[Functional morphology of the bladder and its vascular system in relation to age changes and evolution of BPH].

INTRODUCTION: The increase in the proportion of people with various urinary disorders, which are based on anatomical and functional bladder remodeling due to aging, is currently un-deniable. This problem becomes more relevant due to the elevation in life expectancy. At the same time, the features of bladder remodeling, in particular, the structural changes of its vascular bed, are still practically not described in the literature. In men, the lower urinary tract undergoes additional transformation associated with age due to bladder outlet obstruction caused by benign prostatic hyperplasia (BPH). Despite the long history of studying BPH, the morphological basics of its evolution have not yet been fully elucidated, including the development of lower urinary tract decompensation and, in particular, the role of vascular changes. In addition, structural re-modeling of the bladder muscles in BPH is formed in those with pre-existing age-related changes in both the detrusor and its vascular system, which cannot but influence the dynamics of disease progression. AIM: To study the structural changes of detrusor and its vascular bed associated with age, and to establish the role of their patterns in patients with BPH. MATERIALS AND METHODS: The material was a specimen of the bladder wall obtained dur-ing: a) autopsies of 35 men aged 60-80 years who died from diseases not related to urological or cardiovascular pathology; b) autopsies of 35 men aged 60-80 years who had BPH without blad-der decompensation; c) intraoperative biopsies of 25 men of the same age who undergone surgi-cal treatment for chronic urinary retention (postvoid residual volume of more than 300 ml), bilat-eral hydronephrosis, as complications of BPH. As a control, we used the specimens obtained from 20 males aged 20-30 years who died as a result of violence. Histological sections of the bladder wall were stained with hematoxylin-eosin, according to Mason and Hart. Standard microscopy and stereometry of detrusor structural components and morphometry of the urinary bladder vessels were performed using a special ocular insert with 100 equidistant points. During morphometric examination of the vascular bed the thickness of the middle layer of arteries wall (tunica media) was measured, as well as a thickness of the entire wall of the veins in microns. In addition, a Schiff test and Immunohistochemistry (IHC) of these histological sections were performed. The IHC was evaluated using a semi-quantitative method, taking into account the degree of staining in 10 fields of vision (200). The digital material was processed with the STATISTICA program using the Student's t-test. The distribution of the obtained data corresponded to normal. The data were considered re-liable if the probability of making error did not exceed 5% (p<0.05). RESULTS AND DISCUSSION: In the course of natural aging, a structural remodeling of bladder vascular bed was observed, from the development of atherosclerosis of extra-organ arteries to restructuring of intra-organ arteries due to arterial hypertension. The progression of angiopathy leads to the development of chronic detrusor ischemia, which initiates the formation of focal at-rophy of the smooth muscles, destructive changes in the elastic fibers, neurodegeneration and stroma sclerosis. A long-term BPH leads to compensatory detrusor remodeling with hypertrophy of previously unchanged areas. At the same time, age-related atrophic and sclerotic changes in smooth muscles are accompanied with hypertrophy of individual areas of the bladder detrusor. To maintain adequate blood supply to hypertrophied detrusor areas in the arterial and venous bladder vessels, a complex of myogenic structures is formed that can regulate blood circulation, making it dependent on the energy consumption of specific areas. However, progressive age-related changes in the arteries and veins eventually lead to an increase in chronic hypoxia, im-paired nervous regulation and vascular dystonia, increased blood vessels sclerosis and hyalinosis, and sclerosis of intravascular myogenic structures with loss of their function of blood flow regu-lation, as well as the development of vein thrombosis. As a result, increasing vascular decom-pensation in patients with bladder outlet obstruction results in bladder ischemia and accelerates the decompensation of the lower urinary tract.

[The adaptive structures of the fetal and placental arterial bed in chronic fetoplacental insufficiency].

OBJECTIVE: To reveal the adaptive structures of arteries in the fetal organs and placenta in hypoxia of the latter, by establishing their structure, location, origin, and significance for blood circulation. SUBJECTS AND METHODS: Thirty-four antenatal deaths of fetuses at 28-29 weeks' gestation due to chronic fetoplacental insufficiency and 10 control cases were analyzed. The tissue pieces from different organs of the fetus and its placenta, which underwent histological, histochemical, and morphometric examinations, were explored. RESULTS: The organ blood bed of the fetus and its placenta in hypoplasia of the latter shows the increased development of adaptive arterial formations, the basis for which is smooth muscle fascicles. They have different origin and sites and vary in their structure, specific features of performance, and hemodynamic effects. CONCLUSION: The described formations contribute to the rational distribution of blood flows and in the organ beds and in the area of an undeveloped placenta, by providing the maximally possible reduction in the state of fetal trophic and oxygen deprivation.

