Segmentation of Echocardiographic Images in Murine Model of Chagas Disease

2020 ◽  
pp. 132-142
Author(s):  
Rafael Viana-Camara ◽  
Carlos Brito-Loeza ◽  
Anabel Martin-Gonzalez ◽  
Nidiyare Hevia-Montiel
Keyword(s):  
Chagas Disease ◽  
Murine Model ◽  
Echocardiographic Images

scholarly journals Preclinical Studies in Anti-Trypanosomatidae Drug Development

2021 ◽  
Vol 14 (7) ◽  
pp. 644
Author(s):  
Cintya Perdomo ◽  
Elena Aguilera ◽  
Ileana Corvo ◽  
Paula Faral-Tello ◽  
Elva Serna ◽  
...  
Keyword(s):  
Rural Communities ◽  
Chagas Disease ◽  
Murine Model ◽  
Mammalian Cells ◽  
Drug Candidate ◽  
Murine Macrophages ◽  
Causative Agents ◽  
Trypanosomatid Parasites

The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania are the causative agents of human African trypanosomiasis, Chagas Disease and Leishmaniasis, respectively. These infections primarily affect poor, rural communities in the developing world, and are responsible for trapping sufferers and their families in a disease/poverty cycle. The development of new chemotherapies is a priority given that existing drug treatments are problematic. In our search for novel anti-trypanosomatid agents, we assess the growth-inhibitory properties of >450 compounds from in-house and/or “Pathogen Box” (PBox) libraries against L. infantum, L. amazonensis, L.braziliensis, T. cruzi and T. brucei and evaluate the toxicities of the most promising agents towards murine macrophages. Screens using the in-house series identified 17 structures with activity against and selective toward Leishmania: Compounds displayed 50% inhibitory concentrations between 0.09 and 25 μM and had selectivity index values >10. For the PBox library, ~20% of chemicals exhibited anti-parasitic properties including five structures whose activity against L. infantum had not been reported before. These five compounds displayed no toxicity towards murine macrophages over the range tested with three being active in an in vivo murine model of the cutaneous disease, with 100% survival of infected animals. Additionally, the oral combination of three of them in the in vivo Chagas disease murine model demonstrated full control of the parasitemia. Interestingly, phenotyping revealed that the reference strain responds differently to the five PBox-derived chemicals relative to parasites isolated from a dog. Together, our data identified one drug candidate that displays activity against Leishmania and other Trypanosomatidae in vitro and in vivo, while exhibiting low toxicity to cultured mammalian cells and low in vivo acute toxicity.

scholarly journals Tetradentate polyamines as efficient metallodrugs for Chagas disease treatment in murine model

2016 ◽  
Vol 29 (2) ◽  
pp. 83-93 ◽  
Author(s):  
Francisco Olmo ◽  
Miquel Costas ◽  
Clotilde Marín ◽  
Maria José Rosales ◽  
Rubén Martín-Escolano ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Murine Model ◽  
Disease Treatment

scholarly journals Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

2014 ◽  
Vol 109 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Martha Elba Gonzalez-Mejia ◽  
Enrique Torres-Rasgado ◽  
Leonardo M Porchia ◽  
Hilda Rosas Salgado ◽  
José-Luis Totolhua ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chagas Disease ◽  
Murine Model

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.

Antiparasitic activity of risedronate in a murine model of acute Chagas’ disease

2004 ◽  
Vol 23 (3) ◽  
pp. 286-290 ◽  
Author(s):  
Luciana R Garzoni ◽  
Mariana C Waghabi ◽  
Marcos M Baptista ◽  
Solange L de Castro ◽  
Maria de Nazareth L Meirelles ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Murine Model ◽  
Antiparasitic Activity ◽  
Acute Chagas Disease

scholarly journals Antiproliferative Effects and Mechanism of Action of SCH 56592 against Trypanosoma (Schizotrypanum)cruzi: In Vitro and In Vivo Studies

1998 ◽  
Vol 42 (7) ◽  
pp. 1771-1777 ◽  
Author(s):  
Julio A. Urbina ◽  
Gilberto Payares ◽  
Lellys M. Contreras ◽  
Andreína Liendo ◽  
Cristina Sanoja ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Mechanism Of Action ◽  
Murine Model ◽  
Vero Cells ◽  
In Vivo Studies ◽  
Antiproliferative Effects ◽  
Sterol Biosynthesis Inhibitor ◽  
High Resolution Gas Chromatography

ABSTRACT 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 lower than that of ketoconazole or itraconazole. In a murine model of acute Chagas’ disease, SCH 56592 given at ≥ 10 mg/kg of body weight/day for a total of 43 doses allowed 85 to 100% survival and 90 to 100% cure of the surviving animals, as verified by parasitological, serological, and PCR-based tests, while ketoconazole given at 30 mg/kg day allowed 60% survival but only 20% cure. In a murine model of chronic Chagas’ disease, SCH 56592 was again more effective than ketoconazole, providing 75 to 85% protection from death, with 60 to 75% parasitological cures of the surviving animals, while no parasitological cures were observed with ketoconazole. The results indicate that SCH 56592 is the most powerful sterol biosynthesis inhibitor ever tested against T. cruzi and may be useful in the treatment of human Chagas’ disease.

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

2017 ◽  
Vol 315 ◽  
pp. 12-22 ◽  
Author(s):  
Flavia Lambertucci ◽  
Omar Motiño ◽  
Silvina Villar ◽  
Juan Pablo Rigalli ◽  
María de Luján Alvarez ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Chagas Disease ◽  
Murine Model ◽  
Nrf2 Activation

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.

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.

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