UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal epithelial cells have receptors that recognize bacterial antigens and in some circumstances are actively involved in bacterial internalization. To test the hypothesis that intestinal epithelial cells possess bactericidal capabilities, the bactericidal activity of two intestinal cell lines (IEC-18 and Caco-2) was measured using Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli as test organisms. The relative bactericidal efficacy of these two intestinal cell lines to kill these bacteria was compared against neutrophils (PMN) using a standard in vitro bactericidal assay. The IEC-18 and Caco-2 cells as well as the PMNs killed S. aureus and P. aeruginosa but not E. coli (p < .05). In fact, when tested in serum-free medium, the IEC-18 and Caco-2 cells killed a greater percentage of bacteria than the PMNs (p < .05). The addition of the antioxidant, superoxide dismutase, significantly reversed the bactericidal activity of both Caco-2 cells and neutrophils for P. aeruginosa and S. aureus, while catalase had no effect. Nitric oxide inhibition by NG-nitro-L-arginine methyl ester (L-NAME) had no effect on bactericidal activity of Caco-2 cells. These results indicate that intestinal epithelial cells can kill certain strains of bacteria and may function as "nonprofessional" phagocytes. Additionally, the mechanisms involved in the killing of P. aeruginosa and S. aureus by the Caco-2 and IEC-18 cells appear similar to the PMNs to the extent that bactericidal activity appeared to be oxidant-mediated but not nitric oxide-mediated in both the Caco-2 cell line and in the neutrophils.
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PMID:Caco-2 and IEC-18 intestinal epithelial cells exert bactericidal activity through an oxidant-dependent pathway. 859 21

To study oxidative mechanisms in cyanide toxicity, cyanide-induced generation of intracellular oxidant species was determined by microfluorescence in cerebellar granule cells loaded with the oxidant-sensitive fluorescence dye 2,7-dichlorofluorescin. KCN produced a concentration-dependent (25-200 microM) generation of intracellular oxidant species that was blocked by N-methyl-D-aspartate receptor antagonists (MK-801 or AP5) or by removal of extracellular Ca++ from the incubation medium. To determine the relative contribution of NO and reactive oxygen species (ROS) to the increase of cellular fluorescence after KCN, a selective inhibitor of nitric oxide synthase, a NO scavenger and enzymes that metabolize ROS were added to the incubation medium. Interference with the nitric oxide system (reduced hemoglobin as a NO scavenger or [N(G)-nitro-L-arginine methyl ester [L-NAME] reduced fluorescence by 50%). Addition of enzymes that metabolize peroxide (catalase or superoxide dismutase [SOD]) also reduced fluorescence by nearly 50%. Combination of SOD with hemoglobin or L-NAME provided additional attenuation of the fluorescence and it was concluded that both NO and ROS are generated concurrently after KCN. Furthermore a correlation was observed between NO and ROS formation and levels of malonaldehyde (MDA), a marker of lipid peroxidation. Pretreatment with MK-801 blocked KCN-induced MDA formation, whereas L-NAME partially diminished MDA production. Treatment with a combination of SOD/catalase and L-NAME blocked the KCN-induced lipid peroxidation. In cytotoxicity studies cyanide-induced cell death was blocked by MK-801, whereas partial attenuation was produced by L-NAME; SOD/catalase treatments did not protect the cells. However, significant protection from cyanide-induced cytotoxicity was observed when L-NAME was combined with SOD/catalase. It is concluded that cyanide activates N-methyl-D-aspartate receptors to simultaneously generate both NO and ROS, which may lead to formation of the cytotoxic peroxynitrite anion.
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PMID:Cyanide-induced neurotoxicity involves nitric oxide and reactive oxygen species generation after N-methyl-D-aspartate receptor activation. 861 12

Nitric oxide has been implicated in mediating the neurotoxic effects of ischemia in the brain. However, studies of the effects of nitric oxide inhibition with nitric oxide synthase inhibitors have provided controversial results. One of the reasons for the controversy may be related to the specificity of the nitric oxide synthase inhibitors, such as Nw-nitro-L-arginine methylester (L-NAME), which has recently been questioned. The present work investigated the possible interaction of L-NAME with the enzyme catalase in vitro. Catalase is an iron containing enzyme which could potentially interact with the iron-binding groups of L-NAME. Since the normal function of catalase in the brain is to remove excess hydrogen peroxide, the inhibition of this process could have potentially toxic effects. L-NAME was found to attenuate the catalase inhibiting effects of the known catalase inhibitor cyanamide in vitro, suggesting a competition between cyanamide and L-NAME for catalase. In addition, L-NAME by itself attenuated catalase activity in vitro. These results indicate that in addition to inhibiting nitric oxide synthase, L-NAME may have effects on catalase activity.
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PMID:The nitric oxide synthase inhibitor NW-nitro-L-arginine methylester attenuates brain catalase activity in vitro. 861 53

1. In this study we investigated the role of catalase in relaxation induced by hydroxylamine, sodium azide, glyceryl trinitrate and hydrogen peroxide in isolated rings of rat aorta. 2. Hydrogen peroxide (1 microM-1 mM)-induced concentration-dependent relaxation of phenylephrine (PE)-induced tone in endothelium-containing rings. In endothelium-denuded rings, however, higher concentrations (30 microM-1 mM) of hydrogen peroxide were required to produce relaxation. The endothelium-dependent component of hydrogen peroxide-induced relaxation was abolished following pretreatment with N(O)-nitro-L-arginine methyl ester (L-NAME, 30 microM). L-NAME (30 microM) had no effect, however, on hydrogen peroxide-induced relaxation in endothelium-denuded rings. 3. Pretreatment of endothelium-denuded rings with catalase (1000 u ml-1) blocked relaxation induced by hydrogen peroxide (10 microM-1 mM). The ability of catalase to inhibit hydrogen peroxide-induced relaxation was partially blocked following incubation with 3-amino-1,2, 4-triazole (AT, 50 mM) for 30 min and completely blocked at 90 min. 4. Pretreatment of endothelium-denuded rings with methylene blue (MeB, 30 microM) inhibited relaxation induced by hydrogen peroxide (10 microM-1 mM), sodium azide (1-300 nM), hydroxylamine (1-300 nM) and glyceryl trinitrate (1-100 nM) suggesting that each acted by stimulation of soluble guanylate cyclase. 5. Pretreatment of endothelium-denuded rings with AT (1-50 mM, 90 min) to inhibit endogenous catalase blocked relaxation induced by sodium azide (1-300 nM) and hydroxylamine (1-300 nM) but had no effect on relaxation induced by hydrogen peroxide (10 microM-1 mM) or glyceryl trinitrate (1-100 nM). 6. In a cell-free system, incubation of sodium azide (10 microM-3 mM) and hydroxylamine (10 microM-30 mM) but not glyceryl trinitrate (10 microM-1 mM) with catalase (1000 u ml-1) in the presence of hydrogen peroxide (1 mM) led to production of nitrite, a major breakdown product of nitric oxide. AT (1-100 mM) inhibited, in a concentration-dependent manner, the formation of nitrite from azide in the presence of hydrogen peroxide. 7. These data suggest that metabolism by catalase plays an important role in the relaxation induced by hydroxylamine and sodium azide in isolated rings of rat aorta. Relaxation appears to be due to formation of nitric oxide and activation of soluble guanylate cyclase. In contrast, metabolism by catalase does not appear to be involved in the relaxant actions of hydrogen peroxide or glyceryl trinitrate.
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PMID:The inhibitory effect of 3-amino-1,2,4-triazole on relaxation induced by hydroxylamine and sodium azide but not hydrogen peroxide or glyceryl trinitrate in rat aorta. 871 11

1 The role of nitric oxide (NO) derived from constitutive and inducible nitric oxide synthase (cNOS and iNOS) and its relationship to oxygen-derived free radicals and prostaglandins (PG) was investigated in a carrageenan-induced model of acute hindpaw inflammation. 2 The intraplantar injection of carrageenan elicited an inflammatory response that was characterized by a time-dependent increase in paw oedema, neutrophil infiltration, and increased levels of nitrite/nitrate (NO2-/NO3-) and prostaglandin E2(PGE2) in the paw exudate. 3 Paw oedema was maximal by 6 h and remained elevated for 10 h following carrageenan administration. The non-selective cNOS/iNOS inhibitors, NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) given intravenously (30-300 mg kg-1) 1 h before or after carrageenan administration, inhibited paw oedema at all time points. 4 The selective iNOS inhibitors, N-iminoethyl-L-lysine (L-NIL) or aminoguanidine (AG), failed to inhibit carrageenan-induced paw oedema during the first 4 h following carrageenan administration, but inhibited paw oedema at subsequent time points (from 5-10 h). iNOS mRNA was detected between 3 to 10 h following carrageenan administration using ribonuclease protection assays. iNOS protein was first detected 6 h and was maximal 10 h following carrageenan administration as shown by Western blot analysis. Administration of the iNOS inhibitors 5 h after carrageenan (a time point where iNOS was expressed) inhibited paw oedema at all subsequent time points. Infiltrating neutrophils were not the source of iNOS since pretreatment with colchicine (2 mg kg-1) suppressed neutrophil infiltration, but did not inhibit the iNOS mRNA expression or the elevated NO2-/NO3- levels in the paw exudate. 5 Inhibition of paw oedema by the NOS inhibitors was associated with attenuation of both the NO2-/NO3- and PGE2 levels in the paw exudate. These inhibitors also reduced the neutrophil infiltration at the site of inflammation. 6 Recombinant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (PEGrhSOD; 12 x 10(3) u kg-1), administered intravenously either 30 min prior to or 1 h after carrageenan injection, inhibited paw oedema and neutrophil infiltration, but had no effect on NO2-/NO3- or PGE2 production in the paw exudate. The administration of catalase (40 x 10(3) u kg-1), given intraperitoneally 30 min before carrageenan administration, had no effect on paw oedema. Treatment with desferrioxamine (300 mg kg-1), given subcutaneously 1 h before carrageenan, inhibited paw oedema during the first 2 h after carrageenan administration, but not at later times. 7 These results suggest that the NO produced by cNOS is involved in the development of inflammation at early time points following carrageenan administration and that NO produced by iNOS is involved in the maintenance of the inflammatory response at later time points. The potential interactions of NO with superoxide anion and PG is discussed.
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PMID:Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. 879 51

