Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis

Эффективность специфической профилактики клещевого энцефалита

Vaccination remains the only way to prevent tick-borne encephalitis (TBE). All TBE vaccines are based on strains of the Far Eastern and European subtypes of TBE virus. Currently, the Siberian subtype of the virus, which differs from the vaccine strains, accounts for 80–100% of the genetic population of TBE virus in most of Russia. The proportion of TBE vaccinated patients among those infected was different from year to year in Russia, e.g. 3.9% in 2012 and 1.5% in 2018, there were also some fatal cases registered among vaccinated patients. In this regard, evaluation of the effectiveness of vaccination against various genetic subtypes of TBE is a promising area of research. The purpose of this study was to summarise the results of studies investigating effectiveness of specific prevention of TBE as regards various genetic subtypes of the virus. The paper analyses data on the effectiveness of TBE vaccination in experimental settings and in real life. It was demonstrated that the use of vaccines for prevention of TBE is effective, provided the vaccination coverage is not less than 80%. The paper cites the data from a long-term study of the stability and protective activity of vaccine immunity against TBE virus strains isolated in highly endemic territories. It was established that TBE vaccines have high immunogenic activity and contribute to the production of stable protective antibodies against the strains of the three genetic subtypes of the virus. Protective efficacy of vaccination depends on the number of vaccinations received, the vaccination scheme, gender and age of those vaccinated. The paper concludes by saying that further studies are needed to assess TBE vaccine efficacy in order to improve vaccination tactics, to better understand causes of morbidity and mortality among vaccinated individuals.Вакцинация по-прежнему остается единственной мерой профилактики клещевого энцефалита. Все вакцины для профилактики данного заболевания разработаны на основе штаммов дальневосточного и европейского подтипов вируса клещевого энцефалита. В настоящее время на большей территории России генетическая популяция вируса клещевого энцефалита представлена на 80–100% сибирским подтипом вируса, который отличается от штаммов, используемых для приготовления вакцин. В разные годы в стране показатель вакцинированных среди заболевших клещевым энцефалитом составлял 3,9% в 2012 г., 1,5% в 2018 г., в том числе регистрировались летальные случаи. В связи с этим перспективным направлением исследований является оценка эффективности вакцинации против различных генетических типов вируса клещевого энцефалита. Цель работы — анализ исследований эффективности специфической профилактики клещевого энцефалита против различных генетических типов вируса. В обзоре представлен анализ данных эффективности вакцинопрофилактики клещевого энцефалита в экспериментальных и реальных условиях. Показано, что вакцинопрофилактика клещевого энцефалита в условиях охвата прививками не менее 80% населения является эффективным способом защиты от клещевого энцефалита. Представлены данные многолетнего изучения устойчивости, протективной активности вакцинального иммунитета против штаммов вируса клещевого энцефалита, выделенных на высокоэндемичных территориях. Установлено, что все вакцины для профилактики клещевого энцефалита обладают высокой иммуногенной активностью и способствуют выработке устойчивых протективных антител против штаммов трех генетических подтипов вируса. Показано, что защитная эффективность вакцинации зависит от числа полученных прививок, схем вакцинации, пола и возраста привитых. Сделан вывод о необходимости дальнейшего изучения эффективности вакцин против клещевого энцефалита для совершенствования тактики вакцинопрофилактики, понимания причин заболеваемости и летальности среди вакцинированных лиц

Risk factors and comorbidities in patients with 2d -4 th grade of pelvic organ prolapse

The aim of the study - identification of risk factors and comorbidities in patients with 2-4 grade of pelvic organ prolapse.Цель исследования - выявление факторов риска и сопутствующей патологии у пациенток с ПТО 2-4 степени

Анализ многолетнего опыта изучения инактивированных культуральных вакцин для профилактики f клещевого энцефалита отечественного и зарубежного производства по показателю качества -специфическая активность (иммуногенность)

