Elusive amines: migraine depends on biochemical abnormalities.

The pathogenesis of migraine, as well as cluster headache (CH), is yet a debated question. In this review, we discuss the possible role of tyrosine and tryptophan metabolism in the pathogenesis of primary headaches, including the abnormalities in the synthesis of neurotransmitters. High level of dopamine, low level of norepinephrine, and very elevated levels of octopamine and synephrine were found in the plasma of episodic migraine without aura.

Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis.

Background And Aim: The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system's first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine.

Grape Seeds Proanthocyanidins: Advanced Technological Preparation and Analytical Characterization.

A "green" solvent-free industrial process (patent pending) is here described for a grape seed extract (GSE) preparation (Ecovitis™) obtained from selected seeds of Veneto region wineries, in the northeast of Italy, by water and selective tangential flow filtration at different porosity. Since a comprehensive, non-ambiguous characterization of GSE is still a difficult task, we resorted to using an integrated combination of gel permeation chromatography (GPC) and electrospray ionization high resolution mass spectrometry (ESI-HRMS). By calibration of retention time and spectroscopic quantification of catechin as chromophore, we succeeded in quantifying GPC polymers up to traces at = 30.

Breathomics in Asthmatic Children Treated with Inhaled Corticosteroids.

Background: "breathomics" enables indirect analysis of metabolic patterns underlying a respiratory disease. In this study, we analyze exhaled breath condensate (EBC) in asthmatic children before (T0) and after (T1) a three-week course of inhaled beclomethasone dipropionate (BDP).

Methods: we recruited steroid-naive asthmatic children for whom inhaled steroids were indicated and healthy children, evaluating asthma control, spirometry and EBC (in asthmatics at T0 and T1).

Pathogenesis of Cluster Headache: From Episodic to Chronic Form, the Role of Neurotransmitters and Neuromodulators.

Objective: To describe the role of biochemical anomalies of tyrosine (TYR), tryptophan (TRP), and arginine (ARG) metabolism in patients suffering from episodic and chronic cluster headache (CCH).

Background: The pathogenesis of cluster headache (CH) and the process that transforms the episodic into the chronic form are unknown. However, the accompanying symptoms suggest a dysfunction of the sympathetic system and hypothalamus along with anomalies of metabolism of catecholamines, elusive amines, and nitric oxide (NO) metabolism.

Quantification of Underivatized Amino Acids on Dry Blood Spot, Plasma, and Urine by HPLC-ESI-MS/MS.

Enzyme deficiencies in amino acid metabolism may increase the levels of a single or several compounds in physiological fluids becoming diagnostically significant biomarkers for one or a group of metabolic disorders. Therefore, it is important to monitor a wide range of free amino acids simultaneously and to quantify them. This is time consuming if we use the classical methods and, especially now that many laboratories have introduced Newborn Screening Programs for the semiquantitative analysis, the detection and quantification of some amino acids need to be performed in a short time to reduce the rate of false positives.

Different Circulating Trace Amine Profiles in De Novo and Treated Parkinson's Disease Patients.

Early diagnosis of Parkinson's disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. A new ultra performance chromatography mass spectrometry (UPLC-MS/MS) method was developed to quantify plasmatic TAs, and the catecholamines and indolamines pertaining to the same biochemical pathways.

A prospective pilot study of the effect on catecholamines of mindfulness training vs pharmacological prophylaxis in patients with chronic migraine and medication overuse headache.

Aim: To address whether, in patients with chronic migraine and medication overuse headache, mindfulness-based treatment is associated with changes in plasma levels of catecholamines and elusive amines that are similar to those observed in patients undergoing pharmacological prophylaxis.

Methods: In this non-randomized, clinic-based effectiveness study, patients aged 18-65, with a history of chronic migraine ≥ 10 years and overuse of triptans or non-steroidal anti-inflammatory drugs ≥ 5 years, were enrolled. Upon completion of a structured withdrawal program, patients received either pharmacological prophylaxis or six weekly sessions of mindfulness-based treatment and were followed for 12 months.

Lipopolysaccharide-induced chorioamnionitis and postnatal lung injury: The beneficial effects of L-citrulline in newborn rats.

