Mesenchymal Stem Cell Therapy For Ischemic Heart Disease: Advances And Challenges
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Коноплянников Михаил Анатольевич
Котова Светлана Леонидовна
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Current Pharmaceutical Design |
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Ischemic Heart Disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect and manipulating their cardiomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June 2018.
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Публикация |
Role of a receptor-like kinase K1 in pea Rhizobium symbiosis development
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Порозов Юрий Борисович
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Planta |
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The LysM receptor-like kinase K1 is involved in regulation of pea-rhizobial symbiosis development.
The ability of the crop legume Pisum sativum L. to perceive the Nod factor rhizobial signals may depend on several receptors that differ in ligand structure specificity. Identification of pea mutants defective in two types of LysM receptor-like kinases (LysM-RLKs), SYM10 and SYM37, featuring different phenotypic manifestations and impaired at various stages of symbiosis development, corresponds well to this assumption. There is evidence that one of the receptor proteins involved in symbiosis initiation, SYM10, has an inactive kinase domain. This implies the presence of an additional component in the receptor complex, together with SYM10, that remains unknown. Here, we describe a new LysM-RLK, K1, which may serve as an additional component of the receptor complex in pea. To verify the function of K1 in symbiosis, several P. sativum non-nodulating mutants in the k1 gene were identified using the TILLING approach. Phenotyping revealed the blocking of symbiosis development at an appropriately early stage, strongly suggesting the importance of LysM-RLK K1 for symbiosis initiation. Moreover, the analysis of pea mutants with weaker phenotypes provides evidence for the additional role of K1 in infection thread distribution in the cortex and rhizobia penetration. The interaction between K1 and SYM10 was detected using transient leaf expression in Nicotiana benthamiana and in the yeast two-hybrid system. Since the possibility of SYM10/SYM37 complex formation was also shown, we tested whether the SYM37 and K1 receptors are functionally interchangeable using a complementation test. The interaction between K1 and other receptors is discussed.
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Публикация |
A novel lipopeptaibol emericellipsin a with antimicrobial and antitumor activity produced by the extremophilic fungus emericellopsis alkalina
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Андреев Ярослав Алексеевич
Люндуп Алексей Валерьевич
Крашенинников Михаил Евгеньевич
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Molecules |
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Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies. View Full-Text
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The Anemonia viridis Venom: Coupling Biochemical Purification and RNA-Seq for Translational Research
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Андреев Ярослав Алексеевич
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Marine drugs |
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Blue biotechnologies implement marine bio-resources for addressing practical concerns. The isolation of biologically active molecules from marine animals is one of the main ways this field develops. Strikingly, cnidaria are considered as sustainable resources for this purpose, as they possess unique cells for attack and protection, producing an articulated cocktail of bioactive substances. The Mediterranean sea anemone Anemonia viridis has been studied extensively for years. In this short review, we summarize advances in bioprospecting of the A. viridis toxin arsenal. A. viridis RNA datasets and toxin data mining approaches are briefly described. Analysis reveals the major pool of neurotoxins of A. viridis, which are particularly active on sodium and potassium channels. This review therefore integrates progress in both RNA-Seq based and biochemical-based bioprospecting of A. viridis toxins for biotechnological exploitation. View Full-Text
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How regularities of mortality statistics explain why we age despite having potentially ageless somatic stem cells
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Крутько Вячеслав Николаевич
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Biogerontology |
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Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism’s interaction with its environment. Such staggering multilevel diversity in manifestation of senescence precludes (without methodology of systems biology) development of a correct understanding of its primary causes and does not allow for developing approaches capable of postponing ageing or reducing organisms’ ageing rate to attain health preservation. Moreover, it turns out that damage production and damage elimination processes, the misbalance of which results in the ageing process, can to a large extent be regulated by external signals. The purpose of this report is to provide evidence supporting this view and its compatibility with the regularities of mortality statistics, because the main idea is very simple. Even potentially a non-senescent but certainly not immortal body must start to age under inadequate conditions (like a non-melting piece of ice taken out from the deepfreeze inevitably start to melt at the temperatures above zero Celsius). This conclusion is totally consistent with existing patterns of mortality and with agelessness potential of somatic stem cells. Therefore, there is no need to build up and explore too complicated, computational and sophisticated systems models of intrinsic ageing to understand the origin of this mainly extrinsic root cause of natural ageing, which is controlled by environmental signals. In our case, a simple phenomenological black-box approach with Input–Output analysis is ample. Here Input refers to the environmentally dependent initial force of mortality, whereas Output is a rate of age-related increase of mortality force.
