bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations
Authors: Frostegård Johan , Svenungsson Elisabet , Wu Ruihua , Gunnarsson Iva , Lundberg Ingrid E. , Klareskog Lars , Hörkkö Sohvi , Witztum Joseph L. 
Published: January 2005

AbstractObjectiveCardiovascular disease with premature atherosclerosis is common in patients with systemic lupus erythematosus (SLE). We previously identified elevated levels of oxidized low‐density lipoprotein (OxLDL) together with elevated levels of autoantibodies related to OxLDL as risk factors for cardiovascular disease in female patients with SLE. Autoantibodies to OxLDL are common in SLE and cross‐react with anticardiolipin antibodies (aCL). We therefore hypothesized that lipid peroxidation is enhanced in patients with SLE in general.MethodsOne hundred forty‐seven female patients with SLE and 60 age‐ and sex‐matched controls were compared. A monoclonal antibody to oxidized phospholipids, EO6, was used to determine oxidation epitopes on LDL. Anti‐OxLDL and autoantibodies to malondialdehyde (MDA)–modified LDL, cardiolipin, and oxidized aCL were determined by chemiluminescence technique.ResultsAs determined by binding of EO6, patients with SLE had a higher level of oxidized phospholipids on LDL (P = 0.005) compared with controls. The level of OxLDL (e.g., oxidized phospholipid/apolipoprotein B) was associated with arterial disease (P = 0.006) and renal manifestations (P = 0.04). As reported previously, levels of aCL, autoantibodies to OxLDL, and autoantibodies to MDA‐modified LDL were enhanced and were closely correlated in SLE. Anticardiolipin antibodies from these SLE patients recognized mainly oxidized forms of cardiolipin, indicating that antigenic epitopes on cardiolipin are related to lipid peroxidation in patients with SLE.ConclusionIn general, patients with SLE (particularly those with cardiovascular disease) had more oxidized epitopes on LDL compared with controls. Furthermore, aCL in these patients recognized epitopes generated during lipid peroxidation. Thus, “neo” self antigens on lipoproteins, generated during oxidation, are present in SLE and may be of importance for the development of premature cardiovascular disease and possibly also for other autoimmune phenomena observed in SLE.
Cartilage glycosaminoglycan loss in the acute phase after an anterior cruciate ligament injury: Delayed gadolinium‐enhanced magnetic resonance imaging of cartilage and synovial fluid analysis
Authors: Tiderius Carl Johan , Olsson Lars Eric , Nyquist Fredrik , Dahlberg Leif 
Published: January 2005

AbstractObjectiveTo examine the glycosaminoglycan (GAG) content in cartilage and that in synovial fluid and determine whether they are associated, in patients with an acute anterior cruciate ligament (ACL) injury.MethodsTwenty‐four patients (14 of whom were male) with a mean age of 27 years (range 17–40 years) were assessed with delayed gadolinium‐enhanced magnetic resonance imaging (MRI) of cartilage an average of 3 weeks after an ACL rupture and compared with 24 healthy volunteers. Two hours after an intravenous injection of Gd‐DTPA2− (0.3 mmoles/kg body weight), quantitative measurements of the T1 relaxation time (T1Gd [T1 relaxation time in the presence of Gd‐DTPA]) were made in lateral and medial femoral weight‐bearing cartilage. In the patients, synovial fluid was aspirated immediately before the MRI, and GAG was analyzed using dye precipitation with Alcian blue.ResultsFifteen of the 24 patients had an isolated bone bruise in the lateral femoral condyle, where the cartilage T1Gd was shorter than that in the controls (mean ± SD 385 ± 83 msec and 445 ± 41 msec, respectively; P = 0.004), consistent with decreased GAG content. However, the T1Gd was also decreased in the medial femoral cartilage, where bone bruises were rare (376 ± 76 msec in patients versus 428 ± 38 msec in controls; P = 0.006). The mean ± SD synovial fluid GAG concentration in patients was 157 ± 86 μg/ml and showed a positive correlation with the T1Gd (r = 0.49, P = 0.02).ConclusionThis study indicates that an ACL injury causes posttraumatic edema of the lateral femoral cartilage but initializes a generalized biochemical change within the knee that leads to GAG loss from both lateral and medial femoral cartilage. In cartilage with a high GAG content (long T1Gd), more GAG is released into the synovial fluid, suggesting that cartilage quality is a factor to consider when interpreting cartilage biomarkers of metabolism.
Effect of inhibition of matrix metalloproteinases on cartilage loss in vitro and in a guinea pig model of osteoarthritis
Authors: Sabatini Massimo , Lesur Christophe , Thomas Marie , Chomel Agnès , Anract Philippe , de Nanteuil Guillaume , Pastoureau Philippe 
Published: January 2005

