Uneven flow distribution in the heart induced by endothelin.
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Animals↗
Biomedical subjects
M Tóth
Publications and source records attributed to M Tóth.
No teratogenic effect after clotrimazole therapy during pregnancy.
We evaluated the potential teratogenic effects of vaginal and/or topical administration of clotrimazole in the large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1992). The dataset included 18,515 case pregnancies and 32,804 control pregnancies; 7.1% of case and 7.7% of control women used clotrimazole during pregnancy. Clotrimazole use was not clearly associated with an increase in the total (fetal + birth) prevalence of any congenital abnormality group. There was, however, a suggestion that clotrimazole use was associated with a decrease in the prevalence of undescended testis (prevalence odds ratio = 0.72; 95% confidence interval = 0.54-0.95).
Abnormalities, Drug-Induced↗
Hyperreactio luteinalis in a normal singleton pregnancy. A case report.
BACKGROUND: Hyperreactio luteinalis rarely occurs in normal singleton pregnancy. About 50 such cases have been published. This case is noteworthy because it resulted in extremely enlarged ovaries and was accompanied by a hyperandrogenic state and high level of human chorionic gonadotropin. CASE: A gravida was referred to our department because of large, bilateral, cystic ovaries diagnosed by ultrasonography in the 28th week of gestation. Markedly elevated levels of androgens and human chorionic gonadotropin were noted. During the following six weeks the ovarian masses enlarged, and the hyperandrogenic state worsened. Cesarean section and, because of a bleeding right adnexectomy, left ovarian resection were performed. Histology confirmed the presumed diagnosis of hyperreactio luteinalis. The placenta was unremarkable. Seventeen weeks after surgery the hormone levels were normal. CONCLUSION: Our case suggests the possibility that in certain cases of hyperreactio luteinalis, an idiopathic elevation of human chorionic gonadotropin, can occur even in normal singleton pregnancies. Furthermore, it calls attention to the necessity of ultrasonographic demonstration of ovaries even during late pregnancy.
Adult↗
[Importance of endocrine imaging methods in multiple endocrine neoplasia type 2A proved by mutation analysis].
Multiple endocrine neoplasias are rare, inherited disorders. The authors describe a case history of a patient with multiple endocrine neoplasia type 2A, who presented with unusual clinical manifestations. The diagnosis of phaeochromocytoma, which was the first manifestation of the disorder, was greatly facilitated with radiologic imaging methods. The authors review, on the basis of recent data from the literature, the importance of radiologic methods, which improved due to methodological advance. Finally, the authors emphasize the importance of follow-up for early diagnosis.
Diagnostic Imaging↗
[Endoscopic anatomy of the tympanic cavity].
Development of modern diagnostic procedure requires inframacroscopic description of tympanic cavity. This description has to suit the special requirements of diagnostic endoscopy, too. The authors made an attempt to describe clinical anatomy of the tympanic cavity. For endoscopic investigation transtympanic, transtubal and transmastoidal approaches were used, out of which the transmastoidal has the least clinical importance. Using the transtympanic approach, detailed anatomical description of the medial wall, the auditory ossicles and the stapedius muscle can be given. Using the transtubal approach, the epitympanic region, stapedius and tensor tympani muscle and two major nerves, chorda tympani and tympanic nerve can be also investigated. Using transmastoidal approach, auditory ossicles were seen, but it was possible to identify lateral part of epitympanic recess, as well.
Ear Diseases↗
Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide.
