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Treatment of Experimental Visceral Leishmaniasis with Amphotericin B in Stable Albumin Microspheres. J. A. Sánchez-Brunete, 2004.Hydrophilic albumin microspheres are proposed as a new delivery system for amphotericin B (AMB; AMB microspheres) . The acute toxicity of AMB microspheres was lower than that of the AMB-deoxycholate (AMB-Doc) reference formulation in hamsters . Lethal doses in healthy and infected animals were improved at least eight times . Intravenous bolus administration of doses of AMB microspheres up to 40 mg/kg of body weight did not produce acute symptoms of toxicity . The efficacy of this new formulation was tested against Leishmania infantum-infected hamsters at doses of 2, 10, 20, and 40 mg/kg . With the 2-mg/kg dose, the activity of AMB, as assessed through the parasite load reductions in the liver and spleen and the evolution of antibody levels, was also improved (P < 0.05) by use of the AMB microsphere system . At the higher doses of 10, 20, and 40 mg/kg, reductions in parasite levels of more than 99% were achieved in the liver and spleen after the administration of AMB microspheres . A pharmacokinetic study was performed to study the serum, liver, and spleen AMB concentrations after administration of AMB microspheres and the reference formulation . Interestingly, a significant accumulation of AMB in the spleen and liver was observed after AMB microsphere administration . Our results suggest that this new formulation is a promising alternative to the conventional AMB-Doc formulation for the treatment of visceral leishmaniasis . Identification of Type A, B, E, and F Botulinum Neurotoxin Genes and of Botulinum Neurotoxigenic Clostridia by Denaturing High-Performance Liquid Chromatography. Giovanna Franciosa, 2004.Denaturing high-performance liquid chromatography (DHPLC) is a recently developed technique for rapid screening of nucleotide polymorphisms in PCR products . We used this technique for the identification of type A, B, E, and F botulinum neurotoxin genes . PCR products amplified from a conserved region of the type A, B, E, and F botulinum toxin genes from Clostridium botulinum, neurotoxigenic C . butyricum type E, and C . baratii type F strains were subjected to both DHPLC analysis and sequencing . Unique DHPLC peak profiles were obtained with each different type of botulinum toxin gene fragment, consistent with nucleotide differences observed in the related sequences . We then evaluated the ability of this technique to identify botulinal neurotoxigenic organisms at the genus and species level . A specific short region of the 16S rRNA gene which contains genus-specific and in some cases species-specific heterogeneity was amplified from botulinum neurotoxigenic clostridia and from different food-borne pathogens and subjected to DHPLC analysis . Different peak profiles were obtained for each genus and species, demonstrating that the technique could be a reliable alternative to sequencing for the rapid identification of food-borne pathogens, specifically of botulinal neurotoxigenic clostridia most frequently implicated in human botulism . Long-Chain Acyl-Homoserine Lactone Quorum-Sensing Regulation of Rhodobacter capsulatus Gene Transfer Agent Production. Amy L. Schaefer, 2002.Many proteobacteria use acyl-homoserine lactones as quorum-sensing signals . Traditionally, biological detection systems have been used to identify bacteria that produce acyl-homoserine lactones, although the specificities of these detection systems can limit discovery . We used a sensitive approach that did not require a bioassay to detect production of long-acyl-chain homoserine lactone production by Rhodobacter capsulatus and Paracoccus denitrificans . These long-chain acyl-homoserine lactones are not readily detected by standard bioassays . The most abundant acyl-homoserine lactone was N-hexadecanoyl-homoserine lactone . The long-chain acyl-homoserine lactones were concentrated in cells but were also found in the culture fluid . An R . capsulatus gene responsible for long-chain acyl-homoserine lactone synthesis was identified . A mutation in this gene, which we named gtaI, resulted in decreased production of the R . capsulatus gene transfer agent, and gene transfer agent production was restored by exogenous addition of N-hexadecanoyl-homoserine lactone . Thus, long-chain acyl-homoserine lactones serve as quorum-sensing signals to enhance genetic exchange in R . capsulatus .
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