Determination of Imidazole Dipeptides and Related Amino Acids in Natural Seafoods by Liquid Chromatography-Tandem Mass Spectrometry Using a Pre-Column Derivatization Reagent.

Imidazole dipeptides (IDPs) and taurine (Tau) have several health benefits and are known to be contained in natural seafoods. However, their levels vary widely in different natural seafoods, making their simultaneous determination desirable. Herein, we employ a liquid chromatography-tandem mass spectrometry approach using a novel amino group derivatization reagent, succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl-5-oxoimidazolidin-4-yl) acetate (()-CIMa-OSu), for the simultaneous quantification of IDPs (carnosine (Car) and anserine (Ans)), their related amino acids, and Tau in natural seafoods.

Use of Commercial Mixed-Mode Stationary Phases and Sorbents in the High-Performance Liquid Chromatography Analysis and Solid-Phase Extraction of Ionized and Hydrophilic Bioactive Compounds.

Mixed-mode high-performance liquid chromatography (HPLC) is increasingly used for the analysis of ionic and highly hydrophilic drugs, which are difficult to separate by conventional single-mode HPLC. In the former case, chromatographic separation is achieved using one of the several commercially available mixed-mode stationary phases, typically combinations of reversed and ion-exchange phases. Moreover, mixed-mode stationary phases can be used as solid-phase extraction (SPE) sorbents.

Evaluation of D-amino acid oxidase activity in rat kidney using a D-kynurenine derivative, 6-methylthio-D-kynurenine: An in vivo microdialysis study.

D-Amino acid oxidase (DAO), a D-amino acid metabolizing enzyme, is reportedly associated with the psychiatric disease schizophrenia, suggesting a role for DAO inhibitors in its treatment. We have previously reported that DAO catalyzes the conversion of nonfluorescent 6-methylthio-D-kynurenine (MeS-D-KYN) to fluorescent 5-methylthiokynurenic acid (MeS-KYNA) in vitro. The present study aimed to determine the potential of MeS-D-KYN in evaluating DAO activity in vivo using renal microdialysis technique in rats.

Substituted kynurenic acid derivatives as fluorophore-based probes for D- and L-amino acid oxidase assays and their application in eels.

High levels of D-amino acid oxidase (DAO) are associated with neurological and psychiatric disorders, while L-amino acid oxidase (LAO) exhibits antimicrobial and antitumor properties. The enzymatic conversion of the non-fluorescent kynurenine (KYN) into the endogenous weak fluorescent kynurenic acid (KYNA) by the action of DAO has previously been reported. However, the fluorescence of KYNA can be improved by changing the substituents on the aromatic rings.

Determination of d- and l-Amino Acids in Garlic Foodstuffs by Liquid Chromatography-Tandem Mass Spectrometry.

Black garlic is currently attracting interest as a health food and constituent of commercial supplements; however, no data regarding the d-amino acids within black garlic have been reported. Therefore, the amino acid compositions of methanol extracts from fresh and black garlic were compared herein. We investigated the contents of the d- and l-forms of amino acids in commercial fresh, black, and freeze-dried garlic foodstuffs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a pre-column chiral derivatization reagent, succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl-5-oxoimidazolidin-4-yl) acetate.

Analyzing Citramalic Acid Enantiomers in Apples and Commercial Fruit Juice by Liquid Chromatography-Tandem Mass Spectrometry with Pre-Column Derivatization.

Optically active citramalic acid (CMA) is naturally present as an acidic taste component in fruits, such as apples. The absolute configuration of CMA in such fruits was investigated by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) following pre-column derivatization with a chiral reagent, benzyl 5-(2-aminoethyl)-3-methyl-4-oxoimidazolidine-1-carboxylate. The developed LC-MS/MS method successfully separated the enantiomers of CMA using an octadecylsilica column with a resolution and separation factor of 2.

Direct Fluorescence Evaluation of d-Amino Acid Oxidase Activity Using a Synthetic d-Kynurenine Derivative.

d-Amino acid oxidase (DAO) has been suggested to be associated with the central nervous system diseases, such as schizophrenia. We newly synthesized a nonfluorescent 5-methylthio-d-kynurenine (MeS-d-KYN), which was converted to blue-fluorescent 6-MeS-kynurenic acid (MeS-KYNA, λ = 364 nm, λ = 450 nm) through a one-step reaction by incubation with DAO. It was revealed that fluorescence intensity increased accompanied by commercial porcine kidney DAO activity (unit) with a good correlation ( = 0.

Imatinib induces diastolic dysfunction and ventricular early-repolarization delay in the halothane-anesthetized dogs: Class effects of tyrosine kinase inhibitors.

Imatinib has been reported to induce heart failure and/or QTc prolongation. To better understand their underlying mechanisms, we assessed its effects on cardiohemodynamic, electrocardiographic and echocardiographic variables along with biomarkers of myocardial damage. Imatinib mesylate in doses of 1 and 10 mg/kg was intravenously administered to the halothane-anesthetized beagle dogs (n = 4).

Preparation of imidazolidinone compounds as derivatization reagent for diastereomerization and chromatographic separation of chiral organic acids.

A chiral derivatization reagent for application in LC-tandem mass spectrometry (LC-MS/MS)-based detection, benzyl 5-(2-aminoethyl)-3-methyl-4-oxoimidazolidine-1-carboxylate (CIM-C-NH), which can react with the carboxyl group, was synthesized. Both chiral and non-chiral organic acids such as lactic acid, 2-hydroxybutyric acid, 3-hydroxybutyric acid, acetic acid, succinic acid, tartaric acid, malic acid, and citramalic acid were derivatized with CIM-C-NH; their derivatives were analyzed by LC-MS/MS. We investigated the enantioseparation of chiral organic acids on an octadecylsilica column and obtained the resolution values within 1.

The difference of chows affects mouse physiological conditions.

Acetaminophen-induced liver injury in mice is a model system of human acetaminophen overdose and oxidative stress in vivo. The system is technically established, and we usually obtain severe liver damage in the treated mice; however, it is possible that the degree of liver damage is affected by the type of chow fed to mice. Thus, in this experiment, we investigated the effect of different chows on mice by comparing acetaminophen-induced liver damage, liver antioxidant level, and serum amino-acid concentrations.

A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids.

Kynurenine (KYN) is synthesized from an essential amino acid, tryptophan, by tryptophan 2,3-dioxygenase or indoleamine 2,3-dioxygenase via N-formyl-KYN in vivo. Subsequently, KYN acts as a precursor of some neuroactive metabolites such as kynurenic acid, quinolinic acid, and an important enzyme co-factor, nicotine adenine dinucleotide. These metabolites of tryptophan are a part of the 'kynurenine pathway.

Simultaneous analyses of hemodynamic and electrophysiological effects of oseltamivir along with its pharmacokinetic profile using the canine paroxysmal atrial fibrillation model.

Since information of antiviral drug oseltamivir on the anti-atrial fibrillation (AF) property is still limited, we assessed it using the canine paroxysmal AF model. Oseltamivir in doses of 3 and 30 mg/kg/10 min was intravenously infused to the isoflurane-anesthetized, chronic atrioventricular block dogs (n = 6) with monitoring hemodynamic and electrophysiological variables, in which AF was induced by 10 s of burst pacing on atrial septum. Oseltamivir decreased AF incidence and AF duration, and prolonged AF cycle length in a dose-dependent manner.

Increased Indoleamine 2,3-Dioxygenase Levels at the Onset of Sjögren's Syndrome in SATB1-Conditional Knockout Mice.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by dysfunction of salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Autoantibodies, such as anti-SSA and anti-SSB antibodies, are hallmarks and important diagnostic factors for SS. In our previous study, we demonstrated that SS-like xerostomia was observed in SATB1 conditional knockout (SATB1cKO) mice, in which the floxed SATB1 gene was specifically deleted in hematopoietic cells as early as 4 weeks of age.

Separation of vigabatrin enantiomers using mixed-mode chromatography and its application to determine the vigabatrin enantiomer levels in rat plasma.

Mixed-mode chromatography-comprising a mixed phase with reversed and ionic phases, enabling hydrophobic and ion-exchange interactions simultaneously-was applied to identify vigabatrin enantiomers by HPLC with pre-column fluorescence derivatization with 2,5-dioxopyrrolidin-1-yl (4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate (Ns-MOK-(S)-Pro-OSu). The MOK-(S)-Pro-vigabatrin enantiomers were efficiently separated within 12 min (total analysis time per sample: 28 min, including washing and equilibrium time for the column). The mobile phase was HO/CHOH/10 mM ammonium formate (pH 2.

Development of a Derivatization Reagent with a 2-Nitrophenylsulfonyl Moiety for UHPLC-HRMS/MS and Its Application to Detect Amino Acids Including Taurine.

Taurine (Tau) has some important ameliorating effects on human health and is present in bivalve. For the selective analysis of Tau with other amino acids, we designed a derivatization reagent, 2,5-dioxopyrrolidin-1-yl(4-(((2-nitrophenyl)sulfonyl)oxy)-6-(3-oxomorpholino)quinoline-2-carbonyl)pyrrolidine-3-carboxylate (Ns-MOK-β-Pro-OSu). After derivatization with Ns-MOK-β-Pro-OSu, amino acids with Tau in Japanese littleneck clams were determined through ultra-high-performance-liquid chromatography with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) using an octadecyl silica column.

Development of derivatization reagents bearing chiral 4-imidazolidinone for distinguishing primary amines from other amino acids and application to the liquid chromatography-tandem mass spectrometric analysis of miso.

