Moléculas coestimulatórias na leishmaniose visceral

Visceral leishmaniasis (VL) is endemic in many countries, including Brazil. The protozoan Leishmania infantum, is the etiological agent of VL, and is transmitted by the bite of female sandflies during the blood meal. The majority of subjects when exposed to the parasite do not develop the disease, because of development of Th1 cellular responses. Those who have develop signs of VL such as fever, weight loss, hepatosplenomegaly, have impairment of the cellular immune response, specific to the Leishmania antigens. We evaluated whether the specififc anergy during symptomatic VL, may be associated with changes in T cells costimulatory molecules or their ligands in CD14+ monocytes. There is an increase in CTLA-4 porcentage on CD4+ T lymphocytes (p=0.001) and ICOS on CD4+ and CD8+ T cells (p=0.002 to CD4+ and p=0.003 to CD8+), after stimulation by soluble Leishmania antigen (SLA) during active visceral leishmaniasis, and that there is a higher percentage of these molecules ex vivo, when comparing symptomatic to recovered individuals (p=0.04 to CTLA-4 in CD4+, and p=0.001 to ICOS in CD4+ and p=0.026 to CD8+). Moreover, we found a high gene expression of CTLA-4, OX-40 and ICOS during active VL. CD40, CD80, CD86, HLA-DR and ICOSL molecules do not suffer changes during disease. There is IFN-γ production by the peripheral blood cells, after SLA stimulation, by peripheral blood cells in symptomatic subjects; however, there is a decrease of the ratio IFN-γ/IL-10, which is reversed after clinical recovery. The impairment of some costimulatory molecules pathways during symptomatic VL could inhibit the ability of phagocytes to kill Leishmania and could facilitate their survival and the proliferation inside macrophages.

Um dermatam sulfato antitrombótico do camarão Litopenaeus vanammei inibe a inflamação e angiogênese

Inflammation is combined of a vascular and a cellular reaction, resulting in different cells and tissue responses, both the intravascular and extravascular environment. As the inflammatory process occurs, coagulation proteases, in particular thrombin (FIIa), are able to initiate various cellular responses in vascular biology and therefore is often observed activation of other biological systems, leading to complications during an event inflammatory, such as thrombosis and angiogenesis. Thus, antagonists molecules of these events are interesting models for the development of novel anti-inflammatory drugs. Thereby, it is worth stressing the glycosaminoglycans (GAGs), which are able to interact with several proteins involved in important biological processes, including inflammation and coagulation. Therefore, this study aimed to evaluate the anti-inflammatory, antithrombotic and anti-angiogenic potentials, as well anticoagulant of a dermatan sulfate-like GAG (DS) extracted from the Litopenaeus vannamei cephalotorax. The compound was obtained after proteolysis and purification by ion-exchange chromatography. After total digestion by DS-like compounds digesting lyases (chondroitinase ABC), the DS-like nature was revealed, and then called DSL. The shrimp compound showed reduced anticoagulant effect by the aPTT assay, but high anti-IIa activity, directly and through heparin cofactor II. On inflammation, the compound had a significant inhibitory effect with the reduction of proinflammatory cytokines. Potential Inhibitory were reported in the antithrombotic and anti-angiogenic assay, the latter being dose dependent. As for anti-hemostatic activity, the polysaccharides did not induced significant bleeding effect. Thus, the results shown by the shrimp DS-like compound indicate this glycosaminoglycan as a biotechnology target with prospects for the development of new multipotent drugs.