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Clinical implications of hepatitis b virus rna and covalently closed circular dna in monitoring patients with chronic hepatitis b today with a gaze into the future: The field is unprepared for a sterilizing cure
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Чуланов Владимир Петрович
Волочкова Елена Васильевна
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GENES |
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Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text
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2D/3D buccal epithelial cell self-assembling as a tool for cell phenotype maintenance and fabrication of multilayered epithelial linings in vitro
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Тимашев П.С.
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Biomedical Materials (Bristol) |
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Maintaining the epithelial status of cells in vitro and fabrication of a multilayered epithelial lining is one of the key problems in the therapy using cell technologies. When cultured in a monolayer, epithelial cells change their phenotype from epithelial to epithelial-mesenchymal or mesenchymal that makes it difficult to obtain a sufficient number of cells in a 2D culture and to use them in tissue engineering. Here, using buccal epithelial cells from the oral mucosa, we developed a novel approach to recover and maintain the stable cell phenotype and form a multilayered epithelial lining in vitro via the 2D/3D cell self-assembling. Transitioning the cells from the monolayer to non-adhesive 3D culture conditions led to formation of self-assembling spheroids, with restoration of their epithelial characteristics after epithelial-mesenchymal transition. In 7 days, the cells within spheroids restored the apical-basal polarity, and the formation of both tight (ZO1) and adherent (E-cadherin) intercellular junctions was shown. Thus, culturing buccal epithelial cells in a 3D system allowed us to recover and durably maintain the morphological and functional characteristics of epithelial cells. The multilayered epithelial lining formation was achieved after placing spheroids for 7 days onto a hybrid matrix, which consisted of collagen layers and reinforcing poly (lactide-co-glycolide) fibers and was proven promising for replacement of the urothelium. Thus, we offer an effective technique of forming multilayered epithelial linings on carrier-matrices using cell spheroids that was not previously described elsewhere and can find a wide range of applications in tissue engineering, replacement surgery, and regenerative medicine.
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Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control
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Власова Ирина Ивановна
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Molecules |
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The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes. View Full-Text
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HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome
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Макацария Александр Давидович
Бицадзе Виктория Омаровна
Хизроева Джамиля Хизриевна
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Autoimmunity Reviews |
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The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
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Genetic ablation of adenosine receptor A3 results in articular cartilage degeneration
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Journal of Molecular Medicine |
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Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited cellular catabolic processes in chondrocytes including downregulation of Ca2+/calmodulin-dependent protein kinase (CaMKII), an enzyme that promotes matrix degradation and inflammation, as well as Runt-related transcription factor 2 (RUNX2). Additionally, selective A3 agonists protected chondrocytes from cell apoptosis caused by pro-inflammatory cytokines or hypo-osmotic stress. These novel data illuminate the protective role of A3, which is mediated via inhibition of intracellular CaMKII kinase and RUNX2 transcription factor, the two major pro-catabolic regulators in articular cartilage.