The analysis of the use of the method for the evaluation of specific (immunogenic) activity of vaccines for preventing tick-borne encephalitis (TBE vaccines) against protective dilution (PD50) and the minimum immunizing dose (MID50) has been performed. The method was standardized and submitted to the regulatory documents for TBE vaccines authorized in the Russian Federation. When analyzing the results of the study of specific (immunogenic) activity of TBE vaccines (107 TBE vaccine batches by different manufacturers have been studied) it was confirmed that the choice of real lethal dose (RLD50) indicator of TBE virus (test strain «Absettarov») in the range of 100-3000 LD50, the reasonability of using BALB /c cell-line mice, the effectiveness of the national method of determining immunogenicity in terms of MlD50 for TBE vaccines authorized in the Russian Federation. The reasonability of using immunogenicity reference standard for TBE-OSO 42-28-48 to assess the reproducibility of the experiments, and the homogeneity of laboratory animals in terms of quality. Methods for determining TBE vaccine immunogenicity («specific activity (immunogenicity)» in terms of PD50 and MID50 is applicable both for Russian commercial TBE vaccines and for FSME-Immun vaccine, manufactured by «Baxter Vaccine AG», Austria.Проведен анализ применения метода оценки специфической (иммуногенной) активности современных вакцин клещевого энцефалита (вакцины КЭ) по протективному разведению (ПР50) и минимальной иммунизирующей дозе (МИД50). Метод стандартизован и внесен в нормативные документы на зарегистрированные в Российской Федерации вакцины КЭ. При анализе результатов изучения специфической (иммуногенной) активности вакцин КЭ (исследовано 107 серий вакцин КЭ различных производителей) подтверждены: выбор показателя реальной летальной дозы (РЛД50) вируса КЭ (тест-штамм «Абсеттаров») в пределах 100-3000 ЛД50, целесообразность применения линейных мышей BALB/с, эффективность применения отечественного метода определения иммуногенности по показателю МИД50 для вакцин КЭ, зарегистрированных в Российской Федерации. Подтверждена целесообразность применения стандартного образца иммуногенности вакцины КЭ - ОСО 42-28-48 для оценки сходимости результатов постановки экспериментов и однородности лабораторных животных по качеству. Метод определения иммуногенности вакцин КЭ (показатель качества «Специфическая активность (иммуногенность)» по показателям ПР50 и МИД50 применим как для российских коммерческих вакцин КЭ, так и для вакцины ФСМЕ-Иммун, производства компании «Бакстер вакцины АГ», Австрия

Анализ групповой вспышки трихинеллеза у подростков в Самарской области

Objective. To study the peculiarities of trichinosis on the material of the group flashes.Materials and methods. Described and analyzed outbreak of trichinosis in 14 adolescents aged 13 to 18 years, were hospitalized in pediatric infectious ward of the city of Samara.Results. The source of infection – infected meat badger. The severity of illness depend on the amount of meat eaten, that is, the infectious dose of the pathogen. In severe cases, the incubation period of trichinosis was minimal (7 days), and if less severe – the maximum (from 19,5 to 21 days). Mild course also contributed to the early administration of antiparasitic therapy. Most of the children the disease begins with fever and dyspepsia, half recorded rash.At the height of the disease is predominant myalgias, half of cases – swelling. The peculiarity of the current severe trichinosis were pronounced toxic-allergic syndrome, generalized edema, myalgia and myasthenia gravis, up to a full adinamii, organ destruction: infectious-toxic kidney, cardiomyopathy, fulminant hepatitis, polyserositis with ascites, hydrothorax 3 weekdisease. The temperature in most of the patients wore a doublewavelength character with rises in the disease onset and disease for 2–3 weeks. It noted the duration of the clinical symptoms. The longest was myalgic, half of the patients remained at the time of discharge from the hospital. The features of laboratory parameters (leukocytosis, eosinophilia, ALT, AST, CRP) in various forms of the disease. The diagnosis was confirmed by serology (IgM, Ig G to Trichinella spiralis) in different phases of the disease. All patients received a specific antiparasitic therapy albendazolom secondary therapeutic dosage for 10 days, as well as detoxication, allergen and symptomatic therapy is indicated.Conclusion. Thus, health education among the population and will be a true prevention of trichinosis.Цель. Изучить особенности течения трихинеллеза на материале групповой вспышки.Материалы и методы. Описана и проанализирована вспышка трихинеллеза у 14 подростков в возрасте от 13 до 18 лет, находившихся на стационарном лечении в детском инфекционном отделении больницы города Самары.Результаты. Источник инфекции – зараженное мясо барсука. Тяжесть заболевания зависела от количества съеденного мяса, то есть от инфицирующей дозы возбудителя. В случае тяжелой формы трихинеллеза инкубационный период был минимальным (7 дней), при легкой – максимальным (от 19,5 до 21 дня). Развитию легкой формы способствовало раннее назначение антипаразитарной терапии. У большинства детей заболевание начиналось с лихорадки и диспепсических явлений, у половины регистрировалась экзантема. В разгаре заболевания преобладающими являлись миалгии, у половины заболевших детей – отеки. Особенностью течения тяжелой формы трихинеллеза явились выраженный токсико-аллергический синдром, генерализованные отеки, миалгии и миастении, вплоть до полной адинамии, органные поражения: инфекционно-токсическая почка, кардиомиопатия, реактивный гепатит, полисерозит с асцитом, гидротораксом на 3-й неделе заболевания. Температура у большей части больных носила двухволновый характер с подъемами в дебюте заболевания и на 2–3-й неделе заболевания. Отмечена продолжительность клинических симптомов. Самым продолжительным был миалгический, у половины больных сохранялся к моменту выписки из стационара. Отмечены особенности лабораторных показателей (лейкоцитоз, эозинофилия, АЛАТ, АСАТ, СРБ) при различных формах заболевания. Диагноз подтверждался серологически (IgM, Ig G к Trichinella spiralis) в различные фазы заболевания. Все больные получали специфическую антипаразитарную терапию альбендазолом в средне-терапевтической дозировке в течение 10 дней, а также дезинтоксикационную, гипосенсибилизирующую и симптоматическую терапию по показаниям.Заключение. Проведение санитарно-просветительской работы среди населения актуально и будет являться профилактикой возникновения трихинеллез

