Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Progressive and regressive changes in the nucleus pulposus. Part I. The neonate

Magnetic resonance (MR) imaging, correlated with anatomic sections, was used to characterize the progressive and regressive changes in the nucleus pulposus in neonates. The spines of five fetuses and five full-term infants between 16 and 40 weeks old were studied. In anatomic sections, the nucleus pulposus was sharply demarcated from the anulus fibrosus, Sharpey fibers were conspicuous, and a plate of primitive notochord was evident in the equator of the disk. On long repetition time (TR)/long echo time (TE) or long TR/short TE MR images, Sharpey fibers (low signal intensity) and notochord (low signal intensity) could be differentiated from the high-signal-intensity nucleus pulposus and anulus fibrosus. The major differences between the fetal and infant spines were the amount of notochord in the disk and ossification in the vertebral body.     

痛

黑暗!黑暗!!黑暗!!!这样的世界看不到半点光明。孤独的舞者终究还是孤独地倒下,然后又孤独地消失。黑暗呀,为什么老是缠绕着我?一声“妈妈”划破了天际,却也突不出黑暗的包围。谁来应我一声呀,妈妈,你在哪里呀?我的心在不停地挣扎,告诉自己:“不怕,不怕。”可这是在黑暗里呀,周     

PROGRESSIVE SUPRANUCLEAR PALSY PRESENTING WITH PSYCHIATRIC FEATURES

SUMMARY A patient with progressive supranuclear palsy who presented with psychiatric features is reported. His case illustrates the difficulty of early diagnosis of this condition. Associated psychiatric symptoms are common and may precede the occurrence of gaze palsy. Our patient's behavioural problems responded to fluoxetine.