[Therapy of female hirsutism: current status and new findings].
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Biomedical subjects
Publications and source records attributed to C Costa.
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Tryptophan metabolism has been studied in mice with Harding-Passey melanoma and in controls, after a load of 1.0 g/kg b.w. of L-tryptophan by determining ten urinary metabolites of the kynurenine pathway and some enzyme activities involved in the degradation of this aminoacid. Kynurenine was the only tryptophan derivative excreted in significantly higher quantities in mice with melanoma with respect to the controls. This result is in agreement with a significantly higher activity of hepatic tryptophan pyrrolase in mice with melanoma. Liver kynureninase and liver and kidney kynurenine aminotransferase activities were similar in the two groups of mice. These findings point to a possible role of tryptophan in the biogenesis of melanins in pathological conditions such as in melanoma.
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In order to clarify the role of tryptophan in the patogenesis of senile cataract, we have studied the serum total and free levels of tryptophan in cataract patients as compared with age and sex-matched controls, and the urinary excretion of 10 metabolites after oral load of the amino acid. This excretion increases in the cataract group both as total per cent and as kynurenine. No difference has been found in the free and total serum tryptophan between normal subjects and cataract patients. A possible role of the kynurenines in the pathogenesis of senile cataract is suggested.
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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.
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.
Tryptophan metabolism along the kynurenine pathway has been studied in male and female heterozygous and homozygous adult Gunn rats after load of amino acid before and after exposure to blue light. The percentage of tryptophan metabolites in each group of rats was slightly higher in females than in males. Before irradiation the excretion of metabolites was larger in male and female heterozygous groups than the corresponding groups of the homozygotes. After irradiation only the groups of male and female heterozygous Gunn rats showed a decrease in the total excretion of the metabolites. Therefore blue light exposure dose not seem to influence the metabolism of tryptophan in homozygous Gunn rats.
The effect of light exposure in the enzyme activities, involved in the tryptophan metabolism along the kynurenine pathway, has been studied in male and female adult hetero-and homozygous Gunn rats. Light exposure did not seem to influence these enzyme activities. The groups of non-icteric heterozygotes however showed a higher activity of liver tryptophan pyrrolase than in the groups of icteric homozygotes. Kynureninase activity was similar in all the groups of rats, whereas liver kynurenine aminotransferase activity appeared slightly higher in the groups of male rats with respect to female rats, but no difference existed before and after irradiation. In addition the male heterozygotes showed a higher kynurenine aminotransferase activity in kidneys than the other groups of rats.
Tryptophan metabolism 'via kynurenine' has been studied in rats before and after induction of experimental light-conditioned dermatitis with psoralen. Tryptophan load in animals during the acute phase of dermatitis (one day after induction) causes a markedly increased urinary excretion of total metabolites in comparison with that obtained before dermatitis. During this phase of the skin disease tryptophan pyrrolase activity is significantly increased and kynureninase activity significantly decreased in liver in respect to the control animals. Kynurenine aminotransferase activity shows no significant variations in both liver and kidneys. After 6 days of dermatitis, when the skin damage is in repair, both the excretory values of the urinary metabolites after L-tryptophan load and the enzymic activities are similar to those before dermatitis.
Tryptophan metabolism after load test, along the kynurenine pathway was studied in guinea pigs, before and during the psoralen-induced photodermatitis. This skin injury, during the acute phase, causes a large increase in urinary excretion of total metabolites and a significant increase of liver tryptophan pyrrolase.