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Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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Буздин Антон Александрович
Сорокин Максим Игоревич
Поддубская Елена Владимировна
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Cancers |
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Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs. View Full-Text
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Plasma exosomes stimulate breast cancer metastasis through surface interactions and activation of FAK signaling
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Буздин Антон Александрович
Сорокин Максим Игоревич
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Breast Cancer Research and Treatment |
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Purpose
The interaction between malignant cells and surrounding healthy tissues is a critical factor in the metastatic progression of breast cancer (BC). Extracellular vesicles, especially exosomes, are known to be involved in inter-cellular communication during cancer progression. In the study presented herein, we aimed to evaluate the role of circulating plasma exosomes in the metastatic dissemination of BC and to investigate the underlying molecular mechanisms of this phenomenon.
Methods
Exosomes isolated from plasma of healthy female donors were applied in various concentrations into the medium of MDA-MB-231 and MCF-7 cell lines. Motility and invasive properties of BC cells were examined by random migration and Transwell invasion assays, and the effect of plasma exosomes on the metastatic dissemination of BC cells was demonstrated in an in vivo zebrafish model. To reveal the molecular mechanism of interaction between plasma exosomes and BC cells, a comparison between un-treated and enzymatically modified exosomes was performed, followed by mass spectrometry, gene ontology, and pathway analysis.
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Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis
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Павлов Чавдар Савов
Ивашкин Владимир Трофимович
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Hepatology International |
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Background
Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.
Methods
PUBMED search (until 14 January 2018) was performed. Specific search terms were: ‘(cirrhosis) AND (SIBO OR bacterial overgrowth)’. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.
Results
117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8–47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7–19.0). OR 6.83 (95% CI 4.16–11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.
Conclusion
Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.
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A scientific methodology for expansion of anti-parkinson drug product range
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Пятигорская Наталья Валерьевна (Заместитель директора по научной работе)
Бркич Галина Эдуардовна (Руководитель центра)
Несвижский Юрий Владимирович (Профессор)
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Journal of Pharmaceutical Sciences and Research |
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A Scientific Methodology for Expansion of Anti-Parkinson Drug Product Range Nat a lia Valeryevna Pyatigorskaya Galina Eduardovna Brkich Alexey Nikitich Pavlov Valery Vasilyevich Beregovykh Olga Vladimirovna Evdokimova Sechenov First Moscow State Medical University, Russian Fedetation, 119991, Moscow, Trubetskaya Street, 8-2 Abstract Parkinson's disease (PD) is a chronic and progressive brain disease associat ed primarily with dopamine neurons degeneration of substantia nigra. More than 10 millions of people worldwide are affected by this disease manifested by combination of hypokinesia and rigidity, shaking, and postural instability. The high prevalence of disease has determined the aim of the study: to deve lop a methodology for expansion of anti-Parkinson drug product range. The information analysis methods were used for unbiased evaluation of novel anti-Parkinson drugs creation prospects. A systemic analysis of active pharmaceu tical ingredients (AFIs) used in anti- Parkinson drug products allowed for discovery of most widely used, levodopa being the top one. A comparative assessment of dosage forms used in Parkinson’s disease treatment showed th at they are represented primarily by intestinal gels, tablets, dispersible tablets, capsules, and modified release capsules. The authors conclude, that the novel anti-Parkinson drug pr oduct should contain levodopa in form of an endonasal spray which provides optimal bioavailability due to neces sary excipients (triglycerides, sodium monohydrogen phosphate, volatile and fatty oils, herbal extracts, stabilizers, and flavouring agents).
