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Biomedical subjects

W E Roediger

Publications and source records attributed to W E Roediger.

At least 55 records · Page 3Linked to original sources
PubMed1989

Estimation of phenolic conjugation by colonic mucosa.

Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 1.5 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3.86 (0.66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of 42.9 (3.9) mumol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium. Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa.

Acetaminophen↗
PubMed1989

Assessment of salicylate derivatives for potential use in ulcerative colitis: proposal for a new action of 5-aminosalicylic acid?

The therapeutic efficacy of salicylate drugs for ulcerative colitis in vivo is related to the capacity of each drug to suppress fatty acid oxidation in colonocytes in vitro. The suppression index of fatty acid oxidation (SIFO) was assessed with 17 salicylate drugs of either known or unknown therapeutic efficacy. The high SIFO value of 5-aminosalicylic acid (5-ASA) was reduced to zero when the amino group was replaced with a methyl, nitro, hydroxyl or bromine group. The SIFO of 3-ASA was dose-related and 2- to 3-fold greater than the SIFO of 5-ASA. The antioxidants methyl- or propyl-4-hydroxybenzoate have a high SIFO, but show a 'toxic' action towards colonocytes not observed with 3-ASA, 4-ASA or 5-ASA. A new cellular action proposed for 5-ASA is that acetylation of the amino group of 5-ASA in colonocytes releases free CoA countering sequestration of CoA observed in epithelial cells during active colitis.

Aminosalicylic Acids↗
PubMed1989

Short chain fatty acids as metabolic regulators of ion absorption in the colon.

Between 50%-80% of sodium absorption in the colonic mucosa is dependent upon CO2 generation from SCFAs derived from the colonic lumen. Lumenal starvation leading to diminished SCFAs levels in the colon greatly reduce the absorptive capacity of the colonic mucosa. Mechanisms whereby SCFAs regulate sodium absorption in the colon include 1) an enzyme induced adaptive regulation of SCFA-oxidation in colonocytes, 2) a flexible CO2 supply from SCFA depending upon stimulation or suppression of fatty acid oxidation., 3) the variable sidedness of Na(+)-H+ and Cl(-)-HCO3- exchange pumps in colonic epithelial cells, and 4) colonic epithelial cell membrane synthesis from SCFAs. Precise details of these regulatory mechanisms need to be elucidated by further experimental investigation.

Animals↗
PubMed1988

What sequence of pathogenetic events leads to acute ulcerative colitis?

The etiology of ulcerative colitis remains unresolved despite new immunologic, biochemical, and microbiologic observations made in this disease. A sequence of pathogenetic events has been adduced from abnormalities reported from human and experimental colitis with the express purpose of establishing priority of factors that may lead to an attack of acute ulcerative colitis. The presence of undefined bacterial metabolites in the colonic lumen causing specific breakdown of fatty acid oxidation in colonic epithelial cells is proposed to be the initiating event of the disease process that leads to an immune response and eicosanoid response perpetuating epithelial cell damage. The proposals embody the thesis that primary metabolic damage to colonocytes determines the clinical and pathologic manifestations of ulcerative colitis.

Acute Disease↗
PubMed1988

Role of nitrite and nitrate as a redox couple in the rat colon. Implications for diarrheal conditions.

Colonic levels of nitrite and circulating levels of nitrate are elevated in subjects with chronic diarrhea. The role of colonic epithelial cells in oxidation-reduction of nitrite and consequent control of nitrite and nitrate levels is unknown. Isolated rat colonocytes and isolated loops of colon were used to study oxidation and reduction of nitrate and nitrite. Colonocytes oxidized nitrite to nitrate at a rate of 162 +/- 33 nmol/min.g (dry wt) (n = 6) over 0-20 min, a value increased by addition of 5 mM glucose and 1 mM nicotinamide adenine dinucleotide (p = less than 0.01), but not altered by antibiotics. Nitrite oxidation correlated linearly with the dry weight of isolated colonocytes (r = 0.92), indicating a cellular reaction. Nitrite was absorbed at a rate of 0.28 nmol/min.cm2 (n = 9) from the colonic lumen, which reflected 74% absorption of the available nitrite. Of the absorbed nitrite, 14.3% reappeared in the colonic lumen as nitrate. Colonocytes may be important in oxidizing nitrite to nitrate, thus preventing excess nitrite from entering into the circulation and returning some nitrate to the colonic lumen for respiration by anaerobic bacteria. The interaction of nitrites and colonocytes deserves further study with regard to the oxidation-reduction of nitrite and to the development of colonic neoplasia in chronic diarrheal conditions.

