Pharmacological Support Research Articles

ВЛИЯНИЕ ИНТЕНСИВНЫХ ФИЗИЧЕСКИХ НАГРУЗОК НА АНТИОКСИДАНТНУЮ СИСТЕМУ И МЕРЫ ЕЕ ФАРМАКОЛОГИЧЕСКОГО ПРЕДУПРЕЖДЕНИЯ

The article discusses the effect of increased physical activity on the antioxidant system of the body, the mechanisms of formation of free radicals, their physiological role and pathological effects. During intense physical activity, reactive oxygen species are activated in the human body. Reactive oxygen species can lead to the development of pathological processes, which in turn adversely affects athletic performance. Excessive loads that initiate the activation of free radical oxidation carry the risk of activation of degenerative and dystrophic processes in various body systems. This leads to frequent diseases of the cardiovascular system, respiratory system, as well as injuries. To maintain physical performance during the competitive period and prevent excessive formation of reactive oxygen species, antioxidants are included in the pharmacological support of athletes.

Focus on host/organ unregulated response: a common cause of critical illness.

Focus on host/organ unregulated response: a common cause of critical illness.

THE EFFECT OF GREEN TEA POLYPHENOLS ON THE CHANGE IN THE MITOCHONDRIAL FUNCTION OF HIPPOCAMPAL CELLS IN A DEFICIENCY IN THE ACTIVITY OF MITOCHONDRIAL COMPLEX IV

The aim of the study was to evaluate the effect of green tea polyphenols on changes in the mitochondrial function in conditions of cerebrospecific blockade of mitochondrial complex IV activity. Materials and methods. Male Wistar rats were used in the work, in which the deficiency of mitochondrial complex IV activity was reproduced by direct injection of a 3M sodium azide solution into the hippocampal tissue. Green tea polyphenols and the reference drug ethylmethylhydroxypyridine succinate were administered at the dose of 100 mg/ kg, orally, for 30 days. Subsequently, changes in cognitive deficits in the Y-shaped maze test, the activity of succinate dehydrogenase and cytochrome-c-oxidase in hippocampal tissue were evaluated in rats. Results and their discussion. It was found that in animals without pharmacological support, when sodium azide was administered, there was a decrease in the activity of succinate dehydrogenase and cytochrome-c-oxidase by 29.2% (p < 0.05) and 78.8% (p < 0.05) with a deterioration in the rats' cognitive abilities by 47.6% (p < 0.05). the use of the reference drug and green tea polyphenols increased the activity of succinate dehydrogenase by 30.5% (p < 0.05) and 24.1% (p < 0.05), as well as that of cytochrome c oxidase by 20.9% (p < 0.05) and 56.0% (p < 0.05), respectively. the cognitive deficit in animals which received ethylmethylhydroxypyridine succinate and green tea polyphenols was significantly lower than that in untreated animals. Conclusions. Against the background of sodium azide introduction into the hippocampal tissue of animals, the development of cognitive deficits with a decrease in the activity of succinate dehydrogenase and cytochrome c oxidase is observed. a course administration of green tea polyphenols and a reference drug increased the activity of succinate dehydrogenase and cytochrome-c-oxidase, which contributed to the restoration of cognitive abilities in animals.

Possibilities of regulating the reaction of tissues of the implantation area with pyrimidine preparations after prosthetic repair of the hernia ring in the experiment