AbstractObjectiveTo study the effects of a matrix metalloproteinase (MMP) inhibitor (S‐34219) on osteoarthritis (OA) cartilage cultures and in the meniscectomized guinea pig model of OA.MethodsThe inhibitory activity of S‐34219 on MMPs and aggrecanase was studied by fluorimetry and immunoassay, respectively. The effects of S‐34219 on proteoglycan and collagen degradation were studied in cultures of rabbit and human cartilage. Medial meniscectomy was performed on 29 Hartley male guinea pigs, and these animals were randomly allocated to 1 of 3 groups: a control meniscectomized group (MNXc) receiving the vehicle, or a meniscectomized group receiving either 10 mg/kg or 20 mg/kg S‐34219, administered twice per day by oral gavage for 12 weeks from day 1 after surgery. An additional group comprised sham‐operated animals. Tibial cartilage from the operated left knee was processed for histologic assessment of OA lesions.ResultsThe 50% inhibitory concentration (IC50) of S‐34219 on MMPs 1, 2, 3, 8, 9, and 13 was 55, 0.1, 0.5, 0.1, 0.03, and 0.2 nM, respectively; the IC50 on aggrecanase 1 was 190 nM. In cultured rabbit cartilage, 100 nM S‐34219 strongly inhibited MMP‐dependent degradation of collagen and proteoglycans. A concentration 100 times higher was needed to inhibit aggrecanase‐dependent degradation. In cultures of human OA cartilage, 100 nM S‐34219 inhibited spontaneous type II collagen degradation by 66% and proteoglycan degradation by only 22%. For in vivo studies, treated groups were compared with the MNXc group and the results, expressed as the percentage variation versus MNXc, were as follows: in the 10 and 20 mg/kg groups, a significant decrease (P < 0.05) in global histologic score (−12% and −14%, respectively) was observed, and this was associated with a significant increase (P < 0.05) in cartilage thickness (+19% and +18%, respectively). Neither dose level changed the proteoglycan content.ConclusionIn both treated animal groups, S‐34219 significantly prevented the loss of cartilage thickness, probably by inhibiting collagen breakdown that normally leads to the erosion of fibrillated superficial areas. The absence of a protective effect on glycosaminoglycan loss, both in vitro and in vivo, suggests that aggrecanases may have an important role in cartilage loss. This study reinforces the relevance of these models for testing chondroprotective drugs, and the potential role of dual inhibitors of collagenase and aggrecanase as disease‐modifying drugs in the management of OA.
An approach to understand the complexation of supramolecular dye Congo red with immunoglobulin L chain λ
Authors: Król Marcin , Roterman Irena , Piekarska Barbara , Konieczny Leszek , Rybarska Janina , Stopa Barbara , Spólnik Paweł , Szneler Edward 
Published: January 2005

AbstractCongo red, a dye of high self‐assembling tendency, has been found to form complexes with proteins by adhesion of the ribbon‐like supramolecular ligand to polypeptide chains of β‐conformation. Complexation is allowed by local or global protein instability, facilitating penetration of the dye to the locus of its binding. At elevated temperatures, L chain λ of myeloma origin was found to form two distinct complexes with Congo red, easily differentiated in electrophoresis as slow‐ and fast‐migrating fractions, bearing four‐ and eight‐dye‐molecule ligands, respectively, in the V domain of each individual chain. The slow‐migrating complex is formed after displacement of the N‐terminal polypeptide chain fragment (about 20 residues) from its packing locus, thereby exposing the entrance to the binding cavity. In this work the formation and stability of this complex was studied by molecular dynamics (MD) simulations. The effect of three‐ and five‐molecule ligands introduced to the site binding the dye was also analyzed in an attempt to understand the formation of fast‐migrating complexes. The wedging of the ligand containing five dye molecules, hence longer than established experimentally as the maximum for the slow‐migrating complex, was found to generate significant structural changes. These changes were assumed to represent the crossing of the threshold on the way to forming a fast‐migrating complex more capacious for dyes. They led to almost general destabilization of the V domain, making it susceptible to extra dye complexation. Theoretical studies were designed in close reference to experimental findings concerning the number of dye molecules in the ligand inserted to the site binding the dye, the location of the site in the domain, and the conditions of formation of the complexes. The results of the two kinds of studies appeared coherent. © 2005 Wiley Periodicals, Inc. Biopolymers, 2005
Total chemical synthesis and oxidative folding of δ‐conotoxin PVIA containing an N‐terminal propeptide
Authors: Buczek Pawel , Buczek Olga , Bulaj Grzegorz 
Published: January 2005