Aim Of The Study: The lung architecture of newborns appears to be affected by an inflammatory reaction to maternal choriodecidual layer infection. L-citrulline (L-Cit) was administered to pregnant rats exposed to intra-amniotic lipopolysaccharide (LPS)-induced chorioamnionitis to investigate its effect on neonatal lung injury.

Materials And Methods: The pups were assigned to four experimental groups: 1- pups exposed to intra-amniotic NaCl but not to postnatal L-Cit (Controls); 2 - pups exposed to intra-amniotic NaCl as well as to postnatal L-Cit treatment (L-Cit group); 3 - pups exposed to prenatal LPS but not to postnatal (LPS); 4- pups exposed to prenatal LPS as well as to postnatal L-Cit treatment (LPS + L-Cit).

Metabolomics reveals new metabolic perturbations in children with type 1 diabetes.

Objective: Using an untargeted metabolomics approach we investigated the metabolome of children with type 1 diabetes (T1D) in comparison with healthy peers and explored the contribution of HbA1c and clinical features to the observed difference.

Research Design And Methods: We enrolled children with T1D aged 6-15 years, attending the pediatric diabetes clinic of University of Padova (Italy). Healthy controls were enrolled on voluntary basis and matched for age, sex, pubertal status, body mass index (BMI).

Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.

Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed.

Asymmetric dimethylarginine and related metabolites in exhaled breath condensate of children with cystic fibrosis.

Introduction: Asymmetric dimethylarginine (ADMA) competitively inhibits nitric oxide synthase (NOS). Its levels in specimens from murine models and asthmatic patients are related to inflammation and oxidative stress. Patients with cystic fibrosis(CF) reportedly have higher arginase activity, lower NO production and NOS expression than healthy controls.

Abnormal tyrosine metabolism in chronic cluster headache.

Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns.

Background: Acylcarnitines are biomarkers of fatty acid metabolism, and examining their patterns in preterm newborn may reveal metabolic changes associated with particular conditions related to prematurity. Isomeric acylcarnitines in dried blood spots (DBS) and plasma have never been assessed in preterm infants.

Methods: We studied 157 newborn divided into four groups by weeks of gestational age (GA), as follows: 22-27 wk in group 1; 28-31 wk in group 2; 32-36 wk in group 3; and 37-42 wk in group 4.

A column-switching HPLC-MS/MS method for mucopolysaccharidosis type I analysis in a multiplex assay for the simultaneous newborn screening of six lysosomal storage disorders.

Lysosomal storage disorders comprise a group of rare genetic diseases in which a deficit of specific hydrolases leads to the storage of undegraded substrates in lysosomes. Impaired enzyme activities can be assessed by MS/MS quantification of the reaction products obtained after incubation with specific substrates. In this study, a column-switching HPLC-MS/MS method for multiplex screening in dried blood spot of the lysosomal enzymes activities was developed.

Online trapping and enrichment ultra performance liquid chromatography-tandem mass spectrometry method for sensitive measurement of "arginine-asymmetric dimethylarginine cycle" biomarkers in human exhaled breath condensate.

Background: Exhaled breath condensate (EBC) is a biofluid collected non invasively that, enabling the measurement of several biomarkers, has proven useful in the study of airway inflammatory diseases, including asthma, COPD and cystic fibrosis. To the best of our knowledge, there is no previous report of any analytical method to detect ADMA in EBC.

Objectives: Aim of this work was to develop an online sample trapping and enrichment system, coupled with an UPLC-MS/MS method, for simultaneous quantification of seven metabolites related to "Arginine-ADMA cycle", using the isotopic dilution.

A rapid UPLC-MS/MS method for simultaneous separation of 48 acylcarnitines in dried blood spots and plasma useful as a second-tier test for expanded newborn screening.

Acylcarnitine profiling in dried blood spots (DBS) is a useful method for high-throughput newborn screening of metabolic disorders, but differentiation of isobaric and isomeric compounds is not achievable. Chromatographic methods for separation have already been reported but are specific for short-chain acylcarnitines or time-consuming. The aim of this work was to develop a fast ultraperformance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method for separation and quantification of a large number of acylcarnitines, including dicarboxylic acylcarnitines and hydroxyacylcarnitines, in DBS and plasma samples.

Quantification of underivatised amino acids on dry blood spot, plasma, and urine by HPLC-ESI-MS/MS.

