Automated mass spectrometric analysis of urinary free catecholamines using on-line solid phase extraction.

Analysis of catecholamines (epinephrine, norepinephrine and dopamine) in plasma and urine is used for diagnosis and treatment of catecholamine-producing tumors. Current analytical techniques for catecholamine quantification are laborious, time-consuming and technically demanding. Our aim was to develop an automated on-line solid phase extraction method coupled to high performance liquid chromatography-tandem mass spectrometry (XLC-MS/MS) for the quantification of free catecholamines in urine.

Elevated urinary free and deconjugated catecholamines after consumption of a catecholamine-rich diet.

Context: The biochemical diagnosis of pheochromocytoma depends on the demonstration of elevated levels of catecholamines (i.e. epinephrine, norepinephrine, and dopamine) and their metabolites.

Automated mass spectrometric analysis of urinary and plasma serotonin.

Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim was to develop a rapid, sensitive, and highly selective automated on-line solid-phase extraction method coupled to high-performance liquid chromatography-tandem mass spectrometry (XLC-MS/MS) to quantify low serotonin concentrations in matrices such as platelet-poor plasma and urine.

Exercise enhances whole-body cholesterol turnover in mice.

Purpose: Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels, but the underlying mechanisms have not been fully explored. Exercise might provoke changes in cholesterol and bile acid metabolism and thereby reduce cardiovascular risk. We examined whether voluntary wheel running in mice modulates cholesterol and bile acid metabolism.

Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration.

Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that determine the fate of new tissue within the overall morphogenetic program of the organism is fundamental. We identified novel early signals, mediated by the central nervous system and 3 innexin proteins, which determine the fate and axial polarity of regenerated tissue in planarians.

Psychophysiological biomarkers explaining the association between depression and prognosis in coronary artery patients: a critical review of the literature.

This paper aims to provide an overview of the current state of affairs on psychophysiological factors that may explain the link between depression and adverse outcome in coronary artery disease (CAD) patients. Factors discussed include heart rate variability, inflammation, platelet function, hypothalamus-pituitary-adrenal axis activity, serotonin metabolism and polyunsaturated fatty acids. Evidence suggests the involvement of each of these factors in both depression and CAD, together contributing to the prospective association between depression and cardiac outcome.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

Objective: A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production.

Methods: Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals.

Increased urinary excretion of 3-methoxytyramine in patients with head and neck paragangliomas.

Context: Patients with head-and-neck paragangliomas (HNPGL) are regularly screened for catecholamine excess. The clinical relevance of increased urinary secretion of 3-methoxytyramine is unclear in HNPGL.

Objective: The aim of the study was to assess the prevalence and the clinical, biochemical, and radiological presentation of patients with HNPGL with increased urinary excretion of 3-methoxytyramine.

Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer.

Background: Procalcitonin has been well established as an important marker of sepsis and systemic infection. The authors evaluated the diagnostic and predictive value of calcitonin and its prohormone procalcitonin in medullary thyroid cancer.

Methods: The authors systematically explored the ability of calcitonin and procalcitonin to identify medullary thyroid cancer and predict the endpoints local recurrence and distant metastases, as well as the progression-free survival.

The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT.

Background: Polymorphisms of monoamine-related genes have been associated with depression following life events. The peripartum is a physiologically and psychologically challenging period, characterized by fluctuations in depressive symptoms, therefore facilitating prospective investigations in this gene x environment (G x E) interaction.

Methods: Eighty nine pregnant women filled in two Edinburgh Postpartum Depression Scale (EPDS) questionnaires during pregnancy and two in the postpartum period.

6-[F-18]Fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to conventional imaging with (123)I-metaiodobenzylguanidine scintigraphy, computer tomography, and magnetic resonance imaging in localizing tumors causing catecholamine excess.

Context: Catecholamine excess is rare, but symptoms may be life threatening.

Objective: The objective of the study was to investigate the sensitivity of 6-[F-18]fluoro-l-dihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET), compared with (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy and computer tomography (CT)/magnetic resonance imaging (MRI) for tumor localization in patients with catecholamine excess.

Design And Setting: All consecutive patients with catecholamine excess visiting the University Medical Center Groningen, Groningen, The Netherlands, between March 2003 and January 2008 were eligible.

Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors.

Context: Measurements of the 3-O-methylated metabolites of catecholamines [metanephrines (MNs)] in plasma or urine are recommended for diagnosis of pheochromocytoma. It is unclear whether these tests are susceptible to dietary influences.

Objective: The aim of the study was to determine the short-term influence of a catecholamine-rich diet on plasma and urinary fractionated MNs.

Quick identification of acute chest pain patients study (QICS).

Background: Patients with acute chest pain are often referred to the emergency ward and extensively investigated. Investigations are costly and could induce unnecessary complications, especially with invasive diagnostics. Nevertheless, chest pain patients have high mortalities.

Molecular imaging in neuroendocrine tumors: molecular uptake mechanisms and clinical results.

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods.

Plasma tryptophan, kynurenine and 3-hydroxykynurenine measurement using automated on-line solid-phase extraction HPLC-tandem mass spectrometry.

Tryptophan metabolism plays a key role in several (patho)physiological conditions. In order to study the clinical importance of tryptophan and its predominant metabolites (kynurenines), it is important to be able to measure large series of samples with high accuracy and reliability. We aimed to develop a high-throughput on-line solid-phase extraction-liquid chromatographic-tandem mass spectrometric (XLC-MS/MS) method that enables the measurement of tryptophan and its metabolites kynurenine and 3-hydroxykynurenine in plasma.

Investigating the molecular basis of major depressive disorder etiology: a functional convergent genetic approach.

Genes play a major role in behavioral adaptation to challenging environmental stimuli, but the complexity of their contribution remains unclear. There is growing evidence linking disease phenotypes with genes on the one hand, and the genesis of stress-related disorders like major depression, as a result of exposure to stressful environmental pathogens on the other. Here we illustrate the convergent role of monoaminergic genes in regulating the underlying biological mechanisms of stress and the emotions.

Differential effects of 5-HTTLPR and DRD2/ANKK1 polymorphisms on electrocortical measures of error and feedback processing in children.

Objective: Applying a probabilistic learning task we examined the influence of functional polymorphisms of the serotonin transporter gene (5-HTTLPR) and the D2 dopamine receptor gene (DRD2/ANKK1) on error and feedback processing by measuring electrocortical event-related potentials (ERPs) in 10- to 12-year-old children.

Methods: Three pairwise group comparisons were conducted on four distinguishable ERP components, two of which were response-related, the other two feedback-related.

Results: Our ERP data revealed that children carrying the short (S) variant of the 5-HTTLPR gene process their errors more intensively while exhibiting less habituation to negative feedback with task progression compared to children who are homozygous for the 5-HTTLPR long (L) variant.

Sexual function in patients with metastatic midgut carcinoid tumours.

Background: Sexual dysfunction is a poorly studied aspect of quality of life in patients with midgut carcinoid tumours. We investigated whether carcinoid patients experience sexual problems.

Methods: Patients with metastatic midgut carcinoid tumours filled in a validated questionnaire for sexual dysfunction.

Manipulation of [11C]-5-hydroxytryptophan and 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells.

[(11)C]-5-Hydroxytryptophan ([(11)C]HTP) and 6-[(18)F]fluoro-3,4-dihydroxy-l-phenylalanine ([(18)F]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large amino acid transporters, peripheral decarboxylation (inhibited by carbidopa), and intracellular breakdown by monoamine oxidase (MAO).

Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion.

Background: Previously we observed in patients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan resulted in higher stress responses and higher corticosterone production. Here we tested in carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction is associated with high cortisol production.

111In-octreotide is superior to 123I-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas.

Unlabelled: In this study, we evaluated the diagnostic yield of somatostatin receptor scintigraphy (SRS), I-metaiodobenzylguanidine (MIBG) scintigraphy, and morphologic imaging (CT or MRI) in patients with head and neck paragangliomas.

Methods: In a university hospital setting, patients considered to have head and neck paraganglioma were referred to the outpatient endocrinology department and underwent CT or MRI, SRS, and MIBG imaging. For validation, we used a composite reference standard consisting of clinical and histologic data and CT or MRI, with which SRS and MIBG imaging were compared.