RESUMO
Angiogenic biomarkers, including soluble fms-like tyrosine kinase 1 (sFlt1), are thought to be predictors of preeclampsia onset; however, improvement is needed before a widespread diagnostic test can be utilized. Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14. These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format. Data from this pilot study suggest that sFlt1-1 may be more predictive of preeclampsia than total sFlt1. It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.
Assuntos
Anticorpos Monoclonais/metabolismo , Pré-Eclâmpsia/diagnóstico , Proteínas da Gravidez/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia , Processamento Alternativo/imunologia , Líquido Amniótico/imunologia , Líquido Amniótico/metabolismo , Animais , Células CHO , Cricetulus , Feminino , Humanos , Camundongos , Projetos Piloto , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/imunologia , Gravidez , Proteínas da Gravidez/genética , Proteínas da Gravidez/imunologia , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Sensibilidade e Especificidade , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.