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Biomedical subjects

A Mohácsi

Publications and source records attributed to A Mohácsi.

At least 19 recordsLinked to original sources

Different effects of endothelin-1 on calcium and potassium currents in canine ventricular cells.

Effects of endothelin-1 (ET-1) on the L-type calcium current (ICa) and delayed rectifier potassium current (IK) were studied in isolated canine ventricular cardiomyocytes using the whole-cell configuration of the patch-clamp technique. ET-1 (8 nM) was applied in three experimental arrangements: untreated cells, in the presence of 50 nM isoproterenol, and in the presence of 250 microM 8-bromo-cAMP. In untreated cells, ET-1 significantly decreased the peak amplitude of ICa by 32.3+/-4.8% at +5 mV (P<0.05) without changing activation or inactivation characteristics of ICa. ET-1 had no effect on the amplitude of IK, Ito (transient outward current) or IK1 (inward rectifier K current) in untreated cells; however, the time course of recovery from inactivation of Ito was significantly increased by ET-1 (from 26.5+/-4.6 ms to 59.5+/- 1.8 ms, P < 0.05). Amplitude and time course of intracellular calcium transients, recorded in voltage-clamped cells previously loaded with the fluorescent calcium indicator dye Fura-2, were not affected by ET-1. ET-1 had no effect on force of contraction in canine ventricular trabeculae. Isoproterenol increased the amplitude of ICa to 263+/-29% of control. ET-1 reduced ICa also in isoproterenol-treated cells by 17.8+/-2% (P<0.05); this inhibition was significantly less than obtained in untreated cells. IK was increased by isoproterenol to 213+/-18% of control. This effect of isoproterenol on IK was reduced by 31.8+/-4.8% if the cells were pretreated with ET-1. Similarly, in isoproterenol-treated cells ET-1 decreased IK by 16.2+/-1.5% (P<0.05). Maximal activation of protein kinase A (PKA) was achieved by application of 8-bromo-cAMP in the pipette solution. In the presence of 8-bromo-cAMP ET-1 failed to alter ICa or IK It was concluded that differences in effects of ET-1 on ICa and IK may be related to differences in cAMP sensitivity of the currents.

Action Potentials↗

[In vitro study of endothelium-dependent relaxation and contraction of human atherosclerotic femoral artery].

According to present knowledge, altered arterial reactivity associated with hypertension, atherosclerosis and hypercholesterolemia is related to impaired release of endothelial derived relaxing factor (EDRF). Impaired relaxation followed by enhanced vasoconstriction leads to a well known clinical entities such as unstable angina, acut myocardial infarction. Impairment of EDRF may also account for smooth muscle cell proliferation and migration. Aim of present study was to examine the endothelial dependent response during in vitro conditions in human femoral arteries taken from bypass operation and leg amputation. Examining the contractility, the effect was modulated with nifedipin, EDTA and pertussis toxin, respectively. Endothelium dependent relaxation to acethylcholin and histamine were markedly diminished, while those to calcium ionophore were maintained throughout the study. These results suggest that at least two or more receptor-coupled system may be involved in generation of EDRF. However, direct relaxation of femoral artery to nitrovasodilatators (nitroglycerine) were comparable between control and atherosclerotic artery. Another striking change in atherosclerotic artery was the increased sensitivity to the vasoconstrictions. To eluciadate to exact biochemical mechanism underlying the endothelial dysfunction may help to develop a new vasodilatator drug.

Arteriosclerosis↗

[Lipid lowering treatment in secondary prevention following myocardial infarct].

1081 patients treated with myocardial infarction between 1990-1995 were investigated retrospectively, 652 (60.3%) of the patients were male and 429 (39.7%) were female. 154 (14.2%) patients had an early, while 927 (85.5%) patients had late myocardial infarction. Of the patients with early myocardial infarction 52.3% were smokers, 45.2% had positive family history for ischaemic heart disease or acute myocardial infarction. The lipid parameters were analysed in detail, because 83.3% of the patients were hyperlipoproteinaemic. The mean cholesterol level was 6.91 +/- 1.2 mmol/l, the HDL-C level was 1.19 +/- 0.38 mmol/l, the triglyceride level was 2.66 +/- 1.8 mmol/l, the LDL-C level was 4.71 +/- 1.2 mmol/l. The serum LDL-C and the HDL-C levels of the patients with early myocardial infarction were compared to the desirable levels suggested for secondary prevention. Only 7.2% of the male patients had a cholesterol level below 5.2 mmol/l, while all female patients cholesterol levels were above 5.2 mmol/l. Of the male patients 53.6%, while 78.6% of females had lower triglyceride levels than 2.3 mmol/l 78,6% of the male patients had higher protective HDL-C level in the optimal range (> 1.1 mmol/l). 12.5 percent of the male patients had an LDL-C level lower than the value targeted by secondary prevention (3.0 mmol/l), while all of the female patients LDL-C levels were higher. The authors emphasize the importance of secondary prevention and a more widespread use of lipid lowering treatment for patients after acute myocardial infarction.

