[Medical and Social Problems of Assisted Reproductive Technologies from the Perspective of Pediatrics].

The article presents a literature review over the last few years devoted to the health status and development peculiarities of children born using assisted reproductive technologies (ART) procedures. The statistics shows an explosive increase in the frequency of ART application as a fertility treatment method. The presented data analysis reflects the perinatal outcomes after ART in children, the frequency of congenital malformations and genetic diseases in this population, possible long-term malconditions and pathologies in children born using ART. The overwhelming majority of investigators consider the adverse effect of ART on a child's body to be the result of prematurity and multiple pregnancy (transfer multiple embryos followed by partial reduction). It is stated that the widespread introduction of ART may contribute to the vertical transmission of parental infertility factors in the population. The application of ARTprocedures in some cases is associated with controversial ethical and legal issues (surrogacy, oocyte donation). Further improvements in ART procedures (preimplantation training, medical and genetic diagnosis, reducing the frequency of multiple pregnancy) cannot be stated as an alternative to the general medical and social prevention of reproductive disorders in adolescents and youth.

[Biologically active compounds in the mechanism of formation of reflux-nephropathy in children].

A concept is proposed laying emphasis on the involvement of cytokines, growth factors, prostaglandins, and nitrogen oxides in the mechanism of formation of reflux-nephropathy in children. It is shown that enhanced production of mediators of inflammation and humoral growth factors in patients with vesico-ureter reflux depends on the degree of infiltrative and sclerotic changes in the kidneys. The accompanying dysbalance of pro- and anti-inflammatory cytokines due to increased endogeneous production of TNF-alpha and concomitant decrease of daily BL-10 excretion constitutes an unfavourable prognostic factor of reflux-nephropathy. There is evidence that inclusion of ACE inhibitors (Enap) in therapy of vesico-ureter reflux during 6 months leads to a marked improvement of the structural and functional state of the kidneys. It suggests high renoprotective potential of these preparations and the possibility of their use for prophylaxis of nephrosclerosis in children.

[Endothelial dysfunction in children's chronic glomerulonephritis].

Production of NO, sVCAM-1, Et-1, FV, PAI- 1 was measured in blood sera of children with different forms of chronic glomerulonephritis. Endothelial dysfunction (ED) occurred in the active phase of the disease and persisted during remission regardless of the clinical form of glomerulonephritis. Severity of ED and involvement of its markers depended on morphological type of the disease. Production of endothelin-1 was highest in patients with sclerotic glomerulonephritis and accompanying arterial hypertension. ED caused activation of hemostasis with the prevalence of prothrombotic condition. ED contributed to the progress of glomerulonephritis acting via sclerotization and cell proliferation. Selected markers ED are shown to be of prognostic value in children with chronic glomerulonephritis.

[Chronoinotropic reaction of the hypertrophied myocardium using an electromechanical coupling mathematical model]. / Issledovanie khornoinotropnoi reaktsii gipertrofirovannogo miokarda s pomoshch'iu matematicheskoi modeli élektromekhanicheskogo sopriazheniia.

Static and dynamic chrono-inotropic responses were recorded from both normal and hypertrophic rat auricular myocardium. The slope of the static force-frequency relation from hypertrophied heart was steeper than in the control hearts. The cellular mechanisms underlying changes in the force frequency response associated with hypertrophy of the heart were studied by means of a mathematical model of excitation-contraction coupling. The characteristic features of hypertrophied heart force-frequency relations are shown to be due to the enhanced volume of the intracellular Ca-stores in contrast to the total volume of the cardiomyocyte.

[Effect of prostaglandins on the activity of the isolated rat heart with normal arterial pressure and spontaneous hypertension]. / Vliiani prostaglandinov na deiatel'nost' izolirovannogo serdtsa krys s normal'nym arterial'nym davleniem i spontannoi gipertenziei.

The article discusses the results of experimental study of the effect of prostaglandins E2, A2, and F2 alpha on coronary blood flow and contractility of an isolated and perfused after Langendorff heart of rats with normal arterial pressure. A substantial reduction of the synthesis of prostacycline and prostaglandin-like compounds in the heart of rats with spontaneous hypertension was found. Marked changes were revealed in the cardiac effects of arachidonic and linoleic acids and changes in the reactivity of the heart of rats with spontaneous hypertension to the injection of isoprenaline, oxyfedrine and verapamil. The role of changes in prostaglandin production in the pathogenesis of myocardial insufficiency in arterial hypertension is discussed.

