Biomedical subjects

G Norbiato

Publications and source records attributed to G Norbiato.

At least 55 records · Page 3Linked to original sources

PubMed1991

Sympathetic skin response versus maximum motor and sensory conduction velocity to detect subclinical neuropathy in non-insulin-dependent diabetics.

Conventional motor (MCV) and sensory conduction velocity (SCV) of the ulnar (UN), peroneal (PN) and median nerves (MN) and the areas of sympathetic sudomotor response (SSR) recorded from the middle finger were measured on both sides in 20 normal and 20 non-insulin-dependent diabetic (NIDD) subjects. Conventional statistical tests (t test, linear correlation coefficient r) and discrimination analysis were applied to the above electrophysiological parameters. To evaluate the capability of the tests to separate NIDD diseased from normal nerves, the results were represented as generalized distances, i.e., difference between mean discriminant normalized combinations adjusted for intra-group variability. The r values were 0.92 (P less than 0.01) for the UN, 0.40 (P greater than 0.05) for the PN, and 0.86 (P less than 0.01) for the MN sensory action potential (SAP) amplitudes. No significant differences were found for normalized latencies. The r values of the SSR areas were 0.62 (P less than 0.01) at the right and 0.77 (P less than 0.01) at the left, homolaterally to the side of stimulation. SR and MCV generalized distances were 1.35 and 1.39, respectively. The discriminating power of SSR, MCV and SCV considered together was higher (2.40) than that of MCV and SCV (1.70). Since motor, sensory and autonomic alterations often did not coexist in NIDD, it was possible to find at least one type of involvement in most of the diabetic subjects.

Adult↗

PubMed1991

Effects of a cable car trip on blood pressure and cardiovascular hormones in lowlander and highlander normotensives.

The effects of a cable car trip from 1370 m (4500 ft) to 3460 m (11350 ft) were studied in 6 lowlanders (3 men and 3 women, mean age 31 +/- 4 years, living at an altitude of less than 500 m) and in 10 highlanders (all males, mean age 37 +/- 12 years, ski teachers and cable car workers working for greater than or equal to 6 months/year at a greater than 3000 m). Cuff blood pressure (BP), heart rate, plasma catecholamines, serum renin, aldosterone, ACTH and cortisol were measured immediately before and 20 min after the trip, at rest and at the same air temperature. A handgrip test was also performed under the same conditions. At baseline, lowlanders and highlanders showed significant differences in diastolic BP (86 +/- 5 mmHg in lowlanders and 91 +/- 4 mmHg in highlanders, p = 0.05), plasma noradrenaline (323 +/- 114 pg/ml in lowlanders and 585 +/- 255 in highlanders, p less than 0.05), serum renin (10 +/- 6 pg/ml in lowlanders and 17 +/- 8 in highlanders, p less than 0.05), and serum cortisol (163 +/- 54 ng/ml in lowlanders and 120 +/- 25 in highlanders, p less than 0.01). The acute exposure to high altitude did not modify BP, heart rate or any of the measured cardiovascular hormones in either group. The handgrip test provoked a significant increase in systolic and diastolic BP in both lowlanders and highlanders (p less than 0.01), and this response was not modified by the change in altitude; however, highlanders showed significantly smaller increases in systolic BP than lowlanders at both altitudes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1990

Evidence that cholinergic receptors of muscarinic type may modulate vasopressin release induced by metoclopramide.

Studies were carried out in the rat in order to investigate whether cholinergic mechanisms may be involved in vasopressin (VP) release induced by metoclopramide (MCP). The intravenous injection of MCP induced dose-related increases in plasma VP levels in water-loaded rats. These effects were prevented by atropine sulphate, but not by pirenzepine hydrochloride indicating that activation of cholinergic receptors of M-2 type was possibly required for the biologic response.

Animals↗

PubMed1990

Respiratory-burst stimulants desensitize beta-2 adrenoceptors on human polymorphonuclear leukocytes.

