Anterior pituitary hyperplasia was developed in female Fisher 344 rats by subcutaneously implanted slow-release diethylstilbestrol (DES) capsules. Blood flow was measured in two separate areas of the adenohypophysis using hydrogen clearance method at 6,9, 10, and 13 weeks after the implantation. Blood flow progressively decreased while the DES capsules were in place (normal values in ml/g/min, mean f SD: 0.93 f .12 laterally and 1.15 k .
Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation. As such, it was anticipated they would demonstrate cardiovascular benefit in those with diabetes, indeed early meta-analyses suggested cardiovascular events would be reduced. To date, however, this benefit has failed to materialize, indeed the cardiovascular outcome trials, whilst meeting their primary endpoint of cardiovascular safety, have failed to demonstrate any improvements in stroke or myocardial infarction. This review will explore the data and attempt to answer the question: what went wrong?
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