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Biomedical subjects

A Cavatorta

Publications and source records attributed to A Cavatorta.

At least 19 recordsLinked to original sources

Glomerular hyperfiltration in essential hypertension: hormonal aspects.

Glomerular hyperfiltration is thought to play a pivotal role in causing renal damage in essential hypertension. An increase in glomerular filtration rate can be experimentally induced by an acute oral protein load through still unclarified mechanisms, although hormonal factors have been postulated; in already hyperfiltering nephrons, the capacity to further increase glomerular filtration rate upon stimulation with an acute protein load (i.e. renal functional reserve) would conceivably be reduced, even in the presence of apparently normal renal function. The present study aimed at assessing whether renal functional reserve is preserved and/or is affected by different antihypertensive drugs in essential hypertensive patients without signs of renal function impairment; moreover, we tried to highlight changes in the plasma levels of natriuretic and antinatriuretic hormones potentially involved in the modulation of renal hemodynamics under the chosen experimental conditions. Renal hemodynamic parameters, plasma renin activity, aldosterone and atrial natriuretic factor were measured in fourteen essential hypertensives submitted to an acute oral protein load, alone or with a concomitant administration of either nifedipine or enalapril, as compared with a control carbohydrate meal. Glomerula filtration rate and renal plasma flow rose slightly but not significantly following an acute oral protein load as compared with a carbohydrate meal; no changes were noted in plasma atrial natriuretic factor levels, whereas plasma renin activity decreased. When nifedipine was administered together with the protein meal, both glomerular filtration rate and renal plasma flow increased significantly; there were also, parallel increases in plasma renin activity and atrial natriuretic factor. Administration of enalapril was associated with a decrease in both glomerular filtration rate and renal plasma flow; plasma renin activity showed an expected marked rise, whereas the plasma levels of atrial natriuretic factor were only slightly but not significantly reduced and plasma aldosterone fell. In conclusion, our data suggest that in our patients renal functional reserve was blunted. Clear-cut hyperfiltration was brought about by administration of nifedipine together with a protein meal, whereas enalapril completely abolished even the small increase in glomerular filtration rate seen after protein meal alone. The concomitant alterations in plasma renin activity, aldosterone and atrial natriuretic factor seemed to play no major role in the determinism of the observed renal hemodynamic changes.

Adult

Physiological stimuli to atrial natriuretic peptide secretion in normal humans.

We tested the response of plasma atrial natriuretic peptide (ANP) levels to the following physiological stimuli: postural changes; head-out water immersion; and physical exercise. Plasma ANP (p-ANP) levels were assessed by a specific, sensitive radio-immunoassay. Plasma ANP rose significantly when posture shifted from upright to recumbent for 1 h, but fell again to basal values after 10 min standing. Circadian variations did not affect the posture study. Head-out water immersion produced a prompt and remarkable (sevenfold) increase in p-ANP, with a plateau reached after 1 h and held until the end of the experiment (2 h). Plasma ANP levels were measured in 10 normal subjects performing supine treadmill exercise at 50% of maximum aerobic capacity for 30 min. Plasma ANP rose from baseline supine values after 15 min exercise, and remained elevated during the following 15 min exercise. During the recovery phase ANP showed a trend towards baseline values, with a 38% decrease attained after 30 min. We propose that the above tests could be used as ANP-stimulating manoeuvres in physiological and clinical conditions in man.

Adult

Adrenal response in the pathogenesis of arterial hypertension in workers exposed to high noise levels.

Some neuroendocrine parameters known as stress indices were examined in two groups of healthy male workers in a glass factory: the first group (60 subjects) was exposed to high environmental noise levels [greater than 90 dB(A)]; the second group (52 subjects) was exposed to low noise levels [less than 78 dB(A)]. Subjects with histories of cardiovascular diseases or high arterial pressure were excluded from the study. In both groups serum catecholamines and cortisol, and urinary vanilmandelic and homovanillic acids were evaluated at the beginning and middle of morning and afternoon work-shifts, by high performance liquid chromatography with electrochemical detection. Norepinephrine, epinephrine and vanilmandelic acid were significantly increased (P less than 0.01) during work-shifts in the group exposed to 90 dB(A), compared with baseline levels and also with catecholamine levels in the group exposed to 78 dB(A). Serum dopamine, cortisol and homovanillic acid showed no significant differences. The increased stimulation of the sympatho-adrenal system in response to high and prolonged noise exposure might lead to an abnormal response of the cardiovascular system with increasing arterial pressure values.

