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Biomedical subjects

L Kovács

Publications and source records attributed to L Kovács.

At least 19 recordsLinked to original sources

Action potentials and potassium currents in rat ventricular muscle during experimental diabetes.

Time course of the surface electrical activity was studied in left ventricular trabeculae of Wistar rats made diabetic using streptozotocin. The action potentials were recorded in Tyrode's solution at 32 degrees C, their duration considerably increased in diabetes. By the 8th week, the prolongation was 64% at 25% of repolarization; 112% at 50% and 118% at 75%. Insulin treatment reduced the prolongation of the action potentials although a complete restoration was not achieved. 0.1 mM La3+ moderately shortened the electrical activity both in control and in diabetic trabeculae. Three mM 4-aminopyridine made the time course of control action potentials very similar to the diabetic ones while the action potentials from the diabetic animals were prolonged further to a smaller extent. Whole-cell clamp experiments in isolated ventricular myocytes (20-23 degrees C) showed a considerable decrease and a somewhat accelerated inactivation of the transient outward current (Ito) in diabetes. The steady-state inactivation and the rate of recovery from inactivation of Ito did not change. No alterations in the magnitude and voltage dependence of inward rectifier (IK1) were found around the resting membrane potential. The diabetes-related suppression of Ito explains the decreased repolarization rate of action potentials.

4-Aminopyridine

Use of midazolam ('Dormicum') and flumazenil ('Anexate') in paediatric bronchology.

One hundred and seven bronchological examinations using midazolam narcosis in association with flumazenil were carried out in 100 children (mean age 3.5 years, range 4 months to 14 years) suffering from chronic non-specific lung disease. Rigid bronchoscopy was followed in 49 cases by bronchography. All patients were premedicated with atropine followed by midazolam (0.2 mg/kg intravenously). Ventilation was carried out with nitrous oxide and oxygen in 47 children and with oxygen only in 60 patients. After 3 mins, suxamethonium (2 mg/kg intravenously) was given for muscle relaxation and intubation carried out. Fifty-one of the children ventilated with oxygen only also received fentanyl (0.002 mg/kg intramuscularly), at the same time as atropine, to provide analgesia. After extubation, all patients were given flumazenil (0.1 to 0.2 mg intravenously) to reverse the effects of midazolam. The results showed that midazolam provided effective sedation and comfortable sleep (mean examination time 12 min 50 sec) and it was considered that the method using fentanyl rather than nitrous oxide for analgesia was the most satisfactory one. Patients awakened promptly (1 min) after flumazenil and quick and effective expectoration was noted, particularly important in those who had undergone bronchography. No complications were observed. Since this investigation, a further 500 bronchoscopics have been carried out using this method with the same results. Even though no narcosis equipment is required, it is recommended that, as with other procedures involving narcosis with muscle relaxation, bronchoscopy with these drugs should not be used in out-patients.

Anesthesia

A new computerized polarization--microscopic method for the demonstration of collagen fibers.

A new computerized polarization microscopic method was developed for objective, quick quantitative analysis of anisotropic structures. The paper presents the technology on collagen fibers of kidney and liver preparations. According to the observations the birefringence of one fiber can be characterized not by a single number as it is accepted generally but by a series of data. It suggests that the process of compensation is gradual. One of the explanations of this fact might be that the collagen fibers are inhomogeneous at submicroscopic level. With regard to this assumption, first several birefringent capillary basement membranes of a whole glomerulum were measured simultaneously. In this case, the individual capillaries showed nearly the same retardation. Second, portal zones of normal and cirrhotic livers as functional units were analyzed simultaneously. In the latter case the individual fibers show different birefringence. Comparing the results obtained by their technique with the data of the classic measuring method authors found similarity that proved its validity. Data suggest that the new method seems to be useful in experimental and diagnostic pathology.

Birefringence

[Radioreceptor assay for determination of the anti-progestogen, RU-486 and its active metabolites in the blood].

RU-486 is an antiprogesterone 19-norsteroid with high binding affinity for the progesterone receptor. It can be used with success for termination of early human pregnancy. Since the metabolites of RU-486 are often biologically active, their concentrations in blood can also have clinical significance. We have developed a rapid sensitive radio receptor assay for determination of RU-486 and its active metabolites. Human myometrium progesterone receptor was used as binding protein. The assay is based on the competitive replacement of 3H-ORG-2058 by the active molecular fraction of RU-486 present in the serum. The analytical parameters of this assay are the followings: intraassay percent of coefficient of variation (CV%) is ranged between 7.6 and 10.4%. The interassay CV% was from 7.1 to 16.3. The sensitivity of the receptor assay was 8.7 pmol/tube and the acceptable range was between 10 and 120 pmol/tube. The recovery ranged between 95 and 122% (r = 0.983). These parameters are suitable for the requirement of radioligand binding techniques based on the immunoassays.

Adult

[Prenatal diagnosis of measles infection by transabdominal puncture of the umbilical vein].

Prenatal diagnosis of fetal rubella infection was reported. Maternal infection took place at the 13th week of gestation. Percutaneous umbilical fetal blood sampling was performed at the 22nd week of gestation. 1:400 titre of rubella specific immunoglobulin in fetal sera confirmed the rubella infection. A normal baby was born by cesarean section at term and subsequent ophthalmologic, cardiologic, audiologic follow-up have not revealed any alteration in infant's development. Clinical management of fetal rubella infection was discussed.

Adult

[Significance in unilateral intermittent breast stimulation in prenatal diagnosis].

50 intermittent, unilateral breast stimulation test were studied, which were registered not more than 7 days before labour. The authors wanted to know how informative this method is to the fetal state, how much time it takes and which are the most common side effects. This method was compared with a previously by the authors publicated unilateral, continuous breast stimulation test. It is concluded that the intermittent, unilateral breast stimulation test well indicates the fetal state, though it takes more time, but no hyperstimulation was found in this study. The authors suggest to choose this unilateral, breast stimulation test as a first step because of its simplicity and shortness and cheapness. Only in case of unsuccess the next choice should be the intravenous oxytocin challenge test.

Breast

[Continuous breast stimulation in prenatal fetal diagnosis].

Fifty, high risk pregnancies were studied, where not more than 7 days before labour passed, an unilateral continuous breast stimulation test was performed. The predictive value, the testing time and the side effects of the method were analyzed. According to the results this breast stimulation test reliably indicates the fetal state. The testing time of the endogenous oxytocin challenge test is shorter than that of the exogen oxytocin challenge test. Because of the risk of hyperstimulation the test must be performed with intensive maternal and fetal observation. In the opinion of the authors the breast stimulation test--because of its reliability, shorter testing time and simpleness--should be the first choice among the challenge tests and only in case of a failure comes an exogen oxytocin challenge test into question.

Breast

Contraction threshold and the "hump" component of charge movement in frog skeletal muscle.

The delayed component of intramembranous charge movement (hump, I gamma) was studied around the contraction threshold in cut skeletal muscle fibers of the frog (Rana esculenta) in a single Vaseline-gap voltage clamp. Charges (Q) were computed as 50-ms integrals of the ON (QON) and OFF (QOFF) of the asymmetric currents after subtracting a baseline. The hump appeared in parallel with an excess of QON over QOFF by approximately 2.5 nC/mu F. Caffeine (0.75 mM) not only shifted the contraction threshold but moved both the hump and the difference between the ON and OFF charges to more negative membrane potentials. When using 10-mV voltage steps on top of different prepulse levels, the delayed component, if present, was more readily observable. The voltage dependences of the ON and OFF charges measured with these pulses were clearly different: QON had a maximum at or slightly above the contraction threshold, while QOFF increased monotonically in the voltage range examined. Caffeine (0.75 mM) shifted this voltage dependence of QON toward more negative membrane potentials, while that of QOFF was hardly influenced. These results show that the delayed component of intramembranous charge movement either is much slower during the OFF than during the ON, or returns to the OFF position during the pulse. Tetracaine (25 microM) had similar effects on the charge movement currents, shifting the voltage dependence on the ON charge in parallel with the contraction threshold, but to more positive membrane potentials, and leaving QOFF essentially unchanged. The direct difference between the charge movement measured in the presence of caffeine and in control solution was either biphasic or resembled the component isolated by tetracaine, suggesting a common site of caffeine and tetracaine action. The results can be understood if the released Ca plays a direct role in the generation of the hump, as proposed in the first paper of this series (Csernoch et al. 1991. J. Gen. Physiol. 97:845-884).

Animals

Kinetic properties of intramembrane charge movement under depolarized conditions in frog skeletal muscle fibers.

Intramembrane charge movement was measured on skeletal muscle fibers of the frog in a single Vaseline-gap voltage clamp. Charge movements determined both under polarized conditions (holding potential, VH = -100 mV; Qmax = 30.4 +/- 4.7 nC/micro(F), V = -44.4 mV, k = 14.1 mV; charge 1) and in depolarized states (VH = 0 mV; Qmax = 50.0 +/- 6.7 nC/micro(F), V = -109.1 mV, k = 26.6 mV; charge 2) had properties as reported earlier. Linear capacitance (LC) of the polarized fibers was increased by 8.8 +/- 4.0% compared with that of the depolarized fibers. Using control pulses measured under depolarized conditions to calculate charge 1, a minor change in the voltage dependence (to V = -44.6 mV and k = 14.5 mV) and a small increase in the maximal charge (to Qmax = 31.4 +/- 5.5 nC/micro(F] were observed. While in most cases charge 1 transients seemed to decay with a single exponential time course, charge 2 currents showed a characteristic biexponential behavior at membrane potentials between -90 and -180 mV. The voltage dependence of the rate constant of the slower component was fitted with a simple constant field diffusion model (alpha m = 28.7 s-1, V = -124.0 mV, and k = 15.6 mV). The midpoint voltage (V) was similar to that obtained from the Q-V fit of charge 2, while the steepness factor (k) resembled that of charge 1. This slow component could also be isolated using a stepped OFF protocol; that is, by hyperpolarizing the membrane to -190 mV for 200 ms and then coming back to 0 mV in two steps. The faster component was identified as an ionic current insensitive to 20 mM Co2+ but blocked by large hyperpolarizing pulses. These findings are consistent with the model implying that charge 1 and the slower component of charge 2 interconvert when the holding potential is changed. They also explain the difference previously found when comparing the steepness factors of the voltage dependence of charge 1 and charge 2.

Animals

Adrenergic receptors in human fetal liver membranes.

The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using 3H-prazosin and 3H-dihydroalprenolol, respectively, as radioligand. Heterogenous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycaemia of newborns after treatment of premature labour with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.

Adult

Future direction of abortion technology.

Reliable statistical data indicate that even today abortion is widely used in the regulation of human reproduction, irrespective of whether it is well or badly tolerated. Medical responsibility therefore dictates that abortions should be made as safe as possible in order to safeguard the health of women who cannot avoid abortion. The most advanced development in abortion technology is medical abortion. At present, the best available method is the combination of an antiprogesterone (RU-486) and a low dose of prostaglandin, either in an injection (sulprostone) or in a vaginal pessary (gemeprost). The currently employed treatment schedules are still not optimal. The treatment lasts for at least 48 or 72 hours and close follow-up is needed to assess whether the treatment has been successful or not. The side-effects, however, are negligible, and the medical method is free from the complications of the surgical methods and those of anaesthesia. The high efficacy (95% complete abortion rate at a gestational age up to eight weeks) restricts the risk of surgery and anaesthesia to the 5% failures. Further research is required to develop a more appropriate treatment schedule, preferably a single-shot treatment. At the same time, the prevention of misuse of the medical methods must be guaranteed to achieve a better acceptance of these safe abortion methods by society. For the time being, medical supervision and follow-up seems to be mandatory, and a 'do-it-yourself' home method providing complete privacy must be regarded as unsafe and medically unacceptable.

Abortion, Induced

Comparative study of antioxidant enzymes and lipid peroxidation in cord and maternal red blood cells.

The activities of the antioxidant enzymes and lipid peroxidation were compared in the red blood cells from the blood of 50 mothers and the umbilical cord of 50 full-term healthy neonates. The antioxidant activities (except that of catalase) and the lipid peroxidation were found to be higher in the cord blood. These observations differed from the previous literature data: a parallel could be found only with the concept (connected with oxygen radicals) of the early closure of the ductus arteriosus.

