bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of a standard meal on the absorption of a controlled release pseudoephedrine suspension
Authors: Graves D. A. , Wecker M. T. , Amsel L. P. , Hinsvark O. N. , Bhargava A. K. , Rotenberg K. S. , Meyer M. C. , Straughn A. B. 
Published: October 2006

AbstractThe influence of a standard meal on the extent and rate of absorption of pseudoephedrine from a liquid controlled release (CR) formulation (Pennkinetic System) was studied in 16 normal male volunteers. Equivalent single doses of an immediate release reference syrup (IR‐Sudafed) and the CR suspension were each studied under both fasted and postprandial conditions. AUC results showed no significant influence of food or formulation, indicating that the CR formulation was absorbed to the same extent as the IR product under all conditions. CMAX and TMAX tabulations under fasted conditions indicated that the CR preparation peaked at a lower level at a later time. Food diminished IR CMAXs but the CR suspension's CMAXs and TMAXs were apparently unaffected by food. This study indicates that this CR pseudoephedrine suspension releases drug independently of food intake.
Plasma levels, heart rate, and blood pressure after intravenous, oral, and aerosol administration of reproterol in man
Authors: Hageman R. J. J. , De Zeeuw R. A. , Greving J. E. , Krann J. J. , Koëter G. H. 
Published: October 2006

AbstractThree healthy volunteers received single doses of reproterol (D 1959) by means of intravenous infusion, oral and aerosol application, respectively. Administrations were separated by at least 1 week. Plasma levels were measured by means of high performance liquid chromatography.After infusion, plasma levels showed a steep decline, indicative for a rapid distribution. Even though relatively large amounts of drug were given (up to 540 μg), this phenomenon caused reproterol levels to drop to values near or below the limit of reliable quantitation (1 ng ml−1) within 60 to 90 min. After oral administration of one or two tablets (containing 20 mg reproterol. HC1 per tablet), a very short lag time could be observed, indicating fast absorption. After one tablet, plasma level maxima (of plateau‐type) were 5.6 ng ml−1 and 2.3 ng ml−1 in two subjects, respectively. After two tablets, plateau level maxima around 18 ng ml−1 and 9 ng ml−1 were found, respectively.After inhalation of a metered aerosol (two puffs of 500 μg each) the drug appeared in plasma within minutes, albeit at very low levels, and usually remained detectable at the sub‐nanogram level during the time of the experiment (2 h).Due to the very low levels and to some oscillations in the plasma concentration‐time curves, a detailed pharmacokinetic assessment could not be carried out. Effects on heart rate and blood pressure were negligible. Only during the infusion of high doses (540 μg) was there an increase in heart rate of about 50 to 120 beats min−1. Other side‐effects were also negligible.
Pharmacokinetic analyses with rugfit an interactive pharmacokinetic computer program
Authors: Scaf Arnold H. J. 
Published: October 2006

AbstractRUGFIT is an interactive computer program to fit polyexponential equations to experimental points without the need of assumptions about the number of exponential terms and without the need of initial parameter estimates. The fitting is performed by iterative stripping minimizing the sum of squared residuals. This procedure leads to multiple model equations describing the profile of they‐value in time, that are compared with the test of Boxenbaumet al.The examples analysed in this paper are: a plasma decay curve after an intravenous bolus injection and one after an oral gift, a dA/dtversus time curve with a lag time and a curve possibly reflecting an entero‐hepatic recirculation. The outcomes are, where possible, compared with the outcomes obtained with the computer programs CFT3, NONLIN, and NONLINEAR (SPSS). The latter three programs sometimes run into a local minimum, as the outcomes obtained with RUGFIT were close to the best ones obtained with the other programs.The analyses with RUGFIT show that a choice of an inadequate model equation can lead to a marked error in the value of the area under the curve that may result in a marked error of, for instance, the bioavailability. The procedures of RUGFIT are illustrated in the Appendix. RUGFIT also contains options to calculate microparameters, to simulate dosage regimes, to calculate exponents and intercepts from rate constants and to analyse time effect relationships.
Steady state relative bioavailability and pharmacokinetics of oral propranolol in black and white North Americans
Authors: Sharoky Melvin , Perkal Mark , Turner Robert , Lesko L. J. 
Published: October 2006

