414 research outputs found

    Comparative study of some numerical schemes for a fractional order model of HIV infection treatment

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    A fractional order mathematical model that already exists in the literature, was considered. This model was established to study the effects of medicinal treatment in people infected with the human immunodeficiency virus (HIV). The importance of this study is that the model evaluates, among other parameters, the density of healthy and HIV-infected CD4+4^+ T cells. These data are very necessary for the subject infected by the virus given the effects that an antiretroviral treatment causes in it. The objective of this work is to consider several numerical schemes that involve fractional derivatives in order to compare their behaviors and to obtain a good approximation of the mentioned model solution. Convergence of these schemes will be studied as well as sensitivity with respect to the variation of the parameters eta (drug efficacy) and alpha (fractional derivative order). Furthermore, through the collection of medical records of people living with HIV, it is intended to determine the optimal fractional derivative order for the model and to compare it with the classical model.Fil: Ferrari, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Formación Básica; ArgentinaFil: Lara, Luis Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Física de Rosario. Universidad Nacional de Rosario. Instituto de Física de Rosario; ArgentinaFil: Olguin, Mariela Carina. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Formación Básica; ArgentinaFil: Santillan Marcus, Eduardo Adrian. Universidad Nacional de Rosario. Facultad de Ciencias Exactas, Ingeniería y Agrimensura. Escuela de Formación Básica; Argentin

    Impaired Function of Regulatory T Cells in Type 2 Diabetes Mellitus

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    Pathogenesis of type 2 Diabetes Mellitus (DM) is often associated with chronic low-grade inflammation. This kind of inflammation is characterized by an increased level of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β. From an immunological point of view, an inflammatory response is always followed by an anti-inflammatory response as negative feedback to avoid excessive tissue damages. Regulatory T cells are a subset of cluster of differentiation (CD)4+ T cells that have the function to maintain peripheral tolerance and suppress immune response. This review would discuss the impaired function of regulatory T cells in type 2 DM. DM is a group of metabolic diseases characterized by hyperglycemia due to a defect of insulin secretion or a combination of insulin resistance and relative insulin deficiency. Chronic low-grade inflammation has been known as a key factor in the development of insulin resistance. Regulatory T cells (Treg cells) action through contact and non-contact inhibition could suppress inflammatory response in innate and adaptive immune systems. In type 2 DM, the proportion and function of CD4+CD25+Foxp3+ and CD4+CD25+ regulatory T cell decreases due to the reduced number of Treg cells and the Treg cells depletion contributes to metabolic conditions such as insulin resistance. Moreover, Treg cells are more susceptible to apoptosis, the ability of Treg cells to produce anti-inflammatory cytokines such as transforming growth factor β (TGF-β) and IL-10 decreases, and there is an imbalance between the proportion of Th1/Th17 cells and Treg cells. This inadequate anti-inflammatory response gives rise to the chronic low-grade inflammatory condition in type 2 DM.Keywords: type 2 diabetes mellitus, inflammation, regulatory T cel

    Protease inhibitor associated mutations compromise the efficacy of therapy in human immunodeficiency virus – 1 (HIV-1) infected pediatric patients: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Although the introduction of combined therapy with reverse transcriptase and protease inhibitors has resulted in considerable decrease in HIV related mortality; it has also induced the development of multiple drug-resistant HIV-1 variants.</p> <p>The few studies on HIV-1 mutagenesis in HIV infected children have not evaluated the impact of HIV-1 mutations on the clinical, virological and immunological presentation of HIV disease that is fundamental to optimizing the treatment regimens for these patients.</p> <p>Results</p> <p>A cross sectional study was conducted to evaluate the impact of treatment regimens and resistance mutation patterns on the clinical, virological, and immunological presentation of HIV disease in 41 children (25 male and 16 female) at the Robert Wood Johnson Pediatric AIDS Program in New Brunswick, New Jersey. The study participants were symptomatic and had preceding treatment history with combined ARV regimens including protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Fifteen (36.6%) children were treated with NRTI+NNRTI+ PI, 6 (14.6%) with NRTI+NNRTIs, 13 (31.7%) with NRTI+PIs, and the remaining 7 (17.1%) received NRTIs only.</p> <p>Combined ARV regimens did not significantly influence the incidence of NRTI and NNRTI associated mutations. The duration of ARV therapy and the child's age had no significant impact on the ARV related mutations. The clinico-immunological presentation of the HIV disease was not associated with ARV treatment regimens or number of resistance mutations. However, primary mutations in the protease (PR) gene increased the likelihood of plasma viral load (PVL) ≥ 10,000 copies/mL irrespective of the child's age, duration of ARV therapy, presence of NRTI and NNRTI mutation. Viremia ≥ 10,000 copies/mL was recorded in almost all the children with primary mutations in the PR region (n = 12/13, 92.3%) as compared with only 50.0% (n = 14/28) of HIV infected children without (PR-), P < 0.008. However, CD-4 T cells were not affected by the mutations in the PR gene of the HIV-1 isolates.</p> <p>Conclusion</p> <p>Primary PR resistance mutations significantly increase the likelihood for high viral replication in pediatric patients with moderate/severe HIV-1 infection, which may affect the long-term clinical prognosis of the HIV infected children.</p

    Influence of Immune Status on the Airborne Colonization of Piglets with Methicillin-Resistant Staphylococcus aureus (MRSA) Clonal Complex (CC) 398

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    Colonized vertebrates including humans and pigs are to date the main reservoirs of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). Currently, the mechanisms underlying colonization of pigs are not fully understood. We investigated the influence of piglet pre-immune status on airborne MRSA colonization. Three groups of MRSA-negative piglets were primed and exposed to airborne LA-MRSA (104 colony forming units (cfu)/m3) in an aerosol chamber for 24 h. One group was treated intramuscularly with dexamethasone (1 mg/kg body weight) to imitate weaning stress. The second group was exposed to bacterial endotoxin containing MRSA aerosol. Both conditions play a role in the development of multifactorial diseases and may promote MRSA colonization success. The third group served as control. The piglets' MRSA status was monitored for 21 days via swab samples. At necropsy, specific tissues and organs were analyzed. Blood was collected to examine specific immunological parameters. The duration of MRSA colonization was not extended in both treated groups compared to the control group, indicating the two immune-status influencing factors do not promote MRSA colonization. Blood sample analysis confirmed a mild dexamethasone-induced immune suppression and typical endotoxin-related changes in peripheral blood. Of note, the low-dose dexamethasone treatment showed a trend of increased MRSA clearance

    Expression of MHC II genes

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    Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is the master regulator of MHC II transcription. It is expressed constitutively in dendritic cells (DC) and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications, which are still not very clear. Inappropriate immune responses are found in several diseases, including cancer and autoimmunity. Since CIITA regulates the expression of MHC II genes, it is involved directly in the regulation of the immune response. The knowledge of CIITA will facilitate the manipulation of the immune response and might contribute to the treatment of these diseases

    シェーグレン症候群疾患モデルマウスにおける眼病変の病理学的解析

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    Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by severe inflammation of exocrine glands such as the salivary and lacrimal glands. When it affects the lacrimal glands, many patients experience keratoconjunctivitis due to severely dry eyes. This study investigated the pathological and immunological characteristics of ocular lesions in a mouse model of SS. Corneal epithelial injury and hyperplasia were confirmed pathologically. The number of conjunctival mucin-producing goblet cells was significantly decreased in the SS model mice compared with control mice. Expression levels of transforming growth factor (TGF)-β, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-X-C motif chemokine (CXCL) 12 were significantly higher in the corneal epithelium of the SS model mice than in control mice. Inflammatory lesions were observed in the Harderian, intraorbital, and extraorbital lacrimal glands in the SS model mice, suggesting that the ocular glands were targeted by an autoimmune response. The lacrimal glands of the SS model mice were infiltrated by cluster of differentiation (CD)4+ T cells. Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed significantly increased mRNA expression of TNF-α, TGF-β, CXCL9, and lysozyme in the extraorbital lacrimal glands of the SS model mice compared with control mice. These results add to the understanding of the complex pathogenesis of SS and may facilitate development of new therapeutic strategies

    The role of vitamin D3 and vitamin B9 (Folic acid) in immune system

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    ABSTRACT Background and aims: Vitamins are essential constituents of our diet that Longley have been known to influence the immune system. Vitamin D3 and B9 have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. 1, 25(OH)2D3 metabolizing enzymes and vitamin D receptor (VDR) are present in many cell types including various immune cells such as antigen-presenting-cells, T cells, B cells. Methods: In this mini review, we study 30 novel articles since 2009 to 2015 about the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation, T-helper-cell differentiation and regulation of the immune response. Results: 1, 25(OH)2D3 has direct effect on CD4+ T (T-helper) cells for suppressing various cytokines such as IFN-γ, IL-17, IL-21 and IL-22, while enhancing the regulatory Tcells. In vitro studies show that Treg cells could be differentiated from naive T cells in vitamin B9-reduced condition. Conclusions: These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis and clarify the beneficial roles of vitamins in informing the design of vitamin analogs as pharmacologic agents for the generation and maintenance of a healthy immune condition
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