Animals↗
PubMed1987

Effect of luminal or circulating nitrite on colonic ion movement in the rat.

The disposition of intravenously or luminally administered nitrite across the colonic mucosa and its effect on ion movement into or from the colon was assessed in anesthetized Porton rats using the isolated colon instilled either with sodium chloride (120 mM) or sodium chloride (80 mM) with sodium butyrate (40 mM). Ionic changes in the colon after intravenous injection of 10 mumol NaNO2 were compared with those occurring after injection of 10 mumol NaCl. After intravenous administration of nitrite, both nitrite and nitrate appeared in the colonic instillate in a ratio of 1:1. Nitrite increased chloride absorption (110%) and bicarbonate production (20%) when 40 mM butyrate was included in the instillate. Net sodium absorption, measured in the whole colon, was unchanged. Intravenous nitrite had no effect on ionic movement in the absence of butyrate. When NaNO2 (100 microM) was included luminally with the sodium chloride-butyrate instillate, bicarbonate production rate increased (25%), but sodium and chloride absorption were unaffected. Nitrite concentration in the instillate decreased during the 40-min experimental period at a rate of 0.275 nmol X min-1 X cm-2, and nitrate appeared at a rate of 0.037 nmol X min-1 X cm-2. We conclude that nitrate stimulates bicarbonate production in the colon, probably by stimulating the oxidation of butyrate, the main source of CO2 generation by the colonic mucosa.

Animals↗
PubMed1986

Metabolic basis of starvation diarrhoea: implications for treatment.

The terminal diarrhoea of kwashiorkor or marasmus may be due largely to malnutrition of the intestinal epithelium. Experimental data suggest that the first days of treatment should be devoted to restoration of epithelial function, to prevent worsening of diarrhoea by osmotic food loads.

Amino Acids↗
PubMed1986

Specific metabolic effect of sodium nitrite on fat metabolism by mucosal cells of the colon.

The effect on the mucosa of sodium nitrite that enters the colon from the ileum or transmucosally from the circulation is unknown. Isolated colonic mucosal cells and Roux-en-Y colostomies were used to test whether high doses of sodium nitrite (5-40 mM) had any harmful histological or inhibitory metabolic actions on the mucosa. Luminal instillation of 40 mM NaNO2 (3 ml/24 hr) for 7-14 days produced no microscopic changes in the mucosa either of damage (ulceration, mucus cell depletion) or of new growth (dysplasia, neoplasia). Beta oxidation of bacterial fatty acids (n-butyrate) by colonic epithelial cells in rat and man was enhanced by 50% (P less than 0.001) with 10 mM NaNO2, while oxidation of glucose and amino acid (proline) was not affected. Sodium nitrite significantly depressed ketogenesis (P less than 0.001) by the colonic mucosa of rat and man. In conclusion, sodium nitrite in the presence of bacteria has no damaging effect on the colonic mucosa but causes selective stimulation of fatty acid oxidation in the colonic mucosa of rat and man.

Acetoacetates↗
PubMed1986

Thickening of pelvic fascia in carcinoma of the rectum. Perirectal fascia or Waldeyer's fascia?

Computed tomography (CT) scan of the pelvis unreliably detects metastases to lymph nodes from rectal carcinoma. Alternative features of tumor spread visualized on pelvic CT scan may aid preoperative evaluation. Two patients in a series had thickened perirectal fascia due to tumor involvement. The perirectal fascia was recently described by others from CT scans of the pelvis. The extent of the perirectal fascia shown on CT scan correlated with descriptions of Waldeyer's fascia that stress its expansive nature enveloping internal iliac vessels and lymphatics. The perirectal fascia and Waldeyer's fascia are proposed to be synonymous, and lymphangitis carcinomatosa is proposed to account for a thickened perirectal/Waldeyer's fascia in rectal carcinoma. The fascial thickening also is found in inflammatory pathology of the rectum (probably due to inflammatory lymphangitis), and fascial thickening on pelvic CT scan is thus not an absolute indicator of carcinoma.

