The standard treatment of human leishmaniases involves the use of pentavalent antimony [Sb(V)] compounds, including meglumine antimoniate. The mode of action of these compounds has not been fully elucidated. The possibility that Sb(III) is involved has been suggested; however, the biomolecule that may induce the conversion of Sb(V) to Sb(III) has not yet been identified. In the present study, we investigated both the ability of reduced glutathione (GSH) to promote the reduction of Sb(V) into Sb(III) in meglumine antimoniate and the effects of pH and temperature on this transformation. GSH did promote the reduction of Sb(V) into Sb(III) in a dose-dependent manner. When GSH and meglumine antimoniate were incubated together at a GSH/Sb molar ratio superior or equal to 5:1, all antimony was encountered in the reduced form, indicating a stoichiometry of 5:1 between GSH and Sb(V) in the reaction. The reaction between Sb(V) and GSH was favored at an acidic pH (pH 5) and an elevated temperature (37°C), conditions found within the phagolysosome, in which Leishmania resides. For instance, about 30% of the Sb(V) (concentration, 2mM) was converted to Sb(III) following incubation for 3 days with 10 mM GSH at pH 5 and 37°C. Our data support the hypothesis that Sb(V) would be converted by GSH, or a related thiol compound, to more toxic Sb(III) in the phagolysosome of macrophages.The leishmaniases are a group of diseases produced by invasion of the reticuloendothelial system of a vertebrate host by a parasite of the genus Leishmania. This parasite is found as a motile promastigote in the sandfly; it transforms into an amastigote when engulfed by host macrophages and resides in the acidic environment of secondary lysosomes (1). These diseases are a significant cause of morbidity and mortality in several countries of the world. The treatment of choice for all forms of leishmaniasis depends on pentavalent antimony [Sb(V)]-containing drugs such as meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam). Despite the clinical use of these antileishmanial agents for over half a century, their mechanism of action and the basis for their selective toxicity remain unknown. The hypothesis that Sb(V) acts as a prodrug that is converted to the more toxic trivalent antimony [Sb(III)] at or near the site of action was first suggested by Goodwin and Page (9), after they observed that a host organism can reduce Sb(V) into Sb(III). Recently, hydride generation-atomic absorption spectrometry analysis of serum and urine from patients treated with meglumine antimoniate revealed that 15 to 25% of serum antimony and 50% of urine antimony were trivalent (3, 15). This hypothesis was further supported by the observations that Sb(III) is more toxic than Sb(V) against both parasite stages of different Leishmania species (13,19,21) and that mutants of Leishmania infantum amastigotes selected for resistance to Sb(III) were cross-resistant to Sb(V) inside monocytes (22).Recently, however, Ephros et al. (6) showed that axenically grown amasti...

The antimicrobial activity of substances used as antibacterial agents (solutions of 10% calcium hydroxide, camphorated paramonochlorophenol -PMCC, 2% chlorhexidine digluconate and 10% castor oil plant detergent) on anaerobic bacteria (Fusobacterium nucleatum ATCC 25586, Prevotella nigrescens ATCC 33563, Clostridium perfringens ATCC 13124 and Bacteroides fragilis ATCC 25285), using a broth dilution technique, was evaluated in vitro. For determination of minimum inhibitory and minimum bactericide concentrations (MIC and MBC), two culture broths, Reinforced Clostridial Medium (RCM) and supplemented Brucella, standardized inoculum and serially diluted solutions were used. All antibacterial agents presented antimicrobial activity that varied for different bacteria. There were no differences in the performance of the two broths. Chlorhexidine digluconate was the most effective, with the lowest MICs, followed by castor oil detergent, PMCC and calcium hydroxide. C. perfringens and B. fragilis were the most resistant bacteria to all agents.

A literatura mostra-se muito carente a respeito da ansiedade odontológica na população brasileira. A proposta deste estudo foi a de avaliar a ansiedade expressada entre pacientes, selecionados aleatoriamente, que estavam sendo submetidos ao tratamento odontológico

The possibility of three canals in maxillary second premolars is quite small; however, it must be taken into account in clinical and radiographic evaluations during endodontic treatment. Many times their presence is noticed only after canal treatment, due to continuing postoperative discomfort. This article describes a clinical case of three-canal maxillary second premolars that are endodontically treated.

The present work establishes for the first time the potential of mixed formulations of conventional and pegylated liposomes as a drug delivery strategy for improved treatment of VL.

No abstract

Registraram-se, nos últimos vinte anos, casos autóctones de malária por Plasmodium vivax no Município de Peruíbe (24,19ºS e 47,00ºW), Litoral Sul do Estado de São Paulo, com presença de portadores assintomáticos ou oligossintomáticos associada ou não a parasitemias subpatentes. O problema na área é também conhecido como "bromélia-malária"; os vetores pertencem ao subgênero Kerteszia: Anopheles (K.) cruzii e A. (K.) bellator. A partir do segundo semestre de 1984 foram realizados, semestralmente, inquéritos sorológicos visando a dois objetivos: detectar possíveis fontes de infecção inaparente e obter o perfil sorológico da população, visando à melhoria do conhecimento da dinâmica da transmissão da malária e seu controle no foco. Este compreende 10 localidades, com população de cerca de 3000 pessoas, cuja mobilidade associa-se à presença de visitantes à aldeia indígena; à fazenda de cacau, que incorpora mão-de-obra transitória; em casas de temporada e existência de grupos nos quais a rotatividade se dá em função do processo de posse da terra. Como atividade econômica destaca-se a agricultura de banana e de cacau, além dos cultivos de subsistência. A técnica sorológica utilizada - reação de imunofluorescência indireta (RIFI) - foi processada com antígenos de P. vivax. O valor diagnóstico da RIFI foi confirmado pela identificação de alguns casos autóctones antes que as gotas espessas se revelassem positivas. A distribuição de freqüências de títulos na população foi comparável ao padrão de área de baixa endemicidade. Os soro-positivos predominaram entre o sexo masculino e nos grupos etários acima de 15 anos, faixas a que pertencem os indivíduos produtivos na agricultura e que apresentam uma relação mais estreita com a mata.

The prevalences of intestinal parasitic infections were investigated, between 1995 and 1996, in a household-based sample of 1044 children aged <5 years who lived in the city of São Paulo, Brazil. Only 10.7% of the children were infected, the most prevalent parasites being Giardia duodenalis (5.5%), Ascaris lumbricoides (4.4%) and Trichuris trichiura (1.0%). A comparison between these data and results from two previous population-based surveys, completed in São Paulo in 1974 and 1985, revealed a dramatic decrease in the prevalence of intestinal helminths in this age-group, with less marked changes in the prevalence of Giardia, over the two past decades. Despite the low prevalence of malnutrition (2.4% of stunting and 0.6% of wasting) and intestinal parasites in this population, there was a significant association (P=0.05, after controlling for potential confounding variables) between helminth (but not Giardia) infection and height. The helminth-infected children had a mean height-for-age z-score of-0.412 [95% confidence interval (CI)=-0.637--0.186], compared with one of 0.015 (CI=-0.049-0.079) for the non-infected children. No significant relationship between intestinal parasitic infection and children's weight was detected. In conclusion, a small but significant negative relationship between intestinal helminthic infections and children's growth was detected in an urban environment with low prevalences of both intestinal parasitic infection and malnutrition.