Influence of Inosine on Cerebral Hemodynamics in Space Motion Sickness in Experimental Animals.

BACKGROUND: Motion sickness occurs worldwide in healthy individuals regardless of age, ethnicity, or gender. It is an acute disorder; it can also present as a chronic disorder in some individuals. Motion sickness not only includes vomiting and nausea, but also includes other features such as pallor of varying degrees, cold sweating, headache, drowsiness, increased salivation, and cranial pain, which are severe. Some of the other assessment scales can interpret sickness on exposure to virtual or visual stimulation and while travelling in different types of transport. AIM: The aim of our research is to study the effect of the drug on the level of blood flow and vascular reactivity of cerebral vessels when simulating changes in the cerebral circulation in terrestrial conditions characteristic of hypogravity. METHODS: Chronic experiments were performed on non-anesthetized rabbits with large hemispheres, thalamus and hypothalamus were implanted with the needle-platinum electrodes 150 mm in diameter in the cortex, and local blood flow and vascular reactivity were recorded accordingly. Cerebrovascular disturbances were modeled using an MSAOP (motion sickness of animals in the anti-orthostatic position) with an inclined angle of 45° for 2 hours. Local blood flow (BF) was measured in ml/min/100g of tissue by the method of registration of hydrogen clearance. The vasodilator coefficient of reactivity (CrCO2) was calculated by the ratio of BF against the background of inhalation of a mixture of 7% CO2 with air to the initial BF; vasoconstrictor - in relation to BF on the background of inhalation of 100% O2 to the initial BF (CrO2). A series of experiments were carried out with different routes of drug administration: First, inosine was administered intravenously at a dose of 5 mg/kg immediately before the start of SMS modeling, same dose was administered 30 minutes before the start of exposure. As a control, we used the results of experimental animals under similar conditions without the administration of the drugs. RESULTS: Inosine has pronounced protective properties in cerebrovascular disorders on the background of space motion sickness (SMS) modeling, which is manifested by normalization of BF and restoration of compensatory reactions of cerebral vessels. In the mechanism of cerebroprotective action of inosine, it is able to correct the metabolic processes, which play an important role and help increase the compensatory capabilities and functional stability of the cerebrovascular system under gravitational influences. CONCLUSION: When using inosine orally, the effects are more pronounced than when administered intravenously, which should be taken into account when using it for the prevention of cerebrovascular disorders in extreme conditions.

Pathogenetic Correction of the Enteric Insufficiency Syndrome in Patients with Advanced Peritonitis.

INTRODUCTION: Common purulent peritonitis is one of the most formidable complications in abdominal surgery. Evidence of this is the continuing high mortality rate, which according to various authors, ranges from 11% to 83%. According to modern concepts, the leading role in the development and progression of widespread purulent peritonitis is assigned to enteric insufficiency syndrome (EIS), which occurs in 90-100% of cases. AIM: The aim of the study was to improve the treatment outcomes of patients with peritonitis complicated by the development of enteric insufficiency syndrome and also by developing and introducing into clinical practice a complex of therapeutic measures, including the combined use of enterosorption in combination with antioxidant and antihypoxant therapy. MATERIALS AND METHODS: The evaluation of the effectiveness of the proposed complex therapeutic measures was carried out on the basis of a prospective examination of 83 patients (26 men and 57 women) aged 24 to 76 years with diffuse peritonitis with III-IV degree of operational risk for ASA. The comparison group included 37 healthy people aged from 20 to 54 years. All examined patients were divided into two clinical groups. The first clinical group consisted of 67 patients with EI of the first degree and second clinical group comprising 16 patients with II degree EI. Before the operation, a suspension of enterosorbent was preliminarily prepared. Suspension of DS was injected through the inserted probe using a Janet syringe, creating an exposure for 10-15 minutes; and then restored the free outflow of the contents of the probe. After completion of the surgical intervention, in the conditions of the intensive care unit, enterosorption continued to perform every 8 hours (3 times a day). The study was carried out before the operation and in the terms of the 1-3rd and 10-14th days in the postoperative period. Anti-endotoxin antibodies of classes A, M and G (respectively anti-LPS-IgA, anti-LPS-IgM, anti-LPS-IgG) were determined by ELISA. RESULTS: When used in the postoperative period for the treatment of enteric insufficiency with detoxification and antihypoxic therapy according to the developed method, a favorable effect is noted, which is confirmed by an assessment of the state of antiendotoxin immunity associated with the development of bacterial translocation and enterogenic toxemia. CONCLUSION: The use of the proposed intestinal therapy in combination with antioxidant and antihypoxic therapy helps to prevent the progression of endogenous intoxication, through inactivation and effective clearance of toxic metabolites, reducing the effects of hypoxia, which leads to a significant decrease in membrane-destabilizing effects from the intestinal cell structures and leads to a significant decrease in the expressed specific antigen of the immune system and better clinical outcomes.

