ABSTRACT
BACKGROUND: Hepatic iron overload is common in patients with myelodysplastic syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better understand the mechanisms of iron overload-induced liver injury, we examined the effects of iron overload induced by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling pathway in human hepatic cell line HH4. METHODS AND RESULTS: Hepatic HH4 cells were exposed to FAC to force iron uptake, and cellular responses were determined. Incubation with 5 mM FAC resulted in increased intracellular iron content in a time-dependent manner. High concentration of FAC impaired cell viability and increased level of reactive oxygen species (ROS), and addition of antioxidant reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced intracellular ROS generation. FAC overload significantly increased the phosphorylation of inhibitor of κB-α, p38 mitogen-activated protein kinase (MAPK), and nuclear factor κ light chain enhancer of activated B cells (NF-κB) p65 and promoted the nuclear translocation of NF-κB p65. Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4 cells resulted in restoration of cell viability. CONCLUSIONS: We reported that FAC treatment is capable of inducing both extrinsic death receptor and intrinsic mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS-activated p38 MAPK and NF-κB pathways.
Subject(s)
Apoptosis/drug effects , Ferric Compounds/toxicity , Hepatocytes/drug effects , Iron/metabolism , NF-kappa B/metabolism , Quaternary Ammonium Compounds/toxicity , Reactive Oxygen Species/metabolism , Apoptosis/immunology , Blotting, Western , Cell Line , Cell Survival/drug effects , Hepatocytes/immunology , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Oxidative Stress/drug effects , Real-Time Polymerase Chain Reaction , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Engraftment of clonal hematopoietic precursor cells from patients with myelodysplastic syndrome (MDS) in immunodeficient mice has been difficult to achieve by intravenous (i.v.) injection. We used i.v. coadministration of the human marrow stroma cell line HS27a with CD34+ MDS cells in Nod.cg-Prkdc(scid) Il2rg(tm1wjll) (NSG) mice to provide signals that would facilitate engraftment. Hematopoietic cells from 24 MDS patients were transplanted. Cells from all patients were engrafted, and engraftment was documented in 44 of 46 evaluable mice (95%). Immunohistochemistry revealed human HS27a stroma colocalizing with human hematopoietic cells in mouse spleens. Human CD34+ precursors harvested from marrow and spleen of primary murine recipients, when combined with HS27a cells, were also engrafted successfully in secondary NSG recipients, showing persistence of the original clonal characteristics. This observation supports the concept that clonal markers were present in long-term repopulating cells. We suggest that HS27a stroma cells 'traveled' in direct contact with hematopoietic precursors and enabled their propagation. An essential signal for engraftment appears to be CD146, which is prominently expressed on HS27a cells. This xenotransplantation model will allow to further dissect signals that control engraftment of MDS cells and should be amenable to in vivo treatment studies.
ABSTRACT
PURPOSE: To test the ability of structural parameters (as measured by scanning laser polarimetry (SLP) software 1.0.12 and confocal scanning laser ophthalmoscopy (CSLO) to discriminate between normal and glaucomatous eyes. METHODS: A total of 112 patients with primary open-angle glaucoma and 88 normal individuals were enrolled in the study. All individuals underwent a thorough ophthalmic evaluation, a 24-2 full threshold Humphrey visual field, SLP with the GDx, and CSLO with the TOPSS. Patients with marked cataract or low vision were excluded from the study. Cut-off points were selected and receiver operator characteristic (ROC) curves were created for each individual CSLO and SLP parameter. Finally, multivariate dicriminant formulas were developed in order to achieve a better sensitivity (Se)/specificity (Sp) ratio for the diagnosis of glaucoma, initially separately for each device, and then combining parameters from CSLO and SLP. RESULTS: The mean deviation for the glaucoma group was -10.63 +/- 7.58 dB. Multivariate discriminant formulas resulted in better sensitivity/specificity ratios than any individual parameter, either for CSLO (Se: 90%; Sp: 81%; accuracy: 86%) or SLP (Se: 87%; Sp: 86%; accuracy: 86%). The multivariate formula combining parameters from both devices resulted in an improvement in the ability to diagnose glaucoma. An area under the ROC curve of 0.97 was obtained, with a sensitivity of 93%, a specificity of 91%, and an accuracy of 92%. CONCLUSIONS: The combination of structural parameters derived from CSLO and SLP in a multivariate discriminant formula may enhance the ability to diagnose glaucoma. Further studies investigating a random population are needed in order to test the validity of this formula.
Subject(s)
Glaucoma, Open-Angle/diagnosis , Ophthalmoscopy/methods , Optic Disk/pathology , Optic Nerve Diseases/diagnosis , Discriminant Analysis , Female , Humans , Male , Microscopy, Confocal , Middle Aged , Multivariate Analysis , ROC Curve , Reproducibility of Results , Visual FieldsABSTRACT
Objetivo: Avaliar, através da pletismografia a ar, o efeito que o uso das meias de compressão elástica (30/40mmHg)exerce na hemodinâmica venosa de pacientes em estágio avançado de insuficiência venosa crônica. Método: Avaliaram-se 29 membros de 16 pacientes com idade média de 44,3 anos(três do sexo masculino e 13 do sexo feminino).Em 19 membros havia insuficiência venosa primária, em 10 membros havia insuficiêcia venosa crônica secundária e, de acordo com a classificação clínica CEAP(C - clínico;E - etiológicos;A - anatômicos;P - patofisiológico),12 membros apresentavam grau C4(pacientes com lipodermatoesclerose e pigmentação de pele)e 17 membros apresentavam grau C5(pacientes com lipodermatoesclerose, pigmentação de pele e úlcera de perna cicatrizada).Inicialmente, os pacientes foram submetidos à pletismografia a ar(modelo SDV 2000, Angiotec, Belo Horizonte, Brasil), sem o uso de meia elástica(TO); após o exame, o paciente foi orientado a usar meia elástica(meia extra alta - Kendall, Sara Lee, Brasil)(30/40mmHg,3/4),por um período de 7 a 10 dias. Após esse período de adaptação, o paciente foi submetido a novo exame de plestimografia com a meia (TI). Finalmente, uma hora após a retirada da meia, nova avaliação plestimográfica, foi realizada(T2).O refluxo foi avaliado por duplex scan venoso(ATI,Philips, modelo HDI 5000, transdutor L47). Pacientes com índice tornozelo-braquial <0,8 e incapazes de realizar a pletismografia a ar foram excluídos. Resultados: As meias foram mais efetiva no controle de: volume venoso, índice de enchimento venoso, fração de ejeção e fração de volume residual em pacientes com insuficiência venosa crônica primária. Com o uso das meias, reduziu-se o refluxo venoso, verificando-se a queda do índice de enchimento venoso de T0-6,03ml/s para TI-4,84ml/s(P<0,05). A melhora se verificou, também, no volume venoso, que diminuiu de T0-137,11ml para TI-104,52ml(P<0,05).Com o uso da meia, observou-se a melhora da fração de ejeção,ao comparar-se os momentos T0-6455 por cento e TI-71,24 por cento(p<0,05).Ao retirar a meia, no momento T2-62,93 por cento, houve uma piora da fração de ejeção. As diferenças encontrada na fração de volume residual nos momentos T0-TI mostraram melhora desta variável com o uso da meia elástica.Conclusão: As meias elásticas foram eficazes na melhora do volume venoso, índice de enchimento venoso,fração de ejeção e fração de volume residual, principalemnte nos pacientes com insuficiência venosa crônica primária...
Subject(s)
Humans , Male , Female , Adult , Bandages , Venous Insufficiency/diagnosis , Plethysmography/methodsABSTRACT
Os autores apresentam 7 casos de complicacao de beta-terapia que se manifestaram de 2 a 15 anos apos cirurgia de pterigio. Ressaltam a necessidade de se controlar a dosagem e indicacoes do uso de beta-terapia assim como das proprias indicacoes de cirurgia de pterigio
Subject(s)
Adult , Middle Aged , Humans , Male , Female , PterygiumABSTRACT
Visual receptive fields of neurons in the nucleus of the basal optic root were investigated in pigeons. Their projections could be traced to vestibulo-cerebellum and oculomotor complex by means of antidromic activation. Units in that nucleus showed large peripheral receptive fields and appeared highly sensitive to moving targets, with the majority displaying axis specificity and direction selectivity. The results seem consistent with the proposed role of the accessory optic system in oculomotor reflexes.