Purpose of the study. Study of the possibilities of pharmacological regulation of local and systemic inflammatory response, stimulation of reparative regeneration in prosthetic repair of abdominal wall hernias.Materials and methods. The experiment was carried out on 92 rats of both sexes of a pure line, divided into 4 groups. Group I (control) received only 1 ml of 0.9 % sodium chloride solution. Group II – hydroxyethyldimethyldihydropyrimidine 21 mg/day. Group III – potassium orotate 10.5 mg/day. Group IV – methyluracil 14 mg/day. Under anesthesia a mesh implant 4 × 2 cm was placed in the layer between the hypodermis and the superficial fascia. Animals were withdrawn from the experiment on days 5 (n = 52) and 14 days (n = 40). The site of implantation for histomorphometric studies captured the dermis, hypodermis, implant layer, fascia, and muscle. The preparation and staining of the preparations were carried out with hematoxylin-eosin and by Mallory.Results. 1. On the 5th day after the operation group II (hydroxyethyldimethyldihydropyrimidine) was characterized by pronounced neovasculogenesis (p = 0.002, U-test) and more active processes of formation and maturation of connective tissue (p = 0.024, U-test) with a low immune response to a foreign body (p = 0.044, U- test). III (potassium orotate) and IV groups (methyluracil) were characterized by a pronounced decrease in the inflammatory response with a simultaneous increase in tissue edema (p < 0.001, U-test), slowing down the formation and maturation of connective tissue (p = 0.016, U-test). 2. On the 14th day after the operation, group II (hydroxyethyldimethyldihydropyrimidine) was characterized an increase in the area of neovasculogenesis by 208.0 % (p < 0.001, U -criterion), a decrease in the volume of fluid accumulations by 63.4 % (p < 0.001, U-criterion), an increase in the processes of formation and maturation of connective tissue, mainly due to an increase in the number of fibrocytes by 333.3 % (p < 0.001, U-criterion). The parameters of the immune response to a foreign body had significant differences (p < 0.001, U-test).Conclusion. The use of potassium orotate and methyluracil reduces the inflammatory response in the tissues of the implantation area, however, it is associated with the appearance of liquid components and with a decrease in the formation of connective tissue cells. The use of hydroxyethyldimethyldihydropyrimidine is devoid of the above disadvantages, it is characterized by the predominance of regeneration and neovasculogenesis processes, which allows it to be used as a pharmacological support drug for prosthetic hernioplasty.

Преподавание клинической фармакологии на фармацевтическом факультете Ярославского государственного медицинского университета

The main objectives that arise while teaching future chemists currently include formation of knowledge, abilities and skills of pharmacological support of treatment of diseases that enable effective work aimed at implementation of professional tasks and degree of mastery over labor functions. While teaching clinical pharmacology at the pharmaceutical department, we follow the path of an increased scope of new topics on private matters of the discipline including assessment of effectiveness and safety of medicinal preparations taking into account adverse reactions, issues of pharmacoeconomics, pharmacoepidemiology and provisions of evidence-based medicine. In Russian medicine, it is common to adhere to the principle that moral standards are interwoven into clinical practice. This principle is followed during teaching. Proper management of the educational process will enable students to independently work with literature, critically assess new data and continuously improve their professionalism in future.

Профессиональная этика фармацевтических работников

Professional activity in the sphere of pharmacological support means compliance with moral and ethical standards while fulfillment of labor functions by pharmaceutical professionals. The study purpose was to examine requirements for compliance with ethics and deontology placed on pharmaceutical professionals who carry out their professional activity. Study methods: content analysis, sociological survey, comparative analysis, mathematical and statistical methods, and ranking. Study materials: federal laws, orders of the Ministry of Health of the Russian Federation, occupational standards of pharmaceutical professionals, data from questionnaires of 95 pharmaceutical professionals. The performed analysis of regulatory documentation that regulates compliance with ethics and deontology by pharmaceutical professionals, examination of opinions of pharmaceutical professionals about the functions performed by them, identification of knowledge of those interviewed about constituents of ethics and deontology along with labor functions, fulfillment of which requires compliance with moral and ethical standards, displayed the necessity to improve knowledge and skills in the field of ethics and deontology at all educational levels.

The effectiveness of skilled breathing and relaxation techniques during antenatal education on maternal and neonatal outcomes: a systematic review

BackgroundSeveral studies have investigated the relationship between antenatal education classes and pregnancy outcomes. These studies have shown positive effects on mothers, such as a lower epidural rate in the intervention groups. However, until now, the impact on outcomes for mothers and newborns of antenatal education classes that focus on breathing and relaxation techniques has not been examined.AimInvestigate the effects of skilled breathing and relaxation techniques provided in antenatal education classes on maternal and neonatal birth outcomes.MethodsThe protocol for this study was registered with PROSPERO (ID: CRD42020192289). A systematic literature search was undertaken and completed in January 2022, using the databases MEDLINE, CINAHL, clinicalTrials.gov, Cochrane Library, Embase and MIDIRS according to a priori formulated PICO criteria: population (pregnant women), intervention (antenatal education classes with integrated breathing and relaxation techniques), comparison (antenatal education classes that do not include skilled breathing and relaxation techniques), and outcome (maternal and neonatal outcomes). The quality of the studies was assessed by two reviewers using the standardised instruments RoB 2 and ROBINS-I.ResultsTen studies were included in this review, nine randomised controlled trials and one quasi-experimental study. The results indicate that skilled breathing and relaxation techniques may positively influence self-efficacy, the need for pharmacological support, specifically the use of epidural anaesthesia, and the memory of labour pain. No effects were found in relation to predefined neonatal outcomes. The quality of evidence on maternal and neonatal outcomes is inconsistent across studies, as different antenatal education classes with varying interventions, including breathing and relaxation techniques, were offered in the studies.ConclusionsWomen who attended an antenatal education class with breathing and relaxation techniques appear to benefit from the intervention. This applies to the practical implementation and use of breathing and relaxation techniques during labour, increased self-confidence and self-efficacy, and a increased feeling of being in control during labour. This demonstrates the importance of information provision and a focus on breathing and relaxation techniques in antenatal education.

Five-Year Outcomes in Patients With Fully Magnetically Levitated vs Axial-Flow Left Ventricular Assist Devices in the MOMENTUM 3 Randomized Trial

Although durable left ventricular assist device (LVAD) therapy has emerged as an important treatment option for patients with advanced heart failure refractory to pharmacological support, outcomes, including survival, beyond 2 years remain poorly characterized. To report the composite end point of survival to transplant, recovery, or LVAD support free of debilitating stroke (Modified Rankin Scale score >3) or reoperation to replace the pump 5 years after the implant in participants who received the fully magnetically levitated centrifugal-flow HeartMate 3 or axial-flow HeartMate II LVAD in the MOMENTUM 3 randomized trial and were still receiving LVAD therapy at the 2-year follow-up. This observational study was a 5-year follow-up of the MOMENTUM 3 trial, conducted in 69 US centers, that demonstrated superiority of the centrifugal-flow LVAD to the axial-flow pump with respect to survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump at 2 years. A total of 295 patients were enrolled between June 2019 to April 2021 in the extended-phase study, with 5-year follow-up completed in September 2021. Of 1020 patients in the investigational device exemption per-protocol population, 536 were still receiving LVAD support at 2 years, of whom 289 received the centrifugal-flow pump and 247 received the axial-flow pump. There were 10 end points evaluated at 5 years in the per-protocol population, including a composite of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump between the centrifugal-flow and axial-flow pump groups and overall survival between the 2 groups. A total of 477 patients (295 enrolled and 182 provided limited data) of 536 patients still receiving LVAD support at 2 years contributed to the extended-phase analysis (median age, 62 y; 86 [18%] women). The 5-year Kaplan-Meier estimate of survival to transplant, recovery, or LVAD support free of debilitating stroke or reoperation to replace the pump in the centrifugal-flow vs axial-flow group was 54.0% vs 29.7% (hazard ratio, 0.55 [95% CI, 0.45-0.67]; P < .001). Overall Kaplan-Meier survival was 58.4% in the centrifugal-flow group vs 43.7% in the axial-flow group (hazard ratio, 0.72 [95% CI, 0.58-0.89]; P = .003). Serious adverse events of stroke, bleeding, and pump thrombosis were less frequent in the centrifugal-flow pump group. In this observational follow-up study of patients from the MOMENTUM 3 randomized trial, per-protocol analyses found that receipt of a fully magnetically levitated centrifugal-flow LVAD vs axial-flow LVAD was associated with a better composite outcome and higher likelihood of overall survival at 5 years. These findings support the use of the fully magnetically levitated LVAD. ClinicalTrials.gov Identifier: NCT02224755 and NCT03982979.

Metabolic effects of 3-substituted chromone derivatives in experimental chronic traumatic encephalopathy

