The frequency of obesity in patients with acute pancreatitis, chronic pancreatitis and pancreatic cancer

BACKGROUND: In the XXI century, the frequency of pancreas diseases increased 2–3 times. The expectation that causes a pandemic lead to the development of a number of diseases. The results of studies on the relationship of overweight, obesity with the risk of developing pancreas diseases (acute pancreatitis (AP), chronic pancreatitis (CP) and pancreas cancer (PC)) are very heterogeneous (for AP and PC) and not numerous (for CP). AIMS: to identify the frequency of obesity in AP patients (APр), CP patients (СPр) and PC patients (PCр) and compare these parameters. MATERIALS AND METHODS: at the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: the frequency of obesity in APp, CPp; PCp. RESULTS: The frequency of obesity in APp (13,6%), CPp (24,7%) and PCp (20,0%) did not differ significantly. Among the examined patients, the lowest average BMI (24,2±0,7 kg/m2) was observed in APp (p=0,049). BMI ≥22,5 kg/m2 was found to be associated with AP (OR=0,398; 95%CI 0,195–0,812; p=0,011). An inverse relationship was shown between the BMI and “definite” CP (Exp (B)=0,772; 95%CI 0,632–0,942; p=0,011). In men with CP and in CPp alcoholic etiology, weight deficit was observed significantly more often than in women with CP and in CPp biliary etiology, respectively. Earlier (a year before the present survey), obesity was more common in PCp (55,6%) than in APp (13,6%, χ2=3,3; p=0,000) and CPp (25,8%, χ2=12,0; p=0,001). A history of obesity (in our study one year before PC detection) and PC (OR=4,435; 95% CI 2,180–9,025; p=0,000) direct relationship was shown. CONCLUSIONS: the frequency of obesity in APp, CPp and PCp was similar. The average BMI was higher in APp, than in CPp and PCp. BMI≥22,5 kg/m2 was a protective factor for AP. BMI was inversely associated with “defined” CP. A history of obesity was directly associated with PC

Metabolic Risk Factors and Their Impact on Quality of Life in Patients with Pancreatic Cancer, Acute or Exacerbated Chronic Pancreatitis

Аim: to evaluate metabolic risk factors and their impact on quality of life in patients with pancreatic cancer (PC) and in patients with acute or exacerbated chronic pancreatitis.Materials and methods. Forty-five patients with PC (group 1) and 141 patients with acute pancreatitis or exacerbated chronic pancreatitis (group 2) in an observational multicenter clinical cross-sectional uncontrolled study were examined. Clinical, laboratory and instrumental examination of patients and assessment of risk factors (lipid profile, blood plasma glucose, obesity, arterial hypertension) were carried out in accordance with clinical recommendations. Patients completed the SF-36 questionnaire once to assess quality of life at hospital admission before treatment.Results. In group 1, indicators of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) in blood serum (3.7 ± 0.2; 2.2 ± 0.2 and 0.8 ± 0.1 mmol/L) were lower than in group 2 (5.1 ± 0.1; 3.1 ± 0.1 and 1.2 ± 0.1 mmol/L; p < 0.05). Arterial hypertension was more common in group 1 (55.6 %) than in group 2 (34.8 %; p = 0.013). The presence of arterial hypertension increases the chance of having PC by 2.7 times (p < 0.05). Body mass index parameters, including obesity, as well as parameters of triglycerides, and fasting plasma glucose, did not differ between the groups. Logistic regression analysis revealed a direct relationship with PC HDL hypocholesterolemia (Exp B = 4.976; p < 0.001) and arterial hypertension (Exp B = 2.742; p = 0.027) and an inverse relationship — with hypercholesterolemia (Exp B = 0.204; p = 0.002). The chance of having PC was not associated with age, fasting plasma glucose ³ 7.0 mmol/L, obesity. Quality of life indicators were higher in group 1 than in group 2 on four SF-36 scales: bodily pain (68.1 ± 5.1 and 36.8 ± 2.0; p < 0.001), general health (51.1 ± 2.5 and 38.0 ± 1.7 points; p < 0.001), social functioning (74.7 ± 3.0 and 64.5 ± 2.2 points; p = 0.007), role emotional functioning (28.2 ± 5.2 and 12.5 ± 3.1 points; p = 0.007) and in the general domain “physical component of health” (40.2 ± 1.0 and 33.6 ± 0.8 points; p < 0.001). In group 1 with HDL hypocholesterolemia compared with its absence, the indicators of role emotional functioning (22.2 ± 5.1 and 51.9 ± 13.7 points; p = 0.020) were lower, with arterial hypertension compared with its absence — role physical functioning (5.0 ± 4.0 and 25.5 ± 7.5 points; p = 0.036) and role emotional functioning (16.0 ± 5.1 and 43.3 ± 8.8 points; p = 0.007) were lower.Conclusions. In patients with PC arterial hypertension was more common and the levels of total cholesterol, LDL-C and HDL-C were lower than in patients with acute or exacerbated chronic pancreatitis. The chance of having PC is directly associated with HDL hypocholesterolemia, with arterial hypertension, inversely — with hypercholesterolemia, and is not associated with age, fasting plasma glucose ³ 7 mmol/L, or obesity. In patients with PC, quality of life indicators were higher on four SF-36 scales and on the general domain “physical component of health” than in the group with acute or exacerbated chronic pancreatitis. In patients with PC metabolic factors significantly worsened self-assessment of quality of life in terms of role functioning; in patients with acute or exacerbated chronic pancreatitis there was no such association

