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Value of urinary simple phenol and indican determinations in the diagnosis of the stagnant loop syndrome.

The urinary excretion of phenol, p-cresol, and indican was determined in 7 patients with the stagnant loop syndrome, 26 patients with coeliac disease, chronic pancreatitis, and partial gastrectomy, and 18 control patients. The mean excretion of the compounds in the patients with the stagnant loop syndrome and in the control patients, respectively, was 77 and 2.3 mg/24 h of phenol (p less than 0.05), 164 and 39.5 mg/24 h of p-cresol (n.s.), and 369 and 41.5 mg/24 h of indican (p less than 0.01). When applied as diagnostic tests for the stagnant loop syndrome, the phenol excretion showed 2 false negative results, the p-cresol excretion 3 false negative and 2 false positive results, and the indican excretion 6 false positive results. The combined use of phenol and indican determinations eliminated the number of false positive results with the indican test, and was found most useful as screening procedure. Determination of phenol and indican in a 24-hour urine sample is likely to provide a simple method for selecting patients with signs of abnormal bacterial colonization in the small intestine for more detailed investigations.

Aged

Trypsin inhibitor ingestion-induced urinary indican excretion and pancreatic acinar cell hypertrophy.

Sodium saccharin (NaSacc) has been shown to be a protease inhibitor and to induce an increase in urinary indican, which is a product that is dependent on microbial metabolism of tryptophan. These findings suggest that urinary indican might provide a noninvasive marker of increased pancreatic acinar cell size associated with plant trypsin inhibitor ingestion. The results demonstrate the 7.5% of dietary NaSacc, which increases urinary indican, also increases relative pancreas mass (g/kg body weight), and that these effects are not induced by intravenous infusion of NaSacc. Dietary soybean trypsin inhibitor in the dose range of 17-713 mg/100 g diet was associated with parallel dose-dependent increases in urinary indican and pancreatic acinar cell size (assessed histologically). These findings suggest that measurement of relative urinary indican excretion (microgram/g diet ingested) can provide a noninvasive marker of increased pancreatic acinar cell size in rats that ingest compounds which inhibit digestive proteases.

Animals

The role of urinary indican as a predictor of bacterial colonization in the human jejunum.

To evaluate the role of urinary indican excretion and several common absorptive tests as predictors of bacterial colonization in the human jejunum, we analyzed the relationship between indican excretion and quantitative jejunal cultures, tryptophan absorption, enteric protein loss, fecal nitrogen excretion, D-xylose and lactose tolerance tests, and B12 and fat absorption in 40 subjects. Indican excretion correlated poorly with jejunal colony counts (r = 0.22). Neither tryptophan load or absorption, nor nitrogen excretion were related to indicanuria, but there was a modest correlation between enteric protein loss and urinary indican values (r = 0.54). Lactose tolerance tests and D-xylose, B12 and fat absorption showed no predictive value for identifying patients with high colony counts. Compared to quantitative small bowel culture, none of the tests studied provided suitable methods for screening for bacterial contamination of the human jejunum.

Albumins

Determination of indican and tryptophan in normal and uraemic patients by high-performance liquid chromatography with a new electrochemical detector.

A simple analytical procedure has been developed for the determination of indican and tryptophan in biological fluids by reversed-phase liquid chromatography using a new electrochemical detector consisting of a tubular anode obtained by moulding graphitized carbon black and polyethylene. The hydrodynamic voltammetry of these compounds has been carried out and it has been found that, by operating in isocratic conditions with phosphate buffer (pH 4.0)-methanol (93:7), the reported compounds can be determined directly. The procedure can be applied for the determination of the free compounds on ultrafiltered serum as well as of their total content on serum deproteinized with methanol. Levels of both compounds in normal and uraemic patients have been measured and the relative ratios between free and total content yield a useful marker for patients with renal disease. The limits of quantitation of indican and tryptophan in serum were 5 and 10 ng/ml, respectively. The within-day assay coefficient of variation for total indican and tryptophan ranged from 3.0 to 3.6% and from 3.8 to 4.1%, respectively. The day-to-day assay coefficient of variation for total indican and tryptophan ranged from 3.4 to 3.7% and from 4.6 to 5.0%, respectively.