Morphological and immunohistochemical changes in the liver in coarctation of the aorta during compensation and decompensation stages.

Compensated coarctation of the aorta is accompanied by a decrease in the tone of hepatic vessels, thinning of the vascular walls, and moderate expression of α-SMA. Bundles of intimal muscles, myoelastic sphincters, and polyp-like pads form in the arteries; the muscle rolls in the efferent veins degenerate. Hepatocyte changes are presented by focal involvement of the organelles. Decompensated coarctation is characterized by more pronounced atrophy of hepatic vascular walls and regulatory structures. The expression of α-SMA in the arteries increases, sclerosis develops, and signs of CD34 expression in the sinusoids and perisinusoidal fibrosis emerge. All these shifts are associated with coarse ultrastructural changes in hepatocytes.

Structural and immunohistochemical changes in the hepatic vascular system in compensated and decompensated stenosis of the pulmonary trunk.

Modeling of pulmonary trunk stenosis leads to an increase in hepatic vascular resistance because of veno-arterial and veno-venous reactions. During the compensation phase, bundles of intimal musculature and myoelastic sphincters appear in the arteries, while in the efferent veins hypertrophy of the muscle rolls is observed. The decompensation phase of stenosis is characterized by relaxation of hepatic vascular walls, reduction of the number of arteries with intimal muscles and sphincter structures, and atrophy of muscle rolls in hepatic veins. Sclerotic changes develop in the vascular bed. Failure of the compensatory reactions results in development of chronic hepatic venous plethora with typical morphological manifestations.

[Histological and ultrastructural changes in the liver in experimental pulmonary trunk stenosis at the stage of decompensation].

Pulmonary trunk stenosis was modeled in 25 dog puppies. Structural changes of liver were examined in 8 animals with circulatory decompensation and in 10 control dogs. Material was studied using histological, morphometric, stereometric and electron microscopical methods. Results showed that in decompensated pulmonary trunk stenosis with the hypoxia, the relaxation of the walls of both afferent and efferent hepatic vessels took place, the numbers and the degree of development of arterial adaptational structures (intimal musculature, muscular-elastic sphincters, and polypoid cushions) was reduced, while muscular bolsters in large and medium-sized vessels belonging to hepatic veins system, became atrophic. The adaptational mechanisms failure resulted in the development of chronic hepatic venous plethora.

Peculiarities of compensatory reactions of hepatic vessels during experimental coarctation of aorta.

Morphometric and histological methods were employed to study structural changes of hepatic vessels in dogs with compensated coarctation. Simulation of this conditions in animals decreased vascular tone in the inflow and outflow beds of hepatic blood supply and led to the development of atrophy in the media. At the same time, the number of vessels with intimal musculature, elastic muscle sphincters, and polypoid cushions increased in the hepatic arterial bed, while large outflow veins demonstrated thinning of the muscle cushions. All these alterations play an important role in compensation of the disturbed hemodynamics.

[Polypoid cushions of arterial vessels and their role in control of regional blood circulation].

This work presents the results of studies of polypoid cushions (PC). For elucidation of their structure, morphogenesis and functions, a complex of histological, histochemical, morphometric and experimental methods was used. It was demonstrated that PC could be detected in the arteries of heart, lungs, kidneys, brain and the organs of digestive tract in humans and some animals species except the vessells of the minor circle. PC were found at different levels of vascular bed with the exception of microcirculatory vessels. They were situated in places of arterial branching and sometimes were combined with intimal musculature and musculo-elastic sphincters. Three types of PC were distinguished, which differed in their histological structure. It was shown that the number of PC increased significantly in the cases of circulation disturbances, indicating the importance of hemodynamic factor in their development. The functional role of these structures might be associated with the regulation of regional blood circulation by blocking blood flow and its redistribution within the vascular bed in accordance with the requirements of the organ at a particular moment.

Morphological changes in hepatic vessels during modeling of pulmonary trunk stenosis and after its elimination.