To assess the role of reactive oxygen species and nitric oxide (NO) in the genesis of reperfusion-induced arrhythmias, the effects of reactive oxygen species scavengers and NO synthase inhibitors on the incidence of ventricular fibrillation and irreversible ventricular fibrillation (mortality) were examined. Hearts of anesthetized rats were subjected to 4 min regional ischemia followed by 4 min reperfusion. The animals were treated i.v. with superoxide dismutase, a O2- scavenger, catalase, a H2O2 scavenger, dimethylthiourea, a .OH scavenger, or NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA), NO synthase inhibitors. Superoxide dismutase (430 and 4300 U/kg/min) reduced the mortality from 93% to 43% and 57%, respectively, whereas treatment with catalase or dimethylthiourea did not affect these arrhythmias. L-NAME (0.1 and 0.3 mg/kg/min) reduced the mortality from 93% to 50% and 43%, respectively. L-NNA (0.3 mg/kg/min) reduced the mortality from 93% to 50%. This reduction by the NO synthase inhibitors was abolished by administration of L-Arg. However, L-Arg blocked neither a small increase in systolic blood pressure nor a decrease in heart rate elicited by the NO synthase inhibitors. The combinated treatment of superoxide dismutase (4300 U/kg/min) with L-NAME (0.3 mg/kg/min) reduced the mortality from 93% to 7%. These results suggest that the genesis of reperfusion-induced arrhythmias observed in this model may be in part due to O2- and NO.
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PMID:Involvement of superoxide and nitric oxide in the genesis of reperfusion arrhythmias in rats. 881 24

The effect of Fasciola hepatica excretory-secretory antigen (ESA) on the proliferative response of spleen mononuclear (SpM) cells of normal rats to stimulation with mitogens has been examined. When ESA was added to normal SpM cells, there was a decrease in the proliferative response to concanavalin A (Con A) or lipo-polysaccharide (LPS) in a dose-dependent manner. The addition of indomethacin, which blocks prostaglandin synthesis, or N omega-nitro-L-arginine methyl ester (L-NAME) a specific inhibitor of nitric oxide (NO) synthase, had no effect on the ability of ESA to suppress the proliferative response to Con A. However, supplementation of the culture media with catalase, which degrades hydrogen peroxide (H2O2) or superoxide dismutase (SOD) to remove superoxide anion (O2), resulted in a restoration of proliferation to Con A. When LPS was used as mitogenic stimulus no inhibitor added to the culture restored the proliferation. These results suggest that H2O2 and O2- are involved in the suppressor phenomenon induced by ESA in the T-cell proliferative events.
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PMID:Inhibition of spleen cell proliferative response to mitogens by excretory-secretory antigens of Fasciola hepatica. 919 51

