Quality of life of patients with non-alcoholic fatty liver disease with different thyroid status

The aim. To study the quality of life and psychoemotional state of patients with non-alcoholic fatty liver disease against the background of primary hypothyroidism during the use of ethylmethylhydroxypyridine succinate.Materials and methods. 111 patients with non-alcoholic fatty liver were examined, among them 35 were without thyroid dysfunction, 55 with compensated primary hypothyroidism, 21 with decompensated hypothyroidism. The patients underwent general clinical, biochemical, enzyme-linked immunosorbent assays of blood, instrumental studies, testing according to psychological questionnaires.Results. With decompensation of hypothyroidism, a statistically significant increase in indicators of depression, situational and personal anxiety was revealed in comparison with patients without hypothyroidism. The examined patients showed an increase in the level of situational and personal anxiety. The presence of hypothyroidism in the examined patients significantly worsens these indicators, leading to an increase in the degree of anxiety, aggravated by decompensation of hypothyroidism. A positive dynamic was revealed in the correction of the psychoemotional status of patients in the observation group during the complex treatment with ethylmethylhydroxypyridine succinate: the severity of depression, situational and personal anxiety, manifestations of dyspeptic and reflux syndromes decreased.Conclusion. Hypothyroidism affects the quality of life and psycho-emotional state of patients with non-alcoholic fatty liver disease: it worsens the degree of depression, situational and personal anxiety. The addition of ethylmethylhydroxypyridine succinate to standard therapy with sodium levothyroxine in patients with non-alcoholic fatty liver disease in the setting of hypothyroidism improves the quality of life and psycho-emotional state.

LABOUR CONDITIONS AND POSSIBILITY OF APPLICATION OF ETHYLMETHYLHYDROXYPYRIDINE SUCCINATE IN WORKERS EXPOSED TO FIBROGENIC SILICATE DUST

Labour conditions of workers contacting with fibrogenic silicate dust in isolators’ production were studied. Additional examination included determination of the degree of endothelial disfunction, apoptosis and systemic inflammation. Besides the effect of Ethylmethylhydroxypyridine succinate on these parameters and the lipid profile was evaluated. Atherogenic changes of the lipid profile, moderate endothelial disfunction (level of circulating endotheliocytes is 6,04±1,97*104/l), slight tension of apoptosis (TNF-α 8,11±6,67 pg/ml) and activation of systemic inflammation (C-RP 8,1±4,5 mg/l) were found. Application of Ethylmethylhydroxypyridine succinate led to the partial correction of dyslipidemia and endothelial disfunction without the significant effect on other researching laboratory parameters; significant improvement of respiratory function was noted.

THE EFFECT OF CYTOSTATIC DRUGS ON THROMBOCYTOPOIESIS IN RATS WITH WALKER-256 CARCINOMA

Among malignant neoplasms of women, breast cancer (BC) takes the leading place and is the cause of high mortality and complications. Side effects in the form of anemia, thrombocytopenia, bleeding, etc. often develop during cytostatic therapy, which is the main method of treatment and prevention of further development of the oncological process. In this regard, the problem of reducing side metabolic disorders remains relevant and creates a search field for the use of drugs aimed at stabilizing functions, both at the cellular and organ levels. The aim of the study was to evaluate the effect of cytostatic drugs on thrombocytopoiesis in rats with WALKER-256 carcinoma. The study included 60 rats, which, depending on the type of treatment, were divided into 5 groups. A week after the start of chemotherapy, the greatest increase in the number of platelets was in the presence of liposomal ethylmethylhydroxypyridine succinate. We recorded that the myeloprotective effect was 1/3 better in liposomal ethylmethylhydroxypyridine succinate compared to its non-liposomal form. Therefore, individuals those receiving cytostatic drugs in the treatment of breast cancer need protection from myelopoiesis. In the studies carried out by us, it was shown that oxidative stress occurred in animals against the background of treatment with cytostatics. It was its rapid development that caused damage to the platelet cell membranes. In this regard, we have proposed a drug with a pronounced antioxidant efficacy. The introduction of an antioxidant into the generally accepted standard treatment of a tumor process has made it possible to experimentally select methods for delivering the drug to the targets of damage using liposomal forms. The study obtained data proving the effectiveness of the use of liposomal ethylmethylhydroxypyridine succinate (50 mg / kg), in contrast to its free form, which prevents the development of thrombocytopenia induced by the administration of cytostatic drugs to rats with Walker-256 carcinoma.