BACKGROUND: Adrenomedullin (ADM), a new vasorelaxing and natriuretic peptide, may function as an endogenous regulator of cardiac function, because ADM and its binding sites have been found in the heart. We characterize herein the cardiac effects of ADM as well as the underlying signaling pathways in vitro. METHODS AND RESULTS: In isolated perfused, paced rat heart preparation, infusion of ADM at concentrations of 0.1 to 1 nmol/L for 30 minutes induced a dose-dependent, gradual increase in developed tension, whereas proadrenomedullin N-20 (PAMP; 10 to 100 nmol/L), a peptide derived from the same gene as ADM, had no effect. The ADM-induced positive inotropic effect was not altered by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP8-37, or H-89, a cAMP-dependent protein kinase inhibitor. ADM also failed to stimulate ventricular cAMP content of the perfused hearts. Ryanodine (3 nmol/L), a sarcoplasmic reticulum Ca2+ release channel opener, suppressed the overall ADM-induced positive inotropic effect. Pretreatment with thapsigargin (30 nmol/L), which inhibits sarcoplasmic reticulum Ca2+ ATPase and depletes intracellular Ca2+ stores, attenuated the early increase in developed tension produced by ADM. In addition, inhibition of protein kinase C by staurosporine (10 nmol/L) and blockade of L-type Ca2+ channels by diltiazem (1 micromol/L) significantly decreased the sustained phase of ADM-induced increase in developed tension. Superfusion of atrial myocytes with ADM (1 nmol/L) in isolated left atrial preparations resulted in a marked prolongation of action potential duration between 10 and -50 mV transmembrane voltage, consistent with an increase in L-type Ca2+ channel current during the plateau. CONCLUSIONS: Our results show that ADM enhances cardiac contractility via cAMP-independent mechanisms including Ca2+ release from intracellular ryanodine- and thapsigargin-sensitive Ca2+ stores, activation of protein kinase C, and Ca2+ influx through L-type Ca2+ channels.
Action Potentials↗
[The role of endothelin-1 in diabetes mellitus].
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Diabetic Retinopathy↗
Role of endothelin-1 in diabetes mellitus.
Endothelin-1 is mainly synthesized by the vascular endothelial cells and acts on the vascular smooth muscle. Because of its vasoconstrictor and mitogenic effects it plays a role in the development of vascular diseases. In diabetes mellitus atherosclerosis is accelerated. The authors summarize the available data of the role of endothelin-1 in Type 1 and Type 2 diabetes mellitus and the development of diabetic complication.
Animals↗
p53 protein and its messenger ribonucleic acid in human adrenal tumors.
The role of p53 tumor suppressor gene in the pathomechanism of adrenal tumors was investigated by measuring p53 protein and its messenger ribonucleic acid (mRNA) in 12 normal human adrenals as well as in 56 adrenal tumors (7 aldosterone-producing adenomas, 5 adrenocortical adenomas causing Cushing's syndrome, 19 non-hyperfunctioning adrenocortical adenomas, 5 adrenocortical carcinomas, 12 pheochromocytomas, 3 myelolipomas, 4 ganglioneuromas and 1 hemangioma). The p53 protein concentration was significantly increased in aldosterone-producing adenomas (394+/-36 pg/mg cytosolic protein, mean+/-SE, vs 266+/-18 in normal human adrenals), whereas the concentration of this protein in Cushing's adenomas, non-hyperfunctioning adrenocortical adenomas, pheochromocytomas, and in all but one adrenocortical carcinomas was similar to that measured in normal human adrenal tissues. One adrenocortical carcinoma tissue showed very high p53 protein content (3000 pg/mg cytosolic protein). By contrast, myelolipomas (23+/-20) ganglioneuromas (43+/-15) and a hemangioma (11 pg/mg cytosolic protein) had very low p53 protein content. Northern blot analysis revealed the presence of p53 mRNA in each adrenal tissue examined with highest levels in aldosterone-producing and Cushing's adenomas. It is possible that the differences in p53 protein and/or mRNA contents reflect corresponding differences in the pathogenetic importance of p53 alterations in these types of adrenal tumors.
Adenoma↗
Neurofibromatosis type 1 with pregnancy-associated renovascular hypertension and the syndrome of hemolysis, elevated liver enzymes, and low platelets.
The authors detected a case of neurofibromatosis type 1 complicated with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets, which developed during pregnancy. When the cause of the patient's hypertension was investigated after birth, renal stenosis of the right artery was detected, which was then successfully treated with percutaneous transluminal angioplasty.
Adult↗
Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs.
OBJECTIVES: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. METHODS: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol.kg-1.min-1; n = 6 and 6, respectively) or physiological saline (Group 3, n = 5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. RESULTS: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342 +/- 210 vs. 8.0 +/- 5.2 pmol.l-1, n = 14, P < 0.001. In HPLC analysis pericardial fluid ET-1 was indistinguishable from ET-1(1-21). Infusion of exogenous ET-1 into the pericardial space induced ventricular arrhythmias in all instances, which were associated with 9.7-fold increase in pericardial fluid ET-1 levels. Ventricular tachycardias developed in 9 of 12 animals. The arrhythmogenic effect of ET-1 was more apparent in dogs with the larger dose. Before the onset of arrhythmias, intrapericardial infusion of ET-1 increased QT time (Group 1: 207 +/- 18 to 230 +/- 23 ms, P < 0.01; Group 2: 220 +/- 12 to 277 +/- 17 ms, P < 0.01) and MAP duration at 90% repolarization (at 300 ms cycle length) (Group 1: 192 +/- 9 to 216 +/- 9 ms, P < 0.01; Group 2: 205 +/- 9 to 255 +/- 9 ms, P < 0.001). Hemodynamic variables did not change significantly prior to the onset of ventricular tachyarrhythmias. In Group 3, arrhythmias were not observed and all electrophysiological and hemodynamic parameters remained unchanged. CONCLUSIONS: Administration of exogenous ET-1 into the pericardial space induces ventricular arrhythmias associated with prolongation of QT time and MAP duration. Whether pericardial fluid ET-1 under pathophysiological conditions can ever reach sufficiently high levels to induce ventricular arrhythmias remains to be elucidated.
Action Potentials↗
Birth weight, gestational age and medications during pregnancy.
OBJECTIVE: To determine the effect of medication on birth weight and gestational age in 29,004 healthy newborn infants born to mothers with or without treatment of drugs. METHOD: Birth weight and gestational age were evaluated in healthy control newborn infants in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1991) using multiple regression analysis. RESULTS: Of 114 drugs used in more than 100 pregnant women, 19 had a positive or negative impact. CONCLUSIONS: Further studies should be carried out to identify the possible mechanisms of medication and/or the maternal disorder for which this medication was given.
Birth Weight↗
Presence of immunoreactive endothelin-1 and atrial natriuretic peptide in human pericardial fluid.
This study was undertaken to characterize endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations in human pericardial fluid, blood plasma, right atrial appendage and papillary muscle by use of specific radioimmunoassays. In patients undergoing cardiac surgery (n=16) pericardial fluid mean immunoreactive (ir-) ET-1 and ir-ANP levels were 36-fold and 4-fold higher than corresponding plasma levels, respectively. In high performance liquid chromatography (HPLC) pericardial fluid ir-ET-1 was indistinguishable from human ET-1[1-21] and the majority of pericardial fluid ir-ANP coeluted with human ANP[99-126]. Atrial tissue ir-ET-1 and ir-ANP concentrations were 17-fold and 870-fold higher than in ventricular tissue. Our present study demonstrated for the first time the presence of ir-ET-1 in the pericardial fluid in humans. Human pericardial fluid contained far the highest concentrations of ET-1 among all biological fluids tested thus far. The functions of pericardial fluid ET-1 and ANP on cardiac performance and coronary vascular tone require further investigations.
Adult↗
Interactions between ouabain, atrial natriuretic peptide, angiotensin-II and potassium: effects on rat zona glomerulosa aldosterone production.
