bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of mechanical compression on the vascular permeability of the dorsal root ganglion
Authors: Kobayashi Shigeru , Yoshizawa Hidezo 
Published: October 2002

AbstractThe dorsal root ganglion contains primary sensory neurons and is closely related to low back pain and sciatia. The present study investigated whether endoneurial edema, which is involved in the onset of pain and nerve dysfunction, was increased in the dorsal root ganglion by compression. The influence of mechanical compression on the vascular permeability of the lumbar dorsal root ganglion was determined. The dorsal root ganglion is reported to have a higher vascular permeability compared with other nerve tissues as well as lacking a blood‐nerve barrier. However, only a few studies have assessed the influence of mechanical compression on the dorsal root ganglion, especially its vascular permeability.In dogs, laminectomy was performed at L7 and the dorsal root ganglion of the seventh lumbar spinal nerve was compressed for 1 h using four kinds of clips with various strengths. After clip removal, Evans blue albumin (EBA) or horseradish peroxidase (HRP) was administered intravenously as a tracer. After sacrifice, the EBA‐injected specimens were observed by fluorescence microscopy and the HRP‐injected specimens were observed by light and transmission electron microscopy.After compression of the dorsal root ganglion at 15 gf or more, leakage of tracer into the endoneurial space was markedly increased compared with the sham‐operated group and severe edema was noted. Extravascular leakage of tracer was obvious around venules and capillaries. Electron microscopy showed an increase of extravascular HRP in the gap junctions and fenestrae between endothelial cells due to increased vascular permeability. However, the dorsal root ganglion was covered with a thick perineurium and HRP that leaked from the blood vessels did not enter the epineurium even after compression at 60 gf. It was proven that the increased vascular permeability occurred as well as in leakage of dye within the dorsal root ganglion after a single hour of compression of the dorsal root ganglion. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The role of adsorbed endotoxin in particle‐induced stimulation of cytokine release
Authors: Cho David R. , Shanbhag Arun S. , Hong Chi‐Yuan , Baran George R. , Goldring Steven R. 
Published: October 2002

AbstractNumerous in vitro models have demonstraed the capacity of wear particles to stimulate the release of soluble pro‐inflammatory products with the ability to induce local bone resorption. Recent observations have demonstrated that binding of lipopolysaccharide (LPS) to particulate wear deris can significantly modulate the pattern of cell response in the in vitro models. These findings raise concerns over the possible role of LPS in the athogenesis of aseptic looseing after total joint replacements, and also indicates the importance of controlling for possible confounding effects of LPS contamination in the in vitro models used to study the reactive nature of wear debris. Our studies were undertaken to rigorously analyze the effects of particle‐associated LPS on cell responses and to assess the efficacy ofdifferent treatment protocols to inactivate LPS associated with different particulate materials. Particles of cobalt‐chrome alloy, titanium‐6‐aluminum‐4‐vanadium, titanium nitride and silica were pretreated with LPS and exposed to multiple treatment protocols. When cells were treated with „as‐received”︁ particles prepared by washing in ethanol, small amounts of TNF‐α, IL‐1β, and IL‐1α were detected. In contrast, all particle species pretreated with LPS produced marked increases in TNF‐α, IL‐1α, and IL‐1β release, as well as upregulation of corresponding mRNa levels even after ethanol washing. Boiling the LPS‐pretreated particles in 1% acetic acid or autoclaving and baking the particles also markedly reduced and in some instances abolished the effect of the LPS‐pretreatment. This indicates that LPS binds to the surface of particles of diverse composition and that the bound LPS is biologically active. Treatment protocols to inactivate particle‐associated LPS demonstrated significant differences in effcacy. When the most rigorous treatments were utilized, essentially all LPS activity could be eliminated. Particles treated with these methods retained some capacity to stimulated cytokine release, but activities were markedly reduced. These results provide further evidnce indicating that LPS contamination of particulate materials can markedly enhance their biological activity. This potential confounding effect needs to be carefully monitored and controlled in the in vitro model systems systems used to evaluate wear particles. Furthermore, the presence of particle‐associated endotoxin at the bone‐implant interface in vivo could markedly enhance the adverse biological activity of particulate wear debris. © 2002 Published by Elsevier Science Ltd. On behalf of Orthopaedic Research Society.
The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles
Authors: Soloviev Alexander , Schwarz Edward M. , Kuprash Dmitry V. , Nedospasov Sergei A. , Edward Puzas J. , Rosier Randy N. , O'Keefe Regis J. 
Published: October 2002

