Autocatalytic cycle in the pathogenesis of diabetes mellitus: biochemical and pathophysiological aspects of metabolic therapy with natural amino acids on the example of glycine

In this work systematization (classification) of biochemical and physiological processes that cause disorders in the human body during the development of diabetes mellitus is carried out. The development of the disease is considered as the interaction and mutual reinforcement of two groups of parallel processes. The first group has a molecular nature and it is associated with impairment of ROS-regulation system which includes NADPH oxidases, RAGE receptors, mitochondria, cellular peroxireductase system and the immune system. The second group has a pathophysiological nature and it is associated with impairment of microcirculation and liver metabolism. The analysis of diabetes biochemistry based on different published references yields a creation of a block diagram evaluating the disease development over time. Two types of autocatalytic processes were identified: autocatalysis in the cascade of biochemical reactions and "cross-section" catalysis, in which biochemical and pathophysiological processes reinforce each other. The developed model has shown the possibility of using pharmacologically active natural metabolite glycine as a medicine inhibiting the development of diabetes. Despite the fact that glycine is a substitute amino acid the drop in the glycine blood concentration occurs even in the early stages of diabetes development and can aggravate the disease. It is shown that glycine is a potential blocker of key autocatalytic cycles, including biochemical and pathophysiological processes. The analysis of the glycine action based on the developed model is in complete agreement with the results of clinical trials in which glycine has improved blood biochemistry of diabetic patients and thereby it prevents the development of diabetic complications

Test-System for Identification of Typical and Genetically Altered Variants of Cholera Vibrios, Biovar El Tor, Using Real-Time PCR

The aim of the work was to analyze and assess the results of using PCR test-system “V. cholerae variant ctxB-rtxC FL genes” for identification of Vibrio cholerae O1 with differentiation between typical toxigenic and genetically modified variants in a multiplex format with a real-time hybridization-fluorescent recording of results. Materials and methods. To achieve this goal, a set of reagents for the PCR test-system “V. cholerae O1 variant ctxB-rtxC FL genes”, as well as a method for identifying V. cholerae O1 with differentiation between typical toxigenic and genetically altered variants were utilized. The specificity, specific activity and sensitivity of the developed test-system by the example of 35 V. cholerae O1 strains, 6 V. cholerae non-O1 strains, 5 heterologous strains (Shigella zonnei – 2 strains, one Salmonella typhimurium strain, S. enteritidis, Escherichia coli) were investigated. Results and discussion. The panel of reagents for the PCR test system “V. cholerae variant ctxB-rtxC FL genes” detects DNA fragments of the ctxBCl, ctxBEl, rtxC genes in the genome of toxigenic V. cholerae О1 (has specific activity, analytical sensitivity 1·103 GE/ml) and does not detect these genes in non-toxigenic V. cholerae O1 and non-O1, as well as in heterologous strains of microorganisms (100 % specificity). RF Patent No. 2732448 was granted for the PCR test-system “V. cholerae variant ctxB-rtxC FL genes”. It can be used to increase the efficiency of the epidemiological surveillance system and to carry out a justified scope of anti-epidemic measures in the event of cholera importation into the territory of the Russian Federation

El Tor cholera at the contemporary stage of the seventh pandemia: pathogen evolution, clinical and epidemiological features, laboratory diagnostics

The phenotypic and molecular genetic properties of 133 strains of genetically modified (genovariant) Vibrio cholerae O1 El Tor biovar isolated from patients in Dagestan (1993, 1994, 1998), and compared with 246 strains of a typical toxigenic cholera vibrio El Tor biovar isolated in 1970–1990 at the Caucasus Region. It was found that 48.7% of the studied genetically modified strain variants had mixed phenotypic properties of the El Tor and classic biovars that evidences about a need to include the marker genes of the classical biovar (ctxBCl+, rtxC–) and the El Tor biovar (ctxBEl+, rtxC+) into the existing biotyping scheme. The genes of the El Tor biovar, isolated from patients in Dagestan, contain in addition to the El Tor ones, the genes of the classical biovar (ctxBCl and/or rstRCl), as well as the typical toxigenic cholera vibrios of El Tor, islands of persistence (EPI), pathogenicity (VPI-1 and VPI-2) and pandemicity (VSP-I and VSP-II). However, only the El Tor biovar genovariants were found to bear an integrative and conjugative SXT element with antibiotic polyresistance genes. Epidemic cholera outbreaks caused by the El Tor biovar genovariants that occurred in 1993–1998 at the Caucasus Region, correspond to classical (Asian) cholera based on disease severity. The epidemiological features of modern cholera were studied: the main way for transmission via fecal-oral route for typical El Tor cholera vibrio is waterborne, whereas for the El Tor gene variant — household. Primary infections upon water drinking and using domestic water from surface water bodies infected with typical El Tor vibrios occur outside the family hearth. In case of cholera caused by hybrid El Tor variants, infection is transmitted among family members via domestic factors under low sanitary level. The development of laboratory diagnostics and epidemiological surveillance of modern El Tor cholera is based on the development of PCR test systems taking into account the evolutionary genome transformations