Tocilizumab in SARS-CoV-2 Patients with the Syndrome of Cytokine Storm: A Narrative Review.

INTRODUCTION: Corona virus is a group of viruses that cause diseases in mammals and birds. In humans, these families of viruses can cause respiratory infections from a mild form to fatal. It is preferably called coronavirus. Formally, it is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) and this disease is called coronavirus disease 2019 (COVID-19). SARS-CoV-2 is infectious in humans and the world health organization has announced COVID-19 as pandemic disease. Tocilizumab is a biological agent that inhibits the cytokine, interleukin 6 (IL-6 inhibitor). As SARS-CoV-2 infection leads to the development of cytokine storm syndrome, the drug, tocilizumab, seems to have a positive effect on patients with COVID-19. AIM: To analyze and review the possible effects and efficacy of the tocilizumab (monoclonal antibody against IL-6 receptors) in SARS-CoV-2 patients. MATERIALS AND METHODS: A search was carried out for all recent review articles, which were used to study the SARS-CoV-2 disease and their characteristics. Furthermore, we have analyzed the most recent research articles on monoclonal antibody against IL-6 receptors (tocilizumab) and their possible clinical effects in COVID-19 and its' clinical trials. RESULTS: COVID-19 is a disease caused by SARS-CoV-2 infection. It is a life threatening condition, which can give rise to fatal outcomes if left untreated. However, there are no approved treatments for COVID-19 globally. Furthermore, we can conclude that SARS-CoV-2 is associated with the worsening of lung conditions, characterized by interstitial pneumonia with acute respiratory distress syndrome as a result of cytokine storm syndrome. According to available research data, tocilizumab, a recombinant humanized anti-human monoclonal antibody of IgG1τ (gamma 1, kappa), can improve patient's condition from cytokine storm syndrome by inhibiting the IL-6 (Interleukin 6) receptors. CONCLUSION: The rational use of the tocilizumab in severe and critically ill COVID-19 patients can prevent the development of irreversible lung injury and death of the patient. Three retrospective studies of Xiaoling Xu et al., Pan luo et al., and Paola Tonaiti et al. have shown the efficacy of tocilizumab in severe and critically ill COVID-19 patients. However, we need more randomized research studies with a significant number of patients which can confirm the promising results on tocilizumab treatment in COVID-19 patients. Moreover, ongoing clinical trails such as TOSCA, COVACTA results have not been published yet which are expected to give better and more significant results on tocilizumab's effectiveness and safety.

Structural and Morphological Changes in the Liver Due to Intestinal Endotoxins.

BACKGROUND: Under normal physiological conditions, endotoxin (ET) released during self-renewal of the colibacillus pool is an obligate stimulus for the formation of the immune system and homeostasis of the body. Violation of the barrier function of the intestinal wall and the mechanisms of neutralization of endotoxin lead to systemic endotoxemia of intestinal origin. Its development is facilitated by stress, intoxication, a decrease in nonspecific resistance of the body, as well as damage to the intestinal mucosa and dysbiosis, where the mucous membrane is more vulnerable and permeable to endotoxin. PURPOSE OF THE RESEARCH: The aim of this study is to compare and assess the severity and nature of hepatocyte damage from endotoxin exposure and the degree of manifestation of stress due to oxidation, to determine the characteristics of structural changes in hepatocytes and to assess the oxidation stress during endotoxin intoxication in the experiment with biochemical markers. MATERIALS AND METHODS: The experiments were conducted on 40 non-linear rats, divided into two groups of 20 animals. Group 1 animals received intraperitoneal injections of ET of Escherichia coli drug (Sigma USA K-235) for seven days at a rate of 0.1 mg/kg of the body weight. Animals of the second group served as the control group. Character and stage of liver damage were studied using morphological methods, including electron and light microscopy. In studying oxidizing stress, biochemical methods were used to define the changes, such as conjugated dienes and dienketones, spontaneous oxidizing modification of proteins. RESULTS AND CONCLUSION: 1. The severity and depth of morphological changes in the liver during endotoxin intoxication were correlated with the dynamics of the content of lipid oxidation products (CD and DK, MDA) and proteins. There was a tendency for a more significant increase in the oxidative modification of proteins in serum. This confirms the data on the primary damage of proteins by free radicals. 2. When exposed to intestinal microflora endotoxin, pronounced dyscirculatory changes, fatty and hydropic degeneration of hepatocytes with signs of toxic damage to their nuclei were determined, but at the same time, the increased hyperplastic activity of sinusoidal cells remained associated with the effects of endotoxin. These changes are associated with both the direct toxic effect of endotoxin, and the effects of oxidative stress, in which endotoxin is a potent inducer.