We investigated the effect of respiratory-burst stimulants on beta-2 adrenoceptors in human polymorphonuclear leukocytes (PMNL). Pre-incubation of PMNL with these substances did not affect the number or affinity of the receptors but desensitized them, as shown by the "right-shift" in (-)-isoproterenol competition isotherms. H-7, an established protein kinase C inhibitor, and nimesulide, a new putative inhibitor of this enzyme, blunted both superoxide anion production and beta-2 adrenoceptor desensitization. A positive correlation was found between superoxide anion generation and the "right-shift" in isoproterenol competition isotherm (r = 0.92; p less than 0.01). Desensitization of beta-2 adrenoceptors was not due to superoxide anions per se since incubation of PMNL with superoxide anion scavengers (superoxide dismutase and catalase) did not modify the results.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1989

Role of the Frank-Starling mechanism in maintaining cardiac output during increasing levels of treadmill exercise in beta-blocked normal men.

To determine the effects of beta blockade on hemodynamics during increasing levels of treadmill exercise, 10 healthy volunteers were studied after 1 week of placebo, and then after 1 week of treatment with oral propranolol, 80 mg twice daily, or dilevalol, 400 mg once daily. The study was randomized and double-blind, with a crossover sequence. Hemodynamics were measured by CO2 rebreathing at rest and at 25, 50, 75 and 100% of VO2 max. After placebo, cardiac output increased from 5.8 +/- 2.1 (rest), to 19.4 +/- 6.4 liters/min (100% VO2 max), mainly due to an increase in heart rate from 84 +/- 6 to 169 +/- 15 beats/min. Stroke volume increased from 70 +/- 27 (rest), to 137 +/- 65 ml (25% VO2 max), and then leveled off to 116 +/- 41 at 100% VO2 max. After both beta blockers, exercise cardiac output was maintained at 100% VO2 max: 20.1 +/- 9.3 liters/min with propranolol and 19.1 +/- 8.6 with dilevalol. However, a significant reduction versus placebo values was observed for cardiac output at 25% VO2 max, from 13.7 +/- 5.9 during placebo, to 9.4 +/- 2.5 during propranolol, and to 9.6 +/- 2.3 during dilevalol (both p less than 0.01 vs placebo). Maintenance of cardiac output with both beta blockers at higher levels of exercise came from an increased stroke volume (p less than 0.05 vs placebo), while heart rate (in beats/min) was greatly reduced (propranolol 61.6 +/- 9.4 rest, 90.1 +/- 10.7 at 100% VO2 max; dilevalol 70.8 +/- 6.4 rest, 99.2 +/- 11.8 at 100% VO2 max, p less than 0.01 vs placebo for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1989

Interaction of selected vasodilating beta-blockers with adrenergic receptors in human cardiovascular tissues.

beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.

Adrenergic beta-Antagonists↗

PubMed1989

Identification of alpha 1-adrenergic receptors on sarcolemma from normal subjects and patients with idiopathic dilated cardiomyopathy: characteristics and linkage to GTP-binding protein.

Discontinuous density sucrose gradient centrifugation was used to isolate membrane vesicles from the left ventricle of three normal subjects (one prospective organ donor and two traffic victims whose hearts were obtained 1 hour after death) and nine patients undergoing cardiac transplantation as a consequence of idiopathic dilated cardiomyopathy. Sarcolemma-enriched subcellular fractions, detected in the interface between 8.55% and 25% sucrose, were identified by the increased activity of Na+,K+-ATPase and by enrichment in beta-adrenergic receptor density. The density of beta-adrenergic receptors was lower in vesicles from diseased hearts (610 +/- 71 fmol/mg protein) than in vesicles from normal hearts (1,410 +/- 226 fmol/mg protein; p less than 0.01). alpha 1-Adrenergic receptors were identified in these membrane vesicles by [3H]prazosin binding. Specific binding of [3H]prazosin was about 50% of the total binding at 1 nM, and alpha 1-adrenergic binding sites were saturable at approximately 3 nM. Scatchard analysis revealed 58 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.08 nM) in pathological hearts and 30 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.03 nM) in normal hearts (p less than 0.01). The displacement curve of (-)-norepinephrine in membrane vesicles from normal hearts delineated one subpopulation of alpha 1-adrenergic receptors; the addition of 0.1 mM GTP did not cause right shift. In membrane vesicles from diseased heart, the displacement curve of (-)-norepinephrine disclosed two subpopulations of alpha 1-adrenergic receptors. A right shift that occurred after addition of GTP showed that in this case alpha 1-adrenergic receptors were functionally coupled with GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Alterations in vasopressin regulation in Alzheimer's disease.

A decreased concentration of vasopressin (AVP) in the plasma of patients with Alzheimer's disease has been shown recently and suggests damage to hypothalamic neurosecretory cells. To verify this, osmolar and hypotension (sodium nitroprusside) stimulations on AVP release were applied. The effect of metoclopramide, a powerful stimulator of AVP, was also assessed. Patients with Alzheimer's disease released AVP normally after hypotension. However, AVP response to osmotic stimulation was altered in eight out of 10 patients, owing to low osmoreceptor sensitivity and/or high threshold. Metoclopramide increased AVP in controls but not in patients. Normal AVP response to hypotension in patients with Alzheimer's disease makes it unlikely that there is a significant anatomical loss or damage of hypothalamic neurosecretory cells. Alterations in osmoreceptor function and AVP unresponsiveness to metoclopramide point to damage in the control of AVP release in Alzheimer's disease.

Aged↗

PubMed1987

Identification and characterization of alpha 1- and beta 2-adrenergic receptors in human liver.

Adrenergic receptors were identified in healthy human hepatic tissue from thirty-nine subjects undergoing elective abdominal surgery by using the specific alpha 1-antagonist [3H]-prazosin and the beta adrenergic antagonist [3H]-dihydroalprenolol ([3H]-DHA). [3H]-prazosin binding to plasma membranes was rapid, of high affinity, saturable and stereospecific with a maximal binding capacity (Bmax) of 74.1 +/- 5.5 fmol mg-1 of protein. The displacement curve for (-)-norepinephrine was better explained by a one-site binding and after addition of GTP 0.1 mM the curve was not right-shifted, suggesting the majority of alpha receptors in healthy human liver are of the alpha 1 subtype and not linked to a GTP-binding protein. [3H]-DHA binding to liver plasma membranes was also rapid, of high affinity, saturable and stereospecific with a Bmax 96.5 +/- 10.3 fmol mg-1 of protein of receptors. Computer aided analysis of the displacement curve of ICI 118,551, a subtype selective beta 2-antagonist (IC50 = 62 +/- 2 nM), indicated a one-site binding, thus, showing that beta adrenergic receptors are of the beta 2 subtype. The displacement curve of [3H]-DHA for (-)-isoproterenol was right shifted by GTP indicating that beta 2 adrenergic receptors are linked to a GTP-binding protein in human liver. These results indicate that alpha 1- and beta 2-receptors co-exist in human liver but only beta 2-receptors are linked to a GTP-binding protein.

Cell Membrane↗

PubMed1987

Osmotic and nonosmotic control of vasopressin release in the elderly: effect of metoclopramide.