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Публикация |
ТРАНСПЛАНТАЦИЯ СЕРДЦА КАК МЕТОД ЛЕЧЕНИЯ ПРОГРЕССИРУЮЩЕЙ КАРДИОМИОПАТИИ У БОЛЬНЫХ С ПЕРВИЧНЫМИ МИОДИСТРОФИЯМИ
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Благова Ольга Владимировна (Профессор)
Недоступ Александр Викторович (Профессор)
Несвижский Юрий Владимирович (Профессор)
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КЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ ХИРУРГИЯ. ЖУРНАЛ ИМЕНИ АКАДЕМИКА Б.В. ПЕТРОВСКОГО |
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Первичные миодистрофии это гетерогенная группа наследственных нервно-мышечных заболеваний, характеризующихся прогрессирующей слабостью и дегенерацией скелетных мышц. В общей когорте взрослых больных с синдромом дилатационной кардиомиопатии (ДКМП) доля пациентов с первичными миопатиями невелика (в нашем регистре из 220 больных с синдромом ДКМП 3,6%), но они отличаются молодым возрастом и нередко тяжелым прогрессирующим течением заболевания. Генофенотипические корреляции, принципы стратификации риска и ведения таких больных четко не определены, данные об успешной трансплантации сердца у них и ее месте в их лечении немногочисленны. Цель проанализировать особенности течения кардиомиопатии в рамках генетически верифицированных и неуточненных первичных миопатий и роль трансплантации сердца в ее лечении. Материал и методы. В исследование включены 9 больных, 5 мужчин и 4 женщины, средний возраст 31,4+13,8 года (от 16 до 63) с сочетанием кардиомиопатии и скелетной миодистрофии. Обследование пациентов включало общий осмотр, определение уровня КФК в крови, антител к различным антигенам сердца методом непрямого ИФА, ДНК кардиотропных вирусов в крови и миокарде методом ПЦР, ЭхоКГ, суточное мониторирование ЭКГ по Холтеру; дополнительно проведены МСКТ сердца, МРТ, игольчатая электронейромиография, консультация невролога, эндомиокардиальная биопсия правого желудочка, исследование эксплантированного сердца, биопсия скелетной мышцы, аутопсия. Медико-генетическое консультирование было проведено всем больным. Генетическое исследование включало поиск мутаций в 57 генах методами прямого секвенирования по Сенгеру и полупроводникового секвенирования на платформе PGM IonTorrent. Результаты. Мутации в генах LMNA, EMD и DES были выявлены у 7 из 9 пациентов. Симптомы скелетной миопатии в большинстве случаев предшествовали появлению первых проявлений КМП. Практически у всех пациентов первыми симптомами поражения сердца были нарушения ритма и проводимости. У 2/3 больных при ЭхоКГ выявлена развернутая картина ДКМП. Значимое повышение титра антител к различным антигенам сердца выявлено у 5 больных. 3 больных умерли, еще 3 успешно выполнена трансплантация сердца. Живы без трансплантации только 3 женщины, 2 из них имплантированы устройства (электрокардиостимулятор и CRT-D). Обсуждение. Патогенные мутации верифицированы у 77,8% больных в 3 генах: LMNA, EMD и DES; трансплантация сердца успешно выполнена в каждой подгруппе. Присоединение миокардита является несомненным фактором ухудшения прогноза при различных миопатиях. Выводы. Кардиомиопатии в рамках миопатий имеют неуклонно прогрессирующее течение и плохой прогноз. К 9 мес суммарной конечной точки «смерть + трансплантация» достигли 66,7% больных, летальность составила 33,3%. Женский пол оказался благоприятным прогностическим признаком.
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Публикация |
ЭРАДИКАЦИЯ H.PYLORI: ОЦЕНКА РИСКА И ВОЗМОЖНОСТИ ПРОФИЛАКТИКИ МЕЖЛЕКАРСТВЕННЫХ ВЗАИМОДЕЙСТВИЙ
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Сереброва Светлана Юрьевна (Профессор)
Романов Дмитрий Владимирович (Профессор)
Несвижский Юрий Владимирович (Профессор)
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АНТИБИОТИКИ И ХИМИОТЕРАПИЯ |
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Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.
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The immunotoxicological pattern of subchronic and chronic benzene exposure in rats
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Караулов Александр Викторович (Заведующий кафедрой)
Карсонова Антонина Васильевна (Ассистент)
Несвижский Юрий Владимирович (Профессор)
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Toxicology Letters |
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Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which were subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment. The percentage of CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer. Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The decrease in the total lymphocyte and T cell counts were associated with increased benzene exposure duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4+T cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive correlation between benzene toxicity and indicated increased immune responses, 45-day exposure to benzene appeared to be the most sensitive time point for evaluating benzene cytotoxicity.
