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W E Roediger

Publications and source records attributed to W E Roediger.

At least 37 records · Page 2Linked to original sources
PubMed1993

Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis.

BACKGROUND: Mercaptides (sodium hydrogen sulfide and sodium methanethiol) and mercapto-fatty acid (sodium mercaptoacetate) are reducing agents that help to maintain anaerobic conditions in the colonic lumen. The metabolic effect of these agents on n-butyrate and glucose oxidation in human colonocytes is unknown. METHODS: Isolated human colonocytes were prepared from 31 colectomy specimens, and generation of oxidative metabolites from [1-14C]n-butyrate and [6-14C]glucose was measured in the presence and absence of reducing agents. Injury to cells was judged by diminished production of metabolites. RESULTS: The injurious action of mercaptides at all sites of the colon was of the order of sodium hydrogen sulfide > methanethiol > mercaptoacetate. Significant inhibition of n-butyrate (< 0.005) but not glucose oxidation was observed with sodium hydrogen sulfide in the ascending colon, splenic flexure, and rectosigmoid region. Hydrogen sulfide more significantly inhibited fatty acid oxidation in the rectosigmoid than in the ascending colon (P < 0.02). CONCLUSIONS: Metabolic effects of sodium hydrogen sulfide on butyrate oxidation along the length of the colon closely mirror metabolic abnormalities observed in active ulcerative colitis, and the increased production of sulfide in ulcerative colitis suggests that the action of mercaptides may be involved in the genesis of ulcerative colitis.

Colitis, Ulcerative↗
PubMed1993

Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis?

1. Isolated colonic epithelial cells of the rat were incubated for 40 min with [6-14C]glucose and n-[1-14C]butyrate in the presence of 0.1-2.0 mmol/l NaHS, a concentration range found in the human colon. Metabolic products, 14CO2, acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells was judged by diminished production of metabolites. 2. Oxidation of n-butyrate to CO2 and acetoacetate was reduced at 0.1 and 0.5 mmol/l NaHS, whereas glucose oxidation remained unimpaired. At 1.0-2.0 mmol/l NaHS, n-butyrate and glucose oxidation were dose-dependently reduced at the same rate. 3. To bypass short-chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation, ketogenesis from crotonate was measured in the presence of 1.0 mmol/l NaHS. Suppression by sulphide of ketogenesis from crotonate (-10.5 +/- 6.1%) compared with control conditions was not significant, whereas suppression of ketogenesis from n-butyrate (-36.00 +/- 5.14%) was significant (P = < 0.01). Inhibition of FAD-linked oxidation was more affected by NaHS than was NAD-linked oxidation. 4. L-Methionine (5.0 mmol/l) significantly redressed the impaired beta-oxidation induced by NaHS. Methionine equally improved CO2 and ketone body production, suggesting a global reversal of the action of sulphide. 5. Sulphide-induced oxidative changes closely mirror the impairment of beta-oxidation observed in colonocytes of patients with ulcerative colitis. A hypothesis for the disease process of ulcerative colitis is that sulphides may form persulphides with butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal inflammation.

Animals↗
PubMed1993

Does exclusion of enteral lipid assist remission in Crohn's disease?

Based on the improvement of Crohn's disease (CD) with elemental diets, we treated a patient with recurrent stenosing disease using prednisolone and drastic reduction of oral lipid intake. Complete symptomatic and good radiological improvement took place. A newly proposed hypothesis for CD suggests that enteral lipids together with certain luminal bacterial fragments become strongly antigenic to produce an inflammatory reaction analogous to the adjuvant response. Because of the apparent success of dietary lipid exclusion in this patient, we suggest that it be considered as a future option for management of acute CD.

Adult↗
PubMed1992

Lipogenesis from n-butyrate in colonocytes. Action of reducing agent and 5-aminosalicylic acid with relevance to ulcerative colitis.

