Morphological analysis of interstitial Cajal cells and mast cells in experimental hyperactivity bladder and stress incontinence under influence of pharmacocorrection

The existing data indicate the multifactorial mechanisms of development of the overactive bladder (OAB), but the issue of OAB pathogenesis remains unclear. In more recent times, the neurogenic theory of OAB genesis has being accompanied by the increasing attention to the study of morphological changes that occur in the smooth myocytes of the detrusor and their interaction with the extracellular matrix. Therefore, the objective of our study became the evaluation of distribution of interstitial Cajal cells (ICC) and basophilic granulocytes (BG) in the structural elements of the bladder wall under stress urinary incontinence and its overactivity before and after treatment with Mirabegron, Spasmex, Quercetin and combination thereof with testosterone and estradiol, using histochemical and immunohistochemical methods. The experimental models of OAB and stress urinary incontinence (SUI) presented the increase in the amount and functional activity of BG revealed by histological and immunohistochemical methods, as well as ICC at all terms of OAB monitoring, while the SUI presented with high concentration and functional activity of BG only after 14 days of the experiment. After 28 days, we observed a sharp decrease of the parameters, indicating decompensation and depletion of the functional activity. The number of ICC decreased under SUI after both 14 days and 28 days of the experiment. The group of experimental animals receiving Spasmex and its combination with hormones, presented no significant effect on the quantitative and qualitative composition of BG and ICC at OAB and SUI on Day 14 of the experiment, but the combination with testosterone demonstrated statistically reliable (p0.05). The administration of Mirabegron alone and especially its combination with testosterone and estradiol presented positive trends in histochemical and immunohistochemical expression of BG and ICC. The experiment proved high efficacy of Quercetin in combination with testosterone and estradiol under OAB and SUI, confirmed by stabilization of the functional activity of BG and ICC quantitative composition

The features of pathogenetically directed therapy for chronic pelvic pain syndrome in experimental condition

Experimental methods for investigation were performed on 120 four-month age white mongrel male rats, by the sacral plexus damage in animals through the ligating the largest nerve of the plexus – sciatic nerve, which can be considered as a predictor of pudendopathy and adequate clinical experimental modeling of the prototype method. The experimental animals after 1 month. of modeling were taken medications with muscle relaxant action of the central and peripheral activity and also neurotrophic effect. Comparative assessment of medicines was performed after 2.5 months. by morphological investigation of the pelvic floor and bladder, as well as biochemical analysis of blood, homogenates of the pelvic floor muscles and bladder, with assessment of the α2-macroglobulin, creatine kinase and lactate activity. The results showed that the pudendal nerve neuropathy in the experiment is accompanied by severe changes in the structure of the tissue of the bladder, pelvic floor muscles, nerve structures of the pelvis, as well as hypoxia, proteolysis and tissue destruction. The injection of drugs to experimental animals with reproduced pudendopathy revealed the different efficacy in restoring the structure of the detrusor muscle and the pelvic floor depending on effect of the drug

Possibilities of pharmacological correction of the artifical bladder contractile activity in experimental conditions in vivo.

The aim of this work was to study the possibility of pharmacological correction of the neobladder contractile activity of mini-pigs under the influence of new chemical compounds, m-anticholinergic (solifenacin), selective beta-2 sympathomimetic (ginipral (hexoprenaline)) in vivo. Neobladder, formed from the distal section of ileum, pre-denervated along the anti-mesenteric margin, retains peristalsis, and  given the sharp thickening of the muscle layer, capable to contractile reactions and tone support. New chemical compounds pyrrole-2-carbaldehyde 2- hydroxybenzoylhydrazone (PChBh) and isatin benzoylhydrazone (IBh) demonstrated spasmodic properties directed at smooth muscle in vivo. Compound PChBh (I) showed more pronounced relaxing properties compared to compound IBh (II), reducing basal pressure against KCl by 40.91%, contraction amplitude by 30.63%, contraction rate by 25.49%. Solifenacin, being an m-anticholinergic antagonist, most clearly demonstrated antispasmodic properties in vivo, reducing hypertonicity by 55.23%, amplitude – by 49.31%, frequency of contractions in 10 minutes – by 57.40%, duration of contractions – by 18.18%. Selective beta-2-sympathomimetic hexoprenaline, previously used to relieve hypertonicity of a pregnant uterus actively affects intestinal motility. Hexoprenaline inhibited bladder overactivity with KCl, decreasing basal pressure by 58.75%, the amplitude of the contractions – by 39.62%, frequency rate – by 57.49%, reductions in the duration – by 54.55%. Preparations from the group of m-anticholinergics and selective beta-2-sympathomimetics showed a pronounced antispasmodic effect in experiment in vivo and can be used to correct incontinence in patients after orthotopic bladder repair. The new chemical compounds pyrrole-2-carbaldehyde 2-hydroxybenzoylhydrazone (PChBh) and isatin benzoylhydrazone (IBh) demonstrated antispasmodic properties in the experiment in vitro, and confirmed an antispasmodic effect in the experiment in vivo, promising further research, determining safety and efficacy

Electron microscopic diagnostics of apoptosis processes under simulation conditions in the experiment of acute pyelonephritis and concomitant diabetes mellitus type I and II

According to literature data, in the conditions of the balance of pro- and antiinflammatory factors, the development of the infectious-inflammatory process tends to progress and more severe with subsequent transformation into chronic inflammation with corresponding morphofunctional effects. Under such critical conditions, an apoptosis is likely to play a crucial protective role, which can eliminate the excessive accumulation of aggressive inflammatory effects and effectively eliminate them, which in the future prevents the probable transformation into a persistent form. The aim of the work was to study the features of the early dynamic processes of apoptosis in the tissues of the kidneys under simulation conditions in the experiment of acute pyelonephritis and concomitant diabetes mellitus type I and II. The purpose of the study was to study the features of the early dynamic processes of apoptosis in the tissues of the kidneys under simulation conditions in the experiment of acute pyelonephritis and concomitant type I and type II diabetes. The work was performed on 300 adult Wistar rats, which were divided into 4 groups. Fragments of animal's kidneys were studied and photographed in an electron microscope PEM-100-01. The results showed that after modeling in the animals of pyelonephritis in the nephrons there were no significant ultrastructural changes. The structure of the podocytes of the outer sheet was almost the same as the structure of the podocytes of the control material, and in some cells there were signs of activation of their metabolic activity. In the structure of the podocytes of the inner leaf of the capsule, dystrophic changes of the internal membrane of the mitochondria were established. In kidney medulla, the structure of the glomerulus was more preserved than in the cortical. Pathological changes of the proximal and distal tubular podocytes, as well as interstitial tissue, are more pronounced than the renal glomeruli. Under the modeling of the common model of pyelonephritis and type 1 diabetes, more pronounced morphological changes occur: destructive changes in the endothelial cells of the glomerular capillaries, the homogenization of the structure of the basement membrane occurs and the mesangial tissue is significantly enlarged. In nephrons and tubules of cortex, changes are manifested to a much greater extent than in the kidney medulla. When studying in clinical conditions the pathogenetic features of acute pyelonephritis in conditions of concomitant diabetes mellitus it is expedient to carry out electron microscopic research with the aim of choosing the optimal corrective therapeutic effect and preventing the unfavorable course of infectious and inflammatory process and its transformation into persistent form. EM (electron-microscopic) studies are highly informative in the study of pathological changes and early dynamic processes of apoptosis in renal tissues in the design of acute pyelonephritis and concomitant diabetes mellitus I and II in the experimental conditions

Influence of the autonomic nervous system on the clinical course of overactive bladder

Overactive bladder (OB) is a disease which is very easily diagnosed, but presents considerable difficulties in the choice of treatment mode. At present the specialists turn their attention to this syndrome due to a wide spread of the disease, its negative impact on quality of life, social and economic importance. Pathogenesis of OB is complex. Thus, under conditions of urothelium atrophy which takes place because of estrogen deficiency in postmenopausal women, in violation of its GAG protective layer, barrier function of urothelium are violated, which leads to its damage. The appearence of urination disorder symptoms are associated with the fact that atrophic mucosa of urethra and triangle of bladder are hypersensitive to even minimal portions of urine. Aging process also play a role in OB development including lowering ability of tissues to repair, their elasticity reduction, increased apoptosis and cell atrophy, degeneration of nerve endings, smooth muscle tone change, deterioration of urothelium and its GAG protective layer. It can be a result of manifestation of bladder outlet obstruction that causes OB symptoms in men suffering from benign hyperplasia, prostate cancer and chronic prostatitis

