[The glutathione system in the human gastrointestinal tract. Significance and influence of clinical factors].
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Biomedical subjects
Publications and source records attributed to I Morgenstern.
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The present study was performed to evaluate the levels of the amino thiols cysteine, homocysteine, and glutathione in the colonic mucosa of patients with various intestinal diseases, especially chronic inflammatory bowel disease. Colonic biopsies of macroscopically normal mucosa out of a proximal and distal segment were collected from 187 patients with various intestinal diseases. Protein was assayed in duplicate by the method of Lowry et al (1951), using bovine serum albumin as standard. Total glutathione, cysteine, and homocysteine were quantified by high performance liquid chromatography (HPLC) with fluorescent detection. Only in patients with inflammatory bowel disease were the homocysteine levels in the large bowel mucosa significantly elevated compared with the concentrations in patients with normal mucosa. No significant differences were seen for glutathione and cysteine concentrations in colonic mucosa among the different groups of diseases. No correlation was found between the age of the patients and levels of the amino thiols investigated. GSH content and concentrations of cysteine and homocysteine were similar in male and female subjects. In our study markedly elevated concentrations of homocysteine in the colonic mucosa were observed in patients suffering from ulcerative colitis and Crohn's disease. This finding has been reported already in the literature for plasma homocysteine levels. Increased homocysteine levels in the colonic mucosa and plasma of patients with inflammatory bowel disease may play a role in the pathogenesis of Crohn's disease and ulcerative colitis.
BACKGROUND: Glutathione (GSH) and the cytosolic glutathione S-transferases (GSTs) protect the gastrointestinal mucosa against the toxic effects of a wide variety of compounds, such as reactive oxygen species and electrophiles. AIMS: We wished to investigate the distribution along the upper gastrointestinal mucosa and the influence of clinical variables on components of the GSH system to learn more about factors which control its cytoprotective properties. METHODS: Antral and duodenal biopsies of normal appearing mucosa were collected from 202 patients (104 males, 98 females; mean age 62 years) undergoing upper gastrointestinal endoscopy. GSH content was examined by high pressure liquid chromatography, GST enzyme activity by 1-chloro-, 2, 4-dinitrobenzene conjugation, and levels of the GST classes alpha, pi, and theta by western blot. RESULTS: GSH, GST enzyme activity, and GST alpha levels were significantly lower (p<0.001) in the antrum than in the duodenum (antrum v duodenum: GSH 23.0 (0.7) v 35.0 (1.0) nmol/mg protein; GST activity 626 (19) v 832 (22) nmol/mg protein/min; GST alpha 4.5 (0.5) v 20.0 (0.7) microg/mg protein) while GST pi content was significantly higher (p<0.001) in antral than in duodenal biopsies (16.5 (0.7) v 11.2 (0.5) microg/mg protein). Antral GSH and GST activities were markedly lower in males compared with females (p<0.01). Some drugs (cisapride, diuretics, cortisol, analgesics) increased GST pi and GST alpha content but cytostatic drugs suppressed duodenal GST activity. High intake (>3 days a week) of vegetables enhanced duodenal GST alpha and GST pi and high intake of fruits the antral content of GST theta 1. CONCLUSIONS: The gastrointestinal GSH system represents the antitoxic barrier of the mucosa; its activity is influenced by localisation, sex, and drugs, and its enzymes are stimulated by a high intake of vegetables and fruits.
A problem often considered in operations research and computational physics is the traveling salesman problem, in which a traveling salesperson has to find the shortest closed tour between a certain set of cities. This problem has been extended to more realistic scenarios, e.g., the "real" traveling salesperson has to take rush hours into consideration. We will show how this extended problem is treated with physical optimization algorithms. We will present results for a specific instance of Reinelt's library TSPLIB95, in which we define a zone with traffic jams in the afternoon.
A comparative analysis was performed of the phenotype and function of peripheral blood leukocytes of two age-matched cohorts of industrial workers in chemical plants, one of which was exposed occupationally to high concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Median actual TCDD burdens were 116 ng/kg and 4 ng/kg, respectively. The phenotype analysis of peripheral blood mononuclear cells (PBMC) revealed no significant differences in the proportions of CD3, CD4, or CD8+ T lymphocytes, of CD16+ natural killer cells, and of CD19+ B lymphocytes. However, in PBMC of the TCDD-exposed workers; the proportion of CD8+ memory T cells (CD45R0+) was significantly higher, and that of lymphocytes with naive phenotype (CD45RA+) was significantly lower than in PBMC of the control group. Polyclonal and antigen-specific T-cell activation was assessed in parallel in isolated PBMC as well as in diluted whole blood cultures. In both culture systems the polyclonally stimulated cytokine release did not differ significantly between the two cohorts; however, we found a significantly reduced interferon gamma release in diluted whole blood cultures but not in isolated PBMC cultures of the TCDD-exposed cohort when we performed an antigen-specific T-cell stimulation with tetanus-toxoid. Therefore, we propose that exposure of individuals to high doses of TCDD can partially impair in the "blood milieu" those T-cell/monocyte interactions that are essential for antigen-specific T-cell responses, whereas isolated PBMC of the same donors appear functionally less affected.
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