Chromatography, High Pressure Liquid

Increase in urinary indican excretion in pancreatic steatorrhoea following replacement therapy.

Urinary indican excretion was studied in 5 patients with steatorrhoea of pancreatic origin, 4 patients with steatorrhoea due to other causes, and 5 normal subjects. Treatment with pancreatic extract resulted in an immediate increase in indican excretion to above the normal range in patients with steatorrhoea due to pancreatic insufficiency. Administration of pancreatic extract did not result in a rise in the patients with steatorrhoea not due to pancreatic insufficiency, or in the normal subjects. In one patient with pancreatic insufficiency maintained on a low protein diet, the rise in indican excretion on replacement therapy was much slower and did not reach as high a level as in the patients on a normal protein diet. The possible mechanisms underlying these observations are discussed. It is suggested that the finding of a low indican excretion in the presence of steatorrhoea and its rise to above normal on pancreatic enzyme therapy is strongly suggestive of exocrine pancreatic insufficiency.

Adult

Urinary indican in healthy Indian subjects.

Forty normal subjects have been taken for the present study. The mean Indican excretion was 40.45 mg/24 hrs. The mean jejunal count was 1.96 x 10(3) +/- 5.39 x 10(3) organisms/ml and 40% of the jejunal aspirates were sterile. Wide range of bacteria were cultured bu the coliform organisms were obtained in only 16.6%. There was a significant correlation between Indican excretion and total bacterial count (P less than .01).

Adolescent

Urinary excretion of indican in progressive myoclonus epilepsy without Lafora bodies. The effect of sodium valproate.

Increased urinary excretion of indican was detected in earlier studies of patients with the form of progressive myoclonus epilepsy (PME) where no Lafora bodies are present in the brain and other tissues. Since then, all PME patients have been given sodium valproate and/or clonazepam. In a series of 10 patients now examined the mean excretion was on the same level as that of other epileptic and non-epileptic neurological patients (53 +/- 27 mg/g creatinine). Alternate reduction of the two drugs in one patient over a period of 24 days increased the excretion up to the high level measured earlier (96 mg/g creatinine) and caused marked worsening of the clinical condition while no remarkable changes were observed in another PME patient who received her normal medication. The highest values ever measured were found in one PME patient just before his death. In two patients who had no medication the excretion was also high but returned to the normal level during medication with sodium valproate. It is unknown at the moment whether this change is due to the improved clinical condition of the patients or to the compound itself.

Adult

[Urinary excresion of indican during recovery from malnutrition].

Most indican excreted in the urine comes from the degradation of tryptophan through the action of microorganisms dwelling within the intestinal lumen. Based on this knowledge, the excretion of this compound was investigated during the recovery process of 19 malnourished infants; thus, attempts were made to recognize indirectly whether quantitative modifications take place in the intestinal flora as the state of nutrition is re-established. The results do not suggest the presence of an important variation of the bacterial content within the intestine of these children, at least during the first four weeks of their recovery.

Analysis of Variance

Comparison of the bladder response to indole and sodium saccharin ingestion by male rats.

To ascertain whether the bladder mass increase and epithelial hyperplasia induced by 5% dietary sodium saccharin (NaS) in short-term experiments with rats are caused by increased urinary excretion of indican associated with this treatment, the responses of the urine and bladder induced by 1.5% indole (Id) ingestion were compared with those induced by 5% NaS and 1.5% Id + 5% NaS. Id and NaS, when fed alone, produced equivalent increases in bladder mass and both compounds induced epithelial hyperplasia, but Id ingestion was associated with much greater urinary indican excretion (5 mg/g diet ingested) than was NaS (0.3 mg/g diet ingested). When Id and NaS were ingested together, the bladder mass increase was additive, but the epithelial hyperplasia was not exacerbated over that observed with each alone, and the urinary indican was equivalent to that produced by Id alone. These findings suggest that a high level of urinary indican excretion is associated with an increase in bladder mass and epithelial hyperplasia (Id treatment) but indicate that the relatively low urinary indican level obtained by NaS feeding alone is unlikely to be responsible for the bladder responses noted with this compound.