Catalase

[Clinical pharmacologic study of Tri-Regol tablets (new oral triphase contraceptives)].

Clinical pharmacological investigations have been carried out with the new oral triphase contraceptive, Tri-RegolR. It has been established that pregnancy had not occurred during 235 cycles of 59 patients. Treatment had to be discontinued in two cases because of side effects which might have been caused by the preparation. Subjective and objective side effects occurred in 24 (10.2%) cases. During treatment with Tri-RegolR tablets proteo and steroid hormones--except prolactin--significantly decreased that phenomenon is characteristic of anovular cycle. Among patients that had previously prolonged treatment with Anteovin tablets did not occur hyperprolactinemia. Infertility would not be expected from prolonged administration of the preparation. From relative decrease of serum progesterone levels during treatment with the three preparations conclusion was drawn that the preparations did not prevent physiological conversion of endometrium.

Contraceptives, Oral, Combined

Endogenous digoxin-like substance in the urine of newborns and children.

Endogenous digoxin-like substance (EDLS) in urine has been considered to be the representative of the natriuretic hormone, the endogenous inhibitor of the sodium pump (the sodium-potassium transporting enzyme Na, K-ATPase). Its site of production remains unknown, and so does its chemical nature. It has been suggested however that EDLS and the atrial natriuretic factor represent two distinct natriuretic system. Although the present work does not provide evidence for EDLS to be a natriuretic hormone, it nevertheless supplies data in support of this hypothesis. In preterm neonates, the decreased sodium excretion during the first days of life is accompanied by a parallel decrease in urinary EDLS excretion. The same was observed in a group of children from the infant period through the age of 12-14 years. Both parameters showed in parallel the lowest values in the oldest children examined. Children aged 8-12 years also showed parallel excretion of sodium and ELDS, even if natriuresis was induced in recumbent position and antinatriuresis in upright position. When the children remained recumbent for 24 h there were no differences in sodium and EDLS excretion between daytime and night. Children involved in adequate physical activities during daytime excreted less sodium and EDLS during the day than at night.

Adolescent

Caffeine and the myoplasmic calcium removal mechanisms in cut frog skeletal muscle fibres.

Antipyrylazo III myoplasmic calcium transients were recorded in cut skeletal muscle fibres of the frog (Rana esculenta), using the double vaseline-gap voltage-clamp system. Intracellular calcium removal mechanisms were analysed, using a slightly modified model taken from the literature. Parameter values reported here are generally consistent with those obtained by the original model. Caffeine (0.5 mmol.l-1) moderately enhanced the overall myoplasmic calcium removal. In particular, the rate constant of the non-saturable uptake increased by 51% on the average, but there was a considerable fiber-to-fiber variation. The kinetic features of the binding sites representing the saturable uptake did not change significantly while the concentration of the available sites decreased by 36%. It is concluded that the caffeine-induced changes of the calcium removal components can be explained by supposing an increased resting myoplasmatic Ca2+ concentration in the presence of the drug.

Animals

The effects of Oradexone and Ambroxol pretreatment of the oxidative sensitivity of the red blood cells in preterm infants.

The antioxidant enzyme activities and lipid peroxidation in the red blood cells of cord blood were investigated and compared at different gestation times in preterm and full-term neonates, with and without pretreatment of the pregnant mothers with Oradexone (Dexamethasone) or Ambroxol. Administration of the two drugs not only stimulated the lung surfactant system, but also exerted favourable effects on the antioxidant enzyme activities while the lipid peroxidation was decreased.

Ambroxol

Antiviral activity of tiazofurine against barley stripe mosaic virus.

Tiazofurine (2-beta-D-ribofuranosylthiazole-4-carboxamide) was found to inhibit replication of barley stripe mosaic virus (BSMV) in barley and wheat plants. Treatment with this nucleoside analogue delayed and inhibited symptom development and suppressed virus multiplication. The most effective concentration applied twice as a foliar spray 3 h and one day after inoculation, was 10(-3) M. Decreased virus multiplication was obtained without marked phytotoxicity. Three weeks after treatment the antiviral effect declined.

Antiviral Agents