bluuebunny/crossref_metadata_2025_split huggingface dataset:
An adenosine A2A receptor agonist reduces interleukin‐8 expression and glycosaminoglycan loss following septic arthrosis
Authors: Cohen Steven B. , Leo Brian M. , Baer Geoffrey S. , Turner Maria A. , Beck Gina , Diduch David R. 
Published: March 2005

AbstractThe purpose of this study was to determine whether an adenosine A2A receptor agonist (ATL146e) might augment the current treatment regimen of antibiotics plus irrigation and debridement to prevent the arthritic effects associated with joint sepsis. Staphylococcus aureus bacteria were injected into knees of rabbits, which were divided into 4 treatment groups (12 rabbits per group): no treatment, ATL146e only, antibiotics only, or antibiotics plus ATL146e. Analysis at days 1, 3, and 7 consisted of gross joint appearance, synovial fluid, serum, histologic, immunohistochemical, and biochemical analysis.Synovial fluid cultures at day 7 were negative in all antibiotic and antibiotic plus ATL146e treated knees indicating clearance of bacteria. Average WBC counts from synovial fluid aspirates significantly decreased with treatment of antibiotics alone and antibiotics plus ATL146e. Treatment with antibiotics plus ATL146e significantly decreased the Interleukin‐8 content when compared to other treatment groups (p < 0.001) indicating inflammatory response suppression. Histologic grading resulted in notably improved scores in the antibiotics plus ATL146e group compared to other treatment groups (p < 0.001). Glycosaminoglycan assay values were significantly greater in the ATL146e plus antibiotics group compared to the untreated control group (p < 0.04) indicating chondroprotection.The results of this study indicate that administration of an adenosine A2A agonist in combination with antibiotic therapy diminishes joint WBC chemotaxis and reduces joint inflammation, while not compromising the clearance of intraarticular bacteria in a rabbit model. Early bacterial clearance with modulation of the inflammatory response appears to prevent the early degradative effects of joint sepsis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Altered loading during walking and sit‐to‐stand is affected by quadriceps weakness after total knee arthroplasty
Authors: Mizner Ryan L. , Snyder‐Mackler Lynn 
Published: March 2005

AbstractPurpose: Total knee arthroplasty (TKA) successfully reduces pain, but has not achieved comparable improvements in function. We hypothesized that quadriceps strength affects performance by altering loading and movement patterns during functional tasks.Methods: Fourteen subjects with isolated, unilateral TKA were tested three months after surgery. Quadriceps strength was assessed isometrically and kinematics, kinetics, and EMG were collected during level walking and sit‐to‐stand (STS). Function was assessed using the timed up and go test (TUG), stair climbing test (SCT), and the 6 min walk test (6MW).Results: Functional performance was significantly related to the quadriceps strength of both legs, but was more strongly related to the uninvolved strength (involved rho = –0.43 with TUG; –0.65 with SCT; 0.64 with 6MW) (uninvolved rho = –0.63 with TUG; –0.68 with SCT; 0.77 with 6MW). During STS, subjects shifted weight away from the operated limb (p <0.01). Quadriceps muscle activity and the extension moments at the knee and hip were smaller in the involved compared to the uninvolved (p <0.05). The amount of asymmetry in knee excursion during weight acceptance in gait, the asymmetry in weight bearing from sit‐to‐stand, and the uninvolved hip extension moment during STS were related to the amount of asymmetry in quadriceps strength (rho > 0.56, p < 0.05).Conclusions: Quadriceps weakness in patients with TKA has a substantial impact on the movement patterns and performance of the knee during functionally important tasks.© 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection
Authors: Yang Zheng Rong 
Published: March 2005

Abstract

Motivation
Although the outbreak of the severe acute respiratory syndrome (SARS) is currently over, it is expected that it will return to attack human beings. A critical challenge to scientists from various disciplines worldwide is to study the specificity of cleavage activity of SARS-related coronavirus (SARS-CoV) and use the knowledge obtained from the study for effective inhibitor design to fight the disease. The most commonly used inductive programming methods for knowledge discovery from data assume that the elements of input patterns are orthogonal to each other. Suppose a sub-sequence is denoted as P2P1P1′P2′, the conventional inductive programming method may result in a rule like ‘if P1 = Q, then the sub-sequence is cleaved, otherwise non-cleaved’. If the site P1 is not orthogonal to the others (for instance, P2, P1′ and P2′), the prediction power of these kind of rules may be limited. Therefore this study is aimed at developing a novel method for constructing non-orthogonal decision trees for mining protease data.

