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Biomedical subjects

G Trasforini

Publications and source records attributed to G Trasforini.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Stimulatory effect of angiotensin II upon luteinizing hormone release normal women.

In this study we investigated the effect of intravenous infusion of angiotensin II (AII) on plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in fertile healthy women examined both in the middle follicular phase (MFP) and in the middle luteal phase (MLP). As expected, AII induced a significant increase in blood pressure and plasma aldosterone concentration. In MFP, plasma FSH and LH levels did not show any significant change after AII infusion, if compared to both saline and preinfusion basal values. In MLP, AII significantly increased plasma LH (p less than 0.02 vs. baseline values and p less than 0.01 vs. placebo values), but not plasma FSH. The area under the curve during AII infusion resulted significantly higher than during placebo infusion (p less than 0.001). Therefore, these data demonstrate that peripherally injected AII at pressive dose produces an increase in plasma LH levels in normal women on luteal phase when the circulating concentrations of both estradiol and progesterone are high. The study suggests that AII may have a stimulatory role in the regulation of LH secretion, but this role is closely related to the gonadal steroid plasma levels.

Adult↗

Somatostatin reduces 3H-thymidine incorporation and c-myc, but not thyroglobulin ribonucleic acid levels in human thyroid follicular cells in vitro.

The action of somatostatin (SRIH) on 3H-thymidine (thy) incorporation and on c-myc and thyroglobulin RNA levels in a suspension of follicles from normal and goitrous human thyroid was examined. SRIH, at 10(-7) M concentration, inhibited basal thy incorporation (maximally by 4 h lasting for up 24 h), which effect was greater in goiter than in normal thyroid and was also detected in growing adherent epithelial cells. Moreover, in a follicle suspension SRIH prevented TSH-stimulated thy incorporation, both in normal and in goitrous thyroid. Basal expression of c-myc RNA was not affected by SRIH in either tissue, whereas the TSH-stimulated c-myc RNA level was significantly reduced in goiter. No effect of SRIH was observed on basal or TSH-stimulated thyroglobulin RNA levels. SRIH did not alter basal cAMP concentrations in normal or goitrous follicles, but it significantly reduced TSH-stimulated cAMP accumulation both in normal thyroid and in goiter. Overall, our data indicate a direct inhibitory action of SRIH on growth, but not on differentiation, of human thyroid, probably by a mechanism not entirely cAMP dependent.

Cells, Cultured↗

Circadian profile of plasma calcitonin gene-related peptide in healthy man.

Calcitonin gene-related peptide (CGRP) is known to exert potent cardiovascular effects and is presumed to participate in the neural control of circulation and blood flow. It has been assayed in many physiological and disease conditions, yet virtually nothing is known of the normal fluctuations in its circulating levels. We have studied the variability throughout a 24-h period of plasma concentrations of CGRP in eight recumbent healthy volunteers (four men and four women, 25-37 yr old), after careful standardization of their daily diet and routine schedules. A correlation with the circadian rhythms of blood pressure (BP), heart rate (HR), and plasma aldosterone (PA), PRA, plasma cortisol (PC), and atrial natriuretic peptide (ANP) was also made. Plasma CGRP concentrations ranged from a mean peak value of 18.1 +/- 1.5 pmol/L to a mean lowest value of 11.7 +/- 0.4 pmol/L (P less than 0.05). The mean circadian acrophase of CGRP (calculated by cosinor analysis to occur at 2314 h) anticipated the corresponding acrophases of the other hormones (0122, 0528, 0809, and 0840 h for ANP, PRA, PA, and PC, respectively). Instead, BP and HR rhythms seemed to be antiphasic with the ANP rhythm (calculated acrophases occurred at 1356, 1339, and 1314 h for systolic BP, diastolic BP, and HR, respectively). Our data demonstrate that, like many other hormones, CGRP circulates in plasma with a circadian rhythm. There seems to be a temporal sequence starting with the nocturnal rise in plasma CGRP concentrations and progressing with the ensuing elevations of ANP, PRA, PA, and PC, whereas BP and HR are kept to their lowest values. These findings are in favor of a physiological role of CGRP in the complex regulation of BP homeostasis.

Adult↗

Stimulation of growth hormone and corticotropin release by angiotensin II in man.

