American Journal of Physiology-Gastrointestinal and Liver Physiology, 1994
Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal format... more Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentra...
Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 mal... more Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0·03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0·004). A shorter ischaemic period also reduced the number of lesions (P = 0·02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P <0·05).
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1987
The gastrointestinal epithelium is continuously exposed to reactive oxygen metabolites that are g... more The gastrointestinal epithelium is continuously exposed to reactive oxygen metabolites that are generated within the lumen. In spite of this exposure, the healthy epithelium appears unaffected, suggesting efficient mechanisms for protection against these potentially cytotoxic oxidants. The objective of this study is to characterize the interaction between purified gastric mucin and hydroxyl radicals generated from the interaction between ferric iron and ascorbic acid. We found that both native and pronase-treated mucin effectively scavenged hydroxyl radical and that the scavenging properties were not significantly different. The effective concentration of mucin required for a 50% reduction in malondialdehyde production was approximately 10 mg/ml for both native and pronase-treated mucin. In addition, the iron-ascorbic system produced a dramatic decrease (greater than 50%) in the specific viscosity of mucin that was inhibited by catalase, deferoxamine, and mannitol. Superoxide dismut...
ABSTRACT Sulphasalazine is widely used in the treatment of inflammatory bowel disease. Its exact ... more ABSTRACT Sulphasalazine is widely used in the treatment of inflammatory bowel disease. Its exact mode of action is unclear, but experimental evidence suggests that the active moiety, 5-aminosalicylic acid (5-ASA), modulates all or most of the functions of neutrophils during acute inflammation. These comprise adhesion to vascular endothelium, migration through the vessel wall in response to a chemotactic gradient, and the release of cytotoxic oxidants and proteases. In vitro, 5-ASA has been shown to reduce both neutrophil adhesion and leukotriene B4-mediated chemotaxis. It also provides significant protection against neutrophil-mediated increases in mucosal permeability induced by naturally occurring inflammatory mediators such asN-formyl-methionine-leucine-phenylalanine (fMLP). Which specific neutrophil function is modulated by 5-ASA to provide the latter effect remains unclear, but there is considerable evidence to indicate that it may both scavenge neutrophil-derived oxidants and inhibit their generation. Although such experimental evidence suggests that 5-ASA acts by modulation of neutrophil functions in patients with IBD, this remains speculation. Additional work is needed to define more clearly the therapeutic significance of the neutrophilic actions of 5-ASA.
There are several pathophysiologic conditions in which intestinal inflammation is associated with... more There are several pathophysiologic conditions in which intestinal inflammation is associated with enhanced mucosal permeability, fluid loss, and epithelial cell injury. The objective of this study was to determine the effects of polymorphonuclear leukocyte (PMN)-derived oxidants on ileal mucosal permeability in vivo as well as electrolyte transport and epithelial cell viability in vitro. Using blood-to-lumen clearance of [51Cr]EDTA as a measure of mucosal permeability, we found that luminal perfusion with hydrogen peroxide (H2O2), hypochlorous acid (HOCl), or monochloramine (NH2Cl) produced a dose-dependent increase in mucosal permeability. Perfusion with 0.1 mM, 0.5 mM, and 1.0 mM oxidant produced a 2 +/- 1, 5 +/- 2, and 11 +/- 5-fold increase in mucosal permeability for H2O2, a 2 +/- 1, 8 +/- 3, and 36 +/- 12-fold increase for HOCl, and a 3 +/- 1, 11 +/- 2, and 30 +/- 7-fold increase for NH2Cl. Taurine monochloramine (TauNHCl) was ineffective in enhancing the blood-to-lumen clearance of [51Cr]EDTA. Furthermore, 0.01 mM and 0.1 mM NH2Cl and H2O2 produced significant increases in short-circuit current across rat ileum in vitro, whereas HOCl and TauNHCl were without effect. Tissue resistance and potential difference were not altered, suggesting that NH2Cl, HOCl, and H2O2 were not cytotoxic under these conditions. Cultured intestinal epithelial cells exposed to NH2Cl and HOCl were injured in a dose-dependent manner in vitro, whereas H2O2 and Tau NHCl were nontoxic. Taken together, our data suggest that PMN-derived oxidants may mediate the enhanced mucosal permeability, electrolyte transport, and epithelial cell injury associated with acute inflammation of the bowel.