AbstractSmall disulfide‐rich peptides are translated as larger precursors typically containing an N‐terminal prepro sequence. In this study, we investigated the role of a propeptide in the oxidative folding of an extremely hydrophobic δ‐conotoxin, PVIA. δ‐Conotoxin PVIA (δ‐PVIA) is a 29‐amino acid neurotoxin stabilized by three disulfide bridges. Previous folding studies on δ‐conotoxins revealed that their poor folding properties resulted from their hydrophobicity. However, low folding yields of δ‐PVIA could be improved by the presence of a nonionic detergent, which acted as a chemical chaperone. δ‐PVIA provided an attractive model to investigate whether the hydrophilic propeptide region could function as an intramolecular chaperone. A 58‐amino acid precursor for δ‐PVIA (pro‐PVIA), containing the N‐terminal propeptide covalently attached to the mature conotoxin, was synthesized using native chemical ligation. Oxidative folding of pro‐PVIA resulted in a very low accumulation of the correctly folded form, comparable to that for the mature conotoxin δ‐PVIA. Our results are in accord with the relevant data previously observed for α‐ and ω‐conotoxins, indicating that conotoxin prepro sequences are so‐called class II propeptides, which are not directly involved in the oxidative folding. We hypothesize that these propeptide regions may be important for interactions with protein folding catalysts and sorting receptors during the secretory process. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005
Signal‐amplifying genetic circuit enables in vivo observation of weak promoter activation in the Rhl quorum sensing system
Authors: Karig David , Weiss Ron 
Published: January 2005

AbstractSmall changes in transcriptional activity often significantly affect phenotype but are not detectable in vivo by conventional means. To address this problem, we present a technique for detecting weak transcriptional responses using signal‐amplifying genetic circuits. We apply this technique to reveal previously undetectable log phase responses of several Rhl quorum sensing controlled (qsc) promoters from Pseudomonas aeruginosa. Genetic circuits with Rhl promoters and transcriptional amplification components were built and tested in Escherichia coli. This enabled us to isolate the behavior of the promoters under study from Las and quinolone interactions. To amplify qsc promoter responses to acyl‐homoserine lactones (AHL), the highly efficient λ repressor gene was placed downstream of several Rhl promoters and coupled to a fluorescent reporter under the control of the λ P(R) promoter. With amplification, up to ∼100‐fold differences in fluorescence levels between AHL induced and noninduced cultures were observed for promoters whose responses were otherwise not detectable. In addition, the combination of using signal amplification and performing experiments in E. coli simplified the analysis of AHL signal crosstalk. For example, we discovered that while a C4HSL/RhlR complex activates both qscrhlA and qscphzA1, a 3OC12HSL/RhlR complex activates qscphzA1 but not qscrhlA in our system. This crosstalk information is particularly important since one of the potential uses of amplification constructs is for the detection of specific quorum sensing signals in environmental and clinical isolates. Furthermore, the process of decomposing networks into basic parts, isolating these components in a well‐defined background, and using amplification to characterize both crosstalk and cognate signal responses embodies an important approach to understanding complex genetic networks. © 2004 Wiley Periodicals, Inc.
Foundations of chemical microscopy. 3. derivatives of some chiral phenylalkylamines and phenylalkylamino acids with 5‐nitrobarbituric acid
Authors: Brittain Harry G. , Rehman Michael 
Published: January 2005

AbstractAt one time, 5‐nitrobarbituric acid (also known as dilituric acid) was extensively used as a chemical reagent for the qualitative identification of a variety of basic substances by light microscopy. This methodology was based on evaluation of observed crystal morphologies, because skilled observers could associate a unique crystal habit with the products formed with analytes when those were crystallized using standardized methods. As part of a study to understand the scientific foundations that permitted chemical microscopy to function as a useful analytical technique during its heyday, the products formed by dilituric acid with resolved and racemic phenylalkylamines and phenylalkylamino acids were characterized using a variety of physical analytical techniques. It was found that the different crystal morphologies associated with each of the crystalline adducts were derived from the ability of the systems to form differing structural types and/or hydrate crystal forms upon crystallization. Chirality 17:89–98, 2005. © 2005 Wiley‐Liss, Inc.
Determination of terbutaline enantiomers in biological samples using liquid chromatography with coupled columns
Authors: Walhagen Agneta , Edholm Lars‐Erick , Kened Brit‐Marie , Xiao Liu Chang 
Published: January 2005