The intravenous (IV) infusion of angiotensin II (AII) was administered to seven healthy male volunteers in a randomized placebo-controlled study. As expected, AII induced a significant increase in blood pressure and plasma aldosterone concentrations. AII caused a significant increase in corticotropin (ACTH) and growth hormone (GH) release, but had no effect on the release of thyrotropin (TSH) and prolactin (PRL). These findings suggest that peripherally circulating AII might influence ACTH and GH secretion in humans.

Adrenocorticotropic Hormone↗

Atrial strain is the main determinant of release of atrial natriuretic peptide.

We studied the response of atrial natriuretic peptide to the hemodynamic and renin-aldosterone variations occurring in four patients who developed cardiac tamponade, either occurring in idiopathic fashion in one or secondary to metastatic involvement of the pericardium in three. Right atrial pressure, heart rate and arterial blood pressure were monitored and serial blood samples were taken before and over three hours after pericardiocentesis. During cardiac tamponade, normal levels of atrial natriuretic peptide (mean +/- SEM: 54 +/- 7.4 pg/ml) were observed in the plasma despite increased right atrial pressure (23 +/- 3.8 cm H2O) and heart rates (98 +/- 4.4). Removal of pericardial fluid (540 to 1160 ml) was associated at first with a 200% increase in plasma concentrations of atrial natriuretic peptide (108 +/- 8.8 pg/ml; P less than 0.001), then with a gradual decline toward normal levels, simultaneous with the normalization of right atrial pressure and heart rate. Activity of renin and concentrations of aldosterone in the plasma were increased during tamponade and returned gradually to normal after pericardiocentesis (3.8 +/- 0.9 to 1.2 +/- 0.3 ng/ml/h and 20 +/- 4.2 to 9 +/- 3.2 ng/dl, respectively; P less than 0.01). These data confirm that atrial strain, not intracavitary pressure in itself nor heart rate, is the main determinant of the acute release of atrial natriuretic peptide, which is associated with a suppressing effect on the renin-aldosterone system. In addition, our data indicate that secretion of atrial natriuretic peptide during cardiac tamponade is not stimulated by secondary hyperaldosteronism.

Adult↗

Circadian rhythms of atrial natriuretic peptide, renin, aldosterone, cortisol, blood pressure and heart rate in normal and hypertensive subjects.

The occurrence and extent of a circadian rhythm in the circulating concentrations of atrial natriuretic peptide (ANP) are still matters of controversy. Only a few data are available in humans relating the time structure of plasma ANP levels with the circadian patterns of other hormones and cardiovascular variables. In a group of hospitalized normal volunteers (six men and four women, 16-76 years old), and in a group of hospitalized hypertensives (seven men and three women, 18-76 years old), we investigated the circadian variability of ANP and its temporal relationship with the circadian rhythms of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), plasma aldosterone (PA) and plasma cortisol (PC) levels, by using a chronobiological inferential statistic method. At the end of a synchronizing period of 1 week (the diet and daily schedule were standardized), the subjects underwent automatic BP and HR monitoring, and blood sampling for 24 h. A statistically significant mean circadian rhythm was demonstrated for ANP, BP, HR, PRA, PA and PC in both normal and hypertensive subjects. The mean circadian acrophase of ANP (calculated to occur at around 04.00 h) anticipated the corresponding acrophases of the other hormones; BP and HR rhythms appeared to be in antiphase with ANP rhythm, i.e. the peak of BP and HR rhythms more or less coincided with the trough in ANP rhythm. A significant increase in the daily levels (assessed by the circadian mesor) of ANP was present in hypertensive subjects when compared with normal controls. In essential hypertension the circadian rhythm of ANP was set at higher circulating levels, but otherwise it was similar to the circadian rhythm found in normals. ANP mesors correlated significantly with renin and aldosterone mesors in normal subjects but not in hypertensive patients. ANP appears to anticipate awakening in its circadian periodic rise. On the basis of the considerable acrophase asynchronism, it seems possible to exclude any causal relations between the periodic changes of ANP and the rhythmic fluctuations of the other hormones that we studied. In contrast, important relations may be hypothesized between ANP levels and BP and HR values, on the basis of their antiphase rhythms.

Aldosterone↗

[Effects of somatostatin on human thyroid folliculi in vitro].

