Leukotriene B(4) is essential for selective eosinophil recruitment following allergen challenge of CD4(+) cells in a model of chronic eosinophilic inflammation

Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class It expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4(+) (but not CD4(-)) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4(+) cells ex vivo. MK886 blocked induction of CCL17 Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalburnin-restimulated CD4(+) cells initiate eosinophil recruitment which is strictly dependent on LTB4 production. (C) 2008 Elsevier B.V. All rights reserved.

CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp

Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion. © 2013 Elsevier B.V.

CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Frequency of Candida spp. in the Oral Cavity of Brazilian HIV-Positive Patients and Correlation with CD4 Cell Counts and Viral Load

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

T lymphocyte subsets of the umbilical cord blood of dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Short and long period optimization of drug doses in the treatment of AIDS

Técnicas de otimização numérica são úteis na solução de problemas de determinação da melhor entrada para sistemas descritos por modelos matemáticos e cujos objetivos podem ser expressos de uma maneira quantitativa. Este trabalho aborda o problema de otimizar as dosagens dos medicamentos no tratamento da AIDS em termos de um balanço entre a resposta terapêutica e os efeitos colaterais. Um modelo matemático para descrever a dinâmica do vírus HIV e células CD4 é utilizado para calcular a dosagem ótima do medicamento no tratamento a curto prazo de pacientes com AIDS por um método de otimização direta utilizando uma função custo do tipo Bolza. Os parâmetros do modelo foram ajustados com dados reais obtidos da literatura. Com o objetivo de simplificar os procedimentos numéricos, a lei de controle foi expressa em termos de uma expansão em séries que, após truncamento, permite obter controles sub-ótimos. Quando os pacientes atingem um estado clínico satisfatório, a técnica do Regulador Linear Quadrático (RLQ) é utilizada para determinar a dosagem permanente de longo período para os medicamentos. As dosagens calculadas utilizando a técnica RLQ , tendem a ser menores do que a equivalente terapia de dose constante em termos do expressivo aumento na contagem das células T+ CD4 e da redução da densidade de vírus livre durante um intervalo fixo de tempo.

A comparative evaluation of open loop and closed loop drug administration strategies in the treatment of AIDS.

In recent years, many researchers in the field of biomedical sciences have made successful use of mathematical models to study, in a quantitative way, a multitude of phenomena such as those found in disease dynamics, control of physiological systems, optimization of drug therapy, economics of the preventive medicine and many other applications. The availability of good dynamic models have been providing means for simulation and design of novel control strategies in the context of biological events. This work concerns a particular model related to HIV infection dynamics which is used to allow a comparative evaluation of schemes for treatment of AIDS patients. The mathematical model adopted in this work was proposed by Nowak & Bangham, 1996 and describes the dynamics of viral concentration in terms of interaction with CD4 cells and the cytotoxic T lymphocytes, which are responsible for the defense of the organism. Two conceptually distinct techniques for drug therapy are analyzed: Open Loop Treatment, where a priori fixed dosage is prescribed and Closed Loop Treatment, where the doses are adjusted according to results obtained by laboratory analysis. Simulation results show that the Closed Loop Scheme can achieve improved quality of the treatment in terms of reduction in the viral load and quantity of administered drugs, but with the inconvenience related to the necessity of frequent and periodic laboratory analysis.

In situ expression of mononuclear cell markers and interleukin-2 receptor in renal allograft biopsies of acute rejection and borderline cases

The correct diagnosis of renal allograft rejection may be difficult using only clinical and/or histopathological criteria. Immunological assays should be considered in order to evaluate the phenotype of inflammatory infiltrate in renal allograft biopsies. Immunohistochemical studies were performed to detect mononuclear cells, CD4 and CD8 T lymphocytes, B lymphocytes, macrophages, null cells, and positive cells for interleukin-2 receptors. A total of 41 allograft biopsies classified into three groups were studied: acute cellular rejection (28 biopsies/22 patients), borderline (7 biopsies/5 patients) and control (6 biopsies/6 patients). In the rejection group (RG), increased cellularity was found mainly at the tubulo-interstitial level. Expression of CD8 positive cells was higher in RG when compared to borderline (BG) and control (CG) groups, respectively (0.9 vs. 0.0 vs. 0.35 cells/mm2; p < 0.001). Expression of macrophages was not statistically significant among the three groups (RG = 0.6 vs. BG = 0.2 vs. CG = 0.0 cells/mm2; p < 0.02). In the BG, CD4 + cells predominated (BG = 0.2 vs. RG = 0.05 vs. CG = 0.0 cells/mm2; p < 0.05). Clinically these patients were treated as cases of acute rejection. The numbers and different types of infiltrating cells did not correlate with patient's clinical outcome. Copyright © Informa Healthcare.

Avaliação psicológica de pessoas com HIV

Pós-graduação em Psicologia - FCLAS

Estudo clínico e imunopatológico da infecção experimental em cães com a amostra Jaboticabal de Ehrlichia canis na fase aguda e após o tratamento: expreção de citocinas no baço e sangue e de subpopulações de células imunes no baço

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência das células dendríticas das placas de peyer na modulação das repostas Th1/Th2 em camundongos infectados com Yersinia pseudotuberculosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Imunologia das interações materno-fetais no diabete e na hiperglicemia gestacional leve

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chitosan-alginate membranes accelerate wound healing

The purpose of this study was to evaluate the efficacy of chitosan-alginate membrane to accelerate wound healing in experimental cutaneous wounds. Two wounds were performed in Wistar rats by punching (1.5 cm diameter), treated with membranes moistened with saline solution (CAM group) or with saline only (SL group). After 2, 7, 14, and 21 days of surgery, five rats of each group were euthanized and reepithelialization was evaluated. The wounds/scars were harvested for histological, flow cytometry, neutrophil infiltrate, and hydroxyproline analysis. CAM group presented higher inflammatory cells recruitment as compared to SL group on 2nd day. On the 7th day, CAM group showed higher CD11b+ level and lower of neutrophils than SL group. The CAM group presented higher CD4+ cells influx than SL group on 2nd day, but it decreased during the follow up and became lower on 14th and 21st days. Higher fibroplasia was noticed on days 7 and 14 as well as higher collagenesis on 21st in the CAM group in comparison to SL group. CAM group showed faster reepithelialization on 7th day than SL group, although similar in other days. In conclusion, chitosan-alginate membrane modulated the inflammatory phase, stimulated fibroplasia and collagenesis, accelerating wound healing process in rats.

Chitosan-alginate membranes accelerate wound healing

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)