Relevance. Modeling the conditions of endotoxicosis by introducing bacterial lipopolysaccharide against the background of toxic liver damage is due to the fact that under such conditions the situation that accompanies almost every chronic pathology, including cardiovascular, is reproduced. The release of substances that play a role in the formation of endogenous intoxication causes heart damage in the absence of cardiac pathology, and in its presence worsens the course and prognosis. However, it should be found out whether these changes are the result of only toxic damage to cardiomyocytes or have another morphological basis and what their dynamics are. Objective: to characterize the morphological changes of the myocardium in experimental chronic endotoxicosis. Materials and methods. The research was carried out by modeling endotoxicosis in 18 laboratory animals for 90 days by daily intragastric injection of tetrachloromethane at the rate of 3-5 ml/kg of body weight and every 6th day by intraperitoneally adding bacterial lipopolysaccharide at a dose of 0.2 mg/kg of body weight. Animals were removed from the experiment by decapitation at 30, 60, and 90 days. Animals were removed from the experiment by decapitation after anesthesia with intraperitoneal administration of sodium thiopental at a dose of 50 mg/kg. The control group consisted of 6 intact animals. For histological examination, myocardial tissue was condensed in paraffin, and deparaffinized sections were stained with hematoxylin and eosin, examined for the detection of neutral glycosaminoglycans and acidic mucopolysaccharides, stained with Alcian blue and PAS-reaction according to standard methods, and examined under a Nikon Eclipse Ci-E light microscope. Results. During researching the myocardium at the light-optical level of experimental animals, after 30 days of chronic endogenous intoxication caused by injection of tetrachloromethane and bacterial LPS, it undergoes changes, first of all, it concerned cardiomyocytes: we observe thinned cells around the vessels and unchanged ones at a distance from the vessels. In some of them, hyperchromia of the nuclei and phenomena of contractile damage and fiber fragmentation were noted. Manifestations from the CMC increased during the next period of the experiment: after 60 days, expressed wave-like deformation of fibers with atrophic changes in muscle cells was detected in the myocardium. Hemodynamic changes were characterized by hyperemia, the number of perivascular hemorrhages increased. On the 90th day of the experiment, in addition to inflammatory manifestations and dystrophic-necrotic changes, cardiomyocyte atrophy in combination with expressed interstitial edema was detected in the myocardial tissue of animals. In the stroma, in addition to small foci of perivascular cardiosclerosis, foci of adipocyte growth were determined. Cardiomyocyte defibrillation and hemorrhages were observed in some areas Conclusion. The intensity of structural changes in cardiomyocytes and hemodynamic disorders in chronic endotoxicosis depends on the duration of intoxication and the character of structural changes. The interstitium of the myocardium of rats under experimental endotoxicosis conditions is dystrophic-sclerotic and is manifested by a different combination of edematous and sclerotic manifestations at different stages of exposure to toxicants.
Background. Nowadays, much attention is paid to enterosorption methods that allow cleansing the internal organs and removing extraneous substances out of the body of a sick person. Objective. The aim of the research was to study the effect of microcrystalline cellulose on the microflora of the large intestine. Methods. The study was performed on 50 white laboratory Wistar rats weighing 180-270 g, which were divided into control and experimental groups. The experimental group was daily administered with microcrystalline cellulose at a dose of 500 mg/kg. The study followed ethical standards and recommendations for the humanization of work with laboratory animals according to the “European Convention for the protection of vertebrate animals used for experimental and other purposes” (Strasbourg, 1986, 2010), as well as the requirements of the Commission on Bioethics of I. Horbachevsky Ternopil National Medical University (Minutes No. 66, dated November 01, 2021). The first group involved the intact rats on standard diet, the second – the rats, which received normal feeding of microcrystalline cellulose. Results. In the feces of the experimental white rats treated with microcrystalline cellulose, the level of Escherichia coli in the large intestine decreased by 22 and 25%. The number of these microorganisms increased by 20% in 7 days and by 14% in 14 days. The content of epidermal staphylococci in the stool decreased by 10% on the 7th day of administration. Microcrystalline cellulose increased the number of Staphylococcus aureus by 12%, but decreased the number of enterococci in the feces by 28%. In 7-14 days of the experiment, the content of these bacteria did not change significantly in the colon. In relation to anaerobic microorganisms – bacteroides and clostridia, this supplement caused a slight increase in the number of bacteroides – by 8.64% and the number of clostridia – by 11.54% on the 14th day. The content of fungi of the Candida genus on the 7th and 14th day increased by 8.3%. Conclusions. In the 2nd period of the study, the microbiome of intestinal contents worsened: the process of dysbacteriosis increased, which was manifested by a significant increase in the number of Proteus spp., Staphylococcus aureus, anaerobes (bacteroides, clostridia) and Candida spp., as well as decreased Escherichia coli and Enterococci.
Relevance. Abdominal ischemic disease is a general term that characterizes various clinical syndromes of damage to the organs of the digestive system when blood flow is disturbed in the abdominal part of the aorta and its branches, as a result of which there is a disparity of the blood supply of internal organs to their energy needs with the subsequent development of chronic ischemia and necrosis of cells and tissue. Objective. To establish the characteristic features of the dynamics of the remodeling of the blood vessel of the testicles of rats with dosed stenosis of the aorto-iliac segment. Materials and methods. The experiment was conducted on 48 white outbred sexually mature male rats with an average age of 3 months and a weight of 180-200 g. All animals were divided into two groups: experimental group consisted of 36 animals with simulated dosage stenosis of the aorto-iliac segment and control group (12 subjects). All operative manipulations were performed in compliance with the rules of asepsis and antisepsis. Preliminary anesthetization of the animals was carried out with the intramuscular injections of ketamine (50 mg/ml) in terms of 0.083 mg/g of body weight. After performing a laparotomy through a midsection along the white line of the abdominal wall, the abdominal aorta was isolated and compressed by 1/3 of its diameter by applying a silk ligature. The degree of narrowing was controlled using a metal probe with a cone-shaped tip according to the already known method. On the 1st, 3rd, 7th, and 14th day, the animals were taken out of the experiment and an organometric assessment of the condition of the testicles was carried out with the determination of the following parameters: the weight of the organ was determined using a torsion weight VT-500, the length and width were measured using a caliper. After that, pieces of testicular tissue were taken and fixed in a 10% solution of neutral formalin and 96% ethyl alcohol. The obtained paraffin sections with a thickness of 5-7 μm were stained with hematoxylin and eosin, and microscopic examination of a series of histological sections was carried out. Results. A day after the simulation of experimental stenosis of the aorto-iliac segment, a microscopic examination of the structures of the testicle revealed significant swelling of the stroma of the organ. The interstitial tissue was unevenly located between the tortuous seminiferous tubules, the lumen between which was slightly expanded. At the same time, the internal structure of the tubules remained preserved, layers of spermatogenic cells at different stages of maturation were clearly differentiated in them. On the third day of observation, previously identified signs of disorders of organ blood circulation in the testicles continued to increase. The swelling of the testicular interstitial tissue slightly decreased, but it was accompanied by changes in the structure of the cells of the spermatogenic epithelium, the manifestation of which was the detachment of spermatogonia from the basal membrane of the tubules and the expansion of the spaces between the rows of spermatogenic cells. The walls of the small arteries and arterioles were still significantly thickened. On the 7th day of observation, against the background of a significant decrease in the swelling of the space between the tortuous seminiferous tubules, dystrophic changes in the testicular tissue began to increase. On the 14th day of observation, even more expressed signs of organ hemodynamics violation were observed, and as a result, deviations of the trophism of testicles of experimental animals. Manifestation of such changes were prominent arterial and venous plethora. Large-caliber arteries were significantly filled with blood, and as a result, small and medium-caliber arteries, especially arterioles, had thickened walls and a markedly narrowed lumen. Conclusion. With dosed stenosis of the aorto-iliac segment, significant disorders of central hemodynamics occur, which are characteristic of occlusive diseases of the aorta and its branches. As a result, in the testes of sexually mature male rats, dystrophic changes in the cells of the spermatogenic epithelium occur and the functional activity of the organ decreases, which can form the basis for the development of infertility.
Introduction. The cause of hypertension and coronary heart disease in most cases is hypercholesterolemia. Therefore, for the treatment and prevention of most pharmacotherapy regimens, antiatherosclerotic drugs are used. With a high class of recommendations and level of evidence, high efficiency for primary and secondary prevention of coronary heart disease, statins are widely used in clinical practice. The aim of the study – to improve more rapid, simple, selective, less expensive methods of thin layer chromatography analysis of simultaneous determination of lisinopril and atorvastatin in pharmaceuticals. Research Methods. The present study assessed mobile phases of lisinopril and atorvastatin for TLC. Results and Discussion. Thin layer chromatography can be used to: monitor the progress of a reaction, identify compounds, determine the purity of a substance. Method of simultaneous identification of lisinopril and atorvastatin by TLC was developed. We investigated different mobile phases to optimize the development of analytical methods of lisinopril and atorvastatin by TLC. It was established that the most optimal Rf observed using mobile phase ammonia R (25 %) – propanol R (30:70, v/v). We explored the validation characteristics – specificity and suitability of the chromatographic system that met, the eligibility criteria established by the SPhU. Conclusions. We developed chromatographic method for simultaneous determination of lisinopril and atorvastatin. Propects for future research will be aimed at developing analytical methods of analysis.
Introduction. Innovative pharmaceutical development of various antihypertensive drugs with statins and the creation of domestic fixed-dose combinations of drugs with different effects is an urgent task of modern pharmacy, which will help attract more patients to the treatment and prevention of cardiovascular disease. Pharmaceutical development of atorvastatin and lisinopril by our scientific group proposes for using the ratio of (1/1) for lisinopril (10 mg) and atorvastatin (10 mg). HPLC (High-Performance Liquid Chromatography) technique is adopted as it is considered as the most common technique in realm of quality control analysis. The aim of the study – to evaluate the robustness of HPLC (High-Performance Liquid Chromatography) method for the quantitation of lisinopril and atorvastatin and determine the analytical parameters that present greater influence in the final results of the analysis. Research Methods. An efficient method to assess the robustness of analytical methods is by Youden’s test, by means of an experiment design which involves seven analytical parameters combined in eight tests. In the recent studies, we assessed the robustness of a chromatographic method to quantify lisinopril and atorvastatin in tablets using Youden’s test. Results and Discussion. By using the criteria of Youden’s test, HPLC method proved to be greatly robust regarding content of lisinopril and atorvastatin, when variations in seven analytical parameters were introduced. The most variation in effects of the analytical parameters in retention time (Rt) for lisinopril and atorvastatin HPLC quantitation was when used column supplier. Purospher C8 STAR (55 mm x 4mm, 5 μm) is based on high purity silica and an almost complete surface coverage. Purospher C8 STAR provides excellent peak symmetry for acidic, basic and even chelating compounds, highest column efficiency in terms of the number of theoretical plates, and exceptional stability from pH 1.5 to 10.5. Conclusion. Youden’s test can be applied successfully for the robustness evaluation in validation process of analytical methods and results ontained in our work should be interest to the scientific population dealing with pharmaceutical analytical chemistry.
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