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S Zoppi

Publications and source records attributed to S Zoppi.

At least 37 records · Page 2Linked to original sources
PubMed1991

Androgen resistance associated with a mutation of the androgen receptor at amino acid 772 (Arg----Cys) results from a combination of decreased messenger ribonucleic acid levels and impairment of receptor function.

Analysis of the nucleotide sequence of the coding segment of the androgen receptor gene in a patient (N105) with the receptor-negative form of complete testicular feminization has revealed a single substitution (CGC----TGC) at nucleotide 2476. This alteration results in the conversion of an arginine at amino acid 772 to a cysteine. Introduction of this mutation into an androgen receptor cDNA and transfection of the mutant cDNA into COS cells result in the production of a receptor protein with an alteration in the apparent Kd of ligand binding (3 nM) compared to that of the normal androgen receptor (0.5 nM). The mutant receptor protein predicted for patient N105 also demonstrates thermal instability of ligand binding that is not associated with quantitative or qualitative changes in the immunoreactive androgen receptor protein. When assayed in cotransfection experiments using a mouse mammary tumor virus-chloramphenicol acetyl transferase reporter system, the N105 receptor protein appears to be about a tenth as active as the control receptor. These functional characteristics do not appear sufficient to account for the phenotype of complete testicular feminization and do not explain the profound deficiency of androgen receptor in cultured skin fibroblasts. Quantitative S1 nuclease protection assays reveal that the level of androgen receptor mRNA in fibroblasts from patient N105 is markedly reduced. These results suggest that the phenotype in patient N105 is due to two effects of the nucleotide substitution at residue 2476: the replacement of a crucial amino acid (772) in the hormone-binding domain that impairs the function of any receptor molecules formed and a decrease in the level of androgen receptor mRNA.

Androgen-Insensitivity Syndrome↗
PubMed1991

[Arterial diseases of surgical importance. Long-term control of diet-related risk factors].

From 1980 to 1990 a yearly medical-surgical control was carried out on 950 arteriopathic patients hospitalised in the General and Cardiovascular Surgery Institute, Milan University, during the above mentioned period. The operations for surgical reconstruction were mainly for arteriosclerotic lesions involving the abdominal-peripheral district (750 patients, 79%) and the supra aortic trunks (200 patients, 21%). 84% of the patients were males. Among the patients on follow-up, a relatively modest number (100 patients) did not attend the prescribed diet therapies for several reasons, consequently these patients have been considered as a control group. The comparison, between the patients who attended and those who did not attend the diet, has been made on the basis of the following parameters: cholesterolemia (COL), LDL, HDL, triglyceridemia (TG), VLDL, glycemia (GLI), body mass index (BMI) and arterial pressure (PA). The results have shown a decrease in the absolute normal values of cholesterol, LDL and triglycerides, while they have not shown the same significant variations regarding glycemia and body weight. In accordance with the literature, the diet seems to have obtained satisfactory results, especially regarding the values of lipidemia, with a reduction in the atherogenic risk index. Regarding smoke as a risk factor it has been shown that it is present in 80% of the patients at the beginning: 60% of the patients stop smoking at the moment they are hospitalised and the remaining 20% continue smoking. The hygienic-dietetic intervention is confirmed, also in our experience, as a curative, or even more, a preventive tool against the worsening of an already overt arteriosclerosis as well as a necessary support for drug therapies.

Arteriosclerosis↗
PubMed1990

Characterization of basolateral membrane Na/H antiport in rat jejunum.

Na uptake studies were performed in order to examine the activity of a Na/H exchanger in basolateral membrane vesicles isolated from rat jejunum. Experiments were carried out under voltage-clamped conditions in order to avoid electrodiffusional ionic movements. 1 mM Na uptake was found to be enhanced by an outward proton gradient and its initial rate was further increased by the presence of monensin or nigericin. The pH gradient-driven Na uptake was inhibited by 2 mM amiloride and unaffected by 0.1 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. The initial rate of the proton gradient-induced Na uptake was saturable with respect to external Na, with a Km of 13.6 +/- 1.4 mM and a Vmax of 35.4 +/- 2.2 nmol/mg protein per min. Li competed with Na for the exchange process, whereas K, Rb, Cs, tetramethylammonium had no effect. We conclude that rat jejunal basolateral membrane contains a Na/H exchanger whose properties are similar to those of the antiporter identified in the brush-border membrane.