The study was undertaken to define the relationships between the arginine vasopressin (AVP) response to a pressure-volume stimulus (upright posture test), an osmolar challenge, and metoclopramide injection (20 mg, iv) in normal young and elderly subjects. Besides confirming previous findings of increased AVP responsiveness to osmolar challenge and reduced AVP responsiveness to upright posture in the elderly, we found that metoclopramide stimulated AVP release in both young [from 1.09 +/- 0.05 (mean +/- SD) to 1.77 +/- 0.05 pmol/L; P less than 0.05] and elderly subjects (from 1.54 +/- 0.18 to 4.73 +/- 1.82 pmol/L; P less than 0.01). The response was much greater in the elderly (P less than 0.01). The AVP responses to upright posture and metoclopramide were inversely correlated (r = -0.77; P less than 0.01), suggesting that the elderly have increased sensitivity to stimuli, such as metoclopramide, to counteract their reduced sensitivity to baroreceptor stimulation of AVP release.

Adolescent↗

PubMed1986

Alterations in norepinephrine content and beta adrenoceptor regulation in myocardium bordering aneurysm in human heart: their possible role in the genesis of ventricular tachycardia.

On the assumption that alterations in the adrenergic system may play a role in generating ventricular tachycardia in patients with myocardial post-infarction apical aneurysm, we evaluated norepinephrine concentration, number and affinity of both beta 1 and beta 2 adrenoceptors in perianeurysmatic tissue in twelve patients operated upon for congestive heart failure and recurrent sustained ventricular tachycardia. Concentration of norepinephrine in perianeurysmatic tissue was 0.1 +/- 0.05 micrograms g-1 tissue (n = 8), this value being much lower than that found in papillary muscle (n = 10) from patients with mitral valve stenosis (0.8 +/- 0.02 micrograms g-1 tissue) (P less than 0.01). The total number of beta adrenoceptors (71.4 +/- 7.8 v. 48.0 +/- 5.1 fmol mg-1 protein; P less than 0.01) and the percentage of beta 1 subtype were found to be higher in perianeurysmatic tissue (approximately 90%) than in papillary muscle (approximately 68%). Out of twelve patients with aneurysm, beta 2 adrenoceptors had considerably decreased in three patients and were absent in the remaining nine. Decrease in the neuronally released norepinephrine associated with contrasting behaviours of beta 1 and beta 2 adrenoceptors suggests the presence of a profound alteration in the sympathetic innervation of the perianeurysmatic myocardial tissue that may contribute to the genesis of sustained ventricular tachycardia in patients with postinfarction apical aneurysm.

Adult↗

PubMed1986

Metoclopramide increases vasopressin secretion.

The possibility that metoclopramide (MCP), a potent stimulator of aldosterone secretion, might influence vasopressin secretion in man was studied. MCP (10 mg, iv) increased plasma vasopressin (mean +/- SD) from 1.3 +/- 0.1 to 2.4 +/- 0.1 pg/ml at 10 min and to 2.65 +/- 0.1 pg/ml at 20 min (P less than 0.01) in 10 recumbent normal subjects. No changes in plasma osmolality or peripheral hemodynamics, which might have accounted for the increase in vasopressin, were found. Sulpiride (100 mg iv), haloperidol (2 mg, iv), and domperidone (20 mg, iv), three chemically unrelated antidopaminergic agents, as well as TRH (200 micrograms, iv), failed to modify plasma vasopressin, thus suggesting that the MCP effect on vasopressin is not linked to its antidopaminergic and/or PRL-releasing properties. MCP also was effective in releasing vasopressin in 5 dehydrated subjects, in whom plasma vasopressin increased from 1.9 +/- 0.2 to 3.1 +/- 4 pg/ml (P less than 0.05), and in 5 subjects during steady state water diuresis, in whom free water excretion decreased from 9 to 1 ml/min (P less than 0.01) and plasma vasopressin increased from 0.3 +/- 0.1 to 1.2 +/- 0.2 pg/ml (P less than 0.05). No changes in either vasopressin secretion or free water excretion occurred in 4 patients with severe central diabetes insipidus. These results suggest that MCP stimulates the release of biologically active vasopressin in man.

Adult↗

PubMed1985

Role of blood osmolality in the regulation of vasopressin secretion in man: application of a new radioimmunoassay method for vasopressin.

