Blockade of L-arginine uptake by L-lysine inhibited NOS activity and, conversely, blockade of NOS using N ω -nitro-L-arginine methyl ester (L-NAME) inhibited L-arginine transport. β 2 AR stimulation also caused a membrane hyperpolarization inhibitable by L-NAME, suggesting that the increase in L-arginine uptake occurred in response to NO-mediated hyperpolarization. β 2 AR activation also increased NOS activity and phosphorylation of NOS-3 on serine-1177, and these increases were attenuated by inhibition of protein kinase A (PKA), phosphatidylinositol 3-kinase (PI3K) or Akt, and abolished by coinhibition of PKA and Akt. These findings suggest that β 2 AR-mediated NOS-3 activation in HUVEC is mediated through phosphorylation of NOS-3 on serine-1177 through both the PKA and the PI3K/Akt systems, and is sustained by an increase in L-arginine uptake resulting from NO-mediated membrane hyperpolarization.
We describe the survivorship of the Exeter femoral component in a District General Hospital. Between 1994 and 1996, 230 Exeter Universal cemented femoral components were implanted in 215 patients who were reviewed at a mean of 11.2 years (10 to 13). We used one acetabular implant, the Elite Ogee component, in 218 of the 230 hips. During the period of this study 76 patients (79 hips) died. Of the remaining 139 patients (151 hips), 121 were able to attend for radiological analysis at a minimum of ten years. One patient was lost to follow-up. No femoral component was revised for aseptic loosening. Three hips were revised for deep infection and six acetabular components required revision, four for loosening and two for recurrent dislocation. Taking the 'worst-case scenario' including the one patient lost to follow-up, the overall survival rate was 94.4% at 13 years. Our results confirm excellent medium-term results for the Exeter Universal femoral component, implanted in a general setting. The excellent survival of this femoral component, when used in combination with the Ogee acetabular component, suggests that this is a successful pairing.
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