RESUMO
Chagas' disease, caused by Trypanosoma cruzi, is an urgent and highly prevalent danger that is endemic to Latin America, and which the research community continues to ignore. Each year, Chagas' disease kills more people in Latin America compared to any other parasite-borne disease, including malaria. In addition, between 15 and 18 million people worldwide are afflicted with this potentially lethal disease. Despite these devastating numbers, less than 0.5% of worldwide research and development for neglected diseases was aimed at Chagas' disease. The aim of this review is to draw the attention of biotechnologists to the intriguing parasite that causes Chagas' disease, which is T. cruzi. Additionally, we would also like to convince the community that basic science research can have a profound impact on the diagnosis and treatment of Chagas' disease. In this review, we introduce distinct features of T. cruzi such as its complex life cycle (e.g. the potentially infective extracellular amastigote form), its genome and genomics, as well as proteomic analysis of this parasite. Notably, the PIK pathway has been widely acknowledged as an excellent target for drug discovery to combat this pathogen. Furthermore we also describe how the identification and characterization of PIK genes can aid in neutralizing Trypanosoma infections.
Assuntos
Doença de Chagas/parasitologia , Transdução de Sinais/fisiologia , Trypanosoma cruzi/fisiologia , Trypanosoma cruzi/patogenicidade , Animais , Doença de Chagas/tratamento farmacológico , Descoberta de Drogas , Humanos , Insetos Vetores/parasitologia , Insetos Vetores/fisiologia , Estágios do Ciclo de Vida/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/genéticaRESUMO
Schistosoma mansoni eggs, miracidia and primary sporocysts were labelled with phalloidin-rhodamine to visualize filamentous actin structures. Analysis of these forms by confocal fluorescence microscopy revealed the presence of previously well-defined circular and longitudinal muscle layers. Besides these muscular layers that sustain and provide motility to these parasite forms, we found in these 3 consecutive developmental stages of the parasite previously unidentified actin-rich tubular structures. In the 3 forms, 4 actin-rich tubules could be observed by optical sectioning underneath the well-developed muscle layers. The tubules appear in pairs, transversal to the length of the parasite, and located towards the extremities. By using an anti-flame cell specific antibody we confirmed that the tubules co-localize with flame cells and also determined that the tubule core is filled with microtubules. The additional presence of myosin in these tubules strongly suggests that they are contractile structures.
Assuntos
Estágios do Ciclo de Vida/fisiologia , Proteínas Motores Moleculares/análise , Schistosoma mansoni/química , Schistosoma mansoni/ultraestrutura , Citoesqueleto de Actina/imunologia , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Actinas/análise , Actinas/imunologia , Animais , Anticorpos Anti-Helmínticos/metabolismo , Microscopia Confocal/métodos , Proteínas Motores Moleculares/imunologia , Músculos/química , Músculos/ultraestrutura , Miosinas/imunologia , Miosinas/metabolismo , Oocistos/ultraestrutura , Schistosoma mansoni/crescimento & desenvolvimentoRESUMO
Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/etiologia , Transplante de Medula Óssea/efeitos adversos , Candidíase/prevenção & controle , Fluconazol/uso terapêutico , Infecções Oportunistas/etiologia , Adolescente , Adulto , Transplante de Medula Óssea/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , MasculinoRESUMO
Fungal infection is one of the most important causes of morbidity and mortality in bone marrow transplant (BMT) recipients. The growing incidence of these infections is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease (GvHD). In the present series, we report five cases of invasive mold infections documented among 64 BMT recipients undergoing fluconazole antifungal prophylaxis: 1) A strain of Scedosporium prolificans was isolated from a skin lesion that developed on day +72 after BMT in a chronic myeloid leukemic patient. 2) Invasive pulmonary aspergillosis (Aspergillus fumigatus) was diagnosed on day +29 in a patient with a long period of hospitalization before being transplanted for severe aplastic anemia. 3) A tumoral lung lesion due to Rhizopus arrhizus (zygomycosis) was observed in a transplanted patient who presented severe chronic GvHD. 4) A tumoral lesion due to Aspergillus spp involving the 7th, 8th and 9th right ribs and local soft tissue was diagnosed in a BMT patient on day +110. 5) A patient with a history of Ph1-positive acute lymphocytic leukemia exhibited a cerebral lesion on day +477 after receiving a BMT during an episode of severe chronic GvHD. At that time, blood and spinal fluid cultures yielded Fusarium sp. Opportunistic infections due to fungi other than Candida spp are becoming a major problem among BMT patients receiving systemic antifungal prophylaxis with fluconazole
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Antifúngicos , Aspergilose , Transplante de Medula Óssea , Candidíase , Fluconazol , Infecções Oportunistas , Hospedeiro ImunocomprometidoRESUMO
BACKGROUND AND OBJECTIVES: Immunophenotyping is an essential method for diagnosis and classification of acute myeloid leukemias (AML), and its extensive use could identify blast cell subpopulations with aberrant phenotypes rarely seen in normal myelopoiesis. The aberrant phenotypes have been correlated with clinical, morphological and prognostic features but their occurrence in AML differs in the various studies. DESIGN AND METHODS: In this study, we analyzed 35 cases of AML, examining them for aberrant phenotypes by multiparametric flow cytometry. Co-expression of lymphoid-associated markers in myeloblasts and asynchronous antigen expression were correlated with clinical features. RESULTS: Aberrant phenotypes were found in 88.6% of the cases studied. In this group, cross-lineage antigen expression was present in 34.3% and asynchronous expression in 82.4% of the cases. CD7 was the most frequent lymphoid-associated antigen. Among the cases of asynchronous antigen expression, the most frequent phenotype was CD117(+) and/or CD34(+) in association with CD11c(+), followed by CD15(+) and CD65(+), corresponding to 67.6%, 61.7 and 50.0% of the cases, respectively. Twenty out of 33 patients were available for complete remission assessment. The CD117(+) CD15(+) phenotype correlated significantly with complete remission achievement and with the lack of unfavorable chromosome associations. INTERPRETATION AND CONCLUSIONS: We conclude that aberrant phenotypes, as they are described here, are present in the great majority of cases of AML, asynchronous antigen expression being the most frequent example; and that CD117(+) CD15(+) phenotype shows a relevant association with clinical prognosis.
Assuntos
Imunofenotipagem , Leucemia Mieloide/diagnóstico , Doença Aguda , Adulto , Idoso , Antígenos CD/análise , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Estudos de Coortes , Análise Citogenética , Citometria de Fluxo , Humanos , Leucemia Mieloide/classificação , Leucemia Mieloide/patologia , Pessoa de Meia-Idade , PrognósticoRESUMO
GVHD is one of the most frequent complications of BMT and recently nephrotic syndrome (NS) has been described as a manifestation of chronic GVHD. Here, we present an AA patient who developed NS 1 year after BMT when cyclosporine was stopped. Renal biopsy showed focal sclerosis associated with membranous deposits. He also had other clinical manifestations of chronic GVHD: sicca-like syndrome and colestasis. After 15 days of CsA therapy, he experienced a remarkable improvement in the NS and GVHD as a whole. We comment on immunological mechanisms that could be involved in the pathogenesis of this manifestation.