bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical Prediction of the Phenoxyl Radical Formation Capacity and Cyclooxygenase Inhibition Relationships by Phenolic Compounds
Authors: Ruiz Juan , Pouplana Ramon 
Published: February 2003

AbstractDue to the importance of the O‐H bond dissociation in the antioxidant mechanism of anti‐inflammatory phenols, we studied the biradical process Ph‐OH→PhO.+H. for 25 phenolic compounds using ab initio calculations. Enthalpies of reaction (ΔHr), changes in the electron density at the O‐H bond critical point (ρOH) and total atomic charges of ortho and para carbon atoms strongly correlate with the in vitro inhibition of cyclooxygenase activity by phenols. The most active compounds have large values of the electron density at the O‐H bond (ρOH), thus favouring the O‐H bond dissociation. In contrast, inactive compounds have small values of the electron density at the O‐H bond (ρOH), thus reducing the hydrogen donation ability. These results are also supported by the representation of the molecular electrostatic potentials maps. The prediction of the cyclooxygenase inhibitory activity of the proposed QSAR equations is analysed using the multilineal (MLR) method. Finally, the differences in biological activity are examined by analysing the binding interactions of active compounds in the pocket site of human COX‐2 enzyme structure derived from crystallographic X ‐ray data.
Mechanistic Study on N‐Demethylation Catalyzed with P450 by Quantitative Structure Activity Relationship using Electronic Properties of 4‐Substituted N,N‐Dimethylaniline
Authors: Nanbo Asuka , Nanbo Toshio 
Published: February 2003

AbstractThe mechanism of N‐demethylation by P‐450 was investigated using MO calculation of 4‐substituted N,N‐dimethylaniline. The reactivities of the compounds and their intermediates were examined using the energies of HOMO and SOMO, and frontier electron densities. QSAR analysis using these electronic parameters indicated that one‐electron first transfers from nitrogen to P‐450 and the resultant cation radical forms α‐amino radical, followed by hydroxylation and N‐demethylation.
Reliability of estimation of recombination energies of molecular radical cations by charge exchange and a test of the exoergicity rule
Authors: Youn Yeu Young , Choe Joong Chul , Kim Myung Soo 
Published: February 2003

AbstractCharge exchange occurring in a collision cell of a mass spectrometer was used previously to find the very long‐lived excited electronic states of molecular cations generated by electron ionization. The underlying criterion in the method, called the exoergicity rule, was that only electronically exoergic and resonant processes have large cross sections at low collision energy. The validity of this rule has been checked in this work by estimating the recombination energies of some molecular ions based on the presence/absence of charge‐exchange signals from gases with different ionization energies, and comparing these estimates with the literature values. It is concluded that a recombination energy can be estimated to within an upper limit uncertainty of 0.1 eV with this technique, which validates the exoergicity rule proposed previously. Copyright © 2003 John Wiley & Sons, Ltd.
In vivo biotransformation of 17α‐methyltestosterone in the horse revisited: identification of 17‐hydroxymethyl metabolites in equine urine by capillary gas chromatography/mass spectrometry
Authors: Dumasia M. C. 
Published: February 2003

AbstractThe in vivo phase I biotransformation of 17α‐methyltestosterone in the horse leads to the formation of a complex mixture of regio‐ and stereoisomeric C20O2, C20O3 and C20O4 metabolites, excreted in urine as glucuronide and sulphate phase II conjugates. The major pathways of in vivo metabolism are the reduction of the A‐ring (di‐ and tetrahydro), epimerisation at C‐17 and oxidations mainly at C‐6 and C‐16. Some phase I metabolites have been identified previously by positive ion electron ionisation capillary gas chromatography/mass spectrometry (GC/EI + MS) mainly from the characteristic fragmentation patterns of their methyloxime‐trimethylsilyl ether (MO‐TMS), enol‐TMS or TMS ether derivatives. Following oral administration of 17α‐methyltestosterone to two castrated thoroughbred male horses, the glucuronic acid conjugates excreted in post‐administration urine samples were selectively hydrolysed by E. coli β‐glucuronidase enzymes. Unconjugated metabolites and the steroid aglycones obtained after enzymatic deconjugation were isolated from urine by solid‐phase extraction, derivatised as MO‐TMS ethers and analysed by GC/EI + MS. In addition to some of the known metabolites previously identified from the characteristic mass spectral fragmentation patterns of 17α‐methyl steroids, some isobaric compounds exhibiting a diagnostic loss of 103 mass units from the molecular ions with subsequent losses of trimethylsilanol or methoxy groups and an absence of the classical D‐ring fragment ion were detected. From an interpretation of their mass spectra, these compounds were identified as 17‐hydroxymethyl metabolites, formed in vivo in the horse by oxidation of the 17‐methyl moiety of 17α‐methyltestosterone. This study reports on the GC/EI + MS identification of these novel 17‐hydroxymethyl C20O3 and C20O4 metabolites of 17α‐methyltestosterone excreted in thoroughbred horse urine. Copyright © 2003 John Wiley & Sons, Ltd.
Lacidipine, a potential peroxynitrite scavenger: investigation of activity by liquid chromatography and mass spectrometry
Authors: Garzotti Marco 
Published: February 2003

