The network of pediatric pharmacology training programs.
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Biomedical subjects
Publications and source records attributed to M Kriska.
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The authors describe the withdrawal syndrome of a beta-adrenolytic in neonates manifested above all 10-16 hours after delivery by alternating bradycardia and marked tachycardia independently on the infant's activity. The withdrawal syndromes correlate with the increased heart rate of the mother after delivery. The authors draw attention to the fact that the withdrawal syndrome in the neonate may develop after delivery if the mother used during pregnancy not only addictive drugs affecting the central nervous system but also drugs affecting the cardiovascular system such as the beta-adrenolytic metipranolol.
Using perfusion method the reactivity of rabbit femoral and ear arteries was investigated following the administration of rising noradrenaline doses in four consecutive intervals. Progressive increase of vasoconstrictive activity of vessel segments was found. Results of histological examination showed a progressive de-endothelialization of perfused vessels. The loss of endothelium increased depending on time of action and on intensity of vasoconstrictive stimuli.
Endothelial loss of isolated rabbit femoral artery and renal artery was evaluated during in vitro vessel perfusion. Desquamated endothelial cells were captured on millipore filters from the perfusion solution outflow of the vessel in 3 intervals lasting 5 minutes each. In the first 5 minutes of perfusion the endothelial loss was 1,289.2 +/- 166.5 cells: in the interval after a 30 minute perfusion 4,967.9 +/- 1,428.3 cells were caught on the filters, 3.9 times more than in the first interval. During and after the 2 minutes air bubble perfusion the endothelial catch was 5.5 times greater as compared to the second interval with the average of 27,473 +/- 6,209.6 cells. The present method of quantification of the endothelial cell loss in the in vitro vessel perfusion experiment makes it possible to obtain informations about the actual state of the endothelial lining and to contribute to more precise evaluation of the modulatory effect of the endothelium on vessel reactivity to pharmacological agents.
In the second and third decade of the history of the Medical Faculty, Comenius University in Bratislava, the outstanding personality of Prof. MUDr. Frantisek Svec deserves great recognition. The best years of his productive life were devoted to studies in the field of pharmacology. He worked at the Institute of Pharmacology and Pharmacognostics and was appointed Associate Professor in pharmacology and pharmacognostics in 1937 and Full Professor in 1939 when he became also Head of the Institute. In his teaching commitments executed over long years, he achieved excellent results. Equally outstanding were his scientific achievements. He ranked among the first internationally recognized scientists. His research work was focused on experimental pharmacology and pharmacochemistry, particularly on digitalis cardiotonics. He devoted much of his time to his students, holding different positions, as e.g. chairing the Student Health Institute for a whole decade. In the school year of 1947/1948 he was appointed Dean of the Medical School, Comenius University. After February 1948 he was among the first faculty members who had to experience the injustice and oppression of the totalitarian regime. He was not only divested of his position as dean of the Faculty but he also had to leave the Medical School.
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Although the role of prostaglandins (PG) in the mechanism of dilatation of the ductus arteriosus (DA) has received considerable attention, no data on their possible interaction with the pressure-induced myogenic reaction are available. There is also a lack of information on PG production by the foetal blood vessels of the guinea-pig, in which the DA closes rapidly. Use of the RIA method showed relatively low PG production by isolated foetal guinea pig blood vessels, as represented by the main products, PGI1 and PGE2. When computed in pmol per mg wet weight, the production of 6-keto-PGF1 alpha (an equivalent of PGI2) was statistically significantly higher in the foetal DA (4.06 +/- 1.13) than in the foetal aorta (2.04 +/- 0.33). The isolated DA reacts to a sudden increase in perfusion pressure by marked constriction, which in some cases leads to functional closure of the DA. In 10(-7) to 10(-5) mol.l-1 concentration, PGE2 reversibly inhibits pressure-induced myogenic constriction, while under the same conditions the contractility of the DA in response to oxygen is unaffected. In concentrations of 10(-6)-10(-5) mol.l-1, indomethacin, a blocker of PG biosynthesis, also induces pressure constriction and it raises the basal flow resistance of isolated DA preparations. The results indicate that PGs play a modulator role in the pressure myogenic response of the DA of guinea-pig and rabbit foetuses.
Reactivity of the lung tissue and of a. pulmonalis has been followed by means of isometric contraction of isolated strips. Histamine, acetylcholine and prostaglandin F2 alfa (PGF2 alfa) contracted the lung strips, the amplitude of histamine and acetylcholine induced contraction being significantly higher in grown guinea pigs than in foetuses. Strips of a. pulmonalis reacted with contraction in response to histamine and PGF2 alfa, they were non-reactive against acetylcholine. Magnitude of response of the strips of a. pulmonalis obtained from grown animals was significantly greater only after administration of PGF2 alfa in concentration of 10(-4) mol.l-1. Values of EC50 were significantly changed only by influence of acetylcholine on the lung strips. Isolated preparations of lung and vessel strips allow to characterize pharmacodynamic properties of the lung tissue. They represent a contribution to the evaluation of lung reactivity to xenobiotics.
Under perfusion conditions in vitro the morphologic state of preparations of fetal vessels of the ductus arteriosus and the pulmonary artery was studied by light and electron microscopy. At maintaining standard conditions of perfusion experiments, manipulation of vessels did not result in substantial changes of the endothelium. Storage of the vessel preparations at 4 degrees C for 24 hours did not induce marked morphologic changes, yet the vessels exhibited increased constriction reactivity to noradrenaline which resulted in severe damage of the endothelial lining. Perfusion of the ductus arteriosus by oxygen saturated solution led to vessel constriction and severe endothelial damage. The observed changes should be taken into account on evaluating responses of vascular segments to vasoactive substances.
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Isolated ductus arteriosus responds by marked constriction to increases in perfusion pressure. If, however, these increases exceed 90 mm Hg-130 mm Hg, the vessel suddenly dilates and its responsiveness becomes depressed. The importance of these findings in postnatal closure of ductus arteriosus is discussed.
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The development of changes appearing with the closure of ductus arteriosus was followed in mature rabbit foetuses with the help of light and electron microscopy. In the foetuses, in which there was no spontaneous respiration of atmospheric air before fixation the ductus remained opened. In smooth muscle cells of the media there were enlarged cisternae of the endoplasmic reticulum being partially decayed. The foetuses that respired for about one minute had the ductus contracted to various degree and the endothelial cells were expelled into the lumen. In the foetuses respiring for 10 minutes the ductus were more contracted. The endothelium was considerably waved and the agglomeration of smooth muscle cells appeared. In the endothelial and musclar cells the endoplasmic reticulum was richer, and in a lot of places considerably disturbed. The ductus of foetuses respiring for 15 minutes had the lumen completely closed. The smooth muscle cells had a significantly changed their internal structure. The possibility of the direct transformation of the endoplasmic reticulum of the smooth muscular cells into inclusion bodies during the ductus arteriosus closure is discussed.
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