AbstractMacrophage activation by particulate debris from orthopaedic implants triggers an inflammatory response that ultimately leads to periprosthetic bone resorption and implant failure. TNFα‐has been identified as a critical cytokine involved in the response to debris particles but the mechanisms involved in activation of TNFα synthesis are unclear. The current study demonstrates rapid induction of TNFα following stimulation with titanium particles in the murine macrophage cell line, ANA‐1. Electrophoretic mobility shift assays demonstrated NFκB DNA binding activity within 15 min of exposure to titanium particles, and experiments with an NFκB luciferase promoter confirmed the induction of NFκkB mediated transcription by titanium particles. Furthermore, titanium particles induced a 2‐fold induction in TNFα promoter activity, and mutation of the kB2a site, one of the four NFκkB‐binding sites in the TNFα promoter, resulted in decreased activation. Since NFκkB is a critical regulator of inflammation and is involved in activation of the TNFα promoter, additional experiments were performed to determine the mechanism of NFκkB activation by particles. NFκkB activation was found to be dependent upon proteasome activity, since administration of MG 132, a proteasome inhibitor, blocked NFκkB activation. However, IkBα is only slightly decreased following Ti treatment, in contrast to marked degradation following stimulation with LPS. Recently, another proteasome‐dependent pathway of NFκkB activation has been described involving degradation of p105, a precursor of p50 that binds to p65. p105 degradation occurred following titanium stimulation, suggesting that this recently described mechanism for NFκkB activation is operant in ANA‐1 cells following exposure to titanium particles. These findings demonstrate that activation of the NFκkB signaling pathway is rapidly induced by titanium particles in ANA‐1 cells and is associated with p105 degradation. TNFα induction appears to be mediated, at least in part, through NFκkB binding to the kB2a site of the TNFα promoter. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Cerebral GABA release and GAD activity in protein‐ and tryptophan‐restricted rats during development
Authors: Del Angel‐Meza A.R. , Ramı́rez‐Cortes L. , Adame‐González I.G. , González Burgos I. , Beas‐Zárate C. 
Published: October 2002

AbstractTo evaluate the effects on the GABAergic system, Wistar rats were raised on a chronically protein‐ and tryptophan‐restricted diet with 8% protein, based on either Purina chow or corn. There was a significant decrease in both body and cerebral weight in the restricted animals compared with the control group fed with a 23% protein diet. In animals fed mainly corn, glutamic acid decarboxylase (GAD) activity increased significantly at the ages studied (14, 30, and 60 days) in the cerebral cortex and hippocampus. In the same way, γ‐aminobutyric acid (GABA) release decreased significantly in early life in both brain regions, then increased in 30–60‐day‐old animals corn‐fed predominantly in the cerebral cortex.The reduction in GABA release may be attributable to a decrease in GABAergic cell density, which could induce an over‐activation of 5‐hydroxytryptamine (5‐HTergic) receptors, leading in turn to the observed enhancement of GAD activity. Taken together, these results may represent a plastic response by GABAergic neurons to (5‐HTergic under‐stimulation in mainly corn‐fed animals.
Neurohormonal activation in heart failure after acute myocardial infarction treated with beta‐receptor antagonists
Authors: Persson Hans , Andréasson Karin , Kahan Thomas , Eriksson Sven V. , Tidgren Bo , Hjemdahl Paul , Hall Christian , Erhardt Leif 
Published: October 2002

