bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiologically based modelling of inhibition of metabolism and assessment of the relative potency of drug and metabolite: dextromethorphan vs. dextrorphan using quinidine inhibition
Authors: Moghadamnia A. A. , Rostami‐Hodjegan A. , Abdul‐Manap R. , Wright C. E. , Morice A. H. , Tucker G. T. 
Published: July 2003

Aims  To define the relative antitussive effect of dextromethorphan (DEX) and its primary metabolite dextrorphan (DOR) after administration of DEX.Methods  Data were analysed from a double‐blind, randomized cross‐over study in which 22 subjects received the following oral treatments: (i) placebo; (ii) 30 mg DEX hydro‐bromide; (iii) 60 mg DEX hydro‐bromide; and (iv) 30 mg DEX hydro‐bromide preceded at 1 h by quinidine HCl (50 mg). Cough was elicited using citric acid challenge. Pharmacokinetic data from all non‐placebo arms of the study were fitted simultaneously. The parameters were then used as covariates in a link PK–PD model of cough suppression using data from all treatment arms.Results  The best‐fit PK model assumed two‐ and one‐compartment PK models for DEX and DOR, respectively, and competitive inhibition of DEX metabolism by quinidine. The intrinsic clearance of DEX estimated from the model ranged from 59 to 1536 l h−1, which overlapped with that extrapolated from in vitro data (12–261 l h−1) and showed similar variation (26‐ vs. 21‐fold, respectively). The inhibitory effect of quinidine ([I]/Ki) was 19 (95% confidence interval of mean: 18–20) with an estimated average Ki of 0.017 µM. Although DEX and DOR were both active, the potency of the antitussive effect of DOR was 38% that of DEX. A sustained antitussive effect was related to slow removal of DEX/DOR from the effect site (ke0 = 0.07 h−1).Conclusions  Physiologically based PK modelling with perturbation of metabolism using an inhibitor allowed evaluation of the antitussive potency of DOR without the need for separate administration of DOR.
Oral weekly ibandronate prevents bone loss in postmenopausal women
Authors: Tankó L. B. , Felsenberg D , Czerwiński E , Burdeska A , Jonkanski I , Hughes C , Christiansen C ,   for the Oral Ibandronate Group
Published: July 2003

Abstract.Tankó LB, Felsenberg D, Czerwiński E, Burdeska A, Jonkanski I, Hughes C, Christiansen C (Center for Clinical and Basic Research A/S, Ballerup and Vejle, Denmark; University Hospital Benjamin Franklin, Berlin, Germany; Foundation of Osteoporosis, Krakow, Poland; F. Hoffmann‐La Roche Ltd, Basel, Switzerland; and F. Hoffmann‐La Roche Ltd, Welwyn, UK). Oral weekly ibandronate prevents bone loss in postmenopausal women. J Intern Med 2003; 254: 159–167.Objectives. To investigate the efficacy, safety, and dose‐response of once‐weekly oral ibandronate in the prevention of postmenopausal bone loss.Design. This was a multi‐centre, placebo‐controlled, double‐blind, randomized, 24‐month phase II/III dose‐finding study.Setting. Primary care units in 14 osteoporosis centres.Subjects. A total of 630 women were stratified into four strata according to time since menopause (TSM, 1–3 vs. >3 years) and baseline bone mineral density (BMD; normal: T‐score ≥1 vs. osteopenic: −2.5 ≤ T‐score ≤ 1) of the lumbar spine.Interventions. Within each stratum women were further randomized to receive once‐weekly ibandronate (5, 10, or 20 mg week−1) or placebo for 24 months.Main outcome measures. Efficacy parameters were the relative changes from baseline in spine (L1–4) and hip BMD, and biochemical markers of bone turnover (serum and urinary C‐telopeptide of collagen type I (CTx), osteocalcin, and alkaline phosphatase) measured by dual energy X‐ray absorptiometry and enzyme immunoassays, respectively.Results. Once‐weekly therapy with ibandronate induced dose‐dependent increases in spine and hip BMD. At month 24, differences between the relative changes in spine and hip BMD induced by 20 mg ibandronate and placebo was 4.0 and 2.7%, respectively. Similar or more pronounced differences were seen in osteopenic women of TSM 1–3 years (5.3 and 3.5%) and of TSM >3 years (3.5 and 2.9%), respectively. A dose‐dependent suppression of all biochemical markers of bone turnover was observed with significant decreases in the 20 mg dose groups of all strata at month 24. The overall safety results indicated that once‐weekly oral ibandronate was well‐tolerated at all three doses.Conclusion. Once‐weekly oral therapy with 20 mg ibandronate provides an effective and safe therapy for the prevention of postmenopausal bone loss.
Transfer of T‐DNA and Vir proteins to plant cells byAgrobacterium tumefaciensinduces expression of host genes involved in mediating transformation and suppresses host defense gene expression
Authors: Veena  , Jiang Hongmei , Doerge R.W. , Gelvin Stanton B. 
Published: July 2003

SummaryAgrobacterium tumefaciensis a plant pathogen that incites crown gall tumors by transferring to and expressing a portion of a resident plasmid in plant cells. Currently, little is known about the host response toAgrobacteriuminfection. Using suppressive subtractive hybridization and DNA macroarrays, we identified numerous plant genes that are differentially expressed during early stages ofAgrobacterium‐mediated transformation. Expression profiling indicates thatAgrobacteriuminfection induces plant genes necessary for the transformation process while simultaneously repressing host defense response genes, thus indicating successful utilization of existing host cellular machinery for genetic transformation purposes. A comparison of plant responses to different strains ofAgrobacteriumindicates that transfer of both T‐DNA and Vir proteins modulates the expression of host genes during the transformation process.
COUNTER: from conception to compliance
Authors: Shepherd Peter T. 
Published: July 2003

ABSTRACTCOUNTER was formally launched in March 2002. Within a year Release 1 of the COUNTER Code of Practice had been published, and a number of leading publishers were working towards making their usage reports COUNTER‐compliant. This article describes the background to COUNTER, the main features of the Code of Practice, the current status of its implementation and the next steps for the project. It also stresses the particular benefits to publishers of COUNTER compliance and of COUNTER membership.
Consent processes in common nose and throat procedures
Authors: Chadha Neil K. , Pratap Rohit , Narula Antony A. 
Published: July 2003

The NHS Plan identified the need for changes in consent practice, and led to the issuing of a model consent policy and standard consent forms for use in the NHS. The aim of this study was to determine current consent practices for common rhinology and laryngology procedures.A telephone survey was conducted of 40 otolaryngology Senior House Officers (SHOs) across England and Wales, asking about local consent procedure, and the specific complications discussed before common operations.The responsibility for routine consenting belonged to SHOs in 95 per cent of departments. Model NHS consent forms were used in 72.5 per cent and information sheets given to patients in 25 per cent of departments. The specific operative risks mentioned to patients by the SHOs showed great variability.The provision of standardized consent protocols for each operation, together with information sheets and the model NHS forms, could aid juniors involved in consent and prove beneficial to our patients.
Investigating Gasification Processes of Solid Fuels by in situ Gaspotentiometric Oxygen Probes
Authors: Schotte E. , Lorenz H. , Rau H. 
Published: July 2003

AbstractThis paper describes a novel analytical method that applies a gaspotentiometric oxygen probe (GOP) for characterizing gasification behavior of solid fuels. On the basis of GOP signals a developed gasification model enables the determination of fuel‐specific properties, like effective reaction rate constant and overall activation energy. For its experimental validation two coal cokes were converted with four different gasification agents in a lab‐scale fluidized‐bed reactor. The results obtained will be discussed and compared with literature data. As this advantageous in situ measurement technique is fast, inexpensive, and easy to handle, it makes the GOP a predestined tool for monitoring and controlling gasification processes.
Birth of Neutrino Astrophysics (Nobel Lecture)
Authors: Koshiba Masatoshi 
Published: July 2003

AbstractThe KamiokaNDE experiment for the observation of proton decay, an array of photomultipliers containing over 3 000 tons of water, allowed the observation of charged particles travelling faster than the velocity of light in water. The subsequently developed Super‐KamiokaNDE could be used to measure the amounts, the path, the energies, and the oscillation parameters of neutrinos, generated either by supernova explosions in the sun, or in the atmosphere. This work was awarded the 2002 Nobel Prize in Physics.
The Electrochemical Oxidation of N,N‐Diethyl‐p‐Phenylenediamine in DMF and Analytical Applications. Part I: Mechanistic Study
Authors: Klymenko Oleksiy V. , Giovanelli Debora , Lawrence Nathan S. , Rees Neil V. , Jiang Li , Jones Timothy G. J. , Compton Richard G. 
Published: July 2003

AbstractThe electrochemical oxidation of N,N‐diethyl‐p‐phenylenediamine in dimethylformamide has been studied at platinum and gold microdisk electrodes of various radii between 6.7 and 66 μm. The voltammetric responses revealed two electrochemically reversible waves the second of which becomes larger at higher concentrations and bigger electrode radii. The voltammetric signals have been modelled and the electrochemical oxidation reaction is not inconsistent with an ECrevECE reaction. Kinetic parameters are reported.
Determination of valproic acid (2‐propylpentanoic acid) in human plasma by capillary electrophoresis with indirect UV detection
Authors: Pucci Vincenzo , Mandrioli Roberto , Raggi Maria A. 
Published: July 2003

AbstractA rapid capillary zone electrophoresis method with indirect UV detection was developed and validated for the determination of valproic acid (VPA) in human plasma. The analyses were carried out under optimized conditions, using a buffer system composed of 15 mM benzoate and 0.5 mM cetyltrimethylammonium bromide at pH 6.0, and 25% v/v methanol; 2‐hydroxybutyric acid was selected as the internal standard (IS). The capillary electrophoresis (CE) separation was carried out at a negative potential of 30 kV and the indirect UV detection was operated at 210 ± 20 nm for all assays. The influence of buffer pH, ionic strength, concentration of electroosmotic flow (EOF) modifier and organic modifier on indirect signal response and migration behavior of the organic acid was investigated. Isolation of VPA from plasma was accomplished by a carefully implemented procedure using methanol as the precipitant agent. Using a high ratio of methanol to plasma for deproteinization (4:1), good absolute recovery of the analyte and satisfactory selectivity was obtained. The calibration line for VPA was linear over the 1–100 μg/mL concentration range. Sensitivity was high; in fact, the limit of detection (LOD) of VPA was 150 ng/mL and 450 ng/mL the limit of quantitation (LOQ). The results obtained analyzing real plasma samples from schizophrenic patients under polytherapy with VPA as well as antipsychotic drugs were satisfactory in terms of precision, accuracy and sensitivity.
Elemental speciation analysis in capillary electrophoresis
Authors: Liu Yan‐Ming , Cheng Jie‐Ke 
Published: July 2003

AbstractThe growing awareness of the strong development of the toxicity of heavy metals upon their chemical forms has led to an increasing interest in the qualitative and quantitative determination of specific metal species. Speciation has therefore become an important topic of present‐day analytical research. The development in the elemental speciation analysis by capillary electrophoresis (CE) is reviewed. Various CE separation modes and detection techniques applied are discussed. A comprehensive description of reported methods to date in CE speciation analysis including metals, metalloids and nonmetallic elements is demonstrated. Some examples are presented to demonstrate CE's ability to solve real‐world speciation analysis with emphasis on the applications in biological and environmental samples. Further, some issues concerning the limitations and the future of CE with regard to speciation studies are also discussed.
Determination of low‐molecular‐mass quaternary ammonium compounds by capillary electrophoresis and hyphenation with mass spectrometry
Authors: Buchberger Wolfgang , Schöftner Rainer 
Published: July 2003

AbstractThe determination of quaternary ammonium ions by capillary electrophoresis (CE) is reviewed. The analytes include tetraalkylammonium and alkylbenzyldimethylammonium compounds frequently used as antiseptic and antibacterial agents as well as in various household products, several plant growth regulators and herbicides, by‐products in bile acid sequestrants, and a range of anticholinergic drugs. Besides direct and indirect UV detection, hyphenation with electrospray mass spectrometry is particularly suited for quaternary ammonium ions and may lower the detection limits by two orders of magnitude. In comparison with established liquid chromatographic techniques, CE may exhibits superior separation efficiency. Applications in routine analysis have demonstrated that CE is reliable and robust enough to represent a real alternative to chromatography.
Large‐volume stacking with polarity switching and sweeping for chlorophenols and chlorophenoxy acids in capillary electrophoresis
Authors: Kruaysawat Janpen , Marriott Philip J. , Hughes Jeff , Trenerry Craige 
Published: July 2003

