bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introduction to the “Corporate Objective Revisited” Exchange
Authors: Walsh James P. 
Published: June 2004

Corporate scandals and abuses of various kinds grab the headlines. Reform initiatives quickly follow outrage. The goal is to constrain our firms' ability to destroy value and lives, while at the same time enabling them to produce and deliver high-quality and profitable goods and services in a very competitive global marketplace. Less obvious but no less important, civil society is increasingly asking corporations to invest directly in social life. Regardless of their productive capabilities, firms can field requests to invest in education, health care, infrastructure, and the like. Sometimes the two ambitions seem to be quite compatible, while at other times they seem to be at odds. Leading a business that is at once socially responsive and economically competitive is a daunting managerial challenge. The theoretical challenge posed by these sometimes competing and sometimes complementary demands is no less daunting. Since the rise of the first corporations two thousand years ago, we have been trying to develop a theory of the firm that explains and guides firm behavior. Sundaram and Inkpen enter this complex and charged world to make a case for a theory of the firm grounded in the pursuit of shareholder wealth. Freeman, Wicks, and Parmar will not let their view go unchallenged. They offer a spirited reply. The exchange embodies everything our Crossroads section can be. We are proud to provide a home for this very thoughtful exchange. This is arguably the most important theoretical and practical issue confronting us today. While we gave Sundaram and Inkpen the last word, we know that the debate is far from over. Indeed, we invite others to think hard about these issues and develop their own point of view. The stakes are enormous.
A Comparison of the Steady‐State Pharmacokinetics and Safety of Abacavir, Lamivudine, and Zidovudine Taken as a Triple Combination Tablet and as Abacavir plus a Lamivudine‐Zidovudine Double Combination Tablet by HIV‐1‐Infected Adults
Authors: Crémieux Anne‐Claude , Katlama Christine , Gillotin Catherine , Demarles Didier , Yuen Geoffrey J. , Raffi Francois ,   AZL10002 Study Group
Published: June 2004

Study Objective. To investigate the steady‐state pharmacokinetics of a triple combination tablet containing abacavir (ABC) 300 mg, lamivudine (3TC) 150 mg, and zidovudine (ZDV) 300 mg taken twice/day, and those of ABC 300 mg twice/day plus a double combination tablet containing 3TC 150 mg and ZDV 300 mg twice/day (ABC‐COM).Design. Open‐label, crossover study.Setting. Two hospital‐based clinical research units.Patients. Twelve men infected with human immunodeficiency virus‐1.Intervention. Steady‐state pharmacokinetics of ABC, 3TC, and ZDV were assessed after dosing with ABC‐COM and the triple combination tablet.Measurements and Main Results. Steady‐state pharmacokinetics of ABC, 3TC, and ZDV were similar for the triple combination tablet versus ABC‐COM for the following: geometric mean (GM) area under the serum concentration‐time curve, ABC 6.08 versus 5.87, 3TC 5.51 versus 5.53, and ZDV 1.38 versus 1.46 μg·hr/ml; GM maximum serum concentration (Cmax‐ss), ABC 3.09 versus 3.19, 3TC 1.26 versus 1.40, and ZDV 1.19 versus 1.15 μg/ml; median time to Cmax‐ss, ABC 0.75 versus 0.75, 3TC 1.50 versus 1.24, and ZDV 0.75 versus 0.75 hours; and GM oral clearance, ABC 51 versus 49, 3TC 27 versus 27, and ZDV 217 versus 206 L/hour. The GM half‐lives of ABC and ZDV were similar for both treatments, 1.69 versus 1.58 and 2.30 versus 2.08 hours, respectively.Conclusion. Steady‐state pharmacokinetics of ABC, 3TC, and ZDV were similar in patients who took them as ABC‐COM or as a triple combination tablet.
Bioavailability of the Oral Selective Phosphodiesterase 4 Inhibitor Cilomilast
Authors: Zussman Barry D. , Davie Christopher C. , Kelly John , Murdoch Robert D. , Clark David J. , Schofield J. Paul , Walls Christine , Birrell Claire , Webber Dawn , Quinlan Judith , Ritchie Sally Y. , Carr Alison 
Published: June 2004

