Introduction: The search for and development of new highly active medications and their combinations of the appropriate direction of action remains an urgent problem due to the complications of diabetes mellitus, especially burdened with atherosclerosis, including skin and vascular lesions. Materials and methods: The acute toxicity, histoprotective and dermatoprotective effects of mafusol, rexod, alprostadil and their combinations were studied in male rats with normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Results: The combination of mafusol with rexod is less toxic than mafusol. In arteriovenous insufficiency of the tail, ischemia of the skin fold and skin flap, mafusol (6.25, 12.5 and 25.0 mg/kg in terms of fumarate), rexod (0.01 and 0.02 mg/kg) and especially their combination (6.25 and 0.01 mg/kg) have significant histoprotective, dermatoprotective, hypoglycemic and lipid-lowering effects, both in normoglycemia and alloxan diabetes complicated by exogenous hypercholesterolemia. Alprostadil (10 mg/kg) and especially its combination with mafusol (6.25 mg/kg) have a dermatoprotective effect. Discussion: Rexod reduces the acute toxicity of mafusol. The dermatoprotective effect of mafusol, rexod and, to a greater extent, their combination may be associated with increased microhemocirculation, antihypoxic properties and activation of energy processes in the skin, normalization of carbohydrate and lipid metabolism in alloxan diabetes, complicated by exogenous hypercholesterolemia, increased reserve capacity of the antioxidant system, and possibly with the ability of mafusol and rexod to reduce blood viscosity and improve rheological properties of the blood. The combination of mafusol with alprostadil increases the dermatoprotective activity of the latter. Conclusion: Combinations of mafusol with rexod and alprostadil can be recommended for clinical study as dermatoprotective agents for treating traumatic injuries and diabetes mellitus complicated by atherosclerosis.
Introduction: Insufficient effectiveness of traditional drug therapy in a treatment of patients with chronic generalized periodontitis, as well as high social significance of this problem, determines the need to search for new drugs and their compositions aimed at solving it. Aim of the study: To increase the efficacy of complex treatment of periodontitis with the administration of Soderm®-Forte gel and a new injectable form of Rexod®. Materials and methods: Experiments were performed in 50 male Wistar rats. Experimental periodontitis (EP) was simulated by ligation of the necks of lower incisors. We studied the animals with intact periodontium, untreated EP, and when traditional drug therapy (TDT), as well as the combinations of TDT with Soderm®-Forte gel and additionally with the new injectable dosage form (NIF) of Rexod® were administered. The general condition, behavior, nutrition and body weight of the animals were evaluated. The Schiller-Pisarev test and the Muhlemann-Cowell bleeding index were used, and the amount of crevicular fluid (CF) was measured. The contamination of the marginal gum with microorganisms was determined. Results and discussion: The TDT in EP has a moderate therapeutic effect, which does not lead to a sufficiently high pharmacotherapeutic effect, whereas the combinations of TDT with Soderm®-Forte and, to a greater extent, TDT with Soderm®-Forte and NIF of Rexod® have high therapeutic efficacy, which is statistically confirmed by a sharp decrease in the amount of CF, the Schiller-Pisarev test and the Muhlemann-Cowell bleeding index, as well as absolute suppression of pathogenic microorganisms. Conclusion: The combinations of TDT with Soderm®-Forte gel and NIF of Rexod® in EP in rats can significantly increase the effectiveness of the treatment. The data obtained indicate the expediency of the administration of Soderm®-Forte gel, as well as its combination with NIF of Rexod® in dental practice in the complex therapy of patients with periodontitis.