A radioimmunoassay for plasma arginine vasopressin (AVP) has been developed based on R2 antibody of Thomas and Lee, synthetic standard (Ferring) and extraction on Sep-Pak column. High recovery of AVP (approximately 79%) was achieved with a detection limit of 0.25 pg/ml. By improving the technique of measurement of plasma osmolality an intraassay coefficient of variation less than 1% was obtained. Physiological studies performed with this method demonstrated that AVP becomes undetectable after water loading 20 ml per Kg of water po; (N = 6) and increases in response to hypertonic saline infusion (0.05 ml/kg/min; N = 15) with a linear relationship between plasma osmolality and AVP in individual subjects; this relationship is maintained when the test is repeated in the same subjects. However when pooling all data together, the relationship between plasma osmolality and AVP is best expressed by an exponential relationship. This implies that after AVP release is initiated, the concentration of the hormone increases more rapidly than plasma osmolality and the release is continuous possibly due to recruitment of increasing number of neuronal units whose osmotic threshold varies from individual to individual.

Administration, Oral↗

PubMed1985

Characterization of alpha 2-adrenoceptor binding properties of imidazoline-like drugs, azoloazepine derivatives and beta-phenethylamine-like drugs in human platelet membranes.

To characterize the agonist profile of alpha 2-adrenoceptor agonists (imidazoline-like drugs, azoloazepine derivatives, beta-phenethylamines-like drugs) on human platelets, the characteristics of alpha 2-adrenoceptors (KD, Bmax) have been evaluated and the affinity constants measured by displacement technique and computer-assisted analysis of the curves. Furthermore, since alpha 2-adrenoceptor agonists interact with the post-synaptic receptors in a calcium-operated channel, whether the effect of calcium-entry inhibitors (verapamil, nifedipine, diltiazem) is related to a competition with alpha 2-receptors has also been examined. By Scatchard analysis, it was calculated that in human platelets alpha 2-adrenoceptors have KD = 3.45 nM and Bmax = 247 fmol (mg protein)-1. As far as the potency is concerned, imidazoline-like drugs were the most potent agonists in human platelet alpha 2-adrenoceptors (guanabenz IC50 = 8.6 +/- 0.8 X 10(-8), B-HT 920 IC50 = 2.9 +/- 0.3 X 10(-7), (-)-adrenaline IC50 = 3.4 +/- 0.5 X 10(-7)). Among the calcium-entry inhibitors only verapamil antagonized [3H]rauwolscine binding: the effect was stereospecific, (-)-D 600 being more potent than (+)-D 600. Nifedipine and diltiazem did not affect alpha 2-receptor binding. It is concluded that human platelets alpha 2-receptors share the agonist potency profile of other tissues containing alpha 2-receptors (brain, pre-synaptic junction), and that among calcium-entry blockers only verapamil can antagonize alpha 2-agonists. Nifedipine and diltiazem do not appear to interact stereospecifically with alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1984

Comparison of rat and human left ventricle beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding.

Beta adrenergic receptors were identified in rat myocardial left ventricle and human papillary muscle by using the antagonist radioligand 3H-dihydroalprenolol. The number (37.3 and 44.5 fmol/mg of protein, respectively in rat and man), and the KD (1.6 and 2.8 nM, respectively in rat and man) of beta receptors were not significantly different. Adrenergic receptors of both beta 1 and beta 2 subtypes were found to coexist in the left ventricle. The relative proportions of the two beta receptor subtypes were determined by the use of competition radioligand selective binding and computer modelling techniques employing the subtype selective antagonists ICI 118,551 (beta 2 selective) and atenolol (beta 1 selective) in rat or metoprolol (beta 1 selective) in man. The rat left ventricle contained about 74% beta 1 and 26% beta 2 adrenergic receptors, human left ventricle papillary muscles contained about 69% beta 1 and 31% beta 2. Human and rat left ventricles contain both beta 1 and beta 2 adrenergic receptors with similar affinities. Rat might be a model for the study of human myocardial beta adrenergic receptors.