AbstractInflamed tissues are often characterised by the production of .NO and O2− radicals, which are known to react at an extremely fast rate to produce peroxynitrite (ONOO−). This highly oxidising entity reacts with protein‐bound tyrosine to give 3‐nitrotyrosine, which is considered a biochemical marker of peroxynitrite‐induced damage. Lacidipine is a calcium antagonist indicated for the treatment of mild to moderate hypertension. In the present work, electrospray mass spectrometry with and without liquid chromatography was used to evaluate the capability of lacidipine and two other related molecules as ONOO− scavengers. This capability is compared with that associated with a number of commercial polyphenols described in the literature as efficient scavengers of this cytotoxic agent. The use of mass spectrometry provided rapid quantitative assessment of both the nitration and its reduction, and showed that lacidipine possesses a reasonable capability for reducing in vitro nitration of superoxide dismutase. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of silsesquioxanes by size‐exclusion chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Falkenhagen Jana , Jancke Harald , Krüger Ralph‐Peter , Rikowski Eckhard , Schulz Günter 
Published: February 2003

AbstractLiquid chromatography in combination with spectroscopic methods like matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) or nuclear magnetic resonance (NMR) spectroscopy is a powerful method to characterize silsesquioxanes and silsesquioxane mixtures. As new examples, the formation of silsesquioxyl‐substituted silsesquioxanes [(n‐octyl)7(SiO1.5)8]2O and [(n‐octyl)7(SiO1.5)8O]2[(n‐octyl)6(SiO1.5)8] as well as the cage rearrangement of octa‐[(n‐heptyl)silsesquioxane] to larger structur es [(n‐heptyl)SiO1.5)]n up to n=28 are shown. Copyright © 2003 John Wiley & Sons, Ltd.
McLafferty‐type rearrangement in the collision‐induced dissociation of Li+, Na+ and Ag+ cationized esters of N‐acetylated peptides
Authors: Anbalagan V. , Patel J. N. , Niyakorn G. , Van Stipdonk M. J. 
Published: February 2003

AbstractIn this study we investigated the multi‐stage collision‐induced dissociation (CID) of N‐terminally acetylated di‐, tri‐ and tetrapeptides in the form of C‐terminal ethyl, n‐propyl, isopropyl, n‐butyl and tert‐butyl esters and cationized by the attachment of Li+, Na+ and Ag+. While methyl ester versions of the metal cationized peptides primarily eliminate H2O following collisional activation and dissociation, the ethyl, propyl and butyl ester versions of the peptides exhibit a dissociation pathway consistent with γ‐hydrogen transfer to the C‐terminal carbonyl group, with associated elimination of an alkene, in a McLafferty‐type rearrangement. The rearrangement leaves a metal cationized, free‐acid form of the peptide, as confirmed by comparing the multi‐stage CID of rearrangement products generated from peptide esters with the CID of corresponding metal cationized free‐acid peptides. The transfer of a γ‐hydrogen in the rearrangement reaction was confirmed by investigating the CID of ethyl esters for which the terminal methyl group was labeled with deuterium. We found that the rearrangement product was significantly more abundant, relative to other product ions, when derived from isopropyl and tert‐butyl esters than from ethyl, n‐propyl or n‐butyl ester analogues. Copyright © 2003 John Wiley & Sons, Ltd.
Determination of Tripamide in human urine by high‐performance liquid chromatography and high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry
Authors: Kim Yunje , Hwang Joungboon , Kim Myungsoo , Lee Won 
Published: February 2003

AbstractTripamide is a drug widely used in clinical practice for the treatment of hypertension and edema. This work evaluated a screening method for Tripamide and its urinary metabolites in human urine, using high‐performance liquid chromatography diode‐array detection (HPLC/DAD). Identification of these metabolites was investigated by high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI‐MS/MS) after dosing with 15 mg Tripamide. Acid hydrolysis showed that Tripamide is conjugated in the body. Two suspected metabolites were detected by HPLC/DAD. HPLC/ESI‐MS/MS analysis suggested that these metabolites were probably hydroxylated together with loss of the ‐NH2 group and dehydrogenation. These results will be useful in confirmation methods for Tripamide in doping control. Copyright © 2003 John Wiley & Sons, Ltd.
Exploring the ester‐exchange reactions of diester‐diterpenoid alkaloids in the aconite decoction process by electrospray ionization tandem mass spectrometry
Authors: Wang Yong , Shi Lei , Song Fengrui , Liu Zhiqiang , Liu Shuying 
Published: February 2003

AbstractThe chemical components in the decoctions of Chinese herbal medicines are not always the same as those in the crude herbs because of the insolubility or instability of some compounds. In this work electrospray ionization tandem mass spectrometry was used to explore the ester‐exchange reactions for aconitine‐type diester‐diterpenoid alkaloids occurring during the process of decocting aconite root. The aconitines were screened in a diverse range of samples, including crude aconite, decoction of crude aconite, residues from decoction of crude aconite, prepared aconite, decoction of prepared aconite, decoction of prepared aconite with added palmitic acid, and decoction of a mixture of mesaconitine and hypaconitine standards with liquorice root. It was found that diester‐diterpenoid aconitines were converted into lipo‐alkaloids as well as monoester alkaloids by the decoction of aconite. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitative assay of plasma homocysteine thiolactone by gas chromatography/mass spectrometry
Authors: Daneshvar Parham , Yazdanpanah Mehrdad , Cuthbert Carla , Cole David E. C. 
Published: February 2003

AbstractEnzymatic cyclization of homocysteine forms a reactive thiolactone that may play an important role in its cardiovascular toxicity, but reliable quantitation of the free thiolactone metabolite in physiological fluids has not been reported. We have therefore used a highly selective gas chromatography/mass spectrometry (GC/MS) technique combined with the sensitivity of negative chemical ionization (NCI) to develop a quantitative method for the detection of homocysteine thiolactone (HcyTL) in plasma. To improve accutacy the deuterated isomer d4‐HcyTL was synthesized and added to plasma as internal standard. The plasma was then treated with silica solid‐phase extraction and derivatized with heptafluorobutyric anhydride. The derivative was analyzed by GC/MS in NCI mode with methane as the reagent gas and quantified by analyzing for the HcyTL ion [M− HF] and its d4‐HcyTL counterpart in single‐ion monitoring mode. The calibration curve showed a dynamic linear range up to 40 nmol/L. Within‐day precision (n = 20, nominal concentration 5.2 nmol/L) was 0.96% and between‐day precision was 3.9%, with a detection limit of 1.7 nmol/L and quantification limit of 5.2 nmol/L. Two human plasma samples had HcyTL concentrations of 18 and 25 nmol/L. This facile method for quantitation of homocysteine thiolactone opens the way for more detailed clinical studies of its potential role in homocysteine‐induced arteriosclerosis and vaso‐occlusive disease. Copyright © 2003 John Wiley & Sons, Ltd.
Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol‐3‐sulfate
Authors: Yu Chongwoo , Shin Young Geun , Kosmeder Jerome W. , Pezzuto John M. , van Breemen Richard B. 
Published: February 2003

Abstracttrans‐Resveratrol, a phenolic phytoalexin occurring in grapes, wine, peanuts, and cranberries, has been reported to both have anticarcinogenic, antioxidative, phytoestrogenic, and cardioprotective activities, and to be a weak inhibitor of cytochrome P450 (CYP)3A4, which might have significance for drug–drug interactions. Since trans‐resveratrol is rapidly converted in vivo to primarily trans‐resveratrol‐3‐sulfate, a rapid, selective, and sensitive method using liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed to investigate human cytochrome P450 inhibition by trans‐resveratrol‐3‐sulfate. Effects of trans‐resveratrol and trans‐resveratrol‐3‐sulfate on the metabolism of selective cytochrome P450 substrates (CYP1A2/ethoxyresorufin, CYP2C9/diclofenac, CYP2C19/(S)‐mephenytoin, CYP2D6/bufuralol, CYP3A4/testosterone) were monitored using cDNA‐expressed human recombinant isozymes. For method validation, LC/MS/MS was used to measure the inhibition of various cytochrome P450 isozymes by different concentrations (0–50 μM) of known selective inhibitors. IC50 values of 3.2, 1.4, 8.9, 0.2, and 0.3 μM were obtained for the standard isozyme inhibitors CYP1A2/furafylline, CYP2C9/sulfaphenazole, CYP2C19/tranylcypromine, CYP2D6/quinidine, and CYP3A4/ketoconazole, respectively, which were in good agreement with literature values. trans‐Resveratrol showed IC50 values of 11.6 μM for CYP2C19 and 1.1 μM for CYP3A4, but the IC50 values exceeded 50 μM for all the other CYP isozymes, which indicated no inhibition. No enzyme inhibition was observed for trans‐resveratrol‐3‐sulfate. Our results indicate that trans‐resveratrol is a marginal inhibitor of CYP3A4 and a weak inhibitor of CYP2C19, but its major metabolite trans‐resveratrol‐3‐sulfate is not an inhibitor of any of the cytochrome P450 isozymes investigated. Copyright © 2003 John Wiley & Sons, Ltd.
Stereochemical analysis of 3,4‐methylenedioxymethamphetamine and its main metabolites by gas chromatography/mass spectrometry
Authors: Pizarro Nieves , Llebaria Amadeu , Cano Silvia , Joglar Jesús , Farré Magí , Segura Jordi , Torre Rafael de la 
Published: February 2003

Abstract3,4‐Methylenedioxymethamphetamine (MDMA, ecstasy) is consumed as the racemate but some metabolic steps are enantioselective. In addition, chiral properties are preserved during MDMA biotransformation. A quantitative analytical methodology using gas chromatography/mass spectrometry (GC/MS) to determine enantioselective disposition in the body of MDMA and its main metabolites including 3,4‐methylenedioxyamphetamine (MDA), 4‐hydroxy‐3‐methoxymethamphetamine (HMMA), and 4‐hydroxy‐3‐methoxyamphetamine (HMA) was developed. Plasma and urine samples were collected from a male volunteer. The analysis of MDMA, MDA, and 4‐hydroxy‐3‐methoxy metabolites by GC/MS required a two‐step derivatization procedure. The first step consisted of derivatization of the amine with enantiomerically pure Mosher's reagent ((R)‐MTPCl). Triethylamine was used as a base to neutralize hydrochloric acid formed during the reaction allowing quantitative derivatization, which resulted in a substantial improvement in the sensitivity of the method compared with other previously described techniques. Further treatment with ammonium hydroxide was required since both amine and hydroxyl groups underwent derivatization in the reaction. Ammonium hydroxide breaks bonds formed with hydroxyl groups without affecting amine derivatives. The second derivatization step using hexamethyldisilazane was needed for metabolites containing phenol residues. This derivatization method permitted the stereochemically specific study of MDMA and its main monohydroxylated metabolites by GC/MS. A detailed study of the chemical reactions involved in the derivatization steps was indispensable to develop a straightforward, sensitive, and reproducible method for the analysis of the parent drug compound and its metabolites. Copyright © 2003 John Wiley & Sons, Ltd.
Characterization of micromachined hollow tips for two‐dimensional nanoelectrospray mass spectrometry
Authors: Sjödahl Johan , Melin Jessica , Griss Patrick , Emmer Åsa , Stemme Göran , Roeraade Johan 
Published: February 2003

AbstractIn this work an improved design of chip‐based nanoelectrospray nozzles is reported. Two‐dimensional matrices of out‐of‐plane 10 μm i.d. silicon dioxide tips with a tapered shape were manufactured using deep reactive ion etching technology. Using a peptide sample, six micromachined tips and six commercially pulled silica capillary tips were compared employing an ion trap mass spectrometer. At a flow rate of 100 nL/min, the detectability obtained was approximately the same for the two types of tips. The relative standard deviation of the signal‐to‐noise ratio for the peptides between six different tips was on average 22% for the micromachined tips and 45% for the pulled capillary tips. The usefulness of the micromachined tips for analysis of non‐covalent protein‐ligand complexes was demonstrated by the analysis of a sample of RNase A and cytidine 2′‐monophosphate. In another test, analyzing a tryptic digest of 1 pmol/μL cytochrome C, 18 peptides corresponding to a 82% sequence coverage were detected. Using MS/MS, the whole sequence of an 11 amino acid cytochrome C fragment was obtained. Computer simulations were performed on the shape and magnitude of the electrical field around micromachined and pulled capillary tips. To reach the threshold electric field density at the tip apex required to initiate an electrospray, a higher electrospray voltage was needed for the chip‐based tips compared with pulled capillary tips. This is due to the influence of the chip base. Copyright © 2003 John Wiley & Sons, Ltd.
Identification of Software Process Knowledge Management
Authors: Meehan Bridget , Richardson Ita 
Published: February 2003