Clinical features, pathogenesis and treatment of long-haul COVID‑19 impact on nervous system

The current outbreak of coronavirus SARS-CoV‑2 (COVID-19) has raised great concern worldwide, but its impact on nervous system still needs more investigation. Thirty per cent of symptomatic patients with COVID‑19 will have symptoms that last longer than the typical two weeks, 10 % have symptoms longer than 3 months and this is called ‘long-COVID’. These symptoms affect not only people with severe disease, but also those with milder cases. Many long-haulers experience the same symptoms they had during their initial fight with COVID‑19, such as fatigue, cognitive impairment (or brain fog), difficulty breathing, headache, depression, insomnia and loss of the sense of taste and\or smell. Treatment of those complications with citicoline, ethylmethylhydroxypyridine succinate and vitamin B improves these symptoms in patients but most of them also need cognitive therapy for dehypochondrisation.

Chemotranscriptome analysis of the ethylmethylhydroxypyridine succinate molecule in the context of postgenomic pharmacology

Postgenomic pharmacology deals with the desirable and undesirable effects of drugs in relation to the genome, transcriptome, proteome, and reactome. The transcriptomic activity of ethylmethylhydroxypyridine succinate (EMHPS) has not been previously characterized.Objective: to investigate the dose-dependent effects of EMHPS on the transcription of 12,700 annotated human genes in the neural progenitor cells (NPC.TAK cell line).Material and methods. The paper presents the results of chemotranscriptome analysis of the EMHPS molecule from the point of view of its impact on transcription of the human genome in the NPC.TAK line cells during 24-hour incubation of cells with EMHPS.Results and discussion. The significant dose-dependent effects of EMHPS on transcription (on average, ≥10% transcription changes for each 1 μmol/L of EMHPS) were evaluated for 2,400 of the 12,700 annotated human genes. EMHPS reduced the transcription of groups of the genes that were involved in cell division (n = 226), those in gene expression processes (n = 122), and those in protein synthesis, degradation, and secretion (n = 123). EMHPS increased the transcription of the genes encoding proteins involved in neurotransmission (n = 103) and those in exerting neuroprotective and neurotrophic effects (n = 49).Conclusion. The efficacy of EMHPS may be related to its effect on the transcription of the genes that are involved in neurotransmission and in the showing of neuroprotective and neurotrophic effects.

