Results of in vitro test-KRAStissue reagent kit test to determine indications for target therapy of patients diagnosed with colorectal cancer.

As subjects of the clinical trial, 44 samples of paraffin-fixed tissue were used from patients diagnosed with "colorectal cancer." In the course of clinical trials, 44 samples of paraffin-fixed tissue were analyzed in two series of experiments, that is, 88 clinical-laboratory experiments were carried out, of which 48 experiments with genomic DNA samples with the established negative status of the presence of KRAS gene mutations and 40 experiments with genomic DNA samples with the established positive status of the presence of KRAS gene mutations. Analysis and evaluation of the results of clinical laboratory tests of the medical product "Kit of Reagents for Determination of the Status of KRAS Gene Mutations by PCR-RV Method in a Sample of Human Genomic DNA from Samples of Paraffin-Fixed Tissue (Test-KRAS-tissue) according to TU 21.20.23-006-97638376-2016 "confirmed that it allows to carry out qualitative determination of the status of six mutations of the twelfth codon (Gly12Asp, Gly12Ala, Gly12Arg, Gly12Val, Gly12Ser, Gly12Cys) and one mutation of the thirteenth codon (Gly13Asp) the KRAS gene by real-time allele-specific PCR in human genomic DNA sample from paraffin-fixed tissue samples, with high diagnostic sensitivity rates of 90.9% and diagnostic specificity of 95.0% with a confidence probability of 90%. Reproducibility of results is 100%, which confirms the high reliability of the set.

Combined Effect of NF-κB Inhibitor and ß2-Adrenoreceptor Agonist on Mouse Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.

Experiments on random-bred albino mice showed that NF-κB inhibitor (BAY 11-7082) and ß2-adrenoreceptor agonist (dexmedetomidine hydrochloride) significantly reduced mouse mortality in 4 and 24 h after sepsis modeling (intraperitoneal administration of E. coli) by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The combined administration of NF-κB inhibitor and ß2-adrenoreceptors agonist have an additive effect.

Role of ß2-Adrenoreceptors in Adrenergic Anti-Inflammatory Mechanism in Sepsis.

Experiments on random-bred albino mice showed that of ß2-adrenoreceptor agonist hexaprenaline sulfate significantly reduced mortality of mice from experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h after modeling by reducing blood levels of proinflammatory cytokines TNFα, IL-1ß, and IL-6. The antagonist of ß2AR ICI-118,551 eliminated this effect.

Combined Effects of M1 Muscarinic Acetylcholine Receptor Agonist TBPB and α7n-Acetylcholine Receptor Activator GTS-21 on Mouse Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.

Experiments on random-bred albino mice showed that M1 muscarinic acetylcholine receptor agonist (TBPB) and α7n-acetylcholine receptor agonist (GTS-21) significantly reduced mortality of mice with experimental sepsis (intraperitoneally administration of E. coli) in 4 and 24 h after modeling by reducing blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. Combined treatment with TBPB and GTS-21 determined their additive effect.

Role of α7-Nicotinic Acetylcholine Receptors of B Cells in the Immunotoxic Effect of Organophosphorus Compounds.

Experiments on white non-inbred rats demonstrated that treatment with organophosphorus compound dimethyl dichlorovinyl phosphate (DDVP) decreased T cell-independent antibody production by B cells and blood levels of IL-10 and IL-12; a similar effect was produced by GTS-21, a selective agonist of α7-nicotinic acetylcholine receptor. N-nicotinic receptor antagonist chlorisondamine in combination with DDVP partially prevented suppression of antibody production in comparison with the effect observed during intoxication with DDVP.

[EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

[The diagnostic of chronic syndrome of disseminated intravascular blood coagulation in patients with damaged spleen in remote post-operative period.]

The study was carried out concerning analysis of coagulation homeostasis in 70 patients earlier subjected to damage of spleen because of closed trauma of abdomen. From the moment of surgical intervention passed no less than one year. The age of the examined patients varied from 20 to 50 years. The average age made up to 45±2 years. The males amounted to 50 and females - to 20. The splenectomy was executed in 50 patients out of all. The organs-preserving operations using CO2 -laser were executed in 20 patients out of all. The comparison group consisted of 30 healthy individuals of both gender and the same age. It is established that execution of organs-preserving operations under trauma of spleen prevents development of syndrome of chronic disseminated intravascular coagulation of blood. In patients after splenectomy the signs of this process were detected and at that no clinical manifestations were detected. That is, it is possible to affirm presence of chronic latent ongoing disseminated intravascular coagulation of blood in patients of the given category.

[CHANGES IN THE FUNCTION OF LYMPHOCYTES AND CYTOKINE CONCENTRATION IN BLOOD CAUSED BY THE ACTION OF ATROPINE UNDER CONDITIONS OF ACUTE MALATHION INTOXICATION].

It was established in experiments on noninbred albino rats that acute intoxication with malathion (0.75 LD50) reduced the function of Th1 cells more significantly than the function of Th2 lymphocyte, decreases the activity of B cells and NK cells, blood levels of TNFa, IL-1b and IL-6, IFN-g, IL-2, and IL-4, while not significantly affecting the concentration of IL-10 and IL-13. Atropine (10 mg/kg) under conditions of acute malathion intoxication improved the function of T cells and B lymphocytes, NK cells, as well as the synthesis of immunoregulatory cytokines IFN-g, IL-2, and IL-4. At the same time, atropine in malathion intoxicated rats had no effect on suppression of the synthesis of proinflammatory cytokines TNF, IL-1g and IL-6 as well as the content of anti-inflammatory cytokines IL-10 and IL-13.

Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis.

Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1ß, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.

Changes in immunity parameters and blood cytokine concentrations after chronic nitrile acrylate intoxication.

Experiments on outbred albino rats showed that chronic nitrile acrylate intoxication (60 days, 0.05 LD50 per day subcutaneously) led to reduction of T-dependent humoral immune response (T-independent humoral immune response was less affected); parameters cell immunity were suppressed to a greater extent than parameters of humoral immune reactions. Equal attenuation of the functions of Th1 and Th2 lymphocytes, decrease of the blood levels of immunoregulatory, pro- and anti-inflammatory cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-13), and decrease of acetyl cholinesterase activity in thymic and splenic T lymphocytes were observed.