Malaria at Humaita county, Amazonas state, Brazil: XVII - immune response in patients with Plasmodium falciparum according to gametocytes

Em agosto de 1983, os Autores, estudaram 36 doentes com infecção causada pelo Plasmodium falciparum e 14 indivíduos normais, nascidos na região de Humaitá, que nunca tiveram malária, sem esplenomegalia, com exame parasitológico de sangue e hemaglutinação passiva negativas. Todos eles foram submetidos à observação clínica completa, exame hematológico, exame parasitológico de sangue e tipagem de linfócitos. Os linfócitos foram isolados e congelados em nitrogênio líquido, para posterior tipagem pela formação de rosetas. Os doentes foram classificados em dois grupos de acordo com a presença (13 doentes), ou ausência (23 doentes) de gametócitos antes do tratamento. Houve predomínio de formas graves no grupo de doentes sem gametócitos. Os resultados mostraram diminuição do número de linfócitos T em ambos os grupos de doentes, com ou sem gametócitos antes do tratamento, enquanto que o número de linfócitos B foi normal apenas no grupo de doentes com gametócitos. Essas observações, assim como as que foram relatadas pelos Autores anteriormente, permitem associar a presença de gametócitos circulantes com o número normal de células B em doentes com formas leves de malária causada pelo Plasmodium falciparum.

Experimental infection with Leishmania chagasi in immunosuppressed Balb/c mice: cytokines and parasite burdens

The immune response in leishmaniasis may result in a polarization of the T lymphocyte subpopulation, altering cell phenotype and resulting in immune protection or disease exacerbation. Leishmania may persist in the body either during asymptomatic infections or after treatment, which represents high risk under immunosuppression. The objective of this study was to evaluate the effect of infection with immunosuppression by dexamethasone associated with pentoxifylline on animal weight, spleen weight, spleen and hepatic parasitic load and immunopathology, as well as the IFN-gamma and IL-10 production in spleen cell culture of Balb/c mice infected with Leishmania chagasi. The infection did not cause body weight gain in animals, but both the weight and size of the spleen were increased. The immunosuppression using dexamethasone associated with pentoxifylline affected body weight gain and spleen weight and size in both infected and non-infected animals. The immunosuppression did not significantly alter the course of the splenic or hepatic parasite burden. Dexamethasone and pentoxifylline significantly affected cytokine production, but did not influence the Th1/Th2 ratio in infected animals.

DNA damage and nitric oxide production in mice following infection with L. chagasi

Leishmania chagasi, which causes visceral leishmaniasis in South America, is an obligate intracellular protozoan. Production of nitric oxide by macrophages during the inflammatory response is one of the main microbicidal mechanisms against this parasite. The goal of this study was to evaluate whether L. chagasi infection causes DNA damage in peripheral blood and spleen cells of Balb/c mice and whether such damage may be related to NO production. Balb/c mice were either infected with L chagasi or maintained as controls. The single-cell gel electrophoresis (comet) assay was used to measure DNA damage in peripheral blood and spleen cells, and the Griess reaction was used to measure NO production in the spleen. L chagasi infection induced DNA damage in peripheral blood and spleen cells of infected mice. Macrophages from the control group, challenged with L. chagasi, showed significantly (p < 0.05) greater NO production, compared to non-challenged cells. Treatment of spleen cells with N(G)-monomethyl-L-arginine (LNMMA) caused a significant reduction of NO production and DNA damage (p < 0.05). Our results indicate that L. chagasi induces DNA damage in the peripheral blood and spleen cells and that NO not only causes killing of the parasite but also induces DNA damage in adjacent cells. (C) 2011 Elsevier B.V. All rights reserved.

