Нейровизуализационные характеристики изменений вещества головного мозга при генетической форме микроангиопатии (ЦАДАСИЛ)

Purpose. To evaluate specific changes in MRI of the human brain, associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Materials and methods. We enrolled 24 patients with genetically confirmed CADASIL (19–81 y.o.). The following MRI sequences were performed for every subject: T1 MPR, T2, T2-FLAIR, DTI and SWI. Brain tissue lesions were assessed using STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).Results. In the CADASIL group the following changes were observed (in % of patients): recent small subcortical infarcts – none; lacunes – 54%; white matter hyperintensities (WMH) by Fazekas 1 – 12%, Fazekas 2 – 17%, Fazekas 3 – 71% (sites of predilection: anterior temporal lobe and external capsule); cerebral microbleeds – 42%; enlarged perivascular spaces – 88%; brain atrophy – 27%.Conclusion. Neuroimaging signs of brain lesions are common for all types of cerebral small vessel disease, including CADASIL. However, there are some features in patients with CADASIL. The detection of petechial intraparenchymal hemorrhages is a diagnostically and prognostically useful marker, so it is very important to use gradient echo planar T2* or SWI sequence in the conventional MRI protocol.Цель исследования: оценить нейровизуализационные особенности поражения вещества головного мозга, выявляемые у пациентов с церебральной аутосомно-доминантной артериопатией с субкортикальными инфарктами и лейкоэнцефалопатией (ЦАДАСИЛ).Материал и методы. В исследование было включено 24 пациента с генетически подтвержденным диагнозом ЦАДАСИЛ. Всем пациентам было выполнено МРТисследование в следующих режимах: Т1 MPR, Т2, Т2-FLAIR, DTI и SWI. Поражение вещества головного мозга оценивалось согласно критериям STRIVE (STandards for ReportIng Vascular changes on nEuroimaging).Результаты. При оценке поражения вещества головного мозга были получены следующие результаты: гиперинтенсивность белого вещества выявлена у всех пациентов (Fazekas 1 – 12%, Fazekas 2 – 17%, Fazekas 3 – 71%) с наиболее характерной локализацией поражения в области наружных капсул и полюсов височных долей, в 54% случаев выявлено наличие лакун, недавние малые инфаркты не обнаружены, в 42% случаев определялись микрокровоизлияния, расширенные периваскулярные пространства встречались у 88% пациентов, расширение ликворных пространств – у 27%.Заключение. Нейровизуализационные характеристики поражения вещества головного мозга являются общими для ряда заболеваний, обусловленных патологией сосудов малого калибра, однако существуют характерные паттерны поражения вещества головного мозга у пациентов с ЦАДАСИЛ. Включение в стандартный протокол обследования последовательностей, чувствительных к геморрагическому компоненту (T2*, SWI), а также знание и выявление характерных особенностей поражения вещества головного мозга играют важную роль в постановке диагноза ЦАДАСИЛ и его дифференциальной диагностике с другими заболеваниями сосудов малого калибра, а также с демиелинизирующими процессами

Особенности субпопуляционного состава дендритных клеток у больных ревматоидным артритом

Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Dendritic cells (DCs) as the main antigen-presenting cells play an important role in the pathogenesis of RA. There are two major DC populations: myeloid and plasmacytoid DCs (mDCs and pDCs). B cells as antibody-producing cells also play an important role in the pathogenesis of RA. The probability of achieving low disease activity and clinical and laboratory remission has been proven to be maximal in the very early period of the disease and in the patients who have not been previously prescribed disease-modifying antirheumatic drugs (DMARDs). In this connection, it is necessary to elaborate additional criteria and biomarkers for early RA.Objective: to investigate the subpopulation composition of DCs in patients with early-stage RA.Patients and methods. The investigation enrolled 60patients with RA who met the 2010 ACR/EULAR and the 1987ACR criteria. The patients with RA were divided into two groups: 1) 30patients with early RA (the disease duration was not more than 1 year); 2) 30 patients with advanced RA. A control group consisted of 30 patients with osteoarthritis (OA) who met the ACR criteria. All the patients with RA were treated with DMARDs. The patients with early RA had not previously received DMARDs; after being included in the study, they were prescribed methotrexate 15-20 mg/week. The patients with advanced RA took methotrexate 15-25 mg/week (n=24), sulfasalazine 2 g/day (n=5), or leflunomide 20 mg/day (n=1).At the first stage, the levels of different subpopulations of DCs and B lymphocytes were studied in the patients with early RA before initiation of therapy and in those with advanced RA and in the control persons. At the following stage, the time course of changes was investigated in the subpopulation composition of DCs and B lymphocytes during therapy.Results and discussion. The subpopulations of peripheral blood DCs in early RA were characterized. A subpopulation of mDCs was shown to dominate in the patients with early RA versus those with advanced RA or osteoarthritis (OA). In addition, the patients with RA showed a high B lymphocyte level. It was noted that there was no significant differences in the level of pDCs between RA and OA patients and there was an inverse relationship between the relative peripheral blood level of pDC and disease activity, which confirms the immunosuppressive role of pDCs in the pathogenesis of RA. The levels of mDCs and B lymphocytes during DMARD therapy were ascertained to significantly decrease to those seen in healthy donors.Conclusion. Thus, the findings suggest that the number of mDCs and B lymphocytes increases in patients with early RA, unlike those with OA. In addition, the change in the number of mDCs and B cells during therapy is associated with the dynamics of disease activity and may suppose that mDCs are a target for the action of DMARDs.Ревматоидный артрит (РА) является одним из наиболее распространенных ревматических заболеваний. Дендритные клетки (ДК) играют важную роль в патогенезе РА как основные антиген-презентирующие клетки. Выделяют две основные популяции ДК: миелоидные (мДК) и плазмоцитоидные (пДК). Также важную роль в патогенезе РА играют В-клетки как клетки-антителопродуценты. Доказано, что вероятность достижения низкой активности и клинико-лабораторной ремиссии максимальна в самом раннем периоде заболевания и у тех пациентов, которым базисные противовоспалительные препараты (БПВП) ранее не назначали. В связи с этим необходима разработка дополнительных критериев, а также биомаркеров раннего РА.Цель исследования — изучить субпопуляционный состав ДК у больных РА на ранних стадиях заболевания.Пациенты и методы. В исследование включено 60 пациентов с РА, соответствующих критериям ACR/EULAR 2010 г. и ACR 1987 г. Пациенты с РА были разделены на две группы: в 1-ю группу вошли больные с ранним РА (длительность заболевания не более 1 года, n=30), во 2-ю — с развернутым РА (n=30). Контрольную группу составили 30 пациентов с остеоартритом (ОА), соответствующих критериям ACR. Всем пациентам с РА проводили терапию БПВП. Пациенты с ранним РА ранее не получали БПВП, после включения в исследование им был назначен метотрексат 15—20 мг/нед. Пациенты с развернутым РА получали метотрексат по 15—25мг/нед (n=24), сульфасалазин 2 г/сут (n=5) или лефлуномид 20мг/сут (n=1).На первом этапе проведено исследование уровня различных субпопуляций ДК, а также В-лимфоцитов у пациентов с ранней стадией РА до начала терапии, а также у пациентов с развернутым РА и в контрольной группе. На следующем этапе была изучена динамика субпопуляционного состава ДК и В-лимфоцитов на фоне терапии.Результаты и обсуждение. Охарактеризованы субпопуляции ДК периферической крови при раннем РА. Показано, что у пациентов с ранним РА, в отличие от пациентов с развернутым РА и остеоартритом (ОА), наблюдается доминирование субпопуляции мДК. Кроме того, пациенты с РА характеризуются высоким уровнем В-лимфоцитов. Отмечено отсутствие значимых различий в уровне пДК между пациентами с РА и ОА, также выявлена обратная связь между относительным содержанием пДК в периферической крови и активностью заболевания, что подтверждает иммуносупрессивную роль пДК в патогенезе РА. Установлено значимое снижение содержания мДК и В-лимфоцитов на фоне терапии БПВП до уровня здоровых доноров.Выводы. Таким образом, полученные данные свидетельствуют об увеличении числа мДК и В-лимфоцитов у пациентов с ранним РА в отличие от пациентов с ОА. Кроме того, изменение количества мДК и В-клеток на фоне терапии ассоциировано с динамикой активности заболевания и позволяет предположить, что мДК являются мишенью для воздействия БПВП

