Showing papers by "Matthew B. Grisham published in 1986"

Xanthine oxidase and neutrophil infiltration in intestinal ischemia

Abstract: A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.

Preparation and Characterization of Chloramines

Abstract: Publisher Summary This chapter discusses the preparation and characterization of chloramines. Chloramines represent an important class of leukocyte oxidants and contribute to oxidative microbicidal, cytotoxic and cytolytic activities, the chemical modification of regulatory substances, and the uptake and metabolism of nitrogen compounds. These are products of the reaction of hypochlorous acid (HOCl) or other chlorinating agents with primary and secondary amines. The production of HOCl by leukocytes is the result of peroxidase-catalyzed oxidation of chloride (Cl – ) by hydrogen peroxide (H 2 O 2 ). HOCl is in equilibrium with hypochlorite (OCl – ) and chlorine (Cl 2 ). The most abundant N-moieties available for reaction with HOCl in biological systems are primary amino groups, such as taurine, polyamines, amino sugars, lysine residues, and protein amino termini. Leukocyte peroxidases catalyze the oxidation of bromide (Br – ), iodide (I – ), thiocyanate (SCN – ), and Cl – . N–Cl derivatives are used within minutes of preparation to avoid decomposition or rearrangement. However, most are stable at 4° for hours or days at the appropriate pH.

Cytotoxicity of Chloramines

Abstract: Publisher Summary This chapter describes the cytotoxicity of chloramines. The binding of ligands to the membrane-surface receptors of neutrophilic leukocytes stimulates the reduction of oxygen (O 2 ) to superoxide (O 2 – ) and the secretion of cytoplasmic granule components including myeloperoxidase into the intracellular phagolysosome compartment and the extracellular medium. When neutrophils are incubated with target cells, nitrogen–chlorine (N–Cl) derivatives react with both types of cells so that results are influenced by the neutrophil:target cell ratio and the reactivity of N–Cl derivatives toward neutrophil and target cell components. Methods for evaluating the cytotoxicity of N–Cl derivatives consist of measuring oxidation, chlorination, or other chemical modifications of cell components and measuring lysis or the failure of specific structural or functional components of cells. Stimulated neutrophils undergo a progressive myeloperoxidase-dependent inhibition of O 2 and glucose metabolism. This inhibition results from the reaction of hypochlorous acid (HOCl) with ammonium (NH 4 + ) produced by the cells. Monochloramine (NH 2 Cl) is produced as a result and inactivates neutrophil components.