AbstractThis paper describes approaches for stacking large volumes of sample solutions containing a mixture of chlorophenols and chlorophenoxyacetic acids as their anions in capillary zone electrophoresis, and compares results to standard capillary electrophoresis (CE) and normal stacking modes. In order to increase the amount of sample injected beyond the optimal conditions and maintain high resolution, the sample introduction buffer must be removed after the stacking process is completed. This is achieved by pumping the sample buffer out of the column using polarity switching. Large sample volumes are loaded by hydrodynamic injection, then stacked at the injection buffer/run electrolyte interface, followed by the removal of the large plug of low‐conductivity sample matrix from the capillary column using polarity switching and finally the separation of the stacked anions in a basic buffer (pH 8.65). Around 10‐ and 40‐fold improvement of sensitivity was achieved by normal stacking and large‐volume stacking with polarity switching, respectively, when compared to the standard CE analysis. Sweeping‐micellar electrokinetic capillary chromatography (MEKC) was also investigated for the purpose of comparison to the stacking technique. The method should be suitable for the analysis of these chemical compound classes in industrial chlorophenoxyacetic acid manufacture.
Rigorous Approach to Modeling of a Continuous Aerobic Membrane Bioreactor
Authors: Gehlert G. , Hapke J. 
Published: July 2003

AbstractA rigorous approach to mathematical modeling of a continuous aerobic membrane bioreactor (MBR) for the treatment of wastewater is reported. The idea is to apply the activated sludge model ASM3 to the special configuration of a membrane bioreactor. Therefore, the biochemical processes modeled by the ASM3 were implemented together with mass balances typical of a MBR running at constant TSS. The model parameters were adapted to the properties of an artificial wastewater by using a global search algorithm. The model could be validated by comparing effluent chemical oxygen demand (COD), sludge production and CO2 concentration in the exhaust to the experimental data.
Focus for the future: tackling the ‘pelvic pain’ problem in gynecologic practice — an interactive session
Authors: Walker J.J 
Published: July 2003

AbstractObjective: The clinical management of women with chronic pelvic pain (CPP) and endometriosis involves important issues that exist at the interface between these two conditions. Methods: To address these issues, an interactive session was convened to discuss an empiric algorithmic protocol for the clinical management of CPP and endometriosis presented during the Takeda‐sponsored session as part of the XVI FIGO World Congress of Gynecology and Obstetrics and to monitor the audience response to this approach. Results: Approximately one‐third of the audience responded that they would definitely try this method, approximately 18% were already using it, and approximately 21% would be fairly likely to try it. Thirty percent of the audience was not convinced that the empiric approach is the best management strategy. Conclusion: The advantages of this management strategy should be carefully considered, and discussed with colleagues who do think it is the reasonable treatment approach in selected cases.
Chemokine Receptor 2 (CCR2) in Atherosclerosis, Infectious Diseases, and Regulation of T‐Cell Polarization
Authors: CHARO ISRAEL F. , PETERS WENDY 
Published: July 2003

ABSTRACTInfiltration of tissues by monocyte‐derived macrophages is a prominent component of a wide‐range of diseases, including atherosclerosis, glomerulonephritis, encephalitis, infectious diseases, and virtually all syndromes characterized by chronic inflammation. The molecular signals responsible for this directed migration are incompletely understood, but members of the chemokine family, especially the monocyte chemoattractant proteins (MCPs) (MCP‐1 to MCP‐5) are emerging as key players. Cells that respond to the MCPs do so because they express chemokine receptor 2 (CCR2), the cognate receptor. This review will summarize evidence supporting a key role for CCR2 in the pathogenesis of atherosclerosis, infections with intracellular pathogens, and regulation of the type I adaptive immune response.
Significant Involvement of CCL2 (MCP‐1) in Inflammatory Disorders of the Lung
Authors: ROSE C. EDWARD , SUNG SUNG‐SANG J. , FU SHU MAN 
Published: July 2003

ABSTRACTMounting evidence suggests that CCL2 (MCP‐1) and its hematopoietic cell receptor CC chemokine receptor 2 (CCR2) are involved in inflammatory disorders of the lung. In animal models of allergic asthma, idiopathic pulmonary fibrosis (IPF), and bronchiolitis obliterans syndrome (BOS), CCL2 expression and protein production are increased and the disease process is attenuated by CCL2 immunoneutralization. Mechanisms by which CCL2 may be acting include recruitment of regulatory and effector leukocytes; stimulation of histamine or leukotriene release from mast cells or basophils; induction of fibroblast production of transforming growth factor‐β (TGF‐β) and procollagen; and enhancement of Th2 polarization. Recently, polymorphism for CCL2 has been described with increased cytokine‐induced release of CCL2 by monocytes and increased risk of allergic asthma. These studies identify potentially important roles for CCL2 in these lung inflammatory disorders. While CCL2 inhibition in patients with acute respiratory distress syndrome (ARDS) may be hazardous by interfering with defense against bacteremia, future studies are needed to determine if CCL2/CCR2 antagonism will offer breakthrough therapy for patients with allergic asthma, IPF, or BOS, and to confirm the hypothesis that CCL2 polymorphism places patients at greater risk for these disorders.
Arrest Chemokines
Authors: LEY KLAUS 
Published: July 2003

