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.
The objective: to investigate the dynamics of restoration of the functional state of the renal parenchyma by levels of N-acetyl-β-D-glucosaminidase (NAG) activity in urine and normalization of the main risk factors of calcium-oxalate nephrolithiasis (Ca-Ox NL) – by concentrations of calcium, oxalic and uric acids in urine on the background of application of complex metaphylaxis within a year after stone removal.Materials and methods. 45 patients with Ca-Ox NL before and after the removal of concrements in 1, 3, 6 and 12 months on the background of the use of complex metaphylaxis were examined. The activity of the conditionally renospecific enzyme NAG and concentration of calcium, oxalic and uric acids were analyzed. The personification of metaphylactic measures was performed depending on the characteristics of the risk factors for the development of Ca-Ox NL: the combination of hyperoxaluria with hyperuricemia and hyperuricuria, the combination of hyperoxaluria with hyperuricemia, the presence of significant hyperoxaluria on the background of normouricemia and normouricuria and also depending on hypercalciuria. The control group consisted of 28 practically healthy persons with normal analysis of urine and free of renal diseases.Results. In patients with NL before the removal of the stone, the activity of NAG, calcium, oxalic and uric acid concentrations probably exceeded the control data. In the dynamics of observation there is a gradual decrease in urinary NAG activity, calcium, oxalic and uric acid concentrations. NAG activity and uric acid concentration did not differ from the data in the control group after 12 months, calcium – after 3 months, oxalic acid concentration after 6 months.Conclusion. Restoration of the functional state of tubular nephrotheoia and normalization of concentrations of the main risk factors for the development of Ca-Ox NL on the background of complex metaphylaxis was achieved in almost 95 % of cases. The obtained results can be used to correct and optimize the treatment tactics of patients with Ca-Ox NL after removal of the calculus during the year.
Мета дослідження: вивчення динаміки рівнів екскреції цитокинів ФнП-a та тФр-β1 та активності реноспецифічних ензимів нАГ та β-Гал у сечі дітей з рефлюксуючим мегауретером (МУ) у різні терміни після черезміхурової уретероцистонеостомії. Матеріали та методи. Перед оперативним лікуванням обстежено 45 дітей віком від 4 до 15 років (22 хлопчики, 23 дівчинки), у яких за даними візуалізаційних методів оцінювання діагностовано МУ: 18 пацієнтів з нерефлюксуючим МУ, 27 пацієнтів-з рефлюксуючим МУ до та після реконструктивних операцій. Через 3-4 тиж після операції обстежено 36 пацієнтів, через 4-6 міс-24 особи. референтну групу склали дані, отримані у 25 практично здорових дітей аналогічного віку з нормальними аналізами сечі (без протеїн-, лейкоцит-, еритроцит-та кристалурії, слизу та бактерій). Результати. отримані дані свідчать, що після реконструктивних операцій сечовивідних шляхів у частини хворих є ознаки порушення функції нирки з подальшим її погіршенням. Водночас відомо, що зниження тиску у сечоводі після відновлення уродинаміки з часом призводить до певної нормалізації деяких біомаркерів запалення та проліферації у дітей з вродженими вадами уретеровезикального сегмента (УВс). Заключення. на підставі отриманих результатів можна стверджувати, що кількісні показники вмісту прозапального цитокіну ФнП-a та профіброгенного цитокіну тФр-β1 у сечі, а також рівні активності умовно реноспецифічних ензимів нАГ та β-галактозидаза (β-Гал) сечі у дітей з вродженими вадами УВс є неінвазивними та діагностично інформативними біомаркерами. Вважаємо, що дітей із вродженими вадами УВс доцільно виділити в окрему групу ризику з розвитку нефросклерозу, що потребує проведення своєчасної ренопротекторної терапії. Ключові слова: вади уретеровезикального сегмента, уродинаміка, біомаркери, реконструктивні операції сечовивідних шляхів. Urine enzyme and cytokine levels in the diagnosis of the functional state of the renal parenchyma in children with pathology of the ureterovesicular segment after ureterocystoneostomy G
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