The objective of this study was to investigate whether low bone mass is directly associated with the severity of coronary atherosclerosis in men and postmenopausal women self-referred for evaluation of coronary atherosclerosis and osteoporosis. Low bone mass was evaluated by measurement of bone mineral density (BMD) using quantitative computerized tomography (QCT). Coronary atherosclerosis was evaluated by measurement of coronary calcium (CC) burden using electron beam computerized tomography (EBCT). Using a cross-sectional design, we tested the hypothesis that osteoporosis and coronary atherosclerosis are correlated, age-dependent processes. Study variables were BMD, CC scores, and other known risk factors for osteoporosis and atherosclerosis. Qualifying for the study were 313 postmenopausal women and 167 men. Men had higher baseline CC scores and higher body mass indexes compared to women. In females, those patients with coronary calcification were older and had significantly lower BMD compared to those without calcification. In males, those patients with coronary calcification were older. By univariate correlation analysis, the degree of coronary calcification was inversely associated with BMD in postmenopausal women (P < 0.0001) but not in men. However, after controlling for age, this association was absent for both men and postmenopausal women. Using multivariate logistic regression analysis in women and men separately, age was the only significant predictor of positive CC status and low BMD. Our study suggests that in postmenopausal women and in men, after controlling for age, osteoporosis and coronary atherosclerosis are independent processes.

The effect of nitric oxide (NO) on Na+/H+ exchange (NHE) activity was investigated utilizing Caco-2 cells as an experimental model. Incubation of Caco-2 cells with 10(-3) M S-nitroso-N-acetylpenicillamine (SNAP), a conventional donor of NO, for 20 min resulted in a approximately 45% dose-dependent decrease in NHE activity, as determined by assay of ethylisopropylamiloride-sensitive 22Na uptake. A similar decrease in NHE activity was observed utilizing another NO-specific donor, sodium nitroprusside. SNAP-mediated inhibition of NHE activity was not secondary to a loss of cell viability. NHE3 activity was significantly reduced by SNAP (P < 0.05), whereas NHE2 activity was essentially unaltered. The effects of SNAP were mediated by the cGMP-dependent signal transduction pathway as follows: 1) LY-83583 and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), specific inhibitors of soluble guanylate cyclase, blocked the inhibitory effect of SNAP on NHE; 2) 8-bromo-cGMP mimicked the effects of SNAP on NHE activity; 3) the SNAP-induced decrease in NHE activity was counteracted by a specific protein kinase G inhibitor, KT-5823 (1 microM); 4) chelerythrine chloride (2 microM) or calphostin C (200 nM), specific protein kinase C inhibitors, did not affect inhibition of NHE activity by SNAP; 5) there was no cross activation by the protein kinase A-dependent pathway, as the inhibitory effects of SNAP were not blocked by Rp-cAMPS (25 microM), a specific protein kinase A inhibitor. These data provide novel evidence that NO inhibits NHE3 activity via activation of soluble guanylate cyclase, resulting in an increase in intracellular cGMP levels and activation of protein kinase G.

The present studies were undertaken to examine the possible regulation of apical membrane Cl−/OH− exchanger in Caco-2 cells by protein kinase C (PKC). The effect of the phorbol ester phorbol 12-myristate 13-acetate (PMA), an in vitro PKC agonist, on OH−gradient-driven 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive 36Cl uptake in Caco-2 cells was assessed. The results demonstrated that PMA decreased apical Cl−/OH− exchanger activity via phosphatidylinositol 3-kinase (PI3-kinase)-mediated activation of PKCε. The data consistent with these conclusions are as follows: 1) short-term treatment of cells for 1–2 h with PMA (100 nM) significantly decreased Cl−/OH−exchange activity compared with control (4α-PMA); 2) pretreatment of cells with specific PKC inhibitors chelerythrine chloride, calphostin C, and GF-109203X completely blocked the inhibition of Cl−/OH− exchange activity by PMA; 3) specific inhibitors for PKCε (Ro-318220) but not PKCα (Go-6976) significantly blocked the PMA-mediated inhibition; 4) specific PI3-kinase inhibitors wortmannin and LY-294002 significantly attenuated the inhibitory effect of PMA; and 5) PI3-kinase activators IRS-1 peptide and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] mimicked the effects of PMA. These findings provide the first evidence for PKCε-mediated inhibition of Cl−/OH− exchange activity in Caco-2 cells and indicate the involvement of the PI3-kinase-mediated pathways in the regulation of Cl− absorption in intestinal epithelial cells.

It is important to promote those aspects of ENT surgery that attract people to it, and to argue for greater exposure to ENT during undergraduate and post-graduate training.

Allergic rhinitis affects 20% of the population of the UK. It confers a significant health burden upon the individual as it affects the patient's quality of life and is associated with serious comorbidities including asthma, sinusitis and conjunctivitis. Owing to its prevalence, it has a significant economic impact through its effects on education, productivity and use of healthcare resources. This review focuses on the management of allergic rhinitis and potential future treatments, because of the lack of clear national guidelines and because this illness is often misdiagnosed and mismanaged. The article provides a comprehensive overview of allergic rhinitis and illustrates the assessment criteria for various subcategories.