bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of a novel linear water‐soluble β‐cyclodextrin polymer
Authors: Renard Estelle , Volet Gisèle , Amiel Catherine 
Published: December 2004

AbstractA novel linear water‐soluble β‐cyclodextrin polymer has been prepared by grafting β‐cyclodextrin on poly[(methyl vinyl ether)‐alt‐(maleic anhydride)]. First, lithium hydride was used to obtain the mono‐alkoxide β‐CD. Grafting of β‐CD derivatives to the polymer backbone was then carried out by an esterification method. Using this method, polymers containing various amounts of β‐CD were synthesized. The resulting grafted polymers were characterized by two complementary methods, 1H NMR and IR spectroscopy. The first was used to calculate the degree of substitution for the low amounts of β‐CD. The second method was very useful to evaluate the degree of substitution and the molar ratio of CD especially for high amounts of grafting. Our results indicate good agreement between both methods for intermediate rates. Copyright © 2004 Society of Chemical Industry
Hydrogen‐bonded polyurethane complexes based on 4‐alkoxybenzoic acids as the low molar mass components
Authors: Ambrožič Gabriela , Žigon Majda 
Published: December 2004

AbstractSupramolecular polyurethane complexes based on a polyurethane with a pendant pyridyl unit (PUPy) as the hydrogen bond acceptor and 4‐octyloxybenzoic acid (OOBA) or 4‐butyloxybenzoic acid (BOBA) as the hydrogen bond donor were prepared. The primary driving force for the formation of these complexes is the hydrogen bonding between the pyridyl polyurethane group and the carboxylic acid group, while the urethane group only contributes to the binding of acid molecules to a minor extent. Phase separation in the BOBA/PUPy and OOBA/PUPy systems occurred at low molar ratios: BOBA and OOBA formed amorphous polyurethane complexes at a molar ratio of 0.2, while the OOBA/PUPy complex exhibited a glassy smectic mesophase at a molar ratio of 0.4. In comparison to the previously studied complexes of PUPy and 4‐dodecyloxybenzoic acid (DOBA), where side‐chain ordering prevailed, OOBA/PUPy complexes showed a high tendency of the main‐chain crystallization at molar ratios of 0.4 or higher. This is due to weak overall van der Waals interactions between the short octyl tails and effective intra‐ and/or intermolecular hydrogen bonding between the urethane and pyridyl groups of the polymer backbone. Copyright © 2004 Society of Chemical Industry
Kinetic and mechanistic studies on the hydrolysis and photodegradation of diazepam and alprazolam
Authors: Cabrera C. Gallardo , de Waisbaum R. Goldberg , Nudelman N. Sbarbati 
Published: December 2004

AbstractThe corresponding o‐aminobenzophenones are usually reported as the main degradation products in the hydrolysis of 1,4‐benzodiazepinones. Nevertheless, in previous studies of diazepam (DZ) in acidic aqueous medium we isolated and characterized seven unexpected degradation products. Kinetic measurements under several reaction conditions shed some light on the mechanisms of the complex reactions that are taking place, and photochemical studies give hints on the mechanisms of chlorination and annelation processes. Alprazolam (AL) seems to exhibit an unusually high stability against hydrolysis under several conditions; nevertheless, the structure is sensitive to photolytic cleavage. The photodegradation of AL was studied in aqueous and methanolic solutions. Characterization of the isolated products by 1H and 13C NMR and mass spectrometry revealed that electron transfer, oxidation and rearrangement reactions take place. The influence of several variables such as pH, solvent composition and light irradiation were examined and mechanisms for the formation of three photoproducts are proposed. A specific method for the determination of AL in the presence of photoproducts was developed, which allowed kinetic determinations of the photostability of AL. The photosensitivity observed in some patients treated with AL seems to be due to one of the characterized photoproducts. Copyright © 2004 John Wiley & Sons, Ltd.
Using generic system archetypes to support thinking and modelling
Authors: Wolstenholme Eric 
Published: December 2004

AbstractThis paper provides some context for my paper which won the 2004 Jay Wright Forrester award. It describes the system dynamics challenges I received from a number of people and my response to them, particularly to explore the issue of mismatch in organisations between process and boundary structure. It also describes how I have been using generic archetypes in practice since publication of the original work. Copyright © 2004 John Wiley & Sons, Ltd.
Familial predictors of sibling and romantic‐partner conflict resolution: comparing late adolescents from intact and divorced families
Authors: Reese‐Weber Marla , Kahn Jeffrey H. 
Published: December 2004

