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Side-line Neurological Stimulation: 2 Installments of Intractable Neuropathic Soreness.
EPR spectra of the adducts of the DEPMPO spin trap with free radicals suggest that the interaction of glutathione DNICs and superoxide does not result in the formation of the thiyl radical of glutathione. Here we propose a mechanism of the antioxidant action of glutathione DNICs, suggesting that unstable intermediate complexes are formed upon their interaction with superoxide or lipid radicals. Further, as a result of intramolecular rearrangement, these intermediates decompose without the free radical as the by-products.The effects of intraperitoneal administration of SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) in a dose of 25 mg/kg (the total dose of 350 mg/kg) and SNK-578 (hydrochloride of 2-isobutyl-4,6-dimethyl-5- hydroxypyrimidine) in a dose of 10 mg/kg (the total dose of 140 mg/kg) on tumor growth and concentration of cytokines in the blood serum were studied in female CBA mice. Substances were administrated from the 2nd to 15th days of tumor development. Tumor growth inhibition (TGI) and serum cytokine level were studied on the 7th day after the end of compounds administration (21st day of tumor growth). In intact control group (n=10) median tumor mass was 1255 mg. TGI in the group of animals treated with SNK-411 was 47%; in the group of mice treated with SNK-578 TGI was 87%, tumor mass demonstrated 7.4-fold reduction. Serum concentrations of cytokines (IL-6, IL-10, IL-17A and IFN-γ) in tumor-bearing group of mice were higher versus the intact control group by 229%, 40%, 60% and 81%, respectively. Highly active SNK-578 decreased concentrations of prooncogenic IL-10, IL-17A and proinflammatory IL-6, by 61%, 70% and 29% as compared to tumor-bearing control group. SNK-411 decreased concentrations of prooncogenic IL-10 and IL-17A by 48% and 60%, respectively, and did not affect concentration of IL-6. Taking into consideration that IL-6 participates in autoimmune reactions, we can assume that the immune control is one of the crucial mechanisms of antitumor effect of SNK-578. All results are statistically significant.The dose-dependent effects of plasma exposure to a unipolar nanosecond sliding discharge over the surface of the culture medium in a closed plate on the cells of cerebral endothelium in vitro were studied. Using a 24-well plate, the surface plasma energy density of one pulse was 360 μJ/cm2 at a pulse frequency of 100 Hz. It has been shown that in the creeping discharge plasma there is an active excitation of air molecules, the formation of positive nitrogen and oxygen ions, and the formation of carbon monoxide. In the dose density range of 0-32 J/cm2, the dose-dependent effects were assessed in the 4-12 h post-radiation period. Cell death was analyzed with an assessment of the total number of cells, necrotic cells, cells in apoptosis (phosphatidylserine externalization, internucleosomal DNA fragmentation) and their proliferative activity (Ki67-immunopositive cells). A preliminary assessment of subtle dose-dependent effects indicates the peculiarities of the effect of small doses.An increase in the activity and the appearance of a new isoform of NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37) has been detected in the liver of rats with alloxan diabetes was revealed. This confirms the possibility of MDH involvement in the adaptive reaction of the body under oxidative tress caused by biochemical changes in diabetic animals. The increase in the hepatic MDH activity in rats with experimental type I diabetes mellitus (T1DM) is associated with the formation of an additional MDH isoform in peroxisomes. Data on the expression of the MDH encoding genes mdh1 and mdh2 confirm that in T1DM the increase in MDH activity occurs at the level of transcription of MDH encoding genes. The use of the extract of Helianthus tuberosus led to a marked decrease in the blood glucose concentration of rats with alloxan diabetes, abolished by the change in transcriptional activity of the studied genes and blocked the formation of new MDH isoforms in rats with experimental alloxan diabetes. MRT67307 This suggest that extract of H. tuberosus may be of considerable interest from the point of view of pharmacological correction of metabolic changes during the development of pathologies of this kind.DyeCycle Violet efflux, caused by ATP-binding cassette transporters activity, was analyzed in human colorectal adenocarcinoma cell lines SW480, HT-29, Caco-2 by neans of FACSAria III flow cytometer and ImageStreamX Mk II imaging flow cytometer. Along with similarity of cytometry data obtained on the two instruments, the use of imaging flow cytometry made it possible to characterize the morphology of side population cells, as well as morphology of other cell populations differing in the degree of dye accumulation. The population of cells, which are smaller than the side population cells and practically do not take the dye, is of the special interest. Probably, this population may contribute to the tumor resistance to chemotherapy.The expression of DNA repair (DDB1, ERCC4, ERCC5), leukocyte adhesion (VCAM1, ICAM1, SELE, SELP), endothelial mechanotransduction (KLF4), endothelial differentiation (PECAM1, CDH5, CD34, NOS3), endothelial-to-mesenchymal transition (SNAI1, SNAI2, TWIST1, GATA4, ZEB1, CDH2), scavenger receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) genes in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC) was studied at two time points - after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium using the quantitative PCR. Immediately after MMC exposure, in the exposed HCAEC and HITAEC a decreased expression of almost all studied genes was noted excepted SNAI, which demonstrated a 4-told increase in its expression compared to the unexposed control. Elimination of MMC from the cultures, an increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and a decreased the mRNA level of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes were observed in both cell lines. In addition, HITAEC cells were characterized by a decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, an increased mRNA level of the LDLR and VLDLR genes was noted. Thus, MMC-induced genotoxic stress is associated with the endothelial dysfunction.
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