Experiments on dogs showed that pulmonary trunk stenosis increased the tone of arterial vessels in the liver and led to the development of veno-arterial and veno-venous reactions. The number of vessels with intimal musculature and myoelastic sphincters in the arterial bed increases, and muscle rolls in large hepatic veins are thickened. The walls are hypertrophic in all vessels. Elimination of the defect abolished the previously formed vascular adaptation reactions, the tone in afferent liver vessels decreased, which leads to regression of hypertrophic changes in their tunica media. The number of arteries with intimal musculature and sphincters decreases. Muscle rolls in the efferent hepatic veins are thinned.

Reversibility of changes in hepatic vessels after correction of experimental aortic coarctation.

Structural changes in hepatic vessels were studied in pups with experimental aortic coarctation and animals with corrected defect. Reconstruction of vessels was assayed by functional, morphometric, and histological methods. Aortic coarctation in pups was followed by a decrease in circumferential strain of the wall of hepatic arteries. These changes were accompanied by atrophy and sclerosis of the media. The arterial bed had a greater number of vessels with intimal muscles. Muscle bundles in large hepatic veins underwent dystrophy. After correction of experimental defect, the increase in circumferential strain of arteries was accompanied by hypertrophy of the wall. The number of arterial vessels with intimal muscles decreased, while muscle bundles in hepatic veins were thickened. Sclerosis of hepatic vessels was reversible.

[Changes of the liver blood vessels in the pulmonary trunk stenosis at compensation and decompensation].

Changes of liver blood vessel structure were studied in 23 pups with the model of compensated pulmonary trunk stenosis and in 8 animals with decompensated stenosis during 6-24 months after the establishment of stenosis. The liver of 10 age-matched dogs was used as a control. Material was studied using histological, morphometric and stereometric methods. It was found that after the establishment of pulmonary trunk stenosis and compromise to venous blood outflow from the liver, the tone of the arteries increased as well as the resistance to the blood flow. Besides the venous-arterial reaction, the bundles of oblique-longitudinal smooth muscle cells and musculo-elastic sphincters were shown to be formed in the intima of the afferent vessels, while in the efferent vessels the hypertrophy of the muscular folds took place. In decompensated stenosis, the hypoxia was combined with the relaxation of the walls of both afferent and efferent vessels, the number of arteries with the adaptational structures was decreased, while the muscular folds of hepatic veins underwent atrophy. The failure of adaptation mechanisms resulted in the development of chronic liver venous congestion.

[Effect of some imidazole-4,5-dicarboxylic acid derivatives on the activity of N-methyl-D-aspartate (NMDA) receptors].

The results of experiments on mice showed that some imidazole-4,5-dicarboxylic acid derivatives injected into lateral cerebral ventricles produce a dose-dependent convulsant or anticonvulsant effects, that is, possess the properties of partial NMDA receptor agonists. The most promising partial NMDA receptor agonist selected for further investigation is 2-propylimidazole-4,5-dicarboxylic acid.

[Morphological changes of hepatic vessels in experimental aortal coarctation and after its elimination]. / Morfologicheskie izmeneniia sosudov pecheni pri éksperimental'noi koarktatsii aorty i posle ee ustraneniia.

Structural peculiarities of hepatic vascular bed were studied in 10 intact dogs, 15 pups with hemodynamic model of aortal coarctation (AC) and in 10 animals after AC elimination. To detect the regularities of remodeling of arteries and veins of this organ, morphometric and histological methods were used. In the arteries, branches of portal and hepatic veins AC caused the reduction of the tone and attenuation of the media, associated with the decrease in number and dimensions of smooth muscle cells. Simultaneously, as a result of adaptation, in the intima of the vessels carrying blood to the liver (arteries) the degree of the development of regulatory muscular structures was increased, while similar structures in the blood outflow vessels (hepatic veins) were reduced. Along with adaptational modifications, some pathological changes took place in the liver, which were manifested by sclerosis of vascular walls and stroma. After AC elimination and restoration of hemodynamics, the tone of the vessels was found to increase with the hypertrophy and hyperplasia of the smooth muscles in their media. The degree of development and the number of regulatory structures in the liver inflow vascular bed were reduced, while those in the outflow bed were increased. At the same time, the process of reversal of sclerotic changes in hepatic blood vessels was initiated.

[Structural changes in the intraorgan hepatic arteries during experimental aortic coarctation]. / Strukturnye izmeneniia intraorgannykh arterii pecheni pri koarktatsii aorty v éksperimente.