AbstractThe steady state bioavailability and pharmacokinetics of propranolol over two consecutive dosing intervals were investigated in 18 black and 10 white normal volunteers following the administration of 20 mg of a test and reference oral dosage form, respectively, every 6h. There were no differences (p > 0.05) between dosage forms in the mean (n = 28) area under the plasma concentration‐time curve (AUC), maximum plasma concentration (Gmax) or time to Gmax (tmax) for propranolol or its active metabolite, 4‐hydroxypropranolol. However, as a group blacks had lower plasma concentrations of propranolol and 4‐hydroxypropranolol than whites. The mean AUC and Cmax for propranolol during the second dosing interval (AUC‐2 and Cmax‐2, respectively) were significantly (p < 0.05) lower in blacks, but there were no ethnic differences (p > 0.05) in tmax. The mean AUC and Cmax for the 4‐hydroxylated metabolite during both dosing intervals were significantly (p < 0.05) lower in blacks. Mean oral clearances of propranolol, assuming complete absorption, (range: 42.1–54.5 ml min−1 kg−1) were similar (p > 0.05) in each racial group. There were no substantial changes in heart rate or blood pressure in blacks or whites following propranolol administration. These data suggest that for oral propranolol, blacks have different absorption and disposition characteristics than whites.
Relative bioavailability of a controlled‐release albuterol formulation for twice‐daily use
Authors: Sykes R. S. , Reese M. E. , Chubb J. M. , Meyer M. C. 
Published: October 2006

AbstractA two‐way‐crossover bioavailability study was completed with 15 healthy male volunteers to evaluate the relative bioavailability of an orally administered controlled‐release (CR) formulation of albuterol as compared to the immediate‐release (IR) formulation of albuterol. The CR formulation of albuterol used in this study was based mechanistically on the elementary osmotic pump.1 Each subject received one 8 mg CR tablet every 12 h for 8 consecutive days and one 4 mg IR tablet every 6 h for 8 consecutive days, with 7 days separating each phase. During day 8 of dosing, hourly blood samples (0–12 h) were collected after the morning dose and three additional samples were obtained 16, 20 and 24 h following this dose. Plasma concentrations were measured using a gas chromatography‐mass spectrometry procedure. No statistically significant differences were observed in mean steady‐state values for Cmax AUC(0–12 h) and peak‐to‐trough fluctuations (PTF) in comparing the two dosage formulations. Mean steady state Tmax values were 2.6 and 6.0 h for the TR and CR formulations, respectively.It was concluded that twice daily administration of the controlled‐release formulation of albuterol provides an alternative to four times daily administration of conventional (immediate‐release) albuterol tablets.
Drug distribution in dog brain studied by positron emission tomography
Authors: Agon Philippe , Braeckman Rene , Van Haver Dirk , Denutte Hugo , Goethals Patrick , Donche Hendrick , Vermeullen Franklin , Deman Joris , Kaufman Jean‐Marc 
Published: October 2006

AbstractWe used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C‐labelled antipyrine, imipramine, and quinidine.Twenty‐five sequential scans of a transaxial slice of the head were performed within 90 min; radioactivity in plasma was measured in a gamma‐counter. Following i.v. injection of [11C] antipyrine (50 mg kg−1; 9–68 mCi; n=10), the decay of plasma activity was accompanied by rapid uptake in brain and variable uptake in muscle, immediately followed by a redistribution leading to equalization of the radioactivity in the tissues. Administration of [11C]imipramine (4 mg kg−1; 30–110 mCi; n=8) was followed by a rapid build‐up of a sustained gradient between high brain, and low plasma and muscle radioactivity. After i.v. injection of [11C]quinidine (1 mg kg−1; 11–87 mCi; n=10), radioactivity in brain was low, with higher activity in plasma and muscle throughout the experiment.Positron emission tomography thus revealed for each drug a distinct pattern of distribution consistent with established properties of the compounds. This technique seems promising for the study of early drug distribution, notwithstanding certain limitations.
Comparison of mRNA abundance quantified by gene expression profiling and percentage of positive cells using immunophenotyping for diagnostic antigens in acute and chronic leukemias
Authors: Kern Wolfgang , Kohlmann Alexander , Schoch Claudia , Schnittger Susanne , Haferlach Torsten 
Published: October 2006

AbstractBACKGROUND.Microarray analysis is considered a future diagnostic tool in leukemias. Whereas data accumulate on specific gene expression patterns in biologically defined leukemia entities, data on the correlation between flow cytometrically determined protein expression, which are essential in the diagnostic setting today, and microarray results are limited.METHODS.The results obtained by microarray analysis were compared using the Affymetrix GeneChip HG‐U133 system in parallel with flow cytometric findings of 36 relevant targets in 814 patients with newly diagnosed acute and chronic leukemias as well as in normal bone marrow samples.RESULTS.In a total of 21,581 individual comparisons between signal intensities obtained by microarray analysis and percentages of positive cell as determined by flow cytometry, coefficients of correlation in the range of 0.171 to 0.807 were obtained. In particular, the degree of correlation was high in the following genes critical in the diagnostic setting: CD4, CD8, CD13 (ANPEP), CD33, CD23 (FCER2), CD64 (FCGR1A), CD117 (KIT), CD34, MPO, CD20 (MS4A1), CD7 (range of r, 0.589–0.807).CONCLUSIONS.The present data prove the high degree of correlation between findings obtained by microarray analysis and flow cytometry. They are in favor of a future application of the microarray technology as a robust diagnostic tool in leukemias. Cancer 2006. © 2006 American Cancer Society.
Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells
Authors: Nasreen Najmunnisa , Mohammed Kamal A. , Antony Veena B. 
Published: October 2006

