The correlation between certain tryptophan metabolites and the N-nitrosamine content in the urine of bilharzial bladder cancer patients.

The present work is an up-to-date approach to study the correlation between the excretion pattern of tryptophan metabolites along the kynurenine pathway (after loading with 2 gm. L-tryptophan), and the N-nitrosamine content in urine of bilharzial bladder cancer patients. The control group was composed of healthy subjects who had no reported history of S. haematobium infection and no current bacterial cystitis. The N-nitrosamine content was determined by the colorimetric method of Eisebrand and Preussmann (1970). It was demonstrated that 64 per cent of the patients metabolized the tryptophan load abnormally and the others metabolized it almost normally. Moreover, the N-nitrosamines were present in 43 per cent of controls and 93 per cent of patients have these derivatives in higher values. The presence of an inverse correlation between certain tryptophan metabolites, shown previously to be bladder carcinogens, and the N-nitrosamine content, especially after loading, was interpreted in view of the possible conversion of some tryptophan metabolites into N-nitrosamines either under endovesical conditions or during the execution of the colorimetric determination of these compounds. Therefore, thorough investigation is urgently needed to study the origin of these urinary N-nitrosamines. Moreover, improved method(s) for their colorimetric determination are also urgently needed.

Influence of tryptophan loading on urinary excretion of anthranilic acid and 3-hydroxyanthranilic acid by men and women as determined by alkali flame ionization gas chromatography.

A gas chromatographic method with alkali flame ionization detection is described for the determination of urinary total (free and conjugated) anthranilic acid (AA) and 3-hydroxyanthranilic acid (HAA) as their pentafluorobenzyl esters. Prior to analysis, urine was hydrolysed using hydrochloric acid in a boiling water bath. The highest AA and HAA yields were obtained with 4 M hydrochloric acid and a hydrolysis time of 4 h. The coefficients of variation of the between-run analyses of AA and HAA at the endogenous level were 7.2 and 5.8%, respectively. The average recovery for both substances was 84%. The method described has been used to study the excretion of AA and HAA in the urine of healthy males and females before and after an oral load of tryptophan. Furthermore, the influence of oral contraceptives has been investigated. Results indicate that for both sexes the excretion of AA in the urine was higher than that of HAA, except after tryptophan loading. The excretion of AA by women was higher than by men. For HAA, the results of both sexes were comparable. Furthermore, for neither of the sexes was a diurnal variation of AA or HAA observed. After tryptophan loading, the formation of HAA was increased by more than that of AA. Results obtained for women on oral contraceptives indicate a hormonal-induced inhibition of AA formation.

Tryptophan metabolism in alcoholic pellagra patients: measurements of urinary metabolites and histochemical studies of related muscle enzymes.

Biochemical and enzymatic aspects of tryptophan-niacin metabolism were studied in 15 adult alcoholic pellagra patients and in 14 controls. In addition to the clinical signs of niacin deficiency, most of the pellagra patients had other signs of malnutrition. Plasma tryptophan in pellagra patients was 2.07 +/- 1.27 mumol/dl, and in the controls 4.84 +/- 2.21 mumol/dl (p less than 0.001). The erythrocyte glutamic oxaloacetic transaminase index was 1.94 +/- 0.77 in the pellagra patients and 1.58 +/- 0.73 in the controls. The urinary levels of 3-hydroxyanthranilic acid were 34.49 +/- 21.47 mumol/g of creatinine in the pellagra patients and 14.51 +/- 8.02 mumol/g creatinine in the controls (p less than 0.02). The urinary levels of N'methylinicotinamide were 2.13 +/- 1.18 mg/g creatinine in the pellagra patients and 4.76 +/- 1.94 mg/g creatinine in the controls (p less than 0.01). The excretion of N'-methyl-2-pyridone-5-carboxamide (2-pyridone) was 2.94 +/- 2.37 mg/g creatinine in the pellagra patients and 10.19 +/- 7.49 mg/g creatinine in the controls (p less than 0.01). The histoenzymological activity of 3-hydroxyanthranilate oxidase in the deltoid muscle was higher in the pellagra patients than in the controls, whereas alpha-glycerophosphate dehydrogenase activity was higher in the controls. These results suggest that for alcoholic pellagra patients the tryptophan-niacin pathway is inhibited after the 3-hydroxyanthranilate oxidase step.