Особенности лабораторных исследований при диагностике краснухи у беременных

Introduction: Despite on mandatory vaccination against rubella, the amount of pregnant women without immunity to rubella may exceed 20%. These women represent a risk group for the rubella disease.Objectives: The goals of the presented work are to analyze the cases of anti-rubella IgM detection in pregnant women, and to develop an algorithm for management of such patients.Materials and Methods: Screening has been performed by ELISA test systems company Radim (Italy). In total 799 patients were examined for rubella in 2013, 56 of them were pregnant women.Results. Positive IgM antibodies to rubella in 2013 have been identified in 5 cases, including 4 pregnant women. A detailed analysis of medical history, clinical and laboratory data has been done. In none of these cases the diagnosis of rubella has been confirmed.Conclusions. The main criterion for the diagnosis of rubella in pregnant women with rubella markers in the absence of clinical symptoms must be a dynamic examination, including study on IgM- and IgG-antibodies to rubella virus. The study must be conducted in the same laboratory at intervals of 10–14 days. In most cases, determination of IgG-antibodies avidity helps to estimate the time of infection. In complicated cases it is recommended to use PCR and immunoblot.Актуальность: несмотря на введение обязательной вакцинации от краснухи, количество беременных, у которых отсутствуют защитные антитела, может превышать 20%. Эти женщины представляют группу риска по заболеванию краснухой.Цель работы: проанализировать случаи выявления IgM к краснухе у беременных и разработать алгоритм ведения таких пациенток.Материалы и методы: скрининг проводился методом иммуноферментного анализа на тест-системах фирмы Radim (Италия). В 2013 г. на антитела к краснухе было обследовано 799 пациентов, из них 56 беременных.Результаты. Положительные IgM антитела к краснухе были выявлены в 5 случаях, в том числе у 4 беременных. Проведен тщательный анализ анамнестических, клинических и лабораторных данных. Ни в одном из этих случаев диагноз краснухи не был подтвержден.Выводы. Основным критерием диагностики краснухи у беременных при обнаружении маркеров краснухи и отсутствии клинической симптоматики должно быть динамическое обследование беременной, включающее исследование на IgM- и IgG-антитела к вирусу краснухи. Исследование должно проводиться в одной лаборатории с интервалом 10–14 дней. Определение авидности IgG-антител помогает в большинстве случаев определить давность инфицирования. В сложных случаях необходимо использовать иммуноблот и ПЦР

Идентификация маркеров аденокарциномы желудка на основе биоинформатического поиска и анализа генной экспрессии

