I. A. Pomytkin, V. V. Pisarev, M. E. Merkulov, E. B. Kuznetsova, E. A. Salina, A. Yu. Malygin, N. N. Karkischenko
{"title":"Phase II Clinical Trial of Direkord: Randomized, Double-Blind, Placebo-Controlled, Parallel Group, and Prospective Studies to Select Optimal Dosage and to Study the Efficacy, Safety, and Tolerability in Ischemic Stroke Patients in the Early Recovery Period","authors":"I. A. Pomytkin, V. V. Pisarev, M. E. Merkulov, E. B. Kuznetsova, E. A. Salina, A. Yu. Malygin, N. N. Karkischenko","doi":"10.33647/2074-5982-19-3-87-96","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-87-96","url":null,"abstract":"Direkord is an original drug containing the active substance of dicholine succinate, which improves the sensitivity of insulin receptors in neurons to insulin. The aim of the work was to select an optimal dosage and to study the efficacy, safety, and tolerability of Direkord, a solution for intramuscular injection, in ischemic stroke patients in the early recovery period. In total, 132 patients after the first ischemic stroke in the carotid system, confirmed by computed or magnetic resonance imaging, with the stroke remoteness from 3 weeks to 2 months and the mean age of 64.35±8.03 years, were randomized into three treatment groups. Patients in the first (n=44) and second (n=44) groups received Direkord intramuscularly for two weeks at a dose of 400 mg/day and 600 mg/day, respectively. Patients in the third group received placebo. The treatment response was assessed in terms of improved neurological status, functional state, and cognitive functions, including at least a two-fold decrease in the total score on the NIHSS scale, the total score on the Barthel scale ≥95, and the total score on the MoCA scale ≥26. Four weeks after the onset of the study, 34.1, 43.2, and 18.2% of the patients responded to therapy in the first, second, and third group, respectively. An analysis based on the Fisher’s exact test revealed a statistically significant difference between the groups (p=0.036). These results suggest that Direkord is statistically and clinically significantly superior to placebo at a two-week intramuscular therapy at a dose of 600 mg/day in patients with ischemic carotid stroke in the early recovery period. The safety profile of Direkord when used in various therapy regimens does not differ from that of placebo. The phase III study should confirm the preliminary results obtained in the current work.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135352551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Method for Studying Calcium Homeostasis at the Level of Gastroenteral Environment in Minipigs","authors":"D. A. Ksenofontov, A. A. Ksenofontova","doi":"10.33647/2074-5982-19-3-23-28","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-23-28","url":null,"abstract":"The stages of calcium metabolism at the enteric medium level were studied in experiments on minipigs. Atomic absorption spectrophotometry was used to determine the concentration of calcium in the endogenous and exogenous structures of the chyme while its passing through the small and large intestines, both in different layers of the intestinal wall and in the blood flowing in and out of the intestine. Regularities of changes in calcium concentration in chyme fractions and its predominant accumulation in the dense endogenous fraction in the small intestine were established. Taking into account the hydration of the glycoproteins of the abdominal mucus and its existence in the form of a kind of enteroplasm of the chyme, it is assumed that calcium is involved in the formation of endogenous structures and chyme as a whole by redistributing between soluble and fixed forms of the element. The dynamics of the increase in calcium concentration in the layer of mucous deposits from the distal to the proximal section of the intestinal wall was revealed. In the intestinal mucosa, the calcium concentration is generally lower, although the dynamics follows a similar pattern. The arterio-venous difference in the damage of the digestive tract indicates the predominant excretion of the element into the digestive cavity. The conclusion is made about the role of endogenous chyme structures in maintaining calcium homeostasis not only in the gastroenteric environment, but also in the body as a whole.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135483229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. S. Nesterov, R. A. Ageldinov, D. V. Khvostov, S. L. Lyublinskiy, I. N. Lyublinskaya, V. N. Karkischenko
{"title":"Modification and Improvement of the Liposome Composition of Preputial Gland Extract of Siberian Musk Deer","authors":"M. S. Nesterov, R. A. Ageldinov, D. V. Khvostov, S. L. Lyublinskiy, I. N. Lyublinskaya, V. N. Karkischenko","doi":"10.33647/2074-5982-19-3-29-35","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-29-35","url":null,"abstract":"In this work, we set out to characterize the liposomal form of a new original product based on the preputial gland extract of Siberian musk deer whose composition was modified by an inclusion complex with β-cy- clodextrin. Musk deer liposomes were obtained by an efficient and scalable high-pressure homogenization method. The resulting liposomal product was characterized by transmission electron microscopy, dynamic light scattering, preparative and analytical chromatography, and gas chromatography-mass spectrometry. A specification for the liposomal form of Siberian musk deer extract was developed, which includes all critical indicators of product quality. Homogeneous dispersions of musk deer liposomes with a uniform size distribution were obtained, with the distribution maxima observed at 50 and 240 nm. The high physicochemical stability of the liposomal dispersion was established with the zeta potential value of the obtained nanoparticles ranging from –5 to –35 mV. According to size-exclusion chromatography and mass spectrometry, the incorporation of deer musk target components into liposomes reached 58–75% for musk liposomes in terms of steroid components and total protein. The revealed quality indicators of the studied liposomal product indicate the possibility of obtaining highly effective products based on the liposomal form of musk deer extract, modified with cyclodextrin, as an adaptogen of natural origin with an enhanced and pronounced activity in laboratory performance tests.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135483358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Normothymic Effect of Lithium Ascorbate on Biomedical Models of Pigs","authors":"K. S. Ostrenko","doi":"10.33647/2074-5982-19-3-42-46","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-42-46","url":null,"abstract":"In many developed countries, pigs have long attracted attention as biological models. Pigs are emotionally unstable animals, with a low resistance to stress. In this regard, experiments with pigs as biomedical models can be used to test the long-term use of drugs and their aftereffects. In this work, we set out to test a non-invasive anti-stress drug – lithium ascorbate – for reducing the negative impact of spontaneous stress factors occurring in pigs. Prior to experiments and at six months of age, blood samples were taken from animals. Adrenaline, norepinephrine, cortisol and progesterone, malondialdehyde, thiol-disulfide ratio, and superoxide dismutase activity were determined in the blood plasma. The conducted research allows us to conclude that the stressors arising during the standard production cycle of raising piglets activate the system of biological active centers of pigs, thereby increasing the general reactivity of the body. The obtained experimental data on a set of endocrinological and biochemical parameters indicate that lithium ascorbate in fattening pigs has a positive effect on their antioxidant status.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135483461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Technique for Measuring Electrical Activity of the Brain in Experiments on Laboratory Animals","authors":"N. S. Tropskaya, O. V. Razbitskaya","doi":"10.33647/2074-5982-19-3-53-57","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-53-57","url":null,"abstract":"This article presents a technique for experimental EEG analysis, which includes construction of a frequency spectrum trend, determination of the spectral power of signals in standard frequency ranges, followed by normalization by the maximum value in all channels and in all frequency ranges. This technique can be used to carry out a comparative analysis of data in any time interval, to evaluate the dynamics of changes in each of the main EEG rhythms, to identify the presence of a fronto-occipital gradient and interhemispheric asymmetry, and to evaluate the values of the integral index, which reflects the ratio of high- and lowfrequency rhythms.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recombinant Myostatin: Isolation and Use in Vaccines","authors":"E. M. Koloskova, V. A. Ezerskiy","doi":"10.33647/2074-5982-19-3-17-22","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-17-22","url":null,"abstract":"Protein myostatin is not only a potential target for therapeutic effects in pathologies of the muscular system, but also a tool for biotechnological regulation of the meat productivity of farm animals. The action of myostatin can be blocked by inducing autoantibody synthesis using recombinant myostatin (rMST) as an antigen. E. coli producer strain Bl21/pET28-MSTN was obtained with a high level of recombinant protein expression in inclusion bodies. Purified rMST was used to immunize sheep and rabbits. Using the created ELISA test system for the detection of antibodies to myostatin in the blood of sheep, it was shown that rMST is immunogenic (the working titer of sera is 1/400–1/800). As a result of vaccination of rabbits over a monthly period, the average body weight and average daily weight gain in animals of the experimental groups was observed to increase compared to the control group.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"126 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safety Profile of a New Dimethylaminoethanol Derivative by Oral Administration to Laboratory Animals","authors":"E. B. Shustov, A. E. Kim","doi":"10.33647/2074-5982-19-3-82-86","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-82-86","url":null,"abstract":"A new derivative of dimethylaminoethanol, butanedioic and trans-butenedioic acids (laboratory code ADK-17) was synthesized at the Department of Organic Chemistry (Professor I.P. Yakovlev is the Head of the Department) of St. Petersburg State Chemical and Pharmaceutical University (SPCPU). This is a promising compound planned for use as an oral dosage form. In this work, we aim to evaluate manifestations of the general and specific toxicity of the new drug. Laboratory animals (white mice, rats, rabbits, guinea