AbstractThe purpose of this work was to develop and validate a method for the separation and determination of the enantiomers of terbutaline in plasma and intestinal juice. Terbutaline was extracted from plasma and intestinal juice by liquid‐solid extraction on small C18cartridges. The extract was then analyzed by coupled column liquid chromatography with amperometric detecton. For ciral separation a β‐cyclodextrin phase was used.The within‐day variation (Cv) on spiked plasma samples was in the rane 0.8‐6.4% at 3.8‐33.8 nmol/liter for the (−)‐enantiomer, and 2.6‐23.0% at 1.3‐11.3 nmol/liter for the (+)‐enantiomer. The between‐day variation on spiked plasma samples was 5.5% at 10.7 nmol/liter and 13.6% at 4.3 nmol/liter for the (−)‐ and (+)‐enantiomers, respectively. The within‐day variation for inestinal juice was i the range 0.7‐1.5% at 5.6‐30.0 μmol/liter for the (+)‐enantiomer.
Liquid chromatographic separation of anomeric forms of saccharides with cyclodextrin bonded phases
Authors: Armstrong Daniel W. , Jin Heng L. 
Published: January 2005

AbstractA brief review of sugar stereochemistry is given. The separation of 84 different pairs of anomers was accomplished on both α‐ and β‐cyclodextrin columns. Five different mobile phases were evaluated. The separation of anomers temperature, flow rate, and so on. The separation of anomers that mutarotate is somewhat more difficult than those that do not. Prior knowledge as to the rate of mutaroation is useful so that the chromatographic conditions can be arranged to minimize any deleterious effects on the separation.
Preparation of chiral statonary phase from an α‐amino phosphonate
Authors: Pirkle William H. , Burke John A. 
Published: January 2005

AbstractA chiral statonary phase (CSP) derived from an N‐(3,5‐dinitrobenzoyl)‐α‐aminobenzylphosphonate has been prepared and evaluated for its utility in the direct separation of enantiomers. This CSP, 2, is structurally related to earlier N‐(3,5‐dinitrobenzoyl)‐α‐acids acid‐derived phases (e.g., CSP 1), but the mode of attachment to the support is different. In scope; CSP 2 is qualitaively similar to CSP 1. However, it differs quantitatively from CSP 1, showing either greater or lesser selectivity for different pairs of enantiomers.
Resolution of some β‐hydroxyphenethylamines as N‐(3,5‐dinitrobenzoyl) amides on chiral stationary phases derived from cinchona alkaloids
Authors: Salvadori Piero , Rosini Carlo , Pini Dario , Bertucci Carlo , Uccello‐Barretta Gloria 
Published: January 2005

AbstractThree chiral stationary phases, obtained by derivatizing γ‐mercaptopropylsilanized silica gel with quinine, quinidine, and cinchonidine, have been employed in the resolution of N‐acyl derivatives of β‐hydroxyphenethylamines. The use of circular dichroism for detection and NMR analysis of analyte–selector mixtures provides an experimental basis for preliminary assignment of a recognition mechanism.
Pharmacokinetics of the enantiomers of terbutaline after repeated oral dosing with racemic terbutaline
Authors: Borgström Lars , Chang‐Xiao Liu , Walhagen Agneta 
Published: January 2005

AbstractTerbutaline is a β2‐agonist and administered as the racemic mixture. The pharmacokinetics of the separate enantiomers differ with respect to degree of absorption and clearance. In the present study, repeated doses of racemic terbutaline were given to six healthy volunteers. Plasma was analyzed for the concentrations of the two enantiomers. The observed plasma concentrations at steady state differed from those predicted from the values observed after single dose administration of the separate enantiomers. The difference between the observed and predicted values can be tentatively explained by a combined influence of (−)‐terbutaline on the absorption of (+)‐terbutaline and the influence of (+)‐terbutaline on the elimination of (−)‐terbutaline. The results have implications for the interpretation of effect/concentration studies with terbutaline, but do not affect the doses used in clinical practice.
Stereochemical influences upon the opioid ligand activities of 4‐alkyl‐4‐arylpiperidine derivatives
Authors: Casy A. F. , Dewar G. H. , Al Deeb Omar A.A. 
Published: January 2005