Structural and functional transformation of the small intestine wall in the conditions of the functioning of the artificial urinary reservoir in the experiment

Morphological changes of the wall of the artificial urinary bladder are various and its investigation continues from the moment of the creation of the first conduit on the ileum's section. The aim of the work is to explore the structural-functional transformation of the mucous and the neobladder wall in 12 months after ileocystoplasty in the experimental conditions on mini-pigs. The results of the neobladder's experimental model, created by the execution of cystectomy and ileocystoplasty in 9 experimental mini-pigs are the material of this work. 12 months after the operation of modeling the urinary bladder, animals were removed from the experiment of nembutal overdosing, following the provisions of "The European convention for the Protection of vertebrate animals being in use for experiments or for other scientific purposes". Our morphological changes of the artificial urinary bladder, formed from the segment ileum 12 months after the orthotopic ileoplasty proved significant ultra-structural changes in the neobladder's epithelial layer. Ileum's villi within the conditions of the artificial urinary bladder are decreased and smoothed, epithelial cells are similar to the interjacent epithelium. The connective-tissue plate is thickened and becomes callous, the muscular layer is also thickened. The samples of the ileum, that remained in the normal environment without the compatibility with urine, did not undergo the significant morphological transformations and did not differ from the samples of the intact ileum. The transplantation of the ileum segment for performing new, not-programmed functions causes it to adapt to new conditions, although the urinary bladder and the ileum have different origins and structures from the very beginning. New aggressive conditions and constant contact with urine lead to the transformation of the mucous of the ileum and acquire new features necessary for performing new functions

Possibilities of pharmacological correction of the artifical bladder contractile activity in experimental conditions in vivo.

The aim of this work was to study the possibility of pharmacological correction of the neobladder contractile activity of mini-pigs under the influence of new chemical compounds, m-anticholinergic (solifenacin), selective beta-2 sympathomimetic (ginipral (hexoprenaline)) in vivo. Neobladder, formed from the distal section of ileum, pre-denervated along the anti-mesenteric margin, retains peristalsis, and  given the sharp thickening of the muscle layer, capable to contractile reactions and tone support. New chemical compounds pyrrole-2-carbaldehyde 2- hydroxybenzoylhydrazone (PChBh) and isatin benzoylhydrazone (IBh) demonstrated spasmodic properties directed at smooth muscle in vivo. Compound PChBh (I) showed more pronounced relaxing properties compared to compound IBh (II), reducing basal pressure against KCl by 40.91%, contraction amplitude by 30.63%, contraction rate by 25.49%. Solifenacin, being an m-anticholinergic antagonist, most clearly demonstrated antispasmodic properties in vivo, reducing hypertonicity by 55.23%, amplitude – by 49.31%, frequency of contractions in 10 minutes – by 57.40%, duration of contractions – by 18.18%. Selective beta-2-sympathomimetic hexoprenaline, previously used to relieve hypertonicity of a pregnant uterus actively affects intestinal motility. Hexoprenaline inhibited bladder overactivity with KCl, decreasing basal pressure by 58.75%, the amplitude of the contractions – by 39.62%, frequency rate – by 57.49%, reductions in the duration – by 54.55%. Preparations from the group of m-anticholinergics and selective beta-2-sympathomimetics showed a pronounced antispasmodic effect in experiment in vivo and can be used to correct incontinence in patients after orthotopic bladder repair. The new chemical compounds pyrrole-2-carbaldehyde 2-hydroxybenzoylhydrazone (PChBh) and isatin benzoylhydrazone (IBh) demonstrated antispasmodic properties in the experiment in vitro, and confirmed an antispasmodic effect in the experiment in vivo, promising further research, determining safety and efficacy

The dynamics of the cellular composition of urine sediment in conditions of an artificial bladder