Adult↗

Alteration of lymphocyte membrane phospholipids and intracellular free calcium concentrations in hyperlipidemic subjects.

Hypercholesterolemia has been proposed to influence cell functions via changes in membrane composition. The aim of the present study was to determine whether the membrane phospholipid composition of human lymphocytes is modified in hypercholesterolemia and whether these changes are accompanied by functional modifications. The phospholipid fatty acid contents and intracellular free calcium concentrations were determined in peripheral blood lymphocytes from 13 subjects with serum total cholesterol levels ranging from 4.6 to 8.8 mmol/l. The spontaneous basal rate of thymidine incorporation in lymphocyte of hypercholesterolemic individuals increased, while its relative stimulation by ConA was less effective. Important changes in membrane lipid composition, consisting mainly of decrease of the mass of phospholipids, and of associated polyunsaturated fatty acids were observed in hypercholesterolemia. In contrast, the cell cholesterol content was significantly increased. The intracellular free calcium concentration was enhanced and strongly associated with circulating cholesterol levels, cell cholesterol content and phospholipid fatty acids. These results indicate that hypercholesterolemia is accompanied by profound changes in lymphocyte membrane lipid composition and Ca(2+) handling.

Calcium↗

[Serum elastin peptide concentration and human leukocyte elastase/antiproteinase balance in peripheral obstructive atherosclerosis].

In some pathological states such as therosclerosis tissue destruction may be accelerated due to uncontrolled protease release of polymorphonuclear leukocytes and other events such as decreased concentration and/or the inactivation of main protease inhibitor molecules in the serum. In this study, the authors measured the elastase release of polymorphonuclear leukocytes which increased in atherosclerosis independently of the patients aged compared to healthy young subjects. These findings were similar to the response of polymorphonuclear leukocytes separated from healthy elderly subjects. Simultaneously, the main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy and atherosclerotic subjects were determined. alpha-1-antitrypsin did not decrease significantly, whereas alpha-2-macroglobulin did in sera of atherosclerotic patients compared to age matched subjects (p < 0.05). In contrast, the activity of porcine pancreatic elastase was more effectively neutralized by the plasma obtained from healthy subjects suggesting diminished antiprotease activity of sera obtained from patients. The authors concluded that increased elastase release and decreased antiproteinase activity should be considered in atherosclerotic arterial wall damage. The similarity of the results in aged and therosclerotic subjects suggests that arteriosclerosis is an earlier aging process.

Arteriosclerosis↗

Retrobulbar fibroblasts from patients with Graves' ophthalmopathy induce downregulation of APO-1 in T lymphocytes and protect T cells from apoptosis during coculture.

Retrobulbar fibroblasts are a main target of the immune process in Graves' ophthalmopathy (GO) and have been shown to have unique metabolic qualities. The aim of our study was to analyze the immunoregulatory properties of retrobulbar fibroblasts and particularly whether fibroblasts were able to protect T cells from apoptosis. Retrobulbar fibroblasts from patients with GO spontaneously expressed higher concentrations of HLA class I and HLA class II (p<0.05) than control cells, whereas basal CD54 expression was unimpaired. Stimulation with IFN gamma led to a more pronounced increase in HLA class I, class II and CD54 in autoimmune fibroblasts than in control cells (p<0.05). Fibroblasts from both groups had the capacity to prevent apoptosis in preactivated peripheral T cells during coculture. T cell survival was, however, more pronounced after coculture with retrobulbar fibroblasts than with control cells (p<0.05). Prevention of T cell death was associated with a decreased expression of APO-1 on the T cell surface, whereas the bcl-2 expression of the T cells remained unchanged. Our results suggest that the increased expression of immunoregulatory molecules combined with a pronounced capacity of autoimmune fibroblasts to protect infiltrating T cells from apoptosis might at least partly explain the site selectivity as well as the perpetuation of the extrathyroidal manifestation of Graves' disease.

Apoptosis↗

[Clinical and biochemical parameters of patients with vascular stenosis in the lower extremities in the stage of intermittent claudication].

Clinical and biochemical parameters obtained by complex investigation of 100 patients suffering from intermittent claudication are presented by the authors. After taking the family and case history, we examined the patients and took laboratory tests including several lipid components, blood clotting factors and parameters influencing blood viscosity. The severity of peripheral vascular disease was defined by ankle/arm ratio, carotid arteries were studied by duplex sonography, coronary circulation was examined by ECG, exercise ECG and Thallium-201 isotopic myocardium scintigraphy. In conjunction with lower extremity vascular disease internal carotid stenosis was diagnosed in 62% and coronary stenosis in 52% of cases examined. In 35% all three regions were affected. The degree of carotid stenosis showed a strong correlation to the severity of the claudication, while in case of the coronary disease there was no connection proved, in spite of its high prevalence. Among the risk factors smoking was present in 89%, hypercholesterolaemia in 84%, hypertension in 54%, diabetes mellitus in 13%, impaired glucose tolerance in 42% and positive family history in 39% of cases. Smoking and accumulation of the risk factors showed correlation to the severity of the lower extremity vessel stenosis, while hypertension and carbohydrate metabolism disturbances showed significant correlations to the degree of carotid stenosis. From different lipid parameters only the cholesterol/HDL-cholesterol ratio showed significant correlation to the severity of the arteriosclerosis. The authors refer to intermittent claudication as the risk factor for carotid and coronary disease. They suggest the assessment of the cerebrovascular and cardiac risk in the patients. This way the optimal order of operative and/or non-operative therapy can be realized.

Adult↗

[Clinical cardiac electrophysiological studies in carotid sinus syndrome].

The aim of the present study was to evaluate the impact of electrophysiological study in the diagnosis and treatment of carotid sinus syndrome. The indications for the study include (1) attempting to exclude other cardiogenic causes of syncope; block, tachyarrhythmia, (2) diagnosing a vasodepressor response in the presence of cardioinhibitory type of carotid sinus syndrome, (3) determination of the optimal pacing mode in patients who need pacemaker implantation for treatment. 51 patients, 40 male (78%) and 11 female (22%) with an average age of 62 years suffering from carotid sinus hyperaesthesia--3000 ms ventricular asystole on carotid sinus massage--were investigated with electrophysiological study. The A-H interval in 8 patients (16%), the H-V interval in 5 pts (10%) were prolonged in the His bundle electrocardiogram. In 39 patients (76%) sinoatrial block, in 12 patients (24%) A-H block was found during carotid sinus massage. Early A-H Wenckebach block occurred in 8 patients (16%). Retrograde (V-A) conduction was present in 36 patients (70%) at a frequency of 65-85 bpm, and 22 pts (43%) at a frequency of 120-180 bpm. Sinus node disease was found in 10 patients (20%) according to the sinus node recovery time and sinoatrial conduction time. In 8 patients (16%) supraventricular and in 4 patients (8%) ventricular tachyarrhythmia was induced during study. The atrial stimulation could not prevent the occurrence of A-V block during carotid sinus massage in any of the 51 patients. In 2 patients (4%) the vasodepressor reaction with ventricular stimulation was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes.

The granulocyte-macrophage colony stimulating factor (GM-CSF) is an important in vivo regulator of granulopoiesis and neutrophil functions. It is well-known that the immune response and the transmembrane signalling in immune cells change with aging. We wished to elucidate the effects of GM-CSF in itself and in priming the activities of other inflammatory agents on neutrophils of elderly persons. Neutrophils of 20 healthy elderly (aged 60-90 years) and 20 healthy young (aged 20-25 years) subjects were studied for superoxide anion production, intracellular free calcium mobilization, antibody dependent cellular cytotoxicity (ADCC) and intracellular killing activities. It was found that GM-CSF is unable to prime neutrophils of elderly subjects to the action of FMLP, metenkephalin or opsonized zymosan. By the use of Pertussis toxin and H7 it was demonstrated that a different signal transduction pathway in neutrophils of elderly subjects is activated by GM-CSF or FMLP if compared to that of young subjects. These results suggest that the lack of priming could contribute to the greater susceptibility of the elderly to infections and that the change of the signal transduction mechanism in neutrophils of elderly subjects might partly explain this phenomenon.

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

[Effect of acipimox on diabetes mellitus-associated hyperlipoproteinemia].

The authors give summary on the pathogenesis of hyperlipoproteinaemia in patients with diabetes mellitus. They investigated the effects of acid nicotinic derivate acipimox on lipid metabolism in these patients. They treated with acipimox 15 patients who suffered from non-insulin-dependent diabetes mellitus, as well as II/B, IV type hyperlipoproteinaemia by Fredrickson. They investigated the effect of acipimox on the lipoprotein content and quality in the sera and uric acid and carbohydrate metabolism. The authors found decreased cholesterol, triglyceride, apolipoprotein-B, glycosilated haemoglobin, glucose and uric acid levels in the sera and they found that the atherogenic index decreased too. During the treatment they could not recognise a change in the low-density lipoprotein level of the sera while the high density lipoprotein and apo-A1 level increased.

Adult↗

Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages.

It has been established that phagocytic cells are integral components of advanced arteriosclerotic plaques but their role in plaque formation remains unclear. Therefore, toxic agents, such as superoxide anion produced by polymorphonuclear leukocytes (PMNLs) were studied in a clinically defined group of arteriosclerotic patients suffering from obliterative arteriosclerosis of the lower legs. Owing to a close correlation between O2- generation and calcium, the intracellular free calcium concentrations of PMNLs were measured in a resting state and after stimulation with various agents, for example, opsonized zymosan (OZ), the chemotactic peptide f-met-leu-phe (FMLP), and the calcium ionophore A23187. Healthy aged-matched controls were employed. The patients were divided into two age groups: 30-59 years and 60-80 years. We found that in the younger group of arteriosclerotic patients, superoxide anion production and intracellular free calcium concentrations were increased even in the resting state, and only a slight increase was observed after stimulation compared with healthy controls. Granulocyte responses seemed to be similar, independent of the patient's age, to those found in healthy elderly subjects. Arteriosclerosis appears to be associated with an early aging process expressing marked alterations that are greater than those associated with normal aging.

Adult↗

Sera and leukocyte elastase-type protease and antiprotease activity in healthy and atherosclerotic subjects of various ages.

Serum and granulocyte elastase-type protease activities were determined simultaneously with their main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic (ATS) subjects. The age-related associations of these parameters were also investigated. Serum elastase-type protease activity increased, but not statistically significantly, with aging in both control and ATS subjects. The enhancement of elastase-type protease activity in sera of ATS patients was significantly (p less than .02) greater than control subjects only in the case of the elderly. The granulocytes' elastase activity was significantly greater in granulocytes derived from both middle-aged and elderly ATS patients (p less than .03 and p less than .06) compared to age-matched control subjects. Alpha-1-antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was significantly lower in sera of ATS subjects compared to age-matched control subjects (p less than .01). The conclusion is that increased elastase-type activity and decreased antiproteinase activity should be considered as potential factors in atherosclerotic arterial wall damage. The similarity of the results in the elderly and the ATS subjects suggest that atherosclerosis is an early aging process.

Adult↗

Atypical clinical features of hypo- and hyperthyroidism in elderly age.

The clinical features of senile hypothyroidism and hyperthyroidism differ from the general characteristics of these conditions. This may be explained primarily by the changed response of peripheral tissues to thyroid hormones. Because of the atypical clinical symptoms the recognition of these conditions meets difficulties and, in general, occurs late. Therapy raises further special questions considering primarily cardiac complications and other accompanying diseases (for instance arteriosclerosis, osteoporosis, diabetes mellitus.). The authors analyse data of 171 hypothyroid and 219 hyperthyroid patients as a function of age, primary disease, and the most often occurring impulse generation, impulse conduction disorders.

Aged↗

Incidence of rhythm disorders in hyperthyrosis with special respect of old age form.

Sinus tachycardia and atrial fibrillation are frequent features in hyperthyrosis while sinus node dysfunction is regarded as a rare complication. Bradycardia may cause diagnostic problems mainly in atypical hyperthyrosis of the old age. The authors analysed distribution and age related association of the rhythm disorders in hyperthyrosis. In case of the appearance of Sick Sinus Syndrome (SSS), parameters representing the function of sinus node were studied by electrophysiological investigations. Above the age of 50 years incidences of atrial fibrillation and SSS were significantly increased. The abnormal sinus node function proved to be reversible in a portion of the cases. In old age, in case of occurrence of the symptoms of SSS, possibility of hyperthyrosis also should be considered, especially when indication of permanent pacemaker is established.

Adult↗

[Bartter syndrome].

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Bartter Syndrome↗