Impact of symptoms of eating disorders on the risk of gastrointestinal diseases

The aim of the study - to study the risk of comorbidity of gastrointestinal diseases with eating disordersЦель исследования - изучить влияние симптомов РПП на риск возникновения заболеваний желудочно-кишечного тракта (ЖКТ)

Assessment of the organization of children’s meals in a preschool educational institution in Yekaterinburg

The purpose of the study is to evaluate the organization of nutrition for children aged 3 to 7 years in a preschool educational institution (DOE) in Yekaterinburg based on the menu layout.Цель исследования – оценить организацию питания детей в возрасте от 3 до 7 лет в дошкольном образовательном учреждении (ДОУ) г. Екатеринбурга на основании меню-раскладки

MEDICINAL FORM OF TNF-α FOR LOCAL ADMINISTRATION

Composite preparation of tumor necrosis factor alpha and rheopolyglukin and polyethylene glycol (TNF-α+PG+PEG) was obtained. The specific activity of the samples was 4,13 х 107 IU/mg. The cytolytic activity of drugs TNF-α+PG+PEG and rhTNF-α did not change after 4 months when stored at 6 °С. Preparation TNF-α+PG+PEG provided a moderately prolonged elevation of TNF-alpha in blood of laboratory mice in contrast to TNF-α when they applied to the skin. The composite preparation did not have toxic, allergic and locally irritating action in experiments on laboratory animals

Frequencies of eleven BRCA1 and BRCA2 mutations in random sample of russian breast cancer patients

In this study we were aiming to determine frequencies ot eleven known mutations in BRCA1 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, Cys61 Gly, 2080delA, 2963del10) and BRCA2 (6174delT, 1528delAAAA, 9318delAAAA) in random sample of patients with breast cancer, Russian population (1091 cases). We found 64 mutation carriers (5,87%), primerily with 5382insC (BRCA1) mutation - 4,03% from the sample. We did not detect three mutations: 2963del10 (BRCA1), 1528delAAAA (BRCA2) and 9318delAAAA (BRCA2). We revealed 11 mutation carriers among patients without any anamnesis data supposing hereditary form of breast cancer. Taking into account the range of analyzed random sample and diagnostic panel and detection of listed below mutations in other Russian studies, we assume mutations in BRCA1 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G (Cys61Gly), 2080delA) and BRCA2 (6174delT) tests could be recommended for inclusion in screening programs for revelation of hereditary breast cancer cases.Целью работы было установление частот встречаемости одиннадцати ранее описанных мутаций в генах BRCA1 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, Cys61Gly, 2080delA, 2963del10) и BRCA2 (6174delT, 1528delAAAA, 9318delAAAA) в неотобранной выборке больных раком молочной железы в Российской популяции (1091 человек). Мутации были найдены у 64 человек (5,87%), преобладала мутация 5382insC (BRCA1) -4,03% от выборки. Мутации 2963del10 (BRCA1), 1528delAAAA (BRCA2) и 9318delAAAA (BRCA2) не были обнаружены. В результате исследования выявлено 11 пациенток с мутацией в BRCA1 или BRCA2 без каких-либо данных в анамнезе, позволяющих предположить наследственную форму рака молочной железы. Учитывая размер тестированной неотобранной выборки, широту диагностической панели и нахождение зарегистрированных нами мутаций другими авторами, анализ на мутации в генах BRCA1 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G (Cys61Gly), 2080delA) и BRCA2 (6174delT) может быть рекомендован для включения в скрининговые программы по выявлению наследственных случаев рака молочной железы

Наследственный рак молочной железы: генетическая и клиническая гетерогенность, молекулярная диагностика, хирургическая профилактика в группах риска

5–10 % of breast cancer cases are hereditary, 30 % of them are caused by BRCA1 and BRCA2 mutations (breast / ovarian cancer syndrome). Average cumulative risks of breast and ovarian cancer in BRCA1 mutation carriers run up to 87 % and 44 %, correspondingly. The risk for contralateral breast cancer is also high: after 25 years, 62.9 % of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer develop contralateral breast cancer. The role of single nucleotide polymorphisms in BRCA1 and BRCA2 genes modifying breast and gynaecological cancer risks is actively studied. Genetic testing is performed as a part of genetic counselling. The main inclusion criteria are multiple affected family members with breast / ovarian cancer, breast cancer at young age (under 35–50 years), ovarian cancer at any age, male breast cancer, morphological features of breast cancer (triple-negative, medullar tumors), ethnicity (Jewish ancestry). High-risk individuals carrying BRCA mutations undergo specific surveillance, chemoprophylaxis and surgery protocols. Prophylactic bilateral mastectomy reduces breast cancer risk by 90–94 %.На долю наследственных форм приходится 5–10 % случаев рака молочной железы, 30 % из них обусловлены мутациями в генах BRCA1 / 2 (синдром наследственного рака молочной железы / рака яичников). Средние кумулятивные риски для носителей мутаций в гене BRCA1 достигают 87 % в отношении развития рака молочной железы и 44 % в отношении развития рака яичников. Высок риск контралатерального рака молочной железы: при манифестации первичной опухоли у носителей мутаций в гене BRCA1 в возрасте до 40 лет он составляет 62,9 %. Активно изучается роль однонуклеотидных полиморфизмов, модифицирующих риск развития рака молочной железы и других опухолей женской репродуктивной системы у носителей мутаций в генах BRCA1 / 2. Молекулярная диагностика проводится в рамках медико-генетического консультирования. Основными показаниями для генетического тестирования являются онкологически отягощенный семейный анамнез, рак молочной железы у женщин в молодом возрасте (до 35–50 лет), рак яичников, рак молочной железы у мужчин, морфологические особенности рака молочной железы (трижды негативные, медуллярные опухоли), этническая принадлежность (ашкеназские евреи). В группах высокого генетического риска проводятся профилактические химиотерапевтические и хирургические мероприятия. Показана высокая эффективность профилактических операций в отношении развития рака молочной железы и рака яичников. Двусторонняя профилактическая мастэктомия снижает риск развития рака молочной железы на 90–94 %

НАСЛЕДСТВЕННЫЙ РАК МОЛОЧНОЙ ЖЕЛЕЗЫ И ЯИЧНИКОВ

The annual incidence of breast cancer (BC) in the world is 1,383,000 cases. Genetic predisposition is one of the major risk factors for breast cancer and ovarian cancer (OC). The proportion of hereditary breast cancer ranges from 5 to 10%, which amounts 69 150-138 000 cases. Family history of accumulation of breast cancer and tumors of the female reproductive system have 25% of patients. Thus, patients with hereditary forms and family breast cancer account 345,700 of all diagnosed cases of breast cancer. Hereditary ovarian cancer occurs in 10-17% cases. Hereditary breast and ovarian cancer are characterized by autosomal dominant inheritance with high (incomplete) penetrance, incidence in early age and pronounced phenotypic and genotypic heterogeneity. According to numerous studies, 20-50% of hereditary breast cancer cases and 90-95% of hereditary ovarian cancer cases in women, and from 4 to 40% of breast cancer cases in men are caused by germinal mutations in the BRCA1 and BRCA2 genes. Considering the syndromic pathology of hereditary BC and OC and can also be associated with mutations in genes TP53, CHEK2, MLH1, MSH2, PALB2, PTEN, NBS1, ATM, BRIP1, RAD50, BLM, FGFR2, and others.Ежегодная заболеваемость раком молочной железы (РМЖ) в мире составляет 1 383 000 случаев. Генетическая предрасположенность является одним из основных факторов риска развития РМЖ и рака яичников (РЯ). Доля наследственно-обусловленного РМЖ колеблется от 5 до 10 %, что составляет 69 150-138 000 случаев. Семейную историю накопления РМЖ и опухолей женской репродуктивной системы отмечают 25 % заболевших женщин. Таким образом, пациенты с наследственными и семейными формами РМЖ в целом составляют 345 700 от всех диагностированных случаев РМЖ [1]. Наследственный рак яичников встречается с частотой 10-17 % [2,3]. Наследственные РМЖ и РЯ характеризуются аутосомно-доминантным типом наследования с высокой (неполной) пенетрантностью, ранним возрастом возникновения и выраженной генотипической и фенотипической гетерогенностью [3-6]. По данным многочисленных исследований, 20-50 % наследственного рака молочной железы (НРМЖ) и 90-95 % — наследственного рака яичников (НРЯ) у женщин, а также от 4 до 40 % РМЖ у мужчин обусловлены герминальными мутациями в генах BRCA1 и BRCA2 [2,3,7,8]. С учетом синдромальной патологии НРМЖ и НРЯ могут быть ассоциированы также с мутациями в генах TP53, CHEK2, MLH1, MSH2, PALB2, PTEN, NBS1, ATM, BRIP1, RAD50, BLM, FGFR2 и др. (таблица 1)