Adult↗

PubMed1984

Evidence for a role of a serum factor stimulated by metoclopramide in regulating aldosterone secretion.

The stimulatory effect of metoclopramide upon aldosterone secretion is independent of the known aldosterone-regulating mechanisms (renin, potassium, adrenocorticotropic hormone), is unrelated to its effect on prolactin and is absent when metoclopramide is directly added to isolated adrenal zona glomerulosa cells. To examine the possibility of a "humoral" mediation of aldosterone stimulation by metoclopramide, we evaluated the effect of serum of 10 normal subjects injected with metoclopramide (10 mg i.v.) on aldosterone production by collagenase-dispersed calf adrenal zona glomerulosa cells. Whereas no effect was observed with serum collected before the injection, serum collected from 5 to 30 min after the injection stimulated aldosterone production. The effect was seen 2.5 min after the injection, was significant at 5 min (P 0.05), 10, 15, 20 and 30 min (P 0.01). The effect disappeared 40 min after the injection, when plasma aldosterone in subjects was still elevated (P 0.01). The biological half-life of the factor (t1/2) is about 12.5 min. A significant correlation was found between the maximal aldosterone response to metoclopramide in vivo and the maximal effect of serum in vitro (r2=0.69;P 0.01). We suggest that metoclopramide stimulates aldosterone production in vivo by the increase in serum of a factor which, in turn, stimulates aldosterone and whose physiological significance remains to be evaluated.

Adrenal Glands↗

PubMed1984

Effects of potassium supplementation on insulin binding and insulin action in human obesity: protein-modified fast and refeeding.

To investigate the role of potassium deficiency in the development of glucose intolerance during caloric deprivation, potassium balance was maintained within normality with oral potassium supplementation in a group of obese subjects who underwent protein-modified fast and the results of the study of carbohydrate metabolism (oral glucose test, insulin receptors on monocytes and peripheral glucose utilization as assessed by euglycaemic clamp) were compared with those obtained in a group of obese subjects admitted to protein-modified fast without potassium supplementation. Caloric deprivation without oral potassium supplementation was followed by a negative potassium balance and a decrease of serum potassium levels; a decrease of the peripheral levels of insulin along with an increase in insulin receptors and a striking reduction of peripheral glucose utilization were also observed. The maintenance of normal potassium balance and normal serum potassium levels with oral potassium-chloride supplementation was associated with higher peripheral levels of insulin (P less than 0.01) and improvement of peripheral glucose utilization (P less than 0.01) whereas the binding of insulin to monocytes was unchanged. The data suggest that potassium depletion during protein-modified fast causes a decrease of the peripheral levels of insulin and a resistance to insulin action at the postreceptors sites which is reversed by potassium supply.

Adult↗

PubMed1984

Serotonergic regulation of cortisol secretion in dogs.

The role of serotonin (5-HT) in the control of serum cortisol secretion was studied in 50 conscious beagle dogs. A significant rise in corticosteroids was observed after 1.5 and 3 mg/kg (P less than 0.01) iv fenfluramine, an indirect serotonergic agonist, as well as after 2 (P less than 0.05) and 3 mg/kg (P less than 0.01) iv quipazine, a direct agonist of 5-HT receptors. Both drugs exhibited a dose-related effect. A lower dose of fenfluramine, 0.5 mg/kg, was ineffective when administered iv, but raised serum cortisol (P less than 0.05) after direct injection into a lateral cerebral ventricle, through a chronically implanted brain cannula. The marked increases in corticosteroid concentration produced by the highest fenfluramine and quipazine doses were completely abolished by pretreatment with ketanserin, an antagonist of 5-HT2 receptors, which did not affect cortisol secretion when administered alone. These data suggest that brain serotonergic system plays a role in the control of cortisol secretion in conscious dogs.

Animals↗