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Biomedical subjects

M Tóth

Publications and source records attributed to M Tóth.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effects of genistein on cardiac contractile force and atrial natriuretic peptide secretion in the isolated perfused rat heart.

We examined the effects of a selective protein tyrosine kinase inhibitor, the isoflavonoid genistein, on haemodynamics and atrial natriuretic peptide (ANP) secretion in perfused rat heart preparations. The addition of genistein into the perfusion fluid at concentrations of 11, 22 and 37 microM for 30 min in the spontaneously beating rat hearts caused dose-dependent, sustained increases in contractile force, perfusion pressure and immunoreactive ANP secretion, while heart rate remained constant. The positive inotropic and vasoconstrictor effects of genistein were significantly (P < 0.001) greater in the paced than in spontaneously beating rat hearts. Infusion of the calcium-channel antagonist diltiazem (3 microM) inhibited the genistein-induced positive inotropic effect by 52% (P < 0.001), and KN-62 (1.5 microM), an inhibitor of Ca2+/calmodulin-dependent protein kinase II, by 34% (P < 0.001). The genistein-induced increase in immunoreactive ANP secretion was completely blocked by diltiazem (P < 0.001) while KN-62 delayed (P < 0.02) the increase of immunoreactive ANP concentration in the perfusate. These results show that genistein, at concentrations known to inhibit the activities of protein tyrosine kinases, dose-dependently increased contractile force, coronary vascular tone and ANP secretion from isolated perfused rat hearts. These cardiac effects of genistein may be mediated by elevation of intracellular Ca2+ concentration, as shown by the inhibition of inotropic and secretory effects by both L-type calcium channel antagonist and Ca2+/calmodulin-dependent protein kinase inhibitor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Hypoxia stimulates release of ANP and BNP from perfused rat ventricular myocardium.

We determined the effect of hypoxia on cellular energy state and ventricular atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and endothelin-1 (ET-1) release in an isolated perfused heart preparation after removal of all atrial tissue in 21- to 24-mo-old Wistar-Kyoto rats. After a control period (14 min), the ventricles (n = 6) were exposed to 30 min of hypoxia by changing the gas mixture to N2-CO2 (95:5 vol/vol; hypoxic period) and back to O2-CO2 (95:5 vol/vol) for 30 min (reoxygenation period). Control hearts (n = 6) were perfused throughout the experiment (74 min) with oxygenated Krebs-Henseleit phosphate-free buffer. In parallel experiments, the metabolic state of oxygenated (n = 4) and hypoxic (n = 5) ventricles was assessed using 31P-nuclear magnetic resonance (31P-NMR). Hypoxia caused a rapid decrease in left ventricular peak systolic pressure associated with a 2.1-fold increase (27.6 +/- 2.2 to 58.0 +/- 13.1 fmol/ml; P < 0.05) in the concentration of immunoreactive (ir) ANP and a 1.6-fold increase (2.5 +/- 0.2 to 3.9 +/- 0.5 fmol/ml; P < 0.05) in the [irBNP] (where brackets signify concentration) in the perfusate. In contrast, perfusate [irET-1] (1.2 +/- 0.2 fmol/ml) did not change significantly during hypoxia. 31P-NMR showed that the [ATP]-to-[ADP].[Pi] ratio was reduced during hypoxia with a simultaneous increase in intracellular monophosphates and perfusate [irANP] and [irBNP]. The decrease in the cytosolic pH during hypoxia was small. High-performance liquid chromatography of the perfusates showed that the ANP-like immunoreactive material released corresponded to the processed, low-molecular weight peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Ca(2+)-dependent and Ca(2+)-independent NO-synthesizing activities of human primordial placenta.

In order to localize the site of production of nitrogen monoxide (NO) in first trimester human pregnancy, the cytosol and microsome fractions prepared from homogenized primordial placentas were tested for NO-synthase (NOS) activities by measuring the NADPH-dependent conversion of [3H]arginine to [3H]citrulline. Our results demonstrate that Ca(2+)-dependent enzyme activities are present in both fractions, whereas microsomes exhibit significant Ca(2+)-independent enzyme activity too. The highest specific activity is measurable in the presence of Ca2+ with microsomes, this activity is about 2-fold higher than the Ca(2+)-dependent specific activity of the cytosol. The Ca(2+)-independent specific NOS activity is about 30% of the Ca(2+)-dependent microsomal activity. The microsomal Ca(2+)-dependent NOS activity is inhibited by 50% in the presence of 0.5 mM aminoguanidine (AG), whereas the Ca(2+)-independent activity does not respond to this concentration of AG, suggesting that it is not the inducible isoform of NOS. Our results indicate that (I) NOS activity is present from an early phase of placental development, (II) the NOS activity is of trophoblastic origin, since the primordial placenta is avascular and (III) NO-production by the primordial placenta can proceed in the absence of any Ca(2+)-mobilizing agonist.