Somatostatin (SRIF) inhibits calcitonin and T3-T4 secretion in thyroid. We have investigated the in vitro effect of SRIF on the basal and TSH induced [3H]thy incorporation, thyroglobulin (tgb) RNA and cAMP level in follicular cells, isolated from normal and adenomatous human thyroids. [3H]thy uptake has been evaluated as TCA-precipitable material in 2, 4, 8, 24 h incubated follicles and 24 h incubated adherent cells. Tgb RNA has been quantified with cytoplasmic dot blot hybridization and cAMP level with RIA method. SRIF reduces basal and TSH-induced [3H]thy in both suspension follicles and epithelial adherent cells. However it does not modify tgb RNA nor cAMP levels in incubated follicles. These data suggest a direct antiproliferative effect of SRIF on human thyroid.

Humans↗

In vitro effects of estrogen on tgb and c-myc gene expression in normal and neoplastic human thyroids.

The authors investigated the effects of 17 beta-estradiol (E) and thyroid-stimulating hormone (TSH) on tgb (coding for thyroglobulin), c-myc RNA levels, and [3H]thymidine (thy) incorporation in suspension cultures of normal, adenomatous and carcinomatous human thyroid follicles. The cultured follicles showed decreased tgb RNA and enhanced c-myc RNA levels. In the culture of normal and adenomatous samples E caused a significant increase of [3H]thy incorporation and tgb RNA levels, with no effect on c-myc RNA levels. No effect of E was observed in the carcinomatous thyroid culture. TSH induced a significant increase of [3H]thy incorporation and c-myc expression only in adenoma cultures and a significant increase of tgb RNA levels in both normal and adenomatous samples. TSH had no effect on the carcinoma. The results show that E, like TSH, stimulates in vitro the expression of the tgb gene in differentiated cells, without stimulating the expression of the c-myc proto-oncogene, suggesting a possible action of E on normal thyroid function and perhaps growth, even if not associated with increased c-myc expression.

Cell Division↗

Circadian rhythms of atrial natriuretic peptide, blood pressure and heart rate in normal subjects.

The occurrence and extent of a circadian rhythm in the circulating concentrations of atrial natriuretic peptide (ANP) is still a matter of controversy. In a group of hospitalized normal volunteers (6 men and 4 women, 16-76 years old), we investigated the circadian variability of ANP and its temporal relation with the circadian rhythms of blood pressure (BP) and heart rate (HR), by using a chronobiological inferential statistical method. At the end of a synchronizing period of 1 week (the diet and the daily schedule were standardized), the subjects underwent automatic BP and HR monitoring, and blood sampling for 24 h. A statistically significant mean circadian rhythm was demonstrated for ANP, BP, and HR. The mean circadian acrophase of ANP was calculated to occur around 4 a.m. BP and HR rhythms appeared to be in antiphase with ANP rhythm, i.e. the peak of BP and HR rhythms more or less coincided with a trough in ANP rhythm. ANP appears to be anticipatory in its circadian periodic rise to awakening. Therefore, postural changes cannot fully account for the diurnal variations observed.

Adolescent↗

Does placebo lower blood pressure in hypertensive patients? A noninvasive chronobiological study.

Placebo controlled trials have generally been used in order to evaluate the antihypertensive efficacy of drugs. There is some evidence, though, that blood pressure might not be influenced by placebo. Non-invasive devices for automatic blood pressure monitoring are likely to provide a better assessment of blood pressure response to drugs, as well as to different physiologic and pathologic conditions, than the traditional sphygmomanometric devices. The aim of this study was to investigate the effect of placebo on blood pressure recorded automatically and non-invasively. For this purpose, a chronobiologic approach to the collection, evaluation and interpretation of data seemed most appropriate. A group of 12 patients with a clinical diagnosis of essential hypertension underwent automatic blood pressure monitoring in hospital for 4 days. Measurements were taken every 15 min by an oscillometric instrument with an automatically inflated cuff. After a washout period during which the patients received no treatment, pressure recording was undertaken under basal conditions for 2 days. On the third and fourth days of study, the patients received 2 tablets of placebo, one at 10 a.m. and one at 10 p.m. In each patient a highly significant circadian rhythm was documented for systolic and diastolic pressure, both under basal conditions and during placebo administration. Blood pressure mesors were higher than reference standards and were not significantly affected by placebo. The circadian amplitudes and acrophases did not differ significantly before and during placebo. Our data indicate that automatically recorded blood pressure is not influenced by placebo.