Effectiveness of Specific Prevention of Tick-Borne Encephalitis

Vaccination remains the only way to prevent tick-borne encephalitis (TBE). All TBE vaccines are based on strains of the Far Eastern and European subtypes of TBE virus. Currently, the Siberian subtype of the virus, which differs from the vaccine strains, accounts for 80–100% of the genetic population of TBE virus in most of Russia. The proportion of TBE vaccinated patients among those infected was different from year to year in Russia, e.g. 3.9% in 2012 and 1.5% in 2018, there were also some fatal cases registered among vaccinated patients. In this regard, evaluation of the effectiveness of vaccination against various genetic subtypes of TBE is a promising area of research. The purpose of this study was to summarise the results of studies investigating effectiveness of specific prevention of TBE as regards various genetic subtypes of the virus. The paper analyses data on the effectiveness of TBE vaccination in experimental settings and in real life. It was demonstrated that the use of vaccines for prevention of TBE is effective, provided the vaccination coverage is not less than 80%. The paper cites the data from a long-term study of the stability and protective activity of vaccine immunity against TBE virus strains isolated in highly endemic territories. It was established that TBE vaccines have high immunogenic activity and contribute to the production of stable protective antibodies against the strains of the three genetic subtypes of the virus. Protective efficacy of vaccination depends on the number of vaccinations received, the vaccination scheme, gender and age of those vaccinated. The paper concludes by saying that further studies are needed to assess TBE vaccine efficacy in order to improve vaccination tactics, to better understand causes of morbidity and mortality among vaccinated individuals

Modern Problems of Tick-Borne Encephalitis Specific Prevention. Communication II: Peculiarity of Immunity in Area with Siberian Subtype Domination

Siberian subtype of TBE virus dominates in the most part of Russia outside of the Far East. Peculiarity of immunity induced by Siberian subtype during disease or inapparent infection and change of immunity after vaccination are described in this article. Protective titre of antibodies and persistence of TBE virus (TBEV) in vaccinated organism are discussed

Epidemiological Situation of Tick-Borne Encephalitis in the Kurgan Region (1983–2017)

Relevance.Тhe Ural Federal district (Ural Federal district) is a highly endemic tick-borne viral encephalitis (TBEV) territories in the Russian Federation. The epidemiological situation on the TBEV is studied in Sverdlovsk and Chelyabinsk regions and slightly shown in the Kurgan region. There is no information about the evolution TBEV, the structure of immunity population, vaccine prevention in the Kurgan region. The article presents the dynamics epidemiological situation on TBEV in the Kurgan region over a 30-year period.Materials and methods: Used expedition reports, viral encephalitis named after the Academy of medical Sciences of the USSR for 1983–2007, as well as materials of medical institutions of the Kurgan region 2007–2017. For population immunity used: hemagglutination test (HAI-test), neutralization test (NT). To identify specific antibodies – IgG, IgM, antigen of TBEV, sets of reagents of ELISA from «Vector-Best» were used. To immunotypicalli and genotypically Strains and isolates RNA of TBEV isolated in 1983–2007, used precipitation in agar (RDPA) and by RT-PCR technique in real time with genotypespecific probes.Results and discussions: Kurgan region is a highly TBEV endemic area. the morbidity rate – 18,3 per 100 thousand people 1983. Maximum elevation – 44.1 in 1996 to and decrease to 13.5 in 2000–2012. The immune part of the population according hemagglutination tests, on epidemiologically significant territories is 15–20%, (66% NT), in the regions with sporadic incidence is 8%, (21–50% NT), in non-endemic territories – 3%. At the present stage, the region marked the expansion of nosoareal TBEV due to the previously less significant Eastern regions. In Kurgan region vaccination coverage against TBE 39.3%. The clinical efficacy of vaccination was manifested in an increase in fever forms of TBE disease and a decrease in meningeal and focal forms of the disease. In the period 2004–2012 the number of vaccinated patients was 20.3% of the total number of patients.Сonclusions. Evolution of tick-borne encephalitis manifested the expansion of nosoareal TBEV, increase seasonal activity of ticks, the TBEV Siberian subtype is absolutely dominating