Amino Acid Oxidoreductases↗
PubMed1994

Atrial natriuretic peptide (ANP) responsiveness in patients with hypothyroidism.

Hypothyroidism is known to be associated with abnormalities of kidney function; recently, low atrial natriuretic peptide (ANP) plasma levels have been reported. Aim of the study was to asses ANP, sodium and water responsiveness to an acute saline load. Twelve patients with established primary hypothyroidism and 9 control subjects were studied. ANP was determined in plasma by RIA with extraction, prior to and after the infusion of saline, 500 ml/h for 4 hours. On a similar albeit liberal sodium diet hypothyroid patients excreted less sodium and water (74 +/- 33 (SD) mumol/min and 0.69 +/- 0.15 ml/min, respectively) than control subjects (110 +/- 52 mumol/min; P < 0.05 and 1.06 +/- 0.53 ml/min; P < 0.025, respectively). However, the infusion of saline resulted in a 3-fold increase of sodium output and more than 2-fold increase in urine flow. The exaggerated responsiveness in sodium excretion in patients with hypothyroidism was associated with significantly decreased pre-infusion ANP plasma levels (16.1 +/- 11.1 pg/ml vs. 44.4 +/- 14.4 pg/ml; P < 0.001) and also with sluggish response to the volume expansion (+24% vs. +48%). A significant correlation was found between serum T4 levels and plasma ANP concentrations in 8 patients (r = 0.689; P < 0.05). Although hypothyroid patients tend to retain sodium on a liberal salt diet, their kidney is capable of vigorously eliminating excess sodium when challenged with an acute saline load. This exaggerated responsiveness of sodium excretion can be demonstrated in spite of a sluggish response in ANP. Subnormal ANP levels in hypothyroidism are probably the result of thyroid deficiency.

Adult↗
PubMed1993

Attenuation of diacylglycerol signal in the primordial human placenta: role of phosphatidylcholine formation.

Metabolic conversion of the synthetic DAG, dioctanoylglycerol (DOCG) into the dioctanoyl species of phosphatidic acid (PADOCG) and phosphatidylcholine (PCDOCG) in minced human primordial placenta incubated with [32P]phosphate was studied. Time-course experiments performed with 0.25 mM DOCG revealed a much higher capacity of the placenta to synthetize PCDOCG than PADOCG and indicated the rapid metabolism of PCDOCG. In addition, DOCG stimulated the labeling of PC whereas no such effects on the labeling of lyso-PC and PA were observed. This effect of DOCG is not related to the synthesis of PC de novo, because DOCG did not exhibit any stimulating effect on the synthesis of PC from [3H]glycerol or [3H]glucose. Experiments with varying concentrations of DOCG (0.025-0.5 mM) showed increasing rate of formation of PCDOCG over a concentration range from 0.05 to 0.5 mM whereas 0.5 mM DOCG was the lowest concentration where significant formation of PADOCG was found. Labeling of PC was about 30% over control at 0.125 mM as well as at 0.25 mM DOCG, and decreased below the control level at 0.5 mM DOCG. Labeling of PA and PI was not influenced by these DOCG concentrations. Labeling of PC, either stimulated by DOCG or not, was more sensitive to the inhibitory effect of 1 mM of the DAG analog: dioctanoylethyleneglycol (DOEG) than that of PA. Moreover, 1 mM DOEG inhibited the formation of PCDOCG without such an effect on the labeling of PADOCG. These findings indicate that in the primordial human placenta PC synthesis represents a more efficient attenuation pathway of DAG signal than the formation of PA by DAG kinase.

Diacylglycerol Cholinephosphotransferase↗
PubMed1993

[Multiple endocrine neoplasia].

The authors review present knowledge on multiple endocrine neoplasias types 1 and 2. They discuss in the light of recent literature data, the natural history, diagnosis, differential diagnosis and the optimal diagnostic approaches of these disorders. A short review on the therapeutic modalities draws attention to important differences between sporadic and inherited endocrine tumors. Finally, the authors emphasize recent developments about the genetic background and the importance of molecular biologic techniques, including family screening in the diagnosis of these disorders.