Introduction. Searching for specific and sensitive molecular tumor markers is one of the important tasks of modern oncology. These markers can be used for early tumor diagnosis and prognosis as well as for prediction of therapeutic response, estimation of tumor volume or to assess disease recurrence through monitoring. Gene expression data base mining followed by experimental validation of results obtained is one of the promising approaches for searching of that kind.Objective: to identify several membrane proteins which can be used for serum diagnosis of intestinal type of gastric adenocarcinoma.Materials and methods. We used bioinformatic-driven search using Gene Ontology and The Cancer Genome Atlas (TCGA) data to identify mRNA up-regulated in gastric cancer (GC). Then, the expression levels of the mRNAs in 55 pare clinical specimens were investigated using reverse transcription polymerase chain reaction.Results. Comparative analysis of the mRNA levels in normal and tumor tissues using a new bioinformatics algorithm allowed to identify 3 high-copy transcripts (SULF1, PMEPA1 and SPARC), intracellular content of which markedly increased in GC. Expression analysis of these genes in clinical specimens showed significantly higher mRNA levels of PMEPA1 and SPARC in tumor as compared to normal gastric tissue. Interestingly more than twofold increase in expression level of these genes was observed in 75 % of intestinal-type GC. The same results were found only in 25 and 38 % of diffuse-type GC respectively.Conclusions. As a result of original bioinforamtic analysis using TCGA data base two genes (PMEPA1 and SPARC) were shown to be significantly upregulated in intestinal-type gastric adenocarcinoma. The findings show the importance of further investigation to clarify the clinical value of their expression level in stomach tumors as well as their role in carcinogenesis.Введение. Одна из важных задач современной онкологии – поиск ассоциированных с опухолями молекулярных маркеров, которые могут использоваться для диагностики и прогнозирования рака, оценки степени радикальности операции и последующего лечения, а также раннего выявления рецидивов. Одним из продуктивных вариантов подобного поиска является анализ транскриптомных баз данных с применением методов биоинформатики с последующей валидацией полученных результатов на клиническом материале.Цель исследования – поиск мембранных белков, которые могут быть использованы для сывороточной диагностики аденокарциномы желудка интестинального гистологического типа.Материалы и методы. Идентификацию потенциальных маркеров рака желудка (РЖ) проводили с использованием баз данных Gene Ontology и the Cancer Genome Atlas (TCGA). Последующую оценку дифференциальной экспрессии генов выполняли на парных образцах аденокарциномы и нормальной ткани желудка, взятых от 55 пациентов. Экспрессию генов оценивали с помощью полимеразной цепной реакции с обратной транскрипцией в режиме реального времени по методу ΔCq.Результаты. Сравнительный анализ уровней синтеза матричных РНК (мРНК) нормальных и опухолевых тканей с применением нового алгоритма биоинформатического поиска привел к идентификации 3 наиболее высококопийных транскриптов (SULF1, PMEPA1 и SPARC), внутриклеточное содержание которых заметно повышается при РЖ. При анализе уровня мРНК данных генов в клиническом материале наблюдалось более чем двукратное увеличение уровня экспрессии PMEPA1 и SPARC в 75 % образцов РЖ интестинального гистологического типа. В образцах РЖ диффузного гистологического типа этот показатель составил 25 и 38 % соответственно.Выводы. Использование оригинального биоинформатического подхода, основанного на анализе данных TCGA, позволило выявить 2 гена (PMEPA1 и SPARC), преимущественно экспрессирующихся в опухолях желудка интестинального типа. Полученные результаты свидетельствуют об актуальности дальнейшего исследования роли этих генов в патогенезе РЖ и оценки клинической значимости уровня их экспрессии в опухолевой ткани

Экзосомальные протеазы при колоректальном раке

The objective is to evaluate the level of ADAM10 and ADAM17 (a disintegrin and metalloproteinase) proteases, as well as 20S-proteasomes in blood plasma exosomes of patients with colorectal cancer.Materials and methods. The study included 60 patients with colorectal cancer (T2–4N0–2M0–1) and 10 control patients. The material for the study was EDTA blood plasma. Exosomes of blood plasma were isolated by ultrafiltration with ultracentrifugation. The level of tetraspanin-associated (ADAM10 and ADAM17) and tetraspanin-non-associated (20S-proteasome) proteases was evaluated by flow cytometry and Western blotting.Results. A twice negative subpopulation (ADAM10–/ADAM17–) predominated in blood plasma exosomes of colorectal cancer patients and control patients. The level of ADAM10+/ADAM17– exosomes was significantly higher in the exosomes of the plasma of control patients. There were no significant differences between the ADAM10/ADAM17 subpopulations and the 20S-proteasome level, depending on sex, age and tumor grade. A decrease in the ADAM10+/ADAM17– subpopulation was found in patients with metastatic colorectal cancer with hematogenous metastases compared with patients with T2–4N1–2M0 and 20S-proteasome compared to T2–4N0M0. A decrease in ADAM10–/ ADAM17+ exosomes and 20S-proteasomes level was found in exosomes of patients with colorectal cancer with a metabolic syndrome  in comparison with patients without metabolic disorders.Цель исследования – оценить уровень протеаз ADAM10 и ADAM17 (a disintegrin and metalloproteinase), а также 20S-протеасом в экзосомах плазмы крови больных колоректальным раком.Материалы и методы. В исследование были включены 60 больных колоректальным раком (T2–4N0–2M0–1) и 10 пациентов контрольной группы. Материалом для исследования послужила 3-замещенная калиевая соль этилендиаминтетрауксусной кислоты (ЭДТА) плазма крови. Экзосомы плазмы крови выделены методом ультрафильтрации с ультрацентрифугированием. Уровень тетраспанин-ассоциированных (ADAM10 и ADAM17) и тетраспанин-неассоциированных (20S-протеасомы) протеаз оценивали с помощью проточной цитометрии и вестерн-блоттинга.Результаты. Дважды негативная субпопуляция (ADAM10– / ADAM17–) преобладала как в экзосомах плазмы крови больных колоректальным раком, так и в экзосомах пациентов контрольной группы. Обнаружены статистически значимые различия в уровне ADAM10+ / ADAM17– экзосом у пациентов контрольной группы по сравнению с больными колоректальным раком. Не выявлено значимых различий между субпопуляциями ADAM10 / ADAM17 и уровнем 20S-протеасом экзосом в зависимости от пола, возраста и степени дифференцировки опухоли. У пациентов с метастатическим колоректальным раком с гематогенными метастазами выявлено снижение субпопуляции ADAM10+ / ADAM17– экзосом по сравнению с пациентами с местно-распространенным колоректальным раком (T2–4N1–2M0) и 20S-протеасом по сравнению с пациентами с T2–4N0M0. В экзосомах больных колоректальным раком с наличием метаболического синдрома выявлено снижение ADAM10– / ADAM17+ экзосом и уровня 20S-протеасом по сравнению с больными без метаболических нарушений

