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Biomedical subjects

I Szabo

Publications and source records attributed to I Szabo.

At least 37 records · Page 2Linked to original sources

Improvement of perinatal outcome in diabetic pregnant women.

Obstetrical and perinatal outcomes in newborns of diabetic pregnant women depend on metabolic control and fetal surveillance during pregnancy. The effects of fetal surveillance on perinatal mortality and morbidity was analyzed in diabetic pregnant women with appropriate glucose control in our regional center for diabetes and pregnancy. 480 deliveries complicated by frank or gestational diabetes occurred in our Department in the period of 1988-1999. Perinatal mortality and morbidity, prevalence of premature deliveries, methods of fetal surveillance, options for respiratory distress syndrome (RDS) profilaxis, cesarean section rate, timing of delivery and its indications and occurrence of malformations have been analyzed. It was found that malformation rate and perinatal mortality may be reduced to even lower level than that of in healthy pregnant women by appropriate glucose control and by using the latest methods of intrauterine fetal surveillance including cardiotocography (non stress test and oxytocin challenge test), doppler fetal artery velocimetry and fetal pulse oximetry. Timing of delivery was needed in 35% of the cases with IDDM and 15% of gestational diabetes due to chronic placental insufficiency. If labour induction was needed before the 38 weeks, amniocentesis was performed to test fetal lung maturity. Direct fetal glucocorticoid administration was used to enhance fetal lung maturation in 14 cases. C-section rate was slightly higher than that of in non diabetic pregnant women. Our perinatal morbidity data (macrosomia, hyperbilirubinemia, hypoglycemia, injuries, infections) are comparable with the data from the literature. Although perinatal mortality with the help of thorough fetal surveillance is even better in diabetic pregnant women than in non diabetic patients, future eye should be focused on factors affecting perinatal morbidity, because it is still higher than in newborns of healthy mothers.

Cesarean Section↗

[Orbital tuberculoma].

We present a case of orbital tumor with skin lesions at the lateral cantus. CT scan confirmed the orbital tumor and we considered it to be malignant. The histological examination of a piece of the tumor showed tuberculous characteristics. Patient received treatment with antituberculous drugs and steroids. The tumor decreased after two months of treatment.

Aged↗

Cell volume in the regulation of cell proliferation and apoptotic cell death.

Cell proliferation must - at some time point - lead to increase of cell volume and one of the hallmarks of apoptosis is cell shrinkage. At constant extracellular osmolarity those alterations of cell volume must reflect respective changes of cellular osmolarity which are hardly possible without the participation of cell volume regulatory mechanisms. Indeed, as shown for ras oncogene expressing 3T3 fibroblasts, cell proliferation is paralleled by activation of Na(+)/H(+) exchange and Na(+),K(+),2Cl(-) cotransport, the major transport systems accomplishing regulatory cell volume increase. Conversely, as evident from CD95-induced apoptotic cell death, apoptosis is paralleled by inhibition of Na(+)/H(+) exchanger and by activation of Cl(-) channels and release of the organic osmolyte taurine, major components of regulatory cell volume decrease. However, ras oncogene activation leads to activation and CD95 receptor triggering to inhibition of K(+) channels. The effects counteract the respective cell volume changes. Presumably, they serve to regulate cell membrane potential, which is decisive for Ca(++) entry through I(CRAC) and the generation of cytosolic Ca(++) oscillations in proliferating cells. As a matter of fact I(CRAC) is activated in ras oncogene expressing cells and inhibited in CD95-triggered cells. Activation of K(+) channels and Na(+)/H(+) exchanger as well as Ca(++) oscillations have been observed in a wide variety of cells upon exposure to diverse mitogenic factors. Conversely, diverse apoptotic factors have been shown to activate Cl(-) channels and organic osmolyte release. Inhibition of K(+) channels is apparently, however, not a constant phenomenon paralleling apoptosis which in some cells may even require the operation of K(+) channels. Moreover, cell proliferation may at some point require activation of Cl(-) channels. In any case, the alterations of cell volume are obviously important for the outcome, as cell shrinkage impedes cell proliferation and apoptosis can be elicited by increase of extracellular osmolarity. At this stage little is known about the interplay of cell volume regulatory mechanisms and the cellular machinery leading to mitosis or death of the cell. Thus, considerable further experimental effort is required in this exciting area of cell physiology.