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PUBMED DOI |
Experts’ opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents
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Сергеев Алексей Владимирович (Ассистент)
Николенко В. Н. (Директор)
Несвижский Юрий Владимирович (Профессор)
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Journal of Headache and Pain |
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BACKGROUND:
The 2013 International Classification of Headache Disorders-3 (ICHD-3) was published in a beta version to allow the clinicians to confirm the validity of the criteria or to suggest improvements based on field studies. The aim of this work was to review the Primary Headache Disorders Section of ICHD-3 beta data on children and adolescents (age 0-18 years), and to suggest changes, additions, and amendments.
METHODS:
Several experts in childhood headache across the world applied different aspects of ICHD-3 beta in their normal clinical practice. Based on their personal experience and the literature available on pediatric headache, they made observations and proposed suggestions for the primary headache disorders section of ICHD-3 beta data on children and adolescents.
RESULTS:
Some headache disorders in children have specific features which are different from those seen in adults and which should be acknowledged and considered. Some features in children were found to be age-dependent: clinical characteristics, risks factors and etiologies have a strong bio psycho-social basis in children and adolescents making primary headache disorders in children distinct from those in adults.
CONCLUSIONS:
Several recommendations are presented in order to make ICHD-3 more appropriate for use with children.
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PUBMED DOI |
Age-Related Changes in Morphometric Parameters of Hippocampal Neurons in Humans
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S. E. Shemyakov (professor)
V. N. Nikolenko (director)
Yu. V. Nesvizhskiy (professor)
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Neuroscience and Behavioral Physiology |
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There was an oversight in the Authorship of a recent Images in Urogynecology article titled: Rectocutaneous fistula with transmigration of the suture: a rare delayed complication of vault fixation with the sacrospinous ligament (DOI 10.1007/ s00192-015-2823-5). We would like to include Adj A/P Han How Chuan’s name in the list of authors. Adj A/P Han is a Senior Consultant and Department Head of Urogynaecology at the KK Hospital for Women and Children, Singapore.
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PUBMED DOI |
ROLE OF ORGANISM REACTIVITY AND MUCOSAL IMMUNITY IN MODULATING OF PATHOGENICITY AND VIRULENCE OF OPPORTUNISTIC MICROFLORA IN DYNAMICS OF INFECTIOUS PROCESS AND ALSO IN MACROAND MICROORGANISMS GENE POOLS MAINTENANCE (Роль реактивности организма и мукозальн
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Караулов Александр Викторович (Заведующий кафедрой)
Афанасьев Максим Станиславович (Профессор)
Несвижский Юрий Владимирович (Профессор)
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Инфекционные болезни |
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The review is summarizing for the first time the results of original research and literature data revealing the conditions of opportunistic microflora (OM) pathogenicity and virulence formation in the dynamics of the infectious process, as well as maintenance and formation of gene pools in host cells and microorganisms. It is established, that formation or loss of pathogenic and virulent properties of microorganisms in the body happens under the influence of its external environment, its overall physiological and immunological reactivity, mucosal immunity, as well as with the direct participation of horizontal gene transfer. Newly created microbial pathogens cause infectious-inflammatory diseases. However, acquired pathogenicity factors are lost after recovery. Plasticity of gene pools of the macroorganism and microorganisms allows owners of gene pools to respond adequately to changes in the external and internal body environment, improve and enhance overall and immunological reactivity of the macroorganism in ontogenesis, generate optimal for specific situations symbiotic or antagonistic relationships between them taking into account newly acquired or lost pathogenicity and virulence factors and form new phenotypic or genetic properties of microorganisms. Horizontal genetic transfer is the process of moving the genetic information which is possible between prokaryotic and eukaryotic cells both ways, as well as within a single cell.
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