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Biomedical subjects

M Kurcz

Publications and source records attributed to M Kurcz.

At least 19 recordsLinked to original sources

Neonatal treatment with phenobarbital, zixoryn and chloramphenicol lack of imprinting effect of zixoryn on microsomal enzyme activities.

Two potent microsomal enzyme inducing agents, phenobarbital and flumecinol (Zixoryn) as well as the microsomal enzyme inhibitor chloramphenicol (Chlorocid) were given subcutaneously to newborn rats in the first 5 days of their life. Microsomal cytochrome P-450 and b5 content and various cytochrome P-450 and P-448 dependent enzyme activities were measured at the age of 20 weeks. Phenobarbital had positive imprint effect on aminopyrine N-demethylase activity in female and on aniline hydroxylase activity in male rats. Flumecinol had no imprint effect. Chloramphenicol had a positive imprint on aniline hydroxylase activity in male rats. Sex differences in microsomal enzyme activities were not affected by the xenobiotics used.

Animals↗

Effect of digoxin on human erythrocyte glucose-6-phosphate dehydrogenase activity. A link to natriuretic hormone?

The authors studied the effect of a 0.5 mg intravenous bolus injection of digoxin on human red blood cell glucose-6-phosphate activity under in vivo circumstances. Digoxin administration resulted in a small but statistically significant rise in the enzyme activity. This effect of digoxin seems to support the hypothesis that the circulating sodium transport inhibitor substance or natriuretic hormone found in a group of patients with essential hypertension may be an endogenous digitalis because the two substances act similarly in this respect.

Adult↗

Tripeptide aldehyde protease inhibitors may depress in vitro prolactin and growth hormone release.

The effects of novel nontoxic tripeptide aldehyde inhibitors of proteolytic enzymes were examined in order to investigate the possibility that serine-thiol protease(s) may be involved in PRL and GH secretion. Rat anterior pituitary cells maintained in culture for 7-8 days or freshly taken pituitary quarters were treated with BOC-DPhe-Pro-Arg-H (BOC-dPPA), DPhe-Pro-Arg-H (dPPA), BOC-DPhe-Leu-Lys-H (BOC-dPLL), or BOC-DPhe-Phe-Lys (BOC-dPPL). Newly synthetized [3H]PRL and [3H]GH as well as immunoreactive (i) hormones (iPRL, iGH) were measured in the incubation media and cell homogenates. Four hours of incubation in the presence of 0.1 mM dPPA resulted in a 30% decrease of [3H]PRL and iPRL release by cell cultures; the inhibition by BOC-dPPA was 60% and 48%, respectively. [3H]PRL biosynthesis was unchanged or slightly decreased. The effect of these tripeptide aldehydes on [3H]GH and iGH release was less pronounced but statistically significant. Pituitary quarters treated with 1.0 or 3.0 mM BOC-dPPA release 20% and 57% less [3H]PRL than the controls. In the same system BOC-dPPA in a 1.0 mM concentration did not effect GH secretion, and 3.0 mM BOC-dPPA inhibited [3H]GH output by 27%. Forty micromolars of BOC-dPPL decreased by 47%, 0.2 mM by 79%, and 1.0 mM by 94% [3H]PRL release from pituitary quarters. GH secretion was not influenced. A similar selectivity was observed when BOC-dPLL was used. It is clear that by serine-thiol protease inhibitors whose effects are sequence and dose dependent, PRL and GH release are decreased. The relative inhibiting potency on PRL release was BOC-dPPL greater than BOC-dPLL greater than BOC-dPPA greater than dPPA. The biosynthesis of [3H]PRL was reduced only in the presence of the highest tripeptide aldehyde concentrations or long (8 h) exposure, and only 1.0 mM Boc-dPPL reduced [3H]GH biosynthesis by 30%. The data suggest that proteolysis may be involved in the process of PRL and GH release and the enzyme(s) in question may be serine-thiol protease(s).

Aldehydes↗

Biochemical markers in suicidal patients. Investigations with cerebrospinal fluid amine metabolites and neuroendocrine tests.