Трактография тройничного и лицевого нервов: первый опыт НМИЦ нейрохирургии имени академика Н.Н. Бурденко

Introduction. Digital tensor tractography (DTT) is well-known and efficient method for white-matter tracts visualization. However, few publications show its effectiveness in cranial nerves tractography. The aim of the study is to develop and to implement the protocol for visualizing cranial nerve tracts.Materials and methods. DTT was implemented in 6 patients with vestibular schwannoma (VS) W. Koos 3-4 grade, preliminary coordinated by the study of 5 patients with trigeminal neuralgia. The tracts were “built” using 3D Slicer software.Results. In 5 of 6 cases, full correlation of pre- and intraoperative data was registered. In 1 case, the tracts were non-identifiable.Conclusion. Presented algorithm provides effective preoperative visualization of cranial nerves (V, VII). Obtained results allow to consider the method of DTT a promising technique for preoperative visualization of trigeminal and facial nerves in patients with posterior fossa lesions.Введение. Диффузионная тензорная трактография (ДТТ) является хорошо описанным и широко применяемым методом визуализации проводящих путей белого вещества головного мозга, при этом до последнего времени редко применяющимся для визуализации черепных нервов.Цель исследования: разработка протокола ДТТ для обследования пациентов с вестибулярными шванномами и “построения” трактов V и VII черепных нервов в условиях НМИЦ нейрохирургии, получение и обобщение первого опыта применения метода.Материал и методы. Для изучения применимости методики в хирургии вестибулярных шванном 6 пациентам с опухолями 3-й и 4-й стадии по классификации W. Koos было выполнено предоперационное обследование - МРТ в режимах FSpGR и DTI. После проведения программной обработки снимков выполнено “построение” трактов черепных неров, накладываемых на модель вестибулярной шванномы в програмной среде 3D Slicer.Результаты. Совпадение информации предоперационной трактографии и интраоперационной картины отмечено в 5 случаях из 6. У одного пациента отмечалось “наложение” трактов черепных нервов, не позволившее идентифировать каждый нерв в отдельности.Заключение. Полученные результаты позволяют строить предположение о ходе и направлении пучка волокон белого вещества (путем математической обработки анизотропной диффузии молекул воды внутри самих проводящих путей) и сделать вывод о положении и ходе корешков V и VII нервов относительно поверхности опухоли. Таким образом, в арсенале нейрохирургов появляется эффективный инструмент предоперационной идентификации черепных нервов у больных с опухолями различной локализации. Применение данного метода может повысить безопасность вмешательств и снизить частоту дисфункции черепных нервов

Сравнительный химический анализ внутриглазной жидкости и тканей дренажной зоны глаза при первичной открытоугольной глаукоме

PURPOSE: There are two primary aims of this study:1. To perform a comparative chemical analysis of aqueous humour (AH), scleral tissue, and trabecular meshwork in patients with primary open-angle glaucoma (POAG).2. To evaluate the tissue’s chemical composition at the different POAG stages and with in patients with pseudoexfoliation glaucoma (PEG).METHODS: The concentration of certain chemical elements — carbon (C), nitrogen (N), oxygen (O), aluminum (Al), calcium (Ca), chlorine (Cl), potassium (K), magnesium (Mg), sodium (Na), phosphorus (P), silicon (Si), sulfur (S) — was determined in the dried AH residue, trabecular meshwork and sclera biopsy samples obtained from patients with POAG (stage I and II), patients with pseudoexfoliation glaucoma (PEG), and patients with POAG without pseudoexfoliation material (PEM). Samples were analyzed using a scanning electron microscope (SEM) EVO LS 10 (“Zeiss”,Germany). The chemical composition study was performed with an energy-dispersive spectrometer (EDS) Oxford-XMAX-50 (“Oxford”,UK) in a low-vacuum mode (70 Pa) with an accelerating voltage of 21.5 kV.RESULTS: In the case of POAG (stage I and II) patients, there were significant differences in Cl distribution in dried AH residue and Si distribution in the trabecular meshwork. In the case of pseudoexfoliative glaucoma (PEG) and patients with POAG without PEM, there was a difference in the N distribution in dried AH residue, as well as Ca, Cl, and Na distribution in the trabecular meshwork. During scleral tissue comparative chemical analysis, no significant changes in studied elements’ concentration between patient groups were evident.CONCLUSION: Changes between stage II of POAG and stage III of POAG patient groups may indicate that there is an increase in the electrolyte and acid-base imbalance associated with the progression of the disease. Differences in chemical elements distribution in patients with PEG and in patients with POAG without PEM result from the molecular structure of PEM. The tissue’s water and salt balance and molecular chemical composition alterations provide the following insights for future research in finding the optimal treatment method for patients with all stages and types of glaucoma.ЦЕЛЬ. Провести сравнительный химический анализ внутриглазной жидкости (ВГЖ), склеры и трабекулы при первичной открытоугольной глаукоме (ПОУГ). Оценить химический состав тканей при различных стадиях ПОУГ, а также при псевдоэксфолиативной глаукоме (ПЭГ).МЕТОДЫ. Определено содержание ряда химических элементов: углерода (С), азота (N), кислорода (O), алюминия (Al), кальция (Са), хлора (Cl), калия (К), магния (Mg), натрия (Na), фосфора (P), кремния (Si), серы (S) в сухом веществе ВГЖ, биоптатах трабекулярной ткани и склеры у пациентов со II и III стадиями ПОУГ, а также у пациентов с ПЭГ и ПОУГ без псевдоэксфолиативного материала. Визуализация проводилась с помощью сканирующего электронного микроскопа (СЭМ) ЕVO LS 10 («Zeiss», Германия), исследование химического состава осуществлялось на энергодисперсионном спектрометре (ЭДС) Oxford-X-MAX-50 («Oxford», Великобритания) в режиме низкого вакуума (70 Па) при ускоряющем напряжении 21,5 кВ.РЕЗУЛЬТАТЫ. Выявлены различия в распределении Сl в сухом веществе ВГЖ и Si в трабекуле у пациентов со II и III стадиями ПОУГ. При сравнительном анализе тканей пациентов с ПЭГ и ПОУГ без псевдоэксфолиативного материала (ПЭМ) показано различие в распределении N сухого вещества ВГЖ, а также Ca, Cl, Na трабекулы. При сравнительном анализе элементного состава склеры между указанными группами статистически значимых различий в распределении исследуемых элементов выявлено не было.ЗАКЛЮЧЕНИЕ. Изменения, выявленные при сравнении II и III стадий ПОУГ, могут свидетельствовать о нарастании электролитного и кислотно-основного дисбаланса при прогрессировании заболевания. Отличия в распределении элементов между группами ПОУГ без ПЭМ и ПЭГ обусловлены молекулярным строением ПЭМ. Различия в водно-солевом и молекулярно-химическом составе тканей следует учитывать в дальнейших исследованиях, направленных на поиск оптимального медикаментозного метода лечения пациентов с разными стадиями и формами глаукомы

