The features of power activity within mitochondrions of peripheral blood lymphocytes among in children and teenagers with severe atopic dermatitis

This article presents the findings gained on the metabolic exchange of peripheral blood lymphocytes in children and teenagers with severe atopic dermatitis in the acute phase. It has been revealed that in severe atopic dermatitis accompanied by a decreased metabolic exchange (succinate dehydrogenase NADH-D enzymes activity,) lymphocytes demonstrate a depletion of energetic options (а-glycerophosphate dehydrogenase enzyme activity) used as the most economical way of obtaining power for all metabolic processes in cells.В статье представлены результаты исследования метаболического обмена лимфоцитов периферической крови у детей и подростков с тяжелым течением атопического дерматита в период обострения заболевания. Выявлено, что при тяжелом течении атопического дерматита на фоне снижения биоэнергетического обмена (активность фермента сукцинатдегидрогеназы, НАДН-диафоразы) в лимфоцитах наблюдается истощение энергетических возможностей (активность фермента а-глицерофосфатдегидрогеназа) наиболее экономичного пути получения питания для всех метаболических процессов, происходящих в клетках

Тромботическая окклюзия у пациентов с острым ишемическим инсультом

Currently, reperfusion therapy is the main method of treating patients with ischemic stroke (IS). The safety and efficacy of systemic thrombolytic therapy with a recombinant tissue plasminogen activator in patients with IS within 3 hours, and then 4.5 hours after the onset of symptoms of the disease was demonstrated in the NINDS (1995) and ECASS III (2008) studies. In 2018, based on the results of five studies, clear indications were formulated for performing thrombectomy (TE) in patients with IS, which involve the detection of thrombosis of a large stroke-associated artery. Given the continuous growth in the number of the adult population, which constitutes the bulk of patients with IS, information on the prevalence of patients with thrombotic occlusion of cerebral arteries, who are potential candidates for TE, may be important for regional vascular centers.Aim of study. To describe IS patients admitted within the 6-hour “therapeutic window”.Materials and methods. The study included 145 patients with cerebral IS who were admitted within the first 6 hours after the onset of symptoms of the disease. All patients underwent computed tomographic (CT) angiography in order to verify the occlusion of the cerebral artery.Results. In our study, a correlation was established between the NIHSS severity of IS and the likelihood of verification of stroke-related artery thrombosis by CT angiography, but in 32.6% of patients with severe stroke (NIHSS at least score 14), no thrombotic occlusion was detected, and in 13% of patients with a clinic of mild acute cerebrovascular accident (NIHSS no more than 6), on the contrary, thrombotic occlusion was detected. Mortality in patients with verified thrombotic occlusion of the cerebral artery was higher than in patients without it (38% versus 10.5%, p<0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p><0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p ><0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively). CONCLUSION 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. Keywords: ischemic stroke, reperfusion therapy, cerebral artery thrombosis, cryptogenic stroke>˂0.001). Such a significant difference in the mortality rate was due to the initially more severe stroke (NIHSS at admission 17 [10; 23] versus 5 [2; 10], p˂0.001) in patients with thrombotic occlusion of a stroke-related artery, as well as a higher incidence of severe swallowing disorders (30% versus 9.5%, p˂0.002), which are a risk factor for pneumonia, as well as a higher frequency of such a comorbid background as chronic kidney disease and atrial fibrillation (30% versus 13.7%, p=0.018% and 58% versus 29.5%, p=0.001, respectively).Conclusion. 1. Thrombosis of the cerebral stroke-associated artery was detected in 34.5% of patients with ischemic stroke who were admitted within the first 6 hours from the onset of the disease. 2. The main reason for the failure to perform thrombectomy in patients with ischemic stroke admitted within the 6-hour therapeutic window is the lack of verification of stroke-related artery thrombosis using computed tomographic angiography. Due to thrombosis at a different location (other than thrombosis of the internal carotid artery and / or M1 segment of the middle cerebral artery), 10% of patients with verified thrombosis did not meet the currently existing selection criteria for thrombectomy. В настоящее время реперфузионная терапия является основным методом лечения пациентов с ишемическим инсультом (ИИ). Безопасность и эффективность системной тромболитической терапии при помощи рекомбинантного тканевого активатора плазминогена у пациентов с ИИ в пределах 3 часов, а в последующем 4,5 часа от начала симптомов заболевания была продемонстрирована в исследованиях NINDS (1995) и ECASS III (2008). В 2018 году, основываясь на результатах пяти исследований, были сформулированы четкие показания для выполнения тромбэктомии (ТЭ) у пациентов с ИИ, которые подразумевают выявление тромбоза крупной инсульт-связанной артерии. В условиях непрерывного роста числа взрослого населения, составляющего основную массу пациентов с ИИ, информация о распространенности больных с тромботической окклюзией церебральных артерий, являющихся потенциальными претендентами для выполнения ТЭ, может быть важной для региональных сосудистых центров.Цель исследования. Охарактеризовать пациентов с ИИ, поступающих в 6-часовом «терапевтическом окне».Материал и методы. В исследование включены 145 пациентов с церебральным ИИ, поступивших в первые 6 часов от начала развития симптомов заболевания. Всем пациентам с целью верификации окклюзии церебральной артерии выполняли компьютерную томографическую (КТ) ангиографию.Результаты. В нашем исследовании была установлена корреляция между тяжестью ИИ по шкале NIHSS и вероятностью верификации при помощи КТ-ангиографии тромбоза инсульт-связанной артерии, но у 32,6% пациентов с клиникой тяжелого инсульта (NIHSS не менее 14 баллов) не было выявлено тромботической окклюзии, а у 13% пациентов с клиникой легко протекающего острого нарушения мозгового кровообращения (NIHSS не более 6 баллов), напротив, тромботическая окклюзия была выявлена. Летальность у пациентов с верифицированной тромботической окклюзией церебральной артерии была статистически значимо выше, чем у пациентов без таковой (38% против 10,5%, р<0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p><0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p><0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно). Выводы 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии. Ключевые слова: ишемический инсульт, реперфузионная терапия, тромбоз мозговой артерии, криптогенный инсульт>˂ 0,001). Столь значительная разница между показателями летальности была обусловлена исходно более тяжелым инсультом (оценка по NIHSS при поступлении 17 [10; 23] против 5 [2; 10], p˂ 0,001, статистически значимо) у больных с тромботической окклюзией инсульт-связанной артерии, а также большей частотой статистически значимых грубых расстройств глотания (30% против 9,5%, p˂ 0,002, статистически значимо), являющихся фактором риска развития пневмонии и такого коморбидного фона, как хроническая болезнь почек и фибрилляция предсердий (30% против 13,7%, р=0,018 и 58% против 29,5%, р=0,001 соответственно).Выводы. 1. Тромбоз церебральной инсульт-связанной артерии выявлен у 34,5% пациентов с ишемическим инсультом, поступающих в первые 6 часов от начала заболевания. 2. Основной причиной невыполнения тромбэктомии у пациентов с ишемическим инсультом, поступивших в 6-часовом «терапевтическом окне», является отсутствие верификации тромбоза инсульт-связанной артерии при помощи компьютерной томографической ангиографии. По причине тромбоза другой локализации (отличной от тромбоза внутренней сонной артерии и/или М1 сегмента средней мозговой артерии) 10% пациентов с верифицированным тромбозом не соответствовали существующим в настоящее время критериям отбора для выполнения тромбэктомии.

Кистозная дуоденальная дистрофия. Диагностика и хирургическая тактика на примере типичного случая

Duodenal dystrophy, a chronic inflammation of the aberrant pancreatic tissue in the duodenal wall, is a relatively rare disease in the practice of physicians. The heterotopic pancreas is usually functioning, and the development of acute and chronic pancreatitis in it is even more probable than in the orthotopic gland as a result of an underdeveloped duct system. The progression of ectopic pancreatitis associated with increasing cystic formation could lead to a blockade of the major or minor duodenal papilla and subsequent chronic pancreatitits in the pancreas proper. Furthermore, a malignant transformation of the aberrant pancreas is not a rare occurrence. It is essential to carry out a timely and sharp diagnosis of this condition as it often defines the surgical tactics. The purpose of this report is to present a typical case of cystic duodenal dystrophy.Настоящая статья посвящена одной из дизонтогенетических причин хронического панкреатита - хроническому воспалению ткани поджелудочной железы, эктопированной в стенку двенадцатиперстной кишки. Ранее это заболевание выявлялось только при аутопсии или гистологическом исследовании удаленных панкреатодуоденальных комплексов. В настоящее время благодаря внедрению новых диагностических методов появилась возможность ее точной предоперационной верификации. Последнее обстоятельство позволяет своевременно избрать рациональную хирургическую тактику, что показано на примере клинического наблюдения

