scholarly journals Sensibilidad in vitro a benznidazol, nifurtimox y posaconazol de cepas de Trypanosoma cruzi de Paraguay

Biomédica ◽  
2020 ◽  
Vol 40 (4) ◽  
pp. 749-763
Author(s):  
Nidia Acosta ◽  
Gloria Yaluff ◽  
Elsa López ◽  
Christopher Bobadilla ◽  
Analía Ramírez ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Liver Infusion Tryptose

Introducción. Trypanosoma cruzi, agente causal de la enfermedad de Chagas, exhibe una sustancial heterogeneidad fenotípica y genotípica que puede influir en las variaciones epidemiológicas y clínicas de la enfermedad, así como en la sensibilidad a los fármacos utilizados en el tratamiento.Objetivo. Evaluar la sensibilidad in vitro al benznidazol, el nifurtimox y el posaconazol de 40 cepas clonadas de T. cruzi de Paraguay, con distintos genotipos, huéspedes y localidades de origen.Materiales y métodos. En su estado epimastigote, los parásitos se incubaron en medio de cultivo LIT (Liver Infusion Tryptose) con diferentes concentraciones de cada fármaco en ensayos por triplicado. El grado de sensibilidad se estimó a partir de las concentraciones inhibitorias del 50 y el 90% (IC50 e IC90) y se obtuvieron los valores promedio y la desviación estándar de cada cepa y fármaco. La significación estadística entre grupos se determinó mediante análisis de varianzas con el test no paramétrico de Wilcoxon/Kruskal-Wallis y valores de p<0,05.Resultados. Se observó un amplio rango de respuesta a los fármacos. Se identificaron dos grupos de parásitos (A y B) con diferencias significativas en la sensibilidad al benznidazol (p<0,0001), y tres grupos (A, B, C) en cuanto a la sensibilidad al nifurtimox y el posaconazol (p<0,0001).Conclusiones. En general, las cepas fueron más sensibles al nifurtimox que al benznidazol y el posaconazol. Estas diferencias evidencian la heterogeneidad de las poblaciones de T. cruzi que circulan en Paraguay, lo que debe considerarse en el tratamiento y el seguimiento de las personas afectadas.

Antibody dependent cell-mediated cytotoxicity against Trypanosoma cruzi

Parasitology ◽  
1977 ◽  
Vol 75 (3) ◽  
pp. 317-323 ◽  
Author(s):  
I. A. Abrahamsohn ◽  
W. D. Da Silva
Keyword(s):  
Trypanosoma Cruzi ◽  
Normal Mouse ◽  
Defined Medium ◽  
Lag Phase ◽  
Percentage Reduction ◽  
Splenic Lymphocytes ◽  
Dependent Cell ◽  
Liver Infusion Tryptose ◽  
Per Se

SummaryThis paper describes in vitro antibody dependent cytotoxicity against Trypanosoma cruzi epimastigotes by normal mouse splenic lymphocytes. Cytotoxicity was expressed as the percentage reduction in the number of motile parasites upon incubation with lymphocytes at 37 °C in a denned medium. Failure of the non-motile parasites to regain motility and their ensuring degeneration at 28 °C in liver infusion tryptose (LIT) medium confirmed loss of motility as a criterion of cytotoxicity. Incubation of T. cruzi at 37 °C for 18 h in a defined medium per se did not interfere with motility but was followed by a lag phase of the growth curve in LIT medium at 28 °C. The lag phase was prolonged for T. cruzi which had previously been incubated at 37 °C in the absence of cells.

Unusual dimeric flavonoids from Arrabidaea brachypoda with very significant in vitro and in vivo anti-Trypanosoma cruzi activity

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
C Quitino-da-Rocha ◽  
E Ferreira-Queiroz ◽  
C Santana-Meira ◽  
DR Magalhães-Moreira ◽  
M Botelho-Pereira-Soares ◽  
...  
Keyword(s):  
Trypanosoma Cruzi

Trypanosoma cruzi calreticulin: In vitro modulation of key immunogenic markers of both canine tumors and relevant immune competent cells

Immunobiology ◽  
2020 ◽  
Vol 225 (2) ◽  
pp. 151892 ◽  
Author(s):  
P. Cruz ◽  
E. Sosoniuk-Roche ◽  
I. Maldonado ◽  
C.G. Torres ◽  
A. Ferreira
Keyword(s):  
Trypanosoma Cruzi ◽  
Competent Cells ◽  
Canine Tumors

scholarly journals Complete Inactivation of Blood Borne Pathogen Trypanosoma cruzi in Stored Human Platelet Concentrates and Plasma Treated With 405 nm Violet-Blue Light

2020 ◽  
Vol 7 ◽  
Author(s):  
Katarzyna I. Jankowska ◽  
Rana Nagarkatti ◽  
Nirmallya Acharyya ◽  
Neetu Dahiya ◽  
Caitlin F. Stewart ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Human Plasma ◽  
Blue Light ◽  
Chagas Disease ◽  
Light Treatment ◽  
Platelet Concentrates ◽  
Complete Inactivation ◽  
Pathogen Reduction ◽  
Biochemical Indices

The introduction of pathogen reduction technologies (PRTs) to inactivate bacteria, viruses and parasites in donated blood components stored for transfusion adds to the existing arsenal toward reducing the risk of transfusion-transmitted infectious diseases (TTIDs). We have previously demonstrated that 405 nm violet-blue light effectively reduces blood-borne bacteria in stored human plasma and platelet concentrates. In this report, we investigated the microbicidal effect of 405 nm light on one important bloodborne parasite Trypanosoma cruzi that causes Chagas disease in humans. Our results demonstrated that a light irradiance at 15 mWcm−2 for 5 h, equivalent to 270 Jcm−2, effectively inactivated T. cruzi by over 9.0 Log10, in plasma and platelets that were evaluated by a MK2 cell infectivity assay. Giemsa stained T. cruzi infected MK2 cells showed that the light-treated parasites in plasma and platelets were deficient in infecting MK2 cells and did not differentiate further into intracellular amastigotes unlike the untreated parasites. The light-treated and untreated parasite samples were then evaluated for any residual infectivity by injecting the treated parasites into Swiss Webster mice, which did not develop infection even after the animals were immunosuppressed, further demonstrating that the light treatment was completely effective for inactivation of the parasite; the light-treated platelets had similar in vitro metabolic and biochemical indices to that of untreated platelets. Overall, these results provide a proof of concept toward developing 405 nm light treatment as a pathogen reduction technology (PRT) to enhance the safety of stored human plasma and platelet concentrates from bloodborne T. cruzi, which causes Chagas disease.

scholarly journals Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

1995 ◽  
Vol 182 (1) ◽  
pp. 59-65 ◽  
Author(s):  
I Ferrari ◽  
M J Levin ◽  
G Wallukat ◽  
R Elies ◽  
D Lebesgue ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Adrenergic Receptor ◽  
Molecular Mimicry ◽  
Autoimmune Response ◽  
Extracellular Loop ◽  
Western Blots ◽  
Carboxy Terminal ◽  
Ribosomal Protein P0 ◽  
Positive Chronotropic Effect

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

scholarly journals Chemical Validation of Phosphodiesterase C as a Chemotherapeutic Target in Trypanosoma cruzi, the Etiological Agent of Chagas' Disease

2010 ◽  
Vol 54 (9) ◽  
pp. 3738-3745 ◽  
Author(s):  
Sharon King-Keller ◽  
Minyong Li ◽  
Alyssa Smith ◽  
Shilong Zheng ◽  
Gurpreet Kaur ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Catalytic Domain ◽  
Polypeptide Chain ◽  
Inflammatory Diseases ◽  
New Drugs ◽  
Volume Recovery ◽  
Chronic Pulmonary Diseases ◽  
Potential Inhibitors

