PubMed Health⌕ Search

Biomedical subjects

B Székács

Publications and source records attributed to B Székács.

At least 19 recordsLinked to original sources
PubMed2004

Systematic investigation of different steroid precursors with respect to their effect on superoxide anion production by human neutrophil granulocytes.

Free radicals are involved in several pathological processes in living organisms, for example in athero- and oncogenesis. Some steroids are known to be effective antioxidants, while others do not play any such role. The aim of our study was to examine the antioxidant capability of different metabolites in the synthesis of steroid hormones. As a model, we chose human neutrophils producing superoxide anion, which is the source of many other radicals. Neutrophils were separated from healthy volunteers. Isolated cells were incubated with varying concentrations of steroid compounds and stimulated with N-formyl-Met-Leu-Phe. Superoxide anion production was determined by photometry. Neutrophils incubated with corticosterone and 18-hydroxy-deoxycorticosterone showed a significant reduction in superoxide production, whereas we found a significant enhancement in the presence of 11beta-hydroxyprogesterone. Furthermore, we observed a non-significant decreasing trend after incubation with cholesterol 3-sulphate and an increasing tendency using 11-hydroxyandrostenedione. We were also able to produce newer morphological and functional evidence of the role of myeloperoxidase enzyme in the steroidal antioxidant effect by electronic microscopy and use of sodium hypochlorite in our incubation model. Based on these results, we conclude that not only steroid end products but also their intermediate metabolites, most of which are also present in human plasma, partly influence free radical metabolism. Thus, this study provides further argument for the search for the molecular basis responsible for the antioxidant effect of steroid structures. This may lead to new opportunities for finding really efficient antioxidants, which might perhaps be used in a combined manner with other agents in the fight against certain life-threatening diseases.

Adult↗
PubMed2001

Plasma concentration of myeloperoxidase enzyme in pre- and post-climacterial people: related superoxide anion generation.

Neutrophil granulocytes are involved in the pathogenesis of atherosclerosis also through their free radical generation. The aim of the study was to test how extracellular levels of myeloperoxidase (MPO; a granulocyte enzyme playing role in free radical production) change by age and what effect this change has on the production of the free radical superoxide anion by neutrophils. We also wanted to examine whether the antioxidant effect of different steroid hormones is realized through the MPO. Plasma myeloperoxidase concentrations of healthy blood donors were quantified by ELISA. Superoxide anion production was measured by photometry. Myeloperoxidase concentration was significantly lower in plasmas obtained from older women and men than in those from younger subjects. Adding the MPO inhibitors 4-aminobenzoic acid hydrazide (ABAH) and indomethacin to the granulocytes, the generation of superoxide anion increased and the decreasing effect of the steroids on superoxide production was inhibited. Incubating the neutrophils with the product of the reaction catalyzed by MPO itself (hypochlorite anion), we found significant decrease in superoxide generation. According to our results MPO seems to diminish the production of superoxide anion and so probably has an antioxidant ability. Therefore, its lower plasma levels may contribute to the increasing incidence of atherosclerosis and other free radical mediated disorders in old people. Thus, after further studies MPO might become one of the indicators of cardiovascular risk and the scavenger capacity in general.

Adult↗
PubMed2001

Connexin 43 expression in rat aortic smooth muscle after ovariectomy and hormonal replacement.

The purpose of this study was to determine the effects of ovariectomy and long-term combined sexual hormone replacement on the gap junctional protein, connexin 43 (Cx43) of aortic medial smooth muscle cells in rats. Twenty non-pregnant mature Wistar female rats were divided into five groups (four animals in each group). Group A underwent ovariectomy, Group B underwent ovariectomy and received estradiol propionate, Group C underwent ovariectomy and received medroxyprogesterone acetate and Group D underwent ovariectomy and received both hormones. Group E was sham-operated and used as control. After 15 weeks of treatment, thoracic aortas were removed and immunohistochemistry was carried out using a specific fluorescent antibody against Cx43. Tissue sections were examined by confocal laser scanning microscopy and analysed by the Scion Image program. All five different groups had the same distribution and extent of Cx43 in the aorta. Neither the ovariectomy nor the hormone replacement had any effect on the Cx43 expression of aortic smooth muscle cells in rats as compared to control animals. These results indicate that sexual steroids do not influence the gap junctional protein Cx43 of the medial layer of aorta in rats. They may suggest that the beneficial effects of estrogen are not mediated via gap junctions in the human aorta either.

Animals↗
PubMed2001

Acute, nongenomic vasodilatory action of estradiol is attenuated by chronic estradiol treatment.

Deficiency of estradiol or chronic estrogen treatment may alter the responses to this hormone in many tissues. A possible interaction between the acute nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether acute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment. Female rats were surgically ovariectomized and subjected to either estradiol replacement therapy (estradiol propionate, 450 micrograms/kg/week) or vehicle administration for 5 weeks. Cylindrical segments of the saphenous artery were studied using videocomputerized microarteriography in vitro. Estradiol, in concentrations of 10(-6) to 10(-4) M relaxed norepinephrine precontracted vessel segments in a dose-dependent manner. Magnitude of relaxation observed in arteries of estradiol replaced animals was significantly smaller at all concentrations than that of nonreplaced ovariectomized rats; maximal relaxation in the control ovariectomized group was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomized and estradiol replaced group (P < 0.001). Comparison of acute relaxations in response to papaverine and nifedipine failed to prove a reduced activity of the general relaxation machinery in estradiol replaced animals. We conclude that chronic estradiol replacement can downregulate the acute nongenomic vasorelaxation effect of this hormone in small arteries of ovariectomized rats.

Animals↗
PubMed2001

Estrogen improves impaired musculocutaneous vascular adrenergic reactivity in pharmacologically ovariectomized rats: a potential peripheral mechanism for hot flashes?

Hot flashes are among the most common complaints of perimenopausal women. Despite the high prevalence of the phenomenon, the background to the development of hot flashes is still not completely understood, through a hypothesized central mechanism, involving norepinephrine and luteinizing hormone-releasing hormone (LH-RH) secretion is widely accepted. We studied the influence of sex steroid deficiency and hormone replacement therapy on the biomechanical properties of musculocutaneous arterioles, to see whether a peripheral mechanism also exists in the development of hot flashes. Fifty adult, nulliparous, non-pregnant female Sprague-Dawley rats received pharmacological ovariectomy, and estradiol, medroxyprogesterone, or both hormones. After 12 weeks the saphenous artery was isolated by microdissection. Norepinephrine-induced tone (active tangential strain) was measured as a function of intraluminal pressure in an organ bath. The norepinephrine-induced arterial tone was significantly different between the control group and the ovariectomized animals in the range of 80-150 mmHg intraluminal pressure (p < 0.05). Also, significant differences were found between the ovariectomized group and the animals receiving estradiol monotherapy (p < 0.01 between 80 and 170 mmHg, and p < 0.05 between 180 and 200 mmHg intraluminal pressure). Neither medroxyprogesterone monotherapy nor combined hormone replacement therapy induced significant changes in the norepinephrine-induced vascular tone. The absence of sex steroids leads to decreased reactivity to norepinephrine in small musculocutaneous arteries, while chronic estradiol replacement therapy restores the impaired responsiveness of the vessels. Our data raise the possibility that in addition to the central mechanism, a previously unknown peripheral background mechanism for perimenopausal hot flashes may exist.

Animals↗
PubMed2000

Effects of combined sex hormone replacement therapy on small artery biomechanics in pharmacologically ovariectomized rats.

OBJECTIVES: The purpose of this study was to determine the effects of long-term combined sexual hormone replacement therapy on the biomechanical properties of the small artery wall in castrated female rats. METHODS: 30 non-pregnant mature female Sprague-Dawley rats were pharmacologically ovariectomized with 750 microg/kg triptorelin im. every 4th week. Ten of them received combined hormone replacement in form of 15 mg/kg medroxyprogesterone acetate (MPA) im. every 2 weeks and 450 microg/kg estradiol propionate im. once a week. Ten castrated animals received MPA only. Ten control, castrated animals were given the vehicles of these steroids. Ten other animals were kept parallelly, receiving the vehicles of all drugs (control animals). After 12 weeks of treatment cylindrical segments of the saphenous artery were isolated and cannulated at both ends and subjected to in vitro microarteriographic test. Pressure diameter curves, in the range of 0-200 mmHg, were recorded from segments in normal Krebs-Ringer (nKR) solution, in contraction with norepinephrine (1.6 x 10(-5) M), and then in relaxation with papaverine (2.8 x 10(-5) M). Biomechanical parameters were calculated based on the pressure diameter curves. RESULTS: Combined hormone replacement therapy significantly increased the passive diameter of small arteries, as compared to those from ovariectomized animals without hormone replacement. MPA monotherapy did not alter the vessel diameter, the inner radii at 100 mmHg intraluminal pressure were, 300+/-9 microm in the control castrated, 340+/-7 microm in the estradiol + MPA replaced and 306+/-8 microm in the MPA treated groups (P < 0.05 between the control castrated and the combined treatment groups). The vascular reactivity to norepinephrine or papaverine was not changed significantly either by combined hormone replacement or by MPA monotherapy when compared with ovariectomized controls. No significant alterations were found in wall thickness and distensibility. CONCLUSIONS: These results suggest that chronic medroxyprogesterone pretreatment does not influence the geometric, elastic and contractile properties of small arteries in castrated female rats. The combination of MPA + estradiol increased the morphological lumen: the morphological vasodilatation induced by estrogen, described earlier, was not affected by the addition of this progestin to the regimen.

Animals↗
PubMed2000

In vitro effects of different steroid hormones on superoxide anion production of human neutrophil granulocytes.

Neutrophil granulocytes play an important role in atherogenesis also through their free radical generation. According to recent studies, a point of action by which estrogens can provide protection against atherosclerosis is their inhibiting effect on superoxide anion production. The aim of our study was to test whether this means a common effect of steroids on superoxide production, or whether various steroid hormones have different action on superoxide generation of human granulocytes. Neutrophils were separated from the blood samples of twelve healthy volunteers. Isolated cells were incubated with different concentrations (10(-9), 10(-8), 10(-7) M) of hydrocortisone, aldosterone, cortexolone, 17-beta-estradiol, progesterone, and testosterone. Superoxide anion production was determined by photometry using the reduction of ferricytochrome-C. Compared to that of control cells neutrophils incubated with 17-beta-estradiol, progesterone, testosterone and hydrocortisone showed significantly reduced superoxide production. No significant alteration of superoxide anion production was found after the incubation of cells with aldosterone and cortexolone. It is concluded that similarly to estradiol other sex steroids and cortisol can inhibit the free radical production of human granulocytes, but mineralocorticoid aldosterone and Reichstein's substance S do not show such activity. Our results provide new evidence supporting the theory that certain types of steroid hormones have antioxidant capacity. This may give further reasons for investigating the molecular background of the existence or absence of this property and thus might lead to the development of new free radical scavengers.

Adult↗
PubMed2000

Effect of ovariectomy and hormone replacement therapy on small artery biomechanics in angiotensin-induced hypertension in rats.

OBJECTIVES: To test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depleted state (proposed to increase cardiovascular vulnerability) and with hormone replacement. DESIGN: Biomechanical properties of saphenous artery segments from ovariectomized (n = 10), ovariectomized + chronically angiotensin II infused-(n = 10), and ovariectomized + chronically angiotensin II-infused + sex hormone-replaced (n = 10) rats were studied. METHODS: Surgical ovariectomy was performed. Osmotic minipumps were used for chronic angiotensin II infusion (100 ng/min per kg). For hormone replacement therapy, oestradiol-propionate, 450 microg/kg for 7 days + medroxyprogesterone-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 weeks, cylindrical segments of the saphenous artery were prepared and subjected to in-vitro microarteriographic measurements. Pressure-diameter curves (0-200 mmHg) were recorded in Krebs-Ringer solution, with smooth muscle contracted (norepinephrine, 16 micromol/l) and with relaxed (papaverine, 28 micromol/l). RESULTS: Chronic angiotensin II infusion significantly reduced the inner radius (at 100 mmHg: 298 +/- 17 microm versus 347 +/- 7 microm, P< 0.001), while wall-thickness did not change. Hormone replacement restored the morphological radius (333 +/- 7 microm). Angiotensin II infusion slightly increased the full contraction range of the segments (defined as the percentage difference between fully contracted and fully relaxed diameters), which was further significantly increased by hormone replacement (39 +/- 4%, 46 +/- 8%, 62 +/- 7% at 100 mmHg, in the three groups, respectively; P < 0.05). Despite unaltered stiffness in relaxed state, elastic moduli computed for the contracted segments decreased after hormone replacement. CONCLUSIONS: These observations give further experimental support to the hypothesis that sex hormone replacement might be useful in preventing the development and/or stabilization of postmenopausal hypertension, as well as in treating existing disease.

Angiotensin II↗
PubMed1999

[Changes in the myeloperoxidase activity of human neutrophilic granulocytes and the amount of enzyme deriving from them under the effect of estrogen].