Сравнение экспрессии гена РСА3 в осадках и экзосомах мочи при раке предстательной железы

Introduction. Prostate cancer (PCa) is one of the common oncological diseases in men. Expression of the PCA3 gene in urine is currently used as a molecular genetic marker of PCa.Objective: to comparative analysis of the PCA3 expression in urine sediments and exosomes for the determination of the biomaterial, which allows detecting the PCA3 expression in more efficient manner.Materials and methods. The 12 patients with different stages of PCa and 8 control samples were examined.Results. The diagnostic accuracy of the PCA3 gene expression analysis in this cohort exceeded 90 %. We had not obtained significant differences in the sensitivity and specificity of the PCA3 hyperexpression in the urine sediments compared with exosomes. This result indicates in favor to using urine sediment for the PCA3 analysis as a biomaterial with less time-consuming sample preparation, although the possible advantage of exosomes for the analysis of the expression marker panels requires further studies.Введение. Рак предстательной железы (РПЖ) является одним из наиболее частых онкологических заболеваний у мужчин. В качестве молекулярно-генетического маркера РПЖ в настоящее время используют определение экспрессии гена РСА3 в моче.Цель работы – сравнительный анализ экспрессии гена РСА3 в осадках и в экзосомах мочи для определения биоматериала, позволяющего более эффективно проводить определение экспрессии этого гена.Материалы и методы. Были исследованы данные 12 пациентов с различными стадиями РПЖ и 8 контрольных образцов.Результаты. Диагностическая точность анализа экспрессии РСА3 в этой выборке превысила 90 %. Не выявлено достоверных различий чувствительности и специфичности гиперэкспрессии РСА3 при анализе осадков по сравнению с экзосомами мочи. Это указывает на целесообразность использования осадков мочи для анализа РСА3 как биоматериала с менее трудоемкой пробоподготовкой, однако возможные преимущества экзосом для анализа панелей экспрессионных маркеров требуют дальнейшего изучения

Molecular interactions at the surface of extracellular vesicles

Extracellular vesicles such as exosomes, microvesicles, apoptotic bodies, and large oncosomes have been shown to participate in a wide variety of biological processes and are currently under intense investigation in many different fields of biomedicine. One of the key features of extracellular vesicles is that they have relatively large surface compared to their volume. Some extracellular vesicle surface molecules are shared with those of the plasma membrane of the releasing cell, while other molecules are characteristic for extracellular vesicular surfaces. Besides proteins, lipids, glycans, and nucleic acids are also players of extracellular vesicle surface interactions. Being secreted and present in high number in biological samples, collectively extracellular vesicles represent a uniquely large interactive surface area which can establish contacts both with cells and with molecules in the extracellular microenvironment. Here, we provide a brief overview of known components of the extracellular vesicle surface interactome and highlight some already established roles of the extracellular vesicle surface interactions in different biological processes in health and disease