EXAMINING LOCALLY EXPRESSED mRNA OF INFLAMMATORY MEDIATOR GENES IN A MODEL OF RETINAL PIGMENT EPITHELIUM ATROPHY AND RETINAL DEGENERATION INDUCED BY SUBRETINAL SALINE INJECTION IN RABBITS

Degenerative-dystrophic retinal diseases, particularly age-related macular degeneration (AMD), are now considered to be the lead cause of blindness and low vision in developed countries, with a steadily increasing trend. Recent publications provide evidence for the involvement of inflammatory mechanisms in TMD development and progression unveiled due to advances in innate and adaptive immunity research. However, the immunopathogenesis of atrophic AMD form, “geographic atrophy” (GA) remains largely unstudied. Objective: to investigate local mRNA expression of inflammatory cytokines IL-1β, IL-18, CCL2/MCP-1 in a model of RPE atrophy induced after subretinal injection of 0.9% sodium chloride solution in experimental rabbits. The investigation was carried out in tissue complex retina-RPE-choroid (TC) samples isolated from eyes of 23 albino New Zealand rabbits after modeling RPE atrophy by subretinal injection of 0.9% sodium chloride solution and 5 healthy rabbits lacking eye lesions. Animals in the experimental group (one week before surgical intervention, in the early period, and in the period of sustained RPE atrophy formation) and controls were subjected to optical coherence tomography (OCT) and ocular fundus autofluorescence (FAF). Evaluation of proinflammatory cytokine gene expression levels in TC was performed by RT-PCR. Results. Subretinal injection of 0.01 ml of 0.9% sodium chloride solution induced experimental RPE atrophy development in rabbits vs. control that was associated with multidirectional changes of IL-1β, IL-18, MCP-1/CCL2 gene mRNA expression. Three types of response in the TC, formed during development of atrophic changes and determined by the value of local cytokine gene expression were characterized: 1) hypo/ no response – decreased/no expression; 2) normal response – moderate increase; 3) hyper response – overexpression. 69.6% of animals with persistent atrophy had a moderate to hypertrophic increase in locally expressed mRNA MCP-1/CCL2, whereas 30% cases had significantly increased IL-1β mRNA expression – factors damaging the blood-retinal barrier and contributing to posterior segment immune privilege. It should be taken into account while developing new strategies for treatment of ophthalmic pathology, in particular the currently actively studied and tested options for RPE stem cell transplantation into subretinal space. The data obtained may be useful to investigate various types of RPE atrophy and develop new strategies of ophthalmopathology treatment in preclinical studies

The use of Flash glucose monitoring in children with type 1 diabetes mellitus in real clinical practice

BACKGROUND: In 2018, a Frestyle Libre flash glucose monitoring system (FGM) appeared in Russia and became a potential alternative to the traditional CGM. Studies carried out to date have shown the advantages of FGM over SMBG, but only a few of them relate to real clinical practice, especially in children with type 1 diabetes.OBJECTIVE: To evaluate the efficacy of FGM in children with T1DM in relation to glycemic control indicators, the occurrence of severe hypoglycemia and diabetic ketoacidosis, as well as the satisfaction of patients and their parents with the use of FGM.MATERIALS AND METHODS: Single-center, prospective, observational cohort study. Children 4–18 years old with T1DM and HbA1c level less than 10.0% were invited to participate in the study on intensified insulin therapy (by MDI or CSII). The duration of the patient’s participation in the study was 6 months. At baseline and every 3 months thereafter, face-to-face consultations were conducted with an assessment of the general condition, HbA1c study, an assessment of glycemic indicators, progress in relation to glycemic control targets and correction of the therapy. A total of 228 patients (110 boys and 118 girls) who met the inclusion criteria were included in the study. The median age was 11.2 (8.6–14.7) years, the duration of type 1 diabetes was 3.8 (2–7.1), 136 patients received insulin therapy by CSII for 1.3 (0.8–2.6) years.RESULTS: In the general group of patients, 3 and 6 months after the start of FGM use, the HbA1c values decreased statistically significantly by 0.2%. In addition, the number of children with HbA1c <7.5% increased by 6.1 and 4.9% at 3 and 6 months, respectively, but these changes were not statistically significant. The number of cases of DKA when using FGM decreased by 74%, and the number of cases of severe hypoglycemia by 83%, thus the number of episodes decreased by 4 and 6 times, respectively. Patients and / or their parents rated the ease of use and their experience with FGM on a scale from 0 (strongly agree) to 4 (strongly disagree). The majority of children and parents positively (0 or 1) assessed the convenience of installing and wearing the sensor (72.7–98.2%) using the FGM system in general (75.0–96.4%) and in comparison with the SMBG glucometer (92.3–98.2%).CONCLUSION: The installation and use of FGM is convenient and comfortable for the vast majority of children and parents, while compared to SMBG, the use of FGM is more convenient and simpler, and glucose measurement is much faster and less painful

Диагностика туберкулеза легких в условиях пульмонологического отделения стационара

A clinical case of 23-year old female with pulmonary tuberculosis is described in this article. The patient was admitted to a hospital with preliminary diagnosis of community-acquired pneumonia and negative TB test. Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia is often difficult and could be more difficult in patients with co-existing specific (Mycobacterium tuberculosis) and non-specific infection in the lungs.Дифференциальная диагностика туберкулеза легких (ТЛ) и пневмонии является сложной проблемой на этапе первичного обследования пациента в терапевтической практике. Представлен клинический случай диагностики ТЛ у 23-летней женщины при поступлении в стационар терапевтического профиля с диагнозом внебольничная пневмония при наличии отрицательных специфических тестов на ТЛ. Диагностика также может быть затруднена при наличии сочетанной специфической (микобактерии туберкулеза) и неспецифической инфекции в зоне воспалительного поражения легких

Clinical, hormonal and molecular-genetic characteristics of monogenic diabetes mellitus associated with the mutations in the <i>INS</i> gene

Background: Currently more than 50 mutations of the INS gene are known to affect the various stages of insulin biosynthesis in the beta cells of the pancreas. However only individual cases of diabetes mellitus (DM) associated with heterozygous mutations in the coding region of the INS gene were reported in Russian Federation. We report a group of patients with a clinical manifestation of DM caused by mutations in both coding and non-coding regions of the INS gene. The patients with a mutation in the intron of the INS gene are reported for the first time in Russian FederationMaterials and methods: 60 patients with an isolated course of neonatal DM (NDM), 52 patients with a manifestation of DM at the age of 7–12 months and the absence of the main autoimmune markers of type 1 DM, 650 patients with the MODY phenotype were included in the study. NGS technology was used for molecular genetic research. Author’s panel of primers (Custom DNA Panel) was used for multiplex PCR and sequencing using Ion Ampliseq™ technology. The author’s panel “­Diabetes Mellitus” included 28 genes (13 candidate genes of MODY and other genes associated with DM).Results: 13 heterozygous mutations were identified in 16 probands and 9 relatives. The majority of mutations were detected in patients with PNDM (18.75%) and in patients with an onset of DM at the age of 7–12 months (9.6%). Mutations in the INS gene were detected in 2 patients (0.3%) in the group with the MODY phenotype. Mutations in the INS gene were not detected in patients with transient NDM (TNDM). Analysis of clinical data in patients with PND and onset of diabetes at the age of 7–12 months did not show significant differences in the course of the disease. The clinical characteristics of the cases of MODY10 and diabetes caused by a mutation in the intron of the INS gene are reported in details.Conclusion: The role of INS gene mutations in NDM, MODY, and DM with an onset at the age of 7–12 months was analyzed in a large group of patients. The clinical characteristics of DM due to a mutation in the intron of the INS gene are reported for the first time in the Russian Federation

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS).\ud \ud METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response.\ud \ud RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay.\ud \ud CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS

A multiplatform approach identifies miR-152-3p as a common epigenetically regulated onco-suppressor in prostate cancer targeting TMEM97

Prostate cancer (PCa) is a major cause of morbidity and mortality in men worldwide. MicroRNAs are globally downregulated in PCa, especially in poorly differentiated tumors. Nonetheless, the underlying mechanisms are still elusive. Herein, using combined analysis of microRNAs expression and genomewide DNA methylation, we aimed to identify epigenetically downregulated microRNAs in PCa.Research Center of Portuguese Oncology Institute of Porto (FB-GEBC-27 and 19-CI-IPOP-2016). JR-C and CSG are supported by FCT- Fundação para a Ciência e Tecnologia PhD fellowships (SFRH/BD/71293/2010 and SFRH/BD/92786/2013), SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027, and IG is a research fellow from the strategic funding of FCT (PCT: PEst- UID/DTP/00776/2013 and COMPETE: POCI-01-0145-FEDER-006868). BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012)info:eu-repo/semantics/publishedVersio

Rezul'taty primeneniya Tioktatsida BV v lechenii diabeticheskoy perifericheskoy sensomotornoy neyropatii u deteyi podrostkov s sakharnym diabetom 1 tipa

Цель. Изучение эффективности и безопасности препарата ?Тиоктацид? БВ в детской практике. Материалы и методы. Лечение Тиоктацидом БВ проведено 10 больным СД 1 типа в возрасте от 15 до 19 лет. В течение 3 нед. Тиоктацид БВ назначался по 600 мг 3 раза в день, до приема пищи, далее по 600 мг х 1 раз в день, утром до еды, в течение 2-х мес. Контрольную группу составили 9 пациентов с СД 1 типа (из случайной выборки) с выявленной диабетической полинейропатией. Результаты. В процессе лечения Тиоктацидом БВ не наблюдалось серьезных побочных явлений. В целом по группе частота симптомов нейропатии (боль, жжение, парестезии, онемение) значительно уменьшилась. Симптомы неврологических нарушений (снижение вибрационной, температурной, тактильной чувствительности, рефлексов) достоверно уменьшились. Заключение. Полученные данные подтверждают, что тиоктовая кислота оказывает корригирующее воздействие на проявления ДПН, в виде восстановления нарушенной чувствительности. Причем, положительные результаты получены уже через 3 нед. лечения