Endocrine Gland Neoplasms↗
PubMed1993

Adenosine inhibits the release of atrial natriuretic peptide from the perfused rat heart.

The effect of adenosine on atrial natriuretic peptide (ANP) release was studied in the perfused rat heart model. Adenosine had no effect on the heart rate of the spontaneously beating heart at a concentration of 1 microM, whereas at concentrations of 10 and 100 microM it dose-dependently decreased the frequency by 17 and 55% (P < 0.05 and P < 0.001, respectively). In the spontaneously beating hearts, immunoreactive ANP release was inhibited by adenosine at concentrations of 10 and 100 microM (P < 0.05 and P < 0.01). When heart rate was maintained constant by external pacing, inhibition of ANP release was observed only with 100 microM adenosine (P < 0.01). The results show that adenosine dose-dependently inhibits ANP release from the perfused rat heart. The effect of adenosine on ANP release was partially due to its negative chronotropic effect but the results suggest that adenosine may also have a direct inhibitory effect on ANP release in atrial myocardium.

Adenosine↗
PubMed1993

[Flow-cytometric study of the DNA content in adrenal cortex tumors].

Flow cytometric deoxyribonucleic acid measurements were performed on 26 adrenocortical tumours and 9 non-tumours adrenals. All but one tumours were classified both histologically and clinically as benign, however, two thirds of them had abnormal deoxyribonucleic acid stemlines. Proliferative indices of adenomatous tissues were significantly higher than those of non-tumorous adrenals (p < 0.01). When compared to tumors smaller than 5 cm in size, tumours larger than 5 cm displayed significantly higher proliferative indices (p < 0.01). Thus, flow cytometry appears to have only a limited value in distinguishing between benign and malignant adrenocortical tumours, but it may provide additional information about the prognosis of these tumours.

Adenoma↗
PubMed1993

Direct inhibitory effect of etomidate on corticosteroid secretion in human pathologic adrenocortical cells.

Etomidate has been shown to inhibit corticosteroid secretion in the normal adrenal gland, but its direct effect in human pathologic adrenals has not been clearly established. In the present study the effect of varying doses of etomidate (10(-11)-10(-5) M) was investigated on basal and adrenocorticotrophic hormone (ACTH)-stimulated corticosteroid secretions in isolated adrenocortical cells obtained from two patients with primary aldosteronism (adenoma and micronodular hyperplasia) and in those from a patient with Cushing's syndrome (adenoma). In cells from primary aldosteronism, increasing concentrations of etomidate (10(-11)-10(-5) M) produced a dose-dependent decrease of basal and ACTH-stimulated cortisol, aldosterone, 18-hydroxycorticosterone, and corticosterone secretions (ED50: 10(-9)-10(-8) M for each of these corticosteroids). In the same cells, the secretions of 11-deoxycortisol and deoxycorticosterone were increased in the presence of low (10(-9)-10(-7) M) but not high doses of etomidate (10(-6)-10(-5) M). In cells from Cushing's syndrome the changes in corticosteroid secretion were similar to those found in primary aldosteronism except that aldosterone and 18-hydroxycorticosterone could not be determined due to their low levels. Thus the potent inhibition of corticosteroids in human pathologic adrenocortical cells in the presence of low concentrations of etomidate may be predominantly due to inhibition of the 11 beta-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway.

18-Hydroxycorticosterone↗
PubMed1993

Mineralocorticoid production of adrenal cortical adenomas.

We studied in vitro and in vivo corticosteroid production as well as the presence of symptoms of an increased mineralocorticoid effect in patients with 'silent' adrenal cortical adenomas, and compared these results to those found in patients with classical mineralocorticoid excess syndromes. We found that under in vitro conditions, cells from 'silent' adrenal cortical adenomas (n = 19) produced substantial amounts of both zona glomerulosa and fasciculata steroids, although the production of steroids in these cells was lower compared to that in mineralocorticoid-producing adenoma cells (n = 26). Patients with aldosterone-producing and 'silent' adenomas had significantly increased plasma atrial natriuretic peptide levels, which remained non-suppressible after upright posture and furosemide administration. Of the 25 patients with 'silent' adenomas, 11 had low and non-stimulable plasma renin activity (PRA) before but, in most cases, not after adrenal surgery. When compared to those with normal PRA (n = 14), patients with low PRA 'silent' adenomas (n = 11) had higher blood pressure which was significantly reduced after surgery, and a mild hypokalemia before but not after surgery. Although basal plasma concentrations of aldosterone, 18-hydroxy-corticosterone, corticosterone, deoxycorticosterone, 18-hydroxy-DOC, cortisol,11-deoxycortisol and 17-hydroxy-progesterone (17-OH-P) were not increased in either groups of 'silent' adenomas, ACTH stimulation produced a hyperreactive response for all measured steroids, of which an extremely high 17-OH-P seemed to be one of the most intriguing findings. We consider that these observations in 'silent' adrenal cortical adenomas may justify surgical intervention, irrespective of the size and potential malignancy of these adenomas.