Adrenal Glands

The mechanism of Ca2+i increase in blood cells of spontaneously hypertensive rats.

Cytoplasmic free calcium (Ca2+i) is increased in platelets and lymphocytes of spontaneously hypertensive rats (SHR) and, to a lesser extent, in essential hypertensive patients. In this study, a method was devised to evaluate cellular Ca fluxes and the cellular Ca buffering power by means of the intracellular Ca indicator Quin-2. Ca influx was measured under conditions of Ca-pump inhibition, either by vanadate or ATP depletion. Lymphocytes of 5-month-old SHR were compared with those of normotensive Wistar-Kyoto rats (WKY). In both strains, the Ca entry rate and the cellular buffering capacity were higher in vanadate-treated than in ATP-depleted cells. SH rats exhibited a higher Ca influx and a greater intracellular Ca buffering power when vanadate was used to stop the Ca pump; these differences, however, were abolished in ATP-depleted lymphocytes. It is suggested that Ca entry in lymphocytes is ATP-dependent. Accelerated Ca entry in SHR can account for the previously reported higher levels of intracellular free Ca.

Adenosine Triphosphate

Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.

Animals

Interaction of beta-adrenergic antagonists with local anaesthetic acceptor sites.

H3-dihydroalprenolol (H3-DHA) binding in isolated smooth muscle cells has been studied. Two different binding sites have been detected: a high affinity (highly specific) and a low affinity (nonspecific) binding site. Local anaesthetics are able to displace H3-DHA from nonspecific sites with a rank order of potency that mirrors their local anaesthetic activity. This finding correlates, at the molecular level, with the local anaesthetic properties of beta-blockers, as concluded from classical pharmacological experiments.

Adrenergic beta-Antagonists

Effect of age on the pharmacokinetics of indobufen.

Eighteen patients of both sexes, aging between 54 and 81 years entered a study on the effects of age on the disposition kinetics of indobufen, a potent inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were assayed by HPLC after a single oral dose (200 mg) and after the last dose of a repeated oral schedule (200 mg b.i.d. for 5 days). At steady-state, indobufen plasma levels were about double those after the single dose; plasma level profiles were similar. No significant differences were detected between single dose and steady-state as regards pharmacokinetic parameters of the drug which, at steady-state, were (mean +/- SD, n = 16): Cmax = 32.6 +/- 9.3 micrograms/ml, t 1/2 beta = 12.8 +/- 4.4 h, Pl.Cl. = 14.9 +/- 6.1 ml/min, Vd beta = 223 +/- 63 ml/kg. Evidence of reduced efficiency and rate of indobufen elimination was found in elderly patients compared to young healthy subjects. This is probably because of the age-related decrease in renal function. In the patients of the present study, average Cr.Cl. was about 60 ml/min, corresponding to 50-60% of the normal values in young subjects. A statistically significant correlation was found in patients between drug plasma clearance and Cr.Cl. in agreement with the findings of a previous study on the effects of renal insufficiency on indobufen kinetics. The same dose reduction of indobufen as previously suggested for patients with mild to moderate renal insufficiency should, therefore, be adopted in elderly patients.

Administration, Oral

Cytoplasmic free [Ca2+] is increased in the platelets of spontaneously hypertensive rats and essential hypertensive patients.

The cytoplasmic free calcium concentration [( Ca2+]i) was assessed with the fluorescent dye Quin 2 in platelets and lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), essential hypertensive patients (EHP) and normotensive human control subjects (NCS). [Ca2+]i was significantly higher in the platelets of 8- and 20-week-old SHR in comparison with WKY. However, no difference was evident after weaning. Changes of cellular calcium in hypertensive rats apparently evolved simultaneously with the development of high arterial pressure. [Ca2+]i was significantly higher in platelets of EHP than in NCS. In lymphocytes of SHR, [Ca2+]i was not different from WKY at 4 and 8 weeks, but was increased at 14 weeks and at older ages. In EHP, intralymphocytic [Ca2+] was only modestly higher than in controls. On the whole, the results suggest that control of cytoplasmic calcium in these blood cells is similarly affected in human and animal models of primary hypertension.