Amiloride↗
PubMed1990

Aging and ATPase activities in rat jejunum.

In addition to the well-known (Na,K)-ATPase activity, an ouabain-insensitive Na-ATPase has been evidenced in the basolateral membrane of intestinal and renal cells from different mammals. Basolateral membranes of jejunal enterocytes from rats of different ages, i.e., very young, young, adult and old were separated by self-orienting, Percoll-gradient centrifugation. The total protein content and both Na- and (Na,K)-ATPase activities in initial homogenate and final pellets were analyzed. The dry weight of homogenate and pellet was also determined. The two ATPase activities and the protein content of the basolateral membrane fraction decrease with age when referred to the dry weight of the pellet. This diminution is also evident in the initial homogenate. The activation curve of Na-ATPase, hyperbolic in shape, gives Km and Vmax values unaffected by aging. The same behaviour is true for the kinetic parameters of (Na,K)-ATPase, which has a sigmoidal velocity curve. From these results, it seems that both Na- and (Na,K)-ATPase have the same characteristics in the basolateral membrane of the enterocyte throughout the life span of the animal, but they decrease quantitatively with aging.

Adenosine Triphosphatases↗
PubMed1989

Effect of neonatal estrogenization on testosterone metabolism in the prostate and in the epididymis of the rat.

The present experiments were performed in order to analyze whether the administration of estrogens (single injection of 500 micrograms of estradiol benzoate s.c.) to neonatal male rats might modify the weight of the ventral prostate and the epididymis as well as the metabolism of testosterone in these two organs. The metabolism of testosterone was evaluated in vitro using 14C-radiolabelled testosterone as the substrate. The metabolites dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol), 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol), androstenedione, 5 alpha-androstane-3,17-dione (5-A-dione) and 3 alpha-hydroxy-5 alpha-androstane-17-one (androsterone) were quantified. After neonatal estrogen administration animals were killed on days 22 and 90 of age. The following changes were observed: (1) the body weight, the weight of the testes and of the ventral prostate were lower than in controls on both day 22 and 90; (2) the weight of the epididymides was higher than in controls on day 22 and lower on day 90; (3) in the ventral prostate the in vitro formation of DHT was lower and that of the diols was higher than in control tissue on day 22 of age; (4) the in vitro formation of alpha-reduced metabolites of the 17-keto series (5 alpha-A-dione + androsterone) was higher in ventral prostate of treated animals than in that of controls on day 22; (5) in treated animals, no formation of DHT in the caput epididymis was observed at day 22. On the contrary, at the same age the formation of androstenedione was higher than in controls; on day 90 of age the formation of DHT, androstenedione and the 5 alpha-reduced metabolites of the 17-keto series was identical in caput epididymis of the treated animals and of the controls, while the formation of the diols was higher in the treated than in the controls. The data indicate that neonatal estrogenization may induce important changes in testosterone metabolism in the prostates and in the epididymides of the rat.

Aging↗
PubMed1989

Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content.

The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol); 2) prostatic 5 alpha-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3 alpha-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3 alpha-diol concentrations in the prostatic tissue of the treated men were about 10% of those in untreated men (n = 19; P less than 0.01 for DHT and P less than 0.05 for 3 alpha-diol), and the mean intraprostatic T concentration in the treated men was about 25% of that in the control group (0.10 greater than P greater than 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50% lower (P less than 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P less than 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P less than 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 +/- 1.79 (SD) ng/mL (16.5 +/- 6.2 nmol/L) to 0.27 +/- 0.42 ng/mL (0.9 +/- 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3 alpha-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5 alpha-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1988

Antihormonal activities of 5 alpha-reductase and aromatase inhibitors.

