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Biomedical subjects

M Serio

Publications and source records attributed to M Serio.

249 records · Page 14Linked to original sources
PubMedDate not supplied

5 alpha-reductase inhibitors, chemical and clinical models.

An active site model of 5 alpha-reductase type 2 isoenzyme on an "active-analog approach" and based on 4-azasteroidal inhibitors has been constructed to evaluate the effects on the inhibitory potency of substituents on the steroid A ring. This model has proven able to predict the potential inhibitory activity of 19-nor-10-azasteroid and 6-azasteroid compounds. A model for the evaluation of clinical efficacy of an inhibitor, based on in vitro data, has also been developed and applied to finasteride. This inhibitory potency evaluation of finasteride in human scalp homogenates, plus pharmacokinetic data, allows the calculation of a theoretical in situ inhibition value for human scalp. From the IC50 curve of finasteride in scalp homogenates, it is possible to calculate that for an inhibition level similar to that obtained in prostate with 5 mg of finasteride, the necessary plasma concentration of the drug is 1 microM, a level obtained after the acute administration of 50 mg of finasteride.

Cholestenone 5 alpha-Reductase↗
PubMedDate not supplied

Endothelin-1 is synthesized and biologically active in human epididymis via a paracrine mode of action.

In a previous study, we reported the presence of endothelin-1 and endothelin receptors in the human testis. We have now extended our investigations to the human epididymis. Since sperm appear to be immotile during their transit through the epididymis, it is conceivable that specific local factors promote smooth muscle contraction, enabling sperm transport. In this paper, we show that endothelin-1 mRNA and protein are readily detectable in the epithelial compartment of the human epididymis, and that endothelin converting enzyme- 1, which converts the precursor pro-endothelin-1 into active endothelin-1, is expressed in the epididymis, consistent with active processing of the prohormone. In addition, two classes of endothelin receptors were characterized and located in the muscle cells of the epididymis. These receptors correspond, in terms of affinity constants and capacity, to the previously characterized endothelinA and endothelinB receptor. These receptors appear to be biologically active and mediate the contractile activity of the epididymis in vitro. Our data suggest that endothelin-1, via a paracrine mode of action, may be responsible for sperm progression through this organ.

Endothelin-1↗
PubMedDate not supplied

Dopamine and sympathoadrenal activity in man.

The sympathetic adrenal (SA) activity can be modulated by dopamine (DA) through D2 receptors. In man, using D2 antagonists, it has been demonstrated that endogenous DA plays an inhibitory modulation of the SA system during high degree of SA activation. D2 agonists are able to induce a decrease in norepinephrine (NE) release either in vitro or in vivo. This effect leads, in vivo, to a decrease in blood pressure (BP) and to an activation of arterial baroreceptors. Therefore, in vivo, the D2 mediated inhibition of epinephrine (E) release, which is clearly demonstrated in vitro, is overwhelmed by the baroreceptor-mediated activation of the splachnic nerve. As a consequence, the in vivo administration of D2 agonists can induce a different effect on the net peripheral sympathetic tone of an organ, depending on the balance between the degree of the baroreceptor-mediated sympathetic activation and the inhibitory D2-mediated inhibition of NE release at the tissue level. In the present paper we investigated the in vivo effect of placebo (PL) or acute oral bromocriptine (BC) administration on plasma CA and on the cardiac sympatho-vagal balance of 7 normal volunteers, as assessed by power spectral analysis of heart rate (HR) variability (autoregressive method), either in resting or sitting position. Low frequency (LF) and high frequency (HF) components, both expressed in normalized units (nU), and LF/HF ratio were calculated. BC caused a decrease in BP, plasma NE and no change in HR in resting and sitting position. Plasma E increased in sitting position. At the heart level, after BC, we observed, during rest, an increase in LF and LF/HF ratio and a decrease in HF while in sitting position LF did not increase further. These data show that BC, while reducing BP through a decrease of plasma NE, increases LF/HF ratio (sympathetic tone) without any change in heart rate. These data seem to confirm that BC causes an inhibitory modulation of the SA system acting predominantly at the periphery through D2 presynaptic receptors.