pigs) were used as test systems for the preclinical safety study of the new compound. Manifestations of general toxicity (acute and chronic), local irritant action, allergenic properties, immunotoxic action were studied. The reproductive toxicity of the ADK-17 drug when administered intragastrically was studied. The studied drug was found to exhibit low toxicity, cause no changes in the biochemical and morphological parameters of rats and rabbits under the conditions of course use, and have no negative effects on internal organs. When administered intragastrically in maximum doses, the drug causes no irritating effects. The use of the drug did not lead to the development of a local allergic reaction of an immediate type. Carrying out sensitization in the DTH reaction showed the absence of a sensitizing effect. The study of the immunotoxic effect of the ADK-17 drug showed that its prolonged intragastric administration for 30 days at doses of 93 and 930 mg/kg did not lead to a violation of the humoral immune response and a decrease in antibody production. Setting a delayed-type hypersensitivity reaction also confirms that the drug does not affect the development of cellular immunity. The conducted experimental studies of the drug’s reproductive toxicity in rats showed that its repeated intragastric administration at doses of 50 and 250 mg/kg to pregnant females did not have a negative effect on the reproductive system of laboratory animals, embryo- and fetotoxic, as well as teratogenic effects, having no effect on the antenatal and postnatal development of offspring.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135482768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuromuscular Joint Function Impairment in Leptin-Resistant Mice","authors":"V. A. Prikhodko, T. M. Matuzok, S. V. Okovityi","doi":"10.33647/2074-5982-19-3-77-81","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-77-81","url":null,"abstract":"The study was aimed at exploring and describing the main parameters of neuromuscular joint function in young adult leptin-resistant C57Bl/Ks-db + / + m (db/db) mice. The experiment was carried out on 10 4-month-old male db/db mice and 10 male wild-type control mice, using stimulation electroneuromyography to assess M-wave parameters for m. gastrocnemius and m. biceps brachii . We discovered a decrease in maximal amplitudes along with an increase in the M-wave latency and duration, indicating the presence of combined axonal and demyelinating peripheral nerve injury.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"2012 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135483234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. V. Safronenko, O. M. Kudelina, E. V. Gantsgorn, M. Kh.-B. Buraeva, M. Kh.-B. Buraeva, A. A. Miteneva, L. R. Shvelidze, D. A. Kalmykova, A. A. Ilyina, V. Z. Lachinov
{"title":"Modern Views and Analysis of Promising Approaches to the Treatment of Melanoma","authors":"A. V. Safronenko, O. M. Kudelina, E. V. Gantsgorn, M. Kh.-B. Buraeva, M. Kh.-B. Buraeva, A. A. Miteneva, L. R. Shvelidze, D. A. Kalmykova, A. A. Ilyina, V. Z. Lachinov","doi":"10.33647/2074-5982-19-3-47-52","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-47-52","url":null,"abstract":"Melanoma is a malignant tumor that can rapidly develop resistance to treatment because of its high mutational activity. The introduction of tyrosine kinase receptor inhibitors (BRAF, MEK) and cytotoxic T lymphocyte antigen/receptor inhibitors (CTLA4, PD-1) into clinical practice has led to an increase in patient survival rates. In in vitro studies, combining PIK3 and MEK inhibitors demonstrate a pronounced reduction in tumor cell growth. The phenomenon of synthetic lethality is also promising, allowing the high mutational load of melanoma to be used as a tool for the development of more effective drugs.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135484107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Food Preferences of Captive Siberian Musk Deer — a Producer of Pharmaceutical Raw Materials","authors":"A. M. Zubalii, M. M. Guseva","doi":"10.33647/2074-5982-19-3-10-16","DOIUrl":"https://doi.org/10.33647/2074-5982-19-3-10-16","url":null,"abstract":"Under the conditions of captivity, adequate and balanced feeding becomes a determining factor in the safety of musk deer, contributing to maintaining the health of animals and their reproductive functions and increasing the productivity of deer musk. In this work, the nutrition patterns of Siberian musk deer in the winter period are established. The animals are kept in the nursery of the Altai Branch of the Scientific Center of Biomedical Technologies of FMBA of Russia. The most preferred feed types in the winter diet were found to include (on average, g/head per day): wood lichens Usnea spp. — 290; Betula spp. — 70; Urtica spp. — 80; oatmeal — 70). The nutritional indicators of the identified feed objects were determined. The content of metabolizable energy and nutrients in the daily diet consumed by musk deer was calculated. Thus, one individual consumes 520 g of natural moisture feed or 453 g of dry matter, which contains 3.57 MJ of metabolizable energy per day. The obtained data form a scientific basis for developing feeding diets for captive musk deer.","PeriodicalId":40514,"journal":{"name":"Avances en Biomedicina","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135483987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}