Aim to evaluate the effect of five new 3-substituted chromone derivatives on changes in mitochondrial function and the development of tau pathology in animals under experimental chronic traumatic encephalopathy.&#x0D; Material and methods. Chronic traumatic encephalopathy was modeled in Wistar rats by repeated exposure to a shock wave (2 atm.) on the animal's head for seven days. The studied compounds (X3A1 X3A5) and the reference citicoline were administered 60 minutes after injury at doses of 40 mg/kg and 150 mg/kg orally. On the eighth day of the experiment, changes in the mass coefficient of the brain, the concentration of phosphorylated tau protein in brain tissue and changes in the activity of cytochrome-c-oxidase and succinate dehyrogenase were evaluated in animals.&#x0D; Results. The use of compounds X3A4 and X3A5 equally to citicoline reduced the development of tau pathology, increased the activity of mitochondrial enzymes: cytochrome-c-oxidase by 14.5% (p0.05), 41.9% (p0.05) and 22.6% (p0.05), respectively; succinate dehydrogenase by 28.6% (p0.05); 33.2% (p0.05) and 22.8% (p0.05), respectively. As a result, against the background of the administration of these compounds, an increase in brain mass coefficient was noted in relation to the animals that did not receive a pharmacological support.&#x0D; Conclusion. Administration of chromone derivatives X3A4 and X3A5 to animals with experimental chronic traumatic encephalopathy prevents the development of tau pathology and atrophy of brain tissue, probably due to metabolic action, expressed in the restoration of mitochondrial function.

The hydroethanolic root extract of Psydrax subcordata (DC.) Bridson exhibits antinociceptive and anti-inflammatory effects in animal models

Psydrax subcordata (DC.) Bridson (Rubiaceae) is traditionally used to treat pain and inflammatory conditions in Ghana. There is, however, little scientific evidence to support its use in Ghanaian Traditional Medicine. This study, therefore, evaluated the antinociceptive and anti-inflammatory effects of hydroethanolic root extract of Psydrax subcordata (PSRE) using rodent models. Acute toxicity of PSRE was assessed in the Irwin's test. The antinociceptive effect was evaluated in the acetic acid-induced writhing and formalin-induced nociception tests. Xylene-induced ear oedema test and cotton pellet-induced granuloma models were used to assess the ameliorative effects of PSRE in acute and subacute inflammation. Effect of PSRE on tissue integrity in xylene-induced inflammation was also evaluated by histological examination. Oral treatment of PSRE up to the dose of 5000 mg kg−1 did not produce any lethal effect in mice. Oral PSRE (30–300 mg kg−1) significantly (at least P < 0.01) attenuated nociception in both acetic acid-induced writhing and formalin-induced nociception tests. In the xylene-induced ear oedema test, PSRE decreased acute inflammation dose-dependently. The extract also attenuated transudate and exudate formation in the cotton pellet-induced granuloma test. The findings show that hydroethanolic root extract of Psydrax subcordata possesses antinociceptive and anti-inflammatory properties in rodents. The study provides pharmacological support for the traditional use of the plant in the management of pain and inflammatory conditions.

Mechanisms of the Traditional Chinese Herb Atractylodes lancea against COVID-19 Based on Network Pharmacology and Molecular Docking

Atractylodes lancea (Thunb.) DC. (AL) has been proven to be effective in the treatment of coronavirus disease 2019 (COVID-19). In this study, TCMSP, TCMID, OMIM, GeneCards, PharmMapper and SwissTargetPrediction were used to collect potential targets for AL against COVID-19. The online STRING analysis platform and Cytoscape were used for generating a (protein-protein interaction) PPI network. The Cytoscape and Autodock software were used for determining hub genes and key compounds. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via DAVID database. A total of 84 common targets were obtained. The antiviral pathways were main pathways in traetment. 10 hub genes and key compounds were screened by CytoHubba. We found that AL2, AL6 and AL38 had lower binding energy with key proteins. Our study demonstrated that AL might be used to treat COVID-19 by improving the "cytokine storm", regulating some antiviral pathways, and inhibiting the key protein through which the SARS-CoV-2 invades the host cell. These findings give a pharmacological basis and support for treating COVID-19 with AL.

Discussing Questions of Laser Refractive Surgery in Hyperopia: Literature Review and Clinical Experience

Relevance. Modern keratorefractive surgery is a high-tech field of ophthalmology aimed at solving various problems of correcting a wide range of ametropias.Objective: to formulate recommendations for refractive surgeons when planning the correction of hypermetropic refraction using modern keratorefractive surgery.Materials and methods. An analysis of 20 literature sources and a retrospective analysis of outpatient records of 188 patients with hypermetropia who underwent surgery were carried out.Results. The analysis of the literature and our own clinical study allows us to recommend focusing on the final keratometry after keratorefractive surgery, which should not exceed 48 diopters. Among the analyzed charts of patients in compliance with these criteria, the accuracy of hitting the target refraction in the range of ± 1 D was 98.9 %, the regression did not exceed 0.5 D from that obtained 1 month after surgery in 96.8 %, and the loss of 1 line of BCVA was 3.7 % of cases. Among patients with achieved keratometry above 48 diopters, the loss of line 1 BCVA was 13.8 %, line 2 — 2.7 %.Conclusion. Thus, the tactics of correction of hypermetropia by CRC methods require an integrated approach to the assessment of visual functions, drug preparation for surgery, careful implementation of the surgical stages of the intervention, and rational postoperative pharmacological support.

Exposure–response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations

PurposeTepotinib is a highly selective MET inhibitor approved for treatment of non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Analyses presented herein evaluated the relationship between tepotinib exposure, and efficacy and safety outcomes.MethodsExposure–efficacy analyses included data from an ongoing phase 2 study (VISION) investigating 500 mg/day tepotinib in NSCLC harboring METex14 skipping alterations. Efficacy endpoints included objective response, duration of response, and progression-free survival. Exposure–safety analyses included data from VISION, plus four completed studies in advanced solid tumors/hepatocellular carcinoma (30–1400 mg). Safety endpoints included edema, serum albumin, creatinine, amylase, lipase, alanine aminotransferase, aspartate aminotransferase, and QT interval corrected using Fridericia’s method (QTcF).ResultsTepotinib exhibited flat exposure–efficacy relationships for all endpoints within the exposure range observed with 500 mg/day. Tepotinib also exhibited flat exposure–safety relationships for all endpoints within the exposure range observed with 30–1400 mg doses. Edema is the most frequently reported adverse event and the most frequent cause of tepotinib dose reductions and interruptions; however, the effect plateaued at low exposures. Concentration-QTc analyses using data from 30 to 1400 mg tepotinib resulted in the upper bounds of the 90% confidence interval being less than 10 ms for the mean exposures at the therapeutic (500 mg) and supratherapeutic (1000 mg) doses.ConclusionsThese analyses provide important quantitative pharmacologic support for benefit/risk assessment of the 500 mg/day dosage of tepotinib as being appropriate for the treatment of NSCLC harboring METex14 skipping alterations.Registration NumbersNCT01014936, NCT01832506, NCT01988493, NCT02115373, NCT02864992.

Efficacy Evaluation for Application of Pharmacological Complexes with Indications on Fatigue Prevention

An urgent task today is the formation of scientific approaches to the creation of a system to assess the effectiveness of medical technologies in sports medicine, taking into account the increased requirements not only in assessing their safety, but also with the mandatory analysis of their impact on the parameters of functional readiness of the athlete. We conducted the study using a comprehensive methodological approach developed in terms of the possibility of its application in case of mono-factorial exposure (means of pharmacological support). Aim. To determine the effectiveness of pharmacological agent’s complexes indicated for use in the prevention of fatigue by their effect on physical performance and psycho-emotional state of persons professionally engaged in sports. Material and methods. We performed a retrospective analysis of 30 athletes involved in skiing sports (biathlon, cross-country skiing and cross-country skiing) and evaluated the efficacy of two combinations of pharmacological agents not included in the WADA banned list, indicated for the prevention of fatigue, compared with placebo. Functional state of the athletes was estimated on the 7th and 15th days according to the parameters of endurance testing on the “Norwegian” protocol “until failure”, 5 loading steps, psychoemotional state (hardware-software complex “Diamed-MBS”, psychological status (Lusher test, WAM, Mini-Mult) on the 7th and 15th days. We analyzed the dynamics of general and biochemical blood tests, general urinalysis. Results and discussion. Load time before failure, the main indicator characterizing the success of the athlete’s professional activity, did not differ in all three groups when testing the background values, on the 7th and 15th days of the study, but consistently increased from the beginning to the end of the experiment. On the 15th day, 15 the time of specific load “to failure” in all three groups differed from the corresponding background values (p &lt;0.05) due to the training effect. Application of the evaluated drugs had no effect on the level of IPC index in all three groups, but it tended to increase by the end of the experiment due to the trained athletes. The use of the drugs had no effect on the psycho-emotional and psychological state in all groups under study and at all testing points. Conclusion. Evaluation of the sports medicine technologies effectiveness should be carried out taking into account the requirements for their impact on the functional readiness of athletes, determining the success of professional activity. The studies have revealed no influence of the course application of the schemes of pharmacological agents of GCS and GCM against the background of the standard training program and periodic submaximal physical activity on the functional capabilities of the athletes’ organisms. The possibility of using the developed methodological approach to evaluate the effectiveness of sports medicine technologies based on monofactorial effects is shown, using the example of approved pharmacological agents indicated for reducing fatigue.