The Condition of Post-Vaccination Immunity to the Tick-Borne Encephalitis Virus in the Population Highly Endemic Area with Siberian Subtype Domination

Relevance. Modern inactivated culture vaccines against tick-borne encephalitis (TBE) with at least 70% of the population living in the  natural foci of the FE give a high epidemiological effect. Unresolved  issues are the simplification of the cumbersome vaccination scheme,  the optimal number of revaccinations, the protective titer of  antibodies against the Siberian subtype of the TBE virus dominant in Russia.Goal of this work is to study the state of postvaccinal immunity in the population of the highly endemic area of the Trans-Urals.Materials and methods. 1381 blood serum of the population vaccinated from 3 to 13 times with vaccines was studied: unconcentrated culture inactivated from strain No. 205 of the TBE  virus produced by «Virion», Tomsk, «EnceVir» produced by  «Microgen», Tomsk, produced by Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products of  Russian.To identify specific antibodies – IgG, IgM, antigen of TBE  virus, sets of reagents of ELISA from «Vector-Best» were used.  Neutralizing activity of sera was determined by the index of  neutralization index with 4 strains of the Siberian subtype of TBE  virus.Results. The immune layer among the vaccinated population in 10 districts of the Kurgan region, which differ in epidemiological tension, ranges from 69.9% to 94.6%. The intensity of humoral immunity  varied according to IgG titers in ELISA from 1: 100 – 1: 200 to 1:  3200 (rarely 1: 6400). The duration and intensity of immunity  depends on the number of vaccinations and the number of missed  remote revaccinations. Preservation and intensity of immunity with  reliability P = 95%, higher in persons vaccinated 6–10 times  compared with the group of vaccinated 3 times. In persons who had 4–8 booster dose of vaccine, the immunity persisted for 15–19–36 years with an IgG titer of not more than 1: 100. The neutralizing  activity of the sera of vaccinated individuals with antibody titers from 1:100 to 1: 6400 was studied for the Siberian subtype of BCE. The  degree of protection of the vaccinated population against the doses  of the virus found in individual mites is determined. From the doses  of the virus, 57% of the vaccinated population are most often found  in mites, and from the dose of 105– 8%. Recommendations are  proposed on the tactics of revaccination of the population, depending on the level of immunity

The analysis of a long-term experience of studying inactivated cell-culture vaccines for preventing tick-borne encephalitis of domestic and foreign manufacture in terms of specific activity (immunogenicity)

The analysis of the use of the method for the evaluation of specific (immunogenic) activity of vaccines for preventing tick-borne encephalitis (TBE vaccines) against protective dilution (PD50) and the minimum immunizing dose (MID50) has been performed. The method was standardized and submitted to the regulatory documents for TBE vaccines authorized in the Russian Federation. When analyzing the results of the study of specific (immunogenic) activity of TBE vaccines (107 TBE vaccine batches by different manufacturers have been studied) it was confirmed that the choice of real lethal dose (RLD50) indicator of TBE virus (test strain «Absettarov») in the range of 100-3000 LD50, the reasonability of using BALB /c cell-line mice, the effectiveness of the national method of determining immunogenicity in terms of MlD50 for TBE vaccines authorized in the Russian Federation. The reasonability of using immunogenicity reference standard for TBE-OSO 42-28-48 to assess the reproducibility of the experiments, and the homogeneity of laboratory animals in terms of quality. Methods for determining TBE vaccine immunogenicity («specific activity (immunogenicity)» in terms of PD50 and MID50 is applicable both for Russian commercial TBE vaccines and for FSME-Immun vaccine, manufactured by «Baxter Vaccine AG», Austria