AbstractThe present study examined whether predictors of romantic‐partner conflict may vary as a function of family structure. Using a cross‐sectional design, we tested a mediation model of conflict resolution behaviours among late adolescents from intact () and divorced () families. Adolescents rated conflict resolution behaviours in five dyadic relationships: interparental, mother–adolescent, father–adolescent, sibling, and romantic partner. Mother–adolescent and father–adolescent conflict resolution behaviours mediated the relationship between interparental and sibling conflict resolution. Moreover, both mother–adolescent and sibling conflict resolution behaviours mediated the relationship between interparental and romantic‐partner conflict resolution behaviours. This model was supported for both positive and negative behaviours, and it applied equally well to adolescents from intact and divorced families. Results are discussed in the context of social learning theories and support conflict resolution behaviours within the family spilling over into romantic relationships for adolescents from both intact and divorced families.
The effect of shock wave treatment at the tendon–bone interface—an histomorphological and biomechanical study in rabbits
Authors: Wang Ching‐Jen , Wang Feng‐Sheng , Yang Kuender D. , Weng Lin‐Hsiu , Sun Yi‐Chih , Yang Ya‐Ju 
Published: December 2004

AbstractPurpose. This study was performed to investigate the effect of shock wave treatment on the healing at tendon–bone interface in rabbits.Materials and methods. Thirty‐six New Zealand White rabbits were used in this study. The anterior cruciate ligament was excised and replaced with the long digital extensor. The right knees (study group) were treated with 500 impulses of shock waves at 14kV, while the left knees (control group) received no shock waves. Histomorphological studies were performed in 24 rabbits at 1, 2, 4, 8, 12 and 24 weeks. Biomechanical studies were performed in 12 rabbits at 12 and 24 weeks.Results. There was significantly more trabecular bone around the tendons noted in the study group compared with the control group at different time intervals after 4 weeks (P < 0.05). The contacting between bone and tendon was significantly better in the study group than the control group after 8 weeks (P < 0.05). The tensile strength of the tendon–bone interface was significantly higher in the study group than the control group at 24 weeks (P = 0.018), whereas similar modes of graft failure were noted between the two groups.Conclusion. Shock wave treatment significantly improves the healing rate of the tendon–bone interface in a bone tunnel in rabbits. The effect of shock waves appears to be time‐dependent. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity
Authors: Wang Zaiqi , Gorski J. Christopher , Hamman Mitchell A. , Huang Shiew‐Mei , Lesko Lawrence J. , Hall Stephen D. 
Published: December 2004

BackgroundSt John's wort(Hypericum perforatum) is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 (CYP) isozymes. The effect of St John's wort on CYP activity in vivo was examined with a probe drug cocktail.MethodsTwelve healthy subjects (5 female, 7 male) completed this 3‐period, open‐label, fixed schedule study. Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A) were administered before, with short‐term St John's wort dosing (900 mg), and after 2 weeks of intake (300 mg 3 times a day) to determine CYP activities.ResultsShort‐term administration of St John's wort had no effect on CYP activities. Long‐term St John's wort administration caused a significant (P < .05) increase in oral clearance of midazolam from 121.8 ±70.7 to 254.5 ±127.8 and a corresponding significant decline in oral bioavailability from 0.28 ±0.15 to 0.17 ±0.06. In contrast to the >50% decrease in the area under the plasma concentration‐time curve (AUC) when midazolam was administered orally, long‐term St John's wort administration caused a 20% decrease in AUC when midazolam was given intravenously. There was no change in CYP1A2, CYP2C9, or CYP2D6 activities as a result of St John's wort administration.ConclusionLong‐term St John's wort administration resulted in a significant and selective induction of CYP3A activity in the intestinal wall. St John's wort did not alter the CYP2C9, CYP1A2, or CYP2D6 activities. Reduced therapeutic efficacy of drugs metabolized by CYP3A should be anticipated during long‐term administration of St John's wort.Clinical Pharmacology & Therapeutics (2001) 70, 317–326; doi: 10.1016/S0009‐9236(01)00127‐8
CYP2D6 polymorphism in a Mexican American population
Authors: Mendoza Ricardo , Wan Yu‐Jui Yvonne , Poland Russell E. , Smith Michael , Zheng Yanping , Berman Nancy , Lin Keh‐Ming 
Published: December 2004