Study Objective. To determine the absolute bioavailability of cilomilast, and assess the effects of food, dosing time, and coadministration of antacid agents on its bioavailability and pharmacokinetics in healthy volunteers.Setting. Clinical pharmacology unit.Design. Five prospective pharmacokinetic studies: one single‐blind, dose‐escalating, placebo‐controlled trial; four open‐label, randomized studies.Subjects. Ninety‐six healthy adult volunteers who were nonsmokers.Intervention. In the first study, four subjects received intravenous cilomilast 1, 2, and 4 mg. In the second study, 16 subjects received oral cilomilast 15 mg or intravenous cilomilast 4 mg. In the other three studies, a total of 76 subjects were given single oral 15‐mg doses; one study compared its effects in fed versus fasted subjects, one looked for differences of morning versus evening dosing, and one examined coadministration with aluminum hydroxide‐magnesium hydroxide.Measurements and Main Results. After intravenous administration of cilomilast, plasma concentrations increased in an approximately dose‐proportional manner; the half‐life, approximately 6.5 hours, was dose independent. Cilomilast clearance and volume of distribution were small. After oral dosing, the absolute bioavailability was consistently close to 100%. Absorption was slower in fed subjects than in fasted (median 2‐hr delay in time to reach maximum plasma concentration, average 39% reduction in maximum plasma concentration), but the area under the concentration‐time curve from time zero to infinity (systemic availability) was unaffected. Pharmacokinetic parameters were not influenced by time of dosing or coadministration of antacid.Conclusion. The absolute bioavailability of oral cilomilast was 100%; it was not adversely affected by time of dosing or coadministration with food or antacid.
Hyperbilirubinemia during Quinupristin‐Dalfopristin Therapy in Liver Transplant Recipients: Correlation with Available Liver Biopsy Results
Authors: Linden Peter K. , Bompart François , Gray Sharon , Talbot George H. 
Published: June 2004

Study Objective. To review the liver histopathology in transplant recipients who developed hyperbilirubinemia during therapy with quinupristin‐dalfopristin, a new streptogramin antibiotic, and to ascertain whether objective histologic evidence of adverse drug effect could be correlated to serum bilirubin levels.Design. Retrospective analysis.Setting. University of Pittsburgh Medical Center.Patients. From a database of 34 liver recipients who received quinupristin‐dalfopristin for vancomycin‐resistant Enterococcus faecium infection who were prospectively enrolled in a multicenter, open‐label, emergency‐use protocol, the data for a subset of 25 patients who underwent one or more liver biopsies during therapy were reviewed for this study.Interventions. Quinupristin‐dalfopristin was administered intravenously at 7.5 mg/kg every 8 hours. Available serum bilirubin levels from before, during, and 1 week after therapy were tabulated. Liver biopsy results obtained within 1 week before and during therapy were retrospectively reviewed. Histopathologic results were characterized and correlated to bilirubin level.Measurements and Main Results. Cholestatic changes were already present in 15 of 17 patients who underwent biopsy before therapy. During therapy, the most common findings from 40 biopsies (25 patients) were cholestasis (33 biopsies), acute rejection (10), and periportal inflammation (8). There was no evidence of drug‐specific histopathologic injury.Conclusion. Hyperbilirubinemia in these patients was likely multifactorial and most frequently due to sepsis and prior graft injury.
Drug Therapy and Prevalence of Erectile Dysfunction in the Massachusetts Male Aging Study Cohort
Authors: Derby Carol A. , Barbour Marilyn M. , Hume Anne L. , McKinlay John B. 
Published: June 2004

Study Objective. To examine the association of commonly used drugs with erectile dysfunction (ED) at two time points.Design. Population‐based, cross‐sectional, survey analysis.Participants. Randomly selected cohort of men in the Massachusetts Male Aging Study (MMAS) that included 1476 men for the baseline (1987–1989) and 922 for the follow‐up (1995–1997) analyses.Intervention. Crude associations between specific drug categories were examined with X2 statistics. Logistic regression analysis was used to separate the effect of drugs from the influence of heart disease, hypertension, untreated diabetes, or depressive symptoms.Measurements and Main Results. In the MMAS, medical history, current drug use, and erectile function status were ascertained with in‐home interviews. In unadjusted analyses, thiazide and nonthiazide diuretics, β‐blockers, calcium channel blockers, angiotensin‐converting enzyme inhibitors, benzodiazepines, digitalis, nitrates, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors, and histamine2 receptor antagonists were associated with prevalent ED. Adjustment for comorbidities and health behaviors attenuated these associations, with only nonthiazide diuretics and benzodiazepines remaining statistically significant.Conclusion. Several common drugs may increase prevalence of ED; however, additional data from larger populations are needed to determine whether these associations are independent of underlying health conditions and to explore the effects of dosage and duration of use.
Oral Health of Individuals with Cleft Lip, Cleft Palate, or Both
Authors: Lages Elizabeth Maria Bastos , Marcos Badeia , Pordeus Isabela Almeida 
Published: June 2004

