JVG9, a benzimidazole derivative, alters the surface and cytoskeleton of Trypanosoma cruzi bloodstream trypomastigotes

Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several benzimidazole derivatives. One, named JVG9 (5-chloro-1H-benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target.

Ojo de buey en tomografía hepática / The 'bull's eye' pattern in hepatic tomography

Las infecciones micóticas invasoras se presentan con mayor frecuencia en pacientes con neutropenia posterior al uso de quimioterapia para el tratamiento del cáncer. Se presenta una paciente de 4 años con diagnóstico de leucemia linfoide aguda, quien, luego de la quimioterapia, desarrolló neutropenia febril y diarrea. Recibió tratamiento antibiótico y antimicótico de amplio espectro. Se aisló Candida albicans y se observaron trofozoítos de Entamoeba histolytica en la materia fecal . La paciente desarrolló candidiosis crónica diseminada que fue tratada con anfotericina B y, posteriormente, con fluconazol. Se ilustra la imagen tomográfica conocida como 'ojo de buey' y su correspondiente estudio histopatológico. Candida spp. es la levadura más común en pacientes inmunosuprimidos con tumores hematológicos que reciben quimioterapia. La candidiosis diseminada que se presenta en estos pacientes persiste y se hace evidente clínicamente una vez se resuelve la neutropenia; se denomina candidiosis crónica diseminada. En la paciente se presentaron varios factores de riesgo, como el tratamiento previo con antibióticos de amplio espectro, la colonización del tracto gastrointestinal por Candida y la neutropenia prolongada. El diagnóstico por imagen se hace principalmente por ecografía, tomografía axial computarizada y resonancia magnética. Se han descrito cuatro patrones tanto ecográficos como tomográficos, de los cuales se destacan el tipo 1 ('ruedas entre ruedas') y el tipo 2 ('ojo de buey'), que son característicos de la candidiosis crónica diseminada. El tercer patrón (imágenes hipoecoicas), aunque no es específico de la candidiosis crónica diseminada, es el más comúnmente hallado en ambas técnicas. En la paciente se observaron los patrones 2 y 3, y el diagnóstico se confirmó con el estudio histopatológico.

Invasive fungal infections are more commonly found in patients who develop neutropenia after chemotherapy. A 4-year-old girl with diagnosis of acute lymphoid leukemia developed febrile neutropenia after chemotherapy. Broad spectrum antibiotics and antimycotic therapy were initiated. Candida albicans was isolated and Entamoeba histolytica was observed in stool examination. Chronic disseminated candidiasis had developed and was treated with amphotericin B, initially, and fluconazol. Computed tomography images were obtained that demonstrated a classic 'bull´s eye' pattern; a concurrent histological study confirmed the diagnosis. Candida spp. is the major cause of opportunistic mycosis in immunosuppresed patients receiving chemotherapy for haematologic malignancies. An initial infection results in disseminated candidiasis, which persists and becomes chronic. In the 4-year-old patient, the identified risk factors consisted of a previous therapy with broad spectrum antibiotics, the gastrointestinal tract colonization with Candida albicans and prolonged neutropenia. Imaging diagnoses are made by ultrasonography, computed tomography and magnetic resonance. With ultrasound and tomography, 4 distinct patterns have been described. Pattern 1 ('wheels within wheels') and 2 ('bull´s eye') are important, since they are characteristic of chronic disseminated candidiasis. The third pattern (hypoechoic image) is the most common finding with both techniques. In the current patient, patterns 2 and 3 were seen and the diagnosis was confirmed by histological study.