Enzyme deficiencies in amino acid (AA) metabolism affecting the levels of amino acids and their derivatives in physiological fluids may serve as diagnostically significant biomarkers for one or a group of metabolic disorders. Therefore, it is important to monitor a wide range of free amino acids simultaneously and to quantify them. This is time consuming if we use the classical methods and more than ever now that many laboratories have introduced Newborn Screening Programs for the semiquantitative analysis, detection, and quantification of some amino acids needed to be performed in a short time to reduce the rate of false positives.

Simultaneous quantitative determination of N(G),N(G)-dimethyl-L-arginine or asymmetric dimethylarginine and related pathway's metabolites in biological fluids by ultrahigh-performance liquid chromatography/electrospray ionization-tandem mass spectrometry.

Background: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) formation inhibitor, has emerged as a promising biomarker of NO-associated endothelial dysfunction in cardiovascular diseases as well in chronic renal failure. The interest in potentially fundamental role of this metabolite, in basic and clinical research, led to the development of numerous analytical methods for the quantitative determination of ADMA and dimethylarginines in biological systems, notably plasma, serum and urine.

Objectives: The aim of this work was to present a simple, fast and accurate UPLC-tandem-MS-based method for the simultaneous determination and quantification of arginine, ADMA, SDMA, NMMA, homo-arginine and citrulline.

Surfactant status in preterm neonates recovering from respiratory distress syndrome.

Objective: The goal was to establish whether reduced amounts of pulmonary surfactant contribute to postextubation respiratory failure in preterm infants recovering from respiratory distress syndrome.

Methods: We prospectively recruited preterm infants who needed mechanical ventilation and exogenous surfactant for treatment of moderate/severe respiratory distress syndrome and could not be extubated before day 3 of life. (13)C-labeled dipalmitoyl-phosphatidylcholine was administered endotracheally as tracer before extubation, for estimation of surfactant disaturated phosphatidylcholine pool size and half-life.

Simplified method for microlitre deuterium measurements in water and urine by gas chromatography-high-temperature conversion-isotope ratio mass spectrometry.

Deuterium (2H) in water and urine can be measured by off-line and, more recently, on-line techniques using isotope ratio mass spectrometry (IRMS). We describe a new simple on-line pyrolysis method for the analysis of 2H/1H in water and urine samples by continuous flow IRMS, normally used for 2H/1H measurements in organic compounds. A deactivated column connected the split injector to a high-temperature conversion reactor (TC HD), and 0.

Surfactant disaturated-phosphatidylcholine kinetics in acute respiratory distress syndrome by stable isotopes and a two compartment model.

Background: In patients with acute respiratory distress syndrome (ARDS), it is well known that only part of the lungs is aerated and surfactant function is impaired, but the extent of lung damage and changes in surfactant turnover remain unclear. The objective of the study was to evaluate surfactant disaturated-phosphatidylcholine turnover in patients with ARDS using stable isotopes.

Methods: We studied 12 patients with ARDS and 7 subjects with normal lungs.

Measurement of pulmonary surfactant disaturated-phosphatidylcholine synthesis in human infants using deuterium incorporation from body water.

The aim of the study was to determine surfactant palmitate disaturated-phosphatidylcholine (DSPC-PA) synthesis in vivo in humans by the incorporation of deuterium from total body water into DSPC-PA under steady state condition. We studied three newborns and one infant (body weight (BW) 4.6 +/- 2.

Surfactant disaturated phosphatidylcholine kinetics in infants with bronchopulmonary dysplasia measured with stable isotopes and a two-compartment model.

We previously found a shorter surfactant disaturated phosphatidylcholine palmitate (DSPC-PA) half-life in infants with bronchopulmonary dysplasia (BPD) by using a single stable isotope tracer and simple formulas based on a one-exponential fit of the final portion of the enrichment decay curve. The aim of this study was to apply noncompartmental and compartmental analysis on the entire enrichment decay curve of DSPC-PA and to compare the kinetic data with our previous results. We analyzed 10 preterm newborns with BPD (gestational age 26 +/- 0.

Surfactant-associated protein B kinetics in vivo in newborn infants by stable isotopes.

Surfactant-associated protein B (SP-B) is critical to the biophysical function of pulmonary surfactant. No information is available on SP-B synthesis and kinetics in humans. We administered a 24-h i.