Apoptosis↗

Isolation of morphologically and functionally intact gastric mucosal microvessels rapid communication.

Gastric mucosal microvessels were isolated after arterial perfusion of the rat stomach with magnetized iron oxide suspension. After homogenization of scrapped gastric mucosa, microvessels were initially separated with a high power magnet and further separated and purified by using a nylon sieve. Aliquots of purified microvessels were assessed for viability, histologic appearance, ultrastructure and generation of prostacyclin. Microvessels were plated on Matrigel and cultured in DMEM with high glucose and 10% FBS for 1, 3 or 5 days. After 1, 3 and 5 days of culturing, endothelial viability was assessed with Fast green exclusion, and the basal and stimulated (with calcium ionophore) generation of prostacyclin was determined by assaying aliquots of the incubating medium for 6-keto PGF(1alpha). At 1 and 3 hrs after isolation, microvessels demonstrated intact morphologic structures as reflected by transmission EM and 92+/-4% of viable endothelial cells. The microvessels plated on Matrigel maintained good viability for at least 5 days and generated prostacyclin at the baseline and following ionophore stimulation. These data demonstrate that isolated microvessels cultured under optimal conditions are fully viable and functional.

Animals↗

Cell volume regulatory mechanisms in apoptotic cell death.

One of the hallmarks of apoptosis is cell shrinkage, which--at constant extracellular osmolarity--requires a decrease of cellular osmolarity. Moreover, apoptosis can be elicited by increase of extracellular osmolarity and the resistance of cells towards apoptosis correlates with their ability to regulate their volume in hypertonic environment. On the other hand, CD95-receptor-mediated apoptosis is blunted at moderate increases of extracellular osmolarity. Given the role of cell volume alterations it is not surprising that apoptosis is paralleled by marked alterations of cell volume regulatory mechanisms. Stimulation of the CD95-receptor, which confers apoptosis to a variety of cells, leads to activation of cell volume regulatory anion channel ORCC. However, activation of ORCC is paralleled by inhibition of cell volume regulatory K+ channel Kv1.3. It is only 40 to 60 minutes after triggering of the CD95-receptor when the cells release the organic osmolyte taurine and shrink.

Animals↗

Influence of nicotine, cotinine, anabasine and cigarette smoke extract on human granulosa cell progesterone and estradiol synthesis.

To reveal the well known effect of smoking on the incidence of early abortion, the possible effects of cigarette alkaloids on progesterone and estradiol synthesis were investigated. A suspected cause for early spontaneous abortion is corpus luteum insufficiency. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone and estradiol biosynthesis. Human granulosa cells were obtained from patients undergoing in vitro fertilization and embryo transfer treatment because of infertility. Incubation of the granulosa cells with cotinine, anabasine, with the combination of nicotine, cotinine and anabasine, or with an aqueous extract of cigarette smoke resulted in inhibition of progesterone synthesis. The alkaloids and smoke extract decreased the DNA content of the culture dish. These latter findings suggested a cytotoxic effect of the alkaloids. Both cotinine and anabasine slightly stimulated the synthesis of normalized estradiol. However, nicotine, combination of all three alkaloids, and cigarette smoke extract had no significant influence on estradiol production. Taken together, these data would suggest that cigarette alkaloids inhibit cellular progesterone synthesis both by inhibiting progesterone synthesis and by causing less specific toxic effects to the cell. In contrast, cigarette smoke alkaloids slightly stimulated or had no effect on estradiol production. These concomitant actions of cigarette alkaloids partly explain the higher incidence of early abortion in pregnant women who smoke.

