bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failure of Bay K 8644 to induce RhoA kinase‐dependent calcium sensitization in rabbit blood vessels
Authors: Alvarez SM , Miner AS , Browne BM , Ratz PH 
Published: March 2010

Background and purpose:  RhoA kinase (ROCK) participates in K+ depolarization (KCl)‐induced Ca2+ sensitization of contraction. Whether constitutive, depolarization‐ or Ca2+‐activated ROCK plays the major role in this signalling system remains to be determined. Here, we determined whether Bay K 8644, a dihydropyridine that promotes Ca2+ channel clusters to operate in a persistent Ca2+ influx mode, could cause ROCK‐dependent Ca2+ sensitization.Experimental approach:  Renal and femoral artery rings from New Zealand white rabbits were contracted with Bay K 8644. Tissues were frozen and processed to measure active RhoA and ROCK substrate (myosin phosphatase targeting subunit, MYPT1) and myosin light chain (MLC) phosphorylation, or loaded with fura‐2 to measure intracellular free Ca2+ ([Ca2+]i). Effects of selective inhibitors of contraction were assessed in resting (basal) tissues and those contracted with Bay K 8644.Key results:  Bay K 8644 produced strong increases in [Ca2+]i, MLC phosphorylation and tension, but not in MYPT1 phosphorylation. ROCK inhibition by H‐1152 abolished basal MYPT1‐pT853, diminished basal MLC phosphorylation and inhibited Bay K 8644‐induced increases in MLC phosphorylation and tension. MLC kinase inhibition by wortmannin abolished Bay K 8644‐induced contraction and increase in MLC phosphorylation but did not inhibit basal MYPT1‐pT853. H‐1152 and wortmannin had no effect on MYPT1‐pT696, but 1 µM staurosporine inhibited basal MYPT1‐pT853, MYPT1‐pT696 and MLC phosphorylation.Conclusions and implications:  These data suggest that the constitutive activities of ROCK and a staurosporine‐sensitive kinase regulate basal phosphorylation of MYPT1, which participates along with activation of MLC kinase in determining the strength of contraction induced by the Ca2+ agonist, Bay K 8644.
Effects of cytochrome P450 3A (CYP3A) and the drug transporters P‐glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir
Authors: van Waterschoot RAB , ter Heine R , Wagenaar E , van der Kruijssen CMM , Rooswinkel RW , Huitema ADR , Beijnen JH , Schinkel AH 
Published: March 2010

Background and purpose: Lopinavir is extensively metabolized by cytochrome P450 3A (CYP3A) and is considered to be a substrate for the drug transporters ABCB1 (P‐glycoprotein) and ABCC2 (MRP2). Here, we have assessed the individual and combined effects of CYP3A, ABCB1 and ABCC2 on the pharmacokinetics of lopinavir and the relative importance of intestinal and hepatic metabolism. We also evaluated whether ritonavir increases lopinavir oral bioavailability by inhibition of CYP3A, ABCB1 and/or ABCC2.Experimental approach: Lopinavir transport was measured in Madin‐Darby canine kidney cells expressing ABCB1 or ABCC2. Oral lopinavir kinetics (+/− ritonavir) was studied in mice with genetic deletions of Cyp3a, Abcb1a/b and/or Abcc2, or in transgenic mice expressing human CYP3A4 exclusively in the liver and/or intestine.Key results: Lopinavir was transported by ABCB1 but not by ABCC2in vitro. Lopinavir area under the plasma concentration – time curve (AUC)oralwas increased in Abcb1a/b−/−mice (approximately ninefold vs. wild‐type) but not in Abcc2−/−mice. Increased lopinavir AUCoral(>2000‐fold) was observed in cytochrome P450 3A knockout (Cyp3a−/−) mice compared with wild‐type mice. No difference in AUCoralbetween Cyp3a−/−and Cyp3a/Abcb1a/b/Abcc2−/−mice was observed. CYP3A4 activity in intestine or liver, separately, reduced lopinavir AUCoral(>100‐fold), compared with Cyp3a−/−mice. Ritonavir markedly increased lopinavir AUCoralin all CYP3A‐containing mouse strains.Conclusions and implications: CYP3A was the major determinant of lopinavir pharmacokinetics, far more than Abcb1a/b. Both intestinal and hepatic CYP3A activity contributed importantly to low oral bioavailability of lopinavir. Ritonavir increased lopinavir bioavailability primarily by inhibiting CYP3A. Effects of Abcb1a/b were only detectable in the presence of CYP3A, suggesting saturation of Abcb1a/b in the absence of CYP3A activity.
Ca2+signalling by P2Y receptors in cultured rat aortic smooth muscle cells
Authors: Govindan Sriram , Taylor Emily JA , Taylor Colin W 
Published: March 2010

