RESUMO
Angiotensin may promote endothelial dysfunction through iron accumulation. To research this, bovine endothelial cells (ECs) were incubated with iron (30 µmol·L⻹) with or without angiotensin II (100 nmol·L⻹). After incubation for 6 h, it was observed that the addition of angiotensin enhanced EC iron accumulation by 5.1-fold compared with a 1.8-fold increase for cells incubated with iron only. This enhanced iron uptake was attenuated by losartan (100 nmol·L⻹), d-propranolol (10 µmol·L⻹), 4-HO-propranolol (5 µmol·L⻹), and methylamine, but not by vitamin E or atenolol. After 6 h of incubation, angiotensin plus iron provoked intracellular oxidant formation (2'7'-dichlorofluorescein diacetate (DCF-DA) fluorescence) and elevated oxidized glutathione; significant loss of cell viability occurred at 48 h. Stimulated prostacyclin release decreased by 38% (6 h) and NO synthesis was reduced by 41% (24 h). Both oxidative events and functional impairment were substantially attenuated by losartan or d-propranolol. It is concluded that angiotensin promoted non-transferrin-bound iron uptake via AT-1 receptor activation, leading to EC oxidative functional impairment. The protective effects of d-propranolol and 4-HO-propranolol may be related to their lysosomotropic properties.
Assuntos
Angiotensina II/metabolismo , Endotélio Vascular/metabolismo , Epoprostenol/metabolismo , Ferro/metabolismo , Losartan/farmacologia , Óxido Nítrico/metabolismo , Propranolol/análogos & derivados , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Angiotensina II/química , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Aorta/citologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Epoprostenol/agonistas , Epoprostenol/antagonistas & inibidores , Glutationa/metabolismo , Ferro/efeitos adversos , Sobrecarga de Ferro/prevenção & controle , Losartan/uso terapêutico , Óxido Nítrico/agonistas , Óxido Nítrico/antagonistas & inibidores , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Propranolol/farmacologia , Propranolol/uso terapêutico , Receptor Tipo 1 de Angiotensina/metabolismoRESUMO
OBJECTIVE: The objectives of this case report are as follows: to describe the process of establishing a national laboratory information management system (LIMS) program for clinical and public health laboratories in Vietnam; to evaluate the outcomes and lessons learned; and to present a model for sustainability based on the program outcomes that could be applied to diverse laboratory programs. METHODS: This case report comprises a review of program documentation and records, including planning and budgetary records of the donor, monthly reports from the implementer, direct observation, and ad-hoc field reports from technical advisors and governmental agencies. Additional data on program efficacy and user acceptance were collected from routine monitoring of laboratory policies and operational practices. RESULTS: LIMS software was implemented at 38 hospital, public health and HIV testing laboratories in Vietnam. This LIMS was accepted by users and program managers as a useful tool to support laboratory processes. Implementation cost per laboratory and average duration of deployment decreased over time, and project stakeholders initiated transition of financing (from the donor to local institutions) and of system maintenance functions (from the implementer to governmental and site-level staff). Collaboration between the implementer in Vietnam and the global LIMS user community was strongly established, and knowledge was successfully transferred to staff within Vietnam. CONCLUSION: Implementing open-sourced LIMS with local development and support was a feasible approach towards establishing a sustainable laboratory informatics program that met the needs of health laboratories in Vietnam. Further effort to institutionalize IT support capacity within key government agencies is ongoing.
Assuntos
Sistemas de Informação em Laboratório Clínico/normas , Coleta de Dados/normas , Laboratórios/normas , Software , Órgãos Governamentais , Humanos , Propriedade , Avaliação de Programas e Projetos de Saúde , Garantia da Qualidade dos Cuidados de Saúde , Projetos de Pesquisa , VietnãRESUMO
BACKGROUND: The use of Western blot (WB) as a supplemental test after reactive sensitive initial assays can lead to inconclusive or misclassified HIV test results, delaying diagnosis. OBJECTIVE: To determine the proportion of specimens reactive by immunoassay (IA) but indeterminate or negative by WB that could be resolved by alternative supplemental tests recommended under a new HIV diagnostic testing algorithm. STUDY DESIGN: Remnant HIV diagnostic specimens that were reactive on 3rd generation HIV-1/2 IA and either negative or indeterminate by HIV-1 WB from 11 health departments were tested with the Bio-Rad Multispot HIV-1/HIV-2 Rapid Test (Multispot) and the Gen-Probe APTIMA HIV-1 RNA Qualitative Assay (APTIMA). RESULTS: According to the new testing algorithm, 512 (89.8%) specimens were HIV-negative, 55 (9.6%) were HIV-1 positive (including 19 [3.3%] that were acute HIV-1 and 9 [1.6%] that were positive for HIV-1 by Multispot but APTIMA-negative), 2 (0.4%) were HIV-2 positive, and 1 (0.2%) was HIV-positive, type undifferentiated. 47 (21.4%) of the 220 WB-indeterminate and 8 (2.3%) of the 350 WB-negative specimens were HIV-1 positive. CONCLUSION: Applying the new HIV diagnostic algorithm retrospectively to WB-negative and indeterminate specimens, the HIV infection status could be established for nearly all of the specimens. IA-reactive HIV-infected persons with WB-negative results had been previously misclassified as uninfected, and HIV diagnosis was delayed for those with WB-indeterminate specimens. These findings underscore the limitations of the WB to confirm HIV infection after reactive results from contemporary 3rd or 4th generation IAs that can detect HIV antibodies several weeks sooner than the WB.