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Biomedical subjects

A Costantini

Publications and source records attributed to A Costantini.

At least 55 records · Page 3Linked to original sources

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↗

Epidermal growth factor receptors in human hyperplastic prostate tissue and their modulation by chronic treatment with a gonadotropin-releasing hormone analog.

We characterized the epidermal growth factor (EGF) receptor in the membrane fraction of prostatic tissue from men with benign prostatic hyperplasia (BPH). The maximum specific binding of [125I]EGF to the BPH membrane fraction was achieved after 30-min incubation at 35 C. Analysis of the binding data revealed two classes of binding sites, one of high affinity [Kd, 2.5 +/- 0.5 (+/- SE) x 10(-11) mol/L] and one of lower affinity (2.2 +/- 0.3 x 10(-9) mol/L). [125I]EGF binding was inhibited by excess EGF, but not by insulin, proinsulin, fibroblast growth factor, or insulin-like growth factors I and II. In prostatic tissue of men with BPH treated for 3 months with the GnRH agonist analog Goserelin (Zoladex, depot formulation), the binding capacities of both sites were significantly higher than those of BPH tissue from untreated men (P less than 0.001). These results demonstrate that prostatic tissue from men with BPH contains two classes of specific binding sites for EGF, and their levels are modulated by chronic GnRH agonists treatment.

Aged↗

Conservative surgical treatment of renal cell carcinoma: clinical experience and reappraisal of indications.

During a 14-year period 36 patients who presented with renal cell carcinoma underwent conservative surgical treatment. The patients were divided into 3 groups according to treatment indications and condition of the contralateral kidney: group 1 included patients with a solitary kidney or bilateral tumors, group 2 patients had a damaged contralateral kidney and group 3 patients were without abnormalities of the contralateral kidney. Cumulative 6-year survival rates were 58 per cent for group 1, and 90 per cent for groups 2 and 3 combined. The over-all cumulative 6-year survival rate was 74 per cent. Based on these data extension of the indication for conservative surgical treatment seems to be justified in patients who present with low stage tumors and partial or potential damage to the contralateral organ.

Adult↗

Measurement of testosterone and its 5-alfa-reduced metabolites in human prostatic tissue using isotope dilution mass spectrometry.

5 alpha-Dihydrotestosterone (DHT) has been widely measured in human prostatic tissue using RIA since it is found to be involved in pathogenesis of human prostatic hyperplasia (BHP) and to be the best index for the follow-up of patients affected by prostatic cancer under endocrine treatment. A GC/MS method for the simultaneous determination of testosterone (T), dihydrotestosterone (DHT), 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) in prostatic tissue was developed based on the isotopic dilution technique. Trideuterated internal standards of each compound were previously synthesized in our laboratory. After previous extraction and purification on Sep-Pak C-18 cartridges and Lipidex DEAP columns, T and its metabolites were measured as heptafluorobutyric esters (HFB). Quantitative analysis was performed on a VG 7070 EQ mass spectrometer equipped with a fused silica capillary column using the Selected Ion Monitoring technique. Steroid values (means +/- SD; ng/g tissue) found in 9 human hypertrophic prostates were: T, 0.71 +/- 0.43; DHT, 4.46 +/- 1.41; 3 alpha-diol, 0.34 +/- 0.23; 3 beta-diol, 0.14 +/- 0.32.

Androstane-3,17-diol↗

Altered 1-14C arachidonic acid metabolism in arterial wall from patients with renal cell carcinoma.

The metabolism of 1-14C arachidonic acid (AA) by arterial wall in patients with renal cell carcinoma and in control patients undergoing nephrectomy was investigated by a high pressure liquid chromatography (HPLC) system. No differences in 1-14C AA uptake and in the total amount of metabolites were found between the two groups, whereas the amounts of cyclooxygenase and lipoxygenase pathway (COP and LOP) metabolites produced by patients with renal cell carcinoma were significantly lower and, respectively, higher than those produced by the control group. The COP/LOP ratio was 7.2 +/- 5.5 in the control group in comparison to 1.9 +/- 0.5 in renal cell carcinoma patients. The decrease in COP metabolites was due to a markedly reduced synthesis of prostacyclin (PGI2), with no changes in thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) production. The changes in PGI2 and 12-hydroxy-eicosatetraenoic acid (12-HETE) (metabolite of LOP) vascular production were not related to tumor dimension. The decrease in PGI2 synthesis may represent a factor favoring metastasis and thrombosis in neoplastic patients.

6-Ketoprostaglandin F1 alpha↗

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↗

Treatment of postoperative pain with suprofen injected by the intramuscular route.

The analgesic effect and the tolerability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) 200 mg/ml were compared with lysine acetylsalicylate 0.9 g/2.5 ml; the study included 60 subjects in severe to very severe pain following orthopedic surgery. The trial was performed in randomized single-blind fashion in patients who had given informed consent. The substances were injected into the upper out quadrant; maximally 4 intramuscular injections were given within 2 days. The test population was homogeneous with respect to the anamnestic data. The intensity of pain prior to treatment was comparable in both groups. Statistical analysis of the data revealed that suprofen was at the rating times (15 min to 4 h) significantly superior to the control groups. The investigator's and the patients' final appreciation indicated good to very good effect in 93% of the subjects on suprofen, and in 40 and 47%, respectively, of the patients in the control group. Here, too, suprofen was significantly superior to the reference Substance. Systemic and local tolerability of both drugs was very good. Adverse drug experience (heartburn) occurred in only 1 patient in the control group.

Adult↗

[Effect of hemorheology in the post-operative period].

Very important hemorheological changes characterize the early post-operative period. This research, performed on a group of 10 patients who underwent aorto-ilio-femoral revascularization, enables us to observe that these changes are present also in vascular surgery. In fact, plasma fibrinogen, red cells aggregation and deformability, whole blood viscosity, already modified in the pre-operative period in patients with peripheral arteriopathy, resulted significantly impaired on the 2nd and 6th day after the operation. Such changes must be considered in order to avoid ischemic consequences on microcirculation, the possible onset of deep vein thrombosis as well as an impairment of the prognosis of vascular operations (early and late reobliteration), and in order to perform an adequate and prophylactic corrective treatment.

Adult↗

Comparative pharmacokinetic evaluation of ceftriaxone and cefotaxime in coincidence for short-term antimicrobial prophylaxis in surgery.

In 48 patients undergoing elective gynecological, urological and otorhinolaryngological surgery a pharmacokinetic study after 1 g dose of ceftriaxone or cefotaxime was done. Concentrations of the two antibiotics were studied in interstitial fluid with the suction blister technique and in some tissues collected during the operation. The mean tissue levels were generally higher after ceftriaxone administration than after cefotaxime and for both drugs they were lower than the contemporary drug levels in interstitial fluid. However at the concentrations found almost all aerobic and anaerobic bacteria causing postoperative wound infections are inhibited.

Cefotaxime↗