Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol

Resveratrol, a phenolic substance present in grapes and a variety of medical plants, has been reported to induce vasorelaxation, however the mechanisms are uncertain. In this paper we investigate the possible participation of K(+) channels in the endothelium-independent vasodilatation of rat aorta induced by resveratrol. Resveratrol induced concentration-dependent relaxation of rings with endothelium and without endothelium. We used different potassium channel inhibitors to determine whether the K(+) channels mediated endothelium-independent relaxation of rat aorta induced by resveratrol. Highly selective blocker of ATP-sensitive K(+) channels, glibenclamide, as well as non-selective blockers of K(+) channels, tetraethylammonium, did not block resveratrol-induced relaxation of rat aortic rings. Charybdotoxin, a blocker of calcium-sensitive K(+) channels did not affect the resveratrol-induced relaxation. 4-Aminopiridine, non-selective blocker of voltage-gated K(+) (Kv) channels, and margatoxin that inhibits Kv1 channels abolished relaxation of rat aortic rings induced by resveratrol. In conclusion, we have shown that resveratrol potently relaxed rat aortic rings with denuded endothelium. It seems that 4-aminopiridine and margatoxin-sensitive K(+) channels located in the smooth muscle of rat aorta mediated this relaxation.     

Myocardial protection in cyanotic neonatal lambs

To investigate the susceptibility of cyanotic neonatal myocardium to ischemia and the effectiveness of cardioplegia for protection, we induced cyanosis in 2- to 5-day-old lambs (n = 16) by connecting the left atrial appendage to the main pulmonary artery with a 4 mm polytetrafluoroethylene graft, which produced an arterial oxygen tension of 34.1 +/- 1.2 torr. Seven to 10 days after creation of the model, isolated perfused hearts from cyanotic animals were subjected to 2 hours of ischemia with topical cooling or crystalloid cardioplegia (K = 30 mEq/L) for myocardial protection (both at 15 degrees C). Identical studies were performed on hearts from 16 normoxemic neonatal lambs 5 to 14 days old. The overall effect of cyanosis was to produce a significant impairment in recovery of maximum developed pressure (p less than 0.05) after ischemia. The overall effect of cardioplegia was to produce a significant improvement in recovery of maximum developed pressure, developed pressure at V10 (the balloon volume to produce an end-diastolic pressure of 10 mm Hg during the preischemic period), and peak rate of pressure rise at V10 (p less than 0.05). The protective effect of cardioplegia was more prominent in cyanotic hearts than in normoxemic hearts for recovery of maximum of peak rate of pressure rise and peak rate of pressure rise at V10 (p less than 0.05). End-diastolic pressure at V10 and the diastolic stiffness constant at 10 and 20 mm Hg were all significantly higher after ischemia in the cyanotic hearts than in the normoxemic hearts (p less than 0.05). We conclude that in neonatal hearts cyanosis may increase the vulnerability to ischemia and cardioplegia appears to enhance the recovery of systolic but not diastolic function in these hearts.     

The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is effective in treating intestinal adenomas in humans with Familial Adenomatous Polyposis (FAP) and in preventing intestinal tumors in the C57Bl/6J- Min+ (Min) mouse, an animal model of FAP. Sulindac is a prodrug metabolized by the liver and intestinal flora to a sulfone, which has no anti-inflammatory activity, and a sulfide, which is the active anti- inflammatory metabolite. In this study, we determined which of these metabolites is responsible for the anti-tumor effect of sulindac in Min mice. Min mice were treated with either sulindac sulfone or sulindac sulfide (0.5 +/- 0.1 mg/day). Min mice and homozygous C57Bl/6J-(+/+) normal litter-mates lacking the Apc mutation (+/+) were used as controls. At 110 days of age, all mice were euthanized and their intestinal tracts examined. Control Min mice had 33.2 +/- 6.6 tumors per mouse compared to 0.6 +/- 0.3 tumors for sulindac sulfide-treated Min mice (P < 0.001) and 21.9 +/- 4.5 tumors per mouse for sulindac sulfone-treated Min mice (P > 0.05). Decreased enterocyte apoptosis was observed in Min control mice and Min mice treated with sulindac sulfone. Sulindac sulfide restored to normal the level of apoptosis in the mucosa of Min animals and decreased levels of PGE2 in the small intestine of treated Min animals by 59% (P < 0.001). These data suggest that the anti-tumor effect of sulindac in Apc-deficient animals is mediated by the sulfide metabolite and correlates with suppression of tissue prostaglandin synthesis.      

The barium enema scout film: cost effectiveness and clinical efficacy

The authors prospectively evaluated 1,001 consecutive double-contrast barium enema examinations to determine the efficacy of the preliminary film. The scout films were evaluated for the presence of unsatisfactory amounts of residual feces and clinically significant extracolonic abnormalities. The contrast studies were independently evaluated in a double-blind manner for satisfactory colonic preparation as well as extracolonic abnormalities. The routine use of the scout film resulted in an increase in health care charges and departmental costs. In addition, there was no significant increase in the detection of extracolonic abnormalities. Our data suggest that routine use of scout films prior to contrast studies is unnecessary, although selective use in some clinical situations may be justified.