A main issue in pharmacology is the seek for effective agents for the correction of ED. To study the endothelioprotective effects of 2-ethyl-3-hydroxy-6-methylpyridinium (2e3h6m) nicotinate under conditions of L-NAME-induced oxidation. The L-NAME pattern of induced oxide efficiency (25 mg/g) for one week was used. The endothelial and cardioprotective effect of 2e3h6m nicotinate at an amount of 3.75 mg/kg compared to picamilon 10 mg/kg was examined via the coefficient of ED (QED) and a number of exercise tests. Nicotinate 2e3h6m and picamilon exerted a pronounced endothelioprotective impact on the pattern of L-NAME-induced NO deficiency, which manifested itself in a decrease in the coefficient of endothelial dysfunction (ED). At the same time, 2e3h6m nicotinate (7.6 mg/kg) was 2.1 times more effective than picamilon (10 mg/kg). So, 2e3h6m nicotinate was produced itself as an endothelio and cardioprotector.
Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein.
From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.
Hypoxia and tissue ischemia are the leading factors in the alteration of tissues in many pathological conditions. Prevention and reversion of the effects of local ischemia, which develops during various surgical interventions, is an actual problem of modern medicine. The aim of the present study was to investigate the effect of exenatide and vildagliptin on the survival rate of an isolated pedicle skin flap in sixty adults Wistar rats. Simulation of a pedicle skin graft was performed on the second day of the experiment. After anesthesia under aseptic conditions, a skin graft was cut out: isolated in a plastic bag, the edges of the skin were stitched with interrupted sutures (nylon 3/0). Rats were divided into six groups: control group, exenatide group (10 µg/kg/day subcutaneously for nine days after surgery), vildagliptin group (0.2 mg/kg/day intraperitoneally for nine days after surgery) and pentoxifylline group (100 mg/kg/day intravenously, two hours before the surgical intervention). In the other two groups, glibenclamide (5 mg/kg) were administered before injection of incretin mimetics. On the third, seventh and tenth day, area of the surviving tissue was measured. Subsequently, the survival rate of the skin graft was calculated. The area of the surviving tissue in exenatide and vildagliptin group was 1.5 and 1.7 times more compared to the control group, respectively. Preliminary blockade of ATP-dependent potassium channels by glibenclamide eliminated the protective effect of exenatide and vildagliptin. The increase in the survival of ischemic tissues using exenatide and vildagliptin has been experimentally proved. The current study confirmed the important role of ATP-dependent potassium channels in dermatoprotective properties of incretin mimetics.
Introduction: Currently, there are no safe and ideal medicines for the prevention and treatment of oophorectomy-induced osteoporosis. The development of an effective pharmacotherapy for hypoestrogen-induced osteoporosis is an important task of pharmacology. Materials and Methods: A new supramolecular complex (composition №1) was obtained on the basis of 3-hydroxypyridine derivatives: 2-ethyl-6-methyl-3-hydroxypyridinium 3-pyridinocarbonoate and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate in a ratio of 1:3 by topochemical synthesis. The study of the osteoprotective activity of the supramolecular complex at a dose of 50 mg/kg was performed on 60 white female rats of the Wistar line on a model of hypoestrogen-induced osteoporosis. The effectiveness of the osteoprotective activity of the complex was evaluated on the 57th day of the experiment. Results and Discussion: The new supramolecular complex (composition №1) has osteoprotective activity, which is expressed in improving the indicators of X-ray and histomorphological samples. Oral administration of composition №1 at a dose of 50 mg/kg led to an increase in bone density to values of 2.55±0.02 g/cm3, which is 1.3 times higher than in the control group 1.92±0.01 g/cm3 (p≤0.05) and reduce bone resorption by improving cortical and trabecular bone structures. Conclusion: The obtained data characterize the prospects of studying composition №1 for the correction and prevention of hypoestrogen-induced osteoporosis. Graphical Abstract
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