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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

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

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

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

Findings in routine laboratory examination in progressive myoclonus epilepsy.

Thirty-one patients suffering from progressive myoclonus epilepsy, (also called Unverricht-Lundborg's disease) without Lafora bodies, were examined to check the findings reported in literature and to chart out the main abnormalities in routine laboratory findings. Many alterations could be pointed out, but a high proportion of them were due to factors which are secondary to the syndrome of progressive myoclonus epilepsy: continuous anticonvulsive medication; immobilization; frequent infections; and the patient's poor nutritional condition. The most remarkable finding, and the only one which supported the abnormality reported earlier, was the raised excretion of indican which could not be explained by fermentation in the bowels. The urinary 5-hydroxyindoleacetic acid excretion was a little low, but still within the normal range. The tryptophan and 5-hydroxytryptamine metabolism deserves further investigation in attempting to discover the aetiology of progressive myoclonus epilepsy.

Adolescent

Intestinal absorption of L-tryptophan in scleroderma.

The purpose of this investigation was to study the intestinal absorption of L-tryptophan and to assess the absorptive function of the intestine in scleroderma. The oral L-tryptophan loading test was performed in 31 cases of systemic scleroderma (progressive systemic sclerosis, PSS) and 3 cases of localized scleroderma. Serum levels of tryptophan and urinary excretion of indole-acetic acid (IAA) and indican (IS) were determined in order to assess intestinal absorption of tryptophan. In 10 cases the D-xylose test and in 4 cases Schilling's test was also performed. Furthermore, in vitro binding of L-tryptophan by plasma proteins in PSS and in other skin diseases as controls was studied. The normal increase in serum tryptophan after loading was noted in 17 cases (in 14 cases of PSS with a mild, slow progression in 3 cases of PSS with a severe, rapidly progressing course). In 10 of these cases, urinary excretion of IAA was higher than normal and in normal and in 3 cases excretion of urinary IS was also above normal. On the other hand, in 14 cases of severe, rapidly progressing PSS and in 2 of 3 cases of widespread linear scleroderma, serum levels of tryptophan were markedly depressed after loading, while urinary excretion of IAA and IS was normal. In all 4 cases studied, Schilling's test was normal, and only in 2 of 10 cases of PSS was the D-xylose test abnormal. It is concluded that in the majority of cases of PSS, intestinal absorpiton of tryptophan is normal as also is the absorptive function of the intestine. The slight rise in serum tryptophan after loading in some cases of PSS may be a result of increased binding of tryptophan by albumin.

Adolescent

The ageing gut: a study of intestinal absorption in relation to nutrition in the elderly.

This study was designed to assess the functional efficiency of the ageing small intestine and the possible role of malabsorption in old people with nutritional deficiencies. Fifty subjects aged 65 to 92 years were studied, of whom 33 presented with anaemia, chronic diarrhoea or bone pains, and 17 were apparently healthy 'controls' with no relevant symptoms. Tests of intestinal function included blood xylose and iron absorption curves, a double isotope Schilling test, faecal fat, urinary indican and small bowel radiology, with duodenal aspiration and jejunal biopsy in some cases. On the basis either of steatorrhoea or at least two other abnormal parameters of absorption, there were 15 cases of malabsorption. Thirteen of these had symptoms but two were 'controls'. Four of these had duodenal diverticulosis, two had the post-gastrectomy syndrome, and one had calcific pancreatitis. Malabsorption in the remaining eight cases was not fully explained. The age range of this last group was 72--86 years; one of them had a contaminated small bowel and two showed some evidence of pancreatic insufficiency. Malabsorption emerged as a significant cause of low levels of serum iron, haemoglobin and calcium. The blood xylose test is a useful screening procedure for intestinal malabsorption in old age, but full evaluation calls for investigation of pancreatic function.

Aged

Intestinal bacterial metabolism of protein and bile acids: role in pathogenesis of hepatic disease after jejuno-ileal bypass surgery.

Jejunal bacterial colonization and intestinal metabolism of bile acids and protein by bacteria have been investigated in 12 patients with abnormal liver histology following jeujno-ileal bypass surgery for obesity. Aerobic and/or anaerobic colonic flora was present in jejunal aspirates from 8 of 12 bypass patients, but in none of the controls. Intestinal protein metabolism and bile acid deconjugation (measured by urinary indican excretion and 14C-glycocholic acid breath test) was significantly enhanced in bypass patients. Intestinal bacterial overgrowth, with abnormal intestinal metabolism by bacteria of ingested nutrients and bile acids, could contribute to hepatic disease after bypass surgery via the production of endogenous hepatotoxins.

