Search PubMed⌕ Search

Biomedical subjects

P Vecsei

Publications and source records attributed to P Vecsei.

At least 55 records · Page 3Linked to original sources
PubMed1989

Comparative dose-effect studies with four C-17-spirosteroidal mineralocorticoid synthesis inhibitors.

Interference of three spirolactones and a spiro-oxazolidine with mineralocorticoid biosynthesis in the concentration range of 10(-4)-10(-10) M has been studied in isolated dispersed z. glomerulosa cells. Inhibitory effects on several enzyme activities involved in the late steps of aldosterone synthesis have been determined. Different patterns of enzyme inhibition could be observed for each inhibitor. The points of interference were mostly related to cytochrome P450-C11-activities (i.e. 11 beta-/18-hydroxylation and 18-OH-oxidation).

Aldosterone↗
PubMed1989

18,21-Anhydroaldosterone and derivatives.

18,21-Anhydroaldosterone 8, 18,21-anhydro-19-noraldosterone 9, and 3 alpha, 5 beta-tetrahydro-18,21-anhydro-19-noraldosterone 13, which may be present in acid-processed urine, were prepared by cleaving their 20-ketal derivatives 2, 3, and 12 with hot mineral acid. Compounds 8 and 9 were also made by direct dehydration of aldosterone 5 and 19-noraldosterone 10 in good yield. The reverse ring opening of 8 to 5 could be carried out in moderate yield with an acetic acid-acetic anhydride-perchloric acid mixture, while an analogous ring opening of 9 gave only a poor yield of 10.

Aldosterone↗
PubMed1989

18, 19-Dihydroxycorticosterone: a new metabolite in human urine.

Urines of patients with primary aldosteronism were extracted, the extract repeatedly chromatographed with reversed phase HPLC. The fractions immunoactive against 18-hydroxycorticosterone antiserum and being more polar than the 18-hydroxycorticosterone were further purified, derivatized and investigated by GC/MS. In this manner the natural occurrence of the 18, 19-dihydroxycorticosterone, which was lately synthetized, in human urine was confirmed.

18-Hydroxycorticosterone↗
PubMed1989

Steroid responses to ACTH in women with polycystic ovaries.

Sixty-three women with ultrasonically detected polycystic ovaries (PCO) were investigated for a disorder of adrenal steroid biosynthesis. Serum was obtained before, and at 30 and 60 min after, the administration of 250 micrograms tetracosactrin, and assayed for 17 alpha-OH-progesterone, 21-deoxycortisol, 17 alpha-OH-pregnenolone and dehydroepiandrosterone by radioimmunoassay following paper chromatography. Results were compared with those in 11 women with normal ovaries, seven adult females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), and 15 women heterozygous for this defect. Although the basal-peak steroid concentration differences were significantly greater when ACTH tests were conducted between 1400 and 1700 h than between 0900 and 1000 h, absolute peak steroid concentrations were not different at either time of day. Four of 63 (6.4%) women with PCO had responses to ACTH characteristic of non-classical (late onset) 21OHD CAH, and about half the remainder had responses characteristic of 21OHD heterozygotes. There was no clear cut evidence for a deficiency in 3 beta-hydroxysteroid dehydrogenase activity in women with PCO.

17-alpha-Hydroxypregnenolone↗
PubMed1989

Corticotrophin-releasing factor-like immunoreactivity in human 24 h urine.

This report is the first demonstration of the presence of corticotrophin-releasing factor-like immunoreactive material (CRF-LI) in human urine. Our studies, using immunoaffinity chromatography for extraction, followed by reverse phase high performance liquid chromatography for further purification, and radioimmunoassay for final peptide measurement, suggest that CRF-LI from human urine is similar, if not identical, to human CRF. Urinary CRF-LI excretion in normal subjects was 1.48 +/- 0.69 ng/24 h (mean +/- SD; n = 20) with no significant differences between the sexes. During pregnancy, urinary CRF-LI excretion increased, and a significant correlation between urinary CRF-LI excretion and the gestational age was seen (r = 0.62; P less than 0.0001). We suggest that urinary 24-h CRF-LI excretion may reflect the secretion of CRF into the circulation. Measurements of CRF-LI in the urine may have several advantages over determinations of hormone levels in plasma.

Adolescent↗
PubMed1989

In-vitro steroid production by human granulosa lutein cells in long-term cultures.

delta 4 and delta 5 pathway steroidogenesis by human granulosa lutein cells (GLC) in long-term cultures (6-8 days) was investigated under basal (10% serum + medium + GLC) and stimulated (human chorionic gonadotropins (hCG), 100 mIU/ml) conditions. In the delta 4 pathway, 17-hydroxyprogesterone (17-OHP) secretion increased from 160-fold at 48 hours of culture to 360-fold at 144 hours under basal conditions, when compared with the respective controls (concentrations in the 10% serum added to the medium) (p less than 0.005). HCG further augmented 17-OHP production significantly at 96, 144 and 192 hours of culture. Progesterone (P) secretion behaved similarly, and increased from 150-fold at 48 hours to 560-fold at 96 hours when compared with controls, being further stimulated by hCG. In contrast, androstenedione (A) secretion throughout the entire culture period increased only slightly (3-5-fold) under both basal and stimulated conditions, when compared with the respective controls. In the delta 5 pathway, the secretory pattern of 17-hydroxypregnenolone (17-OHPregn) and dehydroepiandrosterone (DHEA) was similar to that observed with A, and both steroids increased only slightly under basal and stimulated conditions, when compared with their respective controls. In conclusion, 17-OHP and P are secreted in very significant amounts during the entire culture period while 17-OHPregn, DHEA and A are secreted in extremely small amounts. These results demonstrate that the delta 5 pathway is inactive in long-term human GLC cultures while the delta 4 pathway is active in certain portions only.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxypregnenolone↗
PubMed1989

Effects of WY 47987 (atrial natriuretic factor 102-126) in patients with renal insufficiency: a placebo-controlled, randomised study.

We studied renal, hormonal and cardiovascular effects of ANF 102-126 (WY 47987) in seven patients with chronic renal failure (serum creatinine 25-68 mg/l) and in four normal volunteers. ANF or placebo bolus injections were given at 1, 2, and 3 micrograms/kg i.v. (each dose on separate days). As compared to placebo, ANF did not induce changes of renal excretory parameters, of plasma renin and aldosterone or of blood pressure and heart rate in patients. In healthy volunteers, however, the same dose of ANF increased urinary excretion of sodium, potassium, calcium, chloride and phosphorus as well as water, and creatinine clearances, and decreased plasma aldosterone. The data suggest blunted effectiveness of ANF bolus injections in patients with renal insufficiency.

Aldosterone↗
PubMed1988

Aldosterone metabolism in rat renal tissue in vitro. Formation of lipid soluble metabolites.

In the present study the formation of lipid soluble metabolites from 3H-aldosterone was investigated in vitro in isolated kidneys and kidney and liver slices of Sprague Dawley rats. The steroids were separated by HPLC (forward and reversed phase systems) and detected on-line as UV- or 3H-chromatograms. Apart from an unenzymatically formed substance, isoaldosterone, three less polar metabolites were traced (A1, A2, A3). The structure of the quantitatively most important metabolite (A1), was identified as 5 alpha-dihydroaldosterone using a combination of techniques such as chromatographic comparison with reference steroids, antibody binding and mass spectrometry. Evidence for further conversion of DHaldo to 3 alpha, 5 alpha-tetrahydroaldosterone was obtained in chromatographic and antibody binding studies. The formation of metabolites was not dependent on glomerular filtration. Furthermore it displayed regional heterogeneity with highest activity in the outer medulla. Finally it was observed that the in vitro metabolism of aldosterone was not saturable over a range of initial aldo concentration of 10(-9) to 10(-5) M.

Aldosterone↗
PubMed1988

Judgement of the hypothalamic-pituitary-adrenocortical function in psychiatric patients by betamethasone-induced cortisol suppressibility.

Betamethasone induced cortisol suppressibility was examined in 62 drug free consecutively admitted psychiatric inpatients. Betamethasone was choosen instead of the commonly used dexamethasone, because its double half-life compared to dexamethasone and its higher tissue availability. After a base-line evaluation with blood samples drawn at 8 a.m., 4 p.m., and 11 p.m., 0.5 mg or 1.0 mg betamethasone was given orally at 11 p.m. Postbetamethasone cortisol as well as betamethasone blood levels were then measured at the same time points as on the baseline day. In the groups receiving 1.0 mg betamethasone non-depressed patients had significantly (p less than 0.05) lower postbetamethasone cortisol levels than depressed patients for each time point measured whereas 0.5 mg betamethasone did not differentiate depressed from non-depressed patients. Patients with other depressions like schizoaffective psychosis-depressive subtype- or organic brain syndrome with depressive symptomatology demonstrated similar postbetamethasone cortisol profiles as the group of patients with major depression. Betamethasone plasma concentrations differed significantly (p less than 0.001) with respect to the oral dosage with higher values for the 1.0 mg betamethasone groups.