Free radicals which are produced constantly in the human body have a significant role in the development of atherosclerosis. The responsibility of leukocytes for vascular disease has been proved in several ways. Hormonally active women are protected much more against myocardial infarction than men, which fact can be explained partly by endocrinological reasons, too. The authors have set the aim to investigate whether estrogen therapy effects on the one hand the intracellular activity of the granulocyte-enzyme, myeloperoxidase (MPO), which takes place in free radical reactions and on the other hand the amount of MPO released from neutrophils. In the case of women having menopause and being treated with hormone replacement (n = 11) the intracellular activity and the amount of MPO-release increased significantly as compared to the level at the time of starting taking the medicine (p < 0.001). Based on the results it can be supposed that the vasoprotective effect of estrogens is fulfilled through their influence on the MPO enzyme, too. Besides the fact that intensified MPO activity through enhanced consumption might induce the decreased accumulation of H2O2 (a reactive oxygen species, substrate of MPO), MPO also has a role in the termination of the whole process of free radical production in granulocytes by the inactivation of the NADPH-oxidase system. This means that the growing intracellular MPO activity and the increased amount of enzyme released induce the decrease of the amount of free radicals produced during the "respiratory burst" and this is advantageous from the point of view of vasoprotection. The increased MPO activity and the NADPH-oxidase inactivation supposed to be elicited by it, might have further positive consequences since MPO has an effect on HDL-metabolism and the outflow of cholesterol from "foam cells", NADPH-oxidase has a suspected role in LDL-oxidation and NADPH is one of the cofactors of NO-synthase (NOS). The decreased superoxide anion level on the other hand may mitigate the chance of the neutralizing of nitric oxide (NO) by it. The superoxide anion is a potent vasoconstrictor and therefore, its diminished production may be beneficial, i.e. decreases the risk of coronary spasm. The new conceptual synthesis worked out by the authors may provide a possible explanation of the increased susceptibility to infections during steroid treatment, too.

Estrogen Replacement Therapy↗
PubMed1999

The effect of ovariectomy and oestrogen replacement on small artery biomechanics in the rat.

OBJECTIVE: To determine the effects of oestrogen deficiency and hormone replacement therapy on the biomechanical properties of a small artery. SAMPLE: Thirty non-pregnant female Sprague-Dawley rats. METHODS: Twenty animals were pharmacologically ovariectomised by triptorelin and received either oestradiol propionate or its vehicle. Ten other animals received only the vehicle for the same period of time (control group). After 12 weeks of treatment, cylindrical segments of the saphenous artery were isolated and cannulated at both ends. Pressure-diameter curves were recorded from segments in normal Krebs-Ringer, using norepinephrine, and then with papaverine. The vessel segment close to the examined one was histologically evaluated. Serum levels of oestradiol and cortisol were determined. MAIN OUTCOME MEASURES: Biomechanical parameters based on the pressure-diameter curves. RESULTS: Pharmacological ovariectomy decreased the passive diameter of the arteries and oestrogen replacement therapy prevented this. Decreased reactivity to norepinephrine was also restored by oestrogen treatment. Pressure induced myogenic tone was decreased significantly by oophorectomy and increased after oestradiol treatment. No significant changes were found in wall thickness, distensibility, elastic modulus or tangential stress. No significant histological alterations were seen in the vessel wall. Oestradiol levels were significantly decreased in the castrated animals compared with the other two groups. CONCLUSIONS: These results suggest that oestrogen deficiency decreases and oestrogen replacement increases the passive diameter of small peripheral arteries, and that oestrogen enhances the reactivity of vascular smooth muscle. These responses may provide the background mechanisms for the increased incidence of arterial hypertension and hot flushes during the menopause and the ability of oestrogen substitution to prevent them.

Animals↗
PubMed1998

Direct relaxing effect of estradiol-17beta and progesterone on rat saphenous artery.

Although estrogen has been reported to relax large coronary arteries immediately, its direct acute effect on small vessel tone has not been fully defined. In this study, we investigated the effect of estradiol-17beta and progesterone on isolated rat saphenous artery segments-with an internal radius of 250 microm-by measuring the outer diameter of the vessels using in vitro angiometry. Estradiol and progesterone at concentrations of 1-100 and 8.6-86 microM induced a rapid, dose-dependent relaxation of the arterial segments precontracted with norepinephrine. Maximal changes of diameters were 85.8 +/- 10 and 90.9 +/- 8%. Clomiphene citrate, a cytoplasmic receptor antagonist, did not diminish this action of estradiol, with the exception of the highest concentrations of the hormone. Thus a nongenomic pathway for this effect can be suspected. Dexamethasone did not induce similar vasodilation. It is concluded that estradiol and progesterone have similar rapid vasorelaxing effects on small muscular arteries as found previously on coronary arteries.