Alterations of the tryptophan--nicotinic acid metabolism in vitiligo.

Tryptophan metabolism "via kynurenine" is altered in vitiligo: after a load of the amino acid the urinary excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid is decreased, whereas that of xanthurenic acid and its 8-methyl ether is increased. The excretory values of the metabolites suggest a deficiency of the activity of kynurenine hydroxylase and kynunerinase, the enzymes involved in the metabolism of 3-hydroxykynurenine and 3-hydroxyanthranilic acid. The reduced excretion of 3-hydroxykynurenine, a tryptophan metabolite involved in melanin biosynthesis, may indicate a smaller utilization of tryptophan in the biogenesis of the melanins.

[Tryptophan metabolism in patients with vitiligo]. / Studi sul metabolismo del triptofano in pazienti con vitiligine.

Our previous research showed that tryptophan is an important precursor in the biogenesis of melanins. Therefore, with the purpose of observing whether a relationship exists between tryptophan metabolism and diseases characterized by an altered process of skin pigmentation in man, we studied the metabolism of this aminoacid along the kynurenine pathway in 29 vitiliginous patients (11 males and 18 females) and in 21 control subjects (11 males and 10 females) by determining 10 urinary metabolites after an oral loading of 50 mg/kg body weight L-tryptophan. The mean total excretion of the metabolites in patients resulted similar to that of the controls. However, considering the individual metabolites one can observe a decreased excretion of 3-hydroxykynurenine, o-aminohippuric acid and 3-hydroxyanthranilic acid and an increased excretion of xanthurenic acid and of its 8-methyl ether in the group of vitiliginous patients in respect to the controls. These results seem to indicate a decreased formation of nicotinic acid from tryptophan. Moreover, in relation to the fact that 3-hydroxykynurenine could be the metabolite through which tryptophan is involved in melanin biosynthesis, this study supports the hypothesis of a connection of tryptophan metabolism with the lack of pigmentation in vitiligo.

A controlled trial of pyridoxine supplementation in children with febrile convulsions.

A total of 107 children who had been hospitalized following a febrile convulsion were enrolled into the trial. By random allocation, 55 children were treated with pyridoxine hydrochloride (20 mgs twice daily) and the remaining 52 children were treated with a placebo until there had been either a further convulsion or a year had passed without recurrence. Eighty children were adequately followed up and of these, 17 had a recurrent febrile convulsion while receiving medication. Recurrences occurrences occurred in 7 of the 38 children receiving pyridoxine and in 10 of the 42 children receiving placebo (X2 = .346, p greater than 0.5). Initial tryptophan load tests had been abnormal in 34 children, and of these, recurrences occurred in 3 of the 17 who received pyridoxine and in 3 of the 17 who received placebo. It has yet to be shown that pyridoxine supplementation protects children from recurrent febrile convulsions.

Hydroxykynurenine/hydroxyanthranilic acid ratios and febrile convulsions.

Hydroxykynurenine/hydroxyanthranilic acid ratios were measured in children with febrile convulsions, afebrile fits, and fever, as well as in healthy controls. Increased ratios were found not only in the children who had fits but also in the children who were febrile and did not have fits. It is suggested that a raised hydroxykynurenine/hydroxyanthranilic acid ratio does not necessarily indicate vitamin B6 deficiency but may represent a nonspecific response of tryptophan metabolism to stress.

