Chagas disease
Clinical TherapeuticsDrug-Drug Interaction Study of Benznidazole and E1224 in Healthy Male VolunteersE1224 is a prodrug of ravuconazole (RVZ), an antifungal drug with promising anti-Trypanosoma cruzi activity, the causative organism of Chagas disease (CD). This study was designed to assess the pharmacokinetics (PK) and safety interactions of benznidazole (BNZ), the drug of choice for treatment of CD, and E1224 in healthy volunteers.
Clinical TherapeuticsBenznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive PatientsChagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS).
Mechanisms of Action: Physiological EffectsScreening and Identification of Metacaspase Inhibitors: Evaluation of Inhibition Mechanism and Trypanocidal ActivityA common strategy to identify new antiparasitic agents is the targeting of proteases, due to their essential contributions to parasite growth and development. Metacaspases (MCAs) are cysteine proteases present in fungi, protozoa, and plants.
Experimental TherapeuticsPharmacokinetics of Benznidazole in Experimental Chronic Chagas Disease Using the Swiss Mouse–Berenice-78 Trypanosoma cruzi Strain ModelChronic Chagas disease might have an impact on benznidazole pharmacokinetics with potential alterations in the therapeutic dosing regimen. This study aims to investigate the influence of chronic Trypanosoma cruzi infection on the pharmacokinetics and biodistribution of benznidazole in mice.
Clinical TherapeuticsNew Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-UpIn a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two...
Experimental TherapeuticsEfficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of Trypanosoma cruziPyrazolones are heterocyclic compounds with interesting biological properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cyclic AMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease (CD), a...
Experimental TherapeuticsAmlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi InfectionMining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon Trypanosoma cruzi experimental infection. In vitro assays confirmed...
Clinical TherapeuticsCombination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic PhaseChagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are...
Clinical TherapeuticsA Parasite Biomarker Set for Evaluating Benznidazole Treatment Efficacy in Patients with Chronic Asymptomatic Trypanosoma cruzi InfectionOne of the current greatest challenges of Chagas disease is the establishment of biomarkers to assess the efficacy of drugs in a short period of time. In this context, the reactivity of sera from 66 adults with chronic indeterminate Chagas disease (IND) for a set of four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before and...
Experimental TherapeuticsSynergic Effect of Allopurinol in Combination with Nitroheterocyclic Compounds against Trypanosoma cruziCombination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi.