Methods: Yorkshire swine were
made chronically ischemic by placing an ameroid constrictor on the left circumflex coronary artery. Swine were divided into 3 groups and given no drug (control, n = 7), a nonselective cyclooxygenase inhibitor Epigenetics (naproxen 400 mg daily, n = 7), or a selective cyclooxygenase 2 inhibitor (celecoxib 200 mg daily, n = 7). After 7 weeks, coronary angiography was performed. Myocardial function and microvascular reactivity were assessed. Serum and myocardial tissue were analyzed for prostaglandin levels and markers of inflammation and angiogenesis.
Results: The celecoxib group demonstrated significantly increased mean arterial pressure and decreased left ventricular function. Myocardial perfusion in the celecoxib group was similar to control value but less than in the naproxen group. Coronary microvascular contraction in the collateral-dependent territory was increased in the naproxen group but minimally affected in the celecoxib group. Oxidative stress and apoptosis were increased in the celecoxib group. Expression of angiogenic markers vascular endothelial growth factor and phospho-endothelial nitric oxide synthase (ser1177) and tissue levels of prostacyclin were decreased in both celecoxib and naproxen groups. Pevonedistat research buy The naproxen group
had diminished endostatin expression.
Conclusions: Selective and nonselective cyclooxygenase inhibition are more complex in effect than previously published, but they did not decrease collateral-dependent blood flow to the myocardium Thymidine kinase in our model of chronic myocardial ischemia. (J Thorac Cardiovasc Surg 2010;140:1143-52)”
“Acetylcholinesterase (AChE) has been an important
cholinergic factor for the diagnosis of Alzheimer’s disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2[F-18]fluorobenzyl)-4-piperidinyl) ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[F-18]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[F-18]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[F-18]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[F-18]fluoro-CP-118,954 and 4-[F-18]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/mu mol). Brain microPET images of two ICR mice injected with 2-[F-18]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.