Decreasing oesophageal acid exposure in patients with GERD: a comparison of rabeprazole and omeprazole.

BACKGROUND: Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD). AIM: This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD. METHODS: Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period. RESULTS: At the end of study, the percentage time (mean +/- s.d.) with pH < 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 +/- 4.77; 2.53 +/- 4.27; 2.02 +/- 1.71 and 2.91 +/- 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated. CONCLUSIONS: Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.

The role of calcium in mediating phorbol ester- and insulin-stimulated adipocyte lipogenesis.

The roles of protein kinase C, calcium and calmodulin in mediating insulin-stimulated lipogenesis by rat adipocytes were investigated using the protein kinase C activator, phorbol myristate acetate (PMA); the protein kinase C inhibitors, H7 and polymixin B; the calcium ionophore, A23187; the calcium channel blocker, verapamil; and the calmodulin inhibitor, calmidazolium. PMA caused a concentration-dependent, parallel left shift of the insulin-lipogenesis dose response curve. Both PMA- and insulin-stimulated lipogenesis were inhibited by H7 and polymixin B. A23187 enhanced the stimulatory action of both insulin and PMA was not inhibited by H7. The stimulatory effects of insulin and PMA were inhibited by verapamil and calmidazolium. These data indicate that insulin receptor-lipogenesis coupling in rat adipocytes is mediated by protein kinase C-elicited calcium influx and activation of calmodulin.

Inhibition of somatomedin-like activity by serum from streptozotocin-diabetic rats: prevention by insulin treatment and correlation with skeletal growth.

Diabetes mellitus was induced in rats by streptozotocin. This gave rise to a loss of somatomedin activity in serum. The loss of somatomedin activity was due to the presence of inhibitors associated with serum proteins having mol wts of less than 1, 1-10, 30-50, and 300 K. Whereas less than 1, 1-10, and 30-50 kilodalton fractions were not inhibitory in control and insulin-treated animals, greater than 300 kilodalton fraction was inhibitory in control and insulin-treated animals; the inhibitory activity of this fraction in diabetic animals was significantly greater than that in controls and insulin-treated animals. The appearance of these inhibitors in diabetic animals was accompanied by reduced skeletal growth. Treatment of diabetic animals with insulin abolished the somatomedin-inhibitory activity of serum and corrected the skeletal growth deficit. Serum inhibitors of somatomedin may, therefore, be involved in the causation of some of the complications of diabetes, including impaired skeletal growth.

Human plasma fractions inhibit the action of insulin on adipocytes and somatomedin on cartilage.

Since human immunoglobulins exert an insulin-like stimulatory effect on adipocyte lipogenesis at concentrations markedly lower than those found in vivo, and since human serum or plasma are only midly stimulatory, we predicted that human serum probably contains an inhibitor of adipocyte lipogenesis. Supernatant preparations, obtained from the precipitation of immunoglobulins from plasma in 2.5 mol/l ammonium sulphate, were extensively dialysed and tested for their activity on bioassay systems commonly used for measuring insulin. The supernatants produced a marked inhibition of basal and insulin- or IgG-stimulated lipogenesis and glucose oxidation by adipocytes at protein concentrations of 10 mg/l. The supernatants were further purified through ultrafiltration to demonstrate two main inhibitory fractions, 10 to 30 K and 30 to 50 K, which again produced marked inhibition of basal and insulin- or IgG-stimulated adipocyte lipogenesis and glucose oxidation. These fractions were then tested for basal and serum somatomedin-stimulated 35S sulphate uptake by porcine cartilage: both basal and serum somatomedin-stimulated 35S uptake were significantly inhibited (p less than 0.01). Therefore, normal human serum contains at least two peptides which are markedly inhibitory to glucose metabolism and insulin action on adipocytes and 35S transport and somatomedin action on cartilage.