AbstractBackground:Few studies have described how neurohormonal activation is influenced by treatment with beta‐receptor antagonists in patients with heart failure after acute myocardial infarction. The aims were to describe neurohormonal activity in relation to other variables and to investigate treatment effects of a beta1 receptor‐antagonist compared to a partial beta1 receptor‐agonist.Methods:Double‐blind, randomized comparison of metoprolol 50–100 mg b.i.d. (n‐74), and xamoterol 100–200 mg b.i.d (n‐67). Catecholamines, neuropeptide Y‐like immunoreactivity (NPY‐LI), renin activity, and N‐terminal pro‐atrial natriuretic factor (N‐ANF) were measured in venous plasma before discharge and after 3 months. Clinical and echocardiographic variables were assessed.Results:N‐ANF showed the closest correlations to clinical and echocardiographic measures of heart failure severity, e.g. NYHA functional class, furosemide dose, exercise tolerance, systolic and diastolic function. Plasma norepinephrine, dopamine and renin activity decreased after 3 months on both treatments, in contrast to a small increase in NPY‐LI which was greater (by 3.9 pmol/l, 95% CI 1.2–6.6) in the metoprolol group. N‐ANF increased on metoprolol, and decreased on xamoterol (difference: 408 pmol/l, 95% CI 209–607). Increase above median of NPY‐LI (>25.2 pmol/l, odds ratio 2.8, P‐0.0050) and N‐ANF (>1043 pmol/l, odds ratio 2.8, P‐0.0055) were related to long term (mean follow‐up 6.8 years) cardiovascular mortality.Conclusions:Decreased neurohormonal activity, reflecting both the sympathetic nervous system and the renin–angiotensin system, was found 3 months after an acute myocardial infarction with heart failure treated with beta‐receptor antagonists. The small increase in NPY‐LI may suggest increased sympathetic activity or reduced clearance from plasma. The observed changes of N‐ANF may be explained by changes in cardiac preload, renal function, and differences in beta‐receptor mediated inhibition of atrial release of N‐ANF. NPY‐LI, and N‐ANF at discharge were related to long term cardiovascular mortality.
Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1‐year period
Authors: Gradaus Rainer , Kerber Sebastian , Böcker Dirk , Scheld Hans H. , Breithardt Günter , Deng Mario C. 
Published: October 2002

AbstractBackground:the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited.Aims:it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1‐year follow‐up.Methods and Results:in all patients who were referred for cardiac transplant evaluation within a 12‐month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ‐preserving intervention or surgery, either PTCA (n ‐ 11), CABG (n ‐ 4), valve repair (n ‐ 7), multisite pacing (n ‐ 7), or partial ventricular resection (n ‐ 5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n ‐ 17) or received a ventricular assist device (n ‐ 3).Conclusions:within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.
Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure
Authors: Brendorp Bente , Elming Hanne , Jun Li , Køber Lars , Torp‐Pedersen Christian ,   for the DIAMOND Study Group
Published: October 2002

AbstractAims:Drug‐induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation.Methods and results:In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortality On Dofetilide‐CHF (DIAMOND‐CHF) study, both pre‐treatment and on‐treatment day 2–6 QT dispersion was available from standard 12‐lead ECGs. Patients were randomised in a double‐blind manner to receive either placebo or dofetilide, a new class III antiarrhythmic drug. During a median follow‐up of 19 months (minimum 1 year), 179 patients (39%) died (135 patients from cardiac causes). Changes in QT dispersion did not predict all‐cause or cardiac mortality for patients treated with dofetilide in multivariate survival analysis (Risk ratio: 1.02, 95% confidence interval: 0.97–1.08, P>0.4). This finding was independent of pre‐treatment QT dispersion. Dofetilide caused a small QT dispersion increment of 8 ms, not different from the changes seen in the placebo group (3 ms).Conclusion:For patients with CHF and reduced left ventricular systolic function, changes in QT dispersion following treatment with dofetilide do not predict all‐cause or cardiac mortality. The dofetilide‐induced QT dispersion changes are small and comparable to those seen in placebo treated patients.
Detecting early clinical deterioration in chronic heart failure patients post‐acute hospitalisation—a critical component of multidisciplinary, home‐based intervention?
Authors: Stewart Simon , Horowitz John D. 
Published: October 2002