Adenoma↗
PubMed1993

Phosphocholine transferase is more efficient than diacylglycerol kinase as possible attenuator of diacylglycerol signals in primordial human placenta.

Diacylglycerols (DAG) are assumed to play intracellular signal roles in rapidly growing tissues like those present in the primordial human placenta. The aim of the present study was to gain information on the capacity of DAG-kinase and CDP-choline: DAG phosphocholine transferase enzymes to eliminate DAG and behave as possible signal attenuators in these tissues. Previous and present results has provided evidence that Triton X-100 (0.05%, v/v), when incubated with placenta mince, (I) causes the accumulation of DAG by inhibiting DAG-acyltransferase and by a suggested acceleration of phosphatidylcholine (PC) decomposition, (II) inhibits the synthesis of PC and (III) increases the formation of phosphatidic acid (PA) without decreasing the conversion of PA into acylglycerols. Inhibition by the synthetic DAG: dioctanoylglycerol (DOCG) and by the DAG-analog: dioctanoylethyleneglycol (DOEG), of the Triton-induced (3H)PA-accumulation from (3H)glucose and of the increased labeling of PA with (32P)phosphate indicated some DAG-attenuating roles of DAG-kinase, but this mechanism appeared not to be very efficient. The low rate of conversion of DOCG into (32P)PADOCG species in incubations with (32P)phosphate confirmed this view. Compared to the rate of formation of PADOCG, DOCG was eliminated in the form of PCDOCG more than one order of magnitude faster. In addition, DOCG stimulated, whereas DOEG inhibited the formation of endogenous PC. These findings suggest that in the primordial human placenta transformation of DAG into PC by phosphocholine transferase and an attending stimulation of PC synthesis represent a more effective attenuator mechanism than the conversion of DAG into PA by DAG-kinase.

Data Interpretation, Statistical↗
PubMed1993

Low concentration of Triton X-100 inhibits diacylglycerol acyltransferase without measurable effect on phosphatidate phosphohydrolase in the human primordial placenta.

Agents causing accumulation of endogenous diacylglycerols (DAG) may be helpful in studies on the intracellular regulatory effects and on the mechanisms of attenuation of this putative second messenger. In a previous study (Tóth et al., BBA 921 (1987) 417-425) we have shown a marked stimulatory effect of low micellar concentration (0.05%, v/v) of Triton X-100 on the labelling of phosphatidic acid with (32P)phosphate in minced human primordial placenta. The present results demonstrate that 0.05% Triton X-100 inhibits nearly completely the conversion of (3H)diacylglycerols into (3H)triacylglycerols in placenta fragments incubated with (3H)glucose. However, this concentration of the detergent does not have any effect on the appearance of label in the sum of acylglycerols (comprising mono-, di- and triacylglycerols) and phosphatidylcholine, indicating a lack of effect on phosphatidate phosphohydrolase. The about 5-fold elevation of (3H)diacylglycerols was attended by an approximately 3-fold rise in (3H)phosphatidic acid and a 1.3-fold increase in the labelling of phosphatidylcholine. These findings provide supportive evidence that 1,2-DAG was formed due to inhibition of DAG-acyltransferase and suggest that some of the DAG was transformed into phosphatidic acid by diacylglycerol-kinase.

Acyltransferases↗
PubMed1992

Body sodium, atrial natriuretic peptide and blood pressure in diabetes mellitus.