Cell membranes of colonic epithelial cells (CEC) in ulcerative colitis show structural abnormalities which are specific to the disease and which suggest impaired lipogenesis in CECs. Lipogenesis from [1-14C]-n-butyrate, the chief oxidative fuel of colonic epithelial cells, was measured in isolated CECs under control conditions, with or without glucose and in the presence of mercaptoacetate, a major reducing agent in the colonic lumen. Glucose significantly (p < 0.01) stimulated lipogenesis from [1-14C]-butyrate which was reversed by 5 mM mercaptoacetate. Mercaptoacetate significantly diminished CEC thiolase activity (EC 2.3.1.9). 5-Aminosalicylic acid reversed the adverse effects of mercaptoacetate in the saponifiable fraction of extracted lipids. Changes in lipogenesis due to colonic luminal reducing agents would affect the barrier function of CECs a feature relevant to the disease process of ulcerative colitis.

Aminosalicylic Acids↗
PubMed1991

Primary squamous carcinoma of the liver: clinical and histopathological features.

A case of primary squamous carcinoma of the liver is analysed in the light of 21 previously reported cases. Symptoms of abdominal pain, weight loss and intermittent fever were in keeping with those most frequently recorded for the tumour type. Histopathological evaluation suggested metaplastic origin from a cholangiocarcinoma. A squamous carcinoma found in the liver need not reflect metastatic spread and primary tumours can be resected if well localized.

Carcinoma, Squamous Cell↗
PubMed1991

Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis.

Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein. In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate. The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags. The incubation of paracetamol with colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE) value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide. Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4.2 (0.8) nmol/hour. Sulphation was significantly impaired (p less than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour). Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects. Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen.

Acetaminophen↗
PubMed1991

A new hypothesis for the aetiology of Crohn's disease--evidence from lipid metabolism and intestinal tuberculosis.

The stimulus for the immune response in Crohn's disease is unknown. In each of 19 cases of Crohn's disease evaluated by electron microscopy, epithelial cells of the ileum contained phagolysosomes with lamellar layers of lipid. These structures, now termed R or reactant bodies, are the proffered antigenic stimulus. They are proposed to be an amalgam of lipid (cholesterol esters, or phospholipids) and bacterial fragments (mycoplasma, mycobacteria or streptococci), which in combination are hypothesized to produce a powerful immunological response analogous to the adjuvant effect. For disease expression to occur, lipids and specific bacterial populations are needed in the bowel lumen. These factors may account for the success of elemental diets that are low in fat in the treatment of Crohn's disease and for the regional distribution of disease along the intestinal tract.

Adjuvants, Immunologic↗
PubMed1990

The starved colon--diminished mucosal nutrition, diminished absorption, and colitis.

Nutrition of colonic epithelial cells is mainly from short chain fatty acids (SCFAs) produced by bacterial fermentation in the colonic lumen. n-Butyrate contributes more carbon of oxidation to epithelial cells than glucose or glutamine from the vasculature. Incomplete starvation of colonic epithelial cells through lack of luminal SCFAs leads, in the short term, to mucosal hypoplasia with either diminished absorption or diarrhea. A chronic lack of SCFAs or complete organ starvation in conjunction with other factors leads to nutritional colitis, either "diversion colitis" or "starvation colitis." Whether predominantly diarrhea or colitis develops in mucosal malnutrition appears to depend upon the severity and duration of starvation. Ulcerative colitis may be classified as a nutritional colitis in that colonic epithelial cells are unable to utilize SCFAs reflecting epithelial starvation despite abundant SCFAs.

Animals↗
PubMed1990

Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis?

Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells.

Animals↗
PubMed1990

Selective reduction of fatty acid oxidation in colonocytes: correlation with ulcerative colitis.

Attempts were made to define which fatty acid (2:0 to 18:1) was optimally oxidized by isolated colonocytes (colonic epithelial cells) and to select inhibitors of fatty acid oxidation which would be analogous in their action to the inhibition of fatty acid oxidation observed in colonocytes involved with ulcerative colitis. Isolated colonic epithelial cells of Sprague-Dawley rats were used with 2-mercaptoacetate, dichloroacetate, 3-mercaptopropionate, 4-mercaptobutyrate, 4-sulfatebutyrate, 2-bromobutyrate, sulfite ions and nitrite ions. n-Butyrate (4:0) was maximally oxidized to CO2 and ketone bodies (mean value 5.46 mumols/min/g dry wt). Oxidation of butyrate to CO2 was diminished by 2-bromobutyrate, sulfite ions and all mercapto fatty acids. Both fatty acid oxidation and glucose oxidation were significantly inhibited by 2-bromobutyrate, while mercapto fatty acids and sulfite inhibited fatty acid oxidation (p less than 0.01) without significantly changing glucose oxidation. Observation with 2-mercaptoacetate and sulfite correlate with early changes of fatty acid oxidation observed in cases of ulcerative colitis, and warrant further study with isolated colonocytes of man.