Adrenal Medulla↗
PubMedDate not supplied

[Cytokines and chemokines in nephropathies and renal transplant].

Cytokines are soluble factors that are critical for the pathophysiology of the immune system and exhibit other important functions. Cytokines produced by type 1 helper T (Th1) lymphocytes, such as interferon (IFN)-g, play a pathogenic role in proliferative glomerulonephrites (GN), as well as in the acute rejection of kidney allografts. Cytokines produced by type 2 Th (Th2) lymphocytes, such as interleukin (IL)-4, IL-5, and IL-13), predominate in membranous GN and in minimal change disease. More recently, the pathogenic role of some members of the family of chemotactic cytokines (chemokines) in different nephropathies and in the acute and chronic rejection of kidney allografts has also been demonstrated. In particular, the chemokine MCP1/CCL2 has been found to be expressed in the kidneys of subjects with tubulo-interstitial nephritis and seems to play an important role in the sclerotic evolution of both inflammatory and metabolic nephropathies. Interactions between IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 and their shared receptor, CXCR3, seem to be responsible not only for Th1 cell infiltration in acute allograft rejection and in proliferative GN, but also for mesangial cell proliferation typical of the latter condition. In proliferative GN, mesangial cells indeed express both these chemokines and their receptor. Moreover, in the kidneys of subjects suffering from chronic allograft nephropathy, IP-10/CXCL10, Mig/CXCL9 and I-TAC/CXCL11 have been found to be produced by and to act on the proxymal tubular epithelial cells, endothelial cells and smooth muscle vessel cells, suggesting their possible role in both the genesis of tubular atrophy and allograft artheriosclerosis.

Chemokines↗
PubMedDate not supplied

Localization of transferrin receptors (TFRs) in human non functioning thyroid nodules and in extranodular thyroid tissue.

In this research the TFR localization in non functioning human thyroid nodules and in the extranodular thyroid tissue, using an immunohistochemical technique, has been studied. For this study a monoclonal antibody (B3/25) against TFR and the peroxidase technique have been utilized. Moreover a morphometric comparative analysis was carried out based on the following parameters: 1) mean immunoreactive area for microscopic field, 2) mean value of immunoreactive follicular perimeter, 3) integrated optical density, 4) % of immunoreactive area on total examined area in nodular and extranodular tissue. The immunoreactivity was detected in some follicular cells in a number of follicles randomly distributed in the extra nodular tissue. As concern the non functioning thyroid nodules, the positivity was localized in the generality of the follicles both in the flattened epithelial cells of the larger follicles and in the cuboidal cells of the smaller ones. The morphometric parameters confirm a statistically significant difference of immunoreactivity between extranodular and nodular tissue. These results suggest that TF might play a role in the cellular proliferation of thyroid gland.

Cell Division↗
PubMedDate not supplied

Involvement of nitric oxide in hyporeactivity of rat mesenteric vascular bed during endotoxic shock: effect of dexamethasone and endothelin-I.

The present study was carried out on mesenteric vascular bed from LPS-injected rats in order to investigate the cause of hyporesponsiveness in resistance blood vessels, during septic shock syndrome. The involvement of L-Arg/NO pathway was evaluated by administration of L-Arg, which produced a decrease in perfusion pressure in LPS-treated rats, whereas it was ineffective in control rats. Furthermore, DEX-pretreatment in endotoxaemic rats significantly reduced the vasorelaxation by L-Arg, whereas it was ineffective to reverse vascular hyporeactivity occurring in septic shock. In order to evaluate whether hyporesponsiveness could be due to defects in contraction mechanisms, we tested the effect of ET-I. This peptide was able to markedly enhance the contractile response to NA in LPS-treated rats. Our findings suggest that vascular hyporesponsiveness during septic shock may depend on both activation of the L-Arg/NO pathway and alterations in post-receptor mechanisms involving calcium handling.

Animals↗