Objective To evaluate the oral health of children with cleft lip and palate. Design DMFT (dmft) and DMFS (dmfs) were calculated on the basis of visual examination. Periodontal disease was assessed by classical clinical parameters: volume gain, bleeding, probing depth, loss of insertion, gingival recession. and calculus. Patients Seventy-eight individuals aged 1 to 32 years took part in the study. Results The dmft was 2.91 (± 3.99) in the 1- to 5-year-old age group and 2.77 (± 3.15) in the 6- to 12-year-old group. The DMFT averages for the age groups of 6 to 12 years, 13 to 18 years, and 19 to 32 years were 1.87 (± 1.78), 6.46 (± 3.11), and 13.62 (± 6.51), respectively. A total of 5.3% of individuals presented a healthy periodontium, and 86.6% presented with gingivitis and 8% presented with periodontitis. Conclusions The dental and periodontal condition of individuals with cleft lip and palate was similar to the general population in the region in which this study was conducted. Good preventive measures should result in improved oral health similar to the general population and should be emphasized.
Nonhuman Primates as Animal Models for Toxicology Research
Authors: Burbacher Thomas M. , Grant Kimberly S. 
Published: June 2004

AbstractThere is a long history for the use of nonhuman primates intoxicological research. This unit reviews applications in reproductivetoxicology and teratology, neural toxicology and neurobehavioral toxicology, imunotoxicology, respiratory (lung) toxicology, and chemical carcinogenesis.
The Use of Fish‐Derived Cell Lines for Investigation of Environmental Contaminants
Authors: Dayeh Vivian R. , Bols Niels C. , Schirmer Kristin , Lee Lucy E.J. 
Published: June 2004

AbstractThis unit describes protocols for growing salmonid cell lines and using them in in vitro toxicology studies. Cell viability of cultures is assessed with three indicator dyes: alamar blue for metabolic activity, CFDA‐AM for membrane integrity, and neutral red for lysosomal activity. These protocols are essential tools for investigating environmental toxicity at the cellular level.
Sea Urchin Embryos and Larvae as Biosensors for Neurotoxicants
Authors: Buznikov Gennady A. , Slotkin Theodore A. , Lauder Jean M. 
Published: June 2004

AbstractSea urchin embryos and larvae provide an inexpensive high‐throughput system for determining developmental actions of neuropharmacologic agents or environmental neurotoxins in both applied and basic biologic contexts. The use of this system for the testing of chlorpyrifos, 1‐nicotine, lipophilic amides of choline, and ritanserin is described in detail.
Zebrafish: An Animal Model for Toxicological Studies
Authors: Zhang Chaojie , Willett Catherine , Fremgen Trisha 
Published: June 2004

AbstractZebrafish (Danio rerio) has been extensively studied and well described for environmental toxicity studies. Molecular biology and genetics have recently been used to elucidate the underlying mechanisms of toxicity in zebrafish and to predict effects in mammals. The versatile zebrafish is now incorporated in many areas of toxicological programs for assessing human risk and for preclinical drug discovery and screening.
Preclinical Models of Parkinson's Disease
Authors: Bankiewicz Krys S. , Sanchez‐Pernaute Rosario , Oiwa Yoshitsugu , Kohutnicka Malgorzata , Cummins Alex , Eberling Jamie 
Published: June 2004

AbstractParkinson's disease (PD) is a neurodegenerative disorder in which pigmented midbrain neurons progressively die producing a dopamine (DA) deficit in the striatum, which manifests as an akinetic movement disorder. Experimentally induced striatal DA depletion in animals is a valid model of parkinsonism. The capacity of certain substances to damage catecholaminergic neurons has been used extensively to produce DA deficiency in animals. This unit describes methods for inducing parkinsonism in nonhuman primates and rodents using the neurotoxins 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and 6‐hydroxydopamine (6‐OHDA). Additionally, procedures for evaluating the animals are presented.
Measurements of Intracellular Free Calcium Concentration in Biological Systems
Authors: Gunter Karlene K. , Gunter Thomas E. 
Published: June 2004

AbstractIntracellular calcium plays a role in signaling and as a second messenger in many types of cells and its concentration is closely regulated in cells. Two techniques for measuring intracellular free calcium are using fluorescent ratiometric and nonratiometric probes are described in this unit: fluorescent spectroscopy to measure calcium concentrations in a suspension of cells and fluorescent digital imaging microscopy (FDIM) to measure calcium concentrations in plated cells.
In Vitro Methods for Detecting Cytotoxicity
Authors: Ehrich Marion , Sharova Lioudmilla 
Published: June 2004

