Възможности и перспективи за прилагането на Инфлуцид в класическата профилактика на ОРВИ

Профилактичното назначаване на инфлуцид допринася за намаляване в срок от три месеца на честотата, продължителността и тежестта на ОРВИ, което е придружено от спад в цитотоксичната активност на NK-клетките, отговорни за антивирусната защита.Оценката на ефективността на препарата инфлуцид спрямо причинителите на ОРВИ е проведена в открито плацебо контролирано клинично проучване за деца на 5-6-годишна възраст, посещаващи предучилищни детски заведения в епидемичния сезон януари-април 2009 г. (фиг. 1 и фиг. 2) Особено внимание се отделя за изследване влиянието на инфлуцид върху морфологичните показатели на NK-клетките, които са показател за тяхната цитотоксична активност. В състояние на вирусна инфекция NK-клетките атакуват заразените клетки и активността им е повишена. Според изследването (фиг. 3) при профилактично прилагане на инфлуцид се отбелязва явен спад в цитотоксичността на NK-клетките, поради изразеното защитно действие на инфлуцид спрямо развитието на ОРВИ.Анализът на поносимостта на инфлуцид в профилактичен режим на дозиране не показва никакви неблагоприятни и нежелани ефекти

Proposals for the Organization of International Logistics Activities of Agricultural and Agro-Processing Enterprises During the War Period

The agricultural sector is the driver and “point of growth” of the national economy of Ukraine. Agriculture accounts for an average of 16% of gross value added in some regions and play a key role in ensuring food security. However, the current conditions of martial law in Ukraine have led to problems in the organization of logistics activities of enterprises of the agro-industrial complex as a result of non-fulfilment of the terms of contracts; emergence of risks of disruption of the sowing campaign; decrease in final harvest indicators and the level of food security; decrease in the volume of export deliveries of agricultural products; disruption of food supply chains; lack of adequate financing and logistics infrastructure facilities; insufficiently effective use of marketing management tools and a network approach in the process of distributing agricultural products to the final consumer; increase in transaction costs, etc. The article provides a statistical analysis of the main indicators of the development of foreign economic activity of enterprises of the agro-industrial complex of Ukraine in the pre-war period. Barriers that inhibit the effective organization of international logistics activities of agrarian enterprises in wartime have been identified. Priority directions for eliminating existing barriers that prevent the organization of foreign economic logistics activities are proposed, the essence of which is to activate network interaction and partnership relations based on the creation of agro-cluster structures; unification of small farms for the proper execution of contracts, as well as joint activity in the agrarian sphere of two or more companies and different groups of stakeholders to achieve a common goal and a synergistic effect.Аграрний сектор є драйвером і «точкою зростання» національної економіки України. Сільське господарство формує у деяких регіонах у середньому 16% валової доданої вартості та відіграє ключову роль у забезпеченні продовольчої безпеки. Однак сучасні умови воєнного стану в Україні призвели до проблем організації логістичної діяльності підприємств агропромислового комплексу унаслідок невиконання умов контрактів; появі ризиків зриву посівної кампанії; зменшення фінальних показників врожаю та рівня продовольчої безпеки; зниження обсягів експортних поставок сільськогосподарської продукції; порушення ланцюгів постачання продовольства; відсутності належного фінансування та об’єктів логістичної інфраструктури; недостатньо ефективного використання інструментарію маркетингового менеджменту і мережевого підходу в процесі розподілу аграрної продукції до кінцевого споживача; збільшення трансакційних витрат тощо. У статті виконано статистичний аналіз основних показників розвитку зовнішньоекономічної діяльності підприємств агропромислового комплексу України у довоєнний період. Виявлено бар’єри, які гальмують ефективну організацію міжнародної логістичної діяльності аграрних підприємств у воєнний час. Запропоновано пріоритетні напрями усунення існуючих бар’єрів, що перешкоджають організації зовнішньоекономічної логістичної діяльності, суть яких полягає в активізації мережевої взаємодії та партнерських взаємовідносин на основі створення агрокластерних структур; об’єднання дрібним фермерських господарств для належного виконання контрактів, а також спільної діяльності в аграрній сфері двох або більше компаній і різних груп стейкхолдерів для досягнення загальної мети і синергетичного ефекту

Problems of professional training of doctors of general practice – family medicine in the system of postgraduate education.

The article reveals the problems of professional training of family doctors arising in the implementation of measures on preserving and promoting health, preventing diseases in children and adolescents. At present, the doctors of the first level are not able to organize and realize the entire complex of medical and social assistance in the ambulatory clinic at the proper level. The improvement of postgraduate training of family doctors in the field of outpatient pediatric care has been suggested. At the same time, the development of curricula for thematic improvement should be based on studying educational needs of the healthcare system in the region and the ongoing reform processes

Lack of PPARγ in Myeloid Cells Confers Resistance to Listeria monocytogenes Infection

The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPARγ. This prompted us to investigate whether PPARγ in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPARγ (LysMCre×PPARγflox/flox). Loss of PPARγ in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFNγ TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPARγ enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6Chi monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPARγ was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPARγ and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPARγ activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2‐deficient mice (CCR2−/−) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2−/− and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2−/− wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2−/− wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2−/− mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2−/− mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2‐deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.Upon initial tissue injury, CCL2, one of the primary ligands for CCR2, is increased in the wound. This ligand binds the CCR2 receptors that are present on Ly6CHi monocytes, recruiting these cells to the wound, allowing initiation of the macrophage‐mediated inflammatory phase of wound healing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/1/eji4256.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/2/eji4256_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/3/eji4256-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145550/4/eji4256-sup-0002-PRC.pd

Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells

CCR5-binding chemokines produced in the draining lymph node after vaccinia virus infection guide naive CD8+ T cells toward DCs and away from the macrophage-rich zone, thereby facilitating optimal CD8+ T cell activation and cytokine production

Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection

Visualizing early splenic memory CD8+ T cells reactivation against intracellular bacteria in the mouse

International audienceMemory CD8(+) T cells represent an important effector arm of the immune response in maintaining long-lived protective immunity against viruses and some intracellular bacteria such as Listeria monocytogenes (L.m). Memory CD8(+) T cells are endowed with enhanced antimicrobial effector functions that perfectly tail them to rapidly eradicate invading pathogens. It is largely accepted that these functions are sufficient to explain how memory CD8(+) T cells can mediate rapid protection. However, it is important to point out that such improved functional features would be useless if memory cells were unable to rapidly find the pathogen loaded/infected cells within the infected organ. Growing evidences suggest that the anatomy of secondary lymphoid organs (SLOs) fosters the cellular interactions required to initiate naive adaptive immune responses. However, very little is known on how the SLOs structures regulate memory immune responses. Using Listeria monocytogenes (L.m) as a murine infection model and imaging techniques, we have investigated if and how the architecture of the spleen plays a role in the reactivation of memory CD8(+) T cells and the subsequent control of L.m growth. We observed that in the mouse, memory CD8(+) T cells start to control L.m burden 6 hours after the challenge infection. At this very early time point, L.m-specific and non-specific memory CD8(+) T cells localize in the splenic red pulp and form clusters around L.m infected cells while naïve CD8(+) T cells remain in the white pulp. Within these clusters that only last few hours, memory CD8(+) T produce inflammatory cytokines such as IFN-gamma and CCL3 nearby infected myeloid cells known to be crucial for L.m killing. Altogether, we describe how memory CD8(+) T cells trafficking properties and the splenic micro-anatomy conjugate to create a spatio-temporal window during which memory CD8(+) T cells provide a local response by secreting effector molecules around infected cells