Adolescent↗
PubMed1988

Urinary excretion of aldosterone metabolite Kelly-M1 in patients with adrenal dysfunction.

Using tetrahydroaldosterone antibody a radioimmunoassay was developed to measure substance Kelly-M1 (K-M1) in human urine. The normal values were lower than observed by Kelly et al. who discovered the catabolite after giving large doses of exogenous aldosterone. While in essential hypertension the excretion of K-M1 was predominantly within the normal range, elevated values were found in most cases of 21-hydroxylase deficiency, both the simple virilizing and salt losing form, primary aldosteronism, renal hypertension and cystinosis. Our findings suggest that K-M1 may be formed from 21-deoxyaldosterone and/or by microbial intervention from aldosterone or its metabolites.

Adrenal Gland Diseases↗
PubMed1988

Role of intestinal bacteria in the metabolism of aldosterone in man.

Urinary aldosterone metabolites were measured before and after the administration of 1 g/day of kanamycin, a nonabsorbable antibiotic, for 7 days, in 6 normal volunteers and in 11 patients with liver cirrhosis. Urinary excretion of 21-deoxytetrahydroaldosterone (21-deoxy-THAldo) decreased by 40 and 86% from the control values in normal volunteers and in patients, respectively (p less than 0.05), after kanamycin administration. Urinary excretion of 21-deoxyaldosterone (21-deoxy-Aldo) also fell by 48 and 89% in normal subjects and in patients, respectively, but the decrease was significant only in the normal subjects (p less than 0.05). In normal volunteers, urinary free aldosterone and THAldo remained constant, whereas the ratio of 21-deoxy-Aldo to aldosterone and 21-deoxy-THAldo to THAldo decreased from 10.2 to 3.7 and 2.1 to 0.3, respectively (p less than 0.01). These results indicate that intestinal bacteria participate in the metabolism of aldosterone during enterohepatic circulation in man.

Adrenal Cortex Hormones↗
PubMed1987

Immunohistologic localization of corticotrophin-releasing hormone in human tumors.

The authors investigated formalin-fixed, paraffin-embedded human tissues for the presence of corticotrophin-releasing hormone (CRH) using the avidin-biotin-peroxidase technic. Immunopositivity was demonstrated in nontumorous hypothalami, 1 of 8 hypothalamic gangliocytomas, 3 of 9 bronchial endocrine tumors, 1 of 30 small cell lung carcinomas, 1 of 8 ileal endocrine neoplasms, 2 of 20 pancreatic endocrine tumors, 2 of 10 medullary thyroid carcinomas, and 1 of 3 small cell prostate carcinomas. Of the tumors containing immunoreactivity, most were associated with Cushing's syndrome; the ileal and thyroid tumors were not. Adrenocorticotrophic hormone was immunohistochemically localized in two bronchial and one pancreatic tumor, which contained CRH-like immunoreactivity. No CRH was detected in nontumorous extrahypothalamic tissues from which the CRH-containing tumors derived, two mediastinal endocrine carcinomas, six endocrine tumors of the stomach/duodenum/appendix, eight pheochromocytomas, one Merkel cell tumor, and 32 squamous and adenocarcinomas of the lung/gut. CRH-like immunoreactivity may be found in tumors composed of peptide-hormone-producing endocrine cells; hypersecretion of CRH by those neoplasms may be significant in the development of Cushing's syndrome.

Adolescent↗
PubMed1987

21-Deoxyaldosterone excretion in patients with primary aldosteronism and 21-hydroxylase deficiency.