Протонная 3D-МР-спектроскопия в диагностике глиальных опухолей головного мозга

The purpose of this study was an assessment of the proton 3D MR spectroscopy efficacy in diagnosis of primary glial brain tumors.Material and methods. Sixty three patients aged from 20 to 60 years with primary glial brain tumors of varying degrees of malignancy were examined. The ratios of main metabolites indices were evaluated with following comparison with the metabolites obtained in gray and white matter of the opposite hemisphere.The ratios of main metabolites: Cho/Cr, NAA/Cr, Cho/NAA showed significant (p <0.005) differences in the groups of patients with low and high grade gliomas.Results. The obtained data proved the efficacy of the proton 3D MR-spectroscopy in predicting of the glial brain tumors malignancy.Цель исследования: изучение возможностей протонной 3D-МР-спектроскопии в диагностике первичных глиальных опухолей головного мозга.Материал и методы. Всего было обследовано 63 пациента в возрасте от 20 до 60 лет с глиальными опухолями головного мозга различной степени злокачественности. Были оценены индексы соотношений основных метаболитов в опухолевой ткани и их сравнение с метаболитами, полученными в сером и белом веществе противоположного полушария мозга. Индексы соотношений основных метаболитов: Cho/Cr, NAA/Cr, Cho/NAA имели достоверные (p < 0,005) различия при сравнении глиом низкой и высокой степени злокачественности.Результаты. Полученные данные доказывают эффективность метода протонной 3D-МР-спектроскопии в определении степени анаплазии глиальных опухолей головного мозга

The impact of investment in the housing on economic growth

The urgency of the discussed issue is caused by the need to increase the investment in the real sector of the Russian economy as a factor of economic growth; not completely formed structure of the Russian investment market. The main aim of the study is to justify the importance of increasing the investment in the housing sector as a factor of economic growth, based on economic restructuring. The methods used in the study: analysis and synthesis, system analysis, methods of statistical and economic analysis, investment growth theory, method of mathematical modeling. The results: The problems of real capital investment are discussed. The authors have studied the influence of investment decisions of households, particularly in housing on the growth of the national economy. It was shown that housing, as a part of the primary vital human needs, is a powerful stimulus for the development of the national economy. Conclusions: The increase of investment in housing and social infrastructure sector, associated with it, can become a multiplier of many related industries, regions development and one of the foundations of economic growth

The impact of investment in the housing on economic growth

The urgency of the discussed issue is caused by the need to increase the investment in the real sector of the Russian economy as a factor of economic growth; not completely formed structure of the Russian investment market. The main aim of the study is to justify the importance of increasing the investment in the housing sector as a factor of economic growth, based on economic restructuring. The methods used in the study: analysis and synthesis, system analysis, methods of statistical and economic analysis, investment growth theory, method of mathematical modeling. The results: The problems of real capital investment are discussed. The authors have studied the influence of investment decisions of households, particularly in housing on the growth of the national economy. It was shown that housing, as a part of the primary vital human needs, is a powerful stimulus for the development of the national economy. Conclusions: The increase of investment in housing and social infrastructure sector, associated with it, can become a multiplier of many related industries, regions development and one of the foundations of economic growth