Background and purpose: P2Y receptors evoke Ca2+signals in vascular smooth muscle cells and regulate contraction and proliferation, but the roles of the different P2Y receptor subtypes are incompletely resolved.Experimental approach: Quantitative PCR was used to define expression of mRNA encoding P2Y receptor subtypes in freshly isolated and cultured rat aortic smooth muscle cells (ASMC). Fluorescent indicators in combination with selective ligands were used to measure the changes in cytosolic free [Ca2+] in cultured ASMC evoked by each P2Y receptor subtype.Key results: The mRNA for all rat P2Y receptor subtypes are expressed at various levels in cultured ASMC. Four P2Y receptor subtypes (P2Y1, P2Y2, P2Y4 and P2Y6) evoke Ca2+signals that require activation of phospholipase C and comprise both release of Ca2+from stores and Ca2+entry across the plasma membrane.Conclusions and implications: Combining analysis of P2Y receptor expression with functional analyses using selective agonists and antagonists, we isolated the Ca2+signals evoked in ASMC by activation of P2Y1, P2Y2, P2Y4 and P2Y6 receptors.
Being mindful of seven‐transmembrane receptor ‘guests’ when assessing agonist selectivity
Authors: Kenakin Terry 
Published: March 2010

The time‐honored approach of quantifying agonist selectivity through measurement of agonist affinity with binding and efficacy through potency ratios in model assays for prediction of effect in therapeutic systems can fall short of providing useful answers for functionally selective agonists. Agonists are now known to have pluridimensional efficacies that are associated with selected signalling pathways coupled to the receptor. This necessitates specifically tailored assay formats to measure pre‐determined efficacies of ligands to characterize agonist selectivity fully. If such assays can access signalling that directly emanates from the interaction of the agonist‐bound receptor and a cytosolic signalling protein, then the Black/Leff operational model can be used to specifically quantify ‘transduction ratios’ (τ/KA) that fully characterize selective activation of signalling pathways by a given agonist. As whole‐cell processing of pleiotropic signalling cascades imposes cell‐specific phenotypic agonist profiles, ultimately the assessment of agonist selectivity is most reliably done in the therapeutically relevant primary cell system.This article is a commentary on Baker, pp. 1048–1061 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00754.x
Botulinum Toxin, Physical and Occupational Therapy, and Neuromuscular Electrical Stimulation to Treat Spastic Upper Limb of Children With Cerebral Palsy: A Pilot Study
Authors: Rodríguez‐Reyes Gerardo , Alessi‐Montero Aldo , Díaz‐Martínez Leticia , Miranda‐Duarte Antonio , Pérez‐Sanpablo Alberto Isaac 
Published: March 2010

AbstractSpasticity has been successfully managed with different treatment modalities or combinations. No information is available on the effectiveness or individual contribution of botulinum toxin type A (BTA) combined with physical and occupational therapy and neuromuscular electrical stimulation to treat spastic upper limb. The purpose of this study was to assess the effects of such treatment and to inform sample‐size calculations for a randomized controlled trial. BTA was injected into spastic upper limb muscles of 10 children. They received 10 sessions of physical and occupational therapy followed by 10 sessions of neuromuscular electrical stimulation on the wrist extensors (antagonist muscles). Degree of spasticity using the Modified Ashworth scale, active range of motion, and manual function with the Jebsen hand test, were assessed. Meaningful improvement was observed in hand function posttreatment (P = 0.03). Median spasticity showed a reduction trend and median amplitude of wrist range of motion registered an increase; however, neither of these were significant (P > 0.05). There is evidence of a beneficial effect of the combined treatment. Adequate information has been obtained on main outcome‐measurement variability for calculating sample size for a subsequent study to quantify the treatment effect precisely.
Detergent Decellularization of Heart Valves for Tissue Engineering: Toxicological Effects of Residual Detergents on Human Endothelial Cells
Authors: Cebotari Serghei , Tudorache Igor , Jaekel Thomas , Hilfiker Andres , Dorfman Suzanne , Ternes Waldemar , Haverich Axel , Lichtenberg Artur 
Published: March 2010