3-Mercaptopropionic Acid↗
PubMed1990

The effects of enterotoxins and short-chain fatty acids on water and electrolyte fluxes in ileal and colonic loops in vivo in the rat.

The effect of cholera toxin (CT) and Escherichia coli heat-stable enterotoxin (ST) on the ileum and colon was examined in vivo in the rat in an attempt to clarify the effects of enterotoxins on colonic mucosa and to determine if these effects were influenced by short-chain fatty acids (SCFA). Both CT and ST induced similar changes in water and electrolyte fluxes, and the magnitude of these changes in loops of colon was similar to that observed in loops of ileum. The addition of luminal SCFA, acetate, propionate and butyrate did not influence the effect of either toxin in loops of ileum. However, in loops of colon exposed to CT, luminal butyrate (40 mM) largely reversed the effect of CT by converting net water secretion (mean +/- SE, -363 +/- 154 nl.cm-2.min-1) to net water absorption (470 +/- 194 nl.cm-2.min-1) and by significantly reducing the net secretion of sodium ions. In loops of colon exposed to ST, similar effects were observed although net water secretion (-784 +/- 114 nl.cm-2.min-1) was only partially reversed by butyrate (-318 +/- 102 nl.cm-2.min-1). In contrast to butyrate, acetate and propionate did not influence changes in colonic fluxes of water and sodium induced by enterotoxins. Oxidation of butyrate and glucose was observed to be depressed in colonocytes pre-exposed to CT but not to ST. In this model, colonic secretion induced by enterotoxins is similar to that observed in the ileum but differs from ileal secretion in its modulation by luminal butyrate.

Animals↗
PubMed1990

New directions in the aetiology of ulcerative colitis.

The causative factors of ulcerative colitis remain unknown. Cellular biochemistry has revealed altered oxidative metabolism, membrane function and synthesis of mucus in colonic epithelial cells in the early stages of ulcerative colitis. Immune studies have highlighted more precise changes in neutrophil and macrophage function in cells of the lamina propria while microbiological evidence has shown a dysbiosis of colonic bacteria related to entero-adhesion, release of bacterial peptides and formation of secondary bacterial metabolites (mercapto fatty acids). A precise sequence of pathological events still needs to be established to account for an acute attack of ulcerative colitis.

Bacterial Physiological Phenomena↗
PubMed1989

Nitrite and nitrate levels in ileostomy effluent: effect of dietary change.

1. Nitrite and nitrate levels were measured in samples from ileostomy bags or stomal samples of thirty-one ileostomists (twenty-two ulcerative colitis, nine Crohn's disease), 14-16 h after ingestion of a conventional meal or a meal containing a high content of nitrite and nitrate. 2. Ileostomy samples were decolourized with barium chloride, sodium sulphate and charcoal. Nitrite was determined spectrophotometrically by the Griess reaction and nitrate determined as nitrite after reduction with nitrate reductase (EC 1.7.99.4) in the presence of sodium formate. The mean percentage recovery from twenty-six spiked samples was 101.9 (SE 3.5)% for nitrite and 82.9 (SE 3.3)% for nitrate. 3. Ileostomy bag samples were obtained in twenty-nine cases of which ten had measurable nitrite (median 0, range 0-20.7 nmol/g) on a conventional meal compared with twenty-three cases (median 7.2, range 0-31.1 nmol/g) on the test meal (P less than 0.01). Nitrate levels were measurable in sixteen (median 6.7, range 0-48.2 nmol/g) after a conventional meal compared with twenty-one (median 20.5, range 0-53.2 nmol/g) after the test meal (P less than 0.01). 4. Stomal fresh-catch samples were obtained in twenty-four cases: combined nitrate and nitrite was higher in eighteen, lower in four and unchanged in two subjects after the test meal (P less than 0.05). 5. The type of foodstuff ingested can significantly alter measurable levels of nitrite-nitrate in the distal ileum and is one factor determining nitrite-nitrate input into the proximal colon.

Diet↗