TRAF6 and IRF7 Control HIV Replication in Macrophages

The innate immune system recognizes virus infection and evokes antiviral responses which include producing type I interferons (IFNs). The induction of IFN provides a crucial mechanism of antiviral defense by upregulating interferon-stimulated genes (ISGs) that restrict viral replication. ISGs inhibit the replication of many viruses by acting at different steps of their viral cycle. Specifically, IFN treatment prior to in vitro human immunodeficiency virus (HIV) infection stops or significantly delays HIV-1 production indicating that potent inhibitory factors are generated. We report that HIV-1 infection of primary human macrophages decreases tumor necrosis factor receptor-associated factor 6 (TRAF6) and virus-induced signaling adaptor (VISA) expression, which are both components of the IFN signaling pathway controlling viral replication. Knocking down the expression of TRAF6 in macrophages increased HIV-1 replication and augmented the expression of IRF7 but not IRF3. Suppressing VISA had no impact on viral replication. Overexpression of IRF7 resulted in enhanced viral replication while knocking down IRF7 expression in macrophages significantly reduced viral output. These findings are the first demonstration that TRAF6 can regulate HIV-1 production and furthermore that expression of IRF7 promotes HIV-1 replication

Monocyte Scintigraphy in Rheumatoid Arthritis: The Dynamics of Monocyte Migration in Immune-Mediated Inflammatory Disease

Background: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. Methods/Principal Findings: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99m-Tc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4x10(-3) (0.95-5.1x10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. Conclusions/Significance: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention

Genome-Wide Identification of Susceptibility Alleles for Viral Infections through a Population Genetics Approach

Viruses have exerted a constant and potent selective pressure on human genes throughout evolution. We utilized the marks left by selection on allele frequency to identify viral infection-associated allelic variants. Virus diversity (the number of different viruses in a geographic region) was used to measure virus-driven selective pressure. Results showed an excess of variants correlated with virus diversity in genes involved in immune response and in the biosynthesis of glycan structures functioning as viral receptors; a significantly higher than expected number of variants was also seen in genes encoding proteins that directly interact with viral components. Genome-wide analyses identified 441 variants significantly associated with virus-diversity; these are more frequently located within gene regions than expected, and they map to 139 human genes. Analysis of functional relationships among genes subjected to virus-driven selective pressure identified a complex network enriched in viral products-interacting proteins. The novel approach to the study of infectious disease epidemiology presented herein may represent an alternative to classic genome-wide association studies and provides a large set of candidate susceptibility variants for viral infections

The Interferon Response Inhibits HIV Particle Production by Induction of TRIM22

Treatment of human cells with Type 1 interferons restricts HIV replication. Here we report that the tripartite motif protein TRIM22 is a key mediator. We used transcriptional profiling to identify cellular genes that were induced by interferon treatment and identified TRIM22 as one of the most strongly up-regulated genes. We confirmed, as in previous studies, that TRIM22 over-expression inhibited HIV replication. To assess the role of TRIM22 expressed under natural inducing conditions, we compared the effects of interferon in cells depleted for TRIM22 using RNAi and found that HIV particle release was significantly increased in the knockdown, implying that TRIM22 acts as a natural antiviral effector. Further studies showed that TRIM22 inhibited budding of virus-like particles containing Gag only, indicating that Gag was the target of TRIM22. TRIM22 did not block the release of MLV or EIAV Gag particles. Inhibition was associated with diffuse cytoplasmic staining of HIV Gag rather than accumulation at the plasma membrane, suggesting TRIM22 disrupts proper trafficking. Mutational analyses of TRIM22 showed that the catalytic amino acids Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity. These data disclose a pathway by which Type 1 interferons obstruct HIV replication