AbstractAims:To firstly describe the prevalence, characteristics and consequences of early clinical deterioration (ECD) in chronic heart failure (CHF) patients discharged from acute hospital care and, secondly, to examine the potential benefits of a multidisciplinary, home‐based intervention (HBI) in limiting the common sequelae of such deterioration.Methods:This phenomenon was studied in 90 CHF patients assigned to the intervention arm of a randomised study of HBI. ECD was defined as death, unplanned re‐admission or clinical instability (detected at a home visit) within 14 days of hospital discharge. Multivariate analysis was used to determine the independent correlates of ECD. Using these data, a 1:1 case–control ratio of patients assigned to the usual care arm of the study was selected to match those patients exhibiting non‐fatal ECD and subject to HBI. Subsequent morbidity and mortality rates were then compared on the basis of the presence or absence of non‐fatal ECD and/or HBI.Results:Of the 90 patients assigned to HBI, two died suddenly, five required an unplanned re‐admission to hospital and 28 were found to be clinically unstable at a planned home visit, within 14 days of discharge from the index admission. The combined prevalence of ECD this cohort was therefore 39% (35 of 90 patients) and was independently correlated with greater age (OR‐1.1 per yearly increment; P<0.001) and comorbidity (OR‐2.0 per incremental Charlson index of comorbidity score; P<0.001). Patients who exhibited clinical instability at the home visit were significantly more likely to be non‐adherent to prescribed treatment (10 of 28 vs. 9 of 55; P<0.05). Compared to the remainder of the cohort also subject to HBI, despite remedial intervention, patients who exhibited non‐fatal ECD had reduced event‐free survival (11 of 33 vs. 38 of 55; P<0.001), more frequent unplanned re‐admission (0.2 vs. 0.1 admissions/patient/month; P<0.01), and more prolonged hospital stay (1.6 vs. 0.5 days/patient/month; P<0.001) in the subsequent 6‐month period. However, compared to case–controls, these patients (n‐33 in both groups) had fewer days of hospitalisation (1.6 vs. 3.6 days/patient/month; P‐0.05) and, most significantly, were more likely to survive to 6 months (6 vs. 13 died; P<0.05).Conclusion:ECD is a common phenomenon in older CHF patients discharged from acute hospital care and is associated with poorer health outcomes in the longer‐term. Post‐discharge HBI is an important means for identifying and addressing ECD. Although HBI conveys benefits incremental to usual care, these data also provide a sound basis for increasing its effectiveness by applying earlier home visits in selected ‘high‐risk’ patients.
The incomplete Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT)
Authors: Torp‐Pedersen Christian , Køber Lars , Ball Stephen , Hall Alistair , Brendorp Bente , Ottesen Michael Mundt , Berning Jens , Jensen Gorm , Hampton John , Zilles Peter , Eberle Siegfried , Carlsen Jan 
Published: October 2002

AbstractThe aim of this study was to evaluate the efficacy of adding the beta‐blocker bucindolol to standard therapy shortly after a myocardial infarction in a high‐risk population with reduced left ventricular function.MethodsThe study was planned to include 2000 patients with an enzyme confirmed myocardial infarction and severely reduced left ventricular function determined by echocardiography (corresponding to ejection fraction ≤0.35). The primary endpoint was all cause mortality and the secondary endpoints were time to first event of death, progression of heart failure or reinfarction—and the components. The study was closed early due to discontinuation of development of bucindolol by the manufacturer. Therefore, 170 patients were randomised to receive bucindolol and 173 to receive placebo.ResultsThere were 27 deaths in the bucindolol group and 30 in the placebo group, hazard ratio of bucindolol 0.88 (95% confidence limits 0.5–1.5; P‐0.6). There were 9/4 (bucindolol/placebo, P‐0.16) heart failure events and 5/17 (P‐0.01) reinfarctions in the bucindolol/placebo groups.ConclusionDue to early closure it is unknown whether bucindolol changes mortality in high‐risk post myocardial infarct patients when added to best medical therapy. The frequency of reinfarction was significantly reduced.
Selective transport and accumulation of alkanes by Rhodococcus erythropolis S+14He
Authors: Kim In Seon , Foght Julia M. , Gray Murray R. 
Published: October 2002