[Cardiac effects of essential phospholipids and prostaglandin release by the heart in the rat]. / Kardial'nye éffekty éssentsial'nykh fosfolipidov i vydelenie prostaglandinov serdtsem krys.

The article deals with the effect of exogenic phospholipids of vegetative origin enriched with polyunsaturated fatty acids (EPL substance) on prostaglandin release and the activity of the isolated, perfused according to Langendorf , heart of Wistar and Okamoto-Aoki rats with congenital arterial hypertension. Exogenic essential phospholipids were shown to facilitate a significant enhancement of endogenic prostaglandin release and to induce a positive inotropic, negative chronotropic and marked coronarodilating effects. These EPL effects were inhibited by indometacin and were considerably altered in rats with spontaneous hypertension. It was concluded that the cardiac effects of essential phospholipids are modulated by elevated prostaglandin secretion. The role of essential phospholipids in the prostaglandin biosynthesis regulation and the cardiac activity of rats is discussed.

[Effect of coronary arterial occlusion on prostacyclin biosynthesis in dogs of various ages]. / Vliianie okkliuzii koronarnoi arterii na biosintez v nei prostatsiklina u sobak raznogo vozrasta.

In acute experiments in animals of different age, local myocardial ischemia was stimulated, and the pattern of change in prostacyclin biosynthesis by segments of ischemized and normal coronary arteries was studied. Prostacyclin biosynthesis by coronary arterial segments was much more intensive in young animals, as compared to adult ones. Ischemized arterial segments of pups were also shown to produce a much smaller quantity of prostacyclin, as compared to control animals and to adult levels. The demonstrated findings may be making an important pathogenetic contribution to ischemic heart damage.

[Content of endogenous prostanoids in patients with paroxysmal supraventricular disorders of the heart rhythm]. / Soderzhanie éndogennykh prostanoidov u bol'nykh s paroksizmal'nymi nadzheludochkovymi narusheniiami ritma serdtsa.

Blood endogenous prostaglandins, E, F2 alpha, prostacyclin and thromboxane levels were measured in the ascending aorta and the coronary sinus of 32 patients (29 males and 3 females) with paroxysmal supraventricular arrhythmias (atrial fibrillation and supraventricular tachycardia) during the sinus rhythm and an arrhythmic paroxysm. Group 1 was made up by 22 patients with idiopathic cardiac rhythm disorders, and group 2 comprised 10 coronary patients with arrhythmias. A relationship was demonstrated between cardiac endogenous prostanoids balance and the clinical pattern of cardiac rhythm abnormality (duration and frequency of paroxysms) as well as changes in cardiac prostanoid rations associated with tachyarrhythmic paroxysms.

[Effect of ritmilen and allapinin on prostanoid and cyclic nucleotide levels in patients with cardiac rhythm disorders]. / Vliianie ritmilena i allapinina na soderzhanie prostanoidov i tsiklicheskikh nukleotidov u bol'nykh s narusheniiami ritma serdtsa.

The effect of antiarrhythmic drugs, ritmilen and allapinin, on endogenic prostanoid and cyclic nucleotide levels was examined in patients with heart rhythm disorders. Intravenous administration of antiarrhythmic agents is shown to be accompanied with increased release of prostacyclin that has antiarrhythmic properties into myocardial outflow. Both ritmilen and allapinin promoted the predominance of prostacyclin over thromboxane, with its intrinsic arrhythmogenic properties. Ritmilen- or allapinin-induced changes in prostaglandins E and F2 alpha consisted in that PGE prevailed, as compared to PGF2 alpha. There were no significant changes in cyclic nucleotide ratios (cAMP/cGMP) in response to treatment.

[Newly developed stenocardia: functional activity of thrombocytes]. / Vpervye voznikshaia stenokardiia: funktsional'naia aktivnost' trombotsitov.

Platelet function (aggregation, circulating platelet aggregates, platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-PGF1 alpha, platelet count) was evaluated in patients with angina of new onset, as compared to individuals without coronary heart disease, and patients with angina of long standing (28 +/- 4.6 months). Some of the patients with angina of new onset were examined repeatedly 6 to 12 months after the onset of angina. Platelet activity was shown to be significantly higher in patients with stable angina of new onset, as compared to patients with lasting angina, where ADP and serotonin were used as inductors. Platelet aggregation, induced by platelet activation factor and collagen, was similar in all groups. Repeated investigation 6 to 12 months after the first anginal attacks demonstrated that most of platelet functional parameters declined or tended to decline.