The problem of developing androgen antagonists has been tackled so far only by synthesizing steroids able to displace testosterone and other androgens from their specific receptor sites. The observation that testosterone has to be converted intracellularly either to 5 alpha-reduced metabolites (DHT, 3 alpha-diol, etc.) or to estrogens, in order to become fully active on androgen-dependent structures (both central and peripheral), has opened the possibility of creating molecules which prevent these conversions, and which could then block the actions of testosterone. The availability of these new compounds has allowed a better understanding of the selective physiological role of each of the metabolites of testosterone, and to provide the basis for the development of new hormone antagonists to be used in those clinical conditions for which an inhibition of the actions of testosterone is foreseen. The usefulness of these enzyme inhibitors is underlined by some examples described in this paper. The results obtained may permit the formulation of the following conclusions: (1) The conversion of testosterone to its 5 alpha-reduced metabolites occurring in the neuroendocrine structures may represent an essential step for the appearance of the inhibitory feedback effect testosterone exerts on LH secretion; (2) Testosterone exhibits its negative feedback effect on FSH secretion as such and not following the local aromatization to estrogens; (3) Testosterone exerts its effect on the intrahypothalamic stores of LHRH acting as such and not following its local conversion either to 5 alpha-reduced metabolites or to estrogenic molecules; (4) Some of the new enzyme inhibitors (e.g. 4-OH-A) may represent an interesting tool for the treatment and/or the prevention of BPH and possibly of other androgen-dependent diseases (prostate carcinoma, acne etc.), as shown by their ability to prevent the in vitro conversion of testosterone to its 5 alpha-reduced metabolites both in the normal prostate of the rat and in the human BPH tissue.

Animals↗
PubMed1987

New approaches for the treatment of prostatic hypertrophy and cancer.

The present study reports the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone, dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the prostate of adult male rats and in human benign prostatic hypertrophic (BPH) tissue. It has been found that 4-OH-A decreases the formation of DHT and of the diols. When testosterone is used as the substrate, the presence in the medium of 4-OH-A enhances the formation of delta-4-A and of 5-alpha-androstanedione (5-alpha-A); 4-OH-A does not inhibit the conversion of labelled DHT into the diols. Also, the transformation of labelled delta-4-A into 5-alpha-A is not modified by 4-OH-A. On the basis of these findings, it is suggested that 4-OH-A might represent a potential new agent for the prevention and/or treatment of human BPH.

Aged↗
PubMed1986

Studies on the possible existence of two 5 alpha-reductases in the rat prostate.

In the first group of experiments, the in vitro metabolism of labelled testosterone has been studied in the ventral prostate of young (2 months) and old (15 and 22 months) male rats. It has been found that the prostate of 2-month-old animals converts testosterone into dihydrotestosterone (5 alpha-androstane-17 beta-ol-3 one, DHT) and into the diols (5 alpha-androstane-3 alpha-17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol) with considerable yields. The prostate of young animals is also able to convert testosterone into delta 4-androstenedione (delta 4-A), 5 alpha-androstanedione (5 alpha-A) and androsterone (A); however, the amounts of these metabolites are lower than those of DHT and the diols. It has been found that ageing induces major alterations in the prostatic metabolism of testosterone. In particular, a progressive and significant decrease in the formation of DHT and of the diols has been found in animals of 15 and 22 months of age. Advancing age induces, on the contrary, an increase of the formation of delta 4-A and of the 5 alpha-reduced metabolites of the 17-keto series (5 alpha-A + A). In the second group of experiments, the effects exerted by 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro metabolism of labelled testosterone and delta 4-A in the ventral prostate of adult male rats have been studied. It has been found that 4-OH-A, when added to the incubation media, decreases the formation of DHT and of the diols, when labelled testosterone is used as the substrate. The presence in the media of this steroid enhances the formation of delta 4-A and of 5 alpha-A. The transformation of labelled delta 4-A into 5 alpha-A is not modified by the presence in the medium of 4-OH-A. From the two groups of experiments, it is concluded that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to age and to the inhibitory effect of 4-OH-A (and which is responsible for the conversion of testosterone into the 5 alpha-reduced metabolites of the 17-OH series, DHT and the diols), and a second one, insensitive to age and to the effects of 4-OH-A, which affects the conversion of delta 4-A into 5 alpha-A.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1986

In vitro metabolism of testosterone in the rat prostate: influence of aging.

