In this study, the effect of shear stress on the expression of genes of the human endothelin‐1 system was examined. Primary cultures of human umbilical vein endothelial cells (HUVEC) were exposed to laminar shear stress of 1, 15 or 30 dyn cm−2 (i.e. 0.1, 1.5 or 3 N m−2) (venous and two different arterial levels of shear stress) in a cone‐and‐plate viscometer. Laminar shear stress transiently upregulates preproendothelin‐1 (ppET‐1) mRNA, reaching its maximum after 30 min (approx 1.7‐fold increase). In contrast, long‐term application of shear stress (24 h) causes downregulation of ppET‐1 mRNA in a dose‐dependent manner. Arterial levels of shear stress result in downregulation of endothelin‐converting enzyme‐1 isoform ECE‐1a (predominating in HUVEC) to 36.2 ± 8.5%, and isoform ECE‐1b mRNA to 72.3 ± 1.9% of static control level. The endothelin‐1 (ET‐1) release is downregulated by laminar shear stress in a dose‐dependent manner. This downregulation of ppET‐1 mRNA and ET‐1 release is not affected by inhibition of protein kinase C (PKC), or tyrosine kinase. Inhibition of endothelial NO synthase (L‐NAME, 500 μm) prevents downregulation of ppET‐1 mRNA by shear stress. In contrast, increasing degrees of long‐term shear stress upregulate endothelin receptor type B (ETB) mRNA by a NO‐ and PKC‐, but not tyrosine kinase‐dependent mechanism. In conclusion, our data suggest the downregulation of human endothelin synthesis, and an upregulation of the ETB receptor by long‐term arterial laminar shear stress. These effects might contribute to the vasoprotective and anti‐arteriosclerotic potential of arterial laminar shear stress.

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To investigate the metabolic behavior of different disease processes and pathology in epilepsy, fluorodeoxyglucose-positron emission tomography (FDG-PET) images of 280 patients with refractory epilepsy who had been surgically treated were retrospectively analyzed. The image findings were compared with the surgical pathology report. For all the pathology types reported, the major manifestations were regional hypometabolism. Of patients with sclerosis 92.1% (153/166) demonstrated FDG hypometabolism; 5.4% (9/166) were normometabolic and 2.4% (4/166) had increased FDG uptake (hypermetabolism). Of patients with malformation of cortical development, 84.5% (60/71) demonstrated hypometabolism, 8.4% (6/71) hypermetabolism, and 7% (5/71) showed normal metabolism. All of the neoplasms (24/24) and inflammatory processes (25/25) showed regional hypometabolism. The study suggests that although the major findings on FDG-PET in patients with refractory epilepsy are hypometabolic, attention should also be paid to patients with regional hypermetabolism, which might sufficiently localize the seizure origin. It might be worthwhile to repeat the study if no regions of hypometabolism are found and the electroencephalography suggests frequent spiking activity.

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