Integrated RNA-sequencing and network pharmacology approach reveals the protection of Yiqi Huoxue formula against idiopathic pulmonary fibrosis by interfering with core transcription factors

BackgroundIdiopathic pulmonary fibrosis (IPF) is a refractory disease. Therefore, developing effective therapies for IPF is the need of the hour. PurposeYiqi Huoxue Formula (YQHX) is an herbal formula comprising three herbal medicines: Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, CR), Panax notoginseng (Burk.) F. H. Chen (Notoginseng Radix Et Rhizoma, NR) and Panax ginseng C. A. Mey. (Ginseng Radix Et Rhizoma, GR). This study aims to determine the anti-pulmonary fibrosis effect of YQHX and explore its mechanism of action. StudyDesign and Methods: The chemical components in the GR, CR and NR extracts were identified by High Performance Liquid Chromatography. A TGF-β1-induced myofibroblast cell model was used to test the anti-fibrosis effect of GR, CR, NR and YQHX. RNA-sequencing was used to identify the differentially expressed genes (DEGs) after YQHX treatment. Subsequently, gene enrichment analysis and key transcription factors (TFs) prediction for YQHX-regulated DEGs was performed. The active constituents of GR, CR and NR were obtained from the Traditional Chinese Medicine Database and Analysis Platform. Targets of the active constituents were predicted using the similarity ensemble approach search server and Swiss Target Prediction tool. YQHX-targeted key TFs that transcribed the DEGs were screened out. Then, the effect of YQHX on the bleomycin-induced pulmonary fibrosis mouse model was studied. Finally, one of the predicted TFs, STAT3, was selected to validate the prediction accuracy. ResultsSeven, two, and five compounds were identified in the GR, CR, and NR extracts, respectively. YQHX and its constituents-GR, CR and NR-inhibited the expression of fibrotic markers, including α -SMA and fibronectin, indicating that YQHX inhibited TGF-β1-induced myofibroblast activation. RNA-sequencing identified 291 genes that were up-regulated in the TGF-β1 group but down-regulated after YQHX treatment. In total, 55 key TFs that transcribed YQHX-regulated targets were predicted. A regulatory network of 24 active ingredients and 232 corresponding targets for YQHX was established. Among YQHX's predicted targets, 20 were TFs. On overlapping YQHX-targeted TFs and DEGs’ key TFs, six key TFs, including HIF1A, STAT6, STAT3, PPARA, DDIT3 and AR, were identified as the targets of YQHX. Additionally, YQHX alleviated bleomycin-induced pulmonary fibrosis in a mouse model by inhibiting the phosphorylation of STAT3 in the lungs of pulmonary fibrosis mice. ConclusionsThis study provides pharmacological support for the use of YQHX in the treatment of IPF. The potential mechanism of action of YQHX is speculated to involve the modulation of core TFs and inhibition of pathogenetic gene expressions in IPF.

Pharmacological Regulation of the Inflammatory Response under Mesh Implant Prosthetics in the Treatment of Patients with External Abdominal Hernias

