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We report the results of a comparative study of the molecular order and dynamics of phosphatidylcholine (PC) bilayer membranes in the absence and presence of cholesterol, ergosterol and lanosterol, using deuterium (2H) nuclear magnetic resonance (NMR) of deuterated phospholipid molecules, in addition to solid state 13C and 31P-NMR. Using(More)
Neglected Diseases T hrough its impact on worker productivity, premature disability, and death, Chagas disease accounts for 670,000 disability-adjusted life years per annum [1]. This makes it the most important parasitic disease of the Americas. It is both a disease of poverty (Figures 1 and 2) and, like other neglected tropical diseases, also " poverty(More)
A critical review of the development of specific chemotherapeutic approaches for the management of American Trypanosomiasis or Chagas disease is presented, including controversies on the pathogenesis of the disease, the initial efforts that led to the development of currently available drugs (nifurtimox and benznidazole), limitations of these therapies and(More)
New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. Apart from the introduction of eflornithine for the treatment of(More)
Trypanosoma cruzi and Leishmania parasites have a strict requirement for specific endogenous sterols (ergosterol and analogs) for survival and growth and cannot use the abundant supply of cholesterol present in their mammalian hosts. Squalene synthase (SQS, E.C. 2.5.1.21) catalyzes the first committed step in sterol biosynthesis and is currently under(More)
In this article we review the current status of chemotherapeutic approaches for the specific treatment of Chagas disease or American Trypanosomiasis, as well as new rational approaches being developed as a consequence on the increased understanding of the biochemistry and physiology of its causative agent, the protozoan parasite Trypanosoma cruzi. Currently(More)
We investigated the mechanism of action of metabolically stable lysophospholipid analogues (LPAs), with potent anti-tumour and anti-protozoal activity against Trypanosoma cruzi, the causative agent of Chagas' disease. Against the axenically grown epimastigote form of the parasite, the IC(50)s after 120 h for ET-18-OCH(3), miltefosine and ilmofosine were 3,(More)
We describe the in vitro antiproliferative effects of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease in Latin America. The compound was found to be extremely active against the cultured (epimastigote) form of the parasite, equivalent to that present in the(More)
The protozoan parasite, Trypanosoma cruzi, causes the most prevalent parasitic infection in the American continent. It gives rise to life-long infection in humans and results in severe cardiomyopathy or other life-threatening manifestations (Chagas disease) in ~30% of those infected. Animal models and clinical studies indicate that etiological treatment of(More)
The aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea(More)