Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis.

OBJECTIVES: Currently, for actinomycetoma, combined antimicrobial therapy is preferred to the use of a single compound. This is in order to provide a broader-spectrum coverage due to a combinatory or synergistic effect between the drugs, and to decrease the possibility of emergence of natural resistant strains. A new oxazolidinone pro-drug, DA-7218 [(R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl-disodium-phosphate] (recently re-named TR-701), has shown very good in vitro and in vivo activities against several gram-positive bacteria including Nocardia spp. METHODS: In the present work we evaluated the effect of DA-7218 at two different doses, alone and combined with trimethoprim/ sulfamethoxazole (SXT), in an experimental Nocardia brasiliensis actinomycetoma murine model. We also included a negative and a positive control group (linezolid and saline solution respectively). RESULTS: At the end of the treatment period, we observed a clinically and statistically significant difference among the drug receiving groups (combined, alone and linezolid) and the control group (P=0.004). The difference was higher (P= 0.004) between the groups receiving DA-7218 (25mg/kg) alone or combined with SXT, and the control group (saline solution). CONCLUSIONS: In this work we proved that DA-7218 alone and combined with SXT is effective in the treatment of experimental actinomycetoma by Nocardia brasiliensis and that it could be potentially useful in the treatment of human actinomycetoma.

Orally administered gossypol has no effect on eight hamster erythrocytic enzymes.

The effectiveness of gossypol as an antifertilizing agent is due to the severe injuries or death that this drug produces on spermatozoa and spermatides. Several in vitro and in vivo studies have shown that spermatozoal lactic and malic dehydrogenases are inhibited by gossypol; and that these are more susceptible than the somatic enzymes. Notwithstanding, the in vivo effects on other somatic enzymes have been poorly analyzed. The present study shows that gossypol did not produce toxic effects on eight erythrocytic enzymes of male hamsters that were fed daily with 20 mg of gossypol/kg, for 1, 3, 5 or 10 days. The enzymatic activities analyzed were: adenylate kinase, hexokinase, glucose-6-phosphatase, glucose phosphoisomerase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglyceratokinase and pyruvate kinase.

Axenic massive cultivation of Entamoeba histolytica trophozoites in spinner flasks and in a microfermentor.

A medium, PEHPS, whose main components are extracts of ox liver, and ox and swine pancreas (EHP) was used to develop two alternative methods for axenic cultivation of trophozoites in suspension: with magnetic stirrer and with a 14 l capacity microfermentor, giving the first technic yields of 2.36 x 10(5) to 3.08 x 10(5) and the second in a 14 l capacity microfermentor, which produced 1.65 x 10(5) amebas/ml in one batch and 2.94 to 3.65 x 10(5) of such parasites/ml at semicontinuous flux.

PEHPS medium: an alternative for axenic cultivation of Entamoeba histolytica and E. invadens.

Knowledge of Entamoeba histolytica biology in the last 17 years has been acquired largely as a consequence of this parasite's axenic cultivation in TPS-1 or TYI-S-33 media. Unfortunately, there are often low yields in these media, due to variability of their main components, Panmede and yeast extract. We describe a medium, PEHPS, of which the main components are extracts of ox liver, and ox and swine pancreas (EHP). 5 strains of E. histolytica and 2 of E. invadens were quickly and easily adapted to PEHPS and serially cultivated for 3 years. Yields progressively rose initially, and then became stable. Depending on the strain, average yields in the last 6 months of this study were 1.3 to 3.1 x 10(5) amoebae/ml for E. histolytica and 5.5 to 5.7 x 10(5) for E. invadens. All the 18 EHP batches tested supported vigorous amoebal growth. PEHPS had 2 additional advantages: (a) it was stable at 4 degrees C or 25 degrees C for 9 months, and at -10 degrees C for at least 2 years, and (b) it supported amoebal growth with inocula as low as one trophozoite/ml. PEHPS avoids the variability shown by TPS-1 and TYI-S-33, and could therefore be a good alternative for axenic amoebal cultivation.