bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative human study of ibuprofen enantiomer plasma concentrations produced by two commercially available ibuprofen tablets
Authors: Cox S. R. , Brown M. A. , Squires D. J. , Knuth D. W. , Murrill E. A. , Lednicer D. 
Published: October 2006

AbstractTwelve healthy male subjects participated in a two‐way Latin square crossover study in which the treatments were a single 400 mg generic ibuprofen tablet (Tablet A) or a single 400 mg MOTRIN® Tablet (Tablet B). Blood samples were drawn at various times through 12 h after dosing and plasma samples were assayed for ibuprofen enantiomers with a stereospecific capillary gas chromatographic procedure. Concentration‐time data for both enantiomers were in agreement and indicated that drug was absorbed much more quickly from Tablet B than from the Tablet A; enantiomer Tmax values were less than 1.3 h from Tablet B but longer than 4 h from the Tablet A (p<0.001). Also, maximum enantiomer plasma concentrations from the Tablet B were about 50 per cent of the peak concentrations observed from Tablet A (p<0.001). The total extent of drug absorption appeared to be the same in both products. These data clearly indicate that the two tablets are not bioequivalent with respect to either ibuprofen enantiomer.
Pharmacokinetics of nitroglycerin and metabolites in humans following oral dosing
Authors: K. Yu Dale , Giesing Dennis H. , Williams Roger L. , Benet Leslie Z. , Lin Emil T. 
Published: October 2006

AbstractSingle dose oral nitroglycerin (GTN) was administered to six healthy subjects as 6.5, 9.0, and 13.0 mg aqueous solutions in sequential study phases to characterize the oral pharmacokinetics of GTN and the dinitrate metabolites. Blood samples were collected periodically up to 10 h. Plasma concentrations of GTN were measurable in some subjects up to 1/2 and 1 h, respectively, after the 9.0 and 13.0 mg dose. The mean GTN Cmax values of the three solution doses were 0.28, 0.78, and 0.42 ng ml−1 in ascending dosage. The erratic nature of GTN plasma profiles prevented meaningful pharmacokinetic analysis, although tmax was consistently 5 min. In all three treatments, both GTN metabolites (1,2‐and 1,3‐glyceryldinitrates, GDNs) peaked at about 20 min, followed by a distributive phase and a log‐linear decline in concentrations. Terminal half‐lives for both GDNs were approximately 50 min in all three doses. The plasma concentrations of the metabolites were higher than nitroglycerin with 1,2‐GDN exhibiting the highest overall profile.
Standardization of pelvic lymphadenectomy performed at radical cystectomy
Authors: Koppie Theresa M. , Vickers Andrew J. , Vora Kinjal , Dalbagni Guido , Bochner Bernard H. 
Published: October 2006

AbstractBACKGROUND.The number of lymph nodes (LNs) removed during radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder affects overall and disease‐specific survival, but no consensus exists regarding the minimum number of LNs that should be removed. The goal of the current study was to determine if a threshold number of nodes exists, above which taking additional LNs has no clinical benefit.METHODS.A total of 1121 patients were identified who underwent RC for clinically localized TCC of the bladder between January 1990 and April 2004. To determine the relation of LNs removal and overall survival, a Cox proportional hazards model was used with pathologic stage, age, and comorbidity as covariates. A dose‐response curve, adjusted for covariates, was modeled to assess the impact of an increasing number of LNs removed on overall survival.RESULTS.A median of 9 LNs were removed (range, 0–53 LNs). In multivariable analysis, all covariates (number of LNs removed, age, stage of disease, and comorbidity) were found to be predictive of survival. The dose‐response curve for number of LNs versus survival revealed that, when adjusted for covariates, the probability of survival did not plateau but instead continued to rise as the number of LNs removed increased.CONCLUSIONS.No evidence was found that a minimum number of LNs is sufficient for optimizing bladder cancer outcomes when a limited or extended pelvic LN dissection is performed during RC. Instead, the probability of survival continues to rise as the number of LNs removed increases. This study supports a more extended LN dissection at the time of RC, and highlights the challenges of interpreting retrospective LN dissection data. Cancer 2006. © 2006 American Cancer Society.
Survival of men with clinically localized prostate cancer treated with prostatectomy, brachytherapy, or no definitive treatment
Authors: Tward Jonathan D. , Lee Christopher M. , Pappas Lisa M. , Szabo Aniko , Gaffney David K. , Shrieve Dennis C. 
Published: October 2006