[Age-related changes in prostacyclin and thromboxane B2 biosynthesis under normal conditions and in arterial hypertension]. / Vozrastnye izmeneniia biosinteza prostatsiklina i tromboksana B2 v norme i pri arterial'noi gipertenzii.

An experimental radioisotopic study in normotensive male Wistar rats and spontaneously-hypertensive rats (SHR) of Okamoto--Aoki line demonstrated an age-related increase in the biosynthesis of prostacycline (PGI2) from 14C-arachidonic acid by pulmonary and aortal tissues of animals with normal arterial pressure. In SHRs, PGI2 production by lung homogenates did not change essentially with age, but decreased considerably in adult SHRs with stable hypertension. PGI2 biosynthesis by SHR's aortal tissue decreased with age and dropped significantly as arterial hypertension developed. In normotensive rats, the formation of thromboxane B2 (TxB2) by platelets increased with age. Platelet TxB2 biosynthesis was elevated considerably both in young and adult SHRs. Clinically, a significant increase of platelet TxB2 production from exogenous 14C-arachidonic acid was demonstrated in children with essential hypertension.

[Concentration of endogenous prostanoids and cyclic nucleotides in patients with atrial fibrillation]. / Soderzhanie éndogennykh prostanoidov i tsiklicheskikh nukleotidov u bol'nykh s mertsatel'noi aritmiei.

The variations in the content of endogenic prostanoids and cyclic nucleotides in the blood plasma of the coronary sinus and ascending aorta were studied in patients with the idiopathic stable form of atrial fibrillation before and after sinus rhythm recovery effected by electroimpulse therapy. Changes in the levels and ratios of these compounds in the coronary venous and arterial blood were found to be opposite in their trends. A significant elevation in TxB2 levels and the TxB2/6-keto-PGF1 ratio as well as increased cGMP concentrations in the plasma of the coronary venous blood appear to be suggestive of an unfavourable prognosis because patients with such changes developed atrial fibrillation recurrences soon after electroimpulse therapy.

[Changes in kinetics of deaminated biogenic amines in spontaneous hypertension]. / Izmemeniia kinetiki dezaminirovaniia biogennykh aminov pri spontannoi gipertenzii.

Rate of serotonin and benzylamine deamination was increased in liver tissue of rats with spontaneous hypertension. The increase was due to elevation in Vmax value for monoamine oxidases of the A and B types as compared with the corresponding values of control animals. The Vmax value was increased in kidney of hypertensive animals for MAO of the B type (benzylamine as a substrate). At the same time, Km for MAO of the B type was increased in liver tissue, while Km for MAO of the A type was decreased in brain of hypertensive animals. Titration of the MAO active sites exhibited their increased concentration in the B type MAO in liver mitochondria of experimental animals. The data obtained suggest an important role of alterations in the MAO catalytic activity in pathogenesis of spontaneous hypertension.

[Defect in deamination of biogenic amines in spontaneous hypertension]. / Narushenie dezaminirovaniia biogennykh aminov pri spontannoi gipertenzii.

Activity of monoamine oxidases (MAO) of the types A and B (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) has been studied in mitochondrial fractions from brain, heart, liver and kidney of 24-week-old rats of the normotonic strain Wistar Kyoto (WKY) and spontaneously hypertonic rats (SHR). As compared with the WKY rats, in the SHR strain the activity of MAO-A in heart mitochondria was increased 1.5-1.7-fold; in liver mitochondria the activities of both MAO-A and -B were increased 2.6-2.7-fold. In brain mitochondria there was noted only slight tendency towards an increase in MAO-A (substrate: 5-hydroxytryptamine) and MAO-B (substrate: 2-phenylethylamine) activities in the SHR strain as compared with the normotonic animals of the same age. However, in experiments with tyramine as a substrate of MAO the enzymatic activity in SHR brain mitochondria was increased 1.5-fold (P less than 0.05) as compared with the WKY rats. In kidney mitochondria of SHR the activity of MAO (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) did not exhibit any alterations as compared with the control WKY rats.

[Effect of polyunsaturated fatty acids in the diet on prostaglandin formation and the activity of the isolated heart]. / Vliianie polinenasyshchennykh zhirnykh kislot pishchevogo ratsiona na obrazovanie prostaglandinov i deiatel'nost' izolirovannogo serdtsa.