Result
Eighteen sequences of coronavirus polyprotein were downloaded from NCBI (http://www.ncbi.nlm.nih.gov). Among these sequences, 252 cleavage sites were experimentally determined. These sequences were scanned using a sliding window with size k to generate about 50 000 k-mer sub-sequences (for short, k-mers). The value of k varies from 4 to 12 with a gap of two. The bio-basis function proposed by Thomson et al. is used to transform the k-mers to a high-dimensional numerical space on which an inductive programming method is applied for the purpose of deriving a decision tree for decision-making. The process of this transform is referred to as a bio-mapping. The constructed decision trees select about 10 out of 50 000 k-mers. This small set of selected k-mers is regarded as a set of decisive templates. By doing so, non-orthogonal decision trees are constructed using the selected templates and the prediction accuracy is significantly improved.

Availability
The program for bio-mapping can be obtained by request to the author.

Contact
z.r.yang@exeter.ac.uk
α1‐RECEPTOR OR ADENOSINE A1‐RECEPTOR DEPENDENT PATHWAY ALONE IS NOT SUFFICIENT BUT SUMMATION OF THESE PATHWAYS IS REQUIRED TO ACHIEVE AN ISCHAEMIC PRECONDITIONING EFFECT IN RABBITS
Authors: Baba Kaori , Minatoguchi Shinya , Zhang Chengxi , Kariya Tatsuya , Uno Yoshihiro , Kawai Takao , Takahashi Masahiko , Takemura Genzou , Fujiwara Hisayoshi 
Published: March 2005

SUMMARY1. It is reported that α1‐receptors and adenosine A1‐receptors are involved in the ischaemic preconditioning (PC) effect on infarct size (IS). However, it is still unclear to what extent α1‐receptors and adenosine A1‐receptors contribute to the mechanism of PC. Therefore, we investigated the extent of the contribution of α1‐receptors and adenosine A1 receptors to the PC effect on IS and examined the relationship between these receptors and protein kinase C.2. Infarct size was measured in rabbits subjected to 30 min ischaemia and 48 h reperfusion. Tyramine (Tyr) was intravenously administered before 30 min ischaemia in the absence or presence of bunazosin (BN, α1‐receptor blocker) and staurosporine (ST), a protein kinase C inhibitor, respectively. R(‐)N6‐(2‐phenylisapropyl)‐adenosine (PIA), a selective adenosine A1 agonist, was intravenously administered before 30 min ischaemia in the absence or presence of 8‐p‐sulphophenyltheophylline (8SPT), an adenosine blocker and ST, respectively. In the PC groups, BN, BN + PIA, 8SPT, 8SPT + Tyr or placebo saline was injected before or during PC.3. Both Tyr and PIA reduced the IS, which was blocked by BN and 8SPT, respectively. The IS‐reducing effect of Tyr or PIA was blocked by ST. The IS‐reducing effect of PC was completely blocked by BN and 8SPT, respectively. The blocking effect of BN on the IS‐reducing effect of PC was abolished by adding PIA during PC ischaemia. The blocking effect of 8SPT on the IS‐reducing effect of PC was abolished by adding Tyr before PC ischaemia.4. These data suggest that an α1‐receptor dependent pathway exists and an adenosine A1‐receptor dependent pathway, stimulation of both of which activates protein kinase C, then reduces the IS. However, exclusive stimulation of a single α1‐receptor dependent pathway or a single adenosine A1‐receptor dependent pathway alone is not sufficient but the summation of these pathways is required to achieve a PC effect on IS in rabbits.
ANAPHYLACTIC HEPATIC VENOCONSTRICTION IS ATTENUATED BY NITRIC OXIDE RELEASED VIA SHEAR STRESS‐DEPENDENT AND ‐INDEPENDENT MECHANISMS IN GUINEA PIG
Authors: Shibamoto Toshishige , Ruan Zonghai , Cui Sen , Kurata Yasutaka , Koizumi Tomonobu , Kubo Keishi 
Published: March 2005