BackgroundPharmacogenetic data are largely unavailable for Mexican Americans, despite being one of the largest populations in America.MethodsThe CYP2D6 genotype (n = 349) and dextromethorphan hydroxylation phenotype (n = 285) were studied in 380 Mexican American subjects from Los Angeles County.ResultsThe allelic frequency was 22.8% forCYP2D6*2, 10.3% for CYP2D6*4, 7.4% for CYP2D6*10, 2.3% forCYP2D6*5, 1% for CYP2D6*XN (duplication), and <1% for CYP2D6*3 and CYP2D6*17. By using the published antimode for Caucasians, we identified nine subjects as poor metabolizers, an incidence of 3.2%. Of the eight poor metabolizers who were also genotyped, five either were homozygous for the CYP2D6*4 allele (4 cases) or had a combination of CYP2D6*4 and CYP2D6*5 alleles. The mean log10 dextromethorphan/dextrorphan ratio was −2.47 for those classified as extensive metabolizers. The number of functional alleles among the extensive metabolizers correlated strongly with the phenotype, suggesting a gene‐dose effect.ConclusionCompared with previous reports on Caucasian populations, studies show that Mexican Americans appear to possess a lower rate of CYP2D6*4. Frequencies for the other alleles appear to be less divergent between the two groups. This genotypic pattern might be responsible for the lower rate for the poor metabolizer status, as well as for the faster enzyme activity in the extensive metabolizer subjects that was also reflected in our data.Clinical Pharmacology & Therapeutics (2001) 70, 552–560; doi: 10.1016/S0009‐9236(01)00793‐7
Effect of grapefruit juice on digoxin pharmacokinetics in humans
Authors: Becquemont Laurent , Verstuyft Céline , Kerb Reinhold , Brinkmann Ulrich , Lebot Martine , Jaillon Patrice , Funck‐Brentano Christian 
Published: December 2004

ObjectivesGrapefruit juice is responsible for drug interactions mediated by intestinal cytochrome P4503A4 inhibition and possibly P‐glycoprotein inhibition in enterocytes. Our main objective was to determine whether grapefruit juice alters the bioavailability of digoxin, a P‐glycoprotein substrate. The secondary objective was to determine whether the magnitude of the pharmacokinetic interaction was influenced by P‐glycoprotein genetic polymorphism.MethodsTwelve healthy volunteers participated in this open randomized crossover study comparing the effect of grapefruit juice consumption (versus water) on the pharmacokinetics of a single oral dose of digoxin (0.5 mg). The P‐glycoprotein genotype was determined according to MDR1 genetic polymorphism in exon 26 (C3435T).ResultsGrapefruit juice had no significant effect on the maximum plasma drug concentration (Cmax) of digoxin or the area under the plasma concentration‐time curve (AUC) from time zero to 48 hours. However, there was a 9% increase in the digoxin AUC from time zero to 4 hours and from time zero to 24 hours (P = .01) during grapefruit juice administration. The digoxin renal clearance remained unchanged during both periods. No relationship between MDR1 C3435T genotype and early digoxin pharmacokinetic changes could be detected.ConclusionThe modest changes in digoxin pharmacokinetics observed during grapefruit juice ingestion do not support an important P‐glycoprotein inhibition. Under our experimental conditions, grapefruit juice‐mediated P‐glycoprotein inhibition does not appear to play a relevant role in drug interactions, at least when assessed by use of digoxin disposition kinetics.Clinical Pharmacology & Therapeutics (2001) 70, 311–316; doi: 10.1016/S0009‐9236(01)17221‐8
Association of polymorphism in the cytochrome CYP2D6 and the efficacy and tolerability of simvastatin
Authors: Mulder André B. , van Lijf Hans J. , Bon Michelle A. M. , van den Bergh Frank A. J. T. M. , Touw Daan J. , Neef Cees , Vermes István 
Published: December 2004