Background. Free radical oxidation underlies many morbid processes in various organs and tissues, including skin. A major antioxidant preventing the free radical impact is superoxide dismutase (SOD). A particularly valued SOD-containing agent is recombinant human SOD, Rexod, possessing a wide spectrum of medical applications in form of lyophilisate. Marketing of a new Rexod® injection preparation in form of solution requires research into its properties, including the impact on blood microcirculation in skin, especially with the lack of relevant clinical trials.Objectives. Evaluation of anticipated positive effects of the new injection form of Rexod® on blood microcirculation in rat skin.Мethods. The new Rexod® preparation impact on blood microcirculation in skin was studied with laser Doppler fl uometry by recording the following non-oscillatory parameters of the basal blood fl ow: microcirculation (MC), mean squared deviation (MSD) and coeffi cient of variation (CV). Blood fl ow fl uctuations were measured in a wavelet analysis at different frequency bands: 0.0095–0.02, 0.02–0.046, 0.07–0.15, 0.15–0.4 and 0.8–0.16 Hz corresponding to endothelial (Ae), neurogenic (An), myogenic (Am), respiratory (Ar) and pulse (Ap) rhythm amplitudes, respectively.Results. The new Rexod® injection preparation at a dose of 8000 U/kg after 15 min of intraperitoneal administration in rats caused a statistically signifi cant (p < 0.05) increase in the blood fl ow fl uctuation amplitudes Ae (43.1%), An (43.4%), Am (60.8%), Ar (58.3%) and Ap (32.0%) compared to the control group. Because the Ae fl uctuations coincide with nitric oxide (NO) emission episodes, such a growth indicates an elevated NO excretion by endothelial cells leading to endothelium-dependent vasodilation. The observed changes in blood microcirculation in skin are also associated with higher integral values of the basal blood fl ow, MC (33.4% increase), MSD (14.0%) and CV (27.6%), although only MC and CV values were statistically signifi cant (p < 0.05). The results obtained suggest that the new injection form of Rexod® stimulates endothelial NO excretion, exerts adrenergic relaxation in smooth muscle cells of arteriolae and arteriovenular anastomoses, reduces precapillary sphincter and arteriolar contractility through Ca2+-dependent muscle relaxation, affects respiratory modulation of the venular blood microcirculatory compartment and vegetative cardiac support, intensifi es arterial blood fl ow by increasing the cardiac output.Conclusion. Application of the new Rexod® injection form improves blood microdynamics in rat skin via stimulating endothelium-dependent and independent vasodilatation and endothelial metabolism, decelerating adrenergic vasomotor activity and peripheral microvascular resistance. These processes in coupling improve blood fl ow to nutritive microvascular bed and normalise venular outfl ow. Our results provide further insights into pharmacodynamics of recombinant human SOD (Rexod).
Introduction: Periodontitis is the most important problem of modern dentistry. The development of new medicines and treatment regimens for patients with periodontal complex lesions is a strategic direction of modern pharmacology and dentistry. In this view, pride of place goes to morphological research, which allows not only to study the effect of drugs on pathomorphological changes in periodontal tissues, but also to estimate their therapeutic effectiveness. Aim of the study: to determine the nature of the effect of the composition of Soderm®-Forte gel and the new injectable form of Rexod® on the pathology findings in gingival tissue of rats with experimental periodontitis. Materials and methods: Experimental periodontitis (EP) was induced in rats by ligature method. The study was performed according to the following algorithm: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with combinations of TDT with Soderm®-Forte gel and TDT with Soderm®-Forte gel and the new injectable form (NIF) of Rexod®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. The ImageJ software was used for computer morphometry. Results and discussion: Examination of the gum samples revealed moderate therapeutic effects of the TDT. The combinations of TDT with Soderm®-Forte gel and, to a greater extent, TDT with Soderm®-Forte gel and the NIF of Rexod® showed high pharmacotherapeutic efficacy, manifested in rapid regeneration of the gingival tissues. Conclusion: The combination of TDT, Soderm®-Forte gel and the NIF of Rexod® shows the most beneficial effect on the pathological processes in the gum. The pharmacotherapeutic effect of the studied combination promotes the earliest regeneration of damaged gum tissues and reduces the risk of persistent pathology changes in them.
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