Experimental infection of Leishmania chagasi in immunosuppressed balb/c mice: cellular immune response and parasite burden

The immune response to leishmaniasis can result in a polarization of a subpopulation of T lymphocytes, which leads to a different cell phenotype and results in immune protection or exacerbation of the disease. Leishmanias persist in the body both in asymptomatic infections and after treatment, representing risks in terms of immunosuppression. The objective of this study was to evaluate the effects of infection and immunosuppression by dexamethasone associated with pentoxifylline on animal weight, spleen weight, the parasitic load in the spleen and liver, as well as the production of IFN-gamma and IL-10 in spleen cell culture of Balb/c mice infected with Leishmania chagasi. The infection did not alter animal weight gain, but spleen weight and size increased. The immunosuppression, induced by dexamethasone associated with pentoxifylline, affected animal weight gain and weight and size of the spleen (in infected and not infected animals). The immunosuppression did not significantly alter the course of the parasite burden in the spleen and liver. Dexamethasone and pentoxifylline affected the studied cytokine production, but not influenced on Th1/Th2 response in infected animals.

Arquitetura deposicional e evolução tectono-estratigráfica das sequências pré-rifte e rifte, na porção central do Vale do Cariri, Bacia do Araripe, NE do Brasil

A complex depositional history, related to Atlantic rifting, demonstrates the geological evolution during the late Jurassic and early Neocomian periods in the Araripe Basin NE Brazil. Based on outcrop, seismic and remote sensing data, a new model of the tectono-stratigraphic evolution of the section that covers the stages Dom João, Rio da Serra and Aratu (Brejo Santo, Missão Velha and Abaiara formations) is presented in this paper. In the stratigraphic section studied, ten sedimentary facies genetically linked to nine architectural elements were described, representing depositional systems associated with fluvial, aeolian and deltaic environments. Based on the relationship between the rates of creation of accommodation space and sediment influx (A / S) it was possible to associate these depositional systems with High and Low accommodation system tracks. These system tracks represent two tectono-sequences, separated by regional unconformities. The Tectono-sequence I, which includes lithotypes from the Brejo Santo Formation and is related to the pre-rift stage, is bounded at the base by the Paleozoic unconformity. This unit represents only a High Accommodation System Track, composed by a succession of pelitic levels interbedded with sandstones and limestones, from a large fluvial floodplain origin, developed under arid climatic conditions. The Tectono-sequence II, separated from the underlying unit by an erosional unconformity, is related to the rift stage, and is composed by the Missão Velha and Abaiara Formation lithotypes. Changes in depositional style that reflect variations in the A / S ratio, and the presence of hydroplastic deformation bands, make it possible to divide this tectonosequence into two internal sequences. Sequence IIA, which includes the lower portion of the Missão Velha Formation and sequence IIB, is composed by the upper section of the Missão Velha and Abaiara Formations The Sequence IIA below, composed only by the Low Accommodation System Track, includes crossbedding sandstones interbedded with massive mudstones, which are interpreted as deposits of sandy gravel beds wandering rivers. Sequence IIB, above, is more complex, showing a basal Low Accommodation System Track and a High Accommodation System Track at the top, separated by an expansion surface. The lower System Track, related to the upper portion of the Missão Velha Formation, is composed by a series of amalgamated channels, separated by erosion surfaces, interpreted as deposits of a belt of braided channels. The High Accommodation System Track, correlated with the Abaiara Unit, is marked by a significant increase in the A / S, resulting in the progradation of a system of braided river deltas with aeolic influence. Regarding tectonic evolution, the stratigraphic study indicates that the Tectonosequence Rift in the Araripe basin was developed in two phases: first characterized by a beginning of rifting, related to Sequence IIA, followed by a phase of syndepositional deformation, represented by sequence IIB. The first phase was not influenced by the development of large faults, but was influenced by a sharp and continuous decrease of accommodation space that permitted a change in depositional patterns, establishing a new depositional architecture. In turn, the stage of syndepositional deformation allowed for the generation of enough accommodation space for the preservation of fluvial-lacustrine deposits and conditioned the progradation of a braided river-dominated delta system.

