Platelet-activating factor: a mediator for clinicians.
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Biomedical subjects
T A Imaizumi
Publications and source records attributed to T A Imaizumi.
Production of platelet-activating factor by porcine brain microvascular endothelial cells in culture.
Endothelial cells produce platelet-activating factor (PAF), which is the key process in the interactions between the vascular wall and blood cells. To examine the production of PAF in brain microvasculature we have cultured brain endothelial cells and performed a comparative study with aortic endothelial cells. Fresh porcine brain was homogenized, and microvascular endothelial cells were separated by enzyme digestion. The cells were cultured in medium containing epidermal growth factor and bovine brain extract. Endothelial cells from the aorta of the same animal were cultured in a similar manner. Production of PAF was assessed by [3H]acetate incorporation into phospholipids or by radioimmunoassay. Prostacyclin was measured by radioimmunoassay of 6-ketoprostaglandin F 1 alpha. The cells produced 1760 +/- 403 and 2892 +/- 347 dpm/10(6) cells (n = 4) of PAF when stimulated with bradykinin and calcium ionophore A23187, each at 1 microM, respectively. Aortic endothelial cells produced 3911 +/- 2006 and 8052 +/- 2270 dpm/10(6) cells (n = 4), respectively, and these values were significantly higher than those in brain endothelial cells (p < 0.01, U-test). Prostacyclin production was also higher in aortic cells as compared to brain microvascular endothelial cells. In aortic endothelial cells both Ca ionophore A23187 and bradykinin significantly stimulated PMN adherence whereas in brain microvascular cells only Ca ionophore enhanced the adherence. Brain microvascular endothelial cells produce smaller amount of PAF and prostacyclin as compared to aortic endothelial cells, and this fact may imply that the functional integrity of the brain microvascular endothelium is maintained at a low level.
Animals↗
Pyrazolopyridine derivative acts as a novel cyclooxygenase inhibitor: antiplatelet effect in aged patients with ischemic stroke.
OBJECTIVE: To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke. DESIGN: Randomized clinical trial of three graded dose levels. SETTING: A geriatric clinic attached to a nursing home. PATIENTS: Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks. MEASUREMENTS: Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha. MAIN RESULTS: Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings. CONCLUSIONS: We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.
6-Ketoprostaglandin F1 alpha↗