AbstractDetergents are powerful agents for tissue decellularization. Despite this, the high toxicity of detergent residua can be a major limitation. This study evaluated the efficacy of detergent removal from decellularized pulmonary valves (PVs) and the consequences of repopulation with human endothelial cells (HECs). Porcine PVs were treated with 1% sodium deoxycholate (SDC), group A; 1% sodium dodecyl sulfate (SDS), group B; and a mixture of 0.5% SDC/0.5% SDS, group C (n = 5 each). After each of 10 succeeding wash cycles (WCs), samples of the washing solution (WS) were analyzed by solid phase extraction and high performance liquid chromatography for the presence of detergents. Metabolic activity of HEC was also assessed in the WS samples (cytotoxicity and MTS assays). Decellularized and washed PVs were reseeded with HEC. Histological analysis demonstrated efficient tissue decellularization in all groups. Detergents' concentration in all WSs decreased exponentially and was below 50 mg/L after 6, 8, and 4 WCs in groups A, B, and C, respectively. This concentration resulted in no significant toxic influence on cell cultures, and scaffolds could be efficiently reseeded with HEC. In conclusion, intensive washing of detergent decellularized valvular scaffolds lowers the residual contamination below a hazardous threshold and allows their successful repopulation with HEC for tissue engineering purposes.
Shape Optimization of the Diffuser Blade of an Axial Blood Pump by Computational Fluid Dynamics
Authors: Zhu Lailai , Zhang Xiwen , Yao Zhaohui 
Published: March 2010

AbstractComputational fluid dynamics (CFD) has been a viable and effective way to predict hydraulic performance, flow field, and shear stress distribution within a blood pump. We developed an axial blood pump with CFD and carried out a CFD‐based shape optimization of the diffuser blade to enhance pressure output and diminish backflow in the impeller–diffuser connecting region at a fixed design point. Our optimization combined a computer‐aided design package, a mesh generator, and a CFD solver in an automation environment with process integration and optimization software. A genetic optimization algorithm was employed to find the pareto‐optimal designs from which we could make trade‐off decisions. Finally, a set of representative designs was analyzed and compared on the basis of the energy equation. The role of the inlet angle of the diffuser blade was analyzed, accompanied by its relationship with pressure output and backflow in the impeller–diffuser connecting region.
Obstruction of St. Jude Medical Valves in the Aortic Position: Plasma Transforming Growth Factor Type Beta 1 in Patients With Pannus Overgrowth
Authors: Teshima Hideki , Fukunaga Shuji , Takaseya Tohru , Tomoeda Hiroshi , Akashi Hidetoshi , Aoyagi Shigeaki 
Published: March 2010

AbstractThe study investigated the hypothesis that plasma transforming growth factor type beta 1 (TGF‐β1) initiated pannus overgrowth in cases with aortic prosthetic valve dysfunction (PVD). Patients with obstruction of an aortic St. Jude Medical valve in 26 cases (PVD group) and without obstruction in 48 cases (control group) were studied. Plasma TGF‐β1, the intensity of the prothrombin time–international normalized ratio (PT‐INR), and the interruption of an oral anticoagulant medicine were conducted. Plasma TGF‐β1 levels in the PVD group (87.7 ± 29.2 ng/mL) were significantly higher (P < 0.05) than in the control group (73.7 ± 25.2 ng/mL). The interruption of an oral anticoagulant medicine in 54% of the PVD group versus 12% of the control group was identified (P < 0.001). The mean value of the PT‐INR in the PVD group (1.75 ± 0.30) and control group (1.75 ± 0.30) was not significantly different (P = 0.82). In conclusion, elevated levels of plasma TGF‐β1 may play a role in pannus overgrowth.
Catheter‐related Infections via Temporary Vascular Access Catheters: A Randomized Prospective Study
Authors: Nakae Hajime , Igarashi Toshiko , Tajimi Kimitaka 
Published: March 2010

AbstractTemporary vascular access catheters (VACs) are important devices used in acute blood purification therapies. The aim of this study was to determine whether a catheterization duration of 2 weeks increased the risk of nosocomial complications when compared with a 1‐week duration. Fifty‐six patients with 90 double lumen VACs were randomly chosen, and received either 1‐ or 2‐week catheterizations from operators experienced in the placement of such catheters at three sites such as the internal jugular, subclavian, or femoral vein. The characteristics of the VACs, including the sites, procedures, and lengths, were similar in both groups. No significant difference in the rate of catheter colonization was observed between the groups (14.6% vs 26.2%, P = 0.1371). No significant difference in the rate of catheter‐related bloodstream infections was observed between the groups (2.1% vs 4.8%, P = 0.5967). Two‐week indwelling did not increase the risk of infection compared with 1‐week indwelling at any of the sites in critically ill patients.
Region‐specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin
Authors: Hassel Bjørnar , Taubøll Erik , Shaw Renee , Gjerstad Leif , Dingledine Ray 
Published: March 2010

SummaryPurpose:  It is commonly assumed that antiepileptic drugs (AEDs) act similarly in the various parts of the brain as long as their molecular targets are present. A few experimental studies on metabolic effects of vigabatrin, levetiracetam, valproate, and lamotrigine have shown that these drugs may act differently in different brain regions. We examined effects of chronic treatment with levetiracetam or phenytoin on mRNA levels to detect regional drug effects in a broad, nonbiased manner.Methods:  mRNA levels were monitored in three brain regions with oligonucleotide‐based microarrays.Results:  Levetiracetam (150 mg/kg for 90 days) changed the expression of 65 genes in pons/medulla oblongata, two in hippocampus, and one in frontal cortex. Phenytoin (75 mg/kg), in contrast, changed the expression of only three genes in pons/medulla oblongata, but 64 genes in hippocampus, and 327 genes in frontal cortex. Very little overlap between regions or drug treatments was observed with respect to effects on gene expression.Discussion:  We conclude that chronic treatment with levetiracetam or phenytoin causes region‐specific and highly differential effects on gene expression in the brain. Regional effects on gene expression could reflect regional differences in molecular targets of AEDs, and they could influence the clinical profiles of AEDs.
Assessment of the Relationship Between Age and the Effect of Risedronate Treatment in Women with Postmenopausal Osteoporosis: A Pooled Analysis of Four Studies
Authors: Boonen Steven , Klemes Andrea B. , Zhou Xiaojie , Lindsay Robert 
Published: March 2010

OBJECTIVES:To quantify the effect of age on the incidence of osteoporosis‐related fractures and of risedronate treatment on fracture risk in different age groups in women with postmenopausal osteoporosis.DESIGN:Data from four randomized, double‐blind, placebo‐controlled, Phase III studies were pooled and analyzed.PARTICIPANTS:The analysis population (N=3,229) consisted of postmenopausal women with osteoporosis as determined on the basis of prevalent vertebral fractures, low bone mineral density (BMD), or both.INTERVENTION:Patients had received risedronate 5 mg daily or placebo for 1 to 3 years.MEASUREMENTS:The endpoints of interest were the incidence of osteoporosis‐related fractures, clinical fractures, nonvertebral fractures, and morphometric vertebral fractures. The effect of age on fracture risk and treatment benefit was examined using Cox regression models with age and treatment as explanatory variables. The 3‐year fracture risk was estimated for patients in each treatment group at a given age.RESULTS:Irrespective of treatment, fracture risks were greater in older patients (P<.001). On average, for every 1‐year increase in age, a patient's risk for osteoporosis‐related fracture increased 3.6% (95% confidence interval=2.3–5.0%). Irrespective of age, risedronate treatment reduced fracture risk 42%. Risedronate‐treated patients had fracture risks similar to those of placebo‐treated patients 10 to 20 years younger.CONCLUSION:Patients treated with risedronate have a significantly lower fracture risk, similar to that of untreated patients 10 to 20 years younger.
Comparison of Contact Mechanics of Three Meniscal Repair Techniques and Partial Meniscectomy in Cadaveric Dog Stifles
Authors: Thieman Kelley M. , Pozzi Antonio , Ling Hang‐Yin , Lewis Dan 
Published: March 2010

Objective:To evaluate the biomechanical effect of horizontal, vertical, and cruciate suture repairs and partial meniscectomy on contact mechanics of dog stifles.Study Design:Ex vivo experimental study.Sample Population:Cadaveric canine stifles (n=24).Methods:Simulated bucket handle medial meniscal tears were created in cadaveric dog stifles. Tears were treated with 1 of 3 suture repair techniques or partial meniscectomy. Instantaneous contact area (CA), mean contact pressure (MCP), and peak contact pressure (PCP) measurements were recorded with a pressure sensing system. CA, MCP, and PCP for intact stifles (control), stifles with simulated tears, and stifles after treatment were recorded and compared using 1‐way repeated measures ANOVA.Results:Stifles with bucket handle tears had significantly decreased CA, increased MCP and increased PCP when compared with control. All meniscal repair techniques reestablished normal contact mechanics. When comparing meniscal repair and partial meniscectomy, stifles with partial meniscectomy had ∼35% lower CA, 57% higher MCP, and 55% higher PCP than stifles undergoing repair.Conclusions:Contact mechanics obtained from each repair technique were mechanically superior to partial meniscectomy. Performing meniscal repair instead of partial meniscectomy in dogs with select meniscal tears may mitigate the development of degenerative joint disease. Criteria for selection of candidates for meniscal repair should be confirmed with future studies.Clinical Relevance:Based on this ex‐vivo model, meniscal repair will restore normal contact mechanics. Consideration should be given to meniscal repair as treatment for peripheral meniscal tears located in the vascular zone if the meniscal parenchyma is normal.
In Defense of Counterfeiting Illegitimate Money
Authors: Block Walter E. 
Published: March 2010

