scholarly journals Comparative Efficacies of TAK-187, a Long-Lasting Ergosterol Biosynthesis Inhibitor, and Benznidazole in Preventing Cardiac Damage in a Murine Model of Chagas' Disease

2005 ◽  
Vol 49 (4) ◽  
pp. 1556-1560 ◽  
Author(s):  
Milagros Corrales ◽  
Rubén Cardozo ◽  
María Asunción Segura ◽  
Julio A. Urbina ◽  
Miguel Angel Basombrío
Keyword(s):  
Trypanosoma Cruzi ◽  
Comparative Study ◽  
Chagas Disease ◽  
Murine Model ◽  
Ergosterol Biosynthesis ◽  
Cardiac Damage ◽  
Experimental Animals ◽  
Biosynthesis Inhibitor

ABSTRACT We carried out a comparative study of benznidazole and TAK-187, a long-lasting ergosterol biosynthesis inhibitor, with a murine model of Chagas' disease. The results indicated that TAK-187 was more effective than benznidazole in preventing Trypanosoma cruzi-induced cardiac damage in experimental animals.

scholarly journals Enantiomers of Nifurtimox Do Not Exhibit Stereoselective Anti-Trypanosoma cruzi Activity, Toxicity, or Pharmacokinetic Properties

2015 ◽  
Vol 59 (6) ◽  
pp. 3645-3647 ◽  
Author(s):  
Carolina B. Moraes ◽  
Karen L. White ◽  
Stéphanie Braillard ◽  
Catherine Perez ◽  
Junghyun Goo ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model ◽  
Therapeutic Benefit ◽  
Racemic Mixture ◽  
Content Type ◽  
Pharmacokinetic Properties

ABSTRACTWith the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in theirin vitroactivity against a panel ofTrypanosoma cruzistrains;in vivoefficacy in a murine model of Chagas disease;in vitrotoxicity and absorption, distribution, metabolism, and excretion characteristics; andin vivopharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture.

The TcTASV proteins are novel promising antigens to detect activeTrypanosoma cruziinfection in dogs

Parasitology ◽  
2016 ◽  
Vol 143 (11) ◽  
pp. 1382-1389 ◽  
Author(s):  
N. FLORIDIA-YAPUR ◽  
M. MONJE RUMI ◽  
P. RAGONE ◽  
J. J. LAUTHIER ◽  
N. TOMASINI ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Antibody Response ◽  
Chagas Disease ◽  
Murine Model ◽  
High Impact ◽  
Differentially Expressed ◽  
The Novel ◽  
Active Infection ◽  
Recombinant Antigens ◽  
Highly Correlated

SUMMARYIn regions where Chagas disease is endemic, canineTrypanosoma cruziinfection is highly correlated with the risk of transmission of the parasite to humans. Herein we evaluated the novel TcTASV protein family (subfamilies A, B, C), differentially expressed in bloodstream trypomastigotes, for the detection of naturally infected dogs. A gene of each TcTASV subfamily was cloned and expressed. Indirect enzyme-linked immunosorbent assays (ELISA) were developed using recombinant antigens individually or mixed together. Our results showed that dogs with activeT. cruziinfection differentially reacted against the TcTASV-C subfamily. The use of both TcTASV-C plus TcTASV-A proteins (Mix A+C-ELISA) enhanced the reactivity of sera from dogs with active infection, detecting 94% of the evaluated samples. These findings agree with our previous observations, where the infected animals exhibited a quick anti-TcTASV-C antibody response, coincident with the beginning of parasitaemia, in a murine model of the disease. Results obtained in the present work prove that the Mix A+C-ELISA is a specific, simple and cheap technique to be applied in endemic areas in screening studies. The Mix A+C-ELISA could help to differentially detect canine hosts with active infection and therefore with high impact in the risk of transmission to humans.

In vitro studies and preclinical evaluation of benznidazole microparticles in the acute Trypanosoma cruzi murine model

Parasitology ◽  
2020 ◽  
pp. 1-10
Author(s):  
Marcela S. Rial ◽  
Katia P. Seremeta ◽  
Mónica I. Esteva ◽  
Jacqueline Búa ◽  
Claudio J. Salomon ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model ◽  
Morphological Changes ◽  
Quantitative Polymerase Chain Reaction ◽  
Parasitic Infection ◽  
Parasite Load ◽  
Enzyme Linked Immunosorbent Assay ◽  
Significant Difference

Abstract Chagas disease is a serious parasitic infection caused by Trypanosoma cruzi. Unfortunately, the current chemotherapeutic tools are not enough to combat the infection. The aim of this study was to evaluate the trypanocidal activity of benznidazole-loaded microparticles during the acute phase of Chagas infection in an experimental murine model. Microparticles were prepared by spray-drying using copolymers derived from esters of acrylic and methacrylic acids as carriers. Dissolution efficiency of the formulations was up to 3.80-fold greater than that of raw benznidazole. Stability assay showed no significant difference (P > 0.05) in the loading capacity of microparticles for 3 years. Cell cultures showed no visible morphological changes or destabilization of the cell membrane nor haemolysis was observed in defibrinated human blood after microparticles treatment. Mice with acute lethal infection survived 100% after 30 days of treatment with benznidazole microparticles (50 mg kg−1 day−1). Furthermore, no detectable parasite load measured by quantitative polymerase chain reaction and lower levels of T. cruzi-specific antibodies by enzyme-linked immunosorbent assay were found in those mice. A significant decrease in the inflammation of heart tissue after treatment with these microparticles was observed, in comparison with the inflammatory damage observed in both infected mice treated with raw benznidazole and untreated infected mice. Therefore, these polymeric formulations are an attractive approach to treat Chagas disease.