The effects of ouabain, atrial natriuretic peptide, angiotensin-II and potassium on aldosterone production by collagenase dispersed rat zona glomerulosa cells were studied. A-II and 10(-4) M ouabain-induced increases in aldosterone production was inhibited by 10(-9) M ANP at all potassium concentrations examined. 10(-4) M ouabain inhibited the A-II induced increase in aldosterone production at all potassium concentrations. The degree of this inhibition was smaller at higher potassium levels. Ouabain enhanced the inhibitory effect of ANP on A-II-induced aldosterone synthesis at all potassium concentrations. Interactions between A-II, ANP, ouabain and potassium may be of physiological significance in the regulation of aldosterone secretion.
Aldosterone↗
Coexpression of p53 and tissue transglutaminase genes in human normal and pathologic adrenal tissues.
The presence of p53 and tissue transglutaminase (tTG) gene expressions was investigated in human normal and pathologic adrenal tissues with two aims (1) to determine the tissue content of p53 protein, its messenger ribonucleic acid (mRNA) and, especially, tTG mRNA which has not been previously reported and (2) to study possible differences in the coexpression of p53 and tTG in various adrenal disorders. Using Northern blot analysis, p53 and tTG mRNAs were detected in each adrenal tissue examined including 5 normal human adrenals, 6 aldosterone-producing adenomas, 3 Cushing's adenomas, 1 primary nodular adrenocortical hyperplasia causing Cushing's syndrome in an infant, 12 non-hyperfunctioning adrenocortical adenomas, and 4 adrenocortical carcinomas. The results showed a significant positive correlation between these two mRNAs in all adrenal tissues except adrenocortical carcinomas. Compared to normal adrenals, high p53 mRNA levels were observed in aldosterone-producing and Cushing's adenomas and, most markedly, in a tissue from a primary nodular adrenocortical hyperplasia. Also, Cushing's adenomas had significantly higher tTG mRNA contents. Immunohistochemistry for wild-type and mutant p53 protein showed numerous p53 positive cells with a strong nuclear staining in a tissue from a primary nodular adrenocortical hyperplasia, whereas the p53 positive cells were absent, except those with a faint nuclear staining, in all other adrenal tissues. However, all adrenal tissues showed detectable p53 contents by the more sensitive method of luminometric immunoassay (LIA). Using this method, aldosterone-producing adenomas exhibited significantly higher p53 contents than normal adrenal tissues. These observations may support potentially important roles for p53 and tTG in adrenal pathophysiology, especially in mechanisms which influence the evolution and/or progression of aldosterone-producing and Cushing's adenomas and, most probably, hyperplasias.
Adrenal Gland Neoplasms↗
Differential response of basal and tetrahydrobiopterin-stimulated activities of placental type III nitric oxide synthase to sodium dodecyl sulphate: relation to dimeric structure.
The major enzyme isoform that synthesizes nitric oxide (NO) in first trimester human placentae is endothelial or type III NO-synthase (NOS III) which exhibits high specific activity in the microsomal fraction. In the present study, we investigated the possible protective and enzyme-stabilizing role of tetrahydropterin (BH4). The anionic detergent, sodium dodecyl sulphate (SDS) and thermal stress (freeze-thaw) were used as non-specific 'subunit-dissociating' agents, and alterations in enzyme activity and subunit structure were investigated. SDS (> or =0.05% w/v) resulted in significant inhibition both of basal and BH4-stimulated activities of NOS III, but the latter responded more sensitively. Preincubation of microsomes with SDS (> or =0.1%, w/v), followed by incubation in an SDS-depleted reaction mixture led to an inhibition of BH4-stimulated enzyme activity, while no change in the basal activity was noted. This indicated that the SDS effect is only fully reversible in the case of basal activity. Considering that basal activity is due to the presence of endogenous BH4 tightly bound to the enzyme, this differential sensitivity of basal and BH4-stimulated enzyme activities to SDS may be related to a putative differential protective effect of BH4 on the two subunits of the NOS III dimer. Western blot analysis revealed that the SDS-induced inhibition of enzyme activity could not be ascribed to disruption of the dimeric structure. This finding confirms the view that SDS may affect NOS III activity without necessarily deteriorating quaternary protein structure. Nevertheless, BH4 is essential in maintaining dimeric structure under denaturing conditions, e.g. SDS treatment and freezing/thawing; it is even able to reverse the dissociation caused by SDS. A model describing the interaction between BH4 and NOS III, and its implications on the physiology and pathology of the human placenta, is discussed.
