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

Language diversity in urban landscapes: An econometric study

This multidisciplinary study adopts econometric analysis for investigating how different characteristics determine the choice of the language used in the signs of a shopping street. We work with a dataset containing about 200 observations collected in the main shopping streets of the cities of Donostia (Spain) and Ljouwert (The Netherlands). The results corroborate the important assumption that multilingualism and the choice of the language (even in a street sign) is an individual and a social preference. Therefore, understanding individuals' linguistic preference structures is preliminary to the target and design of proper linguistic and social policies

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

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)

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

Routine Violence Risk Assessment in Community Forensic Mental Healthcare

We developed a method for periodic monitoring of violence risk, as part of routine community forensic mental healthcare. The feasibility of the method was tested, as well as its predictive validity for violent and risk enhancing behavior in the subsequent months. Participants were 83 clients who received forensic psychiatric home treatment, and six case managers. The method proved feasible and informative. Violent and risk enhancing behavior could be predicted to a reasonable extent (AUC = .77, 95% CI = .70-.85; respectively .76, .70-.82). Dynamic risk factors had an incremental predictive value over static factors in the prediction of violent behavior (OR = 4.30, 1.72-10.73). The professional judgment of the case managers added further predictive power (OR = 2.16, 1.40-3.33), corroborating the structured professional judgment approach. Finally, unmet needs for care of the client were associated with a reduced risk for violent and risk enhancing behavior (OR = .80, 0.69-0.93, and 0.84, 0.72-0.97). This latter finding suggests that in cases with unmet needs the case manager saw opportunities to do something about the risk. Currently we are testing whether using the method actually prevents violence. Copyright (C) 2009 John Wiley & Sons, Ltd

Use of quercetin in animal feed : effects on the P-gp expression and pharmacokinetics of orally administrated enrofloxacin in chicken

Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken. Absorption rate constant and apparent permeability coefficient of rhodamine 123 were decreased, reflecting efflux function of P-gp in chicken intestine increased by quercetin. Quercetin altered pharmacokinetic of enrofloxacin by decreasing area under curve, peak concentration, and time to reach peak concentration and by increasing clearance rate. Molecular docking shows quercetin can form favorable interactions with binding pocket of chicken xenobiotic receptor (CXR). Results provide convincing evidence that quercetin induced P-gp expression in tissues by possible interaction with CXR, and consequently reducing bioavailability of orally administered enrofloxacin through restricting its intestinal absorption and liver/kidney clearance in broilers. The results can be further extended to guide reasonable use of quercetin to avoid drug-feed interaction occurred with co-administered enrofloxacin or other similar antimicrobials.Peer reviewedFinal Published versio

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

Evidence for a shared etiological mechanism of psychotic symptoms and obsessive-compulsive symptoms in patients with psychotic disorders and their siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples