Hallazgos ultraestructurales renales de pacientes con nefritis intersticial crónica de las comunidades agrícolas en El Salvador / Renal ultrastructural findings of patients with chronic interstitial nephritis from farming communities in El Salvador

Introducción: Desde hace 20 años se presenta en Centroamérica una enfermedad renal crónica que fundamentalmente afecta a hombres agricultores y no asociada a las causas tradicionales. Se caracteriza por presentar una nefritis intersticial crónica, en tanto las características ultraestructurales no se conocen con exactitud. En su origen se invoca el uso de agroquímicos y otros agentes nefrotóxicos, la deshidratación crónica, el consumo de medicamentos, entre otros factores. Objetivo: Describir las características ultraestructurales de la nefritis intersticial crónica en comunidades agrícolas. Método: Se realizó un estudio descriptivo de corte transversal. Se estudiaron muestras de biopsias renales de ocho pacientes con diagnóstico de nefritis intersticial crónica de las comunidades agrícolas. Resultados: De los ocho pacientes estudiados, dos (25 por ciento) trabajaban en labores agrícolas y cinco eran del sexo femenino (62,5 por ciento). Dos de los pacientes (25 por ciento) presentaban una enfermedad renal crónica estadio 2, y seis (75 por ciento) estadio 3. En cinco pacientes se hallaron fagolisosomas con presencia de componente lipídico entremezclado con material electrodenso en células del túbulo distal. En igual cantidad de pacientes se observaron cuerpos mieloides con zonas laminadas y núcleo central en células de túbulo proximal y de los vasos sanguíneos. Conclusiones: En pacientes de comunidades agrícolas que padecen nefritis intersticial crónica se evidencian fagolisosomas y estructuras mieloides en túbulos y vasos renales, cuyo contenido y origen se desconocen(AU)

Introduction: Chronic kidney disease mainly affecting male farmers and not associated to traditional causes has been present in Central America for twenty years. The condition is characterized by the presence of chronic interstitial nephritis, but its ultrastructural features are not fully known. Factors suggested as responsible for its occurrence include the use of agrochemicals and other nephrotoxic agents, chronic dehydration and medicine consumption. Objective: Describe the ultrastructural characteristics of chronic interstitial nephritis in farming communities. Method: A cross-sectional descriptive study was conducted of renal biopsy samples from eight patients diagnosed with chronic interstitial nephritis in farming communities. Results: Of the eight patients studied, two (25 percent) were farm workers and five (62.5percent) were female. Two of the patients (25 percent) had stage 2 and six (75 percent) stage 3 chronic kidney disease. In five patients evidence was found of phagolysosomes with lipid component mixed with electrodense material in distal tubule cells. An equal number of patients had myeloid bodies with laminated areas and central nucleus in proximal tubule and blood vessel cells. Conclusions: Evidence of phagolysosomes and myeloid structures of unknown content and origin was found in renal tubules and vessels of patients from farming communities diagnosed with chronic interstitial nephritis(AU)

Hepatitis B vaccination in adolescents living in Campinas, São Paulo, Brazil / Vacinação contra hepatite B em adolescentes residentes em Campinas, São Paulo, Brasil

Viral hepatitis is an important public health problem in Brazil and around the world.

As hepatites virais constituem importante problema de saúde pública no Brasil e em todo o mundo.

Genetic characterization of Toxoplasma gondii isolates from eared doves (Zenaida auriculata) in Brazil / Caracterização genética de isolados de Toxoplasma gondii de pombos (Zenaida auriculata) no Brasil

Eared doves (Zenaida auriculata), which are common in urban, rural and wild areas in many regions of Brazil, are frequently prey for domestic cats. Therefore Toxoplasma gondii isolates obtained from doves may reflect greater environmental diversity than those from other hosts. The aim of the present study was to evaluate T. gondii seroprevalence, isolate and genotype strains from Z. auriculata. Serum and tissue samples were collected from 206 doves for use in the modified agglutination test (MAT) and mouse bioassay. The prevalence of T. gondii antibodies in the doves was 22.3% (46/206), with titers ranging from 16 to 4096, and T. gondii strains were isolated from 12 of these doves. Five genotypes were detected by means of PCR-RFLP, including ToxoDB genotypes #1, #6, #17 and #65, and one genotype that had not previously been described (ToxoDB#182). This was the first report on isolation of T. gondii from Z. auriculata. This study confirmed the genetic diversity of T. gondii isolates and the existence of clonal type II (ToxoDB genotype #1) in Brazil.