AbstractToxicant‐induced damage to cells (cytotoxicity) can depress cell growth, compromise intracellular metabolic processes, and/or cause loss of cell viability. Methods that indicate these cytotoxic changes following toxicant exposures are provided, including [3H]thymidine uptake to measure cell growth, MTT dye conversion to detect changes in metabolic activity, and trypan blue uptake to indicate loss of cell viability.
Measuring the Activity of Arylamine N‐Acetyltransferase (NAT)
Authors: McQueen Charlene A. 
Published: June 2004

AbstractThis unit describes methods for measuring the activity of arylamine N‐acetyltransferases (NAT). Genetic polymorphisms in NAT 1 and NAT 2 have been associated with susceptibility to aromatic amines carcinogens and effects of therapeutic drugs. Evaluation of the activities associated with substrates of NATs is helpful in elucidating the contribution of these enzymes to the pharmacologic and toxicologic effects of arylamines and hydrazines.
Measurement of Carboxylesterase (CES) Activities
Authors: Hosokawa Masakiyo , Satoh Tetsuo 
Published: June 2004

AbstractMeasurement of Carboxylesterase (CES) Activities (Masakiyo Hosokawa, Chiba University, Chiba, Japan and Tetsuo Satoh, Biomedical Research Institute, Chiba, Japan). Mammalian carboxyesterase (CES) efficiently catalyzes the hydrolysis of a variety of ester‐ and amide‐containing chemicals. CES is involved in detoxification or metabolic activation of various drugs, environmental toxicants, and carcinogens. This unit contains three protocols for measuring CES activities.
Analysis of the Aryl Hydrocarbon Receptor (AhR) Signal Transduction Pathway
Authors: Denison Michael S. , Rogers Jane M. , Rushing S. Renee , Jones Carol L. , Tetangco Selwyna C. , Heath‐Pagliuso Sharon 
Published: June 2004

AbstractAnalysis of the Ah Receptor Signal Transduction Pathway (Michael S. Denison, Jane M. Rohers, S. Renee Rushing. Carol L. Jones, Selwyna C. Tetangico, and Sharon Heath‐Pagliuso, University of California, Davis, California).The protocols in this unit will allow researchers to detect the Ah receptor and characterize its functional activities (i.e., ligand binding, transformation and DNA binding, and gene expression) in their biological test system and to use these methods to detect chemical and biochemical events that affect this signaling system.
Assays for the Classification of Two Types of Esterases: Carboxylic Ester Hydrolases and Phosphoric Triester Hydrolases
Authors: Anspaugh Douglas D. , Roe R. Michael 
Published: June 2004

AbstractAssays for the Classification of Two Types of Esterases: Carboxylic Ester Hydrolase and Phosphoric Triester Hydrolase (Douglas D. Anspaugh and Michael Roe, North Carolina State University, Raleigh, North Carolina). This unit describes assays that quantitate two types of esterase the carboxylic ester hydrolases and the phosphoric triester hydrolases. Carboxylic ester hydrolases include the B‐esterases, which are inhibited by organophosphorus compounds. Among the phosphoric triester hydrolases is aryldialkylphosphatase, which has been called A‐esterase or paraoxonase due to its ability to oxidize paraoxon and other organophosphates. These assays are colorimetric and miniaturized for rapid simultaneous testing of multiple, small‐volume samples in a microtiter plate format. There is also a discussion of the history of esterase nomenclature and the reasons why this large group of enzymes is so difficult to classify.
Human Cytochrome P450: Metabolism of Testosterone by CYP3A4 and Inhibition by Ketoconazole
Authors: Usmani Khawja A. , Tang Jun 
Published: June 2004

AbstractThis unit describes methods for measuring CYP3A4 activity using testosterone as a specific substrate, and for measuring CYP3A4 inhibition using ketoconazole as a selective inhibitor of testosterone oxidation. CYP3A4 is one of the most important and most abundant drug‐metabolizing CYP isoforms in human liver microsomes (∼40% of total CYP), and it has the broadest substrate specificity. It is important to determine whether CYP3A4 is involved in its metabolism.
Overview of Glutathione Function and Metabolism
Authors: Will Yvonne 
Published: June 2004