Experiments on normotensive adult Wistar rats with hearts perfused according to the modified Langendorf technique and Okamoto-Aoki rats with a hereditary determined arterial hypertension kept on the diets with varying content of polyunsaturated acids (PUFA), series 6 and 3, have demonstrated that PUFA deficiency in the diet inhibited prostaglandin (PG) secretion by the heart of hypertensive rats, which was accompanied by the decreased rate of coronary perfusion. It has also been revealed that excess content of linoleic acid in lipid fractions of the diet was followed by an appreciable rise of prostacycline secretion, whereas the linoleic acid increase in the diet by the lowering of the overall amount of PG secreted by the heart of hypertensive rats and drop of the coronary perfusion rate. It has been demonstrated that these changes might be related to the modulations in the content of PUFA, PG precursors, in heart phospholipids.

[Effects of a diet with various polyunsaturated fatty acid contents on the secretion of prostaglandins and ATPase activity in the rat myocardium in total ischemia]. / Vliianie diet s razlichnym soderzhaniem polinenasyshchennykh zhirnykh kislot na vydelenie prostaglandinov i aktivnost' ATF-az v tkani serdtsa krys pri total'noi ishemii organa.

Experiments were made on the heart perfused according to Langendorf's method of adult Wistar and Okamoto-Aoki rats with hereditary arterial hypertension given the diets with varying content of polyunsaturated fatty acids (PUFA). It was demonstrated that under total heart ischemia, there was a maximal increase in the output of prostacycline and prostaglandin E (PGE) by the hearts of hypertensive rats given the diet enriched with linoleic acid. The rats given the PUFA deficient diet and the diet enriched with linoleic acid did not show any substantial changes in PG secretion by the ischemized heart. It was also disclosed that under normoxic perfusion, Na, K-ATPase activity in the heart of hypertensive rats was increased, being significantly inhibited during total heart ischemia. According to the authors, the differences in the changes in PG secretion and Na, K-ATPase activity might be related to a possible effect of lipid diet components and to variations in PUFA content in heart phospholipids.

[Production of cardiac prostanoids and the fatty acid composition of cardiac phospholipids in various types of myocardial hypertrophy]. / Produktsiia kardial'nykh prostanoidov i zhirno-kislotnyi sostav fosfolipidov serdtsa pri razlichnykh tipakh formirovaniia gipertrofii miokarda.

Considerably increased production of cardiac prostanoids and intensified linoleic acid metabolism in the cardiac phospholipids were revealed in physiological myocardial hypertrophy in animals trained by swimming. The formation and secretion of cardiac prostanoids was found to be essentially reduced in pathological myocardial hypertrophy in rats with hereditarily determined arterial hypertension, which is attributed to inhibition of the metabolism of linoleic and linolenic acids in the cardiac phospholipids and to structural and functional disorders in the function of the heart.

[Change in prostaglandin levels and ATPase activity of cardiac membrane fractions during the formation of cerebral hematomas in animals with a hereditary predisposition to stroke]. / Izmenenie soderzhaniia prostaglandinov i aktivnosti ATFaz membrannykh fraktsii serdtsa pri formirovanii tserebral'nykh gematom u zhivotnykh s nasledstvennoi predraspolozhennost'iuk insul'tam.

The formation of subarachnoidal, intragastric, and intracerebral hepatomas provoked by stress in rats hereditarily predisposed to strokes was found to be accompanied by myocardial overstrain and changes in cardiac prostaglandin formations, as well as by a decrease in the activity of ion-transporting enzymes, such as Na, K- and Ca,Mg-ATPases in the plasma membranes, Ca-ATPase in the sarcoplasmic reticulum.

[The effect of a low-frequency magnetic field on erythrocyte membrane function and on the prostanoid level in the blood plasma of children with parasystolic arrhythmia]. / Vliianie nizkochastotnogo magnitnogo polia na sostoianie membran éritrotsitov i soderzhanie prostanoidov v plazme krovi detei s parasistolicheskoi aritmiei.

As shown by clinical and biochemical evidence on 23 parasystolic children, the treatment with low-frequency magnetic field improves humoral and cellular processes participating in cardiac rhythm regulation. There is activation of Ca, Mg-ATPase in the red cells, a reduction of plasma thromboxane levels. Red cell phospholipid composition insignificantly change. Further courses of magnetotherapy may lower the risk of recurrent arrhythmia.