Introduction. Seromas and hematomas of the implantation area are among the most common complications in prosthetic repair of a hernia defect with a mesh implant. The adequate tissue inflammation response to prosthesis implantation is achieved by the local protective role of pro-inflammatory cytokines. With suppression of the body's immune system combined with existing comorbidities, mesh implants result in even greater suppression of the immune system, which is manifested by an inadequate inflammatory response, both local and systemic, leading to the development of complications.Previously, the authors studied the effect of pyrimidine preparation "Xymedon" (INN - hydroxyethyldimethyldihydropyrimidine) on the systemic inflammatory process after prosthetic repair of anterior abdominal wall hernias. Based on the results of the interim study, it was hypothised: Regulation of the inflammation response to prosthesis implantation in hernioplasty manifested by changes in cytokine concentration in the blood can reduce postoperative complications. The aim of the study was to reduce the number of postoperative complications in prosthetic hernioplasty by regulating inflammatory reactions that occur after mesh implants.Materials and methods. Experimental part of the study. The experiment involved 66 rats, both sexes, pure line, which were implanted with mesh prostheses. Animals in group I (n=33) the control one - received 1 ml of 0,9% sodium chloride solution, i.e. received no specific treatment. Animals in group II (n=33) - the main one - received "Ximedon" 21 mg/day as pharmacological support. Blood sampling to determine inflammation markers was performed on the 5th day after the intervention. Animals were withdrawn from the experiment and the implantation site was taken for histological and histomorphometric investigations on the 5th day of the study. The study was carried out in the SPF vivarium at the laboratory of the Center for Genetic Collections of Laboratory Animals, Lobachevsky State University of Nizhny Novgorod. The study consisted of 4 series of experiments (2018-2021). Clinical part of the study. Prospectively (2018 - February 2022), we analyzed clinical outcomes of 101 patients with prosthetic repair (by Liechtenstein, TAPP, eTAR, "sublay") of an aponeurosis hernia defect of the anterior abdominal wall who received treatment in the City Clinical Hospital №7 named after E.L. Berezow. Patients of the "control" group (n=33) received only conventional treatment; patients of the "Ximedon" group (n=68) received 0.5 mg of ximedon 3 times a day for 10 days orally from the first day after the operation. Blood sampling was carried out on the 5th day after surgery. The data obtained were processed and structured using Microsoft Excel 2019 (64 bit), and statistical values were calculated in StatSoft Statistica 12,5 (64 bit).Results. Xymedon has a significant effect on the increase in the area of ​​the vessels of the implantation area in the experiment. Its use is associated with a lower level of C-reactive protein and blood IL-6 on day 5 in the experimental group compared to the control group. In the clinical study ximedon has a significant effect on the cytokine concentration in the blood: C-reactive protein, TNF-a, interleukins 6, 8 and 10. In the experimental study the dynamic of C-reactive protein, blood interleukins 6 and 10 does not significantly differ from the clinical one. In the clinical study, xymedon intake was associated with fewer postoperative complications. Conclusion. The studies performed allow us to consider "ximedon" as a means of pharmacological support for prosthetic repair in external abdominal hernias due to a significant reduction in postoperative complications provided by the ability to regulate inflammation reactions and stimulate reparative regeneration.

Interventions for the prevention of adrenal crisis in adults with primary adrenal insufficiency: a systematic review.

ObjectiveThe incidence of adrenal crisis (AC) remains high, particularly for people with primary adrenal insufficiency, despite the introduction of behavioural interventions. The present study aimed to identify and evaluate available evidence of interventions aiming to prevent AC in primary adrenal insufficiency.DesignThis study is a systematic review of the literature and theoretical mapping.MethodsMEDLINE, MEDLINE in Process, EMBASE, ERIC, Cochrane CENTRAL, CINAHL, PsycINFO, the Health Management Information Consortium and trial registries were searched from inception to November 2021. Three reviewers independently selected studies and extracted data. Two reviewers appraised the studies for the risk of bias.ResultsSeven observational or mixed methods studies were identified where interventions were designed to prevent AC in adrenal insufficiency. Patient education was the focus of all interventions and utilised the same two behaviour change techniques, ‘instruction on how to perform a behaviour’ and ‘pharmacological support’. Barrier and facilitator themes aiding or hindering the intervention included knowledge, behaviour, emotions, skills, social influences and environmental context and resources. Most studies did not measure effectiveness, and assessment of knowledge varied across studies. The study quality was moderate.ConclusionThis is an emerging field with limited studies available. Further research is required in relation to the development and assessment of different behaviour change interventions to prevent AC.