Adult↗

Effect of penbutolol on circadian blood pressure, and renin, aldosterone and cortisol levels in patients with essential hypertension.

We investigated the effect of an orally administered, long-acting, beta-adrenergic blocking agent, penbutolol, on the circadian rhythm of blood pressure (BP) and heart rate (HR), and plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) levels in hospital patients with essential hypertension validated by a chronobiological inferential statistic method. After a wash-out period of three weeks, a group of 8 hypertensive patients (5 women and 3 men, 27 to 41 years old) underwent automatic BP and HR monitoring, and blood sampling for 24 hours in a hospital room before and after 4 weeks of treatment with penbutolol (40-mg tablet once a day at 9 a.m.). In basal conditions, a statistically significant mean circadian rhythm was demonstrated for HR, diastolic BP, PRA, PA, and PC. Systolic and diastolic BP were lowered by penbutolol, with only a minor decrease of HR. The treatment eliminated also the mean circadian rhythm of BP and HR. Penbutolol induced both a remarkable reduction of PRA with disappearance of the related circadian rhythm and a significant decrease in PA levels with maintenance of their circadian rhythmicity. The circadian secretory patterns of PC were similar before and after therapy. In conclusion, long-term treatment with penbutolol appears not only to set BP, PRA and PA values to lower levels, but also to decrease the within-day variation of BP, HR, and PRA. In addition, penbutolol does not influence the 24 h-secretion of PC.

Administration, Oral↗

Slow-release nifedipine: effect on the circadian rhythm of blood pressure in essential hypertension.

The aim of this study was to investigate the effect of orally administered, slow-release, nifedipine tablets on the circadian rhythm of blood pressure and heart rate, in hospital patients with clinical diagnosis of hypertension validated by a chronobiologic inferential statistic method. A group of 14 patients (nine women and five men, 47 to 71 years old) with clinical diagnosis of "essential hypertension" underwent automatic blood pressure and heart rate monitoring in a hospital room for 48 hours. Measurements were taken every 15 min by an oscillometric instrument with automatically inflated cuff. The patients received no treatment during the two proceeding weeks and the first day of the study. On the second day, slow-release nifedipine tablets were administered, one at 10 a.m. and one at 10 p.m. A highly significant circadian rhythm was documented for systolic and diastolic blood pressure, mean arterial pressure and heart rate, both in basal conditions and after nifedipine. Blood pressure mesors were higher than reference standards in basal conditions, and were lowered (average decrease = 20 mmHg for systolic and 9 mmHg for diastolic mesor) by nifedipine. A significant, though minor, elevation of heart rate mesor (from 70 to 75 b.p.m.) was also noted during treatment. The circadian amplitudes of blood pressure and heart rate did not differ significantly before and during treatment. In conclusion, the circadian rhythm of blood pressure is still present with the same amplitude after slow-release nifedipine, but is set at a lower pressure level. Heart rate rhythm is also preserved, with only a minor elevation of its mesor.

Administration, Oral↗

Dermorphin inhibits spinal nociceptive flexion reflex in humans.

Dermorphin (D) is a potent opiate-like peptide isolated from the skin of some species of frogs. Experimental studies in animals indicate that D has a potent antinociceptive effect, while no investigation exists about its analgesic properties in humans. Our study shows that i.v. infusion of 0.16 mg/kg D induces a marked and long-lasting increase in the threshold of nociceptive flexion reflex in healthy volunteers. This effect is also evident in a complete chronic spinal subject, showing that D depresses the nociceptive transmission mainly acting at spinal level. Naloxone, while fully antagonizing the effects of morphine and enkephalin analogue, is able to reverse only partly (ca. 50%) the depressive effect of D on nociceptive spinal reflex. This fact may suggest that D interacts with different spinal opiate receptor populations in inducing analgesia.

Adult↗

Somatostatin inhibits the dermorphin-stimulated thyrotropin release in man.

We have studied the effect of the intravenous administration of somatostatin (SRIF) on the thyrotropin (TSH) response to intravenous dermorphin (D), a new potent opioid peptide, in 7 healthy men. D significantly increased the serum TSH concentration. SRIF administration prior to, during and after D completely prevented the D-induced rise in serum TSH. These results confirm that D stimulates TSH release in man and that this stimulatory effect can be prevented by SRIF.

Adolescent↗