ПНЕВМОЦИСТНАЯ ПНЕВМОНИЯ КАК РЕДКОЕ КЛИНИЧЕСКОЕ ПРОЯВЛЕНИЕ ОСТРОЙ ВИЧ-ИНФЕКЦИИ

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The dynamics of interleukin-6level in HIV-infected patients with herpes zoster

Interleukin-6 plays a central role in antiviral immunity. However, the function of this cytokine in the pathogenesis of herpes zoster is unknown. The objective of this study was todeterminethe dynamicsof serum interleukin-6 level in HIV-infected patients with herpes zoster. 55 patients with herpes zoster (30 HIV-positive and 25 HIV-negative) were included. Serum interleukin-6 levels were measured before acyclovir treatment, on the 3rd day of treatment and after healing of skin lesions. The clinical course and dynamics of laboratory data were also evaluated. The study showed that elevated serum levels of interleukin-6 were associated with HIV-positive status, severity of rash, fever anddecreaseof CD4-lymphocytes. Levels of interleukin-6 in HIV-infected patients were significantly reduced during herpes zoster treatment and reached the level of HIVnegative cohort.Interleukin-6 levels in complicated course of herpes zoster in HIV-infected patients with low CD4-lymphocyte count (less than 350 cells/ml) were significantly higher compared to levels in uncomplicated course of the disease

Cognitive simulation as integrated innovative technology in teaching of social and humanitarian disciplines

© 2017 Authors. Currently, teachers are searching for innovative educational technologies that enhance the effectiveness of educational activities. The purpose of the paper is the development and approbation of cognitive simulation technology in teaching of social and humanitarian disciplines. Based on the integration of sources of innovation, the authors developed the technology of cognitive simulation aimed at the formation of a structured system of knowledge for social and humanitarian disciplines' subject area. Various forms of cognitive map methods used in the learning process (analysis, synthesis, projection, and simulation) allow developing the analytical and predictive abilities of students, and strengthening their educational motivation. The technology use is proposed for the first time for all socio-humanitarian disciplines in the process of vocational training, which contributes to the formation of inter-subject communications , spatial understanding of events, and transformations of reality. The empirical study carried out by the authors on the implementation of this technology in the educational process (the students of 3 universities, totaling 315 people participated in the study) confirmed the productivity of the technology and the possibility of its adaptation to various disciplines of social and humanitarian sphere

Динамика уровня неоптерина у пациентов с опоясывающим герпесом

Neopterin is a specific marker of cellular immunity and monocytes/macrophages activation. Correlation between serum neopterin levels and clinical features of herpes zoster is unknown.The objective of the study was to determine the concentration of serum neopterin in patients with herpes zoster.Methods: 55 patients with herpes zoster (30 HIV-positive and 25 HIV-negative) were included. Serum neopterin levels were measured three times during the observation period (before onset of treatment with acyclovir, on the 3rd day of treatment and after healing of skin lesions). The clinical course and dynamics of laboratory data were also evaluated.Results: The study showed that elevated serum neopterin levels were found in all patients with herpes zoster. Neopterin concentrations were significantly reduced during acyclovir treatment (from 30 (17; 32) to 12 (11; 27) nmol/L) (p = 0,0000001), but remained above the upper limit of normal by the time skin lesions were healed in most patients. Neopterin levels before and after treatment weren’t associated with HIV-status. Neopterin concentration was slightly higher in patients with HIV infection on the third day of observation only, that could reflect the abnormal immunoreactivity of this host. Neopterin levels in patients with varicella zoster viremia were higher compared to patients without viremia on the third day of treatment with acyclovir (23.5 (12,7; 30,0) and 12 (4,2, 24,5) nmol/L, respectively, p = 0,037).Conclusions: These results suggest that the dynamics of serum neopterin could be a marker of effectiveness of immune response in herpes zoster.Неоптерин является специфическим маркером активации клеточного и моноцитарно-макрофагального звеньев иммунной системы. Связь уровня сывороточного неоптерина с особенностями клинического течения опоясывающего герпеса не известна.Цель: изучить концентрацию сывороточного неоптерина у больных опоясывающим герпесом.Материалы и методы: в исследование были включены 55 пациентов с клинической картиной опоясывающего герпеса (30 ВИЧ-позитивных, 25 – с отрицательным ВИЧ-статусом). Трижды за период наблюдения измерялся уровень неоптерина в сыворотке крови (до начала лечения ацикловиром, на 3-й день лечения и после заживления высыпаний). Оценивались клиническое течение опоясывающего герпеса и динамика лабораторных показателей.Результаты: было установлено, что уровень неоптерина повышен у всех больных с опоясывающим герпесом. В динамике лечения ацикловиром концентрация неоптерина достоверно снижалась (с 30(17;32) до 12(11;27) нмоль/л) (p=0,0000001), но оставалась выше нормальных значений к моменту заживления высыпаний у большинства пациентов. Уровень неоптерина до начала и после окончания курса лечения не различался в зависимости от ВИЧ-статуса. Только на третий день наблюдения концентрация неоптерина была несколько выше у пациентов с ВИЧ-инфекцией, что отражает изменённую реактивность иммунной системы в данной группе больных. У пациентов с варицелла зостер виремией содержание неоптерина на третий день лечения ацикловиром было выше по сравнению с больными без виремии (23,5(12,7;30,0) и 12(4,2;24,5) нмоль/л соответственно, p=0,037).Заключение: полученные данные свидетельствуют, что динамика уровня сывороточного неоптерина может служить показателем эффективности иммунного ответа при опоясывающем герпесе

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

The dynamics of neopterin level in patients with herpes zoster

Neopterin is a specific marker of cellular immunity and monocytes/macrophages activation. Correlation between serum neopterin levels and clinical features of herpes zoster is unknown.The objective of the study was to determine the concentration of serum neopterin in patients with herpes zoster.Methods: 55 patients with herpes zoster (30 HIV-positive and 25 HIV-negative) were included. Serum neopterin levels were measured three times during the observation period (before onset of treatment with acyclovir, on the 3rd day of treatment and after healing of skin lesions). The clinical course and dynamics of laboratory data were also evaluated.Results: The study showed that elevated serum neopterin levels were found in all patients with herpes zoster. Neopterin concentrations were significantly reduced during acyclovir treatment (from 30 (17; 32) to 12 (11; 27) nmol/L) (p = 0,0000001), but remained above the upper limit of normal by the time skin lesions were healed in most patients. Neopterin levels before and after treatment weren’t associated with HIV-status. Neopterin concentration was slightly higher in patients with HIV infection on the third day of observation only, that could reflect the abnormal immunoreactivity of this host. Neopterin levels in patients with varicella zoster viremia were higher compared to patients without viremia on the third day of treatment with acyclovir (23.5 (12,7; 30,0) and 12 (4,2, 24,5) nmol/L, respectively, p = 0,037).Conclusions: These results suggest that the dynamics of serum neopterin could be a marker of effectiveness of immune response in herpes zoster

Eleven papers in analysis

This collection of eleven papers covers a broad spectrum of topics in analysis, from the study of certain classes of analytic functions to the solvability of singular problems for differential and integral equations to computational schemes for the partial differential equations and singular integral equations

ВАРИЦЕЛЛА ЗОСТЕРНАЯ ИНФЕКЦИЯ У ВЗРОСЛЫХ ВИЧ-ИНФИЦИРОВАННЫХ ПАЦИЕНТОВ

Varicella zoster infection (VZI) in HIV patients is a socially important condition, which is still poorly studied. In the present study, VZI case histories were examined for 141 HIV patients treated at S.P. Botkin Clinical Hospital in 2012. In most cases (92%), the disease took the form of zona serpiginosa. Complications were detected in 27% of cases, ophthalmological manifestations being predominant. A significant association between complicated VZI and low CD4+ cell counts was foundВарицелла зостерная инфекция (ВЗИ) у ВИЧ-инфицированных больных имеет большое социальное значение. В связи с тем, что ВЗИ на фоне ВИЧ-инфекции изучена недостаточно, целью исследования было охарактеризовать течение данной патологии. Проведен анализ случаев ВЗИ у 141 пациента с ВИЧ-инфекцией, а госпитализированных в Клиническую инфекционную больницу им. С.П. Боткина в 2012 г. В большинстве случаев заболевание протекало в форме опоясывающего герпеса (92%). Осложненное течение отмечалось в 27% случаев, среди которых преобладали офтальмологические осложнения. Низкий уровень CD4-лимфоцитов был достоверно ассоциирован с наличием осложнений при опоясывающем герпесе

Cholinergic Signaling Regulates Macrophage Migration During Acute and Chronic Inflammation via Α7 Nicotinic Acetylcholine Receptor

The a7 nicotinic acetylcholine receptor (a7nAChR) expressed on macrophages, a critical link between the neural and immune systems, provides a defense mechanism during inflammatory diseases. Release of acetylcholine in target tissues activates a7nAChR, a necessary element of the cholinergic anti-inflammatory pathway, inhibiting pro-inflammatory signaling pathways via NF-kB. However, other potential aspects of a7nAChR function are not well understood. The purpose of our project is to evaluate the role of a7nAChR activation in macrophage migration and accumulation at the site of inflammation. We first evaluated the survival of WT and a7nAChR-/- mice during LPS-induced endotoxemia. We found that a7nAChR-/- mice have significantly decreased survival compared to WT. We next examined differences in monocyte migration by tracking adoptively transferred, fluorescently labeled a7nAChR-/- and WT monocytes in the model of LPS-induced endotoxemia using flow cytometry and imaging flow cytometry. We found that a7nAChR-/- monocytes have significantly reduced migration to the lung, liver, and spleen during endotoxemia, in both a7nAChR-/- and WT recipient mice. Based on this result, we investigated if adoptive transfer of WT or a7nAChR-/- monocytes would decrease or improve survival in LPS-induced endotoxemia. Adoptively transferred, unlabeled WT monocytes improved survival in a7nAChR-/- recipient mice, though this effect did not reach significance. Survival was unaffected by adoptive transfer of a7nAChR-/- monocytes. Notably, this data coincides with the protective role of both macrophages and a7nAChR during sepsis that has been demonstrated in multiple recent publications. To reveal a potential mechanism, we tested the effect of a7nAChR-deficiency on the expression of adhesive and chemokine receptors at the macrophage surface. We selected 10 receptors to evaluate via qRT-PCR and flow cytometry. Our qRT-PCR experiments demonstrated a significantly reduced expression in CCR5, CCR2, integrin αMß2, and integrin αXß2 in a7nAChR-/- peritoneal macrophages, when compared to WT. The reduction in expression of CCR2 and αXß2 was corroborated by our flow cytometry results. Interestingly, the decrease in CCR5 and αMß2 was lower, but still detectable, and this discrepancy can be attributed to post transcriptional regulation of these receptors. The role of these receptors was further investigated in an in vitro 3D migration assay. Macrophages deficient in a7nAChR showed significantly decreased migration within a fibrin matrix (integrin αMß2 dependent) along a RANTES gradient (CCR5-mediated). The reduction in the migration of a7nAChR-/- macrophages toward MCP-1 (CCR2-mediated) did not reach significance, although still measurable. This experiment confirmed the chemokine-independent contribution of αMß2 to mesenchymal macrophage migration. These protective effects of αMß2 and CCR5 during sepsis were reported previously and are related to the regulation of monocyte recruitment and efflux at the site of inflammation. In summary, we discovered a new link between the parasympathetic nervous system and immune response based on a7nAChR-regulated macrophage migration during inflammation. The signaling pathway downstream of a7nAChR that modulates αMß2 and CCR5 expression is yet to be identified and is the objective of our ongoing investigation