21-Deoxyaldosterone appears in urine in free and conjugated forms. Total excretion is best determined after acid hydrolysis (pH 1) of urine, followed by extraction, repeated chromatographic purification, and quantitation of the steroid by RIA. 21-Deoxyaldosterone excretion was normal in 70% of patients with essential hypertension (n = 18), while 30% (n = 8) had more or less elevated values. In patients with primary aldosteronism (n = 21) elevated as well as normal values of urinary 21-deoxyaldosterone were found, indicating that in some patients aldosterone may be formed not only from corticosterone but also from the 21-deoxy compound. In patients with 21-hydroxylase deficiency (n = 21) urinary 21-deoxyaldosterone was invariably elevated, whether the patients had the virilizing or salt-losing form of the disease. Although the clinical manifestations of the salt-losing form seem unrelated to the inability to convert 21-deoxyaldosterone to aldosterone, the determination of 21-deoxyaldosterone adds insight into the biosynthesis of aldosterone in primary aldosteronism and 21-hydroxylase deficiency.

Adolescent↗
PubMed1987

Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone in essential hypertension and primary aldosteronism.

The effects of ovine corticotropin releasing factor (o-CRF) on plasma aldosterone, 18-OH-corticosterone (18-OHB), plasma adrenocorticotropin (ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma (APA) and two with idiopathic hyperaldosteronism (IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension (EHT, 5 with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100 micrograms iv of o-CRF (226% and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses (840 +/- 156, and 419 +/- 121 ng/dl.hr, respectively) were also significantly greater (p less than 0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF-induced ACTH, and possibly other proopiomelanocortin (POMC)-derived peptides.

18-Hydroxycorticosterone↗
PubMed1987

In pregnancy, corticotropin-releasing-factor in maternal blood and amniotic fluid correlates with the gestational age.

Immunoreactive corticotropin-releasing factor (IR-CRF) was measured in maternal plasma and amniotic fluid. Significant correlations between both IR-CRF levels in maternal plasma (p less than 0.001, n = 82, r = 0.458) and IR-CRF levels in amniotic fluid (p less than 0.001, n = 81, r = 0.424) and the gestational age were seen. We conclude that CRF may regulate the ACTH cortisol axis in the placenta-fetus unit.

Amniotic Fluid↗
PubMed1986

Radioimmunoassay of urinary 21-deoxytetrahydroaldosterone in primary aldosteronism and 21-hydroxylase deficiency.

A radioimmunoassay of 21-deoxytetrahydroaldosterone was developed. Normal daily excretion of the unconjugated metabolite was 1.2 +/- 1.3 micrograms and of the glucuronized metabolite, 11.9 +/- 7 micrograms. The tetrahydroaldosterone/21-deoxytetrahydroaldosterone ratio varied more in patients with primary aldosteronism than in control subjects. Thus, measurements of the urinary excretion of the tetrahydroaldosterone or 21-deoxytetrahydroaldosterone alone did not provide an accurate expression for aldosterone production. Their sum correlated well with the clinical condition, i.e. clear-cut elevation in patients with primary aldosteronism. The diminished tetrahydroaldosterone/21-deoxytetrahydroaldosterone ratio found in patients with 21-hydroxylase deficiency may be attributed to increased bacterial conversion of tetrahydroaldosterone to 21-deoxytetrahydroaldosterone but could also stem from a deficiency implicating zona glomerulosa (aldosterone biosynthesis) regardless of the stage and clinical presentation of the disease.

Adrenal Hyperplasia, Congenital↗
PubMed1986

HPLC isolation and GC-MS characterization of a compound strongly cross reacting with tetrahydroaldosterone antiserum.

Urines from patients with hypertension and elevated aldosterone levels, i.e. primary aldosteronism due to adrenal adenoma or hyperplasia or carcinoma were extracted, paper chromatographed and thereafter chromatographed repeatedly with normal phase and repeatedly with reversed phase HPLC systems in an attempt to find new metabolites of aldosterone. Specific 3 alpha-hydroxy-5 beta-tetrahydroaldosterone antiserum was used in a radioimmunoassay system to detect possible aldosterone metabolites in the HPLC fractions after each isolation step. The immunoactive HPLC fractions were derivatized and analysed by GC-MS. A relatively nonpolar compound, 11 beta:18(S),18:20 alpha-diepoxy-5 beta-pregnan-3 alpha-ol, was isolated and identified in this manner. This material was originally described by Kelly et al., in 1962 after loading human subjects with huge amounts (25-160 mg) of exogenous aldosterone. This material has not yet been described from endogenously produced aldosterone. Very small amounts, if any, were similarly isolated from the urine of a control subject. Therefore, this compound could prove to be a new marker for hypertension due to hyper-production of aldosterone.

Aldosterone↗