SUMMARY1. The role of shear stress in nitric oxide (NO)‐mediated attenuation of anaphylactic venoconstriction was studied using an isolated ovalbumin‐sensitized guinea pig liver.2. Guinea pigs were actively sensitized by a subcutaneous injection of 1 mg ovalbumin. Two weeks after sensitization, the livers were perfused with diluted blood under constant flow or constant perfusion pressure. The constant flow could result in increased shear stress during constriction, while the constant perfusion pressure could prevent changes in shear stress. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre‐ and postsinusoidal constriction was evaluated. Hepatic anaphylaxis was induced by an injection of ovalbumin (4 µg) into the perfusate, the volume of which was 40 mL.3. Under either constant flow or pressure, anaphylaxis caused venoconstriction of predominantly presinusoids over postsinusoids, although anaphylactic venoconstriction under constant pressure was significantly greater than that under constant flow. When shear stress was held constant by maintaining constant perfusion pressure, a NO synthase inhibitor, Nω‐nitro‐l‐arginine methyl ester (l‐NAME, 100 µmol/L), potentiated similarly both pre‐ and postsinusoidal constriction induced by anaphylaxis. This suggests that hepatic anaphylaxis shear stress‐independently generates NO, resulting in dilatation of both pre‐ and postsinusoidal vessels in a similar magnitude. In contrast, when shear stress was allowed to rise under constant flow, anaphylactic presinusoidal constriction was preferentially potentiated by l‐NAME.4. Hepatic anaphylaxis can increase NO production in a shear stress‐independent manner and dilates similarly both pre‐ and postsinusoids, while NO produced in a shear stress‐dependent manner attenuates predominantly venoconstriction of the presinusoids where shear stress is preferentially increased.
Short‐term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity
Authors: Bergfors M. , Barnekow‐Bergkvist M. , Kalezic N. , Lyskov E. , Eriksson J. W. 
Published: March 2005

AbstractAim: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity.Method: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% ofVO2maxand (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l−1and insulin was infused at 56 mU m−2 min−1for 120 min.Results: The insulin‐mediated glucose disposal rate (M‐value) for the steady‐state period (60–120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady‐state period into 20‐min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60–80 min (P = 0.04) and 80–100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work.Conclusion: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.
Chronic aerobic exercise enhances components of the classical and novel insulin signalling cascades in Sprague–Dawley rat skeletal muscle
Authors: Bernard J. R. , Crain A. M. , Rivas D. A. , Herr H. J. , Reeder D. W. , Yaspelkis B. B. 
Published: March 2005

AbstractAim:  The aim of this study was to provide a more extensive evaluation of the effects of chronic aerobic exercise on various components of the insulin signalling cascade in normal rodent skeletal muscle because of the limited body of literature that exists in this area of investigation.Methods:  Male Sprague–Dawley rats were assigned to either control (n = 7) or chronic aerobic exercise (n = 7) groups. Aerobic exercise animals were run 3 day week−1 for 45 min on a motor‐driven treadmill (32 m min−1, 15% grade) for a 12 week period. Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 μU mL−1 insulin to determine what effect chronic aerobic training had on various components of the insulin signalling cascade, c‐Cbl protein concentration and c‐Cbl phosphorylation.Results:  Twelve weeks of aerobic training did not alter skeletal muscle Akt 1/2 protein concentration, Akt Ser 473 phosphorylation, Akt Thr 308 phosphorylation, Akt 1 activity, aPKC‐ζ protein concentration, aPKC‐λ protein concentration or c‐Cbl protein concentration. In contrast, chronic aerobic exercise increased insulin‐stimulated phosphatidylinositol 3‐kinase, Akt 2 kinase and aPKC‐ζ/λ kinase activities, as well as c‐Cbl tyrosine phosphorylation, in a fibre type specific response to aerobic training. In addition, chronic aerobic exercise enhanced insulin‐stimulated plasma membrane glucose transporter 4 (GLUT4) protein concentration.Conclusion:  Collectively, these findings suggest that chronic aerobic exercise enhances components of both the classical and novel insulin signalling cascades in normal rodent skeletal muscle, which may contribute to an increased insulin‐stimulated plasma membrane GLUT4 protein concentration.
Non‐invasive monitoring of muscle blood perfusion by photoplethysmography: evaluation of a new application
Authors: Sandberg M. , Zhang Q. , Styf J. , Gerdle B. , Lindberg L.‐G. 
Published: March 2005