AbstractSelective transport and accumulation of n‐alkanes by Rhodococcus erythropolis S+14He was studied by growing cells on n‐hexadecane, n‐octadecane or the branched alkane pristane, and on mixtures of hydrocarbons. Ultrastructural analysis by transmission electron microscopy (TEM) revealed hydrocarbon inclusion bodies present in cells grown on the three alkanes, but not in cells grown on soluble media or exposed to nonmetabolized 2,2,4,4,6,8,8‐heptamethylnonane (HMN). n‐Hexadecane had the highest rates of accumulation within the cells and higher overall consumption rates relative to the other alkanes. These rates decreased when the molar concentration of n‐hexadecane was decreased in hydrocarbon mixtures, but at the same time the accumulation of n‐hexadecane in intracellular inclusions became increasingly selective. Sodium azide significantly inhibited the accumulation of n‐hexadecane, consistent with an active transport mechanism for accumulation. These results indicate that R. erythropolis S+14He is able to selectively discriminate and preferentially transport n‐hexadecane from mixtures of structurally similar alkanes into intracellular inclusions by an energy‐driven transport system. This selective membrane transport of hydrocarbon isomers has potential application for separations, bioprocessing, and the development of novel biosensors. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 650–659, 2002.
HPLC determination of phenylpropanolamine in pharmaceutical OTC preparations
Authors: Nakashima Kenichiro , Kanehara Saori , Kaddoumi Amal 
Published: October 2002

AbstractA convenient HPLC method to determine phenylpropanolamine (PPA) in addition to phenylephrine (PE) and chlorpheniramine (CPA) in commercially available over‐the‐counter (OTC) preparations has been developed. Sample solutions were prepared by dilution with water or methanol followed by filtration and direct injection into the HPLC system. The mobile phase was a mixture of methanol–acetonitrile–acetic acid (0.1 M)–triethylamine (20:20:60:0.6, v/v/v/v) containing sodium heptanesulfonate (0.5 mM) as an ion pair. The separation was achieved on a reversed‐phase ODS column with detection wavelength set at 254 nm. The compounds showed good linearity in the range 2.5–1000 µM with detection limits ranged from 0.13 to 0.48 µM. PE, caffeine and CPA were well separated when present together with PPA. The method was applied to the determination of PPA in pharmaceutical preparations including hard and soft capsules. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of inhaled clenbuterol in horse urine by GC/MS2
Authors: Van Eenoo P. , Delbeke F. T. , Deprez P. 
Published: October 2002

AbstractClenbuterol, a β‐adrenergic agonist, is used in the treatment of recurrent airway obstruction in horses. It is prohibited by horse racing authorities, because of its stimulating and growth‐promoting properties. However, information on detection times of clenbuterol after administration by nebulization is lacking. In this study, a fast, sensitive quantitative GC‐MS2method for the detection of clenbuterol in urine was developed. Alkaline liquid–liquid extraction was followed by derivatization to a cyclic methyl boronate derivative and analysis on a Finnigan MAT GCQ instrument. Method validation showed good linearity in the range 0.1–2.0 ng/mL, excellent repeatability and specificity. The limit of quantitative detection of the method was 0.1 ng/ml. Different instrumental parameters of the ion trap mass spectrometer were changed to increase the number of diagnostic ions for the cyclic methyl boronate derivative of clenbuterol. The influence of these changes and their applicability within the requirements and the criteria for mass spectrometry set by the responsible regulatory bodies are discussed. Clenbuterol was administered via nebulization to five standardbred mares (0.4 µg/kg body weight). Analysis of the urine samples resulted in the detection of clenbuterol, as early as 2 h post administration and for up to 36 h post treatment. Generally, maximum urinary concentrations of 1.2 ng/mL were reached after ­6–9 h. Copyright © 2002 John Wiley & Sons, Ltd.