Anabasine↗

Barbiturates inhibit progesterone synthesis in cultured Leydig tumor cells and human granulosa cells.

Screening drugs used in obstetrical practice for effects on steroid hormone synthesis revealed that phenobarbital inhibited progesterone synthesis in MA-10 Leydig tumor cells. The inhibition was apparently a drug class effect since it could be reproduced by other barbiturates. Barbiturate blockade was reversible and could be bypassed in the MA-10 cells by using 22-hydroxycholesterol. Human granulosa cell progesterone synthesis was also inhibited in a dose dependent fashion by phenobarbital, secobarbital and barbituric acid. Significant inhibition occurred in dose ranges that would be therapeutic for treating epilepsy. From these data we conclude that barbiturates block steroidogenesis by inhibiting cholesterol transport to the cholesterol side chain cleavage enzyme.

Anticonvulsants↗

[Exophthalmos in giant cerebral arteriovenous vascular malformations].

We present the most important ophthalmologic signs related to the angiocinematographic aspects in two patients presenting giant arteriovenous malformations in the frontal part of the brain. In both cases the first clinical sign of the disease was unilateral proptosis associated with scleroconjunctival arteriovenous malformation. In the presented cases we could not establish any relationship between the intensity of the proptosis, the scleroconjunctival vascular malformation and the size of the intracranial arteriovenous malformation. We point on the importance of the proptosis associated with scleoconjunctival vascular malformation representing the first signs in intracranial arteriovenous malformations.

Adult↗

Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases.

The n-type K+ channel (n-K+, Kv1.3) in lymphocytes has been recently implicated in the regulation of Fas-induced programmed cell death. Here, we demonstrate that ceramide, a lipid metabolite synthesized upon Fas receptor ligation, inhibits n-K+ channel activity and induces a tyrosine phosphorylation of the Kv1.3 protein in Jurkat T lymphocytes. Tyrosine phosphorylation of the n-K+ channel correlated with an activation of the Src-like tyrosine kinase p56lck upon cellular treatment with the ceramide analog C6-ceramide. Because genetic deficiency of p56lck or inhibition of Src-like tyrosine kinases by herbimycin A prevented ceramide-mediated n-K+ channel inhibition and tyrosine phosphorylation, we propose a ceramide-initiated activation of p56lck resulting in tyrosine phosphorylation and inhibition of the n-K+ channel protein.

Ceramides↗

Specific blockade of slowly activating I(sK) channels by chromanols -- impact on the role of I(sK) channels in epithelia.

Chromanols, which were recently shown to inhibit cAMP-mediated Cl- secretion in colon crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B specifically inhibited I(sK) channels with an IC50 of 7 micromol/l without affecting the delayed rectifier Kv1.1 or the inward rectifier Kir2.1. Moreover, several other chromanols displayed the same rank order of potency for I(sK) inhibition as demonstrated in colon crypts. Finally, we tested the effects of the previously described I(sK) blocker azimilide on cAMP mediated Cl- secretion in rat colon crypts. Similar to 293B azimilide inhibited the forskolin induced Cl- secretion. These data suggest that I(sK) protein induced K+ conductances are the targets for the chromanol 293B and its analogues, and azimilide.

Animals↗

The high-conductance channels of yeast mitochondrial outer membranes: a planar bilayer study.

The high-conductance channels present in the outer membranes of wild-type and porin-less yeast mitochondria have been characterized electrophysiologically after incorporation in planar bilayer membranes. The most prominent activity was ascribed to a voltage-dependent, substate-rich, cationic channel which generally inactivated at potentials positive in the cis compartment, in agreement with the observations from patch-clamp experiments on porin-less mitoplasts. This channel has been identified as the so-called "peptide-sensitive channel" (PSC). We also observed similar channels displaying either no inactivation, or inactivation at both positive and negative potentials. These latter properties match those already described for mammalian and yeast PSC, respectively. These different behaviors are tentatively explained as arising from the presence, or lack of, peptides bound to the PSC. Very high conductances, apparently due to cooperative gating, were frequently displayed. In wild-type membranes, activity ascribable to the porin was also observed.

Electric Conductivity↗

Activity of histamine metabolizing and catabolizing enzymes during reperfusion of isolated, globally ischemic rat hearts.

Myocardial ischemia-reperfusion injury increases both tissue levels and release of histamine. To study the possible effects of ischemia-reperfusion on histamine metabolism tissue activities of histidine decarboxylase (HDC), histamine N-methyl transferase (HNMT) and diamine oxidase (DAO) were investigated in isolated rat hearts subjected to either 20 min global ischemia and 40 min reperfusion (n = 10) or control perfusion (n = 8). Histamine in the coronary effluent increased from 21 +/- 4 nmol/min (mean +/- SEM) before ischemia to 55 +/- 5 and 50 +/- 7 nmol/min after 4 and 10 min reperfusion (p < 0.004 and p < 0.004). Tissue HDC activity did not change during observation in any group. HNMT activity was unchanged in controls, but increased from 0.37 +/- 0.04 to 0.84 +/- 0.18 and 0.96 +/- 0.22 pmol methylhistamine/mg protein hour after 4 and 10 min reperfusion (p < 0.008 and p < 0.01). DAO decreased similarly in controls and ischemic-reperfused hearts during observation. In conclusion, the previously observed increase of tissue histamine during reperfusion cannot be explained by increased histamine synthesis or decreased histamine catabolism.

Amine Oxidase (Copper-Containing)↗

Modulation of macrophage phagocytic activity by cell wall components of Candida albicans.

Cell wall components of the pathogenic yeast Candida albicans have been shown to possess significant immunomodulatory activity both in vivo and in vitro. We have previously found that an ethylenediamine (EDA) extract of the Candida cell wall exhibits significant immunosuppressive activity. In an effort to further characterize the immunomodulatory activity of the EDA extract, we attempted to determine the effect of this extract on macrophage phagocytic activity. Our results show that nonelicited peritoneal macrophages treated for 24 or 48 hr with the EDA extract fail to phagocytize Candida yeast cells normally. We have observed that the phagocytosis of Candida is mediated by a combination of lectin-like receptor-, Fc receptor-, and complement receptor-type 3 (CR3)-dependent processes. Results show, however, that the most efficient uptake of this organism is dependent on CR3-mediated phagocytosis. Experiments carried out under various opsonic conditions suggest that the level of CR3-mediated phagocytosis of Candida is depressed following EDA extract treatment. These results show that a substantial mechanism of macrophage phagocytosis is depressed following contact with cell wall components of Candida.

Animals↗

Histamine release and its effects in ischaemia-reperfusion injury of the isolated rat heart.

Histamine is released from the heart during ischaemia-reperfusion injury. As histamine has cardiac effects, we investigated the role of histamine in ischaemia-reperfusion injury of isolated rat hearts. A Langendorff-model with 30 min global (37 degrees C) ischaemia followed by 60 min reperfusion was employed. The effects of ischaemia alone (n = 10, group 1.1 + n = 10, group 2.1, 2 different series), and ischaemia with H1- and H2-receptor blockade with cimetidine (10 microM, n = 10), chlorpheniramine (10 microM, n = 8), terfenadine (10 microM, n = 8), and promethazin (10 microM, n = 9), or both cimetidine and chlorpheniramine (n = 8), were studied. Histamine was measured in the coronary effluent and cardiac tissue of group 1.1. Release of histamine increased from 6.5 +/- 1 pmol min-1 before ischaemia to 19 +/- 3 pmol min-1 at the start of reperfusion. Ischaemia decreased left ventricular developed pressure to 18 +/- 11% (1.1) and 50 +/- 11% (2.1) of initial value (mean +/- SEM) at the start of reperfusion. Left ventricular end-diastolic pressure increased from 0 to 79 +/- 8 mmHg (1.1) and 39 +/- 9 (2.1) mmHg, while left ventricular systolic pressure was unchanged (101 +/- 12% in 1.1 and 101 +/- 10% in 2.1). Severe arrhythmias were induced in 90 (1.1) and 30 (2.1)% of the hearts, while coronary flow decreased during reperfusion. H2-blockade did not modify the changes in left ventricular pressures, coronary flow, or heart rate induced by ischaemia. Three different H1-blockers increased left ventricular systolic pressure, inhibited the decrease of developed pressure, attenuated the increase of end-diastolic pressure, and totally inhibited reperfusion arrhythmias. The effect of both blockers together was similar to that of H1-blockers alone. Coronary flow was increased during reperfusion in two of the groups with H1-blocker compared with ischaemic controls. Increased release of histamine from ischaemic-reperfused rat hearts concurred with depression of left ventricular function and arrhythmias during early reperfusion. Cardiac dysfunction during reperfusion was attenuated by three different H1-receptor blockers.