ABSTRACTIn most organs, leukocyte attachment to the endothelium of blood vessels requires capture and rolling before firm adhesion is initiated by integrin activation and/or redistribution, which can be initiated by immobilized chemokines binding their cognate receptors on rolling cells. Such arrest chemokines are present on the endothelial surface under physiologic or pathologic conditions, necessary, and sufficient to trigger arrest. Although many chemokines can be immobilized and cause arrest of rolling cells in flow chambers, only four have so far been shown to function as arrest chemokines under physiologic conditions, although the actual number could be much higher. Secondary lymphoid tissue chemokine (SLC) (CCL21) on high endothelial venules triggers arrest of rolling lymphocytes, and keratinocyte‐derived chemokine (KC) (mouse Gro‐α, CXCL1), monocyte chemoattractant protein‐1 (MCP‐1) (CCL2), and regulated on activation, normal T cell exposed and secreted (RANTES) (CCL5) trigger arrest of rolling monocytes. Remarkably, no arrest chemokine for neutrophils under inflammatory conditions has been found so far.
Chemokine Induction of Integrin Adhesiveness on Rolling and Arrested Leukocytes Local Signaling Events or Global Stepwise Activation?
Authors: ALON RONEN , GRABOVSKY VALENTIN , FEIGELSON SARA 
Published: July 2003

ABSTRACTThe arrest of rolling leukocytes on target endothelium is predominantly mediated by integrins, which pre‐exist in largely inactive states on circulating immune cells and need to be activated in situ. These adhesion receptors acquire high avidity upon encounter with endothelial‐displayed chemokines or chemoattractants, which are ligands to specific G protein‐coupled receptors (GPCRs) on the leukocyte surface. In order to arrest, the leukocyte must constantly integrate endothelial‐based signals as it moves along the vessel wall. It is unclear whether the chemokine signal is locally transmitted at the endothelial contact zone or whether the rolling leukocyte accumulates successive chemokine signals to reach a threshold global activation. Recent in vitro and in vivo data suggest that the induction of high integrin avidity by endothelial chemokine‐transduced Gi‐signals is a general mechanism that has evolved to locally enhance integrin avidity to ligand within subseconds at restricted leukocyte‐endothelial contacts. In addition, a second specialized mechanism, involving stepwise signals integrated by selectin ligands on rolling cells, seems to activate integrins on the entire leukocyte surface. This GPCR‐independent and much slower pathway (101–102 seconds) is transmitted through rolling engagements of neutrophils, primarily on E‐selectin. We propose that these two mechanisms are differentially used by distinct leukocyte subsets at various vascular beds, providing much larger combinatorial diversity of integrin activation on rolling leukocytes than previously predicted.
Single‐dose pharmacokinetics and tolerability of pegylated interferon‐α2b in young and elderly healthy subjects
Authors: Gupta Samir K. , Glue Paul , Jacobs Sheila , Belle Donna , Affrime Melton 
Published: July 2003

Aims  To assess the single‐dose pharmacokinetics and tolerability of pegylated interferon‐α2b (PEG‐Intron) in young and elderly healthy subjects.Methods  In this parallel‐design study, a single 1 µg kg−1 PEG‐Intron dose was given subcutaneously to 24 subjects in the age groups 20–45, 65–69, 70–74 and 75–80 years (n = 6/group). Blood sampling and tolerability assessments were performed up to 168 h postdose.Results  The pharmacokinetic parameters were similar in all age groups. The elderly to young subject ratios for Cmax were 91.1, 79.5, and 107% for the 65–69 years, 70–74 years and 75–80 years groups, respectively. The corresponding values for AUC(0–∞) and CL/F were 111, 102 and 108%, and 82.5, 95.8 and 86.4%, respectively. Mean differences from the 20 to 45 years group and the 65–69 years, 70–74 years and 75–80 years groups for PEG‐Intron Vd/F were 108, 128 and 104%, respectively. None of these differences was statistically significant based on ANOVA. Results from a Dunnett's test (as post hoc assessment) confirmed that the pharmacokinetic parameters of Group II, Group III or Group IV were not different from those of Group I. Almost all (23/24; 96%) subjects reported typical interferon‐α side‐effects (flu‐like symptoms, headache). One elderly patient had a myocardial infarction 12 h postdose, but recovered fully.Conclusions  There are no pharmacokinetic reasons for initial dose adjustment of PEG‐Intron based on age.