Fascia↗
PubMed1986

Anion control of sodium absorption in the colon.

The regulatory functions of anions in colonic absorption of sodium are unknown. Absorption of sodium ions was assessed with chloride, butyrate, nitrite, sulphate and oxalate anions in segments of proximal/distal colon and in defunctioned colon. Efficiency of sodium absorption was related to availability of CO2 in mucosal cells: CO2 availability was enhanced (P less than 0.01) by sodium nitrite or diminished (P less than 0.01) in defunctioned colon. Sodium nitrite stimulated absorption of sodium in the distal colon where bicarbonate secretion predominated and n-butyrate stimulated absorption of sodium in the proximal colon where hydrogen ion secretion predominated. Sodium absorption was very significantly diminished (P less than 0.01) in defunctioned colon. Results indicate that sodium absorption in the colon is both a double anion exchange system as well as cation/anion co-transport. Anions act differently on sodium absorption along the length of the colon and prolonged lack of anions plays a part in sodium malabsorption of the defunctioned colon.

Absorption↗
PubMed1986

Detectable colonic nitrite levels in inflammatory bowel disease--mucosal or bacterial malfunction?

In the healthy colon, sodium nitrite stimulates mucosal metabolism of short-chain fatty acids and absorption of ions, both functions that are impaired in the mucosa of patients with ulcerative colitis (UC). To assess the role of nitrite in colonic inflammatory disease, sodium nitrite was measured in rectal dialysate of 49 subjects (18 controls, 23 UC and 8 other colitis). None of the control or quiescent UC patients had measurable levels of nitrite while 78% of patients with acute UC and 38% of patients with other colitis had measurable nitrite levels (acute UC vs. other colitis chi 2 = 5.555, p less than 0.02). Functional activity of the colonic mucosa, judged by bicarbonate output, was impaired in all subjects with measurable nitrite levels in UC. Detection of nitrite in acute colitis suggests impaired oxidation of nitrite to nitrate in the colonic mucosa or impaired luminal reduction of nitrite to NH4 by bacteria.

Ammonia↗
PubMed1986

Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation.

There is some evidence that failure of fatty acid or beta-oxidation in the epithelium of the colonic mucosa is associated with the development of ulcerative colitis. We tested the hypothesis that inhibition of fatty acid oxidation in the colonic mucosa of the rat reproduces the histological, clinical and biochemical lesions of acute ulcerative colitis of man. A specific inhibitor of beta-oxidation, sodium 2-bromo-octanoate, was instilled rectally for 5 days or exposed to isolated colonic epithelial cells which were subsequently tested for their ability to beta-oxidize n-butyrate. Weight loss, bloody diarrhoea and histological lesions occurred with 2-bromo-octanoate treated rats but not control animals. Ketogenesis and 14CO2 production was inhibited by 2-bromo-octanoate. Of 12 animals mucosal ulceration developed in six out of eight surviving animals and in all four animals that died. Ulceration, mucus cell depletion, vessel dilatation and increases of inflammatory cells were the most prominent histological changes. Present observations indicate that inhibition of beta-oxidation produces acute colitis and suggests that inhibition of beta-oxidation is primary rather than secondary in the genesis of ulcerative colitis. A search for agents producing such biochemical lesions in man should be undertaken.

Animals↗
PubMed1984

Sodium absorption with bacterial fatty acids and bile salts in the proximal and distal colon as a guide to colonic resection.

Rates of sodium absorption in the presence of bacterial fatty acids and bile salts are unknown along the length of the colon. Such information may guide resection of colon with a view to leaving colon most optimal for ion absorption. Absorption of sodium and permeability of the colonic mucosa to 51Cr EDTA was measured in the proximal (PC) and distal colon (DC) instilled with NaCl (120 mM), n-butyrate (40 mM) and chenodeoxycholic acid (1 or 2 mM) in varying combinations. Sodium absorption in the PC was 123.6 +/- 19 (nmoles/min/cm2)(n = 7) with saline alone and was doubled (P less than .001) when 40 mM n-butyrate replaced chloride anions. Sodium absorption in the DC with saline alone was 106.9 +/- 18 without significant alteration by addition of n-butyrate. CDC (1 mM) diminished sodium absorption in the PC and DC. Diminished sodium absorption induced by bile salts was significantly reversed by n-butyrate in the PC but not DC. Permeability of 51Cr EDTA was greatest with 2 mM CDC in the distal colon. Mucosal function--sodium absorption with SCFAs, permeability changes, and protection by bacterial fatty acids from sodium losses due to bile salts--was superior in the PC compared with DC. Our results suggest that it may be preferable to preserve the proximal rather than distal colon in operations of the colon to secure optimal absorption of sodium.