ObjectiveBecause clinical data about the therapeutic consequences of polymorphic oxidation of simvastatin by CYP2D6 have not been well reported, we sought to investigate the possible link between polymorphism of CYP2D6 and the efficacy and tolerability of simvastatin treatment in a group of 88 patients with hypercholesterolemia.MethodsTheCYP2D6 genotype was determined with use of polymerase chain reaction and restriction fragment analysis, whereas the CYP2D6 phenotype was determined by monitoring the dextromethorphan metabolism.ResultsFour of 5 patients with 2 defectiveCYP2D6 alleles discontinued the therapy at a low daily dose because of adverse events, with a significant mean decrease in the cholesterol levels of 0.23 mmol/L per milligram of simvastatin in the daily dose. In the group of 28 patients with 1 mutatedCYP2D6 gene, 13 did not tolerate the therapy, whereas a mean decrease in the cholesterol levels of 0.20 mmol/L per milligram of simvastatin was found. One patient with a multiplication of theCYP2D6 gene showed a cholesterol reduction of only 0.01 mmol/L per milligram of simvastatin, at a maximal daily dose of 40 mg. Only 9 patients of the group of 54 persons who were homozygous for the wild‐type allele discontinued the therapy because of intolerance. In that group, a mean decrease of cholesterol of 0.10 mmol/L per milligram of simvastatin was observed.ConclusionsOur data provide evidence that the cholesterol‐lowering effect of simvastatin is influenced by CYP2D6 polymorphism. The clinical use of this knowledge may allow for more efficient individual therapies.Clinical Pharmacology & Therapeutics (2001) 70, 546–551; doi: 10.1016/S0009‐9236(01)25429‐0
Effect of rifampin and tobacco smoking on the pharmacokinetics of ropivacaine
Authors: Jokinen Mika J. , Olkkola Klaus T. , Ahonen Jouni , Neuvonen Pertti J. 
Published: December 2004

ObjectiveOur objective was to assess the effect or rifampin (INN, rifampicin) and tobacco smoking on the pharmacokinetics of ropivacaine.MethodsA randomized, 2‐phase, crossover study was performed in both a group of 10 healthy nonsmokers and a group of 8 healthy smokers. In both groups each subject ingested daily for 5 days either placebo or 600 mg rifampin. On day 6 each subject received intravenously over 30 minutes a single dose of 0.6 mg/kg ropivacaine. Ropivacaine, 3‐hydroxyropivacaine (3‐OH‐ropivacaine), and (S)‐2′,6′‐pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 hours and 24 hours, respectively. Pharmacokinetic parameters were calculated with noncompartmental methods, and t tests were used for comparisons between the phases and between the smokers and nonsmokers. The electrocardiogram was monitored for 3 hours.ResultsThere were no statistically significant differences in the area under the plasma concentration‐time curve (AUC), plasma clearance (CL), or half‐life (t1/2) of ropivacaine between the smokers and nonsmokers. However, smokers excreted in urine 31% more 3‐OH‐ropivacaine and 62% less PPX than nonsmokers did. Rifampin decreased the AUC of ropivacaine in nonsmokers by 52% and in smokers by 38%. In nonsmokers rifampin increased the CL of ropivacaine by 93% and shortened its t1/2 by 25%. In smokers rifampin increased the CL of ropivacaine by 47% and shortened its t1/2 by 20%. Rifampin decreased the urinary excretion of 3‐OH‐ropivacaine in nonsmokers by 74% and in smokers by 68%, and it increased the excretion of PPX by 97% and 158%, respectively. No clinically significant differences in the QTc times were found between the groups or treatments.ConclusionsTobacco smoking increases the excretion of 3‐OH‐ropivacaine in urine, probably because of the increased cytochrome P450 (CYP) 1A2‐mediated metabolism of ropivacaine, and decreases the excretion of CYP3A4‐formed PPX in urine. Rifampin considerably increases the metabolism of ropivacaine to PPX and decreases the metabolism to 3‐OH‐ropivacaine in both nonsmokers and smokers.Clinical Pharmacology & Therapeutics (2001) 70, 344–350; doi: 10.1016/S0009‐9236(01)29243‐1
Ritonavir increases loperamide plasma concentrations without evidence for P‐glycoprotein involvement
Authors: Tayrouz Yorki , Ganssmann Beate , Ding Reinhard , Klingmann Andrea , Aderjan Rolf , Burhenne Jürgen , Haefeli Walter Emil , Mikus Gerd 
Published: December 2004

BackgroundThe antidiarrheal drug loperamide is frequently used to treat ritonavir‐associated diarrhea in patients with human immunodeficiency virus. The absence of marked central opioid effects has been attributed to its low bioavailability and its poor penetration of the blood‐brain barrier, both of which might be altered by ritonavir, a potent P‐glycoprotein and cytochrome P4503A inhibitor.MethodsA 16‐mg dose of loperamide was administered to 12 healthy male and female volunteers together with either 600 mg of ritonavir or placebo. Detailed pharmacokinetics of loperamide and its metabolites were determined over 72 hours. Central opioid effects were measured by evaluation of pupil diameter, cold pressor test, and transcutaneous PCO2 and PO2.ResultsRitonavir caused a major pharmacokinetic interaction, increasing the area under the concentration‐time curve of loperamide from 104 ± 60 h · pmol/ml after placebo to 276 ± 68 h · pmol/ml and delayed formation of the major metabolite desmethylloperamide (time to reach maximum concentration after drug administration [tmax], 7.1 ± 2.6 hours versus 19.6 ± 9.1 hours). The urinary metabolic ratio of loperamide increased 3 times whereas the total molar amount of loperamide and metabolites excreted in urine remained unchanged. No central pharmacodynamic effects were observed after coadministration of loperamide with either ritonavir or placebo.ConclusionThis study demonstrates a major metabolic interaction probably by cytochrome P4503A4 with no evidence of P‐glycoprotein involvement. This might explain the lack of central effects after ritonavir.Clinical Pharmacology & Therapeutics (2001) 70, 405–414; doi: 10.1016/S0009‐9236(01)35864‐2
The predominant polyphenol in the leaves of the resurrection plantMyrothamnus flabellifolius, 3,4,5 tri-O-galloylquinic acid, protects membranes against desiccation and free radical-induced oxidation
Authors: MOORE John P. , WESTALL Kim L. , RAVENSCROFT Neil , FARRANT Jill M. , LINDSEY George G. , BRANDT Wolf F. 
Published: December 2004

The predominant (&gt;90%) low-molecular-mass polyphenol was isolated from the leaves of the resurrection plant Myrothamnus flabellifolius and identified to be 3,4,5 tri-O-galloylquinic acid using 1H and 13C one- and two-dimensional NMR spectroscopy. The structure was confirmed by mass spectrometric analysis. This compound was present at high concentrations, 44% (by weight) in hydrated leaves and 74% (by weight) in dehydrated leaves. Electron microscopy of leaf material fixed with glutaraldehyde and caffeine demonstrated that the polyphenols were localized in large vacuoles in both hydrated and dehydrated leaves. 3,4,5 Tri-O-galloylquinic acid was shown to stabilize an artificial membrane system, liposomes, against desiccation if the polyphenol concentration was between 1 and 2 μg/μg phospholipid. The phase transition of these liposomes observed at 46 °C was markedly diminished by the presence of 3,4,5 tri-O-galloylquinic acid, suggesting that the presence of the polyphenol maintained the membranes in the liquid crystalline phase at physiological temperatures. 3,4,5 Tri-O-galloylquinic acid was also shown to protect linoleic acid against free radical-induced oxidation.
ADP-ribosylation of integrin α7 modulates the binding of integrin α7β1 to laminin
Authors: ZHAO Zhefeng , GRUSZCZYNSKA-BIEGALA Joanna , ZOLKIEWSKA Anna 
Published: December 2004

The extracellular domain of integrin α7 is ADP-ribosylated by an arginine-specific ecto-ADP-ribosyltransferase after adding exogenous NAD+ to intact C2C12 skeletal muscle cells. The effect of ADP-ribosylation on the structure or function of integrin α7β1 has not been explored. In the present study, we show that ADP-ribosylation of integrin α7 takes place exclusively in differentiated myotubes and that this post-translational modification modulates the affinity of α7β1 dimer for its ligand, laminin. ADP-ribosylation in the 37-kDa ‘stalk’ region of α7 that takes place at micromolar NAD+ concentrations increases the binding of the α7β1 dimer to laminin. Increased in vitro binding of integrin α7β1 to laminin after ADP-ribosylation of the 37-kDa fragment of α7 requires the presence of Mn2+ and it is not observed in the presence of Mg2+. In contrast, ADP-ribosylation of the 63-kDa N-terminal region comprising the ligand-binding site of α7 that occurs at approx. 100 μM NAD+ inhibits the binding of integrin α7β1 to laminin. Furthermore, incubation of C2C12 myotubes with NAD+ increases the expression of an epitope on integrin β1 subunit recognized by monoclonal antibody 9EG7. We discuss our results based on the current models of integrin activation. We also hypothesize that ADP-ribosylation may represent a mechanism of regulation of integrin α7β1 function in myofibres in vivo when the continuity of the membrane is compromised and NAD+ is available as a substrate for ecto-ADP-ribosylation.