and heart rate levels. Our data demonstrate that in patients with fatal familial insomnia the changes detectable in the rhythmic component of diurnal blood pressure variability result in a pattern of secondary hypertension. Disturbances in thalamic, pituitary-adrenal, and autonomic functions seem to be involved in mediating these changes.

Adrenocorticotropic Hormone↗

Evidence that enhancement of cholinergic tone increases basal plasma levels of calcitonin gene-related peptide in normal man.

To investigate the influence of the cholinergic system on the modulation of the circulating levels of calcitonin gene-related peptide (CGRP) under basal conditions in normal man, the effects of an acetylcholinesterase inhibitor, pyridostigmine bromide, and a muscarinic receptor blocker, pirenzepine, were studied in 16 normal subjects (8 females and 8 males). Pyridostigmine (120 mg, orally) induced a significant (P < 0.01) rise in basal plasma CGRP, while it reduced systolic and diastolic blood pressure. In all subjects, pirenzepine (0.6 mg/kg, i.v. bolus) was unable to modify the basal CGRP level. In conclusion, a pharmacologically induced enhancement of cholinergic tone resulted in an increase in CGRP, whereas muscarinic receptor blockade had no effect on CGRP levels or blood pressure. Therefore, the cholinergic system seems to be involved in the control of CGRP release in man, acting as a positive modulator. However, the available data do not indicate that there is a tonic cholinergic tone responsible for CGRP secretion under physiological conditions.

Adult↗

Progressive disruption of the circadian rhythm of melatonin in fatal familial insomnia.

Fatal familial insomnia (FFI) is a disease characterized by loss of sleep activity due to selective thalamic degeneration. To assess the secretory pattern of melatonin (MT) in FFI, we studied two cases of overt disease under standardized conditions and polysomnographic control. Each patient underwent repeated 24-h study sessions, and MT was assayed at 30-min intervals. Six healthy volunteers were used as controls. Slow wave sleep was never recorded, whereas occasional episodes of enacted dreaming accompanied by rapid ocular movements and complex muscular activities were documented, with no detectable rhythm. Plasma MT concentrations gradually decreased as the disease progressed. A significant circadian rhythm was detected in the earlier recordings, with decreasing amplitudes with disease progression. Complete rhythm obliteration was achieved in the most advanced stage. Normally placed nocturnal acrophases were detected in the earlier stages, but then a shift toward the daytime hours was observed. Thalamic lesions of FFI appear to determine a progressive disruption of the sleep/wake cycle accompanied by decreased circulating levels of MT, with progressive alterations in the circadian rhythm of this hormone. On the other hand, decreased secretion of MT may contribute to the sleep disturbances of FFI.

Adult↗

Circadian variation in the occurrence of fatal pulmonary embolism. Differences depending on sex and age.

Published studies have indicated a circadian variation in the occurrence of several acute cardiovascular events, e.g., myocardial ischemia, myocardial infarction, sudden cardiac death and cardiac arrest. The aim of this study was to determine if there is a circadian variation in the occurrence of fatal pulmonary embolism, and to evaluate possible differences in the temporal pattern in relation to sex and age. 230 cases of fatal pulmonary embolism (74 out-of-hospital and 156 hospitalized) observed in a general hospital over a 9-year period were considered. The total sample was stratified both by sex and into four groups by age including, respectively, subjects aged less than 60 years (group A), between 60 and 69 (group B), between 70 and 79 (group C) and 80 years and over (group D). The data were analyzed by the single cosinor method. A significant morning pattern was found for the total population (p = 0.011), females (p = 0.033), and age subgroups C and D (p = 0.015 and 0.008), with respective acrophases at 11.57, 11.23, 10.54 and 13.24. A morning pattern in the onset of fatal pulmonary embolism is confirmed for the total population, although sex and age seem also to play an important role.

Age Factors↗

Effect of dermorphin on behavior and hippocampal electrical activity in rabbits.

Dermorphin, a naturally occurring heptapeptide that selectively binds to mu-opioid receptors, was injected intravenously 0.4 mg/kg in male rabbits. Eight days before injection the spontaneous behavior of the animals was observed in a neutral environment in the absence of external stimuli. At the same time, hippocampal EEG was recorded by telemetry. After dermorphin injection, the same experimental procedure was repeated. Behavior showed a strong increase in quiet immobility and a concomitant reduction in voluntary activities as compared to control periods. Treatment did not affect either the pattern or the frequency of hippocampal electrical activity.

Analgesics, Opioid↗

Effect of deltorphin on behavior and hippocampal electrical activity in rabbits.