Animals

The effect of saccharin ingestion on the excretion of microbial amino acid metabolites in rat and man.

Low dietary levels of sodium saccharin (0-2%) fed to male rats for 6 weeks produced a dose-related increase in the urinary excretion of p-cresol, a major microbial metabolite of tyrosine. Some animals fed higher levels of saccharin (5-7.5%) for 6 weeks excreted increased amounts of p-cresol, but many excreted negligible amounts so that the overall dose-response relationship was bell shaped. After 20 weeks of exposure, all rats in the higher dose groups showed increased p-cresol excretion and by 26 weeks the 7.5% saccharin group showed a 36-fold increase over animals fed the 0% saccharin diet. The urinary excretion of phenol, another microbial amino acid metabolite, was constant in animals fed dietary levels of saccharin below 2% for 6 weeks, but was virtually abolished at higher levels. The excretion of indican (formed from indole, a microbial metabolite of tryptophan) was increased by saccharin in a dose-related fashion at all time points, but showed only a 3-fold increase at 7.5% compared with the 0% group. p-Cresol may therefore prove more sensitive than indican as an indicator of altered microbial metabolism due to saccharin. In a separate study the effect of 7.5% saccharin on p-cresol and indican excretion was shown to be largely reversible and the excretion of phenol increased rapidly when saccharin was withdrawn from the diet. Chronic saccharin administration to man at high doses (1 g/day for 4 weeks) had no perceptible effect on the excretion of these three metabolites.

Amino Acids

Hepatic detoxification and hepatic function in chronic active hepatitis with and without cirrhosis.

The detoxification capacity of the liver in chronic active hepatitis (CAH) without liver cirrhosis (LC) is not sufficiently known. Therefore, we examined, in 156 patients with morphologically proven CAH of different stages, plasma ammonia, free phenols, indican, glucuronic acid and urea synthesis rate as parameters for liver detoxification. We found a significant increase of ammonia, phenols, and indican and a significant decrease of glucuronic acid and urea synthesis rate parallel to the stage of CAH without LC. In 34 CAH patients with complete recovery, a retrospective 10-year follow-up was possible. Parallel to the normalization of liver morphology and general liver tests, detoxification parameters also normalized. However, the detoxification disorders in CAH without LC are mild in nature and do not produce hepatic encephalopathy. Probably, they are caused by a reduced synthesis of the urea-cycle enzymes and of glucuronyltransferase in the liver.

Ammonia

Purple urine bags.

Purple urine drainage bags were found in 7 of 71 chronically catheterized elderly women. The purple staining of the bags is due to a violet discoloration (indirubin) of the plastic of the catheter bag and fine blue crystals of indigo in the urine. The colors are formed from the substrate indoxyl sulfate (indican) and all 7 patients had bacteria in the urine that would produce blue colonies on agar enriched with the urine (filter sterilized) of the patients involved. Organisms identified were Providencia or Klebsiella species. Indican excretion was higher in patients with purple urinary catheter bags than in controls.

Aged

Microbial amino acid metabolites and bladder cancer: no evidence of promoting activity in man.

1. Indole, p-cresol and phenol are microbial amino acid metabolites which show co-carcinogenic or promoting activity in animal studies. Their involvement in the development of human bladder cancer has been determined by measuring the urinary excretion of indican (indoxyl sulphate) and conjugated phenols. 2. Thirty-two patients (22 males, 10 females) with histologically confirmed carcinoma of the urinary bladder and a similar number of age and sex matched controls took part in the study. The excretion of indican, p-cresol and phenol showed wide interindividual variability, but did not differ significantly between the two groups. 3. The findings indicate that these endogenous metabolites do not contribute significantly to the development of human bladder cancer.

Aged

Blue collection bag after ileal diversion.

Five children with ileal diversions have shown asymptomatic blue staining of the urine collection bags. A tryptophan derivative (indican) in the urine that oxidizes to indigo blue on exposure to air is thought to be the cause of this benign transient phenomenon.

Adolescent