[Complicated gastric cancer and modern treatment approaches]. / Oslozhnennye formy raka zheludka ­ sovremennye podkhody k lecheniyu.

Among all patients with gastric cancer, 40% admit to the hospitals due to cancer-related complications. The most common complications of gastric cancer are bleeding (22-80%), malignant gastric outlet obstruction (26-60%), and perforation (less than 5%). The main treatment methods for gastric cancer complicated by bleeding are various forms of endoscopic hemostasis, transarterial embolization and external beam radiotherapy. Surgical treatment is possible in case of ineffective management. However, surgical algorithm is not standardized. Malignant gastric outlet stenosis requires decompression: endoscopic stenting, palliative gastroenterostomy. Surgical treatment is also possible (gastrectomy, proximal or distal resection of the stomach). The main problem for patients with complicated gastric cancer is the lack of standardized algorithms and abundance of potential surgical techniques. The aim of our review is to systematize available data on the treatment of complicated gastric cancer and to standardize existing methods.

Anti-Inflammatory Effect of Technologically Processed Antibodies to the Molecules of the Major Histocompatibility Complex in a Model of Acute Inflammation In Vivo.

The anti-inflammatory effect of technologically processed antibodies (TPA) to immune targets (MHC I and MHC II) was assessed in the carrageenan-induced rat paw edema model. The parameters "increase in edema" and "suppression of edema" significantly decreased (p<0.05) against the background of treatment with TPA and the reference drug indomethacin compared to the placebo group. The tested TPA produced an anti-inflammatory effect.

Antiallergic Effects of Technologically Processed Antibodies to MHC II.

The risk of developing anaphylactic reactions to medications introduces additional difficulties for effective pharmacotherapy. Using a model of systemic anaphylaxis in mice, we showed that preventive administration of a preparation containing technologically processed antibodies (TPA) to MHC II induces an anti-anaphylactic effect comparable to that of dexamethasone (when assessing the severity of systemic anaphylaxis 30 and 60 min after challenge injection of the model antigen ovalbumin). The revealed activity may be related to the ability of TPA to MHC II to regulate the antigen presentation system and shift the immune response towards the production of IgG instead of IgE typical of anaphylactic reaction.

Efficacy of Raphamin against Pneumococcal Infection: a Preclinical Study.

The aim of the study was to evaluate the activity of Raphamin in a model of non-lethal pneumococcal infection caused by Streptococcus pneumoniae 3 in BALB/c mice. The drug or placebo was administered intragastrically 3 days prior to infection, 2 h before and 2 h post infection, and then for 3 full days, alone or in combination with antibiotic (amoxicil-lin/clavulanic acid). Raphamin monotherapy significantly decreased bacterial load in the lungs in comparison with placebo (p<0.05) which was comparable to the effect in antibiotic alone or combined with Raphamin. Raphamin prevented reproduction of Streptococcus pneumoniae in the lower respiratory tract and its combination with the antibiotic was safe and did not reduce the efficacy of amoxicillin/clavulanic acid.

Analysis of General Toxicity of Ergoferon.

For antibody-based drugs, it is important and relevant to study their toxic effects, which can often become limiting when prescribing this type of therapy. General toxicity of antiviral drug Ergoferon based on technologically processed antibodies was studied on sexually mature animals. Analysis of acute toxicity showed the absence of lethal outcomes when the drug was administered to adult rats at the maximum tolerated doses. In a study of repeated dose toxicity, no adverse effects of the drug were detected.

Combined Drug with Antibacterial Effect Supports the Normal Intestinal Microflora.

Widespread use of antibiotics leads to an imbalance of normal intestinal microflora and to the development of multidrug resistance. The problem can be solved by administration of the antibiotics in combination with the drugs that have an immunotropic effect. We studied the effect of the drug containing technologically processed affinity purified antibodies to IFNγ, CD4 receptor, ß2-microglobulin of MHC class I, and ß2-domain of MHC II combined with antibiotics on the composition of intestinal microflora of pigs and the total number of microbiome resistance genes. Using the methods of NGS sequencing and quantitative PCR, we found that the drug contributes to the maintenance of normal microflora and, consequently, to the symbiotic relationship of the host with microflora, and prevents the reproduction of pathogenic bacterial species. Analysis for the presence of the resistance genes of gastrointestinal microorganisms showed that the drug does not affect the qualitative and quantitative composition of these genes of the intestinal microbiome.

Efficacy of the Technologically Processed Antibodies to the Brain-Specific S100 Protein in a Rat Model of Hemorrhagic Stroke.

We studied the ability of technologically processed antibodies to the brain-specific S100 protein (drug Prospekta) to reduce the brain lesion area, neurological disorders, and mortality in a rat model of hemorrhagic stroke. Technologically processed antibodies to S100 exerted a positive effect on all these parameters (brain lesion area, survival rate, neurological status according to the Menzies scale, and proportion of contralateral turns). This allows us to recommend further research into the spectrum of pharmacological activity and the mechanism of action of technologically processed antibodies to S100 in order to expand the indications for their use after the necessary clinical trials.

Nootropic Activity of Prospekta in a Blind Placebo-Controlled Study in a Model of Focal Cerebral Ischemia in Rats.

Analysis of the pharmacological activity of the original drug Prospekta in a rat model of focal cerebral ischemia revealed its nootropic effect: course treatment in the post-ischemic period led to recovery of the neurological status of animals at the peak of neurological deficit. Evaluation of the therapeutic potential of the drug in morphological and functional CNS disorders allowed us to conclude that it is advisable to carry out further studies of its biological activity at the preclinical stage (the results obtained in animals were successfully confirmed in a clinical trial of drug efficacy in the treatment of moderate cognitive disorders in the early recovery period after ischemic stroke). Studies of the nootropic activity in other pathologies of the nervous system are also promising.

Safety of the Drug Prospekta: a Preclinical Study of Acute and Repeated Dose Toxicity.

General toxic effect of the drug Prospekta (modified affinity purified antibodies to the brain-specific S100 protein) was studied on mature male and female mice and rats: acute toxicity with double intragastric and intraperitoneal administration of the maximum permissible doses at a 2-h interval, repeated dose toxicity with intragastric administration of the maximum permissible and close to therapeutic doses for 6 months. No lethal and toxic effects on animals were observed, including no toxic effects on vital systems, i.e., CNS and cardiovascular system, as well systems with the functions that may be temporarily disrupted (excretory and digestive systems). All the differences between animals of the experimental and control groups varied within the physiological range. It can be concluded that the drug produces no general toxic effect on laboratory animals.

Antiviral Activity of Technologically Processed Antibodies to CD4 Receptor against Influenza Infection.

The antiviral activity of technologically processed antibodies to CD4 receptor was evaluated a model of sublethal A/California/04/2009 (H1N1)pdm09-induced influenza infection in female BALB/c mice. The technologically processed antibodies increased animal survival rate by 50% in comparison with the placebo group (p<0.05), which correlated with significant inhibition of virus replication in the lungs (p<0.05). The reference drug Tamiflu increased mouse survival rate (by 47%), decreased the virus titer in the lungs, and prevented body weight loss (p<0.05 in comparison with the placebo group by all parameters). The intrinsic protective activity of technologically processed antibodies to CD4 receptor was demonstrated, which manifested in a decrease in viral load in the lower respiratory tract and an increase in the survival rate.

[Susceptibility of animal species to experimental SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) infection].

Due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs to treat COVID-19. The choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.The purpose of this review was to summarize the relevant data concerning the susceptibility of laboratory animals to SARS-CoV-2. This paper describes the most virus-susceptible animal species that can be used to reproduce coronavirus infection, stressing the main advantages and disadvantages of each of them.According to the latest data, small rodents (Rodentia) and non-human primates (Strepsirrhini) are commonly used in the scientific community to model coronavirus infection. The viral load in the upper and lower parts of the respiratory system, clinical symptoms of infection (weight loss, body temperature and general health status), pathomorphological picture in target organs and the production of antibodies after infection are considered to the main markers of pathology. Despite the vast amount of data, none of the described models of SARS-CoV-2 infection may be considered a gold standard, since they do not reproduce all spectrum of morphological and pathogenetic mechanisms of infection, and do not fully reflect the clinical picture observed in patients in human population.Based on the analyzed literature data, we suppose that Syrian hamster (Mesocricetus auratus) and mice (Muridae) expressing the angiotensin converting enzyme receptor 2 (ACE2) are the most suitable animal species for their use in experiments with SARS-CoV-2 infection. The development of neutralizing antibodies makes it possible to evaluate the efficacy of vaccines, while the course and severity of symptoms infection makes the use of mice and hamsters especially popular for screening pharmacological substances with antiviral mechanism of action, when their administration can prevent or slow the disease progression.

[Ultrasound in the diagnosis and treatment of abdominal abscesses]. / Ul'trazvukovoe issledovanie v diagnostike i lechenii abstsessov briushnoi polosti.

OBJECTIVE: To improve the results of surgical treatment of abdominal abscesses using ultrasound-assisted drainage. MATERIAL AND METHODS: There were 103 cases of percutaneous ultrasound-assisted drainage of intraperitoneal abscesses for the period from 2012 to 2017. Patients who underwent drainage of intraorganic and retroperitoneal abscesses associated with pancreatic necrosis were excluded from the study. RESULTS: Complete recovery was observed in 101 (98%) out of 103 patients within 10-73 days. CONCLUSION: Ultrasound-assisted drainage is an effective procedure for abscesses. This method has demonstrated high efficiency, availability and safety without need for open approach. This method may be a reliable alternative to open surgery, for example in emergency surgical hospitals.

Ergoferon Increases IL-2 Production by Activated Lymphocytes.

We studied the effects of Ergoferon on the production of antiviral cytokine IL-2 by type 1 CD4+T cells. Preincubation of Jurkat cells with Ergoferon increased IL-2 secretion by these cells after stimulation with phorbol 12-myristate 13-acetate/ionomycine in comparison with the placebo group. The data prove that Ergoferon is capable of activating cell cascades involved in the realization of the antiviral immune response.

Effects of Release-Active Antibodies to CD4 Receptor on the Level of lck-Kinase in Cultured Mononuclear Cells from Human Peripheral Blood.

For evaluation of effects of release-active antibodies to CD4 on cultured lymphocytes from human peripheral blood, we measured intracellular content of lck-kinase cell-based ELISA. In cells treated with release-active antibodies to CD4, the content of intracellular lck-kinase significantly (p<0.01) decreased in comparison with the control (purified water processed in a similar way). Phytohemagglutinin had no effect on the concentration of lck-kinase in cells. The decrease in the content of CD4-associated lck protein suggests that the preparation enhanced intracellular coupling of lck-kinase with T-cell receptor and potentiated T-cell immune response.

[The biomarkers in medicine: search, choice, study and validation].

The sphere of application of biomarkers is expanding every year and already comprises their using as indicator of presence or absence of disease, response to therapy, efficiency of medications or pre-clinical model of diagnostic parameter and even participant of process of search of mechanism of effect of medications. Hence, it is impossible to overestimate significance of studying of biomarkers. The article is dedicated to systematization and structuring of present information concerning biomarkers, starting from primary screening and completing with validation of chosen molecule or characteristic.

Subetta Enhances Sensitivity of Human Muscle Cells to Insulin.

Addition of Subetta to insulin (10 nM) increased insulin-stimulated glucose uptake 43% (p<0.001). Moreover, glucose uptake stimulated by insulin (10 nM) in the presence of Subetta was similar to that stimulated by 300 nM insulin. These findings suggest that Subetta significantly enhanced insulin sensitivity of tissues through stimulation of glucose transport to myocytes mediated by glucose transporter 4.

Subetta increases phosphorylation of insulin receptor ß-subunit alone and in the presence of insulin.

It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor ß-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor ß-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the 'phosphorylated-insulin receptor ß-subunit/total insulin receptor ß-subunit' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its ß-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug's antidiabetic effect.

[Study of efficacy of anaferon pediatric in mice infected by pandemic influenza virus A(H1N1/09)v].

AIM: To study efficacy of anaferon pediatric in mice infected by pandemic influenza virus A(H1N1/09)v. MATERIALS AND METHODS: Influenza virus strain A/California/07/2009 (H1N1)v was used. Three groups of BALB/c mice intranasally inoculated with influenza virus were studied. First group received solution of Anaferon pediatric during 5 days before and 8 days after inoculation, 2nd group received Tamiflu during 5 days after inoculation. Distilled water was administered orally to mice from control group. RESULTS: It was shown that Anaferon pediatric used as preventive and treatment agent in mice intranasally inoculated with 100% infectious dose of influenza virus strain A/ California/07/2009 (H1N1)v had antiviral effect, which expressed in 10-fold decreased reproduction of influenza virus in lungs of infected mice compared to control group measured 4, 6, and 8 days after inoculation. CONCLUSION: Use of anaferon pediatric before and after inoculation with influenza virus A(H1N1/09)v was not less effective than use of Tamiflu after inoculation.

Antiviral activity of Anaferon (pediatric formulation) in mice infected with pandemic influenza virus A(H1N1/09).

Anaferon (pediatric formulation) administered in the therapeutic-and-prophylactic regimen to mice receiving intranasally 100% infecting dose of A/California/07/2009(H1N1)v influenza virus exhibited an antiviral effect and 10-fold reduced the production of influenza virus in the lungs of infected mice on days 4, 6, and 8 after infection compared to the control (distilled water). The efficiency of Anaferon (pediatric formulation) administered before and after infection with A/California/07/2009(H1N1)v influenza virus was not inferior to the use of Tamiflu after infection.

Anaferon (pediatric formulation) in prophylactics of acute respiratory viral infection in children.

Prophylactic treatment with anaferon (pediatric formulation) in children groups reduced total morbidity and incidence of acute respiratory viral infections and shortened the duration of fever, intoxication, and catarrhal syndromes. No allergic and other reactions caused by administration of the preparation were noted.