Ekbom syndrome: a case report

IntroductionEkbom syndrome is a clinical term for delusional parasitosis, a condition characterized by the belief that one’s skin is infested by invisible parasites. Despite having no medical evidence, patients strive to prove their illness and interpret different sensations and symptoms as infestation with parasites.ObjectivesOur objective was to present a case report of a patient with Ekbom syndrome with detailed clinical information and treatment complications.MethodsWe included patient’s history, psychiatric evaluation, complete diagnostic work-up, therapy and follow-up.ResultsA 60-years old female patient was admitted to her first hospital treatment in our psychiatric clinic. Upon admittance, she was extremely tense, preoccupied with the idea that bed bugs have infested her body. She showed extensive medical documentation, including numerous dermatologic reports regarding her condition, interpreting them in accordance with her delusions. In attempt to help herself and “release” the bugs, she harmed herself causing multiple skin lesions across her body and face. The treatment was complicated with secondary skin infections, ulcers, cellulitis and oedemas. Initial treatment with olanzapine was switched to risperidone due to side-effects (sedation, increase of appetite, weight gain). Gradually, with pharmacological treatment, psychoeducation and support, remission was achieved, but poor insight to her previous condition and psychiatric symptoms remained.ConclusionsEkbom syndrome presents a serious disorder that can be complicated with secondary somatic complications, often requiring involvement of different medical specialists. Moreover, lack of insight into the need for psychiatric treatment can lead to therapy discontinuation and relapse of symptoms.DisclosureNo significant relationships.

Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients.

OBJECTIVES:To evaluate safety and clinical outcomes of extracorporeal immunomodulation treatment with a selective cytopheretic device (SCD) in COVID-19 ICU patients with multiple organ failure.DESIGN:Two-center, prospective, single-arm treatment clinical trial.SETTING:ICUs at two academic medical centers between September 2020 and July 2021.PATIENTS:Twenty-two COVID-10 patients in the ICU with acute respiratory distress syndrome who required mechanical ventilation. Nearly all included patients in the intervention group except one had acute kidney injury requiring continuous renal replacement therapy (CRRT). Sixteen subjects meeting enrollment criteria were selected as contemporaneous controls from a concurrent prospective registry CRRT trial.INTERVENTION:Treatment with an SCD integrated into a continuous renal replacement extracorporeal blood circuit for up to 10 days to provide autologous leukocyte cell processing to immunomodulate the hyperinflammatory disease state of COVID-19.MEASUREMENTS AND MAIN RESULTS:SCD treatment in COVID-19 ICU patients with multiple organ failure demonstrated an acceptable safety profile with no device-related serious adverse events. Treatment of these patients resulted in the selective removal of highly activated circulating leukocytes as determined by flow cytometry. Significant reductions were observed in the elevated plasma levels of eight cytokines and biomarkers, including interleukin (IL)6, IL15, IL10, and soluble ST2, which are predictive of mortality in COVID-19 patients. Significant improvements of leukocytosis and Po2/Fio2 ratios occurred during treatment not observed in the control group. SCD-treated subjects had a reduction in 60-day mortality of 50% compared with 81% in the control cohort. The subjects who received greater than 96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (p < 0.012).CONCLUSIONS:Extracorporeal immunomodulation therapy with an SCD demonstrated safety without any device-related serious adverse events. As a rescue therapy in COVID-19 ICU patients progressing to multiple organ failure despite maximal pharmacologic and organ support interventions, SCD treatment resulted in improved clinical outcomes. This autologous leukocyte cell processing technology may provide a new approach in the treatment of unremitting hyperinflammation of COVID-19.

The Role of Perioperative Levosimendan in Patients with Reduced Ejection Fraction undergoing Cardiac surgery in Reducing Post-operative Hemodynamic Support

BACKGROUND: Acute perioperative left ventricular dysfunction is a major complication affecting patients subjected to cardiac surgery and is associated with increased mortality. Levosimendan as a “calcium sensitizers” with inodilator effect improves myocardial contractility by sensitizing troponin C to calcium without increasing myocardial oxygen consumption and without impairing relaxation and diastolic function. AIM: The aim of this study was to evaluate the effect of perioperative levosimendan compared to the conventional management used in the patient with poor left ventricular function undergoing cardiac surgery to reduce the need of post-operative pharmacological and mechanical circulatory support. METHODS: It is prospective observational studies were patients undergoing cardiac surgery divided into two groups of 25 patients each. The first group received conventional management while the other group received levosimendan additionally duration and type of post-operative pharmacological support, duration of mechanical ventilation, durations of ICU and hospital stays, and major outcomes, and data about the need of mechanical support were collected. RESULTS: In the levosimendan, fewer patients required vasoactive agents post-surgery (Noradrenaline) compared to the conventional group, yet the use of inotropic support (adrenaline) in the 2nd day and the need of mechanical circulatory support was equal in both groups. The mortality was equal in both groups. CONCLUSION: Perioperative levosimendan may reduce the need of vasoactive agents postoperatively, but it does not reduce the need of inotropic nor mechanical support.