Antioxidants↗
Endothelin-converting enzyme-1 mRNA expression in human cardiovascular disease.
Endothelin-converting enzyme-1 (ECE-1) plays a substantial role in activation of the endothelin (ET) system by cleaving the precursor, big ET-1, to the active peptide ET-1. The aim of this study was to investigate whether ECE-1 mRNA expression is modified in human cardiovascular disease. ECE-1 expression was related to echocardiographic data, drug treatment, age, sex, and NYHA heart failure classification. A quantitative PCR assay (qPCR) was established to measure ECE-1 mRNA in these samples. The ECE-1 measurements were normalized over a simultaneously performed GAPDH qPCR. The results indicate a higher ECE-1 expression level in atrial tissue samples of patients who have experienced a myocardial infarction compared with those who did not (ECE-1/GAPDH: 5.81 +/- 0.76 fg/ng; n = 21 vs. 3.20 +/- 0.51 fg/ng; n = 22; p = 0.007). The transverse diameter of the left atrium over 37 mm was associated with a lower ECE-1 expression (ECE-1/GAPDH: 3.11 +/- 0.69 fg/ng; n = 18 vs. 5.12 +/- 0.65 fg/ng; n = 25; p = 0.044). In assessing the drug treatment, decreased ECE-1 expression could be observed in patients who received a beta-blocker (ECE-1/GAPDH: 3.90 +/- 58 fg/ng; n = 31 vs. 5.81 +/- 0.76 fg/ng; n = 12; p = 0.077). These data suggest an involvement of the ET system is cardiovascular disease that may be clinically important.
Aspartic Acid Endopeptidases↗
Endothelin does not interact with angiotensin II in the coronary vascular bed of anesthetized dogs.
We postulated that individually subthreshold circulating levels of angiotension II (Ang II) and endothelin-1 (ET-1) might induce fulminant coronary vasoconstriction when both are present. In 16 pentobarbital-anesthetized, open-chest mongrel dogs, blood pressure, heart rate, and standard ECG were registered continuously. Coronary blood flow (CBF) was measured in the left anterior descending coronary artery (LAD) by an electromagnetic flow probe. Drugs were administered into the LAD via an indwelling catheter. Bolus injections of Ang II (7.8 x 10(-13) to 3.9 x 10(-11) M) and ET-1 (10(-12) to 10(-9) M) induced a dose-dependent decrease in CBF (delta CBFmax -82 +/- 10% for Ang II and -91 +/- 8% for ET-1). Simultaneous Ang II and ET-1 boluses had slightly smaller effects on CBF than the calculated additive figure. Five-minute infusions of Ang II (10(-12) to 10(-10) M/min) and ET-1 (5 x 10(-12) to 2 x 10(-10) M/min) induced a slight decrease in CBF (delta CBFmax -12 +/- 9% for Ang II and -19 +/- 9% for ET). Background ET-1 or Ang II infusions did not alter the dose-response curve of the other drug. Simultaneous Ang II and ET-1 infusions at different rates (10(-12) to 10(-10) M/min for Ang II and 5 x 10(-12) to 2 x 10(-10) M/min for ET-1) over 5 min had similar effects on CBF as the calculated additive figure (delta CBFmax -35 +/- 17% for the joint administration of the highest doses). We conclude that after simultaneous administration into the dog coronary artery, Ang II and ET-1 do not interact sufficiently to induce fulminant vasoconstriction.
Anesthesia, General↗