AbstractCounterfeiting legitimate money is, and ought to be, a crime, not only under the libertarian law code but under the rules and regulations of all civilized orders. But what about counterfeiting money that is per se illegitimate; that is, is itself counterfeit? Is that a licit human action? The present article argues, somewhat paradoxically, that it is. It offers a counterpart to two authors—Murphy (2006) andMachaj (2007)—who take the opposite point of view.
Racial Fractionalization and School Performance
Authors: Hall Joshua C. , Leeson Peter T. 
Published: March 2010

AbstractThe literature on racial “peer effects” suggests that diversity improves at least some students' school performance. However, a literature in economic development posits that diversity may negatively affect school performance by undermining the efficient provision of education. This article empirically tests this claim, which we call the “public goods channel,” by examining the relationship between racial diversity and student performance in Ohio's school districts. We find that moving from a completely homogenous school district to one in which two racial groups have equal population shares is associated with a 7–17.5 percentage point decline in the passage rate on the state math exam, holding per pupil spending across districts constant. These results suggest that racial diversity is negatively associated with school performance but that the public goods channel is not responsible for this relationship.
Health Perception and Health Care Access: Sex Differences in Behaviors and Attitudes
Authors: Gil‐Lacruz Marta , Gil‐Lacruz Ana I. 
Published: March 2010

AbstractThis article analyzes the link between men's and women's perceptions of health and the demand for health goods and services. The study examines access to the health care system in a community characterized by social and economic variance. The data have been taken from a health survey carried out in a suburb of the city of Zaragoza in Spain. The sample (1,032 people over the age of 15) was selected according to specifications of sex, age, and place of residence. The sample shows a confidence interval of 95.5 percent with a ±3 margin of error. Descriptive and inferential statistical techniques are used. Sex differences are reflected in social conditions, lifestyles, health perception, and health care behaviors. The research describes how differences in health attitudes can be contextualized by the neighborhood. The results of this type of research are essential for the design of preventive strategies that are better adapted to need.
An Economic Approach to Capital Allocation
Authors: Zanjani George 
Published: March 2010

AbstractThis article starts with primitive assumptions on preferences and risk. It then derives prices consistent with a social optimum within an insurance company and the consumer‐level capital allocation implied therein. The allocation “adds up” to the total capital of the firm (a result echoing findings in the congestion pricing literature—where optimal tolls exactly cover the rental cost of the highway). The allocation follows each consumer's share of recoveries in states of insurer default, weighted by the severity of the default in terms of welfare impact. However, the article argues that an economic approach technically restricts only the capital allocated to marginal units of coverage: inframarginal units could in principle receive different allocations.
Permutation Tests for Stochastic Ordering and ANOVA: Theory and Applications with R by BASSO, D., PESARIN, F., SALMASO, L., and SOLARI, A.
Authors: Berger Vance W. 
Published: March 2010

Permutation Tests for Stochastic Ordering and ANOVA: Theory and Applications with R(D. Basso, F. Pesarin, L. Salmaso, and A. Solari)Vance W. Berger

A Comprehensive Guide to Factorial Two‐Level Experimentation(R. W. Mee)Steven G. Gilmour

Data and Safety Monitoring Committees in Clinical Trials(J. Herson)Roger F. Liddle

Marginal Models for Dependent, Clustered, and Longitudinal Categorical Data(W. Bergsma, M. Croon, and J. A. Hagenaars)Ivy Liu

Applying Quantitative Bias Analysis to Epidemiologic Data(T. L. Lash, M. P. Fox, and A. K. Fink)Lawrence McCandless

The Phylogenetic Handbook: A Practical Approach to Phylogenetic Analysis and Hypothesis Testing, 2nd edition(P. Lemey, M. Salemi, and A.‐M. Vandamme, Editors)Mike Steel