Lipopolysaccharide-Induced Cellular Activation May Participate in the Immunopathogenesis of Visceral Leishmaniasis Alone or in HIV Coinfection

Visceral Leishmaniasis (VL) is an infectious disease which constitutes a serious public health problem, integrating the list of neglected tropical diseases. The disease is characterized by a Leishmania-specific immune suppression T-cell depletion and a decrease of other hematopoietic cells. In parallel, an immunostimulatory response also occurs, represented by polyclonal B lymphocytes, T-cell activation, and systemic proinflammatory responses. Parasite antigens were believed to mediate both suppression and activation mechanisms, but these concepts are constantly being revised. Similar to reports on HIV/AIDS, we have proposed that gut parasitation by amastigotes and lymphocyte depletion could also affect gut-associated lymphoid tissue, leading to mucosal barrier breach and predisposing to microbial translocation. An increment of plasmatic lipopolysaccharide (LPS) levels observed in Brazilian VL patients was implicated in the reduced blood CD4+ and CD8+ T cell counts, systemic T-cell activation, pro-inflammatory cytokines and MIF plasma levels, suggesting that a bacterial molecule not associated with Leishmania infection can exert deleterious effects on immune system. Recent results also pointed that the proinflammatory response was potentiated in VL/HIV-AIDS coinfected patients. The LPS-mediated cell activation adds another concept to the immunopathogenesis of VL and can bring a rational for new therapeutic interventions that could ameliorate the management of these patients

Antitrypanosomal butanolides from Aiouea trinervis

In a search for new antitrypanosomal agents in the Brazilian flora, the ethanol extract of the xylopodium from Aiouea trinervis (Lauraceae) exhibited in vitro activity against the epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas disease. Bioassay-guided chromatographic fractionation of the ethanol extract afforded three butanolides, isoobtusilactone A (1), epilitsenolide C2 (2), and epilitsenolide C1 (3). Butanolides 1 and 3 were more active against T. cruzi epimastigotes than the reference drug benznidazole (by 8.9-fold and 3.2-fold, respectively), while 2 proved inactive. Compounds 1 and 3 showed low cytotoxicity in mammalian Vero cells (CC50> 156 μmol L-1) and high selectivity index (SI) values for epimastigotes (SI = 56.8 and 28.6, respectively), and 1 was more selective than benznidazole (SI = 46.5). Butanolide 1 at 24 μmol L-1 also led to cell cycle alterations in epimastigote forms, and inhibited the growth of amastigote cells in more than 70 %. In silico ADMET properties of 1 were also analyzed and predicted favorable drug-like characteristics. This butanolide also complied with Lipinski’s rule of five and was not predicted as interference compound (PAINS). This is the first report on the isolation of these bioactive butanolides under the guidance of in vitro trypanocidal activity against T. cruzi

Elaboração de pasta de amendoim acrescida de Albumina: alternativa proteica: Preparation of peanut paste with added Albumin: a protein alternative

A procura por produtos que supram a carência nutricional de forma saborosa, prática e com valor acessível tem se demonstrado uma preocupação do consumidor, que busca uma alimentação saudável. A vantagem na utilização de suplementos nutricionais permite elevar a ingestão calórico-nutricional naqueles indivíduos que não podem valer-se de uma grande quantidade de alimentos para a obtenção dos macronutrientes, além da praticidade de transporte e a quantidade personalizada de consumo, de acordo com a necessidade específica de um dado nutriente livre do excesso calórico. Os nutrientes protéicos são atrativos pelo fácil preparo e altíssimo valor biológico, como é o caso da proteína do soro do leite (whey protein) e da clara do ovo desidratada (albumina) (HARAGUCHI et al., 2006). A albumina trata-se de uma proteína de alta qualidade e de ótima digestão, seu consumo como suplemento tem ajudado na regeneração e crescimento muscular, além de suas propriedades nutricionais como aminoácido, a albumina é sintetizada no fígado e é responsável pelo carreamento de substâncias no sangue. A pasta de amendoim obtida por trituração do grão, apresenta características organolépticas agradáveis, além da facilidade de consumo e incorporação na alimentação, estudos comprovam os seus benefícios a saúde: auxilio na perda de peso, melhora de perfil glicêmico e saciedade. O consumo necessário de proteínas recomendados pela RDA (Recommended Dietary Allowance) é de 75g por dia de proteínas, tais quantidades são de difícil alcance devido a diversos fatores como: preço, rotina e hábito alimentar. O presente trabalho tem por objetivo a elaboração de uma pasta de amendoim acrescida de albumina, sendo essa base ideal para incorporação de albumina, mascarando o gosto considerado por muitos desagradável. Toda preparação da pasta foi realizada manualmente estabelecendo como parâmetro confiável a realização dos testes em triplicada e utilizando as seguintes porcentagens de albumina: 15%, 20% e 25% (estabelecidos após testes entre a equipe de análise sensorial, para que o produto final não fosse destinto ao original e seus semelhantes). Os resultados obtidos evidenciaram que a concentração de 15% da amostra foi a mais expressiva em quantidades de proteínas tendo um aumento de 23,7% quando comparada a concentração média de 3,8g de seis marcas distintas de  pastas de amendoim integral  encontradas para compra nos dois mercados do município de Marília e quando comparada a base original, o aumento foi 4,1g para 4,7g (aumento de 14,6%), sem que haja alterações significativas na espalhabilidade, conservação, palatabilidade, bem como um aumento de 5kcal quando comparada ao valor energético da pasta de amendoim base.  Assim o objetivo pode ser considerado atingido, onde estudos posteriores se fazem necessários para que permitam o aumento de concentração e analise sensorial e aceitabilidade do público permitindo uma perspectiva de mercado

Leishmania (Viannia) naiffi : rare enough to be neglected?

In the Brazilian Amazon, American tegumentary leishmaniasis (ATL) is endemic and presents a wide spectrum of clinical manifestations due, in part, to the circulation of at least seven Leishmaniaspecies. Few reports of Leishmania (Viannia) naiffiinfection suggest that its occurrence is uncommon and the reported cases present a benign clinical course and a good response to treatment. This study aimed to strengthen the clinical and epidemiological importance of L. (V.) naiffiin the Amazon Region (Manaus, state of Amazonas) and to report therapeutic failure in patients infected with this species. Thirty Leishmania spp samples isolated from cutaneous lesions were characterised by multilocus enzyme electrophoresis. As expected, the most common species was Leishmania (V.) guyanensis (20 cases). However, a relevant number ofL. (V.) naiffi patients (8 cases) was observed, thus demonstrating that this species is not uncommon in the region. No patient infected withL. (V.) naiffievolved to spontaneous cure until the start of treatment, which indicated that this species may not have a self-limiting nature. In addition, two of the patients experienced a poor response to antimonial or pentamidine therapy. Thus, either ATL cases due to L. (V.) naifficannot be as uncommon as previously thought or this species is currently expanding in this region

IFNG +874T/A polymorphism is not associated with American tegumentary leishmaniasis susceptibility but can influence Leishmania induced IFN-γ production

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma is a key cytokine in the protective responses against intracellular pathogens. A single nucleotide polymorphism (SNP) located in the first intron of the human IFN-γ gene can putatively influence the secretion of cytokine with an impact on infection outcome as demonstrated for tuberculosis and other complex diseases. Our aim was to investigate the putative association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and also the influence of this SNP in the secretion of IFN-γ <it>in vitro</it>.</p> <p>Methods</p> <p>Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and 609 healthy volunteers were evaluated. The genotype of +874 region in the IFN-γ gene was carried out by Amplification Refractory Mutational System (ARMS-PCR). <it>Leishmania</it>-induced IFN-γ production on peripheral blood mononuclear cell (PBMC) culture supernatants was assessed by ELISA.</p> <p>Results</p> <p>There are no differences between +874T/A SNP frequency in cases and controls or in ML versus CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower levels of IFN-γ than TA/TT genotypes. In mucosal cases, high and low IFN-γ producers were clearly demonstrated but no differences in the cytokine production was observed among the IFNG +874T or A carriers.</p> <p>Conclusion</p> <p>Our results suggest that +874T/A polymorphism was not associated with either susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could be involved in the pathogenesis of leishmaniasis by influencing the amount of cytokine released by CL patients, although it could not prevent disease development. On the other hand, it is possible that in ML cases, other potential polymorphic regulatory genes such as TNF-α and IL-10 are also involved thus interfering with IFN-γ secretion.</p

Importância da Atuação da Equipe Multiprofissional na Humanização da Assistência na UTI

OBJECTIVE: To elucidate the role of the multidisciplinary health team in the humanization of care in Intensive Care Units. METHOD: The present study consists of a review of the integrative literature, using the PICO strategy, where "p" population: Multiprofessional health team, "I" interest: Evaluation of the performance of the multiprofessional team in relation to humanization in the Intensive Care Unit o "C" and "O" Context: Performance of the multiprofessional team in the humanization of the ICU. The filter used for the searches was with the descriptors; (Patient Care Team) AND (Humanization of care) AND (Intensive Care Unit). RESULTS: The final sample consisted of 6 studies that resulted in two topics for discussion: training and professional performance in care with a focus on the disease and feelings experienced in the ICU. CONCLUSION: It was possible to conclude that there is a need for further studies focused on the theme and that mention strategies for its implementation. &nbsp;OBJETIVO: Elucidar a atuação da equipe multiprofissional de saúde na Humanização da assistência em Unidades de Terapia Intensiva. MÉTODO: O presente trabalho consiste em uma revisão de literatura integrativa, utilizada a estratégia PICO, sendo “p” população: Equipe multiprofissional de saúde,“I” interesse: Avaliação da atuação da equipe multiprofissional em relação a humanização em Unidade de Terapia Intensiva o “C” e “O” Contexto: Atuação da equipe multiprofissional na humanização da UTI. O filtro utilizado para as buscas foi com os descritores; (Equipe de assistência ao paciente) AND (Humanização da assistência) AND (Unidade de terapia intensiva). RESULTADOS: A amostra final foi constituída por 6 estudos que resultaram em dois tópicos para discussão: formação e atuação profissional no cuidado como foco na doença e sentimentos vivenciados na UTI. &nbsp;CONCLUSÃO: Foi possível concluir que necessitam mais estudos voltados para temática e que mencionem estratégias para sua implementação

HIV/AIDS-associated visceral leishmaniasis in patients from an endemic area in Central-west Brazil

An increase in morbidity associated with visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)/AIDS patients has been described in Africa and the Mediterranean. Despite the high endemicity of VL and HIV-1/AIDS in Brazil, this association has not been thoroughly investigated. Our aim was to evaluate the epidemiologic and clinical characteristics of VL-HIV-1/AIDS cases from Central-west [Mato Grosso do Sul (MS)] Brazil. Medical records of 23 VL-HIV-1/AIDS patients were reviewed. Patients were predominantly adult males (87%) and 34.8% of the patients were intravenous drug users (IVDU). Leishmaniasis was the first opportunistic infection in 60% of the HIV-1 patients. Fever occurred in all patients, although splenomegaly and hepatomegaly were absent in 21.7% of the cases. CD4+ T-cell counts were below 200 cells/mm³ in 80% of the cases and the counts did not increase after clinical remission despite antiretroviral therapy. The first drug chosen to treat the cases was antimonial, but the therapeutic regimen was altered to amphotericin B in 12 of 17 cases due to side effects. Relapses were reported in 56.5% of the patients. IVDU may constitute an important risk factor for the transmission of both diseases in MS. VL-HIV-1/AIDS patients in MS share similar clinical characteristics as those from other endemic regions worldwide. Thus, these findings are critical for improving the surveillance of VL-HIV/AIDS patients