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1994
Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal format... more Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentra...
Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 mal... more Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0·03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0·004). A shorter ischaemic period also reduced the number of lesions (P = 0·02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P <0·05).
American Journal of Physiology-Gastrointestinal and Liver Physiology, 1987
The gastrointestinal epithelium is continuously exposed to reactive oxygen metabolites that are g... more The gastrointestinal epithelium is continuously exposed to reactive oxygen metabolites that are generated within the lumen. In spite of this exposure, the healthy epithelium appears unaffected, suggesting efficient mechanisms for protection against these potentially cytotoxic oxidants. The objective of this study is to characterize the interaction between purified gastric mucin and hydroxyl radicals generated from the interaction between ferric iron and ascorbic acid. We found that both native and pronase-treated mucin effectively scavenged hydroxyl radical and that the scavenging properties were not significantly different. The effective concentration of mucin required for a 50% reduction in malondialdehyde production was approximately 10 mg/ml for both native and pronase-treated mucin. In addition, the iron-ascorbic system produced a dramatic decrease (greater than 50%) in the specific viscosity of mucin that was inhibited by catalase, deferoxamine, and mannitol. Superoxide dismut...
ABSTRACT Sulphasalazine is widely used in the treatment of inflammatory bowel disease. Its exact ... more ABSTRACT Sulphasalazine is widely used in the treatment of inflammatory bowel disease. Its exact mode of action is unclear, but experimental evidence suggests that the active moiety, 5-aminosalicylic acid (5-ASA), modulates all or most of the functions of neutrophils during acute inflammation. These comprise adhesion to vascular endothelium, migration through the vessel wall in response to a chemotactic gradient, and the release of cytotoxic oxidants and proteases. In vitro, 5-ASA has been shown to reduce both neutrophil adhesion and leukotriene B4-mediated chemotaxis. It also provides significant protection against neutrophil-mediated increases in mucosal permeability induced by naturally occurring inflammatory mediators such asN-formyl-methionine-leucine-phenylalanine (fMLP). Which specific neutrophil function is modulated by 5-ASA to provide the latter effect remains unclear, but there is considerable evidence to indicate that it may both scavenge neutrophil-derived oxidants and inhibit their generation. Although such experimental evidence suggests that 5-ASA acts by modulation of neutrophil functions in patients with IBD, this remains speculation. Additional work is needed to define more clearly the therapeutic significance of the neutrophilic actions of 5-ASA.
There are several pathophysiologic conditions in which intestinal inflammation is associated with... more There are several pathophysiologic conditions in which intestinal inflammation is associated with enhanced mucosal permeability, fluid loss, and epithelial cell injury. The objective of this study was to determine the effects of polymorphonuclear leukocyte (PMN)-derived oxidants on ileal mucosal permeability in vivo as well as electrolyte transport and epithelial cell viability in vitro. Using blood-to-lumen clearance of [51Cr]EDTA as a measure of mucosal permeability, we found that luminal perfusion with hydrogen peroxide (H2O2), hypochlorous acid (HOCl), or monochloramine (NH2Cl) produced a dose-dependent increase in mucosal permeability. Perfusion with 0.1 mM, 0.5 mM, and 1.0 mM oxidant produced a 2 +/- 1, 5 +/- 2, and 11 +/- 5-fold increase in mucosal permeability for H2O2, a 2 +/- 1, 8 +/- 3, and 36 +/- 12-fold increase for HOCl, and a 3 +/- 1, 11 +/- 2, and 30 +/- 7-fold increase for NH2Cl. Taurine monochloramine (TauNHCl) was ineffective in enhancing the blood-to-lumen clearance of [51Cr]EDTA. Furthermore, 0.01 mM and 0.1 mM NH2Cl and H2O2 produced significant increases in short-circuit current across rat ileum in vitro, whereas HOCl and TauNHCl were without effect. Tissue resistance and potential difference were not altered, suggesting that NH2Cl, HOCl, and H2O2 were not cytotoxic under these conditions. Cultured intestinal epithelial cells exposed to NH2Cl and HOCl were injured in a dose-dependent manner in vitro, whereas H2O2 and Tau NHCl were nontoxic. Taken together, our data suggest that PMN-derived oxidants may mediate the enhanced mucosal permeability, electrolyte transport, and epithelial cell injury associated with acute inflammation of the bowel.
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Papers by Christoph Ritter