scholarly journals A comparative study of posaconazole and benznidazole in the prevention of heart damage and promotion of trypanocidal immune response in a murine model of Chagas disease

2010 ◽  
Vol 36 (1) ◽  
pp. 79-83 ◽  
Author(s):  
Bianca P. Olivieri ◽  
Judith Tibisay Molina ◽  
Solange L. de Castro ◽  
Mirian Claudia Pereira ◽  
Claudia M. Calvet ◽  
...  
Keyword(s):  
Immune Response ◽  
Comparative Study ◽  
Chagas Disease ◽  
Murine Model ◽  
Heart Damage

scholarly journals A Cysteine Protease Inhibitor Protects Dogs from Cardiac Damage during Infection by Trypanosoma cruzi

2005 ◽  
Vol 49 (12) ◽  
pp. 5160-5161 ◽  
Author(s):  
S. C. Barr ◽  
K. L. Warner ◽  
B. G. Kornreic ◽  
J. Piscitelli ◽  
A. Wolfe ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Protease Inhibitor ◽  
Chagas Disease ◽  
Cysteine Protease ◽  
Therapeutic Target ◽  
Troponin I ◽  
Myocardial Damage ◽  
Cysteine Protease Inhibitor ◽  
Cardiac Damage ◽  
Histopathological Lesion

ABSTRACT Cruzain is an essential cysteine protease of Trypanosoma cruzi and a therapeutic target for Chagas' disease. Eight dogs were infected with T. cruzi; three were treated with an inhibitor of cruzain, K777, for 14 days. Treatment with K777 abrogated myocardial damage by T. cruzi, as documented by histopathological lesion scores and serum troponin I levels.

scholarly journals Prevention of electrocardiographic and histopathologic alterations in the murine model of Chagas' disease by preinoculation of an attenuated Trypanosoma cruzi strain

1989 ◽  
Vol 31 (4) ◽  
pp. 248-255 ◽  
Author(s):  
Carlos Alberto Cuneo ◽  
Emma Molina de Raspi ◽  
Miguel Angel Basombrio
Keyword(s):  
Trypanosoma Cruzi ◽  
Supraventricular Tachycardia ◽  
Chagas Disease ◽  
Atrioventricular Block ◽  
Murine Model ◽  
Sinus Bradycardia ◽  
Pathogenic Strain ◽  
St Elevation ◽  
Group 3 ◽  
Cruzi Infection

The effects of infection with Trypanosoma cruzi on the electrocardiographic tracings of mice were studied in 4.groups of animals: (1) normal; (2) infected with a pathogenic T. cruzi strain (TS COB); (3) immunized with 3 intraperitoneal inocula of 10(6) attenuated T. cruzi epimastigotes (TCC) and (4) immunized-infected, which sequentially received the treatments of groups 3 and 2. Infection and protection were confirmed by xenodiagnosis and histopathology. Isolated alterations such as extrasystolia, 1st degree atrioventricular block, arrhythmia and ST elevation were observed in normal as well as infected mice. However, tracings taken repeatedly on each mouse over a 293 day period revealed a set of alterations which were more frequently seen in infected (14/22) than in normal (4/27) animals (p = 0.00048). These alterations consisted of supraventricular tachycardia, sinus bradycardia and persisting, first degree AV blocks, often associated to pacemaker changes. Inoculation of attenuated T. cruzi (group 3) did not increase these alterations (2/27 mice) but significantly prevented their development after challenge with the pathogenic strain (1/19 versus 14/22 mice, p = 0.000095). Thus, preimmunization reduced not only parasitemia but also a pathogenic consequence of T. cruzi infection. This evidence is relevant for immunoprevention studies against Chagas' disease.

scholarly journals Buthionine Sulfoximine Has Anti-Trypanosoma cruzi Activity in a Murine Model of Acute Chagas' Disease and Enhances the Efficacy of Nifurtimox

2008 ◽  
Vol 52 (5) ◽  
pp. 1837-1839 ◽  
Author(s):  
Mario Faúndez ◽  
Rodrigo López-Muñoz ◽  
Gloria Torres ◽  
Antonio Morello ◽  
Jorge Ferreira ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model ◽  
Parasite Burden ◽  
Buthionine Sulfoximine ◽  
Acute Chagas Disease

ABSTRACT l-Buthionine (S,R)-sulfoximine (BSO) at a dose of 220 mg/kg of body weight/day showed an anti-Trypanosoma cruzi effect in infected mice, increasing their survival rate and decreasing the parasitemias and parasite burden in the hearts. Treatment with BSO plus nifurtimox caused an increase in the survival rate in comparison to the rates with treatment with each drug alone.

Analogues of Fenarimol Are Potent Inhibitors of Trypanosoma cruzi and Are Efficacious in a Murine Model of Chagas Disease

2012 ◽  
Vol 55 (9) ◽  
pp. 4189-4204 ◽  
Author(s):  
Martine Keenan ◽  
Michael J. Abbott ◽  
Paul W. Alexander ◽  
Tanya Armstrong ◽  
Wayne M. Best ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Murine Model
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