AbstractBACKGROUND.The optimal treatment for men with early stage prostate cancer remains undefined. Survival of such patients after surgery, brachytherapy, or no definitive therapy was investigated specifically to determine the impact of age at diagnosis.METHODS.In all, 60,290 men diagnosed with organ‐confined, low and moderate grade prostate cancer between 1988 and 2002 were retrospectively identified from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Prostate cancer‐specific mortality (PCSM) and any‐cause mortality (ACM) were determined. Outcomes for patients treated by brachytherapy, surgery, or receiving no definitive treatment were compared using the Wilcoxon test, stratified by T‐stage and grade, and using multivariate analysis.RESULTS.The median follow‐up time was 46 months (range, 0–189 months). For men under age 60 at diagnosis, PCSM at 10 years was 1.3%, 0.5%, and 3.7% for surgery, brachytherapy, and no definitive therapy, respectively. For men age 60 and older the PCSM was 3.8%, 5.3%, and 8.4%, respectively. On univariate and multivariate analysis, surgery and brachytherapy resulted in statistically equivalent PCSM and ACM, and both had a significantly lower PCSM and ACM versus no definitive therapy.CONCLUSIONS.A better survival was observed in men treated with a definitive therapy. The magnitude of the benefit on PCSM or ACM was similar for both definitive therapies irrespective of age. Cancer 2006. © 2006 American Cancer Society.
Mice expressing high levels of soluble CD14 retain LPS in the circulation and are resistant to LPS‐induced lethality
Authors: Jacque Berri , Stephan Kristin , Smirnova Irina , Kim Bobae , Gilling Damian , Poltorak Alexander 
Published: October 2006

AbstractDespite significant progress in understanding the origin of soluble CD14 (sCD14), its physiological function remains largely unknown. Recent research has produced contradictory observations suggesting that sCD14 may have either beneficial or detrimental properties in protection against LPS‐induced endotoxin shock. To resolve this controversy and to establish a mouse model suitable for elucidation of the functions of human CD14 (hCD14) in vivo, we generated several lines of transgenic mice bearing different copy numbers of the hCd14 transgene on a murine Cd14–/– background. The hCD14 was entirely capable of complementing loss of mouse CD14 to mediate cellular responses to LPS. Serum levels of sCD14 in a founder with multiple copies of the transgene were several times higher than in transgenic animals with a single copy of Cd14. Furthermore, mice with high levels of hCD14 were hypo‐responsive to LPS and survived a lethal dose of LPS. Further inquiry into the mechanism of the hypo‐response to LPS revealed that protection is associated with the higher amounts of circulating LPS. Most of this circulating LPS can be immunoprecipitated with anti‐CD14 antibodies. These results suggest that sCD14 blocks circulating LPS by limiting the amount of monocyte‐bound LPS and thus reduces inflammatory responses.
A critical role for ICOS co‐stimulation in immune containment of pulmonary influenza virus infection
Authors: Humphreys Ian R. , Edwards Lorna , Snelgrove Robert J. , Rae Aaron J. , Coyle Anthony J. , Hussell Tracy 
Published: October 2006

