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    The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in rats

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    BACKGROUND:Quinolinic acid and other kynurenine metabolites of the oxidative metabolism of tryptophan play an important role in several pathophysiological conditions. We aimed to study the effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway.METHODS:Enzyme activity was investigated in liver, kidneys and small intestine obtained from Sprague-Dawley rats of various ages (1 week, 2-3, 12 and 18 months).RESULTS:We found age-related differences in the liver tryptophan 2,3-dioxygenase, small intestine indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase activities, which decreased significantly with age. Also liver kynureninase activity declined with age, while the activity in kidneys did not show an evident age-related pattern from 2-3 months to 18 months of age. Liver kynurenine oxoglutarate transaminase was quite similar through all considered age groups, while the activity in kidneys was significantly lower in newborn rats and progressively increased up to 12 months, then significantly decreased at 18 months of age. Liver and kidney 3-hydroxyanthranilate 3,4-dioxygenase progressively and significantly increased from newborns to 12 months of age; in the group of rats aged 18 months, the enzyme activity tended to diminish, although not significantly. The liver aminocarboxymuconate-semialdehyde decarboxylase activity increased up to 12 months of age, then tended to decrease at 18 months, while in the kidneys, in which the activity was higher than in the liver at all the considered ages, the activity remained constantly elevated from 2-3 months to 18 months of age.CONCLUSIONS:A progressive decline in the enzyme activities involved in tryptophan metabolism along the kynurenine pathway in rat tissues was found with age, except for aminocarboxymuconate-semialdehyde decarboxylase, which, on the contrary, was increased after 2-3 months to the other older groups of age. The altered metabolism of tryptophan with ageing can lead to a decreased biosynthesis of nicotinic acid, tryptophan being the major source of body stores of NAD coenzymes, which are involved in almost all biogenetic and biosynthetic pathways of the organism

    Changes in serum tryptophan during antiviral therapy with recombinant alfa-interferon in chronic hepatitis C

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    The most effective treatment of chronic hepatitis C (HCV) available to date is represented by interferon-α (IFN-α), alone or in combination with ribavirin. However, the therapy presents adverse effects, including depressive symptoms. As IFN-α can cause an alteration of the tryptophan metabolism and a consequent reduced synthesis of serotonin, we have designed a study aimed to investigate the effect of IFN-α therapy on the serum levels of tryptophan and on the development of depression in patients affected by the hepatitis C virus. Nine patients with HCV were enrolled while treated with IFN-α2a (3 MU thrice/week) plus ribavirin (15 mg/kg/day) for six months. All patients were evaluated by a hepatologist and received two self-administered scales [Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS)]. Blood samples were collected before treatment and at one month and six months of therapy. Tryptophan, 5-hydroxytryptophan and serotonin were analysed by HPLC with a spectrofluorometric detector. In all cases, a significant decrease of serum tryptophan concentrations from baseline (17.60 ± 1.08 mg/ml) to one month (13.94 ± 1.18 mg/ml) and six months (12.68 ± 0.64 mg/ml) with an increase of symptoms of depression was obtained, whereas 5-hydroxytryptophan and serotonin levels did not show any variation during the therapy from baseline values. The preliminary results suggest that IFN-α plays a role in serum tryptophan reduction and the development of depressive symptoms

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    A study of tryptophan metabolism via serotonin in ventricular cerebrospinal fluid in HIV-1 infection using a neuroendoscopic technique

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    In this paper we report the study of tryptophan metabolism via serotonin in ventricular CSF in HIV-1 infection in order to investigate the origin of tryptophan metabolites in the human brain. The patients (n=4) were affected with non-communicating hydrocephalus. One of these also was suffering from HV-1 infection. The CSF was withdrawn from different sites of the cerebral cavity with a neuroendoscopic procedure which allows an accurate exploration of all the cerebral ventricles. The measurement of tryptophan, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin was carried out by HPLC with fluorometric detection. In HIV-1 infection the highest concentration of tryptophan is present in the CSF of the choroid plexus; however, the levels are markedly lower than those in hydrocephalic individuals (control group). 5-Hydroxytryptophan CSF content is higher in HIV-1 infection than in hydrocephalic controls in all districts examined. Regarding serotonin, a great difference appears in the choroid plexus and in the pituitary recess between the HIV-1 infected patient and the control group. The values of 5-hydroxyindoleacetic acid are much lower in the CSF of the HIV-1 infected patient than in hydrocephalic controls. Melatonin levels appear to fluctuate largely but, in the HIV-1 infection, a great variability is present among the sites of CSF withdrawal. The third ventricle contains the highest concentration of melatonin and the choroid plexus and the pituitary recess the lowest. All the melatonin concentrations in HIV-1 infection are largely different than in hydrocephalic controls. This is the first report on the measurement of tryptophan metabolites via serotonin in ventricular CSF in HIV-1 infection

    Protein and non-protein (free and protein-bound) tryptophan in legume seeds

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    The contents of protein and non-protein (free and protein-bound) tryptophan and of proteins in the flours of nine legume seeds were determined. Lupins and soybeans showed the highest protein concentrations, followed by groundnuts, beans, broad beans, lentils, vetches, chick-peas, and peas. Protein tryptophan content is higher in soybeans and lower in peas (502 and 192 mg/100 g of dry flour, respectively) than in the other legumes, which also contain non-protein tryptophan. Chick-peas show the highest value of free tryptophan and groundnuts the lowest (58.2 and 2.24 mg/100 g of dry flour, respectively). Tryptophan appears to be bound to water-soluble proteins and to proteins soluble at pH 8.9. In particular, chick-peas contain a high amount of tryptophan bound to water-soluble proteins, followed by beans. The results are evaluated, considering the importance, not only of protein, but also non-protein tryptophan, for assessing the nutritive value of a protein in food

    Serum levels of tryptophan, 5-hydroxytryptophan and serotonin in patients affected with different forms of amenorrhea

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    Tryptophan (Trp) is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT) through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5-hydroxytryptophan (5-HTP) in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P ≤ 0.05) lower in the anorexic (11.64 0.53 mug/ml, mean S.E.) than in the control (12.98 0.37 mug/ml) groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed.This study shows that women affected by various forms of amenorrhea present an altered metabolism of tryptophan via serotonin and, in particular, markedly high differences are observed between the two subgroups of anorexic patient
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