STC1 and PTHrP modify carbohydrate and lipid metabolism in liver of a teleost fish

Stanniocalcin 1 (STC1) and parathyroid hormone-related protein (PTHrP) are calciotropic hormones in vertebrates. Here, a recently hypothesized metabolic role for these hormones is tested on European sea bass treated with: (i) teleost PTHrP(1-34), (ii) PTHrP(1-34) and anti-STC1 serum (pro-PTHrP groups), (iii) a PTHrP antagonist PTHrP(7-34) or (iv) PTHrP(7-34) and STC1 (pro-STC1 groups). Livers were analysed using untargeted metabolic profiling based on proton nuclear magnetic resonance (1H-NMR) spectroscopy. Concentrations of branched-chain amino acid (BCAA), alanine, glutamine and glutamate increased in pro-STC1 groups suggesting their mobilization from the muscle to the liver for degradation and gluconeogenesis from alanine and glutamine. In addition, only STC1 treatment decreased the concentrations of succinate, fumarate and acetate, indicating slowing of the citric acid cycle. In the pro-PTHrP groups the concentrations of glucose, erythritol and lactate decreased, indicative of gluconeogenesis from lactate. Taurine, trimethylamine, trimethylamine N-oxide and carnitine changed in opposite directions in the pro-STC1 versus the pro-PTHrP groups, suggesting opposite effects, with STC1 stimulating lipogenesis and PTHrP activating lipolysis/β-oxidation of fatty acids. These findings suggest a role for STC1 and PTHrP related to strategic energy mechanisms that involve the production of glucose and safeguard of liver glycogen reserves for stressful situations.Portuguese Foundation for Science and Technology (FCT) SFRH/BD/103185/2014info:eu-repo/semantics/publishedVersio

Electroconvulsive Therapy in the Netherlands A Questionnaire Survey on Contemporary Practice

Objective: To investigate contemporary Dutch practice of electroconvulsive therapy (ECT) and adherence to national and international ECT guidelines. Methods: Among psychiatrists from all Dutch ECT sites in university and general hospitals (n = 24) and psychiatric hospitals (n = 11), a survey was conducted regarding (1) characteristics of practitioners and institutions, (2) clinical practice of ECT, and (3) technical aspects of ECT Adherence to 16 criteria selected from (inter)national guidelines was scored. Results: Response rate was 94% (all 24 university and general hospitals and 9 of 11 psychiatric hospitals), Most respondents had extensive experience with ECT (median, 10 years; interquartile range, 4-15 years). Annually, approximately 8.5 sessions of ECT per 10,000 inhabitants were administered. In all ECT sites, 24% used exclusively bilateral electrode placement, 26% used ultrabrief pulse width, and 36% used dosage titration methods. Many practitioners had no knowledge of pulse width (42%) or of current characteristics (12%). Of the 16 investigated criteria, 14 were followed in at least 75% of the institutions. Conclusions: Although still increasing, the use of ECT in the Netherlands remains modest. Electroconvulsive therapy is generally practiced according to (inter)national guidelines. Electroconvulsive therapy is mostly started unilaterally, and generally, age-dependent dosage methods are being used. Knowledge on pulse width and current characteristics is limited. The implementation of updated guidelines might offer the opportunity to further improve practice and stimulate availability of ECT

Assessment of methylphenidate-induced changes in binding of continuously infused [C-11]-raclopride in healthy human subjects:correlation with subjective effects

Rationale: The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders. It has been shown that information on endogenous dopamine (DA) release can be obtained noninvasively by combining positron emission tomography with a dopaminergic challenge. This approach is based on the assumption that an injected radiolabeled ligand competes with the neurotransmitter for the same receptor. Increases in DA release will therefore result in a decreased binding of the radioligand.Objectives: We investigated the effect of the DA reuptake blocker methylphenidate (MP) on the binding of the D-2 receptor ligand [C-11]-raclopride (RAC). Methods: The effect of a 0.25 mg/kg intravenous dose of MP was studied in six healthy volunteers. RAC was administered as a bolus followed by constant infusion, and subjective effects were assessed using verbal rating scales. Results: Control scans without MP administration showed that the mean RAC binding reached stable values approximately 30 min after start of the infusion. MP administration induced a 24% decrease in RAC binding in the total striatum. Correlations were found between the MP-induced change in euphoria and the percent change in binding potential (Delta BP) in the dorsal striatum and between baseline anxiety and Delta BP in the dorsal and middle striatum. We also found a negative correlation between baseline BP in the dorsal striatum and change in euphoria. Conclusions: Our results comply with previous findings, indicating the feasibility of the bolus infusion design combined with a relatively low MP dose to study dopaminergic (dys)function

5-HT1A receptor imaging in the human brain:Effect of tryptophan depletion and infusion on [F-18]MPPF binding

The 5-HT1A receptor has been implicated in a variety of physiological processes, psychiatric disorders, and neurodegenerative disorders. [F-18]MPPF is a useful radioligand for quantitative imaging of 5-HT1A receptors in human subjects. Previous studies have shown that the binding of some radioligands is sensitive to changes in neurotransmitter concentration, whereas in other cases, binding is not affected. In the present study we investigated if [F-18]MPPF binding to the 5-HT1A receptor is sensitive to changes in 5-HT. Changes in 5-HT levels were achieved by influencing its synthesis through tryptophan depletion, including a tryptophan-free amino acid drink 4.5 h prior to the PET scan and tryptophan infusion (10 mg/ml, 50 mg/kg, 30 min, starting 60 min prior to the PET scan). Binding of [F-18]MPPF in the brain of six healthy, male volunteers was compared in these two conditions. Mean binding potentials in the medial temporal cortex, cortical regions, and raphe nucleus did not significantly differ between the two conditions. The results of the study show that, under the experimental conditions used, [F-18]MPPF binding was not affected. It is hypothesized that the increases in 5-HT levels needed to produce a measurable effect on [F-18]MPPF binding would be significantly greater than that possible with tryptophan manipulation. Therefore, in pathological conditions, where such large increases in 5-HT levels are not expected, [F-18]MPPF seems a useful ligand to measure 5-HT1A receptor distribution without the interference of endogenous 5-HT. (C) 2002 Wiley-Liss, Inc