Thymic lymphomas in Wistar rats exposed to N-methyl-N-nitrosourea (MNU)

The Brazilian Agency for the Environment (IBAMA) recently adopted an alternative medium-term multiple-organ assay system with the Wistar rat strain for detection of the carcinogenic potential of pesticides. Originally, this initiation-promotion protocol was established in Japan with the isogenic Fischer 344 male rat. Among the initiating agents used in that assay, N-methyl-N-nitrosourea (MNU) rapidly induces malignant lymphoma and leukemia and early mortality of rats from different strains. This study was developed to evaluate whether the outbred Wistar rats are also similarly susceptible to MNU. Particularly, it aimed to evaluate the dose-response relationship and to register the MNUinduced pre-neoplasia and neoplasia that may develop in the lympho-hematopoietic system (LHS) of the Wistar rat within a medium-term period. Four groups of male Wistar rats were treated during 2 weeks with vehicle or with MNU (80, 160 or 240 mg/kg body weight, i.p.). After sacrifice at the 12th and 20th weeks, the thymus, spleen, bone marrow, cervical and mesenteric lymph nodes and liver were collected for analysis. At the 20th week, LHS malignant tumors and benign vascular tumors occurred only in the high- and intermediate-dose MNU-treated animals. Four animals treated with 240 mg/kg developed diffuse thymic lymphomas; two others, treated respectively with 240 mg/kg and 160 mg/kg, developed spleen hemangiomas. The present observations indicate that the Wistar strain is as susceptible as other strains to the early development of MNU-induced LHS (pre)neoplasia. Therefore, this strain seems suitable to be used as test system in bioassay protocols that adopt MNU as an initiating agent for carcinogenesis.

Virulence profiles of ten Paracoccidioides brasiliensis isolates obtained from armadillos (Dasypus novemcinctus)

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis ( PCM), the most important systemic mycosis in Latin America. The armadillo, Dasypus novemcinctus, has been confirmed as the primary natural reservoir of this fungus. Its geographic distribution is similar to that of human PCM. In this study, virulence profiles of 10 P. brasiliensis isolates from different armadillos and of two clinical isolates were tested in an experimental hamster model. Pathogenicity was evaluated by counting cfu and performing histopathological analysis in the testis, liver, spleen and lung. Circulating specific antibodies were measured using enzyme- linked immunosorbent assay ( ELISA). All isolates from armadillos were virulent in the model, with dissemination to many organs. The clinical isolates, which had long been stored in cultured collections, were less virulent. The isolates were classified into four virulence categories according to number of cfu per gram of tissue: very high, high, intermediate and low. This study confirms that armadillos harbor pathogenic genotypes of P. brasiliensis, probably the same ones that infect humans.

Isolation of coccidioides brasiliensis from armadillos (Dasypus noveminctus) captured in an endemic area of paracoccidioidomycosis

Paracoccidioides brasiliensis, the causative agent of paracoccidioidomycosis (PCM), was first isolated from armadillos from the Amazonian region where the mycosis is uncommon. In the present study, we report on the high incidence of PCM infection in armadillos from a hyperendemic region of the disease. Four nine-banded armadillos (Dasypus novemcinctus) were captured in the endemic area of Botucatu, São Paulo, Brazil, killed by manual cervical dislocation and autopsied under sterile conditions. Fragments of lung, spleen, liver, and mesenteric lymph nodes were processed for histology, cultured on Mycosel agar at 37 degrees C, and homogenized for inoculation into the testis and peritoneum of hamsters. The animals were killed from week 6 to week 20 postinoculation and fragments of liver, lung, spleen, testis, and lymph nodes were cultured on brain heart infusion agar at 37 degrees C. Paracoccidioides brasiliensis was isolated from three armadillos both by direct organ culture and from the liver, spleen, lung, and mesenteric lymph nodes of hamsters. In addition, one positive armadillo presented histologically proven PCM disease in a mesenteric lymph node. The three armadillos isolates (Pb-AL, Pb-A2, and Pb-A4) presented thermodependent dimorphism, urease activity, and casein assimilation, showed amplification of the gp43 gene, and were highly virulent in intratesticularly inoculated hamsters. The isolates expressed the gp43 glycoprotein, the immunodominant antigen of the fungus, and reacted with a pool of sera from PCM patients. Taken together, the present data confirm that armadillos an a natural reservoir of P. brasiliensis and demonstrate that the animal is a sylvan host to the fungus.

Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats

A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetyl amino fluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-10, and transforming growth factor betal (TGF-beta1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-gamma production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia. (C) 2003 Elsevier B.V. All rights reserved.

Experimental paracoccidioidomycosis in high and low antibody responder mice of Selection IV-A

High (H) and low (L) responder mice were selected for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). In this selection, the difference in antibody responsiveness between H and L lines (HIV-A and LIV-A mice, respectively) was shown to depend mainly on macrophage function. The more rapid catabolism of antigens by macrophages in L mice has been suggested as the main cause of the low antibody production. Due to this high macrophage activity, L animals have been described as more resistant than H animals to intracellular pathogens. These animals were utilized as an experimental model of paracoccidioidomycosis. HIV-A and LIV-A mice were infected with Paracoccidioides brasiliensis by the intravenous route. As expected, H mice were more susceptible to P. brasiliensis with a shorter survival time and higher levels of specific antibodies when compared to L mice. Contrasting with the survival time, the lungs, spleen and liver from H mice showed typical nodular granulomas containing epithelioid and giant cells and few fungi. on the other hand, in LN-A mice, the lesions of these organs were characterized by looser granulomas with irregular borders and the presence of a large number of fungi, However, the adrenal gland showed different lesion patterns. In H mice these lesions were extensive and characterized by loose granulomas with numerous fungi, while in LIV-A mice the lesions were small and limited to the cortex. Moreover the HIV-A mice presented higher levels of serum corticosterone when compared to LIV-A ones. The higher susceptibility of H mice could be attributed to the extensive lesions of the adrenal glands. These results suggest the use of the H line from the IV-A Selection as an experimental model for further studies of adrenal involvement in paracoccidioidomycosis.

Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax)

Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

Síndrome de ativação macrofágica em paciente com lúpus eritematoso sistêmico juvenil

A hemofagocitose reativa ou síndrome de ativação macrofágica (SAM) é uma complicação das doenças inflamatórias sistêmicas, causada por expansão de células T e macrófagos, com produção maciça de citocinas pró-inflamatórias, ocorrendo mais freqüentemente na artrite idiopática juvenil sistêmica e raramente no lúpus eritematoso sistêmico juvenil (LESJ). OBJETIVO: Relatar um caso de LESJ que evoluiu com SAM precipitada por infecção e infarto esplênico, com desfecho fatal. RELATO DE CASO: Uma menina de 7 anos, com diagnóstico de LESJ desde os 5 anos, evoluiu com artrite em atividade, alopecia intensa, citopenias, cefaléia, infecções respiratórias recorrentes e elevação intermitente de transaminases. Os anticorpos anti-DNA e anticardiolipina IgG e IgM foram identificados e a biópsia renal evidenciou glomerulonefrite lúpica de classe III. A paciente foi tratada com pulso de metilprednisolona, prednisona, azatioprina e hidroxicloroquina. Após dois anos, na vigência de pneumonia apresentou abdome agudo e convulsões, evoluindo para o choque hemorrágico fatal após esplenectomia, que evidenciou infarto esplênico e infiltração maciça por macrófagos hemofagocíticos CD163+. CONCLUSÃO: A revisão do desfecho sugere a SAM precipitada por infecção e sobreposta a atividade inflamatória do lúpus com febre persistente, citopenias, disfunção hepática, hepatomegalia e esplenomegalia, como efeitos do excesso de produção de citocinas. Os anticorpos anticardiolipina podem ter tido papel precipitante na coagulopatia, que resultou infarto esplênico e choque hemorrágico.

Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats

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

Polysaccharide fraction of Agaricus brasiliensis avoids tumor-induced IL-10 production and changes the microenvironment of subcutaneous Ehrlich adenocarcinoma

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

Lack of Chemopreventive Activity of Agaricus blazei Mushroom on the Development of 1,2-Dimethylhydrazine-Induced Colonic Aberrant Crypt Foci in Rats

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