АКТУАЛЬНЫЕ ПРОБЛЕМЫ ТУБЕРКУЛЕЗА У ПОДРОСТКОВ ИЗ ОЧАГОВ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

The article characterizes respiratory tuberculosis in adolescents exposed to tuberculous infection. Exposure to tuberculosis in the family or when contacting close relatives makes the biggest contribution into development of the disease unless the patient is isolated from those exposed. Advanced and severe forms of tuberculosis with bacillary excretion are detected, compromising the life quality of adolescents. The main causes of late diagnostics are poor performance of TB services, primary medical units, low level of health education aimed at the increase of motivation to have planned medical examinations in the general population and to take relevant sanitary and hygienic measures in the sites of infection. Adolescents from the sites with bacillary excretion, and, first of all, if multiple or extensive drug resistant tuberculosis is detected, are to be considered a high priority group facing the risk to develop the disease with more frequent monitoring and deeper examination. In primary medical units, should any sings typical of tuberculosis be presented, it is sensible to add skin tests (Mantoux test and test with tuberculous recombinant allergen) to the minimum diagnostic procedures. Organizational, methodical and health education activities in the sites of infection are to be improved.Дана характеристика туберкулеза органов дыхания у подростков из контакта с больным туберкулезом. Набольшее значение для развития заболевания имеет контакт в семье и с близкими родственниками без изоляции контактирующих лиц от больного. Выявляются тяжелые, распространенные процессы с бактериовыделением, которые снижают качество жизни заболевшего подростка. Основные причины поздней диагностики – недостатки в работе противотуберкулезной службы, первичной медико-санитарной помощи (ПМСП), низкий уровень санитарно-просветительной работы по повышению мотивации населения к плановым обследованиям и соблюдению санитарно-гигиенических мероприятий в очаге. Подростки из очагов с бактериовыделением, в первую очередь при обнаружении микобактерий туберкулеза с множественной/широкой лекарственной устойчивостью, должны рассматриваться как приоритетная группа риска развития заболевания с более частым мониторингом, углубленным обследованием. В учреждениях ПМСП при наличии клинических признаков, таких же как при туберкулезе, целесообразно включить в диагностический минимум кожные иммунологические тесты (проба Манту и проба с аллергеном туберкулезным рекомбинантным). Необходимо совершенствование работы организационно-методической и санитарно-просветительной работы в очагах

HIV-1-Infected and Immune-Activated Macrophages Induce Astrocytic Differentiation of Human Cortical Neural Progenitor Cells via the STAT3 Pathway

Diminished adult neurogenesis is considered a potential mechanism in the pathogenesis of HIV-1-associated dementia (HAD). In HAD, HIV-1-infected and immune-activated brain mononuclear phagocytes (MP; perivascular macrophages and microglia) drive central nervous system (CNS) inflammation and may alter normal neurogenesis. We previously demonstrated HIV-1-infected and lipopolysaccharide (LPS) activated monocyte-derived macrophages (MDM) inhibit human neural progenitor cell (NPC) neurogenesis, while enhancing astrogliogenesis through the secretion of the inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), in vitro and in vivo. Here we further test the hypothesis that HIV-1-infected/activated MDM promote NPC astrogliogenesis via activation of the transcription factor signal transducer and activator of transcription 3 (STAT3), a critical factor for astrogliogenesis. Our results show that LPS-activated MDM-conditioned medium (LPS-MCM) and HIV-infected/LPS-activated MDM-conditioned medium (LPS+HIV-MCM) induced Janus kinase 1 (Jak1) and STAT3 activation. Induction of the Jak-STAT3 activation correlated with increased glia fibrillary acidic protein (GFAP) expression, demonstrating an induction of astrogliogenesis. Moreover, STAT3-targeting siRNA (siSTAT3) decreased MCM-induced STAT3 activation and NPC astrogliogenesis. Furthermore, inflammatory cytokines (including IL-6, IL-1β and TNF-α) produced by LPS-activated and/or HIV-1-infected MDM may contribute to MCM-induced STAT3 activation and astrocytic differentiation. These observations were confirmed in severe combined immunodeficient (SCID) mice with HIV-1 encephalitis (HIVE). In HIVE mice, siRNA control (without target sequence, sicon) pre-transfected NPCs injected with HIV-1-infected MDM showed more astrocytic differentiation and less neuronal differentiation of NPCs as compared to NPC injection alone. siSTAT3 abrogated HIV-1-infected MDM-induced astrogliogenesis of injected NPCs. Collectively, these observations demonstrate that HIV-1-infected/activated MDM induces NPC astrogliogenesis through the STAT3 pathway. This study generates important data elucidating the role of brain inflammation in neurogenesis and may provide insight into new therapeutic strategies for HAD

Abrogated Inflammatory Response Promotes Neurogenesis in a Murine Model of Japanese Encephalitis

Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

ACTUAL ISSUES OF TUBERCULOSIS IN ADOLESCENTS EXPOSED TO TUBERCULOSIS INFECTION

The article characterizes respiratory tuberculosis in adolescents exposed to tuberculous infection. Exposure to tuberculosis in the family or when contacting close relatives makes the biggest contribution into development of the disease unless the patient is isolated from those exposed. Advanced and severe forms of tuberculosis with bacillary excretion are detected, compromising the life quality of adolescents. The main causes of late diagnostics are poor performance of TB services, primary medical units, low level of health education aimed at the increase of motivation to have planned medical examinations in the general population and to take relevant sanitary and hygienic measures in the sites of infection. Adolescents from the sites with bacillary excretion, and, first of all, if multiple or extensive drug resistant tuberculosis is detected, are to be considered a high priority group facing the risk to develop the disease with more frequent monitoring and deeper examination. In primary medical units, should any sings typical of tuberculosis be presented, it is sensible to add skin tests (Mantoux test and test with tuberculous recombinant allergen) to the minimum diagnostic procedures. Organizational, methodical and health education activities in the sites of infection are to be improved

Informative value of rapid microbiological diagnostic tests and experience in studying a procalcitonin assay in the evaluation of the activity of a mycobacterial population in children and adolescents with destructive pulmonary tuberculosis

The performed investigation showed that the specific feature of a group of children and adolescents with destructive pulmonary tuberculosis is the frequent absence of sputum (64.7%). The informative value of sputum examination for Mycobacterium tuberculosis (MBT) DNA by a polymerase chain reaction assay was significantly higher than that of oropharyngeal lavage (100 and 20.5%, respectively; p < 0.001). Drug resistance in MBT was determined by a microarray test in only 16 (23.5%) out of 68 patients for lack or paucity of DNA in the diagnostic material. Initial chemotherapy regimens were used in these patients in terms of definite resistance. In the other 52 (72.5%) cases, empirical chemotherapy regimens taking into account the possible risk for drug resistance in MBT from their history data and clinical and X-ray findings were given before drug resistance tests or in the absence of bacterial excretion. The first estimates of procalcitonin levels in the children and adolescents with destructive pulmonary tuberculosis may suggest that the positive tests are indicative of the high activity of a mycobacterial population. In the patients with positive procalcitonin tests, unlike those with negative ones, bacterial excretion was significantly more frequently detected by both luminescence microscopy and inoculation Bactec MGIT 960: 85.7 and 20.8%, respectively (p < 0.001), 100 and 50.0%, respectively (p < 0.005)