Abnormal plasma levels of serine, methionine, and taurine in transient acute polymorphic psychosis

The present study explored the usefulness of plasma amino acid concentrations in discriminating a subgroup of patients with transient acute polymorphic psychoses characterized by psychosensory symptoms (APP+ patients). Levels of amino acids in the plasma of APP+ patients were compared with levels in psychiatric patients with other types of psychotic symptomatology and a healthy control group. Both the APP+ patients with bipolar affective disorder had significantly lower plasma concentrations of serine compared with concentrations in the other groups studied. Since the plasma concentrations of taurine and methionine were also different in the APP+ patients, the ratio of taurine to the product of serine and methionine (the TSM ratio) was used in an attempt to increase the sensitivity in discriminating these patients. The TSM ratio in the APP+ patients was significantly higher than those in the other groups studied, except for the patients with bipolar affective disorder. It appears that the determination of serine and the TSM ratio in the plasma of psychotic patients may be a useful diagnostic validator in a group of patients with acute polymorphic psychoses

Changes in serine metabolism by a serum factor present in a group of episodic psychotic patients

__Abstract__ Addition of serum, obtained from patients suffering from an acute psychosis characterized by dysperceptions, to the culture media of fibroblasts altered the amino acid metabolism in these cells. After subculturing of fibroblasts in the presence of serum obtained from these patients, the concentrations of both serine and methionine were decreased in the medium as well as in the fibroblasts. Moreover, the concentration of taurine in the fibroblasts was increased. The specific activities of serine hydroxymethyltransferase and cystathionine β-synthase were also measured in the fibroblasts. It was found that both enzyme activities were significantly higher after subculturing with patients' serum as compared with serum obtained from healthy controls. It is concluded that a factor, present in the serum of these acute psychotic patients, is responsible for the observed changes in serine, taurine, and methionine concentrations in the fibroblasts as well as for the increased enzyme activities mentioned

Isolation and characterization of enzyme activities deiodinating thyroid hormone

It is well established that in man peripheral deiodination of T4 accounts for most of the biologically active T3 and virtually all of the inactive rT3• In several situations reciprocal changes in serum T3 and rT3 levels occur, which indicates that enzymatic deiodination is not an uncontrolled process. To get more insight into the regulation and mechanism of thyroid hormone metabolism, basic knowledge of the deiodinating enzyme(s) is necessary. Therefore, the aim of this study was to localize, purify and characterize the iodothyronine deiodinase( s). The availability of pure enzyme preparations will not only facilitate the elucidation of the molecular mechanism of thyroid hormone regulation, but also answer the question of whether one or two enzymes are involved in the deiodination of T4• In Chapter 2, in vitro observations of the enzymatic deiodination of iodothyronines are described. In addition to a review of the literature, results from my own work are also included. The results of this work are discussed in relation to the findings by other investigators.In the following chapters, which are papers already published, my investigations of the enzymatic deiodination of several iodothyronines in rat liver preparations are described in detail

Eicosanoid and amino acid metabolism in transient acute psychoses with psychedelic symptoms

It has been hypothesized that a disturbance of glutathione (GSH) metabolism might be a common factor in many psychiatric disorders. The aim of the present study was to test this hypothesis in transient acute psychotic patients with distorted perceptions. Since the metabolism of GSH is related to that of thromboxane B 2 (TXB 2), prostaglandin E (PGE) and some amino acids, we determined these substances in the plasma of 15 patients and 17 normal controls. Plasma concentrations of TXB 2 were significantly higher and concentrations of serine and tryptophan were significantly lower in patients than in controls. Large variation was observed in plasma PGE levels in patients, although mean values did not differ significantly from controls. These results are consistent with the hypothesis that the metabolism of GSH is impaired in transient psychotic states

Validation of the determination of amino acids in plasma by high-performance liquid chromatography using automated pre-column derivatization with o-phthaldialdehyde

A sensitive and reproducible fully automated method for the determination of amino acids in plasma based on reversed-phase high-performance liquid chromatography and o-phthaldialdehyde pre-column derivatization is described. A 5-μm Spherisorb ODS 2 column (125 × 3 mm I.D.) was selected for routine determination. Over 40 physiological amino acids could be determined within 49 min (injection to injection) and 48 samples could be processed unattended. The coefficients of variation for most amino acids in plasma were below 4%. We were also able to measure trace amounts of amino acids in plasma normally not detected in a routine analysis. The results obtained with the method described compared favourably with those of conventional amino acid analysis (r = 0.997) and were in excellent agreement with those of other laboratories (r = 0.999)

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-α therapy

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-α (IFN-α). Animal studies showed that IFN-α administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-α. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-α, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-α are unlikely to contribute to definite psychiatric disturbance

Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations

Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer’s disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (ρ = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

Background: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS. In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo. To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. Findings: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states. ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. Conclusions: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. Trial registration: ISRCTN0751814