Abstract. The aim of the work was to experimentally study the effect of the created injectable drug basic fibroblast growth factor (bFGF) with the controlled release on morphological changes and indicators of renospecific enzymes in the ischemic kidney (experiment on rabbits). Methods. Studies on the release dynamics of the created bFGF drug were performed in vitro and the study of the induction of bFGF angiogenesis in the model of the chick chorioallantoic membrane of the chicken was performed. The experimental model was performed in 25 rabbits: in 10 rabbits we studied the effect of 1-8 months of "pure ischemia" of the kidney without injection of the drug (control); in 12 rabbits 1 month after the creation of the model of ischemia in the renal parenchyma was injected the prolonged-acting drug bFGF, deposited on our polymeric carrier at a dose of 5 μg (experiment). The reference group consisted of 3 intact rabbits. Histological examinations of renal tissue and morphometric examinations with the determination of vascular coefficient (VC) and interstitial coefficient (IC) were performed. Enzymological indicators of enzyme activity in the homogenate of the renal parenchyma were determined by biochemical methods; statistical analysis was performed. Results. Using chick chorioallantoic membrane as a model it was preliminarily demonstrated that developed injectable prolonged-acting drug bFGF deposited on a polymeric carrier based on cross-linked modified heparin, effectively enhances neoangiogenesis. The results of morphological and morphometric studies with the determination of vascular and interstitial coefficients showed, that the injection of the prolonged-acting drug bFGF in all cases was accompanied by an increased blood supply in the kidneys and neoangiogenesis, which reduced the effects of ischemia. Injection of bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 3-4 months completely prevented the development of initial sclerotic and atrophic changes, that developed in the kidney during this period under the influence of chronic ischemia without bFGF. Injection of prolonged-acting bFGF at a dose of 5 μg in the model of chronic segmental renal ischemia for 5-8 months prevented expressed sclerotic and atrophic changes, that developed under the influence of chronic ischemia during this period without the use of bFGF. As a result of biochemical studies, the activation and normalization of indicators of renospecific tubular enzymes in the ischemic kidney under the action of the created experimental drug bFGF were determined. Conclusions. Therapy of ischemic changes in the kidney with the developed injectable long-acting drug bFGF at a dose of 5 µg in the experimental model of chronic ischemia protects the organ from hypoxic damage, has a positive effect on the structural and functional state and metabolism of the kidney, and prevents the development of nephrosclerosis.
В умовах ДУ «Інститут урології НАМН України» досліджено 61 особу з каменем нирки. Пацієнтів було роз поділено на дві групи: І група -30 осіб з єдиною ниркою (ЄН), ІІ група -31 особа з двома нирками. Середній вік хворих -37,5±2,4 року (чоловіків -67,2%, жінок -32,8%). Лікувальна програма складалася з монотерапії рослинним уролітиком Флавія ® (Swiss Caps. AG, Швейцарія) протя гом 3 міс по 1 капсулі двічі на добу після їди. Призначення монотерапії фітоуролітичним засобом Флавія ® протягом 3 міс сприяло позитивній динаміці у лікуванні усіх пацієнтів. Визначення розміру каменю було достовірним на разі застосування спіральної комп'ютерної томографії (СКТ) та на відміну від ультразвукового дослідження (УЗД) надава ло більш реальні дані (при УЗД конкременти були більшими на 17,2-20,6% від справжніх розмірів). Визначення щільності каменів за допомогою СКТ денситометрії характеризувало склад каменів, як композитний (оксалатно кальцієвий та уратно кальцієвий), з позитивною динамікою зменшення щільності на тлі лікування у І групі на 21,7%, у ІІ групі -на 33,9%. На тлі вживання Флавії ® у І групі повне розчинення каменів відбувалося у 13,3%, часткове -у 73,3% пацієнтів, в осіб ІІ групи аналогічні процеси відбувалися у 16,1% та 64,5% відповідно. Відсутність ефекту від монотерапії спостерігали у І групі у 13,3%, у ІІ групі -у 19,3% пацієнтів. Відмінність у ди наміці між групами полягала у більш кращому зменшенні щільності каменів у ІІ групі (33,9% від 21,7% у разі ЄН), а при УЗД -дані характеризувалися вірогідним хибнопозитивним збільшенням розміру каменів в обох групах. Ключові слова: уролітіаз, єдина нирка, уролітик, Флавія ® .
Urolithiasis (URL) is a common urological disease that often appears in the population, has a high recurrent rate and a significant impact on the social status of the population. Almost half of patients with URL disease are people with ureteric stones, 95% of which have secondary genesis. The main methods of treatment of such patients are extracorporeal shock-wave lithotripsy (ESWL) and ureterolithotripsy (URS). It is important in these cases to determine morphological changes (inflammation, edema, sclerosis, necrosis, etc.) that appear in the ureter in the placement of the stone and may reduce the effectiveness of minimally invasive treatment or/and removal of fragments during URS. The objective: studying morphological changes of the ureter wall in patients with ureterolithiasis in the zone of the calculus in dependence of the duration of clinical manifestations. Materials and methods. We have studied histological changes of the ureter wall in the location of the stone in patients with ureterolithiasis. We explored the ureter wall in patients depending on duration of typical manifestations of ureterolithiasis, which were 7-en days long, 30 days, and more than 2 months. Results. If the stone in the ureter is up to 7 days, it does not cause significant microscopic changes of the ureter wall. If the stone been in the ureter during 1 month, more significant morphological changes are determined with desquamation of the urothelium, edema and inflammatory changes in the submucosal membrane. In case of the duration of the calculi in the ureter is more than 2 months, we noted the exfoliation of the urothelium with the denudation of the basement membrane. In the submucosal layer there is an edema, diffuse disorganization of connective tissue fibers, fragments of growth of granulation tissue and dense connective tissue in the form of separate layers. Conclusion. With increasing duration of the disease in the wall of the ureter increases the manifestations of inflammatory, sclerotic and necrotic changes. Such changes have a direct impact on the quality of visualization of the calculus during endoscopic interventions, the rate of fragmentation and extraction (elimination) of fragments, as a consequence, increase the overall duration of the operation and the risk of intra- and postoperative complications.
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