AbstractLung pathology observed during influenza infection is due to direct damage resulting from viral replication and bystander damage caused by overly exuberant antiviral immune mechanisms. In the absence of universally effective vaccines and antiviral therapies, knowledge of the cellular components required for immune containment of influenza is essential. ICOS is a late co‐stimulatory molecule expressed by T cells 12–24 h after activation. We show for the first time that inhibition of ICOS with a monoclonal antibody reduces pulmonary T cell inflammation and associated cytokine expression. Surprisingly however, this reduction in T cells was not accompanied by an alleviation of weight loss and illness. Furthermore, lung viral titres were elevated following anti‐ICOS treatment, suggesting that the beneficial outcome of reducing T cell pathology was masked by enhanced virus‐induced damage and innate inflammation. This study demonstrates the delicate balance that exists between pathogen burden and pulmonary T cell inflammation during influenza infection and highlights the critical role of ICOS in this response.
Neutralization of IL‐17 by active vaccination inhibits IL‐23‐dependent autoimmune myocarditis
Authors: Sonderegger Ivo , Röhn Till A. , Kurrer Michael O. , Iezzi Giandomenica , Zou Yu , Kastelein Robert A. , Bachmann Martin F. , Kopf Manfred 
Published: October 2006

AbstractThe most common reason for heart failure in young adults is dilated cardiomyopathy often resulting from myocarditis. Clinical studies and animal models provide evidence that an autoimmune response against heart myosin is the underlying reason for the disease. IL‐12 has been suggested to play a key role in development of experimental autoimmune myocarditis (EAM), as IL‐12p40 and IL‐12Rβ1 knockouts are protected from disease. In this study, we have compared IL‐12p40–/– mice, IL‐12p35–/– mice and mice treated with a neutralizing IL‐23 antibody in EAM and found that in fact IL‐23, not IL‐12, is responsible for inflammatory heart disease. However, these cytokines appear to have redundant activity for priming and expansion of autoreactive CD4 T cells, as specific T cell proliferation was only defective in the absence of both cytokines. IL‐23 has been suggested to promote a pathogenic IL‐17‐producing T cell population. We targeted IL‐17 by capitalizing on an active vaccination approach that effectively breaks B cell tolerance. Neutralization of IL‐17 reduced myocarditis and heart autoantibody responses, suggesting that IL‐17 is the critical effector cytokine responsible for EAM. Thus, targeting of IL‐23 and IL‐17 by passive and active vaccination strategies holds promise as a therapeutic approach to treat patients at risk for development of dilated cardiomyopathy.See accompanying commentary: http://dx.doi.org/10.1002/eji.200636760
Synthesis of Methyl Metallocenecarboxylates [{η4‐Ph4–n(SiMe3)nC4}Co{η5‐MeOC(O)C5H4}] (n = 1, 2) and Their Desilylation Reactions: Structural Studies and Conversion to Metallocenecarboxylic Acids and Their Alcohol Derivatives
Authors: Gupta Hanuman P. , Kumar M. Senthil , Upreti Shailesh , Elias Anil J. 
Published: October 2006

