Biomedical subjects

R Castello

Publications and source records attributed to R Castello.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Immunohistochemical localization of 11-hydroxysteroid dehydrogenase in rat kidney with monoclonal antibody.

Monoclonal antibody (MAb) against 11-hydroxysteroid dehydrogenase (11-HSD) has been raised by immunization of female balb/c mice. 11-HSD from solubilized rat renal microsomal protein could be bound in a modified ELISA using antimouse IgG and MAb against 11-HSD. On Western blots of solubilized rat renal microsomes the MAb recognized a single protein band of an approximate molecular weight of 35 kD. Immunohistochemical staining of rat renal tissue with the above MAb and the APAAP staining technique displayed a heterogenous reginal and subcellular distribution: glomeruli and arterioles were practically devoid of specific staining, as were epithelial cells in inner and outer medulla. Intense immunostaining was observed in PCT and particularly in PST, appearing granular with highest density around the nuclei. Here the enzyme bound to intracellular membranes may exert an autocrine function such as signal inactivation. In contrast to cortex, staining of interstitial cells was observed in renal medulla. The latter localization is compatible with the concept of a paracrine function of 11-HSD which might prevent corticosterone from gaining access to collecting duct cells.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Clinical and haemodynamic effects of ketanserin in lean and obese hypertensive patients.

Systemic and central haemodynamics were evaluated in 10 lean and 10 obese hypertensive patients (World Health Organization stage I-II) after treatment for 8 weeks with a serotoninergic antagonist, such as ketanserin. Blood pressure and heart rate were recorded and first-pass radionuclide angiocardiography was performed to determine cardiac output, cardiac index and ejection fraction of the left ventricle; total peripheral resistance was also calculated. In both obese and lean patients, ketanserin significantly reduced diastolic (P less than 0.05) and mean (P less than 0.005) blood pressure but no significant changes in systolic blood pressure, cardiac output, cardiac index and ejection fraction were observed in lean and obese hypertensive patients. Total peripheral resistance was significantly (P less than 0.05) reduced in lean patients but in obese hypertensives it was only moderately reduced. It is concluded that monotherapy with ketanserin is effective in treating mild to moderate hypertension in both lean and obese hypertensive patients, without interfering with left ventricular performance.

Adult↗

PubMedDate not supplied

In vivo studies on the role of the peripheral benzodiazepine receptor (PBR) in steroidogenesis.

In various steroidogenic cell models, mitochondrial preparations and submitochondrial fractions, the expression of the mitochondrial 18 kDa peripheral-type benzodiazepine receptor (PBR) protein confers the ability to take up and release, upon ligand activation, cholesterol. Thus, cholesterol becomes available to P450scc on the inner mitochondrial membrane. These in vitro studies were validated by in vivo experiments. Treatment of rats with ginkgolide B (GKB), specifically reduced the ligand binding capacity, protein, and mRNA expression of the adrenocortical PBR and circulating glucocorticoid levels. Treatment with GKB also resulted in inhibition of PBR protein synthesis and corticosterone production by isolated adrenocortical cells in response to ACTH. The ontogeny of both PBR binding capacity and protein directly paralleled that of ACTH-inducible steroidogenesis in rat adrenal cells and in rats injected with ACTH. In addition, the previously described suppression of luteal progesterone synthesis in the pregnant rat by continuous in vivo administration of a gonadotropin-releasing hormone agonist may be due to decreased luteal PBR ligand binding and mRNA. These results suggest that (i) PBR is an absolute prerequisite for adrenocortical and luteal steroidogenesis, (ii) regulation of adrenal PBR expression may be used as a tool to control circulating glucocorticoid levels and (iii) the stress hypo-responsive period of neonatal rats may result from decreased adrenal cortical PBR expression.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Byciclic compounds with potential antiulcer and/or antisecretory activity. III--2-substituted tetrahydrothiazolo-[5,4-c]pyridines.

As the ultimate result of a long-term search for new bicyclic molecules potentially endowed with antiulcer and/or antisecretory activity, simple urea derivatives of 2-guanidino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine [(VIII), Fig. 1; X = 0, R = alkyl], displaying a strong inhibition of stress- and ASA-induced gastric ulcers and of basal gastric secretion, were found. Their potency does compare very favourably with that of cimetidine and ranitidine and approaches that of famotidine. On spontaneously beating guinea pig atria they behaved as inhibitors of the histamine H2-receptor. In contrast with cimetidine and ranitidine but like other recently described inhibitors (famotidine included), the most active compounds (VIII) caused a surmountable antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The onset of action was slow, while the inhibitory effect was hardly reversed by washing. The rational development of the research and the synthetic approach, as well as a quantitative assessment of both in vitro and in vivo potencies in comparison with the best known, clinically used drugs, are shown in detail.

Animals↗