Autoantibodies against beta-adrenoceptors might be involved in different cardiomyopathic diseases such as idopathic dilated cardiomyopathy, Chagas' disease and ventricular arrhythmias. To study the effects of such antibodies on the whole heart, we made use of a new technique allowing the measurement of Ca++ transients as well as action potentials in Langendorff preparations of mouse hearts. Mouse antibodies directed against the second extracellular loop of the beta2-adrenoceptor induced conduction blocks which could be washed away by the beta2-adrenoceptor inverse agonist ICI118,551, confirming the specificity and non-toxicity of these events.
View Article and Find Full Text PDFWithin the context of microorganism/host interactions, those which last over weeks are expected to be sensitive to more or less sustained and targeted immuno-intervention, such as delivery of cytokines known to operate as down-regulators of acute inflammatory processes. IL-10 has received growing attention as a potential tool in immunotherapy, due to its anti-inflammatory and immunosuppressive properties. Therefore, using two experimental models of long-term interactions between parasites and laboratory mice, we monitored some effects of the systemic delivery of an adenovirus (Ad) expressing EBV-derived IL-10 (vIL-10) designated Ad-vIL-10.
View Article and Find Full Text PDFTrypanosoma cruzi target molecules that might regulate the host immune responses have not yet been fully identified. In the present study, we demonstrate that the parasite-released molecule (Tc52) was able to synergize with IFN-gamma to stimulate nitric oxide production by macrophages. This synergistic effect was also observed at the level of inducible nitric oxide synthase gene expression.
View Article and Find Full Text PDFIn previous studies, molecular and immunological approaches have been used to characterize the Trypansosoma cruzi elongation factor 1gamma (TcEF-1gamma). A primary sequence homology search revealed that the TcEF-1gamma N-terminal domain showed significant homology to glutathione S-transferases (GSTs). Although studies have suggested the involvement of EF-1gamma in the protein synthesis machinery, the exact function of this protein, particularly the role of its GST-like domain, is not fully understood.
View Article and Find Full Text PDFThe cloning and sequencing of the gene coding for Trypanosoma cruzi elongation factor 1 alpha (TcEF-1 alpha) was performed by screening a T. cruzi genomic library with a probe obtained through the polymerase chain reaction (PCR) amplification of T. cruzi DNA using two oligonucleotides deduced from the sequence of T.
View Article and Find Full Text PDFInt J Antimicrob Agents
December 1995
Trypanothione reductase (TR) is the primary enzyme responsible for the reduction of trypanothione, the analog of glutathione found in trypanosomatidae. We have discovered a series of diphenylsulfides which are potent inhibitors of TR and have no activity on mammalian glutathione reductase. These compounds are also active in vitro on various stages of the parasite.
View Article and Find Full Text PDFWe have previously isolated and characterized a Trypanosoma cruzi cDNA encoding a polypeptide with a molecular mass of 52 kDa (Tc52) sharing significant homology to glutathione S-transferase. In the present study, by molecular and immunological approaches, we showed that Tc52 is preferentially expressed by dividing forms of the parasite: (e.g.
View Article and Find Full Text PDFVenom from three different snake species was tested in vitro against the protozoan parasites Trypanosoma cruzi and Leishmania donovani infantum. Two of them, Cerastes cerastes and Naja haje, exerted a significant growth inhibition of T. cruzi and L.
View Article and Find Full Text PDFIn previous studies, we reported the characterization of three Trypanosoma cruzi proteins with molecular masses of 45, 30 and 25 kDa eluted from a glutathione agarose column (these proteins were named TcGBP). Using antibodies against TcGBP native proteins we could isolate from a lambda ZAPII epimastigote cDNA library cDNA clones encoding the 30 and 25 kDa proteins. Comparison of the two sequences with amino acid sequences in several data banks revealed that both protein sequences were highly homologous to human and Artemia salina elongation factor 1 beta.
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