[3-hydroxyanthranilic acid content in the urine of bladder cancer patients]. / Soderzhanie 3-oksiantranilovoi kisloty v moche bol'nykh rakom mochevogo puzyria.

The work has shown the possibility to determine immunologically 3-OAA-antigen in the urine of bladder cancer patients, which is absent in the urine of healthy individuals. By the identity reaction the authors proved the supposed structure of the detected antigen, i. e. the presence of 3-oxianthranilic acid in it. The data obtained may lie in the basis of the immunodiagnostic test to bladder cancer.

Metabolic abnormalities of tryptophan and nicotinic acid in patients with rheumatoid arthritis.

The mean plasma total tryptophan concentration of 13 long-standing rheumatoid arthritis patients was found to be lower than that of seven nonrheumatoid control subjects, but the plasma nicotinic acid concentration was unchanged. In the rheumatoid patients the urinary excretion of the tryptophan metabolites, kynurenine, xanthurenic acid and 3-hydroxyanthranilic acid, was increased several fold, but the excretion of N-methylnicotinamide was normal. These findings are discussed in relationship to the dietary intakes of tryptophan, nicotinic acid and pyridoxine, the effect of antirheumatoid drugs on plasma tryptophan and liver tryptophan pyrrolase, and requirement of rheumatoid patients for pyridoxine.

Tryptophan metabolism in Japanese and British women and its relationship to endogenous steroid levels.

The excretion of the tryptophan metabolites L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid, by normal Japanese and British pre-menopausal, menopausal and post-menopausal women was measured after a loading dose of L-tryptophan. No significant difference was found between the mean excretion levels of the two races. A correlation with the level of plasma oestradiol and the excretion of L-kynurenine and also with the total of the four metabolites was found in pre-menopausal British women but not in Japanese women.

[Tryptophan metabolism in vitiligo]. / Obmen triptofana pri vitiligo

An activity of tryptophan pyrrolase was not observed in skin of healthy persons and of patients with vitiligo. Content of serotonin was similar in skin of normal persons and in skin of patients with normal pigmentation and in depigmented area. But content of serotonin in blood and excretion of anthranilic acid were decreased in the patients as compared with healthy persons. Excretion of kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, kynureninic, xanthurenic and 5-hydroxyindolyl acetic acids was increased in patients and this increase was more distinct after loading with 1-tryptophan. The data obtained suggest that kynurenine and serotonin pathways of tryptophan metabolism were intensified in vitiligo.

[Tryptophan-load in progressive scleroderma (author's transl)]. / Der Tryptophan-Stoffwechsel bei der progressiven Sklerodermie

This presentation describes effects of oral tryptophan loading (5.0 g DL) on tryptophan metabolism in healthy subjects (n = 10) and persons with progressive scleroderma. N1-methylnicotinamide (N1MN), 3-hydroxyanthranilic acid (3 HAA), kynurine (KN), tryptamin (TA), xantheurenic acid (XA) were determinated. Alterations of tryptophan metabolism were evaluated by 24 h urinary excretions of the following metabolites: 5-hydroxy indolacetic acid (5 HAA) and indole-3-acetic acid (IAA). The pathological pathways were discussed, especially the way and influence of serotonine.

Experimental biharzial bladder cancer: tryptophan metabolism in nonhuman primates experimentally infected with Schistosoma haematobium.

A nonhuman primate species infected with Schistosoma haematobium provided a model system for controlled studies on biharzial bladder cancer. Urinary excretion of tryptophan metabolites by capuchin monkeys (Cebus apella) was similar to that of humans when expressed per g creatinine. Liver tryptophan oxygenase activity of the capuchin monkeys was comparable to that of humans. Excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid was elevated above control levels in capuchin monkeys infected experimentally with S. haematobium. The capuchin-S. haematobium system closely resembles the human biharziasis system and offers a reproducible laboratory model system for the controlled study of the parasitology, pathogenesis, and biochemistry of biharzial bladder cancer.