141 female psychiatric patients, suffering from major depression, schizophrenia, alcohol dependence or adjustment disorder, were investigated for their 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and cortisol level in the cerebrospinal fluid (CSF). Dexamethasone suppression tests were also performed in 111 cases, and TRH/TSH tests in 40 subjects. Fifty-two patients were hospitalized following a recent suicide attempt, 18 of which were made using a violent method. The other 34 attempters took tranquilizer or sedative overdoses. CSF 5-HIAA was significantly lower in violent attempters in all 4 diagnostic categories. CSF HVA was higher in those taking drug overdoses, but only in depression (and less markedly in schizophrenia). CSF cortisol did not differ among either diagnostic or suicidal subgroups. Dexamethasone suppression was more frequently abnormal in suicidal patients than in nonattempters, and this difference was more important where the overall nonsuppression rate was lower. Maximal TSH response to TRH showed an inverse correlation with CSF 5-HIAA, and it was lowest in the nonattempter group. The difference between violent suicide attempters and nonattempters in their TSH response was significant. Since these biochemical changes were more or less independent of clinical diagnoses, it seems relevant to explore further the biological background of human aggression and suicide as a separate research direction.

Adult↗

Changes in hypophyseal luteinizing hormone (LH) content during fetal and early postnatal life, and capacity of fetal and early postnatal pituitaries to synthesize and release LH in vitro.

The developmental pattern of hypophyseal luteinizing hormone (LH) during fetal and early postnatal life, and the capacity of fetal and early postnatal pituitaries to synthesize, release and store LH in the absence of any hypothalamic influence were investigated. Pituitary radioimmunoassayable LH was detectable by fetal day 12; its level remained low up to fetal day 17 and thereafter continued to increase up to postnatal day 2 with sharp rises occurring between day 17 and 18 of gestation and after birth. Cultured fetal and early postnatal pituitary primordia were able to synthesize, to release and store the hormone, however, the pattern of these cellular functions varied according to the animal age when explantation was performed. Data derived from cultured pituitaries showed a gradual rise in the daily hormone content of the medium between fetal day 13 to 17. From fetal day 19 onwards, however, the daily discharge of LH decreased. These findings suggest that the fetal and early postnatal pituitary has the capacity to synthesize and release LH, furthermore after a period of independent differentiation hypothalamic signals appear to be required for pituitary hormone release.

Animals↗

The effect of dexamethasone on cerebrospinal fluid monoamine metabolites and cortisol in psychiatric patients.

The effect of 1 mg dexamethasone on CSF levels of 5-hydroxyindoleacetic acid (5 HIAA), homovanillic acid (HVA) and cortisol (CS) was investigated in 100 psychiatric inpatients: 45 subjects had their lumbar punctures 1-4 days following dexamethasone administration, and the results were compared with those from 55 other patients investigated before drug ingestion. All patients were women, and none had received psychotropic medication for at least two weeks before the study. Seven subjects consented to two LPs both before and after dexamethasone. As expected, cortisol in the CSF significantly decreased after dexamethasone: the decrease was greatest 10 hours following the drug. HVA showed a weak and transient elevation after 10 hours only. CSF 5 HIAA was found to be significantly increased in postdexamethasone samples and high levels were still found even after 82 hours. Diagnostic differences (major or minor depression, schizophrenia, alcohol abuse or dependence) did not account for the observed differences. Repeated CSF examinations in seven subjects corroborated these findings: all cortisol values were decreased and all 5 HIAA values were increased after dexamethasone while HVA values showed random changes. The data may suggest that serotonergic mechanisms may be involved in dexamethasone action in the CNS. In addition, dexamethasone administration can alter CSF 5 HIAA level, a possible factor which should be taken into consideration in CSF studies.

Adult↗

Studies on the prolactin response induced by electroconvulsive therapy in schizophrenics.

Electroconvulsive therapy (ECT) and simulated ECT (SECT)-induced prolactin response has been studied in 14 schizophrenic males. Cortisol, growth hormone, and thyroid stimulating hormone (TSH) changes have been measured simultaneously. The prolactin rise was significantly higher after ECT than after SECT. Cortisol increase after ECT did not exceed significantly the elevation after SECT. Changes in growth hormone and TSH concentrations were inconsistent and non-significant. On the basis of the results it may be assumed that ECT-induced prolactin response is a consequence of specific transmitter changes in the CNS and not a result of stress reaction or generalized neuronal discharge. ECT-induced prolactin response was negligible in two cases. Both patients were chronically hospitalized schizophrenics resistant to therapy. Whether the prolactin response or its absence is of predictive value with respect to prognosis or effect of ECT remains to be seen.