The in vitro metabolism of labelled testosterone has been studied in the ventral prostate of young (2 months) and old (15 and 22 months) male rats. It has been found that the prostate of 2-month old animals converts testosterone into dihydrotestosterone (5-alpha-androstane-17-beta-ol-3-one, DHT) and into the diols (5-alpha-androstane-3-alpha,-17-beta-diol and 5-alpha-androstane-3-beta,17-beta-diol) with considerable yields. The prostate of young animals is also able to convert testosterone into delta-4-androstenedione (delta-4-A), 5-alpha-androstanedione (5-alpha-A) and androsterone (A); however, the amount of these metabolites are lower than those of DHT and the diols. Aging induces major alterations in the prostatic metabolism of testosterone. In particular, a progressive and significant decrease in the formation of DHT and of the diols has been found in animals of 15 and 22 months of age. Advancing age induces, on the contrary, a progressive and significant increase of the formation of delta-4-A. The total amounts of 5-alpha-reduced metabolites of the 17-keto series (5-alpha-A + A) are higher at 15 and 22 months than at 2 months of age. This increase appears to result from an enhanced formation of 5-alpha-A at 15 months, and of A at 22 months. The present data show that aging exerts important effects on the metabolism of testosterone in the ventral prostate of the rat. The results may help explaining why the old rat does not develop spontaneously the syndrome of benign prostatic hypertrophy (BPH), as it occurs in other species (dogs and humans).

Aging↗
PubMed1986

Effect of 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A) on the 5 alpha-reduction of androgens in the rat prostate.

The present study reports the effects exerted by 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A), three steroids known to inhibit the aromatization of androgens to estrogens, on the in vitro metabolism of labelled testosterone (T), dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the ventral prostate of adult male rats. It has been found that ATD, in the concentration tested, does not influence the conversion of labelled T into DHT, but decreases the formation of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol (diols). On the contrary, 4-OH-A and 4-Ac-A simultaneously decrease the formation of DHT and the diols. When T is used as the substrate, the presence in the medium of these three steroids enhances the formation of delta-4-A and of 5 alpha-androstanedione (5 alpha-A). ATD, but not 4-OH-A and 4-Ac-A inhibits the conversion of labelled DHT into the diols. The transformation of labelled delta-4-A into 5 alpha-A is not modified by either ATD or 4-OH-A, while 4-Ac-A exerts only a small inhibition. These results suggest that the three aromatase inhibitors tested are able to profoundly modify the metabolism of T in the ventral prostate of the rat. In particular: 4-OH-A and 4-Ac-A are able to inhibit the conversion of T into DHT; ATD is able to inhibit the conversion of DHT into the diols; ATD and 4-OH-A do not inhibit the process of 5 alpha-reduction of delta-4-A into 5 alpha-A, while 4-Ac-A exerts only a minor effect. It is suggested that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to the inhibitory effect of the steroid tested and which is responsible for the conversion of T into the 5 alpha-reduced metabolites of the 17-OH series (DHT and the diols), and a second one, insensitive to the effects of the three steroids, which affects the conversion of delta-4-A into 5 alpha-A.

Androgens↗
PubMed1986

In vitro effects of an aromatase inhibitor on 5 alpha-reductase activity in human hypertrophic prostatic tissue.