AbstractThe synthesis and stereochemistry (configuration and preferred solute conformation) of some 4‐alkyl (methyl, n‐propyl, isobutyl)‐4‐(3‐hydrxyphenyl)‐1‐methylpiperidines and corresponding 3‐methyl diastereoisomeric pairs are reported, together with their in vivo and in vitro activities as opioid ligands. All potent agonists exhibit a preference for axial 4‐aryl chair conformations when protonated, and stereochemical analogies with rigid opioids of the benzomorphan class are discussed. Antagonist properties are found in compounds with preference for equatorial 4‐aryl chairs, notably the cis 3,4‐dimethyl derivative.
Optical resolution of β‐lactams by chiral HPLC on tris(phenylcarbamate)s of cellulose and amylose
Authors: Okamoto Yoshio , Senoh Toshiaki , Nakane Harumi , Hatada Koichi 
Published: January 2005

AbstractSeparation and optical resolution of 6 diastereomers and 25 racemates of β‐lactams were examined by HPLC on chiral stationary phases composed of six cellulose and one amylose tris(phenylcarbamate) derivatives. Most β‐lactams were optically resolved at least by one of the derivatives. The absolute configuration of β‐lactams was estimated by CD spectroscopy.
Metabolism of halazepam by rat liver microsomes: Stereoselective formation and n‐dealkylation of 3‐hydroxyhalazepam
Authors: Lu Xiang‐Lin , Yang Shen K. 
Published: January 2005

AbstractMetabolism of halazepam [7‐chloro‐1,3‐dihydro‐5‐phenyl‐1‐(2,2,2‐trifluoroethyl)‐2H‐1,4‐benzodi epin‐2‐one, HZ] was studied by incubation with liver microsomes prepared from untreated, phenobarbital (PB)‐treated, and 3‐methylcholanthrene (3MC)‐treated male Sprague–Dawley rats. Metabolites of HZ were separated by normal‐phase HPLC. Relative rates of HZ metabolism by liver microsomes prepared from untreated and treated rats were PB‐treated ≫ untreated > 3MC‐treated at low concentration of microsomal enzymes (0.25 mg protein per ml of incubation mixture) and PB‐treated ≫ 3MC‐treated ≈ untreated at high concentration of microsomal enzymes (2 mg protein per ml of incubation mixture). The relative amounts of major metabolites were found to be 3‐hydroxy‐HZ (3‐OH‐HZ) > N‐desalkylhalazepam (NDZ, also known as N‐desmethyldiazepam and nordiazepam) ≫ oxazepam (OX) for all three rat liver microsomal preparations and the distribution of metabolites was independent of microsomal enzyme concentrations. Enantiomers of 3‐OH‐HZ were resolved by HPLC on a Chiralcel OC column (cellulose trisphenylcarbamate coated on silica gel, particle size 10 μm). 3‐OH‐HZ enantiomeres have racemization half‐lives of ∼ 150 min in pH 4,7.5, and 10 aqueous solutions. 3‐OH‐HZ formed in the metabolism of HZ by liver microsomes prepared from untreated and treated rats were found to have 3R/3S enantiomer rations of 37/63 (untreated), 55/45 (PB‐treated), and 36/64 (3MC‐treated), respectively. N‐dealkylation of 3‐OH‐HZ by liver microsomes from PB‐treated rats was substrate enantioselective; the 3R‐enantiomer was N‐dealkylated faster than 3S‐enantiomer. The results indicated that the stereoselective C3‐hydroxylation of HZ is dependent on the cytochromes P‐450 present in the rat liver microsomal preparations; pro‐R in liver microsomes from PB‐treated rats and pro‐S in liver microsomes from untreated and 3MC‐treated rats, respectively.
Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14α‐demethylase (cytochrome p‐45014dm): A model study with stereoisomers of triadimenol and purified cytochrome p‐45014dm from yeast
Authors: Yoshida Yuzo , Aoyama Yuri 
Published: January 2005

AbstractThe effect of the four triadimenol stereoisomers on the purified yeast lanosterol 14α‐demethylase (cytochrome P‐45014DM), the primary target of azole antifungal agents, was studied. (1S,2R)‐Triadimenol was the most potent demethylase inhibitor and bound quantitatively to the enzyme below 0.05 μM. This isomer also interfered with the chemical reduction of cytochrome P‐45014DM and the binding of CO to the cytochrome. The other isomers showed a lower inhibitory effect on the enzyme, and the order of activity was (1R,2R) > (1R,2S) ≧ (1S,2S). Based on these findings and the reported preferred conformations for the triadimenol stereoisomers (Anderson, N.H. et al., Pestic. Sci. 15:310–316, 1984), it is predicted that orientation of the hydrophobic tert‐butyl and p‐chlorophenyl groups relative to the azole nitrogen is important to fit the antifungal agent in the active site of the demethylase.