Adult↗

Major metabolic pathways and hormone production in unstimulated monolayer cultures of the rat anterior pituitary.

In cell cultures derived from anterior pituitary glands of rats, enzyme activities of cell homogenates and hormone (GH, PRL, LH, and FSH) content of the culture media were measured. Sex differences in enzyme activities representing major metabolic pathways (citrate cycles, pentose cycles, and glycolysis) were demonstrated both in freshly dispersed cells and in 8-day-old cultures; in cultures of both sexes enzyme activities increased during cultivation. In cultures derived from female rats, cell protein doubled by the 12th day and remained constant for up to the 24th day in culture, whereas enzyme activities showed changes suggesting that cell metabolism shifted to anaerobic glycolysis during cultivation. In the culture media the presence of four pituitary hormones was demonstrated for as long as 3 weeks of cultivation with variable secretion dynamics; the release of gonadotropic hormones diminished gradually whereas that of GH remained constant and PRL levels increased with time. These results indicate that under strictly defined culture conditions pituitary cells may function in spite of profound metabolic changes.

Acid Phosphatase↗

Activity alterations of metabolic enzymes in the anterior pituitary of female rats during acute and chronic starvation, as well as after refeeding.

The activity of glycolysis and hexose monophosphate shunt decreases while the activity of some oxydative enzymes and acid phosphatase increases in the anterior pituitary of adult female rats during starvation. The alterations depend on the severity of starvation. The polypeptide hormone production also decreases. A close relationship exists between the metabolic activity of the gland and its endocrine function.

Acid Phosphatase↗

Changes of lactic dehydrogenase activity and combination of its subunits in rat anterior pituitary during puberty and in maturity, as well as during estrous cycle on the actue effect of estradiol and after castration.

LDH activity in the female rat anterior pituitary increases substantially at the opening of the vagina, after the gradual increase up to the 90st day no important change occurs. During the estrous cycle activity reaches its peak during the estrus, and lowest in ghe proestrus. Molecular organization of the enzyme shows a change only at the opening of the vagina, i. e. a sudden decrease of H/M ratio occurs, value of which does not change during the estrous cycle. Pituitary LDH activity and subunit ratio in males remains constant during life. LDH activity excess in mature female rat pituitary, being about the double as compared to males, develops at the age of about three months, the difference in H/M ratio however is manifest already during puberty. Anterior pituitary LDH activity and structure of the enzyme are affected by sexual hormones, primarily by estradiol, under physiological conditions, too. After ovariectomy LDH activity decreases gradually. The value before the opening of the vagina to be considered as basal level, develops in the 4th postoperative week. H/M ratio decreases by 20 per cent one week after the operation and shows no change thereafter. Orchidectomy involves but a minor activity and H/M ratio decrease. Experimental findings on activity and subunit ratio are related presumably to prolactin cells and suggest that sexual hormone feedback effects in addition to polypeptide production pituitary metabolism.

Animals↗

The role of estrogens in the regulation of lactate dehydrogenase activity and its submolecular organization in rat anterior pituitary.

Estrogens increase LDH activity and decrease H/M subunit ratio in rat anterior pituitary in both the experimental circumstances and the physiological conditions. The cellular messengers mediating estrogenic effect are structure- and stereospecific. The activity increasing and subunit ratio decreasing potency of the three tested estrogens was of following decreasing order: 17 beta-estradiol, estrone, and estriol. 17 alpha-estradiol did not affect activity parameters and submolecular organisation of the enzyme. The estrogen induced activity increase is consequence of the enhanced de novo enzyme protein synthesis which could be inhibited by Actinomycin-D. The lack of adrenocorticoids did not involve the alteration of LDH activity and H/M ratio in female rat anterior pituitary. Accordingly, these steroids do not mediate estrogenic action. 17 beta-estradiol had a substantial increasing effect on LDH activity in the subrenal implanted pituitary homografts and decreased H/M subunit ratio. Pituitary LDH activity in androgenized female rats decreased only after the removal of the polycystic ovaries. The two latter observations suggest that hypothalamic hormones are not involved in the regulation of pituitary LDH activity and its submolecular organization. De novo synthesis of LDH enzyme protein and the regulation its submolecular organization is induced by the direct action on anterior pituitary cells of the estrogens.

Adrenalectomy↗