We designed and synthesized three novel derivatization reagents bearing chiral 4-imidazolidinone, namely succinimidyl 2-(3-((benzyloxy)carbonyl)-1-methyl, ethyl, and -phenyl-5-oxoimidazolidin-4-yl)acetates (CIMs), for use in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The CIMs were able to discriminate primary amines from other compounds such as secondary amines and phenols, based on their unique m/z reduction of precursor ion to form product ion in MS/MS. As amino acid derivatization reagents, the CIMs were compared in terms of enantioseparation of amino acid and detection sensitivity.

Increased inosine levels in drug-free individuals with at-risk mental state: A serum metabolomics study.

Aim: At-risk mental state (ARMS) has been recently attracting attention with respect to the improvement of the management and outcome of psychiatric diseases, such as schizophrenia. Since only a few studies have reported on biological alterations in ARMS, serum metabolomics was carried out in ARMS subjects and healthy controls using liquid chromatography with high-resolution mass spectrometry.

Methods: Serum samples were collected from ARMS subjects (n = 24; male: 12; female 12) and age- and sex-matched healthy controls (n = 23 male: 11, female: 12).

Fluorimetric determination of the enantiomers of vigabatrin, an antiepileptic drug, by reversed-phase HPLC with a novel diastereomer derivatization reagent.

Herein, determination of an antiepileptic drug, (±)-vigabatrin (VB), was performed by reversed-phase HPLC with fluorimetric detection using a newly designed and synthesized fluorescence derivatization reagent, 2,5-dioxopyrrolidin-1-yl (4-{[(2-nitrophenyl)sulfonyl]oxy}-6-(3-oxomorpholino)quinoline-2-carbonyl)prolinate [Ns-MOK-(R)- or (S)-Pro-OSu]. During the derivatization of VB with Ns-MOK-(R)-Pro-OSu at 60°C, the nosyl (Ns) group, which was introduced to protect a phenolic hydroxy group, was released within 30 min to produce MOK-(R)-Pro-VB, which was detected fluorimetrically at 448 nm with an excitation wavelength of 333 nm. The VB enantiomers were separated on an octadecylsilica (ODS) column with a resolution value of 5.

LC-MS/MS Analysis of Thiol-Containing Amino Acids in Exosomal Fraction of Serum.

It has been suggested that thiol-containing amino acids could be used as biomarkers for diseases associated with oxidative stress. We investigated the thiol-containing amino acids, homocysteine (Hcy), cysteine (Cys), glutathione (GSH) and γ-glutamylcysteine (γ-GluCys), in commercial human serum by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) after precolumn derivatization with 4-fluoro-7-sulfobenzofurazan. This method was applied to determine the composition of thiol-containing amino acids in exosomes prepared from the serum.

Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.

Importance: Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted.

Objective: To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features.

Design, Setting, And Participants: This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019.

Alterations in methionine to homocysteine ratio in individuals with first-episode psychosis and those with at-risk mental state.

Background: Disturbance of the methionine (Met) cycle, which produces Met from homocysteine (Hcy), is suggested to be involved in several diseases, including psychiatric disorders. This study was aimed to investigate both levels of Met and Hcy in serum from individuals with first-episode psychosis (FEP) and individuals with at-risk mental state (ARMS).

Method: We measured serum Met and Hcy levels in individuals with FEP (n = 13) and ARMS (n = 30) using HPLC with fluorescence detection and LC-ESI-MS/MS.

Alteration in plasma docosahexaenoic acid levels following oral administration of ethyl icosapentate to rats.

Objectives: Ethyl icosapentate, a prodrug of eicosapentaenoic acid (EPA), has been prescribed to not only hyperlipidemia, but also psychotic patients. We have examined the impact of an orally administered polyunsaturated fatty acid (PUFA), ethyl icosapentate, on the plasma concentrations of seven other types of fatty acids and one metabolite (3-hydroxybutyrate, 3-HB) using rats.

Design: and Methods: A commercial omega-3 PUFA, EPA, formulation (ethyl icosapentate, Epadel®) was administered orally to Sprague-Dawley rats (15, 50, 100 mg/kg,  = 4-8) and changes in the plasma fatty acid concentrations were investigated by HPLC using fluorescence detection.

Serum d- and l-lactate, pyruvate and glucose levels in individuals with at-risk mental state and correlations with clinical symptoms.

Aim: Little information exists on the peripheral metabolite levels in individuals with at-risk mental state who meet the criteria for a high-risk state of psychosis. Here, we aimed to investigate serum levels of glucose, pyruvate and d- and l-lactate, which may act as a signalling molecule for learning and memory in neuronal cells.

Methods: High performance liquid chromatography or commercial kits were used to assess serum metabolites in individuals with attenuated psychosis symptoms of at-risk mental state (n = 24, men = 12) who were not receiving antipsychotics.

An Adult Case of Herpes Simplex Virus-associated Granulomatous Encephalitis.

Brain granuloma occurs under certain conditions. Herpes simplex virus (HSV) causes granulomatous encephalitis in children; however, it has been rarely reported in adults. A 74-year-old man with a history of herpes simplex encephalitis suffered recurrent seizures.