Hydrogen photoproduction by nutrient-deprived Chlamydomonas reinhardtii cells immobilized within thin alginate films under aerobic and anaerobic conditions.

A new technique for immobilizing H2-photoproducing green algae within a thin (<400 microm) alginate film has been developed. Alginate films with entrapped sulfur/phosphorus-deprived Chlamydomonas reinhardtii, strain cc124, cells demonstrate (a) higher cell density (up to 2,000 microg Chl mL(-1) of matrix), (b) kinetics of H2 photoproduction similar to sulfur-deprived suspension cultures, (c) higher specific rates (up to 12.5 micromol mg(-1) Chl h(-1)) of H2 evolution, (d) light conversion efficiencies to H2 of over 1% and (e) unexpectedly high resistance of the H2-photoproducing system to inactivation by atmospheric O2. The algal cells, entrapped in alginate and then placed in vials containing 21% O2 in the headspace, evolved up to 67% of the H2 gas produced under anaerobic conditions. The results indicate that the lower susceptibility of the immobilized algal H2-producing system to inactivation by O2 depends on two factors: (a) the presence of acetate in the medium, which supports higher rates of respiration and (b) the capability of the alginate polymer itself to effectively separate the entrapped cells from O2 in the liquid and headspace and restrict O2 diffusion into the matrix. The strategy presented for immobilizing algal cells within thin polymeric matrices shows the potential for scale-up and possible future applications.

Possible cardioprotective effect of angiotensin-converting enzyme inhibitors during treatment of American tegumentary leishmaniasis with meglumine antimoniate.

We conducted an observational retrospective study to identify factors associated with prolongation of corrected QT (QTc) interval during treatment of American tegumentary leishmaniasis with meglumine antimoniate. A group of 108 patients with normal ECG before treatment were included. Thirty-one patients (29%) developed increase of QTc interval beyond 0.44s in the second ECG performed after an average of (mean+/-S.D.) 12.6+/-4.9 days. After univariate and multivariate analysis, the age was associated with prolonged QTc interval, and the use of angiotensin-converting enzyme (ACE) inhibitors demonstrated a protective factor. These results identify elderly as a risk factor to develop prolonged QTc due to antimonial therapy (odds ratio: 1.1; 95% confidence interval: 1.01-1.12), and suggest that use of ACE inhibitors is a possible cardioprotective agent (odds ratio: 0.3; 95% confidence interval: 0.003-0.34). Further studies using prospective methodology are necessary to define the role of ACE inhibitors as prophylactic agent in high-risk patients.

Glucantine resistant Leishmania promastigotes are sensitive to pentostam

Diferentes amostras de leishmania foram analisadas quanto à susceptibilidade in vitro ao pentostam - uma cepa de L. (V) braziliensis considerada sensível ao glucantine, três cepas (duas L. (V) braziliensis e uma L. (L) amazonensis) consideradas naturalmente resistentes ao glucantine, uma linhagem resitente (L. (V) guyanensis) selecionada in vitro pela exposiçäo em alta concentraçäo de droga. A elevada sensibilidade destas amostras em contraposiçäo à resistência observada para a glucantine sugere existir relaçäo entre a estrutura química e a atividade destes compostos. Estes dados indicam a necessidade de uma avaliaçäo comparativa de atividade clínica do pentostam e do glucantime no tratamento da leishamniose

Glucantime resistant Leishmania promastigotes are sensitive to pentostam.

Growth inhibition in vitro tests were used to study the susceptibility to pentostam of different Leishmania strains involved in cutaneous and mucocutaneous leishmaniasis--one glucantime sensitive strain, three naturally glucantime resistant strains and one glucantime resistant line developed by in vitro drug exposure. Contrasting with the high degree of glucantime resistance, all strains were sensitive to pentostam. These differences suggest that there is some relationship between chemical structure and in vitro activity for these antimonial compounds. These data justify a clinical re-evaluation to compare therapeutic efficacy of glucantime and pentostam in the treatment of leishmaniasis.

Leishmania donovani: antagonistic effect of S-adenosyl methionine on ultrastructural changes and growth inhibition induced by sinefungin.

Sinefungin, an antifungal and antiparasitic nucleoside antibiotic, is a very potent antileishmanial agent in vitro and in vivo (Bachrach et al. 1980, FEBS Letters 121, 287-291; Neal et al. 1985, Transactions of the Royal Society of Tropical Medicine and Hygiene 79, 85-122). It was previously shown that this molecule is a competitive inhibitor of AdoMet for transmethylases (Paolantonacci et al. 1986, Molecular and Biochemical Parasitology 21, 47-54; Avila et al. 1987, Molecular and Biochemical Parasitology 26, 69-76) and that it induces shape changes of Leishmania donovani promastigotes as observed by light microscopy (Lawrence and Robert-Gero 1990; Bulletin de la Societé Française de Parasitologie 8, 13-18). In the present work the effect of the antibiotic on the ultrastructure was analyzed by electron microscopy. The main changes induced at sublethal concentrations (0.26 microM sinefungin for 16 hr) were progressive rounding, decreased motility, enlargement of the flagellar pocket, and shortening and loss of the external part of the flagellum. The comparison with control cells showed shorter Golgi saccules and fragmentation of the trans-Golgi network into vesicles, indicating a stimulated Golgi apparatus activity. This result, associated with the enlarged flagellar pocket, suggests an unbalanced cytoplasmic exchange between exocytosis and endocytosis. These effects are quite different from those induced by tunicamycin (Dagger et al. 1984, Biology of the Cell 50; 173-180) or paromomycin. In addition, other nucleoside and nonnucleoside growth inhibitors failed to induce similar changes. AdoMet antagonized the sinefungin-induced shape changes and ultrastructural modifications but had no effect with respect to other growth inhibitors. This suggests that the sinefungin activity at the cellular level is specifically related to competition with AdoMet. A comparative study of N-methylation and carboxylmethylation of proteins in sinefungin-treated promastigotes showed that the antibiotic preferentially inhibits the latter, catalyzed by protein-O-methyltransferases. These enzymes are known to regulate the function of various proteins involved in secretion. Overall the results suggest that one of the main targets of sinefungin in exponentially growing cells is the protein carboxylmethylation involved in membrane transport.