To determine the effects of 4-hydroxy-4-androstene-3,17-dione (4-OH-A) on the in vitro conversion of testosterone (T) to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone, DHT), 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstan-3 beta, 17 beta-diol (diols), human benign hypertrophic prostatic (BPH) tissue was incubated with 4-14C-T as substrate, in the presence of 4-OH-A (10(-8) to 10(-6) M); the amounts of the 5 alpha-reduced metabolites formed were quantitated. The effects of 4-OH-A were compared with those of 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (4-MA), a known inhibitor of the 5 alpha-reductase. In the absence of 4-OH-A and 4-MA, human BPH tissue converted T to DHT and the diols readily. Both 4-OH-A and 4-MA induced significant and dose-related decreases in the formation of both DHT and the diols. The degree of inhibition induced by the different concentrations of 4-OH-A and 4-MA were 31, 41, 72% and 57, 87, 97%, respectively. The decreased formation of the diols was a consequence of the decreased availability of DHT (the immediate precursor of the diols) and was not due to direct effects of the inhibitors on the 3-hydroxysteroid dehydrogenases; both 4-OH-A and 4-MA were totally unable to modify the conversion of DHT to the diols, when 4-14C-DHT was used as substrate. Thus, 4-OH-A inhibits the process of 5 alpha-reduction of T in BPH tissue. This molecule might represent a potential new agent for the prevention and/or treatment of human BPH.

5-alpha Reductase Inhibitors↗
PubMed1985

Effectiveness and reliability of medium term treatment with a diet rich in olive oil of patients with vascular diseases.

In the present work we investigated the usefulness of olive oil in a standard hypolipidemic diet suitable for the secondary prevention of atherosclerosis. Some patients who had received a diet with a P/S value of 1.3 were turned to a diet, rich in olive oil, with a P/S ratio of 0.52; the same number of patients were fed on with the initial diet. The main differences we found were a decrease of LDL cholesterol parallel to an increase of HDL cholesterol in the patients fed on the diet rich in olive oil. No modifications were found in these patients as far as hemostatic function and liver functional tests are concerned.

Adult↗
PubMed1984

Inhibin.

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Animals↗
PubMedDate not supplied

A low cost computerized system for data management in a surgical department.

A computerized system is necessary for a surgical ward in order to document systematically the performed activity and set up a follow-up for patients. The aim of this paper is to report a program to store, recall and processing clinical data concerning fundamental information about the hospitalized patients. The main characteristic of this system is its low cost, due to the low initial hardware investment and the easy introduction of data. The use of the program does not require trained personnel. The surgeon itself, setting out simple tests, is able to obtain clinical and statistical informations of epidemiologic interest, concerning surgical cases, incidence of complications and other parameters. The system has proven itself as the basis for future highly specialized data bases for scientific and clinical research.

Computers↗
PubMedDate not supplied

Synergistic effect of testosterone and of a luteinizing hormone-releasing hormone agonist on androgen receptor content in the ventral prostate of castrated rats.

The aim of the present experiment was that of studying the effect of an LHRH agonist analog on the prostatic content of cytosol and nuclear salt-extractable and salt-resistant androgen receptors (AR). Castrated rats were treated for six days with the LHRH agonist WY 40972 (A), with testosterone enanthate (T) or with A plus T. Intact adult male rats and castrated rats treated with the vehicle served as controls. The animals were sacrificed 18 h after the last subcutaneous injection. The ventral prostates were quickly removed and submitted to subcellular fractionation for the determination of cytosol and nuclear AR content. In addition, the weights of the prostates and of the seminal vesicles were recorded, and serum levels of LH and FSH were evaluated by radioimmunoassay. The dissociation constants (Kd) of cytosol and nuclear AR, on the order of 1 x 10(-9) M, were not affected by the various treatments. Conversely, the combined treatment with T and A induced a significant increase of nuclear AR in the prostatic tissue, when compared to the levels found in castrated rats treated with T alone and in intact rats. The treatment with T was able to restore the reproductive organs to their normal weights. The treatment with A inhibited the hypersecretion of gonadotropins induced by castration. The results show that, under the conditions of the present experiment, A exhibits a synergistic effect with T on nuclear AR content in the rat ventral prostate. The results also suggest that A acts directly on this androgen-dependent structure.

Animals↗