Architecture and life forms of

Thymus jenisseensis is endemic to Southern Siberia. The structure of Thymus jenisseensis were studied with the use of an architectural approach. The architectural unit consist of branched compound skeletal axis of the 1st and 2nd order, and is repeated many times in the structure of adults. As a result of studying the architectural units of individuals growing in different sites of a coenopopulation, in the upper border of the forest belt (Tsagan-Shibetu, Republic of Tuva), differences were identified. An architectural unit consisting of branched orthotropic or ascending basisympodially accreting compound skeletal axes develops on a site of a dry riverbed; an architectural unit consisting of branched orthotropic or ascending acrosympodially accreting compound skeletal axes develops on a site of high-altitude steppe on a plain. The diversity of compound skeletal axes in the structure of architectural units contributes to the formation of two biomorphs (dwarf subshrub and dwarf shrub), changes in the vitality and duration of development of T. jenisseensis individuals. The identified features of architecture are morphological mechanisms of adaptation of the species to living conditions

Application of the original method of intra-operative electrophysiological stimulation of recurrent laryngeal nerve with surgical interventions on the neck organs

The OBJECTIVE was the reduction in the frequency of specific complications of surgical treatment of patients with pathology of the thyroid and parathyroid glands using the original method of monitoring the neuro-functional activity of the recurrent laryngeal nerve.METHODS AND MATERIALS. The research was conducted in two stages. At the first stage, the object of the topographic-anatomical study was 50 male and female corpses. The research, based on the fixed material, was focused upon the study of the anatomic special features of recurrent laryngeal nerves, their relations with neighboring structures, the study of peculiarities of recurrent laryngeal nerve syntopy and its neighboring structures to find the least traumatic way of incision during electroneurophysiological monitoring of activity. At the second stage, the object of the study was 60 patients with a benign pathology of the thyroid gland, who were operated on with the use of the original method of intra-operational visualization and control method over neuro-functional activity of recurrent laryngeal nerve.RESULTS. The frequency of the three different variants of topographic-anatomical position of recurrent laryngeal nerve depends on the side of the body. The safest, stable and the fastest one to be found is the left recurrent laryngeal nerve. Postoperative unilateral paresis of the larynx, diagnosed in 4 of 60 patients, is regarded as postischemic. Two-sided paresis of the larynx was diagnosed in 1 patient.CONCLUSION. This method allows to minimize the development of severe intraoperative complications, to reduce the frequency of postoperative paralysis and paresis of the larynx. Intra-operative visualization of recurrent laryngeal nerves is especially necessary during the repeated surgeries with postoperative scar transformations with wrong syntopy of neck organs and vascular-nerve structures, which makes it possible to minimize the number of postoperative paralyses and paresis of larynx and to get positive effect without carrying out the intubation of trachea among patients with postoperative paralysis of larynx or stenosis, and to avoid more serious damage of larynx or trachea in case of intubation

Chemistry for Sustainable Development 17 (2009) 507511 501 Seasonal Dynamics of Riccardin C Accumulation in Primula macrocalyx Bge

