RESUMO
In a cohort of 257 infants with congenital heart disease admitted to the pediatric intensive care unit, 22 infants had positive cultures for extended-spectrum beta-lactamase or AmpC Gram-negative bacteria. These infants had longer exposure to broad-spectrum antibiotics, greater support with invasive devices and longer intensive care and hospital lengths of stay.
Assuntos
Proteínas de Bactérias , Infecção Hospitalar/microbiologia , Infecções por Bactérias Gram-Negativas/complicações , Cardiopatias Congênitas/complicações , Resistência beta-Lactâmica , beta-Lactamases , Estudos de Casos e Controles , Citrobacter/enzimologia , Estudos de Coortes , Estado Terminal , Enterobacter/enzimologia , Escherichia coli/enzimologia , Feminino , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Klebsiella/enzimologia , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco , Serratia/enzimologiaRESUMO
Amyloid beta (Abeta) immunotherapy for Alzheimer's disease has shown initial success in mouse models of Alzheimer's disease and in human patients. However, because of meningoencephalitis in clinical trials of active vaccination, approaches using therapeutic antibodies may be preferred. As a novel antigen to generate monoclonal antibodies, the current study has used Abeta oligomers (amyloid beta-derived diffusible ligands, ADDLs), pathological assemblies known to accumulate in Alzheimer's disease brain. Clones were selected for the ability to discriminate Alzheimer's disease from control brains in extracts and tissue sections. These antibodies recognized Abeta oligomers and fibrils but not the physiologically prevalent Abeta monomer. Discrimination derived from an epitope found in assemblies of Abeta1-28 and ADDLs but not in other sequences, including Abeta1-40. Immunoneutralization experiments showed that toxicity and attachment of ADDLs to synapses in culture could be prevented. ADDL-induced reactive oxygen species (ROS) generation was also inhibited, establishing this response to be oligomer-dependent. Inhibition occurred whether ADDLs were prepared in vitro or obtained from Alzheimer's disease brain. As conformationally sensitive monoclonal antibodies that selectively immunoneutralize binding and function of pathological Abeta assemblies, these antibodies provide tools by which pathological Abeta assemblies from Alzheimer's disease brain might be isolated and evaluated, as well as offering a valuable prototype for new antibodies useful for Alzheimer's disease therapeutics.