Matrix metalloproteinases (MMPs) mediate demyelination and breakdown of the blood-nerve barrier in peripheral neuropathies. Matrix metalloproteinases and tissue inhibitor of metalloproteinase 1gene ...expression and secretion were studied in cells of the human Schwann cell line ST88-14 stimulated with Mycobacterium leprae and tumor necrosis factor (TNF) and in nerve biopsies from patients with neural leprosy (n = 21) and nonleprous controls (n = 3). Mycobacterium leprae and TNF induced upregulation of MMP-2 and MMP-9 and increased secretion of these enzymes in cultured ST88-14 cells. The effects of TNF and M. leprae were synergistic, and anti-TNF antibody blockage partially inhibited this synergistic effect. Nerves with inflammatory infiltrates and fibrosis displayed higher TNF, MMP-2, and MMP-9 mRNA than controls. Leprous nerve biopsies with no inflammatory alterations also exhibited higher MMP-2 and MMP-9; tissue inhibitor of metalloproteinase 1 wassignificantly higher in biopsies with fibrosis and inflammation. Immunohistochemical double labeling of the nerves demonstrated that the MMPs were mainly expressed by macrophages and Schwann cells. The biopsies with endoneurial inflammatory infiltrates and epithelioid granulomas had the highest levels of MMP-2 and MMP-9 mRNA detected. Together, these results suggest that M. leprae and TNF may directly induce Schwann cells to upregulate and secrete MMPs regardless of the extent of inflammation in leprous neuropathy.
Os testes pré-transfusionais de acordo com legislação vigente representam um papel importantíssimo na segurança transfusional, no entanto, a eficácia desses testes depende da qualificação dos ...profissionais que os executam, bem como da qualidade dos reagentes utilizados. A membrana eritrocitária é composta de pelo menos 378 antígenos eritrocitários. Os reagentes comerciais utilizados para PAI devem contemplar os antígenos mais imunogênicos e que podem induzir a formação de aloanticorpos clinicamente significantes. O sistema RH é um sistema altamente polimórfico, contendo 56 antígenos, incluindo antígenos compostos e o antígeno f (RH6) é um exemplo, expresso quando hemácias possuem c (RH4) e e (RH5) no mesmo haplotipo (cis). O objetivo deste trabalho consiste em um alerta para a fabricação das hemácias de triagem, descrevendo o relato de um caso em que a PAI apresentou resultado negativo devido a configuração antigênica do kit comercial e PC maior apresentou resultado incompatível (grau de aglutinação: 4+), devido à presença de anticorpos anti-f.
A PAI foi realizada utilizando a metodologia de aglutinação em coluna automatizada (Gel teste, Erytra/Eflexis®, Grifols), reagentes de hemácias e cartões DG LISS/Coombs. Para a identificação de anticorpos irregulares, foram utilizados o Identisera Diana/Extend e Diana P/EXtend P. A prova de compatibilidade maior foi executada utilizando a mesma metodologia (gel teste-LISS/Coombs).
Paciente E.R.A., PAI realizada na agência transfusional utilizando hemácias Serascan fenótipos R1R1, R2R2e R1R2Di(a+) demonstrou resultado negativo. Ao realizar provas de compatibilidade com duas unidades de glóbulos os resultados demonstraram incompatibilidade com as duas bolsas. Testes adicionais foram realizados incluindo hemácias com e sem tratamento enzimático. Os resultados demonstraram positividade em LISS/Coombs somente com a célula rr. Os anticorpos foram potencializados com a utilização de hemácias tratadas com enzima papaína. Fenótipo do paciente D+C-E+c+e- (R2R2). A Identificação dos anticorpos irrregulares demonstrou a presença de anticorpos com especificidade anti-f em LISS/Coombs e em enzima além do anti-f, foram detectados aloanticorpos adicionais com especificidade anti-e. Os anticorpos anti-f, pertencem ao Sistema RH e podem estar envolvidos em reações transfusionais. Esses anticorpos podem ser comumente encontrados, no entanto, os diagramas das hemácias comerciais podem não contemplar essa descrição do antígeno f, dificultando a identificação do anticorpo, embora possam inferir a fenotipagem de acordo com a presença dos antígenos c(RH4) e e(RH5) no mesmo haplotipo (cis). Dessa forma concluímos que analisar o fenótipo das hemácias comerciais utilizadas na rotina de PAI é de extrema importância e ressalta a necessidade em incluir na fabricação dos kits de triagem de anticorpos irregulares, hemácias fenótipo f+; a fim de evitar falsos resultados negativos de PAI e possíveis reações transfusionais.
This paper describes the in vitro antiviral evaluation of 27 different marine sponges (Porifera) collected off Brazilian coastline in the search for novel drug leads. With these sponges aqueous and ...organic extracts were prepared and tested for anti-herpetic (HSV-1, KOS strain), anti-adenovirus (human AdV serotype 5) and anti-rotavirus (simian RV SA11) activities. The evaluation of the cytotoxicity and potential antiviral activity of these extracts were performed by using MTT assay. Results were expressed as 50% cytotoxicity (CC50) and 50% effective (EC50) concentrations, respectively, in order to calculate the selectivity indices (SI=CC50/EC50) of each extract. From the 40 sponge extracts tested, 17 extracts showed antiviral action in different degrees. The results concerning the antiviral activity were obtained by using three different strategies: (1) simultaneous assay, when sponge extracts were added to the cells at the same time of the viruses; (2) pre treatment assay, when sponge extracts were added to the cells 15 h prior to the viruses infection; and (3) post treatment assay, when the viruses were added to the cells and remained during 2 h prior to the addition of sponge extracts. The antiviral assays with HSV-1/KOS and AdV-5 showed more promising results when the pre treatment test was employed. In relation to the RV-SA11 virus, only the simultaneous assay showed antiviral activity. The extracts presenting the most promising results were the aqueous extracts of Cliona sp., Agelas sp.2, Tethya sp., Axinella aff corrugata, Polymastia janeirensis and Protosuberites sp., and these extracts deserve special attention in further studies.
Various allylbenzenes and propenylbenzenes have been hydroformylated with a 97–99% chemoselectivity using bis(μ-acetate)(1,5-cyclooctadiene)rhodium(I) as a catalyst precursor. Regioselectivity of the ...hydroformylation can be controlled by the nature of phosphorus auxiliary ligands. The Rh-NAPHOS (2,2′-bis(diphenylphosphino)methyl-1,1′-binaphthyl) system promotes the hydroformylation of allylbenzenes into linear aldehydes in near 95% selectivity and propenylbenzenes into branched aldehydes with a formyl group in α-position to phenyl ring in near 90% selectivity, while the Rh-dppp (1,3-bis(diphenylphosphino)propane) system gives branched aldehydes with a formyl group in β-position in near 70% selectivity starting from allylbenzenes. The regioselectivity of Rh-diphosphine systems correlates with a ligand bite angle. Both the rate and regioselectivity of the hydroformylation are largely influenced by the basicity of monophosphine auxiliary ligands, however, no correlation between their steric characteristics and the regioselectivity has been observed.
Despite its high prevalence, nonulcer dyspepsia is still difficult to study, due to the lack of adequate tools to measure significant outcomes. The objective of this study was to develop and validate ...a symptom-focused, disease-specific questionnaire to evaluate patients with nonulcer dyspepsia. For that, the questionnaire was carefully written following widely accepted terminology, so as to facilitate translation and validation in other languages and cultures. The questionnaire was developed using Rome I terminology for symptoms, which were evaluated according to their intensity, duration, and frequency when applicable. Thirty-one patients with nonulcer dyspepsia, as well as 31 sex-and age-matched volunteers without digestive problems were used to assess the internal consistency, reproducibility, responsiveness, content validity, and discriminant validity of the questionnaire. Another 31 functional dyspeptic patients were enrolled for assessment of criterion validity. Cronbach's alpha coefficient was 0.82. The intraclass correlation coefficient for the scores obtained 7 days apart was 0.86. The mean score obtained after 3 months of treatment was 16.4, vs. 23.03 at baseline (P = 0.001). Two blinded gastroenterologists agreed that the questionnaire adequately evaluated nonulcer dyspepsia. The median symptoms score for controls was 0, vs. 22.5 for dyspeptic patients (P = 0.001). An inverse correlation was observed between quality of life and dyspeptic symptoms (R = -0.28, P = 0.026). The proposed questionnaire has high degrees of both reproducibility and responsiveness. As this questionnaire was based on Rome I International Consensus terminology, it is expected that it will be easy to translate and validate.
A highly evolved relationship exists between the parasitic flatworm
Schistosoma mansoni and its vertebrate hosts that include the use of host immune signals by parasites. The
S. mansoni infection was ...studied in two strains of mice genetically selected, over 18 generations of assortative mating, for extreme phenotypes of susceptibility (TS) and resistance (TR) to immunological tolerance. The objective was to observe whether the different host genetic backgrounds affected the outcome of experimental schistosomiasis. Fecal egg excretion, tissue egg count, worm recovery, and adult worm morphology and morphometry were monitored throughout the period of infection. TR mice presented total fecal egg excretion and thickness of tegument in adult male worms significantly higher than TS mice. Therefore, the comparative analysis of mice with extreme phenotypes of immunological response turns out to be useful in host–parasite relationship studies. Our results suggest that the TR mouse immunological profile provides a more favorable environment for the development of
S. mansoni.
To evaluate the possible role of parasitemia on Chagas' disease reactivation in Chagas' disease/human immunodeficiency virus (HIV) coinfection cases and the impact of HIV coinfection on Trypanosoma ...cruzi genetic diversity, 71 patients with Chagas' disease (34 HIV+ and 37 HIV-) were surveyed. Moreover, 92 T. cruzi stocks from 47 chronic chagasic patients (29 HIV+ and 18 HIV-) were isolated and analyzed by multilocus enzyme electrophoresis and a random amplified polymorphic DNA procedure. High parasitemia appeared to play a major role in cases of Chagas' disease reactivation. In HIV+ patients, the genetic diversity and population structure (clonality) of T. cruzi was similar to that previously observed in HIV- patients, which indicates that immunodepression does not modify drastically genotype repartition of the parasite. There was no apparent association between given T. cruzi genotypes and specific clinical forms of Chagas' disease/HIV associations.
226 methanol and water extracts representing 74 mainly native plant species found in Amazonas State, Brazil, were tested at a standard concentration of 500 mu g/mL for lethality towards larvae of the ...brine shrimp species Artemia franciscana. Several cytotoxic plant species were identified in this work: Aspidosperma marcgravianum, A. nitidum, Croton cajucara, Citrus limetta, Geissospermum argenteum, Minquartia guianensis, Piper aduncum, P. amapense, P. capitarianum, P. tuberculatum and Protium aracouchini. The results were analyzed within the context of the available traditional knowledge and uses for these plants.
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