AbstractAim:  To evaluate a specially developed photoplethysmographic (PPG) technique, using green and near‐infrared light sources, for simultaneous non‐invasive monitoring of skin and muscle perfusion.Methods:  Evaluation was based on assessments of changes in blood perfusion to various provocations, such as post‐exercise hyperaemia and hyperaemia following the application of liniment. The deep penetrating feature of PPG was investigated by measurement of optical radiation inside the muscle. Simultaneous measurements using ultrasound Doppler and the new PPG application were performed to elucidate differences between the two methods. Specific problems related to the influence of skin temperature on blood flow were highlightened, as well.Results:  Following static and dynamic contractions an immediate increase in muscle perfusion was shown, without increase in skin perfusion. Liniment application to the skin induced a rapid increase in skin perfusion, but not in muscle. Both similarities and differences in blood flow measured by Ultrasound Doppler and PPG were demonstrated. The radiant power measured inside the muscle, by use of an optical fibre, showed that the near‐infrared light penetrates down to the vascular depth inside the muscle.Conclusions:  The results of this study indicate the potentiality of the method for non‐invasive measurement of local muscle perfusion, although some considerations still have to be accounted for, such as influence of temperature on blood perfusion.
Transcriptional responses of rat skeletal muscle following hypoxia‐reoxygenation and near ischaemia‐reperfusion
Authors: Aravindan N. , Williams M. T. , Riedel B. J. C. J. , Shaw A. D. 
Published: March 2005

AbstractAim:  The effect of ischaemia/reperfusion or hypoxia/reoxygenation on gene expression has not been extensively studied. We hypothesized that in skeletal muscle, tissue hypoxia of similar magnitude but induced by different mechanisms would lead to different transcriptional responses.Methods:  Muscle gene transcription was assessed using microarray analysis and reverse transcriptase polymerase chain reaction in 18 rats exposed to regional hind limb near ischaemia/reperfusion (n = 6), hypoxia/reoxygenation (n = 6) or sham operation (n = 6). Hypoxic burden was measured by the area under the PtO2–time curve.Results:  PtO2 was reduced in both the near ischaemia/reperfusion and hypoxia/reoxygenation groups. Although the hypoxic burden was similar, the genomic response was different for each condition. Near ischaemia/reperfusion had a greater effect on gene expression than hypoxia/reoxygenation. Using stringent criteria for changes in gene expression (i.e. more than or equal to twofold change vs. control) unique patterns of gene expression could be identified suggesting individualized transcriptional responses to each of these injuries. Several genes, including insulin‐like growth factor 1 (IGF‐1) and cyclin‐dependent kinase inhibitor (p27Kip1) were induced by both injury types and these may have potential clinical application as markers of tissue damage. In contrast, no single gene was downregulated by both injury conditions.Conclusions:  The mechanism of skeletal muscle hypoxia has a profound effect on its subsequent transcriptional response. We identified several potential candidates as markers of skeletal muscle ischaemic damage.
Effects of cold‐water immersion on VEGF mRNA and protein expression in heart and skeletal muscles of rats
Authors: Kim J. C. , Yi H. K. , Hwang P. H. , Yoon J. S. , Kim H. J. , Kawano F. , Ohira Y. , Kim C. K. 
Published: March 2005

AbstractAim:  The effects of cold exposure on gene and protein expression of vascular endothelial growth factor (VEGF), in heart and skeletal muscles, were studied in male adult Wistar rats.Methods:  Cold immersion was accomplished by submerging the rats in shoulder‐deep water maintained at ∼18 °C, either acutely (1 h) or chronically (1 h day−1, 5 days week−1 for 20 weeks). The expressions of VEGF mRNA and protein in heart, gastrocnemius, and soleus muscles were examined by Northern and Western blotting and competitive‐polymerase chain reaction techniques.Results:  The expressions of VEGF mRNA and protein were markedly increased in cardiac muscle of the cold‐immersed group, particularly in the 1‐hour exposure group, whereas VEGF mRNA and protein in gastrocnemius were decreased significantly after an acute exposure. Although the protein level in gastrocnemius remained low in the chronically exposed group, the expression of mRNA of VEGF165 with chronic exposure in this group returned to the control level and that of VEGF206 was 15% greater than that in controls. The expression of mRNA for VEGF165 in soleus was also lowered by acute cold exposure, although that for VEGF206 was stable. However, VEGF protein was increased by 50%. After 20 weeks, all of these parameters were increased over the levels found in the controls.Conclusion:  These results suggest that the VEGF gene may be a major regulatory factor in cardiac and skeletal muscle adaptation to the cold environment stimulating angiogenesis and thermogenesis.
Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects
Authors: Lilja Jari J. , Backman Janne T. , Neuvonen Pertti J. 
Published: March 2005