ANTITROMBOTIC ACTIVITY OF A NEW BENZIMIDAZOLE DERIVATIVE WITH A SPATIALLY DIFFICULT PHENOLIC SUBSTITUTE IN ITS STRUCTURE

The aim of the study was to investigate antithrombogenic properties of compound RU-1144 with previously identified pronounced antiplatelet and antioxidant activities. The thrombosis induced by Ferric chloride (FeCl3) was carried out in rats’ carotid artery, in comparison with the known antiaggregant drugs - acetylsalicylic acid (ASA) and clopidogrel, as well as with the antioxidant preparation - ethylmethylhydroxypyridine succinate (EMHPS).Materials and methods. The antithrombotic activity of compound RU-1144 was studied on the model of the rats with carotid artery thrombosis, induced by the application of 50% ferric chloride (FeCl3), and the Global Thrombosis Test model (the Görög Thrombosis Test). The evaluation of this type of activity was carried out by prolonging the time of a blood clot formation. The studies of the compound RU-1144 effect on the bleeding time parameter were performed in mice. Acetylsalicylic acid, clopidogrel and EMHPS were used as reference drugs.Results. The antithrombotic effect of the RU-1144 substance revealed in the model of arterial thrombosis induced by the application of ferric chloride (FeCl3), exceeded that of both acetylsalicylic acid and clopidogrel by 3.5 times and that of EMHPS by 2.9 times. In the model of the in vitro Global Thrombosis Test (the Görög Thrombosis Test), compound RU-1144 reduced the thrombogenic potential of the blood equally with acetylsalicylic acid and clopidogrel. The assessment of “the bleeding time”, caused by the RU-1144 substance, showed that the prolongation of bleeding was twice as less pronounced than that caused by ASA and clopidogrel.Conclusion. The performed studies demonstrated a pronounced antithrombotic activity of compound RU-1144, which exceeded that of acetylsalicylic acid, clopidogrel and EMHPS, while the ability to prolong the bleeding time was reliably lower than that of reference drugs.Abbreviations: EMHPS-ethylmethylhydroxypyridine succinate; ASA - acetylsalicylic acid.

Chronic cerebral ischemia: review of published works, pathogenetic approaches to therapy

Chronic сеrebral ischemia is one of the leading causes of morbidity, mortality and disability in the Republic of Kazakhstan. According to the data from Ministry of Healthcare of the Republic of Kazakhstan, the overall morbidity of the country’s population due to diseases of the circulatory system registered in health care organizations has increased almost three times from 1998 to 2017 over the past 20 years. According to world publications, on average, the incidence of Chronic сеrebral ischemia in the world is relatively high among the elderly, occurring in two-thirds of people over 65 years of age. It is also observed in 50% of people aged 50 to 65 years and in 25% of people aged 45 to 50 years. Purpose. To review of epidemiological data, risk factors, causes, pathogenetic mechanisms, diagnostic algorithms and principles of treatment of Chronic сеrebral ischemia. Material and methods. The literature review on Chronic сеrebral ischemia data was conducted using the Pubmed search engine in Medline electronic databases from 2009 to 2019. Results and discussion. A total of 45 research papers were included. This review examines epidemiological data, risk factors, causes, pathogenetic mechanisms, diagnostic algorithms and principles of therapy for Chronic сеrebral ischemia disease. In the etiopathogenesis of Chronic сеrebral ischemia, a significant part is played by the combination of risk factors known as vascular comorbidity and being the main cause of deaths. Vascular comorbidity is characterized by the involvement into a single pathological process of all risk factors that form Chronic сеrebral ischemia, which lead to a change in cerebral circulation with hypoxia of the brain substance and a cascade of biochemical changes, and subsequently results in diffuse, multi-focal changes in the brain substance. In a case of comorbidity of the atherosclerotic process with dyslipidemia, narrowing of the lumen of the arteries with an increase in the permeability of their wall membranes can be observed, with further damage to the endothelium, activation of synthesis by leukocytes, platelets, endotheliocytes of chemotaxis factors, kinins, growth factors, with the accumulation of active oxygen, peroxidation with the formation of oxidative stress. Chronic сеrebral ischemia therapy with vascular comorbidity, in which all risk factors are В тексте переправлены стилистические и ортографические ошибки. involved in a single pathological process, provides the prevention of polypragmasia, and the assignment of certain pathogenetic drugs aimed at the same pathogenesis that leads to the formation of Chronic сеrebral ischemia. Conclusion. It is most rational to use an antioxidant/antihypoxant in therapy. Such pathogenetic drugs include antioxidant therapy. Among other antioxidants/antihypoxants used in routine practice, Mexidol (ethylmethylhydroxypyridine succinate) is characterized with the strongest evidence base. Keyword: chronic brain ischemia, chronic cerebral circulatory insufficiency, vascular comorbidity, ethylmethylhydroxypyridine succinate, Mexidol.