Study on Hemostimulating Properties of Granulocyte-Macrophage Colony Stimulating Factor

The hemostimulating properties of granulocyte-macrophage colony-stimulating factor (GM-CSF) make possible its clinical use in alleviating side effects of anti-cancer radio- and chemotherapy, in bone marrow transplantation, and in the treatment of some primary immunodeficiency conditions associated with leukopenia. The State Research Center of Virology and Biotechnology “Vector” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing has developed a high-performance technology for production of recombinant human GM-CSF (rhGM-CSF) based on a recombinant E. coli strain. The aim of the study was to assess hemostimulating activity of the rhGM-CSF preparation obtained using the new developed technology, as observed in cell culture and in the mice model of myelosuppression induced by cyclophosphamide administration. Materials and methods: in vitro evaluation of rhGM-CSF hemostimulating activity was performed by MTT assay in the commercial HL-60 promyelocytic leukemia cell culture with preliminary suppression of cell growth rate by adding a low concentration of dimethyl sulfoxide to the medium. In vivo studies were carried out in CBA/CaLac mice with cyclophosphamide-induced myelosuppression. The hemostimulating properties of the drug were evaluated after subcutaneous administration of 1–175 µg/kg doses for 4–5 days, following administration of a cytostatic agent. The total number of leukocytes and the content of their morphological forms were determined in blood samples taken at different time points after the drug administration. The statistical processing of the experimental data was based on analysis of variance using Statgraphics v. 5.0 software. Results: the proliferative activity of HL-60 cells incubated with the rhGM-CSF preparation for 72 hours was shown to be dose-dependent. The highest values of the increase in proliferative activity associated with an increase in the drug dose were observed in the concentration range from 0.04 to 0.64 ng/mL (proliferative activity increased by 11–18% when the dose was increased twofold). The experiments in mice demonstrated a two-phase pattern of the dose-dependent effect. The drug showed the highest hemostimulating effect at the dose of 90 µg/kg. Conclusions: the rhGM-CSF preparation obtained using the new developed technology has a pronounced hemostimulating activity confirmed by both in vitro and in vivo test systems

DEVELOPMENT OF A REAL-TIME RT-PCR-BASED TEST PANEL FOR ASSESSMENT OF CYTOKINE PROFILE IN MONONUCLEAR CELLS FROM BLOOD AND SYNOVIAL FLUID IN RHEUMATOID ARTHRITIS

Abstract. An imbalance between pro- and anti-inflammatory cytokine synthesis plays a crucial role in pathogenesis of rheumatoid arthritis (RA), including erosive joint lesions. Differences in cytokine profiles of RA patients are sufficiently investigated. However, possible interrelations between cytokine profile, immune inflammation, RA progression, and the disease prognosis require further investigations. Due to active search for novel targets in anti-cytokine therapy of RA, evaluation of cytokine levels in peripheral blood and synovial joint fluid remain quite relevant. Therefore, novel methods aimed to determine mRNA expressed by cytokine genes are thought to be promising. Our research was intended to develop test systems for quantitative determination of mRNAs for the following cytokines: TNFα, IL-1β, IL-6, IL-8, IL-17, IL-15, IL-10, IFNγ, IL-4, IL-2. Present article concerns specificities of the developed test systems, description of their technical principles, as well as comparative studies of cytokine gene expression in peripheral blood and synovial joint fluid in RA patients. (Med. Immunol., 2008, vol. 10, N 6, pp 563-570)