Inhibition of nitric oxide (NO) synthesis results in coronary vasoconstriction. Using a Langendorff rat heart preparation, we tested the hypothesis that this vasoconstriction is caused by the unopposed effect of the autacoids prostaglandin H2 (PGH2) or thromboxane A2 (TxA2) or both through a mechanism that involves oxygen free radicals. The vasoconstriction induced by NO synthesis inhibition was studied with two different NO synthase inhibitors, N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-monomethyl-L-arginine (L-NMMA). We found that the decrease in coronary flow (CF) induced by L-NAME (from 19.3 +/- 0.9 to 13.2 +/- 0.9 ml/min; p < 0.001) and L-NMMA (from 20.1 +/- 0.4 to 15.0 +/- 0.3 ml/min; p < 0.001) was completely blocked by the cyclooxygenase inhibitor indomethacin. A different cyclooxygenase inhibitor (ibuprofen), a PGH2/TxA2-receptor antagonist (SQ29548), and a TxA2 synthase inhibitor (CGS 13080) also completely abolished the vasoconstrictor effect of L-NAME, suggesting that this vasoconstriction is mediated by TxA2. Two different scavengers of superoxide radical anions (O2-), the enzyme superoxide dismutase (SOD) and a cell-permeable SOD mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), also blocked the vasoconstriction induced by NO synthesis inhibition. In contrast, catalase, which inactivates hydrogen peroxide (H2O2), failed to do so, indicating that O2- is needed for the vasoconstrictor effect of L-NAME, whereas H2O2 is not. To determine whether O2- acts on the conversion of PGH2 to TxA2 or at the receptor or postreceptor level, we studied whether the vasoconstriction induced by exogenous PGH2 or the TxA2 receptor agonist U46619 is blocked by scavengers of O2-. CF decreased by 50% with PGH2 (from 21 +/- 2.1 to 10.6 +/- 5.8 ml/min; p < 0.01), and this decrease was abolished by SOD and Tempol but not catalase. However, SOD had no effect on the vasoconstriction induced by U46619, which decreased CF by 45% (from 17.3 +/- 2.5 to 9.5 +/- 1.8 ml/min; p < 0.01). In addition, PGH2 increased the release of TxB2 (the stable metabolite of TxA2) in the coronary effluent (from 5.1 +/- 1.2 to 136.1 +/- 11.8 pg/ml/min). The release of TxB2 was significantly lower in hearts treated with SOD (76.8 +/- 14.2 pg/ml/min) and CGS (65.7 +/- 13.9 pg/ml/min). We conclude that the coronary vasoconstriction induced by inhibition of NO synthesis is the result of the unopposed effect of the autacoid TxA2 through activation of its receptor, and that O2- is necessary for conversion of PGH2 to TxA2.
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PMID:Autacoids mediate coronary vasoconstriction induced by nitric oxide synthesis inhibition. 938 42

We studied the mechanism of reoxygenation injury of cerebral microvessels in cultured rat brain capillary endothelial cells (BCECs). BCECs were isolated from rat cerebral cortices by a two step enzymatic treatment. The monolayers of BCECs were subjected to anoxia for 20 minutes followed by reoxygenation for 3 hours. Cell damage was assessed by measuring the leakage of intracellular lactic dehydrogenase (LDH). The control group was anoxia/reoxygenated BCECs without any protective reagents. To study the protective effect of free radical scavengers and antioxidants, superoxide dismutase, catalase, deferoxamine, oxypurinol, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) was applied during anoxia/reoxygenation. Thus 7 experimental conditions were established. Lactic dehydrogenase (LDH) leaked from reoxygenated BCECs due to cell membrane damage. This leakage was almost totally suppressed by superoxide dismutase, indicating that reoxygenation injury of BCECs is mediated by superoxide generation. The other scavengers and antioxidants partially suppressed LDH leakage. Reduction of Ca2+ in the culture medium from 1.6 mM to 0.016 mM also suppressed LDH leakage. These results indicate that BCECs subjected to anoxia/reoxygenation become potent generators of superoxide anion, which is thought to be responsible for reoxygenation injury. The superoxide generation partially depends on the xanthine oxidase and cyclooxygenase pathways. As L-NAME partially suppressed LDH leakage peroxynitrite may contribute to reoxygenation injury of BCECs. The extracellular Ca2+ concentration also plays a critical role in the reoxygenation injury of BCECs.
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PMID:The mechanism of free radical generation in brain capillary endothelial cells after anoxia and reoxygenation. 941 71

We investigated the proliferative response to mitogens of spleen mononuclear (Spm) cells from Cryptococcus neoformans-infected rats. We determined reactive oxygen intermediates (ROI) and nitric oxide (NO) production by peritoneal and Spm cells, and evaluated the correlation of the proliferative response with NO and ROI production. The proliferative response of Spm cells from infected rats dramatically decreased at 14 and 21 days postinfection (PI). The unresponsiveness of Spm cells from 14-day infected rats was not abrogated by the addition of L-NAME and AG, indicating that NO is not involved in the antiproliferative response of experimental cells. When SOD, catalase, and indomethacin were added to the cultures, the suppression was still observed, indicating that ROI and prostaglandins are not involved in the unresponsiveness of lymphocytes. The proliferative response of lymphocytes from 14-day infected rats was significantly improved when cultures were made in the presence of Con A and exogenous IL-2. Additionally, a purified T-rich fraction from infected rats cultured with control macrophages recovered the normal proliferative response. This result indicates that macrophages from infected rats mediate the unresponsiveness of lymphocytes, probably by reducing the ability of lymphocytes to secrete IL-2.
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PMID:Lack of involvement of nitric oxide in the macrophage-mediated inhibition of spleen cell proliferation during experimental cryptococcosis. 943 93

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