Animals↗
PubMed1996

[Emergency situations in hypertension].

Hypertensive emergency is an acute, perilous state connected with a marked increase of peripheral vascular resistance and the decrease of tissue perfusion. Its development depends on the rate of blood pressure elevation, on the severity of developed hypertension and the state of the vascular system. Although hypertensive emergencies can be grouped also on symptomatological and etiological basis, regarding the therapeutic measures to be taken, they appear in two well distinguishable forms. In case of hypertensive crisis treatment has to be started without delay, possibly in a few minutes, in states involving the risk of hypertensive crisis treatment has to be initiated within a few hours to avoid extensive damage of the vital organs or fatal outcome. The acute, but controlled reduction of blood pressure must not surpass 15-25% of the medium value. In hypertensive crisis, if possible, parenteral medication--as first aid--urapidil, verapamil, in states with endangering hypertensive crisis sublingual nifedipine, captopril, nitroglycerin may be applied, however in the different emergency states therapeutic intervention has to be individually determined.

Administration, Sublingual↗
PubMed1996

Evidence for genetic variability in venous responsiveness.

Alterations in adrenergic mediated vascular responsiveness and glucose metabolism have been implicated in the pathogenesis of essential hypertension. We sought for a human model to study possible interactions between the two pathogenetical factors. In a group of Latin-Americans there is a predominance of diabetes mellitus, impaired glucose tolerance and obesity, while the rate of hypertension is unexpectedly low (lower than in the normal population). Here we demonstrate attenuated alpha 1 adrenergic mediated vasoconstriction in the above group, suggesting a possible protective mechanism against the development hypertension.

Adrenergic alpha-Agonists↗
PubMed1996

Effect of ACE inhibition by benazepril, enalapril and captopril on chronic and post exercise proteinuria.

Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.

Adult↗
PubMed1995

[Basic principles of current trends in the management of hypertension and kidney disease in pregnancy].

The approach to renal disease and hypertension in pregnancy has dramatically changed over the past two decades. As opposed to the past, now almost all the female patients with underlying renal disease can have successful pregnancy, and we are able to manage most of the renal complications occurring during the pregnancy. In this article the authors give an extensive review of the results of recent studies, concerning this subject. The options to prevent the predictable complications, the most recent therapeutic guidelines and the outcome of these patient's pregnancies are discussed, focused on the changes, compared to the recent past.

Adrenergic beta-Antagonists↗
PubMed1993

[Quality of life and antihypertensive therapy].

The patients' well-being during antihypertensive treatment markedly influences their compliance. Therefore, in the last several years the effect of antihypertensive medications on the quality of life has been examined all over the world. The terminological and methodical problems at the field of quality of life resulted in difficulties regarding the comparison of the results of different working groups. This review is focused on the results of randomised, double-blind studies. We found that ACE inhibitors, calcium channel blockers and selective beta blockers have the most beneficial effect on the quality of life.

Adrenergic beta-Antagonists↗
PubMed1993

TxA2-PGI2-PGF2 alfa responses in the kidney to blood pressure reduction induced by vasodilator/vasorelaxing agents with different action in patients with essential hypertension.

In blood pressure (BP) reduction induced by gallopamil, hydralazine and prazosin in patients with essential hypertension a common trend was found in renal prostanoid production which included increased TxB2 excretion and/or augmented TxB2/6-keto-PGF1alfa ratio and, with the exception of response to prazosin, enhanced PGF2alfa excretion. Role of direct biochemical actions by the drugs in these responses was excluded by in vitro experiments with kidney slices from rats. The clinical and in vitro experimental findings suggested a mediator role of sympathetic activation but not that of the increased renin release in the urinary eicosanoid responses. Significant correlation was observed between the changes in reabsorbed amounts of sodium and excreted amounts of TxB2 and PGF2alfa. The results suggest that the reactivity of pressure type prostanoids in the kidney could be considered as part of a more complex renal counteraction to BP decrease.

Adolescent↗