AbstractThe effective and explicit management of knowledge has been presented as a key factor in the survival of companies in current business environments. The software development business is no different. The authors of this paper investigated two software processes in three small software development companies to identify the explicit and tacit knowledge management in these processes. They examine their findings under the four knowledge management categories of creation, storing, sharing and leverage. In many cases, while the knowledge exists, it is not made explicit within the organization. Making the knowledge explicit should make the software processes more effective. Therefore, the authors make recommendations for the small software development company as to how to do this. Whether this approach can ultimately help the small software development company to move to higher levels of maturity is a research question which needs to be further explored. Copyright © 2003 John Wiley & Sons, Ltd.
The Holon Framework and Software Process Improvement: A Radiotherapy Project Case Study
Authors: Bell G. A. , Cooper M. A. , Qureshi S. 
Published: February 2003

AbstractThis paper discusses the Holon Framework, which aims to control and improve the software development process. It is an interdisciplinary approach that is derived from software engineering and the systems movement. We outline key characteristics of software process control and improvement. Criticisms of the orthodox algorithmic cost models are identified to justify the use of alternative mathematical techniques such as system dynamics. We argue that mathematical techniques used in planning can be linked with hard systems thinking. Therefore, the essence of hard systems thinking is highlighted, and a serious weakness identified, to explain the development of soft methodologies and soft systems thinking. A significant limitation of soft systems methodology is highlighted to substantiate the need to combine it with the goal/question/metrics methodology. We justify the case study approach given the nature of the investigation. An overview of the Holon Framework is provided. The soft part of the framework, which is linked to improvement, is employed to identify relevant problems and generates a baseline metrics programme. The research design of the case study is used to evaluate our findings. Finally, we outline future work in employing the hard part of the framework, which is linked to control; this will complete the full cycle of the approach. Copyright © 2003 John Wiley & Sons, Ltd.
Learning from Failures
Authors: Dalcher Darren , Tully Colin 
Published: February 2003

AbstractThis paper addresses the topic of failures in computer‐based systems. It does so in three stages: first it describes failure cases in a single domain, that of computer‐based ambulance despatch systems; then it discusses some of the features of those cases; finally it considers the importance of reporting and analysing failures, in order to discover their causes and to learn lessons that will help eliminate those causes of failure in the future. Failure, it is argued, provides a valuable learning opportunity that may lead, when recognized, to better practice and future success. Copyright © 2003 John Wiley & Sons, Ltd.
Formation of Amylose‐Lipid Complexes and Effects of Temperature Treatment. Part 1. Monoglycerides
Authors: Tufvesson Fredrik , Wahlgren Marie , Eliasson Ann‐Charlotte 
Published: February 2003

AbstractThe formation of amylose‐lipid complexes of form I (amorphous structure) and form II (crystalline structure) during heating was studied by differential scanning calorimetry (DSC) for a range of monoglycerides and for monoglyceride mixtures. The temperature treatment applied to amylose‐monoglyceride‐mixtures were either the first scan in DSC (10 °C/min, 15‐144 °C) or a prolonged heat treatment where the samples were kept at 100 °C for 24 h before being analysed in DSC. The temperature treatment influenced which type of complex was formed, and how much, whereas the thermal stability (as judged from the transition peak temperature) was only marginally influenced. It is shown in this study that all the investigated monoglycerides were able to give complex form I as well as complex form II, although the conditions for the formation differed between the monoglycerides. It was found that a simple DSC‐scan was enough for formation of complex form II for the shortest monoglycerides (glycerol monocaprin, glycerol monolaurin and glycerol monomyristin), whereas in case of the longer monoglycerides and monoglyceride mixtures the prolonged heat treatment was required for formation of complex form II. Moreover, the monoglyceride mixtures gave only form II at conditions where the individual components in the mixtures gave both form I and form II.