Correlation of susceptibility to ortho-aminoazotolueneinduced hepatocarcinogenesis with Car and Ahr signaling pathway activation in mice

Ortho-aminoazotoluene (OAT) is a potent hepatocarcinogen for most strains of mice. It has previously been shown that OAT application activates the aryl hydrocarbon receptor (Ahr) and the constitutive androstane receptor (Car) in the mouse liver. Both of these receptors are directly involved in the process of hepatocarcinogenesis. In this study, we investigated the effect of chronic OAT administration on the mRNA expression levels of Ahr, Car and their target genes Cyp1a1 and Cyp2b10 in the liver of DD/He (DD) and CC57BR/Mv (BR) mouse strains contrasting in sensitivity to hepatocarcinogenesis. The inflammatory response of these strains was also studied. Male mice of both strains received OAT oil solution at the dose of 225 mg/kg body weight four times within two months. Control animals received the equivalent solvent amount. Mice were sacrificed on days 1 and 4 after the last OAT administration. Gene expression levels in the liver were determined by real-time PCR. The inflammatory response was evaluated by serum concentration of tumor necrosis factor alpha (TNF-alpha). In resistant BR mice, OAT induced a pronounced and prolonged increase in Cyp1a1 mRNA, showing primarily Ahr activation, while the DD strain displayed a more pronounced elevation of Cyp2b10 expression, indicative of Car activation. In addition, a strong inflammatory response to OAT was recorded in DD mice but not in BR. It is assumed that the prevalence of Ahr signaling pathway activation over Car signaling pathway activation is a factor of resistance to OAT-induced hepatocarcinogenesis

Расчет допустимых отклонений между данными маммографии и ультразвукового исследования при определении локализации непальпируемых образований молочных желез с помощью программы для ЭВМ Mammography Sono Analyzer

Objective: standard deviation calculation in determining non-palpable breast masses localization: mammography and sonography data for a more accurate pre-surgical diagnostics and labeling.Materials and methods. We have applied the Mammography Sono Analyzer (MSA) software for studying 52 women 37 to 76 years old with non-palpable breast masses for comparing the focal mass localization based on mammography and sonography data. The patients were divided into 3 groups based on the breast size: small (S), medium (M) and large (L). Results. Standard deviation between mammography and sonography data gas been obtained: S – 1,0 cm maximum, M – 2,0 cm maximum, L – less than 2,5 cm.Conclusions. The MSA software allows to determine the standard deviations of non-palpable breast masses localization for breast of different size taking into consideration the mammography and sonography data.Цель исследования: расчет допустимых отклонений при определении локализации непальпируемых очаговых образований молочных желез, полученных двумя разными методами: маммографии (ММГ) и УЗИ, для более точной предоперационной диагностики и маркировки.Материал и методы. С помощью программы Mammo graphy Sono Analyzer (MSA) нами было обследовано 52 женщины в возрасте от 37 до 76 лет с непальпируемыми образованиями молочных желез для сопоставления данных локализации очаговых образований, полученных при ММГ и УЗИ молочных желез. При исследовании пациенты были разделены на 3 группы в зависимости от размеров молочных желез: маленькие (“S” – от англ. small), средние (“M” – от англ. medium) и большие (“L” – от англ. large).Результаты. Были получены данные допустимых отклонений по локализации между ММГ и УЗИ: для размера S – не превышающие 1,0 см, для размера M – не превышающие 2,0 см, для размера L – не более 2,5 см. Заключение. При получении различия в данных при ММГ и УЗИ с помощью программы MSA можно определить допустимость отклонений по локализации непальпируемых очаговых образований для различных размеров молочных желез

Genomics and proteomics of the liver fluke <em>Opisthorchis felineus</em>

The causative agent of opisthorchiasis, the liver fluke Opisthorchis felineus (Rivolta, 1884) is one of the helminths of humans and animals in Russia. Together with closely related species of trematodes O. viverrini (Poirier, 1886) and Clonorchis sinensis (Loos, 1907), O. felineus is a part of a triad of epidemiologically important trematodes in the family Opisthorchiidae. Adult O. felineus worms infest the hepatobiliary system of warm-blooded animals and might provoke the development of severe pathologies, including malignancy of bile duct epithelium. The high medical importance of O. felineus attracts the attention of researchers. This review briefly summarizes the data about O. felineus genomics and proteomics. The review provides a comparative analysis of the number of genes and sizes of nuclear genomes of a number of flatworms, the distribution of intron lengths, as well as results of synteny between the O. felineus, O. viverrini and C. sinensis genomes. Special attention is paid to a particular form of RNA processing known as trans-splicing, widely presented in the opisthorchiid genomes. We also provide the results of a comparative analysis of the xenobiotic metabolizing system between parasitic and free-living flatworms. Moreover, data on parasitic granulins, which are potential promoters of cholangiocyte neoplasia, are also presented. Data on the O. felineus genomics and proteomics provide first insights into the structural and functional organization of the genome of this parasitic flatworm with a complex life cycle as well as provide a significant contribution to our understanding of “host-parasite” interaction and evolution of this group of parasitic flatworms