AbstractThe reaction of (2‐phenylethynyl)trimethylsilane (Me3SiC≡CPh) with [{η5‐MeOC(O)C5H4}Co(PPh3)2] generated in situ results in the exclusive formation of two isomers of methyl metallocenecarboxylates, namely [{trans‐η4‐Ph2(Me3Si)2C4}Co{η5‐MeOC(O)C5H4}] (1) and [{cis‐η4‐Ph2(Me3Si)2C4}Co{η5‐MeOC(O)C5H4}] (2). The reaction of [{η5‐MeOC(O)C5H4}Co(PPh3)(Me3SiC≡CPh)] with PhC≡CPh yields the methyl metallocenecarboxylate [{η4‐Ph3(Me3Si)C4}Co{η5‐MeOC(O)C5H4}] (3) along with [{η4‐Ph4C4}Co{η5‐MeOC(O)C5H4}] (4). The reactions of 1, 2 and 3 with Bu4NF in dmso results in the desilylated complexes [(trans‐η4‐Ph2H2C4)Co{η5‐MeOC(O)C5H4}] (5), [(cis‐η4‐Ph2H2C4)Co{η5‐MeOC(O)C5H4}] (6) and [(η4‐Ph3HC4)Co{η5‐MeOC(O)C5H4}] (7), respectively. Compounds 5, 6 and 7 yield the carboxylic acids [(trans‐η4‐Ph2H2C4)Co{η5‐HOC(O)C5H4}] (8), [(cis‐η4‐Ph2H2C4)Co{η5‐HOC(O)C5H4}] (9) and [(η4‐Ph3HC4)Co{η5‐HOC(O)C5H4}] (10) upon treatment with KOtBu in dmso. Reduction of 5 and 7 with LiAlH4 in thf gives the alcohol complexes [(trans‐η4‐Ph2H2C4)Co(η5‐HOCH2C5H4)] (11) and [(η4‐Ph3HC4)Co(η5‐HOCH2C5H4)] (12) in good yields. Compounds 1–7 and 11 were characterized structurally. These structural studies show interesting variations in the orientations of the cyclobutadiene‐bound phenyl groups when the silyl groups are systematically removed from the cyclobutadiene moiety. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Material Aspects of the Design and Operation of Direct Borohydride Fuel Cells
Authors: Cheng H. , Scott K. , Lovell K. 
Published: October 2006

AbstractThe direct borohydride fuel cell (DBFC) has attracted increasing interest as a potential high power source for mobile and portable applications. Engineering design plays an important role in the development of the DBFC. This paper reports data for the selection of anode, cathode, and membrane materials for the DBFC. The best DBFC performance is achieved with a Au anode, a Pt cathode, and a 3541P ion exchange membrane. The use of non‐precious catalysts, e.g., Ag, leads to promising results.
A Dynamic Simulation Tool for the Battery‐Hybrid Hydrogen Fuel Cell Vehicle
Authors: Moore R. M. , Ramaswamy S. , Cunningham J. M. , Hauer K. H. 
Published: October 2006

AbstractThis paper describes a dynamic fuel cell vehicle simulation tool for the battery‐hybrid direct‐hydrogen fuel cell vehicle. The emphasis is on simulation of the hybridized hydrogen fuel cell system within an existing fuel cell vehicle simulation tool. The discussion is focused on the simulation of the sub‐systems that are unique to the hybridized direct‐hydrogen vehicle, and builds on a previous paper that described a simulation tool for the load‐following direct‐hydrogen vehicle. The configuration of the general fuel cell vehicle simulation tool has been previously presented in detail, and is only briefly reviewed in the introduction to this paper. Strictly speaking, the results provided in this paper only serve as an example that is valid for the specific fuel cell vehicle design configuration analyzed. Different design choices may lead to different results, depending strongly on the parameters used and choices taken during the detailed design process required for this highly non‐linear and n‐dimensional system. The primary purpose of this paper is not to provide a dynamic simulation tool that is the “final word” for the “optimal” hybrid fuel cell vehicle design. The primary purpose is to provide an explanation of a simulation method for analyzing the energetic aspects of a hybrid fuel cell vehicle.
Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: Six month's experience
Authors: Barnhart Marion I. , Chen Shan‐Te , Salley Steven O. , Puro Henry 
Published: October 2006