Animals↗

On-line recognition and quantitation of coeluting hypoxanthine and guanine in reversed-phase high-performance liquid chromatography of placental tissue extracts: photodiode-array detection and spectral analysis of coeluting peaks.

In a reversed-phase HPLC method, optimized for resolution and quantitation of nucleosides and nucleobases in human term placental extracts, guanine coeluted with hypoxanthine. Three numerical techniques that treat spectral data generated by photodiode-array detection to yield indices of peak purity were compared for sensitivity of on-line recognition of overlapped guanine and hypoxanthine peaks in chromatograms of 7.0 microM hypoxanthine containing 0.075-0.54 microM guanine. These techniques were purity parameter, the average wavelength of a peak spectrum (lambda w), peak area ratio, and peak absorbance ratio. Purity parameter of a 7.0 microM hypoxanthine peak containing 1% guanine was significantly different from that of pure hypoxanthine (P < 0.01); peak area and peak absorption ratios were four and seven times, respectively, less sensitive than purity parameter. In chromatograms of human term placental extracts, purity parameter values generated on-line signalled the presence of guanine in hypoxanthine peaks. Quantitation of coeluting hypoxanthine and guanine was performed on-line from dual-wavelength detection at 249 and 278 nm via calibration curves for both analytes at these wavelengths. Hypoxanthine and guanine concentrations in seven samples from five human term placentas were 41-161 and 3-76 nmol/g, respectively. These findings demonstrate that on-line signalling of hypoxanthine and guanine coelution is achieved by purity parameter, area ratio, and absorbance ratio, that purity parameter is the most sensitive index of coelution, and that quantitation of the coeluting analytes can be performed on-line. These approaches should be applicable to recognition and quantitation of coeluting analytes in chromatograms of mixtures of nucleosides and nucleobases such as occur in extracts of other tissues.

Chromatography, High Pressure Liquid↗

Release of histamine from isolated rat hearts during reperfusion is not dependent on length of ischemic insult, or contents of histamine in cardiac tissue.

Release of histamine (H) by ischemia-reperfusion injury was investigated in isolated rat hearts (Langendorff model). The effect of 10, 15, 20, 25, 30, 40 and 60 min ischemia (n = 10 each) on H in the coronary effluent and in cardiac tissue was studied after 4 min reperfusion. Release of creatine kinase and lactate dehydrogenase in the coronary effluent increased with time of ischemia. Tissue H increased from 95 +/- 10 ng/g rat heart (mean +/- SEM) before ischemia to max 148 +/- 10 ng/g after 20 min ischemia (p < 0.002), and increased also after 15 (p < 0.01), 25 (p < 0.01), and 30 min (p < 0.045). H in the coronary effluent increased after 15 (from 16 +/- 3 to 26 +/- 2 pmol/min, p < 0.044), 30 (26 +/- 6 pmol/min, p < 0.027), and 60 min ischemia (47 +/- 6 pmol/min, p < 0.0044). Release of H during ischemia-reperfusion is neither dependent on the severity of the ischemic insult, nor on the level of tissue H.

Animals↗