Diabetes mellitus (DM) is frequently associated with hypertension for which an independent pathomechanism has been suggested. We studied 26 patients with insulin-dependent (IDDM) and 18 patients with non-insulin-dependent (NIDDM) uncomplicated DM; all patients were in metabolic balance and none of them had hypertension. Exchangeable body sodium (NaE was estimated by isotope dilution, using appr. 1.1 Mbq 24NA. In a subset of 8 IDDM and 8 NIDDM patients atrial natriuretic peptide (ANP) plasma concentration was determined prior to and after the infusion of 2000 ml physiological saline over 2 hr. NaE was significantly increased both in IDDM and NIDDM patients (104.4 +/- 11.4% and 109.9 +/- 8.0% of the normal value for healthy subjects of identical body surface area; p < 0.05 and < 0.001 resp.). Mean blood pressure (MBP) correlated significantly with NaE in both groups (r = 0.364 and r = 0.520; p < 0.05 and < 0.025, resp.) but not in healthy control subjects (r = 0.112; N.S.). Resting ANP levels were not significantly different in IDDM (34.9 +/- 11.3 pg/ml), NIDDM (42.6 +/- 11.7 pg/ml) or control subjects (40.9 +/- 17.2 pg/ml) however the infusion of saline resulted in a significantly greater increase of plasma ANP in the NIDDM patients (to 82.9 +/- 43.2 pg/ml; P < 0.01) than in the controls (55.6 +/- 23.7 pg/ml; P < 0.01) which was associated with a significantly less increase in sodium excretion (UNAV) in the NIDDM patients (+86% vs. 3170%; P < 0.02) indicating down-regulation of ANP receptors in the kidney of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Possibilities of antioxidant therapy in the prevention of side effects of amiodarone].

The authors demonstrated the generation of a very reactive phenyl radical from amiodarone in a reducing molecular environment by pulse radiolysis study. The various antioxidants are probably not capable of preventing the generation of phenyl radical, as well as to protect against its damaging effects on the neighboring molecules. Electron microscopic studies from lung tissue of in vivo treated rats showed that the simultaneous Silibinin (a flavonoid type antioxidant) treatment with amiodarone decreased significantly the lysosomal phospholipoidosis induced by amiodarone compared with the amiodarone treated group, but it didn't prevent entirely the accumulation of lysosomal phospholipids. The in vitro lysosomal beta-glucuronidase enzyme release measured from the liver tissue of in vivo treated rats increased significantly on amiodarone treatment, the antioxidants used (Silibinin, and the dihydroquinoline type MTDQ-DA) didn't exert any favorable effect. The authors discuss in details the possible relationships between free radical reactions and lysosomal phospholipoidosis.

Amiodarone↗
PubMed1991

Atrial natriuretic peptide (ANP) in patients with chronic renal failure on maintenance haemodialysis.

Atrial natriuretic peptide (ANP), a recently discovered cardiac hormone, is an important regulator of body fluid homeostasis. Twenty patients with established chronic renal failure and on maintenance haemodialysis were studied before and after dialysis with capillary dialysers. ANP was determined by RIA after extraction. Mean (+/- SD) pre-dialysis ANP concentration was 146 +/- 51 pg/ml and decreased significantly during dialysis to 68 +/- 38 pg/ml (p less than 0.001). Per cent and absolute changes in plasma ANP level correlated significantly with concomitant changes in body weight (r = 0.764; p less than 0.001 and r = 0.558; p less than 0.01, resp.) but not with changes in serum creatinine, blood pressure or serum electrolytes. The obtained results indicate that ANP levels in patients with chronic renal failure are elevated mainly due to fluid overload, and the rapid fall in ANP concentration observed during haemodialysis is caused by the removal of excess fluid from the body.

Adult↗
PubMed1991

Endothelin-induced long-lasting mesenteric vasoconstriction: a hypothetical mechanism of non-occlusive intestinal infarction.

The in vivo mesenteric vascular effect of the novel, endothelium-derived endogenous polypeptide, endothelin-1 (ET-1) was examined in experiments performed on pentobarbital-anesthetized dogs. Blood supply to a segment of the small bowel was measured simultaneously with an electromagnetic flow probe and computer-assisted thermography which senses flow-dependent infrared irradiation. It was found that close mesenteric arterial injections of ET-1 produced long-lasting flow decreases of considerable magnitude: the single dose of 1 nmol reduced blood flow by nearly 90 percent, and even the minimal single amount of 1 pmol produced statistically significant vasoconstriction. The thermographic analysis proved the homogenous character of these reactions. Unlike vascular responses elicited by most of the known vasoconstrictive agents, the ET-1-induced spastic effects were maintained without a continuous exposure (drug infusion). All features that characterize the spastic ET-1 action qualify the peptide for a hypothetical candidate of mediating the nonocclusive mesenteric ischemic syndrome.

Animals↗