High rate of mutations in the BRCA1, BRCA2, CHEK2, NBN, and BLM genes in Russian ovarian cancer patients

Background. The early diagnosis of ovarian cancer (OC) is an important problem in modern gynecological oncology due to significant detection rates for late-stage tumors. Intensive screening of patients from high-risk groups that include OC predisposition gene mutation carriers is indicated.Subjects and methods. An unselected group of 202 patients with OC and two control groups of blood donors: 591 healthy females; 1197 persons (including 591 females, 606 males) were examined. Patients and healthy individuals who identified themselves as ethnic Russians and residents of the Russian Federation participated in the study. Whole peripheral blood samples were collected at the Clinical Subdivisions of the N.N. Blokhin Russian Cancer Research Center and at the Department of Transfusiology of the Acad. B.V. Petrovsky Russian Research Center of Surgery in 2012–2013. Informed consent was obtained from all the participants. DNA was extracted using a Prep-GS-Genetics reagent kit. Real-time polymerase chain reaction genotyping assay was carried out by melting-curve analysis employing an BRCA SNP genotyping kit(BRCA1 and BRCA2 gene mutations) and original oligonucleotides (CHEK2, NBN, and BLM gene mutations). Thirteen population-specific mutations, including 7 (185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, and 2080delA) in the BRCA1 gene, 1 (6174delT) in the BRCA2 gene, 3 (1100delC, IVS2+1G>A, and 470T>C) in the CHEK2 gene, 1 (657delACAAA) in the NBN gene, and 1 (1642C>T) in the BLM gene, were genotyped. Polymerase chain reaction was performed using a DTprime real-time detection thermal cycler.Results and discussion. BRCA1 and BRCA2 gene mutations were detected in 46 (22.8 %) patients with OC; the prevailing mutation in the BRCA1 gene was 5382insC (58.7 %). OC was diagnosed in 32.6 % of the patients aged 51 years or older. The rate of moderate-penetrance mutations (1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene) was 0.5–1.0 % in the group of OC patients and 0–0.3 % in the control group of healthy women. The majority of these patients (5/6) were diagnosed with OC at age less than 50 years. The CHEK2 mutation, 470T>C, was more frequently encountered in the control group (6.6 %) than in the OC patient group (5.0 %). High rate of the CHEK2 mutation, IVS2+1G>A, was first shown for OC patients in the Russian Federation, the odds ratio was 11.9 (95 % confidence interval, 9.5–14.3; p = 0.056). It was preliminarily concluded that it played an important role in the development of OC in the Russian population; our findings should be verified in further investigations. The difference in the rate of mutations, such as 1100delC, IVS2+1G>A and 470T>C in the CHEK2 gene, 657del5 in the NBN gene, 1642C>T in the BLM gene, were insignificant in the patient and control groups, which may be related to the low population rate of these genetic markers and, in case of the CHEK2 mutation, 470T>C, may be linked to its low penetrance. By taking into account the fact that numerous studies have proven the clinical significance of all examined moderate-penetrance mutations whose prevalence in the Russian population has been confirmed by the authors of this paper, the inclusion of the mutations in a diagnostic panel to detect hereditary predisposition to OC is substantiated. The associated risks are higher for the rare mutations leading to the formation of truncated nonfunctional proteins, which are 1100delC and IVS2+1G>A in the CHEK2 gene, 657del5 in the NBN gene, and 1642C>T in the BLM gene. The penetrance of the CHEK2 mutation, 470T>C, is lower, which should be kept in mind during medical genetic counselling.Conclusion. The total rate of mutations in the BRCA1, BRCA2, CHEK2, NBN, and BLM genes in patients with OC was 30.7 %, which determines the expediency of molecular genetic screening in this category of patients