AbstractGlutathione is a key player in reduction processes in the cell. It is responsible for maintaining thiol groups of intracellular proteins by providing reducing power for cysteine, dihydolipoate, CoA, ascorbate, and vitamin E. It also plays a role in reduction of NTPs to dNTPs. Glutathione is also involved in detoxification of endogenous and exogenous compounds, participates in the synthesis of leukotrienes and prostaglandins, serves as a cofactor for various enzymes, stores and transports cysteine, and may be involved in cell cycle regulation and thermotolerance.
Measurement of Glutathione Conjugates
Authors: Shultz Michael A. , Morin Dexter , Chan Katherine Watt , Buckpitt Alan R. 
Published: June 2004

AbstractThe involvement of reactive metabolites in cancer and cellular necrosis has been well established. The nucleophile, glutathione, provides a major mechanism of intracellular protection from electrophilic metabolites. Conjugation with glutathione to generate stable, water‐soluble metabolites has been utilized to determine the nature and rates of formation of precursor reactive metabolites. In addition, because activities of the glutathione transferases may play a key role in tissue/cellular susceptibilities to electrophilic compounds, measurement of catalytic activities of these proteins can play an important role in discerning the underlying mechanisms of cell‐selective toxicities. This unit outlines HPLC methods found to provide good separation of glutathione conjugates and includes two additional procedures that can be utilized in experiments where high throughput assays are needed for measuring transferase activities.
Analysis of Superoxide Dismutase Activity
Authors: McCord Joe M. 
Published: June 2004

AbstractMeasuring the activity of superoxide dismutases (SODs), the enzymes responsible for maintaining the steady state level of hydrogen peroxide, is challenging because the substrate is unstable at physiological pH and it reacts with itself. Fortunately the rate of reaction with dismutase is far greater than the rate of self reaction. As described in this unit, this activity can be measured indirectly based on competition between SOD and an indicator molecule that reacts avidly with superoxide to produce a measurable change in absorption, thus it is possible to measure total SOD activity or that of CuZn‐SOD and MnSOD. The activity can also be measured by an activity stain applied to thin‐film agarose or native polyacrylamide gels.
Measurement of MnSOD and CuZnSOD Activity in Mammalian Tissue Homogenates
Authors: Spitz Douglas R. , Oberley Larry W. 
Published: June 2004

AbstractThree basic forms of mammalian SODs exist and they are distinguished by their sizes and locations. SOD enzyme activity is not easily monitored by direct measurement because the substrate disappearance is very rapid at physiological pH. Activity can be measured as described in this unit by a number of indirect competitive inhibition assays based on the principle that the superoxide anion radical will reduce an inhibitory substrate [such as nitroblue tetrazolium (NBT) or cytochrome c] and SOD activity will reduce the rate of reduction in a competitive fashion. The SOD‐mediated inhibition of the indicator substrate reduction can then be quantitated and plotted as a function of the quantity of protein added to the reaction to construct an inhibition curve.
Measurement of Ascorbic Acid and Dehydroascorbic Acid in Biological Samples
Authors: Lykkesfeldt Jens 
Published: June 2004

AbstractAscorbic acid and dehydroascorbic acid are commonly used biomarkers of oxidative stress in a variety of experimental models. However, the accurate measurement of these labile compounds remains a challenge both in terms of sample collection and analysis. Determination of dehydroascorbic acid most commonly involves indirect measurement. The concentration is calculated by subtraction of the measured ascorbic acid concentration from that of total ascorbic acid analyzed after reduction of the dehydroascorbic acid present; a method referred to as the subtraction method. Consequently, successful determination of dehydroascorbic acid is dependent upon proper sample handling, quantitative reduction of the compound, and accurate quantification of both ascorbic acid and total ascorbic acid. The unit presents a detailed introduction to ascorbate analysis in biological samples and discusses common problems and pitfalls. The analytical method described is based on reversed‐phase HPLC with coloumetric detection. This method includes co‐analysis of isoascorbic acid and uric acid. Where applicable, uric acid can conveniently be used as an endogenous intrasample standard that significantly improves the accuracy of the subsequent dehydroascorbic acid calculation.
Measurement of ALA Synthase Activity
Authors: Sinclair Peter R. , Gorman Nadia , Cornell Neal W. 
Published: June 2004

AbstractIn most cells, δ‐aminolevulinate (ALA) synthase is the rate‐limiting enzyme in heme synthesis. It is inducible by drugs and toxins and is feedback regulated by heme. This unit describes a radiometric assay using [14C]succinate as a substrate and a colorimetric assay based on the conversion of ALA to a pyrrole.