Adult

Hypercalcemic encephalopathy in the course of hyperthyroidism.

A hypercalcemic condition can be observed in association with hyperthyroidism. The case of a patient suffering from hypercalcemia and hyperthyroidism is reported. A confusional state and EEG alterations, among which diffuse monomorphic delta rhythms were remarkable, are shown. As soon as normalization of calcemia was achieved, a rapid clinical and EEG improvement took place. A hypothetical interpretation is proposed, according to which a prolonged, though inconstant, and mild hypercalcemia in the course of hyperthyroidism could determine an encephalopathy, concealing in some way thyrotoxic symptoms.

Brain Diseases

Why is [Ca2+]i increased in blood cells in primary hypertension?

In order to explore a previously observed association between raised blood cell cytosolic calcium [Ca2+]i and primary hypertension, resting levels of [Ca2+]i in the Milan hypertensive rat strain (MHS) were measured. The [Ca2+]i was increased significantly at 7 weeks in MHS (116 +/- 8 versus 93 +/- 6 mumol/l, P < 0.005, n = 7) and non-significantly at 5 weeks (109 +/- 7 versus 85 +/- 9 mumol/l, n = 5). In Okamoto-Aoki spontaneous hypertensive rats (SHR), calcium fluxes were measured with Quin 2 in platelets and lymphocytes. Calcium influx was measured during calcium-pump inhibition either with vanadate or ATP-depletion. Influx was increased in vanadate-treated (but not in ATP-depleted) cells of SHR. This suggests an ATP dependence of calcium influx in blood cells which is more pronounced in SHR. Calcium efflux was determined when the influx was stopped by external EGTA. Calcium efflux was [Ca2+]i-dependent and was moderately increased in SHR. The faster efflux in SHR was due to higher [Ca2+]i. The [Ca2+]i-dependency of calcium efflux was comparable in SHR and Wistar-Kyoto (WKY) rats. These results suggest that a slight but significant rise of cytosolic calcium occurs in blood cells in primary hypertension. In Okamoto-Aoki SHR this rise was due to a higher calcium entry rate.

Aminoquinolines

Studies on the etiology of the experimental neuropathy from industrial adhesive (glues).

Chickens treated by paintbrushing with glue distillate (used in shoe industries), hydrocarbon mixture and TOCP in hexane, developed paralysis (4/5); in these, we have demonstrated a diffuse degeneration of the myelinic sheath of the peripheral and central neurites. Besides TOCP, cyclohexane (because of its higher concentration in the glue distillate and in the hydrocarbon mixture) may be indicated as responsible for occupational neuropathy.

Adhesives

Nephrotoxicity of chromium. Remarks on an experimental and epidemiological investigation.

Observations conducted on a group of workers exposed to chromium (who showed a rapid urinary excretion of the metal and progressive increase of clearance with cumulative years of exposure), induced the authors to evaluate the nephrotoxic action of chromium in rats exposed to acute and chronic intoxication. The progressive Cr accumulation in the renal cortex during the course of testing explains the increase of the excreted fraction of filtered Cr, and therefore, the clearance, of the metal through the reduction of the tubular lumen-epithelium gradient. Paralleling the anatomical lesions (demonstrated only at the level of the proximal tubular cells), are the increasing modifications of the cellular lesion or altered reabsorption registered by several urinary indicators. Similar changes were found in subjects chronically exposed to the metal; their reversibility is linked to the possibility of repairing the epithelial damage by stopping exposure.

Animals

[Relation between environmental concentration, urinary elimination and body burden of chromium in occupationally exposed workers].

Biological and environmental monitoring of chromium exposure was carried out on 20 welders working with special electrodes in the manufacture of tank-cars. The workers were divided in groups, according to the different degree of chromium accumulation, which was determined by renal clearance of diffusible chromium. A closed linear relationship between TWA concentration of hydrosoluble chromium in air and urinary excretion of the metal at the end of exposure was observed. The parameters of regression lines in welders with more (clearance 10 ml/min) or less (clearance 5 ml/min) accumulation of chromium suggest that the renal burden influences not only the basal excretion, but also the excretion at the end of exposure. We underline the difficulty in the determination of correct biological limits if we take them from TLV in air. We must at least consider the degree of accumulation in exposed workers too.

Air Pollutants