Маркеры почечного повреждения, липидного обмена и карбонильного стресса у пациентов с сахарным диабетом I типа и разным уровнем альбуминурии

The aim of this work was to study the levels of podocalyxin and β-2-microglobulin and parameters of lipid metabolism and carbonyl stress in type 1 diabetes mellitus (T1DM) patients with different levels of albuminuria.Materials and methods. 56 men of reproductive age with T1DM were divided into two groups: 24 patients with stage A1 albuminuria (group A1) and 32 patients with stage A2 albuminuria (group A2). The control group consisted of 28 healthy men. The levels of renal function markers, lipid metabolism parameters, and methylglyoxal were assessed using enzyme immunoassay and spectrophotometric and fluorometric methods.Results. Higher values for total cholesterol, triacylglycerol, and very-low-density lipoprotein medians in both groups A1 and A2 were found. In these groups, increased podocalyxin and methylglyoxal medians were revealed. Correlation analysis in the group A1 showed the presence of a relationship between the glomerular filtration rate (GFR) and creatinine. In the group A2, correlations between the generally accepted parameters of kidney injury (the albumin / creatinine ratio and GFR) and the duration of the disease and between GFR and the creatinine and methylglyoxal levels in the blood were identified. The podocalyxin level in this group correlated with the β2- microglobulin and methylglyoxal levels and lipid metabolism parameters. The level of β2-microglobulin correlated with the lipid metabolism parameters.Conclusion. Regardless of the level of albuminuria, men with T1DM had significantly increased levels of podocalyxin, lipid metabolism parameters, and methylglyoxal, as well as strong relationships between these parameters. The data of this study can be used for development of potential strategies for prevention and early treatment of diabetic nephropathy.Цель – изучение уровня подокаликсина, β-2-микроглобулина, показателей липидного обмена и карбонильного стресса у пациентов с сахарным диабетом (СД) I типа и разным уровнем альбуминурии.Материалы и методы. Проведено обследование 56 мужчин репродуктивного возраста с СД I типа, разделенных на две группы: 24 пациента с альбуминурией стадии А1 (группа А1) и 32 – с альбуминурией стадии А2 (группа А2). Контрольную группу составили 28 здоровых мужчин. Оценивался уровень почечных маркеров, компонентов липидного обмена и метилглиоксаля (МГ) с использованием иммуноферментных, спектрофотометрических и флюорометрических методов.Результаты. Установлены более высокие значения медиан общего холестерина, триацилглицеридов и липопротеидов очень низкой плотности в обеих группах с СД I типа. В данных группах отмечались также повышенные значения медианы подокаликсина и основного показателя карбонильного стресса – МГ. Проведенный корреляционный анализ в группе А1 показал наличие зависимости уровня скорости клубочковой фильтрации (СКФ) и креатинина. В группе А2 отмечались связи общепринятых показателей почечного повреждения (соотношения альбумин/креатинин и СКФ) с длительностью заболевания, показателя СКФ с уровнем креатинина и МГ. Уровень подокаликсина в данной группе коррелировал с уровнем β2-микроглобулина, МГ, показателей липидного обмена; β2-микроглобулин имел взаимосвязи с параметрами липидного обмена.Заключение. У мужчин с СД I типа вне зависимости от уровня альбуминурии отмечаются значительно более высокий уровень подокаликсина, увеличенные показатели липидного обмена и МГ, а также наличие тесных взаимосвязей между этими параметрами, что может быть использовано для разработки потенциальных стратегий профилактики и ранней терапии диабетической нефропатии

Использование низкобелковых обогащенных крахмаломучных продуктов в диетотерапии больных фенилкетонурией детей в возрасте старше 1 года

Background. The nutrition of children with phenylketonuria includes specialized starch-based products, the range of which is constantly expanding. Our aim was to study the safety of the composition of starchy flakes enriched with a complex of fat-soluble vitamins, natural fruit and berry additives used in the food of children with phenylketonuria. Methods. The study included children under the age of 14 years who were compliant with the previously conducted hypophenylalanine diet, without acute infectious, severe somatic or neurological diseases. The investigated products (starch-rye, wheat, and wheat fruit flakes with a complex of provitamin A and vitamin E) were prescribed instead of previously used low-protein confectionery products in the amount of 20–25 g/day for children under 6 years, 30–40 g — for children aged 6 years and over. The products were given with the recommendation to use alternately, with a duration of at least 10 days, totally for 30 days of the study. The safety of the products was assessed by phenylalanine concentration in the blood (determined by the fluorimetric method). In addition, we assessed the organoleptic qualities of the products and the dynamics of physical development of children. Results. The study included 15 children, mean age 4.4 ± 1.9 years. The initial concentration of phenylalanine in the blood varied from 1.6 to 3.9 mg%, the median — 2.2 mg% (2.0; 2.8). In 30 days after inclusion of starchy flakes in the diet, the content of phenylalanine in the blood did not change and was 2.5 mg% (2.2; 2.7); p = 0.859. The organoleptic properties of the products were rated «excellent» by all patients and their parents (in children under 6 years, only according to the parents’ assessment). The indicators of physical development did not change. There was no adverse events (allergic reactions, dyspepsia, refusal to take food). Conclusion. Introduction of new functional products — low-protein starchy flakes enriched with a vitamin complex and natural fruit and berry additives — in the diet of children with phenylketonuria allows to maintain the level of phenylalanine in the blood at the level of reference values.Обоснование. В питании детей с фенилкетонурией широко используют специализированные продукты на основе крахмалов, ассортимент которых постоянно расширяется.Цель исследования — изучить безопасность состава хлопьев крахмаломучных, обогащенных комплексом жирорастворимых витаминов, натуральными плодовыми и ягодными добавками, используемых в пище детей с фенилкетонурией.Методы. В исследование включали детей в возрасте до 14 лет, комплаентных к ранее проводимой гипофенилаланиновой диете, без острых инфекционных, тяжелых соматических или неврологических заболеваний. Исследуемые продукты — крахмалоржаные, пшеничные и пшеничные плодово-ягодные хлопья с комплексом провитамина А и витамина Е — назначали взамен применявшихся ранее низкобелковых кондитерских изделий в количестве 20–25 г/сут детям младше 6 лет, по 30–40 г — детям, достигших возраста или старше 6 лет. Продукты выдавали с рекомендацией использовать поочередно, продолжительностью не менее 10 сут, всего на 30 сут исследования. Безопасность продуктов оценивали по концентрации фенилаланина в крови (определяли флюориметрическим методом). Дополнительно оценивали органолептические качества продуктов и динамику физического развития детей.Результаты. В исследование включили 15 детей, средний возраст 4,4±1,9 года. Исходная концентрация фенилаланина в крови варьировала от 1,6 до 3,9 мг%, медиана — 2,2 мг% (2,0; 2,8). Через 30 сут после включения в рацион крахмаломучных хлопьев содержание фенилаланина в крови не изменилось и составило 2,5 мг% (2,2; 2,7); р=0,859. Органолептические свойства продуктов были оценены на «отлично» всеми пациентами и их родителями (у детей в возрасте до 6 лет — только согласно оценке родителей). Показатели физического развития не изменились. Нежелательные явления (аллергические реакции, диспепсии, отказ от приема продуктов) не зафиксированы.Заключение. Введение в рацион детей с фенилкетонурией новых функциональных продуктов — хлопьев крахмаломучных низкобелковых, обогащенных витаминным комплексом и натуральными плодовыми и ягодными добавками, позволяет сохранять уровень фенилаланина в крови на уровне референсных значений.ИСТОЧНИК ФИНАНСИРОВАНИЯ Работа выполнена при поддержке гранта Федерального государственного научного учреждения «Всероссийский научно-исследовательский институт крахмалопродуктов» Федерального агентства научных организаций (Московская область). Для целей исследования использовались продукты, безвозмездно предоставленные производителем (опытное производство ФГНУ «ВНИИК» ФАНО).КОНФЛИКТ ИНТЕРЕСОВ Т.Э. Боровик, Н.Н. Семёнова, О.Л. Лукоянова, Н.Г. Звонкова, Т.В. Бушуева, Т.Н. Степанова, В.А. Скворцова — проведение научно-исследовательских работ при поддержке компаний Heinz, Semper, Хипрока Нутришион Ист Лимитед. И.М. Гусева, Е.А. Рославцева, А.К. Геворкян, С.Т. Быкова, Т.Г. Калинина, С.Г. Калиненкова подтвердили отсутствие конфликта интересов.ВЫРАЖЕНИЕ ПРИЗНАТЕЛЬНОСТИ Выражаем благодарность к.м.н. С.Г. Калиненковой (Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского) за участие в выполнении лабораторной части данного исследования. 

Ekaterinburg Atelier of Andrey Voronikhin

Рассматриваются екатеринбургские работы, прямо и косвенно связанные с именем выдающегося русского зодчего, высказывается предположение о руководящей роли самого архитектора, круга его единомышленников на одном из отрезков деятельности уральской казенной камнеобработки.The article describes some works made in Yekaterinburg and either directly or indirectly connected with the name of the outstanding Russian architect. The author considers the architect's leading role and his partners' role in the creation thereof during a historic period in the state stone working of the Urals