AbstractThe impact of chronic inhalation of diesel exhaust (DE) on alveolar lung was studied in 24 Hartley guinea pigs. Groups were sacrificed sequentially at 2 weeks, 3 months and 6 months of exposure to either 750 μg or 1500 μg DE particles (DEP) per m3 along with age‐matched concurrent controls. Although qualitative ultrastructural changes were noticed during this time interval and dosage schedule, there was no evidence of pathologic changes such as fibrosis or emphysema. The cellular uptake of DEP was striking. By 2 weeks three alveolar cell types (alveolar macrophages, epithelial type 1 cells and interstitial macrophages) plus one type of granulocytic leukocyte (eosinophils) confined DEP within phagosomes without evidence of cytotoxicity. A certain phagosomal DEP population had a bull's eye appearance and diameters of 0.0727 ± 0.01 μm. Morphometric analysis applied to electron micrographs demonstrated that arithmetic mean tissue thickness of the air–blood barrier was generally increased (p < 0.05) during DE exposure. For the 750 μg DE sets, the increase over control (1.56 μm) was 41% at 2 weeks, 46% at 3 months and 77% at 6 months while the 1500 μg DE set at 6 months exceeded control by 130%. Increases in absolute tissue volumes of interstitium and epithelial type 2 cells largely accounted for the increased tissue thickness. Harmonic mean tissue thickness for controls remained near 0.537 ± 0.03 μm for the study interval, contrasting with values for 3 and 6 month 750 μg DE and 6 month 1500 μB DE sets which increased. However, the diffusion capacity of the lung determined morphometrically was not decreased in DE exposed sets. Although cellular uptake of DEP and increased prominence of secretory epithelium were dose/duration related, absence of linearity suggests adaptative responses.
The effects of five weeks treatment with dinitro‐o‐cresol‐ or trifluralin‐containing pesticides on the germ cells of male mice
Authors: Nehéz M. , Selypes A. , Páldy A. , Mazzag E. , Berencsi G. , Jármay K. 
Published: October 2006

AbstractThe effects of two pesticides, the insecticide‐herbicide Krezonit E, which contains 50% dinitro‐o‐cresol, and the herbicide Olitref, which contains 26% trifluralin (2,6‐dinitro‐N.N ‐dipropyl‐4‐trifluoromethylaniline), on the gonads and germ cells of male mice were studied. The pesticides were given twice a week for 5 weeks in i.p. doses of 0.6 mg kg−1 for Krezonit E and 6.0 mg kg−1 for Olitref. These doses are 1% of the i.p. LD50. Cytogenic analysis of germ cells carried out from 3 weeks onwards after the last treatment day showed that Olitref significantly increased the frequency of germinal chromosomal abnormalities at 6–7 weeks after treatment. This pesticide increased the frequency of autosomal univalents X/Y separations at meiotic metaphase and multivalent configurations. Krezonit E did not increase significantly the number of chromosomal abnormalities, although there was some increase at 3 weeks, mainly in the form of autosomal univalents.
An in vitro model of alcohol and acetaldehyde teratogenicity
Authors: Thompson P. A. C. , Folb P. I. 
Published: October 2006

AbstractC3H mouse embryos were supported in an in vitro culture system over 28‐h periods between 8 and 10 days post‐conception. Morphological development over this critical period of organogenesis was monitored in the following respects: somite count; presence or absence of heart beat; central nervous system size and symmetry; neural tube fusion. Total embryo DNA synthesis, determined by 3H‐thymidine uptake of the embryo over the last 4 h of the culture period, was compared with morphological findings. The effects of varying concentrations of ethanol and acetaldehyde, respectively, on morphology and DNA synthesis were determined at the dose levels tested. Both ethanol and acetaldehyde were toxic to the mouse embryos at this stage of their development, and reasonably close correlation was found between morphological abnormalities and reduction in DNA synthesis.
Comparison of somatic and germ cell models for cytogenetic screening
Authors: Holden Henry E. 
Published: October 2006

AbstractA variety of in vivo mammalian test models are available for screening of chemicals for mutagenicity at the chromosomal level. These models have been grouped into those focusing on somatic cell effects and those dealing with germ cell effects. An analysis of available literature indicates that 76 compounds have been tested from chromosome effects in both somatic and germ cells. Of these, concordant results (positive–positive or negative–negative) were obtained with 58 compounds. Of the remaining 18 compounds with discordant results, all were positive in somatic cells, but negative in germ cell assays. These results suggest an inherent relative insensitivity of germ cells themselves to mutagenic chemicals. In the context of screening for safety evaluation purposes, this analysis suggests that a negative somatic‐cell response can be taken as highly predictive of negative results in a germ cell assessment.
Inhibition of human erythrocyte and plasma cholinesterases by methamidophos
Authors: Robinson Casey P. , Beiergrohslein Donald 
Published: October 2006

