Rachycentron canadum (cobia) lectin promoted mitogenic response in mice BALB/c splenocytes.

The mitogenic lectins are invaluable tools to study the biochemical changes associated with lymphocyte activation and proliferation of various immune cells. Rachycentron canadum lectin (RcaL) was detected and purified from serum of cobia fish. The aim of this study was to evaluate the proliferative response and cytokine production in splenocytes of mice in vitro stimulated with RcaL lectin; Canavalia ensiformis lectin (Con A) was used as positive control. A high proliferation index was induced by RcaL in relation to control cells. Furthermore, RcaL induced higher IL-2 and IL-6 production in relation to control. The cell viability was 90% in splenocytes treated with RcaL lectin, but RcaL promoted significant late apoptosis after 24 and 48 h in relation to control. RcaL induced proliferative responses suggesting that this lectin can be used as a mitogenic agent in immunostimulatory assays.

American tegumentary leishmaniasis: cytokines and nitric oxide in active disease and after clinical cure, with or without chemotherapy.

The influence of immune response on the treatment of American tegumentary leishmaniasis is pointed by several authors, and the existence of protective immunity in self-healed patients (SH) is also suggested. Thus, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin (IL-) 10, IL-17, IL-22 and nitric oxide (NO) production was determined in PBMC culture supernatants from patients with active disease (AD) and after therapy, SH patients and healthy subjects, in response to the soluble antigen of Leishmania (Viannia) braziliensis. It was demonstrated that, during the active disease, there is a predominance of IFN-γ and TNF-α, indicating a proinflammatory phase of the response; IL-17 is also highlighted at this clinical state. Also, TNF-α was slightly increased in patients after therapy. NO secretion was noticed in SH individuals, while IL-17 appeared in low levels in these patients and seems to be regulated by NO. The presence of IL-10 was observed in all groups of patients. From this study, we can suggest that in the active disease and after clinical cure, with or without chemotherapy, specific cellular immunity takes part against Leishmania, but with some similarities between the clinical states. Thus, it indicates that the mediators herein described are necessary for the cure to occur.

Mitogenic response and cytokine production induced by cramoll 1,4 lectin in splenocytes of inoculated mice.

Cramoll 1,4 is a lectin with specific glucose/mannose binding, which is extracted from seeds of Cratylia mollis Mart. Many assays have shown the cytokine expression activity and anti-inflammatory profile of this lectin. The aim of this study was to evaluate the immunostimulatory response, in vitro, of splenocytes in mice previously inoculated, in vivo, with C. mollis (Cramoll 1,4) and Canavalia ensiformis (Con A) lectins. Results demonstrated higher proliferation indexes induced by Cramoll 1,4 than Con A lectin in relation to all experimental groups. Cramoll 1,4 and Con A also induced high levels of IL-2, IL-6, IFN-γ and nitric oxide production. Moreover, Cramoll 1,4 did not induce apoptosis and stimulated a significant number of cells in the S phase of the cell cycle. Results showed that Cramoll 1,4 lectin induces proliferative response and suggested that this lectin can be used as a mitogenic agent in immunostimulatory assays.

Clinical and immunological aspects of envenomations by Bothrops snakes: [review]

Accidents caused by snakes, especially in tropical and subtropical countries, still constitute a serious public health problem due to the lack of knowledge of health professionals and the precariousness of health systems in the regions where most accidents occur. Snake venoms contain a range of molecules that may provoke local swelling, pain, renal and respiratory insufficiencies. The study of the effects of each molecule on humans can help the development of complementary therapy. Similarly, the knowledge of clinical aspects of envenomations provides a better identification and implementation of appropriate treatment. In addition, to understand Bothrops envenomations and improve the therapeutic strategy, it is necessary to understand and study the role of important inflammatory mediators, particularly nitric oxide (NO), cytokines and the complement system.

Immunophenotypic characterization of patients with American cutaneous leishmaniasis prior to and after treatment in Pernambuco, Brazil

Leishmania infections induce a specific activation of host immunological response, particularly characterized by T cell expansion. Studies indicate the importance of the balance between CD4+ and CD8+ T cells, in which the first ones would have their number reduced during the healing process. Meanwhile, CD25+ T cells have been associated with the suppression of the immune response. Since the immune response has an essential role in both healing and progression of diseases, this study aimed to identify the percentage of CD3+, CD4+, CD8+, CD16+ and CD25+ T cells in the peripheral blood of patients afflicted with American cutaneous leishmaniasis (ACL) - before and after treatment - and healthy controls. Peripheral blood was collected and transferred to cytometry tubes containing monoclonal antibodies specific for cell surface markers CD3, CD4, CD8, CD16 e CD25. The immunophenotypic and morphometric parameters of cells were determined by flow cytometry and the results demonstrated a significant increase in the number of T CD8+ cells after treatment, suggesting a cytotoxic T cell response. An increase in CD25+ T cells in patients with active ACL and after treatment was also observed, suggesting the participation of these cells in the modulation of the exacerbated effector response.

Immunological studies and in vitro schistosomicide action of new imidazolidine derivatives

Schistosomiasis is a major public health problem with 207 million people infected and more than 779 million at risk. The drug of choice for treating schistosomiasis is praziquantel (PZQ); however, it is inefficient against immature forms of schistosomes. The aim of this study was to test new imidazolidine derivatives LPSF/PT09 and LPSF/PT10 against adult Schistosoma mansoni worms. IC50, cytotoxicity, immune response and cell viability assays were also available for these imidazolidines. Different concentrations of imidazolidine, from 32 to 320 »M, promoted motor abnormalities in breeding and unpaired worms, and death in 24 hours at higher concentrations. Although LPSF/PT09 and LPSF/PT10 did not affect IFN-³ and IL-10 production, they induced nitric oxide production and showed a similar behavior to praziquantel on cell death test. Thus, these new imidazolidine derivatives should undergo further study to develop schistosomiasis drugs.

Recent insights on the medicinal chemistry of metal-based compounds: hints for the successful drug design.

Although more complex than usually described, the anticancer action mechanism of cisplatin is based on binding to DNA. Following this line of reasoning, most the metal-based compounds discovered soon after cisplatin were designed to acting as DNA-binding agents and their pharmacological properties were thought to be correlated with this mechanism. Apart from the DNA structure, a significant number of proteins and biochemical pathways have been described as drug targets for metal-based compounds. This paper is therefore aimed at discussing the most recent findings on the medicinal chemistry of metal-based drugs. It starts illustrating the design concept behind the bioinorganic chemistry of anticancer complexes. Anticancer metallic compounds that inhibit the protein kinases are concisely discussed as a case study. The accuracy and limitations of molecular docking programs currently available to predict the binding mode of metallic complexes in molecular targets are further discussed. Finally, the advantages and disadvantages of different in vitro screenings are briefly commented.

Evaluation of memory immune response to mycobacterium extract among household contact of tuberculosis cases.

The human immune response to tuberculosis (TB) is especially mediated by T CD4(+)lymphocytes. However, more studies are needed in order to understand the exact role of each cytokine in the mechanisms for cures. In this article, our aim was to analyze the production of TNF-alpha, IL-10, and IFN-gamma in peripheral blood mononuclear cells (PBMCs) among the household contacts of common primary TB cases, with or without histories of active TB infection, who were negative to parasitological and HIV tests. In order to characterize the cytokine production, PBMCs from these groups were stimulated with whole-protein extract of M. tuberculosis (WPE) antigen (rAgTb) for 24 and 48 hr. The culture supernatants were collected and IFN-gamma, TNF-alpha, and IL-10 were assayed using capture ELISA. There were no statistical differences between primary TB cases and their household contacts with or without previous histories of lung TB. Our results suggest that T memory cells, T regulatory cells, and the Th1/Th2 dichotomy may be responsible for the results described in this article. Further studies are currently underway.

Immunization with cytoplasmic repetitive antigen and flagellar repetitive antigen of Trypanosoma cruzi stimulates a cellular immune response in mice.

In previous studies, we demonstrated that CRA and FRA recombinant proteins, used for diagnosis of Chagas' disease, elicited a humoral immune response in susceptible and resistant mice. To understand better the immune response to these proteins, we have evaluated, the cellular immune response in CRA- and in FRA-immunized BALB/c and C57BL/6 mice. A specific cellular lymphoproliferative response was observed in both strains of mice. Spleen cell cultures mainly from CRA-immunized C57BL/6 and FRA-immunized BALB/c mice produced high levels of IFN-y, indicating the induction of a Type 1 immune response. Regarding the T cell subsets, CD4+ T cells were the major source of IFN-y in CRA- and FRA-immunized mice. These results suggest that CRA and FRA are important immunogens in inducing a Type 1 immune response and that they may be considered as potential vaccine antigens.

Protective immunity of single and multi-antigen DNA vaccines against schistosomiasis

We evaluated the usefulness of the combination of three plasmids encoding tegumental (pECL and pSM14) and muscular (pIRV5) antigens of the Schistosoma mansoni on improving the protective immunity over the use of a single antigen as DNA vaccines. Female BALB/c mice were inoculated twice with 25 æg DNA plasmid within two weeks interval. The challenge was performed with 80 cercarias of a regional isolate of S. mansoni (SLM) one week after the last immunization. Six weeks after challenge, all mice were perfused for worm load determination. The following groups were analyzed: saline; empty vector; monovalent formulations of pECL; pSM14 and pIRV5 and also double combinations of pECL/pIRV5 and pIRV5/pSM14 and a triple combination of pECL/pIRV5/pSM14. The protection was expressed as a percentage of worm loads in each group compared with the saline group. The results obtained were 41 percent (p < 0.05); 52 percent (p < 0.05); 51 percent (p < 0.05); 48 percent (p < 0.05); 55 percent (p < 0.05); 45 percent (p < 0.05); 65 percent (p < 0.05) for each group respectively