PHARMACOLOGICAL CORRECTION OF CEREBRAL BLOOD FLOW DISTURBANCES IN WOMEN WITH ARTERIAL HYPERTENSION IN POSTMENOPAUSE

Aim: to study cerebral blood flow and cholesterol metabolism in menopausal women with arterial hypertension (AH); to evaluate dynamics of cerebral blood flow parameters and plasma lipid concentrations in these patients during 6-month antihypertensive and hypolipidemic therapy.Material and methods: 24 women with AH of I and II grade were examined. They were in postmenopausal period of life during 7,1±0,5 years. At the beginning of the study all women were prescribed moexipril as monotherapy, daily dose 7,5 – 15 mg. Patients with initial dislipidemia were prescribed lipid reducing drug atorvastatin in 10mg daily dose additionally to the antihypertensive therapy. Therefore all the patients were divided into two groups: I – monoteraphy with moexipril (13 people), II – combined therapy with moexipril and atorvastatin (11 people). At the beginning of the study and after 6 months all the patients passed through ultrasonic Dopplerography of vessels of head and neck, rheoencephalography, their lipoproteidogrammes were studied.Results: During 6-month therapy all the patients showed proved decrease in systolic and diastolic blood pressure, also positive dynamics of neuropsychological status, improvement in cerebral blood flow according to the results of Dopplerography of vessels and rheoencephalography. Normalization of plasma lipid spectrum was noted. More significant positive changes in cerebral hemodynamic parameters and plasma lipid spectrum were observed in patients, who received combined therapy with antihypertensive and lipid reducing drugs.Conclusion: Deterioration of cerebral hemodynamics is typical for women with long-lasting AH. The most positive influence on cerebral perfusion was received due to combined therapy with moexipril and atorvastatin

Leprosy in the Guise of Skin Tuberculosis — Complexities of Diagnostics

Objective: demonstration of the case of the leprosy late diagnosis at the female patient previously watched with the diagnosis «skin tuberculosis». Materials and Methods. A 69 years old female patient watched from 2011 to 2016 with the diagnosis «skin tuberculosis» and was cured with weak effect; in 2016 the diagnosis «skin tuberculosis» was not confirmed. She undergone assessment at the State Research Centre for Dermatovenereology and Cosmetology of the Ministry of Health of the Russian Federation. The assessment included bacterioscopy of skin scrapings, pathomorphological studies of biopsy samples, molecular genetic testing. Results. On the grounds of complaints, medical history, data of surveying and physical examination, results of the clinical-laboratory studies the following diagnosis was stated: «dimorphous leprosy, leprosy BB (multibacillary leprosy, border line leprosy, active stage). Conclusion. The present observation indicates that the variety of leprosy clinical presentations and lack of suspicions on account of this ultra-rare disease lead to late diagnosis

Bladder cancer: treatment after progression. Results of the second retrospective analysis of data on the efficacy of vinflunin in patients with metastatic urothelial cancer in real clinical practice in Russia

Objective. There is the second generalized analysis of administration of vinflunine in real clinical practice in Russia.Materials and methods. This analysis gathered 15 patients with urothelial carcinoma treated using this medicine in 8 cancer centers in Russia. We assessed efficacy, safety profile of vinflunine in this subset of patients.Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 73.3 %, one patient demonstrated complete response. Median of response duration accounts for 3.8 months. Six-month and 1-year survival rate made up 93.3 %. Adverse events were observed in 53.5 %, with only one episode of neutropenia 4 grade.Conclusion. In our second analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, we confirm expediency to administer of vinflunine for metastatic urothelial carcinoma

Enhanced regulatory gene expressions in the blood and articular cartilage of patients with rheumatoid arthritis

Objective: to study the expression ratio of the non-tissue specific regulatory genes mTOR, р21, ATG1, caspase 3, tumor necrosis factor-а (TNF-а), and interleukin-6 (IL-6), as well as matrix metalloproteinase 13 (MMP-13) and X type collagen (COL10A1), cartilage resorption-associated MMP13 and COL10A1 in the blood and knee articular cartilage in patients with rheumatoid arthritis (RA). Subjects and methods. Twenty-five specimens of the distal femoral articular cartilage condyles were studied in 15 RA patients (mean age 52.4+9.1 years) after endoprosthetic knee joint replacement and in 10 healthy individuals (mean age 36.0+9.1 years) included into the control group. Twenty-eight blood samples taken from 28 RA patients (aged 52+7.6 years) prior to endoprosthetic knee joint replacement and 27 blood samples from healthy individuals (mean age 53.6+8.3 years; a control group) were also analyzed. Real-time quantitative polymerase chain reaction was applied to estimate the expression of the mTOR, p21, ATG1, caspase 3, TNF-а, IL- 6, COL0A1, and MMP-13 genes. The levels of a protein equivalent in the p70-S6K(activated by mTOR), p21, and caspase 3 genes concerned was measured in the isolated lymphocyte lysates, by applying the commercially available ELISA kits. Total protein in the cell extracts was determined using the Bradford assay procedure. Results. The cartilage samples from patients with end-stage RA exhibited a significantly higher mTOR, ATG1, p21, TNFа, MMP-13, and COL10A1 gene expressions than did those from the healthy individuals. At the same time, IL6 gene expression was much lower than that in the control group. The expressions of the mTOR, ATG1, p21, TNFа, and IL 6 genes in the blood of RA patients were much greater than those in the donors. Caspase 3 expression did not differ essentially in the bloods of the patients with RA and healthy individuals. The bloods failed to show MMP-13 and COL10A1 expressions. High mTOR and p21 gene expressions were accompanied by the elevated concentrations of the corresponding proteins in the cell lysates of the patients with RA compared to the controls. Conclusion. The findings suggest for the first time that regulatory mTOR, ATG1, p21, and TNFа gene expressions are enhanced in the blood and articular cartilage of RA patients. These changes are accompanied by the increased expression of MMP 13 gene that is responsible for articular cartilage resorption. Therefore, the higher expression of the examined regulatory genes in the blood of RA patients may be indicative of articular cartilage degradation