Preferred sunspot longitudes: Non-axisymmetry and differential rotation

As recently found, the distribution of sunspots is non-axisymmetric and spot group formation implies the existence of two persistent active longitudes separated by 180 degrees. Here we quantitatively study the non-axisymmetry of sunspot occurrence. In a dynamic reference frame inferred from the differential rotation law, the raw sunspot data show a clear clustering around the persistent active longitudes. The differential rotation describing the dynamic frame is quantified in terms of the equatorial angular velocity and the differential rotation rate, which appear to be significantly different from those for individual sunspots. This implies that the active longitudes are not linked to the depth of sunspot anchoring. In order to quantify the observed effect, we introduce a measure of the non-axisymmetry of the sunspot distribution. The non-axisymmetric component is found to be highly significant, and the ratio of its strength to that of the axisymmetric one is roughly 1:10. This provides additional constraints for solar dynamo models.Comment: 7 pages, 8 figures, Astronomy and Astrophysics, in pres

Mechanisms of trematodiases pathogenicity: the presence of the secretory proteins from the liver fluke Opisthorchis felineus in the gallbladder tissues of the patients with chronic opisthorchiasis

Opisthorchiasis caused by the liver fluke Opisthorchis felineus infection remains a serious public health problem in the former USSR and Eastern European countries. O. felineus infests the bile ducts, the liver and gallbladder of many fish-eating mammalian species, including humans. Opisthorchiasis leads to a number of related diseases of the liver and pancreas: liver fibrosis, cholangitis, cholecystitis, liver cysts and pancreatitis. Excretory-secretory products of the parasite are considered to be key factors in host-parasite relationships and mediate pathogenic pleiotropic effects on the host organism.The aim of this study was to determine the helminthic proteins (thioredoxin peroxidase and glutathione-S-transferase) in the gallbladder tissues of the experimental animals and patients with opisthorchiasis disease. We demonstrated by immunohistochemistry assay using antibodies against recombinant O. felineus proteins that thioredoxin peroxidase and glutathione-S-transferase could be detected in the biliary duct epithelium of the experimental animals and in human gallbladder tissues. Moreover, these proteins could also be detected in human gallbladder infiltrated cells and underlying connective tissues. The results are important for understanding the molecular mechanisms of opisthorchiasis pathogenesis, as well as for improvement of the immunodiagnostics of the opisthorchiasis and opisthorchiasis-related diseases

Experimental opisthorchiasis: a study of blood cells, hematopoiesis and startle reflex in laboratory animals

One of the species of the family Opisthorchiidae, Opisthorchis felineus (O. felineus), causes severe disturbances in humans and animals, and so it is the subject of important research studies. Two weeks after infection we compared the impact of O. felineus invasion on the changes in blood cells composition, bone marrow hematopoiesis and behavioral startlereflex in inbred C57BL/6 male mice and Syrian hamsters (Mesocricetus auratus). Considerable interspecies differences were revealed for many parameters estimated. It was found that the relative weight of the main organ of the peripheral immune system – spleen, is significantly larger in mice than in hamsters. Moreover, the infection with O. felineus caused a significant enlargement of the spleen only in mice. More pronounced changes in the blood cells composition, which was accompanied by activation of hematopoietic stem cells of myeloid and erythroid set, were determined in hamsters. Blood changes in the response to infection in mice were less severe and were not accompanied by the changes in colony formation. Mouse acoustic startle reaction differed from hamster one too. The expression of the startle reaction and the value of pre-pulse inhibition were discriminated in animals of two species. Infected hamsters had no reaction of habituation  to the sound stimulus. In addition, the maturation of O. felineus worms was faster in hamsters than in mice. Data obtained suggest a greater resistance of mice to O. felineus infection, but do not exclude the availability of mice as a model in the study of processes taking place in the host during the development of experimental opisthorchiasis

Эффекты одно- и семикратного введения комплекса альбендазола с динатриевой солью глицирризиновой кислоты хомячкам, инвазированным Opisthorchis felineus

The purpose of the research is to evaluate the effect of albendazole as part of the supramolecular complex with disodium salt of glycyrrhizic acid obtained by solid-phase mechanical treatment.Materials and methods. The anthelmintic activity of the complex and its effect on the host organism was assessed on hamsters infected with Opisthorchis felineus by single and 7-fold administration at 45 days after infection. After 21 days, we counted the number of helminthes in the liver, and conducted a morphometric analysis of the liver and spleen, and detected biochemically the activity of alanine aminotransferase and aspartate aminotransferase in the animals’ blood serum.Results and discussion. The number of O. felineus significantly decreased after 7-fold, but not a single, administration of albendazole (ABZ) and ABZ-Na2GA complex (1 : 10). The administrated substances had no effect on the weight gain of the animals and the daily consumption of the pellets. At the same time, ABZ only as part of the complex normalized the weight of the liver and spleen in hamsters infected with O. felineus and reduced the alanine aminotransferase activity. Consequently, a longer administration of ABZ as part of the complex with disodium glycyrrhizinate has not only a pronounced anthelmintic effect, but also improves some of the physiological parameters of hamsters to a greater extent than a pure substance.Цель исследований – оценить действие альбендазола в составе супрамолекулярного комплекса с динатриевой солью глизирризиновой кислоты, полученного методом твердофазной механической обработки.Материалы и методы. Оценку антигельминтного действия комплекса и его влияния на организм хозяина проводили на хомячках, инвазированных Opisthorchis felineus, при одно- и семикратном введении через 45 сут после заражения. Через 21 сутки после этого подсчитывали число гельминтов в печени; проводили морфометрический анализ печени и селезенки, а также биохимическое определение активности ферментов аланинаминотрансферазы и аспартатаминотрансферазы в сыворотке крови животных.Результаты и обсуждение. Число O. felineus существенно снижалось после семикратного, но не однократного, введения альбендазола (АБЗ) и комплекса АБЗ-Na2ГК (1 : 10). Вводимые вещества не оказывали влияния на прирост массы тела животных и суточное потребление гранул. При этом только в составе комплекса АБЗ нормализовал массу печени и селезенки у инвазированных O. felineus хомячков и снижал активность фермента аланинаминотрансферазы. Следовательно, более длительное введение АБЗ в составе комплекса с динатрия глицирризинатом оказывает не только выраженный антигельминтный эффект, но и в большей степени, чем чистое вещество, улучшает некоторые физиологические показатели хомячков

Коррекция микроциркуляторных нарушений в комплексном лечении больных с острой эмпиемой плевры и пиопневмотораксом

Results of treatment of 548 patients with acute empyema and pyopneumothorax are shown. An application of freshly frozen or cryosupernatant plasma, heparin or proteinase inhibitors provides an improvement in microcirculation at the inflammation area and allows better outcome equally with the adequate drainage of the pleural space.Дан анализ результатов лечения 548 больных с острой эмпиемой плевры и пиопневмотораксом. Применение свежезамороженной или криосупернатантной плазмы, введение гепарина и ингибиторов протеиназ способствует улучшению микроциркуляции в очаге воспаления, что наряду с адекватным дренированием гнойника в плевральной полости и рациональной антибиотикотерапией позволяет улучшить исходы заболевания

Антигенные свойства рекомбинантного аналога белка легумаин трематоды Opisthorchis felineus, вызывающей описторхоз у человека

We estimated potential of protein legumain from opisthorchiasis agent O. felineus for application in immunodiagnosis of this disease. Bacterially expressed recombinant protein (rOF49-leg) showed strong difference in Enzyme-linked immunosorbent assay (ELISA) between infected and negative sera. These results suggest the potential of this antigen for development of serodiagnostic test for human opisthorchiasis.Работа посвящена оценке применимости белка легумаин возбудителя описторхоза O. felineusдля иммунодиагностики этого заболевания. Рекомбинантный белок (rOF49-leg), клонированный и экспрессированный в E. coli, в иммуно-ферментном анализе (ИФА) продемонстрировал различие в иммунореактивности между инфицированными и здоровыми сыворотками. Эти результаты показывают потенциальную пригодность этого антигена для разработки серодиагностических тестов на описторхоз