The evaluation of the urine cytological profile in the dynamics of adaptation of the orthotopic bladder to the functional properties of the urinary reservoir and determination of the connection between the cellular composition of the urine with the functional role of the formed from the intestinal fragment neocyst in experimental conditions and in humans. The material in experimental study were the results of a cytological study of the urine sediment obtained from 21 female pigs (mini-pigs). The portion of urine had received in experimental animals one month after orthotopic ileocystoplasty, 6 months and 1 year later and prepared as smear from the resulting precipitate. The level of lymphocytes, neutrophils, erythrocytes, as well as the superficial, intermediate and basal epitheliocytes evaluated during study. An analysis of the cell composition of centrifugal smears from the neocyst were performed in 21 patients with bladder cancer undergoing cystectomy and the formation of an orthotopic bladder, at various periods after surgery, from 3 months to 5 years. The preparation of a centrifugal sediment and the subsequent production of smears carried out as well as experimental animals

Ультраструктурна адаптація слизової оболонки ортотопічного ілеального сечового міхура в динаміці у віддаленому періоді в експерименті

Мета. Оцінити в експерименті ультраструктурні зміни слизової оболонки ортотопічного сечового міхура (СМ) карликових свиней через 12 міс після виконання ілеоцистопластики. Матеріали і методи. Експериментальні дослідження проведені на 18 самицях карликових свиней віком 4 – 15 міс, яким виконали цистектомію із формуванням ортотопічного СМ з клубової кишки. Результати. В ультраструктурі слизової оболонки штучно створеного СМ під тривалим впливом сечі стовпчасті клітини в епітеліальному шарі поступово заміщалися клітинами іншого типу, за структурою близькими до епітелію СМ, для виконання його повноцінної функції. Власна пластинка слизової оболонки мала явища деструктивного характеру переважно клітинних елементів, на окремих ділянках волокнисті структури переважали над клітинними. Висновки. Ультраструктурні зміни слизової оболонки штучно створеного СМ через 12 міс після ілеоцистопластики свідчать про її повну трансформацію і адаптацію з елементами еволюції та пристосування до нових умов життєдіяльності

Application of methods of biological feedback in diagnostics and conservative treatment of female urinary incontinence

Изучены особенности биоэлектрической активности мышц тазового дна, эффективность метода биологической обратной связи (БОС) в сочетании с электромиографической триггерной электростимуляцией мышц тазового дна у больных с различными формами недержания мочи. Установлено, что у большинства больных стрессовой или смешанной формами недержания мочи наблюдается выраженное снижение активности показателей электромиограммы и мышечного тонуса тазовых сфинктеров с компенсаторним напряжением мышц промежности, трудностями в мышечном контроле сфинктерного аппарата уретры. Использование метода БОС в сочетании с триггерной электростимуляцией мышц сфинктерного аппарата тазовых органов и мышц промежности позволяет уменьшить проявления нарушений резервуарно-эвакуаторной функции мочевого пузыря у 85 % пациенток с недержанием мочи.The aim of the study was to examine the features of the bioelectrical activity of the muscles of the pelvic floor, study the effectiveness of biofeedback in conjunction with electromyographic electrical trigger stimulation) of the pelvic floor in patients with various forms of urinary incontinence. It was found that most patients with stress or mixed incontinence forms observed marked reduction in activity indicators EMG and muscle tone of the pelvic sphincters with compensatory voltage perineal muscles, difficulty in muscle control in urethral sphincter system, as evidenced by the Rest Average rate increase and decrease Work Average with increase of corresponding indices of Work Deviation (by 38%) and Rest Deviation (by 53%). The use of biofeedback in conjunction with ETS muscle sphincter apparatus of the pelvic organs and muscles of the perineum to reduce manifestations of violations of reservoir — the evacuation of the bladder in 85% of patients with urinary incontinence. The results of this study confirm the need for the widespread introduction of information, method of affordable biofeedback combined with ETS pelvic floor muscles. Indicators of bioelectrical activity of the pelvic floor muscle, skin impedance and peripheral resistance indexes allow for dynamic control of the efficiency of treatment of the disease