Animals↗
PubMed1984

Colonic bicarbonate output as a test of disease activity in ulcerative colitis.

No available test objectively measures impairment of function of the inflamed colonic mucosa in ulcerative colitis. To study function we assessed rectal bicarbonate output by rectal dialysis in the presence of water and bacterial fatty acid (n-butyrate) in 21 controls, 18 patients with acute ulcerative colitis, 12 patients with ulcerative colitis in remission, and 12 patients with other forms of colitis. In acute ulcerative colitis, compared with controls, bicarbonate output and pH was reduced (p less than 0.001); stimulated bicarbonate output with bacterial fatty acid (incremental bicarbonate output) was reduced by 80% in acute ulcerative colitis (p less than 0.01). Results indicate that bicarbonate output is a useful and selective test of mucosal function in acute ulcerative colitis. A diminished incremental bicarbonate output with n-butyrate supports the view of inadequate oxidation of bacterial fatty acids in vivo by the mucosa in ulcerative colitis. Whether the test will prove to be an index of prognosis or will aid choice between medical or surgical therapy requires further study.

Acute Disease↗
PubMed1982

Trophic effect of short chain fatty acids on mucosal handling of ions by the defunctioned colon.

Sodium and water absorption were measured in defunctioned loops of colon of dogs either in the presence or in the absence of the bacterial fatty acid, n-butyrate. In freshly defunctioned colonic loops n-butyrate enhanced sodium absorption twofold (P less than 0.05) and promoted sodium absorption for 48 h. In the absence of n-butyrate, defunctioned loops lost the ability to absorb sodium and water within 48 h. Pre-treatment of colonic loops with fatty acids for 3 h significantly diminished (P less than 0.05) sodium and water losses into the colonic lumen compared with loops pre-treated with saline only. Butyrate was absorbed at a steady rate even when no sodium was absorbed. Results suggest that fatty acids act on the colonic mucosa to exert a trophic effect on absorption of sodium. This trophic effect determines the efficiency of absorption of ions and could have clinical implications in the genesis of postoperative diarrhoea.

Animals↗
PubMed1982

Value of small bowel enema in incomplete intestinal obstruction.

The usefulness of small bowel enema X-ray examination was evaluated in 11 patients in whom a provisional diagnosis of incomplete small bowel obstruction was made. Dilute barium was introduced through a nasojejunal tube. In one patient intubation of the jejunum was unsuccessful. In six patients the suspected obstruction was confirmed and information obtained about the site of obstruction. The small bowel enema X-ray examination was normal in three patients and subsequent clinical outcome was uneventful. In one patient, with normal findings on small bowel enema X-ray examination, acute obstruction developed after two days, necessitating operation. Small bowel enema X-ray examination appears a worthwhile adjuvant to clinical assessment but decisions for operative intervention still need to be based on clinical evaluation of patients.

Adolescent↗
PubMed1982

Luminal ions and short chain fatty acids as markers of functional activity of the mucosa in ulcerative colitis.

Luminal concentrations of short chain fatty acids (SCFA), ammonia, sodium and potassium were measured in colonic dialysate of 16 control subjects and in 65 cases with ulcerative colitis (UC), which were graded according to mucosal changes into mild (1), moderate (2), or severe (3) inflammatory activity. Sodium concentrations were mildly but not significantly increased in severe ulcerative colitis while luminal potassium concentrations were markedly decreased in severe ulcerative colitis (p less than 0.025). Concentrations of SCFA were increased in severe ulcerative colitis. Butyrate concentrations were significantly raised in all stages of active ulcerative colitis even when other fatty acids were not raised. Of all the parameters a lowered pH and raised butyrate concentration most strikingly correlate with the severity of mucosal change. Results indirectly suggest that control of luminal pH, potassium secretion and utilisation of butyrate by the colonic mucosa are impaired with progressive mucosal inflammation.

Adult↗