AbstractMethamidophos (O, S‐dimethyl phosphoramidothioate) inhibition of human erythrocyte and plasma cholinesterase was studied in vitro. The pseudo‐biomolecular rate constant of inhibition was 3.14 ± 0.22 × 103 M−1 min−1 for erythrocyte cholinesterase and 1.85 ± 0.01 × 103 M−1 min−1 for plasma cholinesterase. Thus methamidophos, although quite toxic to mammals, is a slow, rather non‐selective inhibitor of human cholinesterases, as was also observed previously in rats.
Hepatic effects of orally administered styrene in rats
Authors: Srivastava S. P. , Das Mukul , Mushtaq M. , Chandra S. V. , Seth Prahlad K. 
Published: October 2006

AbstractAdult male rats receiving styrene by gavage (200 or 400 mg kg−1, 6 days a week) for 100 days exhibited a significant dose‐dependent increase in hepatic benzo[a]pyrene hydroxylase and ammopyrine‐N‐demethylase, a decrease in glutathione‐S‐transferase and no change in glucose‐6‐phosphatase. A decrease in the activity of mitochondrial succinic dehydrogenase and β‐glucuronidase was also observed. Activity of acid phosphatase was decreased only at the higher dose level. Levels of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated only at the higher dose level. The absolute and relative weights of the liver of control and treated animals showed no significant difference. Histopathological studies of the liver tissue revealed tiny areas of focal necrosis, consisting of few degenerated hepatocytes and inflammatory cells at the higher dose level only.
Parameters affecting the mutagenic activity of cigarette smokers' urine
Authors: Recio Leslie , Enoch Harry , Hannan M. A. 
Published: October 2006

AbstractCigarette smoke is a complex chemical mixture which displays a number of biological activities including mutagenesis. The absorption of smoke components by the lungs results in their systemic distribution, which then leads to the presence of mutagens in the urine. The detection of mutagenic substances in the urine by short‐term bioassays has been suggested for use in monitoring human exposure to various carcinogenic/mutagenic substances. In this connection, we felt that further studies on the mutagenic activity present in cigarette smokers' urine were needed. In the present studies, the dose–response relationship between the number of cigarettes smoked versus urine mutagenic activity and the persistence of mutagens in the urine after the cessation of smoking have been examined. The studies were carried out on a group of smokers and non‐smokers in Lexington, Kentucky. Although a dose–response relationship (urine mutagenicity versus the number of cigarettes smoked per day) was not observed in the group of smokers assayed, a linear dose–response relationship was detected in an individual smoker who smoked a varying number of cigarettes over eight successive days. In another smoker who ceased smoking, mutagens were detected in the urine for one week. The urine mutagenicity data from a group of smokers and non‐smokers should prove useful in extending this technique to the monitoring of other environmental exposure.
Non‐mutagenicity of 2‐Methyl‐2,3‐Epoxybutane and factors influencing the mutagenicity of 2,3‐Epoxybutane
Authors: De Meester C. , Mercier M. , Poncelet F. 
Published: October 2006

AbstractThe compound 2,3‐epoxybutane (2,3‐EB) is a direct mutagen for the base‐pair‐substitution‐sensitive strains TA 1530, TA 1535 and TA 100, in the absence and in the presence of metabolic activation by liver S9‐mix. Under the same experimental conditions, the 2‐methyl derivative of 2,3‐EB was not mutagenic, up to 10 mg per plate. The parent compound (2,3‐EB) was more active on strain TA 1530 in the presence of liver S9‐mix. This was observed at every epoxide concentration tested. The increase of mutagenicity depended on the S9 concentration, the mix composition and to a small extent on the method utilized.