Structural changes of intraorganic hepatic arteries were studied in 8 control dogs and 20 pups with hemodynamic model of aorta coarctation. Experimental animals were observed within the terms from 1 month to one year. Histological and morphological methods were used to assess the state of hepatic vessels. The investigations performed resulted in the discovery of the complex of adaptive and pathological changes in the hepatic arterial bed. The first were the reactive atrophy of the hepatic arteries wall with decrease of smooth myocytes number and parameters in the media and the appearance of musculo-elastic sphincters, Conti pillows and smooth myocytes bundles in the intima. The latter lied in the arterial and arteriolar wall sclerosis in liver. Pathological changes grow proportionally with the terms of the experiment.

[A "neuromyo-test-response 01" device for neuromuscular function control during anesthesia]. / Pribor dlia kontrolia neiromyshechnoi funktsii vo vremia narkoza "Neiromiotest-otvet-01".

The paper outlines the technical data and procedure of using a new "neuromyotest-response-01" device designed by the Novye Pribory (New Devices) Medical Engineering Center (Samara) for estimation of the level of neuromuscular block.

[A granulopoiesis inhibitor. Synthesis and biological activity]. / Ingibitor granulopoéza. Sintez i biologicheskaia aktivnost'.

Three schemes of synthesis for pentapeptide Glp-Glu-Asp-Cys-Lys-OH were compared was carried out. Acetamidomethyl protection was used for the mercapto group of cysteine. For the same purpose, cystine was used as the starting compound for synthesis. The optimal method was shown to be the solid phase method with S-acetamidomethyl cysteine protection that can be removed by mercuric acetate before the cleavage of a peptide from a polymer. The stabilized peptide inhibits proliferation of bone marrow cells of patients with chronic myeloleukemia 5- to 20-fold and has a less pronounced effect (up to 2-fold inhibition) on peripheral blood cells. Thus, its application for the therapy of hemoblastoses is promising.

[The effect of certain factors on binding of tert-butyloxycarbonylamino acids to Merrifield polymer during interphase catalysis and assessment of racemization of the bound amino acid]. / Vliianie nekotorykh faktorov na prisoedinenie tret-butiloksikarbonilaminokislot k polimeru merrifilda v usloviiakh mezhfaznogo kataliza i otsenka ratsemizatsii prisoedinennoi aminokisloty.

In order to reduce the influence of hydrogen bonds on the acylamino acid salts attachment to the chloromethylated resin, it is proposed to use compounds that can compete for the hydrogen bonds formation. The best solvent proved to be hexamethylphosphoric triamide. Use of interphase catalysts, e.g., tributyl-p-nitrobenzyl ammonium, also gives good results. The racemization degree of the amino acids attached to solid support by means of the interphase catalysis does not exceed that of amino acids loaded on the polymer according to Gisin's method.

[The analgesic action of new enkephalin analogs]. / O boleutoliaiushchem deistvii novykh analogov énkefalinov.

The enkephalin analogue peptide IKB-901 containing epsilon-ACA and cysteine with the modified S-end shows an analgetic activity in rats (1 micron, intrathecally and 5 mg/kg intravenously) and in cats (0.35 and 0.7 mg/kg intravenously). Naloxone (0.1 mg/kg) prevents the analgetic effect of peptide. The coadministration of the peptide and the enkephalinase inhibitor D-phenylalanine (0.35 and 10 mg/kg, respectively) enhances analgesia and displays an antihypertensive effect in nociceptive stimulation.

[Immunoenzyme method of determining trace amounts of proinsulin in recombinant human insulin]. / Immunofermentnyi metod opredeleniia sledovykh kolichestv proinsulina v rekombinantnom insuline cheloveka.

An enzyme immunoassay (ELISA) for the detection of human proinsulin has been developed based on the interaction of the absorbed proinsulin with the antiserum against the synthetic proinsulin C-peptide. In the presence of high concentrations of insulin, the sensitivity of the assay slightly decreases due to the competitive adsorption of insulin onto the polystyrene carrier with the binding constant 800-1000 times less than that of proinsulin. A method is proposed for the interpretation of ELISA data based on analysis of a weighed dry insulin sample, which enables the detection of a 0.02-0.1% admixture of proinsulin in the chromatographically purified recombinant human insulin.