Abstract Season al dyn amics has been studied for a metabolite accumulation in Primula macrocalyx Bge. with respect to its major component, bisbibenzyl riccardin C 1, an inhibitor of inducible NO synthase. Seven introduced populations of the plant have been investigated. A wild-growing P. macrocalyx population was used as a reference. It has been demonstrated the harvesting of plant raw material for the purpose of bisbenzyl 1 isolation is appropriate for carrying out after plant flowering, during the fruiting stage. Besides, in the course of the investigation there were 3′, 4′, 5′-trimethoxyflavone 2 and perrottetin Å 3 isolated from the acetone extract of P. macrocalyx

INDUCTION OF T-CELL IMMUNE RESPONSE IN CHRONIC HCV-INFECTED PATIENTS WITH UNDERLYING DENDRITIC CELL IMMUNOTHERAPY

A key role of T cells in viral elimination and  absence  of strong  T cell responses  in patients with chronic hepatitis C virus (HCV) infection presumes that activation of antigen-specific T cells may be a promising approach to enhance treatment efficacy. Given the central role of dendritic cells (DCs) in the induction of T cell response, the aim of our study was to evaluate  effects of DC immunotherapy upon  immunological parameters in chronic HCV infection. Ten patients with chronic hepatitis C (genotype 1) were vaccinated with monocytederived DCs, generated in presence of IFNα (IFN-DCs) and pulsed with recombinant HCV Core (1–120) and NS3 (1192–1457) proteins. The vaccination protocol included as initiating procedure (one injection per week, ns = 4) and maintaining treatment (one  monthly injection, ns = 6), with subsequent follow up for 6 months. The immunotherapy was not associated with serious adverse events,  significant  post-vaccination reactions, or increased hepatitis C activity, according to biochemical tests. Ex vivo studies have shown that immunotherapy elicited  strong and stable immune response  to Core and moderate response  to NS3 protein, which manifested as a significant  increase  of MNC proliferation and  IFNγ production in response  to Core  and  enhancement of IFNγ production (without higher  proliferation rates),  in response  to NS3.  DC  immunotherapy also led to increase  of ConA-induced MNC proliferation up  to normal levels indicating a recovery  of mitogenic T cell  reactivity. Meanwhile, T cell  activation did  not  elicit  antigen-specific Th2  response  and  expansion of CD4+CD25+CD127  regulatory T cells.  Despite induced immune response, the  immunotherapy with  DCs was not  accompanied by decreased viremia  levels. Nevertheless, a transitory decrease of viral load  in four patients and stable decrease of viremia  in two patients as well as an inverse correlation between  NS3-specific proliferation and viremia  (Rss = 0.62; p < 0.05) by the end of 6-month follow-up indicated that  the antigenspecific T cells may have a potential to control viral replication

Structure, stability, and biological activity of bacteriophage T4 gene product 9 probed with mutagenesis and monoclonal antibodies

Gene product (gp) 9 connects the long tail fibers and triggers the structural transition of T4 phage baseplate at the beginning of infection process. Gp9 is a parallel homotrimer with 288 amino acid residues per chain that forms three domains. To investigate the role of the gp9 amino terminus, we have engineered a set of mutants with deletions and random substitutions in this part. The structure of the mutants was probed using monoclonal antibodies that bind to either N-terminal, middle, or C-terminal domains. Deletions of up to 12 N-terminal residues as well as random substitutions of the second, third and fourth residues yielded trimers that failed to incorporate in vitro into the T4 9(-)-particles and were not able to convert them into infectious virions. As detected using monoclonal antibodies, these mutants undergo structural changes in both N-terminal and middle domains. Furthermore, deletion of the first twenty residues caused profound structural changes in all three gp9 domains. In addition, N-terminally truncated proteins and randomized mutants formed SDS-resistant "conformers" due to unwinding of the N-terminal region. Co-expression of the full-length gp9 and the mutant lacking first 20 residues clearly shows the assembly of heterotrimers, suggesting that the gp9 trimerization in vivo occurs post-translationally. Collectively, our data indicate that the aminoterminal sequence of gp9 is important to maintain a competent structure capable of incorporating into the baseplate, and may be also required at intermediate stages of gp9 folding and assembly.status: publishe