ABSTRACT Trypanosoma cruzi phosphodiesterase (PDE) C (TcrPDEC), a novel and rather unusual PDE in which, unlike all other class I PDEs, the catalytic domain is localized in the middle of the polypeptide chain, is able to hydrolyze cyclic GMP (cGMP), although it prefers cyclic AMP (cAMP), and has a FYVE-type domain in its N-terminal region (S. Kunz et al., FEBS J. 272:6412-6422, 2005). TcrPDEC shows homology to the mammalian PDE4 family members. PDE4 inhibitors are currently under development for the treatment of inflammatory diseases, such as asthma, chronic pulmonary diseases, and psoriasis, and for treating depression and serving as cognitive enhancers. We therefore tested a number of compounds originally synthesized as potential PDE4 inhibitors on T. cruzi amastigote growth, and we obtained several useful hits. We then conducted homology modeling of T. cruzi PDEC and identified other compounds as potential inhibitors through virtual screening. Testing of these compounds against amastigote growth and recombinant TcrPDEC activity resulted in several potent inhibitors. The most-potent inhibitors were found to increase the cellular concentration of cAMP. Preincubation of cells in the presence of one of these compounds stimulated volume recovery after hyposmotic stress, in agreement with their TcrPDEC inhibitory activity in vitro, providing chemical validation of this target. The compounds found could be useful tools in the study of osmoregulation in T. cruzi. In addition, their further optimization could result in the development of new drugs against Chagas' disease and other trypanosomiases.

Isolation of blood and intracellular forms of Trypanosoma cruzi from rats and other rodents and preliminary studies of their metabolism

Parasitology ◽  
1978 ◽  
Vol 76 (2) ◽  
pp. 159-176 ◽  
Author(s):  
W. E. Gutteridge ◽  
B. Cover ◽  
Maria Gaborak
Keyword(s):  
Trypanosoma Cruzi ◽  
Blood Cells ◽  
Light And Electron Microscopy ◽  
Deae Cellulose ◽  
Whole Body ◽  
Differential Centrifugation ◽  
Γ Irradiation ◽  
Hind Limb Muscle ◽  
Radio Tracer

SummaryIsolation of blood and intracellular forms of Trypanosoma cruzi was made mainly from rats (90–110 g) which had received 580 rad of whole-body γ-irradiation not more than 24 h before subcutaneous inoculation with 107 trypomastigotes of the Sonya strain of T. cruzi. Unirradiated chinchillas (250–350 g) were, however, used for some experiments. Blood forms were isolated using a technique involving differential centrifugation to remove most of the erythrocytes and DEAE–cellulose chromatography to remove the remaining blood cells. Overall recoveries were usually in the range 30–70%. Parasites were mainly (approximately 98%) broad forms and were motile, metabolically active (as judged by respiratory and radio-tracer incorporation studies) and had lost none of their infectivity for mice. Intracellular forms were isolated from hind-limb muscle tissue. This was disrupted in an MSE tissue homogenizer and the homogenate incubated with DNase, collagenase and trypsin. Parasites, contaminated only by a few blood cells, were then obtained by differential centrifugation. For purer preparations, a terminal sucrose gradient step was used. Recoveries ranged between 40 and 70%. About 1–3% of the parasites isolated were epimastigotes and trypomastigotes; the remainder are probably best collectively termed ‘amastigotes’, though they were pointed and most had a short, free flagellum. They were undamaged as judged by light and electron microscopy and metabolically active as judged by respiratory and radio-tracer incorporation studies. However, the infectivity for mice of both these purified preparations and the initial cell homogenates could be accounted for by the epimastigotes and trypomastigotes present in them. Preliminary biochemical studies with isolated parasites have shown that blood, intracellular and culture forms of T. cruzi have a respiratory system which is in part sensitive to CN- and that all forms synthesize nucleic acids and proteins when incubated in vitro. There appears, however, to be a lack of DNA synthesis in blood stages, and thus it is not surprising that these forms do not divide.

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