A B S T R A C T The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3',5'-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE1 (maximal effect at 0.03 mM) and PGE2. The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE1 and PGE2 again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE1 and vice versa. It was concluded, therefore, that the SCC response to PGE1, like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE1 and NaF were the same in CT-treated and control mucosa. Cyclic 3',5'-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE,. A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is con-

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The systemic bioavailability of free fatty acid (FFA) forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared with ethyl ester (EE) forms is dependent on the presence of intestinal lipases and is highest during consumption of high-fat meals. Given that patients with cardiovascular disease are advised to reduce dietary fat intake, potentially lowering the bioavailability and therapeutic benefit, the hypothesis that FFA forms provide for higher bioavailability compared with EE forms under low-fat diet conditions was tested where the pharmacokinetics of the FFA form (Epanova™) were compared with those of an ethyl ester form (Lovaza®) following repeat dosing. Fifty-two healthy male and female subjects were equally allocated to one of two open-label, parallel-group cohorts. Following a Therapeutic Lifestyle Changes diet for a minimum of 7 days, blood samples were drawn for endogenous values for EPA and DHA over a 24-hour period. Subjects were then administered 4 × 1 g capsules of either Epanova (OM3 FFA) or Lovaza (OM3 EE) once daily for 14 days, following which serial blood samples were drawn over a 24-hour period to characterize the bioavailability of EPA and DHA from the respective formulations. In addition, changes from baseline in lipid profile were explored. Systemic bioavailability, as measured by area under the curve from time zero to 24 hours (AUC0-τ) and the maximum measured plasma concentrations during the 0–24 hour dosing interval (Cmax,ss) of unadjusted total plasma EPA + DHA were approximately 3-fold and 3.9-fold higher, respectively, for Epanova relative to Lovaza. Following baseline adjustment, the magnitude of difference in bioavailability was approximately 5.8-fold and 6.5-fold higher in AUC0-τ and Cmax, respectively, for Epanova relative to Lovaza. Serum triglycerides were reduced by a significantly greater extent (P = 0.013) for Epanova relative to Lovaza (21% versus 8%). The bioavailability of the FFA forms of EPA and DHA in Epanova are significantly greater than the bioavailability from the EE forms present in Lovaza under low-fat dietary conditions normally recommended for patients with cardiovascular disease. This increased bioavailability may lead to improved triglyceride-lowering in patients with hypertriglyceridemia.

The aim of the study was to determine the effects of 8 weeks of moderate exercise training, on 24-hour free living energy expenditure in previously sedentary post-menopausal women. The experimental group (EX) included 9 women. Ten non-exercising control subjects (CON) were recruited to undergo pre- and post-testing. Estimated total daily energy expenditure (TDEE), total 24-hour heart beats (HB), total energy intake (TEI), resting metabolic rate, maximal oxygen consumption (VáO2max), body composition, and submaximal heart rate were measured before and after the exercise intervention. Body composition did not change (body fat % in CON 34.0 +/- 4.0% vs. 33.9 +/- 3.6% and EX 34.1 +/- 4.0% vs. 34.0 +/- 3.4%). Mean submaximal heart rate during steady-state exercise in EX was lower after training compared to CON (p < .05); however, VáO2max did not increase significantly (CON 1.96 +/- 0.23 vs. 1.99 +/- 0.24 l L O2/min and EX 1.86 +/- 0.39 vs. 1.94 +/- 0.30 L O2/min). Neither estimated TDEE (CON, 11.6 +/- 2.0 vs. 11.4 +/- 2.78 MJ; and EX 11.4 +/- 3.3 vs. 11.5 +/- 2.5 MJ, pre vs. post, respectively), RMR (CON 134.2 +/- 9.4 vs. 136.9 +/- 15.0 KJ/kgFFM/day, and EX 138.4 +/- 6.4 vs. 140.7 +/- 14.2 KJ/kgFFM/day, pre vs. post, respectively), TEI (CON 7.9 +/- 2.2 vs. 8.2 +/- 2.5 MJ, and EX 9.4 +/-1.6 vs. 8.3 +/- 2.8 MJ), nor HB (CON 110,808 +/- 12,574 vs. 107,366 +/- 12,864 beats, and EX 110,188 +/- 9,219 vs. 114,590 +/- 12,750 beats) change over 8 weeks in either group. These data suggest that a moderate exercise program may not impact on TDEE, RMR, TEI, or HB in previously sedentary, older women.