Functional activity of blood polymorphonuclear leukocytes as an oxidative stress biomarker in human subjects.

In the present work, we studied the role of polymorphonuclear leukocytes (PMN) in aged individuals and coronary heart disease (CHD)-bearing patients, two physiopathological processes associated with overproduction of reactive oxygen species (ROS). The effects of antioxidant supplementation on the functional activity of PMN from CHD patients were also determined. The function of PMNs was evaluated by measuring of phagocytosis, killing activity, and ROS production. Luminol amplified chemiluminescence (CL) was used to estimate ROS production by stimulated PMNs. Total cholesterol and the LDL-cholesterol fraction from CHD patients were found to be higher than those recommended, returning to normal levels after antioxidant therapy. PMN CL of CHD patients was found to be higher than the associated control groups. Antioxidant therapy administrated to CHD patients lead to an increase in the killing activity accompanied by a decrease in PMN CL of these subjects. The study also showed that killing activity of PMN from human subjects over 60 years was significantly lower than the activity measured in younger subjects. PMN CL produced after stimulation was found to be positively correlated with the increasing age of human subjects (r=.946, p < .01).

[Inefficacy of diltiazem in restenosis prevention after coronary angioplasty]. / Ineficácia do diltiazem na prevenção da reestenose após angioplastia coronária.

PURPOSE: To evaluate the efficacy of diltiazem in preventing restenosis after balloon angioplasty (PTCA). METHODS: Eighty-nine patients who were undergone to successful PTCA, were divided them in 2 groups (G): A) 44 patients (50%) who received diltiazem (180 mg tid) immediately after PTCA and were kept on it for 6 months); B) 45 patients (50%) who received placebo. Fifty two lesions were dilated in GA and 54 in GB. Patients were excluded from analysis for several reasons, including: necessity of diltiazem or others calcium channel blockers use; heart failure, bradicardia, AV block of any degree, PTCA to chronic total occlusion, ostial lesions and AMI less than 30 days prior to PTCA. Patients were randomized to either the active drug or placebo in a double blind fashion. Restenosis was defined as a 50% lesion. Patients underwent late angiography either at 6 months or sooner if clinically indicated. RESULTS: Both G were similar to age > 70 years (A = 7% vs B = 4%-p = NS), sex (A = 13% vs B = 11%-p = NS), stable angina (A = 43% vs B = 51%), unstable angina (A = 57% vs B = 49%-p = NS) and single vessel (A = 91% vs B = 87%-p = NS) or multivessel (A = 9% vs B = 13%-p = NS) PTCA. We studied 39/44 (89%) patients in GA and 43/45 (96%) in GB (p = NS). We observed restenosis in 17/39 (43%) in GA and 16/43 (37%) in GB (p = NS). The restenosis rate per lesion was 39% in GA and 31% in GB (p = NS). CONCLUSION: Diltiazem was ineffective in the prevention of restenosis following PTCA.

Effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes.

In vitamin A-deficient children, increased rates of bacterial infections in the intestine have been observed. The adherence of bacteria is a prerequisite for invasion. Thus, the effect of vitamin A deficiency on the adherence of fimbriated and nonfimbriated Salmonella typhimurium to isolated small intestinal enterocytes was studied. Male weanling rats matched by weight were divided into three groups: one group was fed a vitamin A-free diet for 8-12 weeks; another was given the same diet supplemented with retinol acetate; a third group matched for age served as controls. The vitamin A-deficient group showed a significantly lower growth rate and lower serum retinol levels than either the retinol acetate-supplemented or control groups. In all the groups, S. typhimurium possessing mannose-sensitive fimbriae adhered to enterocytes in significantly larger numbers than the nonfimbriated strains. The number of fimbriated S. typhimurium bound to enterocytes from the proximal small intestine was significantly higher in the vitamin A-deficient rats than in the pair-fed vitamin A-supplemented group (19.3 +/- 14.9 versus 7.8 +/- 5.0; p less than 0.05) or the control group (19.3 +/- 14.9 versus 8.7 +/- 3.5, p = 0.01). The specific activities of the enterocytes lactase, sucrase, and maltase and the protein content in the vitamin A-deficient rats were similar to those in the controls. These results demonstrate that vitamin A deficiency in rats is associated with the increased ability of S. typhimurium to adhere to proximal small intestinal enterocytes. However, the possible changes in the membrane of the enterocyte do not include decreases in brush border disaccharidases or protein content.

Concanavalin A promotes adherence of Salmonella typhimurium to small intestinal mucosa of rats.

A number of dietary lectins have been shown to resist proteolytic digestion. These lectins interact with the small intestinal mucosa causing structural and functional changes. Concomitant to these changes, bacterial overgrowth was reported and a possible interaction between lectins and bacteria in the small intestine was postulated. The aim of this study was to investigate the effect of various lectins on adherence of Salmonella typhimurium to both isolated small intestinal enterocytes and ligated intestinal loops. Isolated intestinal cells or ligated intestinal loops were incubated with [3H] adenine-S. typhimurium in the presence or absence of concanavalin A, phytohemagglutinin, peanut agglutinin, and wheat germ agglutinin. Only concanavalin A promoted the adherence of various strains of nonfimbriated S. typhimurium to isolated viable intestinal cells. Other lectins showed no effect on the adherence. In situ studies showed that bacterial binding was increased in concanavalin A-treated intestinal loops, supporting the significance of the experiments in vitro. These data suggest that lectins may act by promoting bacterial adherence to the small intestine, thereby facilitating colonization and infection, and leading to bacterial overgrowth.

Clinical trial of clonidine hydrochloride as an antisecretory agent in cholera.

Clonidine hydrochloride (an alpha 2-adrenoceptor agonist) was tested for antisecretory effects in patients with cholera in a randomized controlled trial. Nineteen adults with diarrhea due to Vibrio cholerae were treated with clonidine (0.9 mg/24 h orally for 72 h) and 18 served as controls. During the first 24 h of treatment and for 24 h afterwards, the mean +/- SD concentrations of sodium (in millimoles per liter) in the stools of clonidine-treated patients were 120.6 +/- 10.9 and 112.3 +/- 11.9, which were significantly lower than 135.5 +/- 17.1 and 125.0 +/- 16.4 in the controls (p less than 0.01). Stool chloride concentrations (in millimoles per liter) were also significantly less in the clonidine group during the same periods: 82.1 +/- 16.8 and 62.4 +/- 19.4 vs. 92.1 +/- 18.3 and 78.0 +/- 23.0, respectively (p less than 0.05). Concentrations of potassium but not bicarbonate were also significantly reduced in the stools of clonidine-treated patients (p less than 0.05). However, there were no significant differences in the mean +/- SD stool volumes (in liters) between the clonidine and the control group in any of the six 12-h periods after treatment or in the cumulative volumes in 72 h (24.2 +/- 10.6 and 22.9 +/- 8.3, respectively). We conclude that clonidine causes modest reduction of stool electrolyte loss but does not significantly reduce fecal fluid loss in patients with cholera.