Pombos silvestres (Zenaida auriculata), comuns em áreas urbanas, rurais e selvagens em muitas regiões do Brasil, são frequentemente predados por gatos domésticos. Sendo assim, os isolados de T. gondii obtidos de pombos podem refletir uma maior diversidade ambiental do que os outros hospedeiros. O objetivo do presente estudo foi avaliar a soroprevalência, isolar e genotipar T. gondii de Z. auriculata. Amostras de soro e tecido foram coletadas de 206 pombos para o teste de aglutinação modificado (MAT) e o bioensaio em camundongos. A prevalência de anticorpos contra T. gondii em pombos foi 22,3% (46/206), com títulos variando de 16 a 4096, e T. gondii foi isolado de 12 pombos. Cinco genótipos foram detectados por PCR-RFLP, incluindo os genótipos ToxoDB #1, #6, #17, #65 e um genótipo não descrito anteriormente (ToxoDB#182). Esse é o primeiro relato de isolamento de T. gondii de Z. auriculata. Este estudo também confirmou a diversidade dos isolados de T. gondii e a presença de tipo clonal II (ToxoDB #1) no Brasil.

Interferon-γ inhibits group B Streptococcus survival within human endothelial cells

Endothelial dysfunction is a major component of the pathophysiology of septicaemic group B Streptococcus (GBS) infections. Although cytokines have been shown to activate human umbilical vein endothelial cells (HUVECs), the capacity of interferon (IFN)-γ to enhance the microbicidal activity of HUVECs against GBS has not been studied. We report that the viability of intracellular bacteria was reduced in HUVECs activated by IFN-γ. Enhanced fusion of lysosomes with bacteria-containing vacuoles was observed by acid phosphatase and the colocalisation of Rab-5, Rab-7 and lysosomal-associated membrane protein-1 with GBS in IFN-γ-activated HUVECs. IFN-γ resulted in an enhancement of the phagosome maturation process in HUVECs, improving the capacity to control the intracellular survival of GBS.

Atividade antimicrobiana de diferentes fármacos contra Mycobacterium abscessus organizada em biofilmes ou localizada em fagossomos / Antimicrobial activity of different drugs against Mycobacterium abscessus in biofilms organized or located in phagosomes

A Mycobacterium abscessus subspécie abscessus é um pesadelo quando envolvida em infecção pulmonar que são incuráveis, a despeito do uso de antimicrobianos com atividade in vitro, caso o tratamento não inclua a ressecção cirúrgica da área afetada. É a micobactéria patogência de crescimento rápido mais frequentemente isolada de culturas de sítios pulmonares. Há um número reduzido de opções terapêuticas para o tratamento dessas infecções, e é ainda mais reduzido o número de antimicrobianos que atingem concentrações terapêuticas no compartimento intracelular, em particular no fagossomo. O número limitado de antimicrobianos disponíveis para tratamento apontam a necessidade de determinação do perfil de susceptibilidade frente a antimicrobianos isolados e em combinação, nos compartimentos intra e extracelular. Os objetivos deste estudo foram avaliar: a sensibilidade de M. abscessus estruturadas em biofilmes e presentes no interior dos macrófagos; a ocorrência de sinergismo quando da associação entre fármacos, inibidores de betalactamase e o anti-inflamatório. As combinações entre os antimicrobianos foram apenas indiferente quanto ao FIC e a atividade dos fármacos em biofilme e em macrófagos é bacteriostático

Mycobacterium abscessus subspecies abscessus is a nightmare when involved in lung infection that is incurable, despite the use of antibiotics with in vitro activity, if the treatment does not include surgical resection of the affected area. It is a MCR - rapidly growing mycobacteria pathogenic most frequently isolated from cultures of lung sites. There are a small number of therapeutic options for the treatment of such infections is further reduced and the number of drugs that reach therapeutic concentrations in the intracellular compartment, particularly in the phagosome. The limited number of antimicrobials available for treatment indicate the need for determining the susceptibility profile against antimicrobials alone and in combination, in the intra and extracellular compartments. The objectives of this study were sensitivity of MCR structured biofilms and present in macrophages, the occurrence of synergism when the association between drugs, beta-lactamase inhibitors and anti-inflammatory. Combinations of antimicrobials were just indifferent and the activity of drugs on biofilms and macrophages was bacteriostatic

Alteraciones en el reclutamiento y activación de proteínas Rab durante la infección micobacteriana: [revisão] / Alterations in recruitment and activation of Rab proteins during mycobacterial infection: [review]

En el fagosoma, Mycobacterium spp. altera la activación y reclutamiento de diferentes proteínas “del gen Ras de cerebro de rata”, comúnmente conocidas como Rab. En este manuscrito se revisa una serie de reportes que han demostrado que los fagosomas que contienen micobacterias tienen una expresión mayor y sostenida de Rab5, Rab11, Rab14 y Rab22a, y menor o ninguna expresión de Rab7, Rab9 y Rab6. Esto se correlaciona con aumento de la fusión de estos fagosomas con endosomas tempranos y de reciclaje, lo que les permite mantener ciertas características de compartimentos tempranos, permite que las bacterias obtengan acceso a nutrientes y previene la activación de mecanismos contra la micobacteria. La expresión de mutantes constitutivamente activos de las Rab de endosomas tempranos impide la maduración de fagosomas que contienen esferas de látex o micobacterias inactivadas por calor. Mientras que su silenciamiento, mediante ARN de interferencia o mediante dominantes negativos, induce la maduración de fagosomas micobacterianos. Los mecanismos exactos por los que las micobacterias alteran la dinámica de expresión de estas GTPasas, afectando la maduración fagolisosómica, no se han establecido. El problema podría explicarse por defectos en el reclutamiento de las proteínas que interactúan con Rab, como la cinasa-3 del fosfatidilinositol y el antígeno endosómico temprano 1. La identificación de los mecanismos empleados por Mycobacterium spp. para interrumpir el ciclo de activación de las Rab, será esencial para comprender la fisiopatología de la infección micobacteriana y útil como posibles blancos farmacológicos.

At the phagosome level, Mycobacterium spp. alters activation and recruitment of several “Ras gene from rat brain” proteins, commonly known as Rab. Mycobacterial phagosomes have a greater and sustained expression of Rab5, Rab11, Rab14 and Rab22a, and lowered or no expression of Rab7, Rab9 and Rab6. This correlates with increased fusion of the phagosomes with early and recycling endosomes acquiring some features of early phogosomes, allowing the bacteria to gain access to nutrients and preventing the activation of anti-mycobacterial mechanisms. The expression of constitutively active mutants of Rab from the early stage endosomes prevents the maturation of phagosomes containing latex beads or heat-inactivated mycobacteria. Silencing of these mutants by interference RNA or dominant negative forms induces the maturation of mycobacterial phagosomes. The mechanisms have not been established by which mycobacteria alter the expression of these GTPases and thereby shift the phagolysosomal maturation. The problem can be explained by alterations in the recruitment of proteins that interact with Rab, such as phosphoinositide 3-kinases and early endosomal antigen 1. Identifying the mechanisms used by Mycobacterium spp. to disrupt the cycle of Rab activation will be essential to understand the pathophysiology of mycobacterial infections and usefully to potential drug targets.

CD40, autophagy and Toxoplasma gondii

Toxoplasmagondii represents a pathogen that survives within host cells by preventing the endosomal-lysosomal compartments from fusing with the parasitophorous vacuoles. The dogma had been that the non-fusogenic nature of these vacuoles is irreversible. Recent studies revealed that this dogma is not correct. Cell-mediated immunity through CD40 re-routes the parasitophorous vacuoles to the lysosomal compartment by a process called autophagy. Autophagosome formation around the parasitophorous vacuole results in killing of the T. gondii. CD40-induced autophagy likely contributes to resistance against T. gondii particularly in neural tissue.

Actin-interacting and flagellar proteins in Leishmania spp: bioinformatics predictions to functional assignments in phagosome formation

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented.