Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) es un chinche hematófago asociado generalmente al ciclo silvestre del Trypanosoma cruzi Chagas, 1909, agente etiológico de la Enfermedad de Chagas. Las incursiones de... more
Panstrongylus geniculatus (Latreille, 1811) (Reduviidae: Triatominae) es un chinche hematófago asociado generalmente al ciclo silvestre del Trypanosoma cruzi Chagas, 1909, agente etiológico de la Enfermedad de Chagas. Las incursiones de este insecto en domicilios ubicados en zonas urbanas y periurbanas causan alarma en la población y se hacen cada vez más frecuentes. Como un aporte al conocimiento disponible sobre la biología y ecología de P. geniculatus como especie transmisora de T. cruzi en este tipo de ambientes, se propuso como objetivo explorar la influencia de seis variables ambientales (altitud, precipitación mensual, humedad relativa, temperatura media, radiación solar y velocidad del viento) sobre la distribución de especímenes de esta especie capturados en domicilios de 12 localidades del Área Metropolitana de Caracas (AMC). La evaluación parasitológica de los 39 insectos examinados mostró que cerca del 90% de ellos presentaron formas flageladas en sus heces. La mayor can...
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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed during both the acute and chronic phases of the disease, is characterized by an inammatory... more
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed during both the acute and chronic phases of the disease, is characterized by an inammatory mononuclear cell infiltrate that includes CD4+ T cells. It is known that Th1 cytokines help to control infection. The role that Treg and Th17 cells may play in disease outcome, however, has not been completely elucidated. We performed a comparative study of the dynamics of CD4+ T cell subsets after infection with the T. cruzi Y strain during both the acute and chronic phases of the disease using susceptible BALB/c and non-susceptible C57BL/6 mice infected with high or low parasite inocula. During the acute phase, infected C57BL/6 mice showed high levels of CD4+ T cell infiltration and expression of Th1 cytokines in the heart associated with the presence of Treg cells. In contrast, infected BALB/c mice had a high heart parasite burden, low heart CD4+ T cell ...
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Despite the fact that Leishmania parasites are transmitted exclusively by the bite of an infected sand fly, there are few reports concerning the relationship of this factor on Leishmania infection. Two models were developed, one using... more
Despite the fact that Leishmania parasites are transmitted exclusively by the bite of an infected sand fly, there are few reports concerning the relationship of this factor on Leishmania infection. Two models were developed, one using needle injection and the second based on natural transmission by the vector. During the natural transmission of Leishmania, sand flies inoculate low numbers of metacyclic promastigotes, along with saliva, into the skin of the mammalian host. It has previously been revealed by experimental mouse models of cutaneous Leishmaniasis that infection in a subcutaneous site is enhanced following co-inoculation of parasites with sand fly saliva. Extending these observations to a dermal model of disease, we take into account the fact that most individuals who live in endemic areas are exposed to saliva from uninfected flies before the bite that transmits infection. We developed a model of cutaneous Leishmaniasis with L. major in BALB/c and C57Bl/6 (B/ 6) mice tha...
Chagas' disease, a protozoan infection by the kinetoplastid Trypanosoma cruzi, constitutes a major public health problem in Latin America. With the use of mouse models of both short- and long-term forms of the disease, the... more
Chagas' disease, a protozoan infection by the kinetoplastid Trypanosoma cruzi, constitutes a major public health problem in Latin America. With the use of mouse models of both short- and long-term forms of the disease, the efficacy of D0870, a bis-triazole derivative, was tested. D0870 was able to prevent death and induced parasitological cure in 70 to 90 percent of animals, in both the short- and long-term disease. In contrast, currently used drugs such as nifurtimox or ketoconazole prolonged survival but did not induce significant curing effects. D0870 may be useful in the treatment of human long-term Chagas' disease, a condition that is currently incurable.
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Research Interests: Engineering, Physics, Chemistry, Flow Cytometry, Biology, and 14 moreCytokines, Medicine, Multidisciplinary, Mice, Female, Animals, PLoS one, Chagas disease, Fluorescent Antibody Technique, Trypanosoma Cruzi, Transforming Growth Factor Beta, Interleukin, Interferon gamma, and real time polymerase chain reaction
Research Interests: Organic Chemistry, Medicinal Chemistry, Biology, Calcium, Medicine, and 15 moreCercopithecus aethiops, Mice, Animals, Chagas disease, Ciencias Biológicas, Trypanosoma Cruzi, Medicinal, Trypanocidal Agents, Triazoles, Ergosterol, Amiodarone, Molecular Structure, Acute Disease, Drug synergism, and Pharmacology and pharmaceutical sciences
Research Interests: Medical Microbiology, Biology, Pharmacokinetics, Medicine, Mice, and 15 moreChronic Disease, Female, Animals, Drug Resistance, Chagas disease, Trypanosoma Cruzi, Antimicrobial agents, Side Effect, Trypanocidal Agents, In Vitro Studies, Triazoles, Murine Model, Acute Disease, minimal inhibitory concentration, and Pharmacology and pharmaceutical sciences
Research Interests: Medical Microbiology, Biology, Treatment, Medicine, In Vitro, and 15 moreMice, Female, Animals, Drug Resistance, Animal Model, Antifungal Activity, Chagas disease, In Vivo, Spectrum, Antimicrobial agents, Side Effect, Biological activity, Thiazoles, minimal inhibitory concentration, and Pharmacology and pharmaceutical sciences
Chagas' disease is a serious public health problem in Latin America, and no treatment is available for the prevalent chronic stage. Its causative agent, Trypanosoma cruzi , requires specific endogenous sterols for survival, and we... more
Chagas' disease is a serious public health problem in Latin America, and no treatment is available for the prevalent chronic stage. Its causative agent, Trypanosoma cruzi , requires specific endogenous sterols for survival, and we have recently demonstrated that squalene synthase (SQS) is a promising target for antiparasitic chemotherapy. E5700 and ER-119884 are quinuclidine-based inhibitors of mammalian SQS that are currently in development as cholesterol- and triglyceride-lowering agents in humans. These compounds were found to be potent noncompetitive or mixed-type inhibitors of T. cruzi SQS with K i values in the low nanomolar to subnanomolar range in the absence or presence of 20 μM inorganic pyrophosphate. The antiproliferative 50% inhibitory concentrations of the compounds against extracellular epimastigotes and intracellular amastigotes were ca. 10 nM and 0.4 to 1.6 nM, respectively, with no effects on host cells. When treated with these compounds at the MIC, all of the ...
Research Interests: Microbiology, Kinetics, Medical Microbiology, Biology, Enzyme Inhibitors, and 14 morePublic Health, Medicine, Cell Division, Mice, Female, Animals, Lipid metabolism, Software Requirement Specification, Trypanosoma Cruzi, Pyridines, Antimicrobial agents, Body Weight, Trypanocidal Agents, and Pharmacology and pharmaceutical sciences
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Research Interests: Electron Microscopy, Biology, Scanning Electron Microscopy, Transmission Electron Microscopy, Biological Chemistry, and 10 moreMagnetic Resonance Spectroscopy, Medicine, Biological Sciences, Animals, Biological, CHEMICAL SCIENCES, Trypanosoma Cruzi, Subcellular Fractions, Diphosphates, and Medical and Health Sciences
We have investigated the antiproliferative effects of SCH 56592, a new experimental triazole, against Trypanosoma(Schizotrypanum) cruzi, the etiological agent of Chagas’ disease in Latin America. SCH 56592 blocked the proliferation of the... more
We have investigated the antiproliferative effects of SCH 56592, a new experimental triazole, against Trypanosoma(Schizotrypanum) cruzi, the etiological agent of Chagas’ disease in Latin America. SCH 56592 blocked the proliferation of the epimastigote form of the parasite in vitro at 30 nM, a concentration 30- to 100-fold lower than that required with the reference compounds ketoconazole and itraconazole. At that concentration all the parasite’s endogenous sterols (ergosterol, 24-ethyl-cholesta-5,7,22-trien-3β-ol, and its 22-dihydro analogs), were replaced by methylated sterols (lanosterol and 24-methylene-dihydrolanosterol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of the drug was inhibition of the parasite’s sterol C-14α demethylase. Against the clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37°C, the MIC of SCH 56592 was 0.3 nM, again 33- to 100-fold lo...