To clarify the role of delta-opioid receptors on modulation of hippocampal electrical activity and behavior, deltorphin (DT), a naturally occurring heptapeptide that selectively binds to delta-opioid receptors, was intravenously (IV) administered to rabbits. For this purpose, at 8-day intervals, the effects of IV administration of normal saline and IV infusion of synthetic DT (1 mg/kg b.wt. for 2 min) on the spontaneous behavior in neutral environment, both in absence of any external stimulus and after the introduction of a stuffed predator, were examined in seven adult male rabbits, on separate and successive occasions. During each session of experimental procedure, hippocampal EEG was also recorded by telemetry. Behavioral activity showed an increase in alert and reactive immobility after the peptide injection in comparison with that observed during control period (saline administration). Under DT treatment the frequency of hippocampal electrical activity decreased, and a reduction in rhythmicity of electrical pattern was also observed in presence of stressful stimulus. These findings show that DT may affect neural and behavioral elements related to the control of attentional and emotional processes, suggesting a modulating role of delta-opioid receptors.

Animals↗

Modulatory effect of the renin-angiotensin system on the plasma levels of calcitonin gene-related peptide in normal man.

Calcitonin gene-related peptide (CGRP) has positive chronotropic and inotropic effects in animals and humans, and produces the most potent vasodilation known for an endogenous peptide. Yet, a physiological role for CGRP in the regulation of vascular tone and blood pressure has not been demonstrated. We studied the effects of 1) assumption of the upright position and 2) iv infusion of angiotensin-II (sequential doses of 8, 16, and 32 ng/kg.min, each dose for 20 min) in eight normal subjects (four men). Serial venous blood samples were taken to determine the plasma CGRP, epinephrine, norepinephrine, and aldosterone levels and PRA. Blood pressure and heart rate were continuously monitored at the finger with a Finapres 2300 instrument. After assumption of the upright posture, a quick rise in plasma CGRP levels was observed together with the expected increases in plasma norepinephrine and aldosterone and PRA. A transient increment was also observed for diastolic blood pressure and heart rate. Angiotensin-II infusion caused dose-dependent increases in plasma CGRP and aldosterone concentrations, already significant at the lowest infusion rate and parallel with the blood pressure rise. Plasma catecholamines significantly increased only at higher infusion rates. Our data demonstrate that modifications of plasma CGRP concentrations are part of the normal response to postural and vasomotor changes. These findings suggest a physiological role for CGRP in regulation of the peripheral vascular tone and possibly blood pressure in man.

Adult↗

Stress-induced activation of sympathetic nervous system is attenuated by the delta-opioid receptor agonist deltorphin in healthy man.

To examine the role of delta-opioid receptors in the regulation of the sympathoadrenomedullary system, the effects of the highly selective delta-opioid receptor agonist deltorphin (DT) on plasma catecholamine responses to insulin-induced hypoglycemia (IIH) and cold pressor test (CPT) have been investigated in normal subjects in two separate studies. DT failed to modify basal plasma levels of both norepinephrine (NE) and epinephrine (E). DT completely suppressed the IIH-evoked elevation of NE, whereas it attenuated the E response by 20%, with the DT-induced decrease in E release failing to achieve statistical significance. DT completely blocked the release of both NE and E elicited by CPT. We conclude that specific delta-opioid receptor stimulation exerts an inhibitory effect on NE release induced by both IIH and CPT. These findings provide evidence that delta-opioid receptors may influence the autonomic sympathetic reactivity.

Adult↗

Atrial natriuretic peptide and circadian blood pressure regulation: clues from a chronobiological approach.

A critical review of the data available in the literature today permits a better understanding of the multiple actions of atrial natriuretic peptide (ANP) on the cardiovascular system. Moreover, the results of chronobiological studies suggest a role for this peptide in the determination of the circadian rhythm of blood pressure (BP). ANP can affect BP by several mechanisms, including modification of renal function and vascular tone, counteraction of the renin-angiotensin-aldosterone system, and action on brain regulatory sites. A series of interrelated events may follow from very small changes in the plasma levels of ANP. The endpoints are blood volume and BP reduction, but they are rapidly offset (mainly by reactive sympathetic activation) as soon as blood volume or pressure is threatened. The circadian rhythms of BP and ANP are antiphasic under normal conditions and in essential hypertension. The loss in the nocturnal decrease of BP is accompanied by a comparable loss in the nocturnal surge of ANP in hypertensive renal failure and hypotensive heart failure. In the latter condition, BP and ANP variabilities correlate significantly both before and after therapy-induced functional recovery, independently of the mean BP levels. Autonomic function modulates the secretion of ANP, which seems more apt to determine only transient changes in BP levels, as suggested by the short half-life of the peptide and the buffering role of its clearance receptors. There is now sufficient evidence that ANP contributes to short-term control over BP and electrolyte balance, in contrast and in opposition to the renin-angiotensin-aldosterone system, which is involved primarily in long-term BP control. By interfering with other well-established neurohormonal factors, ANP appears to be an additional modulator of the circadian rhythm of BP.

Animals↗

Differences in blood pressure regulation of congestive heart failure, before and after treatment, correlate with changes in the circulating pattern of atrial natriuretic peptide.

The mechanisms underlying altered BP regulation in congestive heart failure are unknown. This study examines the possibility that differences in circadian blood pressure (BP) regulation between the normal and the failing heart correlate with changes in the circulating pattern of atrial natriuretic peptide (ANP). Twelve normotensive patients with coronary artery disease were studied over two separate 24-h periods, the first during acute exacerbation of congestive heart failure (radionuclide-determined ejection fraction at rest was less than 30%) and the second after therapy-induced functional recovery (ejection fraction was more than 40%). BP monitoring at 10-min intervals and intra-atrial blood samples for ANP assays at hourly intervals were obtained. Significant correlation between ejection fraction and the indexes of circadian BP variability (standard deviation of the 24-h pressure mean and day-night pressure difference) were found both before and after treatment. Ejection fraction was independent of the BP means (24-h, daytime and night-time). BP variability, 24-h mean and daytime mean were higher after treatment. ANP means were lower after treatment, whereas ANP variability was higher. The indexes of BP and ANP variability correlated both before and after treatment, whereas the BP and the ANP means were independent. These findings demonstrate that differences in BP regulation of CHF before and after effective treatment correlate with changes in the circulating pattern of ANP. We speculate that by modulating ANP release, the heart could be actively involved in BP regulation as part of the compensatory mechanisms aimed at protecting against circulatory overload.

Aged↗

Circadian rhythm of calcitonin gene-related peptide in uncomplicated essential hypertension.

OBJECTIVE: To assess the existence of an altered circulating pattern of calcitonin gene-related peptide (CGRP) in hypertension. DESIGN: The 24 h variation in plasma CGRP was measured and compared in 10 patients affected by uncomplicated essential hypertension and in nine age- and sex-matched healthy volunteers. The diurnal variations in blood pressure, atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma aldosterone and plasma cortisol were also assessed. METHODS: Recumbency studies were performed under standardized, drug-free conditions beginning at 0800 h. Venous samples were drawn every 4 h for 24 h and hormone levels were assessed with specific radioimmunoassays. The blood pressure was measured every 15 min with a SpaceLabs 90207 monitor. RESULTS: The mean 24-h plasma CGRP concentrations were significantly lower in the hypertensive group than in the control group. In both groups a circadian rhythm was present with the same pattern, but at a lower level in hypertension. A temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the elevations of ANP, PRA, and plasma aldosterone and cortisol was apparent in both groups. The nocturnal rise in the CGRP and ANP concentrations coincided with the blood pressure and the heart rate falls. CONCLUSIONS: Our data show that CGRP is lower than normal but maintains its circadian variability and its relationship with the diurnal variations in blood pressure and other hormones known to be active on the cardiovascular system.

Adult↗

delta-Opioid receptors and the secretion of growth hormone in man: effect of opioid delta-receptor agonist deltorphin on GH responses to GH-releasing hormone and insulin-induced hypoglycemia.

To investigate the role of delta-opioid receptors in the modulation of growth hormone (GH) secretion, we compared in normal subjects the effect of the highly selective delta-opioid receptor agonist Deltorphin (DT) on the GH secretion responses to pituitary (GH-releasing hormone, GHRH)- and hypothalamic (insulin-induced hypoglycemia, IIH)-mediated stimuli. DT blunted the GH response to IIH, whereas it had no effect on the GH response to GHRH. It is concluded that in man DT-induced activation of delta-opioid receptors exerts an inhibitory action on hypoglycemia-stimulated GH secretion. Based on the lack of an effect of DT on the GH response to GHRH, we suggest that DT may modulate the secretion of GH through suprapituitary mechanisms.

Adult↗

Loss of nocturnal increase in plasma concentration of atrial natriuretic peptide in hypertensive chronic renal failure.

Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24-hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/- 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP.

Adult↗

Effect of deltorphin on pituitary-adrenal response to insulin-induced hypoglycemia and ovine corticotropin-releasing hormone in healthy man.

To determine the role of delta-opioid receptors in the modulation of hypothalamic-pituitary-adrenal activity, we studied in normal subjects the effect of the highly selective delta-opioid receptor agonist deltorphin (DT) on the secretion of ACTH, cortisol, and arginine vasopressin in response to insulin-induced hypoglycemia. In an attempt to clarify the site of opiate modulation of ACTH secretion, we also studied in normal subjects the effect of DT on the ACTH response to ovine CRH-41. DT blunted the ACTH, cortisol, and arginine vasopressin responses to insulin-induced hypoglycemia, whereas it had no effect on the ACTH and cortisol responses to CRH. We conclude that DT-induced activation of delta-opioid receptors exerts an inhibitory influence on hypoglycemia-stimulated ACTH secretion. Based on the lack of an effect of DT on the ACTH response to CRH, we postulate that DT may modulate the secretion of ACTH through suprapituitary mechanisms.

Adrenocorticotropic Hormone↗