Adult

The effects of high dietary concentrations of sodium saccharin on in vivo metabolism of xenobiotics in rats.

The effect of feeding a diet containing 7.5% sodium saccharin on the conjugation of [14C]phenol has been studied during neonatal development in male and female rats using a two-generation protocol. Decreased formation of phenol sulphate was observed in the F1 saccharin-treated rats from 4 wk of age and this was compensated for by an increase in the formation of quinol glucuronide. This shift in the conjugation pattern of [14C]phenol, with an increase in oxidation, was not sex specific. The daily excretion of indican was significantly increased from 5 wk of age. Feeding a diet containing 7.5% sodium saccharin did not affect in vitro activities of the enzymes involved in the conjugation reactions, that is, aryl sulphotransferase and uridine-5'-diphosphate glucuronyltransferase. The incorporation of 5% cysteine into the diet of saccharin-treated rats for 1 wk prevented the change in conjugation of [14C]phenol observed in the saccharin-treated animals. Absorption of sodium [35S]sulphate from the gastro-intestinal tract was not appreciably affected by a high dietary concentration of sodium saccharin. A high dietary concentration of saccharin affected the conjugation of 3-hydroxyanthranilic acid during neonatal development, possibly as a result of sulphate depletion.

3-Hydroxyanthranilic Acid

Diabetic neuropathic cachexia associated with malabsorption.

Diabetic neuropathic cachexia is characterized by neuropathic pain and severe weight loss of unknown aetiology. We describe four patients with diabetic neuropathic cachexia who were found to have malabsorption. Four diabetic patients presented with neuropathic pain, anorexia, depression and weight loss of 16 (range 10-21) kg. None complained of diarrhoea. There were three males and one female, median age 54 (46-67) years. A butterfat test showed a serum turbidity difference of 9 (6-10) light scattering units (normal greater than 60 units). The median serum xylose was low and there was delayed urinary xylose excretion. Urinary indicans, small bowel histology, liver function tests, and thyroid and renal function were normal. Ultrasound scans of liver, gall bladder and pancreas, and endoscopic retrograde cholangiopancreatogram were normal. The patients were treated with pancreatic supplements and a high calorie diet. Three have completely recovered and the other patient is improving. Thus these cases of diabetic neuropathic cachexia appeared to be associated with malabsorption which may be due to pancreatic dysfunction. It is suggested that the management of diabetic neuropathic cachexia should include the investigation and treatment of malabsorption.

Aged

A study of urinary tryptophan metabolites in relation to the phenylalanine content of semi-synthetic diets in a patient with phenylketonuria.

The influence of different phenylalanine (Phe) levels in semi-synthetic diets on the urinary excretion of tryptophan (Try) metabolites was studied in one untreated phenylketonuric (PKU) patient. Low dietary Phe decreased the excretion of indoleacetic acid, indolelactic acid, indican and Try but did not increase 5-hydroxyindoleacetic acid. Under the low Phe diet, the excretion of N-acetyltryptophan, kynurenic and xanthurenic acid are greatly increased in the urine after a Try load. The possible significance of the extensive acetylation of Try and Phe is discussed in relation to the low blood levels of Try and PKU and to the phenomenon of decreasing blood Phe levels in PKU.

Adult

Enhancing effect of allopurinol on the induction of bladder cancer in rats by n-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated. Four groups of rats were given normal diet or normal diet supplemented with 0.005% allopurinol, 0.188% FANFT, or 0.005% allopurinol-0.188% FANFT. Transitional cell carcinomas appeared in 3 of 30 rats (10%) at 15 weeks and in 7 of 44 rats (16%) at 20 weeks in the FANFT-treated group; the carcinomas appeared in 14 of 35 rats (40%) at 15 weeks and in 27 of 50 rats (54%) at 20 weeks in the FANFT-allopurinol-treated group. Growth rate was not affected by allopurinol and FANFT. Allopurinol alone caused no morphological change in the epithelial cells of the urinary bladder but decreased hepatic cytosol nitroreductase activity. FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content. FANFT increased the urinary excretion of anthranilic acid glucuronide, kynurenine, acetylkynurenine, and 3-hydroxykynurenine and decreased indican and o-aminohippurate excretion. Allopurinol did not alter the effects of FANFT on the acid-soluble thiol content of liver and blood or the excretion of urinary tryptophan metabolites.

Allopurinol