AimsCase reports suggest that gemfobrozil can increase the anticoagulant effect of warfarin. Because gemfibrozil inhibits CYP2C9 in vitro, we studied its effects on the pharmacokinetics and pharmacodynamics of racemic warfarin.MethodsIn a randomized cross‐over study, 10 healthy subjects ingested 600 mg gemfibrozil or placebo twice daily for 8 days. On day 3, they were administered a single dose of 10 mg racemic R‐S‐warfarin orally. The concentrations of R‐ and S‐warfarin in plasma and thromboplastin time were monitored up to 168 h.ResultsGemfibrozil decreased the mean (±SD) area under the plasma concentration‐time curve [AUC(0–∞)] of S‐warfarin by 11%, from 19.9 ± 5.2 mg l−1 h to 17.6 ± 4.7 mg l−1 h (95% CI on the difference −3.7, −0.78; P < 0.01) and that of R‐warfarin by 6% from  31.3 ± 7.5 mg l−1 h during  the  gemfibrozil  phase  to  29.5 ± 6.9 mg l−1 h during the placebo phase (95% CI −3.3, −0.33; P < 0.05). There were no significant differences in the elimination half‐lives of S‐ or R‐warfarin between the phases. Gemfibrozil did not alter the anticoagulant effect of warfarin.ConclusionUnexpectedly, gemfibrozil slightly decreased the plasma concentrations of R‐ and S‐warfarin. Displacement of warfarin from plasma albumin by gemfibrozil or its interference with the absorption of warfarin could explain the present findings. Usual therapeutic doses of gemfibrozil seem to have limited effects on the pharmacokinetics and pharmacodynamics of single dose warfarin in healthy subjects.
Raloxifene pharmacokinetics in males with normal and impaired renal function
Authors: Czock David , Keller Frieder , Heringa Mette , Rasche Franz Maximilian 
Published: March 2005

AimsTo compare raloxifene pharmacokinetics between renally impaired and healthy subjects.MethodsRaloxifene 120 mg was administered to 10 males with renal impairment (creatinine 2–4 mg dl−1) and to 10 healthy males. Data were analysed by two noncompartmental and one compartmental nonlinear regression methods.ResultsThe medians (95% confidence interval) of the area under the curves (AUC) were 35.1 (25.8, 74) and 20.5 (16.8, 28.0) h ng ml−1 per mg kg−1, P < 0.01, and of the clearances (CL/F) were 28.5 (13.5, 38.8) and 48.8 (35.8, 59.4) l h−1 kg−1, P < 0.01, in renally impaired and healthy subjects, respectively. 95% Confidence intervals on the differences for AUC and CL/F were 6.5–44.1 and −35.1 to −7.9, respectively.ConclusionExposure to raloxifene was twice as high in males with renal impairment compared with healthy subjects.
Insertion/deletion polymorphism of the ACE gene and adherence to ACE inhibitors
Authors: Schelleman H. , Klungel O. H. , Van Duijn C. M. , Witteman J. C. M. , Hofman A. , De Boer A. , Stricker B. H. Ch 
Published: March 2005

AimsWe investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug.MethodsThis was a cohort study among 239 subjects who started ACE inhibitor therapy. A Cox proportional hazard model was used to calculate relative risk (RR).ResultsDuring follow‐up there was no significant difference between subjects with the DD, ID or II genotype (DD vs II; RR = 1.17, 95%CI: 0.78, 1.77 and ID vs II; RR = 1.06, 95%CI: 0.73, 1.55) in adherence.ConclusionsThe I/D polymorphism of the ACE gene does not influence the adherence to ACE inhibitors.