AbstractBACKGROUND.The over‐expression of the ephrin‐A1 ligand receptor EphA2 is associated with the growth and metastatic potential of tumors. Although EphA2 is expressed in a variety of tumors, its expression and function in malignant mesothelioma (MM) remain unknown. The authors hypothesized that expression of the receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic migration of MM. They also hypothesized that silencing EphA2 expression by using small‐interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs and induces apoptosis in MMCs.METHODS.The expression of EphA2 in MMCs and in normal pleural mesothelial cells (PMCs) was studied by using real‐time quantitative polymerase chain reaction analysis and Western blot analysis. The growth of MMCs was determined with the WST‐1 cell‐proliferation assay. The haptotactic migration of MMCs and PMCs was determined with a Boyden chamber assay. Expression of caspases was determined with calorimetric assays.RESULTS.The results demonstrated that silencing the receptor EphA2 by siRNA significantly reduced the proliferation and haptotactic migration of MMCs compared with controls. Over‐expression of EphA2 with plasmid pcDNA/EphA2 enhanced the proliferation and haptotaxis of MMCs significantly. Knocking down EphA2 expression initiated caspase‐9–mediated apoptosis in MMCs.CONCLUSIONS.The current results suggested that constitutive expression of EphA2 may contribute to the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective therapeutic target in patients with mesothelioma. Silencing the receptor EphA2 gene is a novel approach for the containment of growth and migration of tumor in patients with malignant mesothelioma. Cancer 2006. © 2006 American Cancer Society.
NFAT transcription factors in control of peripheral T cell tolerance
Authors: Serfling Edgar , Klein‐Hessling Stefan , Palmetshofer Alois , Bopp Tobias , Stassen Michael , Schmitt Edgar 
Published: October 2006

AbstractThe Ca++‐regulated calcineurin/NFAT cascade is one of the crucial signalling pathways that controls adaptive immunity. However, a number of novel experimental data suggest that, in addition to their role in T cell activation, NFATc transcription factors play also a decisive role in the generation of peripheral tolerance against self‐antigens. This function of NFATc factors is mediated by controlling activation‐induced cell death and clonal anergy of T helper cells and the activity of regulatory T cells. The multi‐functional role of NFATc proteins characterize these transcription factors as key regulators of immunological tolerance and, if dysregulated, of development of autoimmune diseases.
An empirical analysis of US and Japanese health insurance using age–period–cohort decomposition
Authors: Fukuda Kosei 
Published: October 2006

AbstractAggregate data on household health insurance expenditure in the US and Japan that are classified by period and age are decomposed into age, period, and cohort effects by using the Bayesian cohort models. These models are developed to overcome the identification problem involved in cohort analysis. Despite the differences between the health insurance systems of the two countries, three interesting empirical findings are obtained. First, in both the countries, the age effects are the most influential, and the cohort effects have negligible influence. The latter provides a striking policy implication since the generational imbalance in social security expenditures is widely recognized in developed countries. Second, in both the countries, the period effects show a roughly upward trend. Finally, the age effects exhibit a roughly upward movement for all age groups in the US; however, in Japan, these effects show a downward movement for the 55–59 age group due to the changes in the health insurance system on retirement. Copyright © 2006 John Wiley & Sons, Ltd.
Combined two‐generation reproduction‐teratogenesis study of zearalenone in the rat
Authors: Becci Peter J. , Johnson William D. , Hess Frederick G. , Gallo Michael A. , Parent Richard A. , Taylor Jean M. 
Published: October 2006

AbstractThe toxicity of zearalenone was studied in two generations of Wistar rats over approximately 10 months. Zearalenone was administered in the diet; the dose levels used were 0, 0.1, 1.0 and 10.0 mg per kg body weight per day in all generations. Animals in the F0 generation were bred twice to produce F1A and F1B generations. The F1A generation was bred to produce the F2A generation. The only lesion found at necropsy that could be attributed to zearalenone administration was increased medullary trabeculation of the femur in animals given the high dose. A dose‐related increase in absolute and relative thyroid, pituitary and adrenal gland weights occurred in male and female rats of both the F1 and F1A generation. The alteration in the weights of these endocrine organs is probably a result of the estrogenic activity of zearalenone. Feeding of zearalenone caused decreases in fertility, number of viable offspring per litter and numbers of corpora lutea, implantations and resorptions per dam. Statistically significant differences were noted in the incidences of a number of skeletal and soft tissue abnormalities in both the F1B and F2A1 fetuses, especially at doses of 1.0 and 10.0 mg kg−1. These lesions most likely indicate a delay in fetal development. Unequivocal teratogenic effects could not be defined.
Comparative toxicity of dietary T‐2 toxin in rats and mice
Authors: Hayes M. A. , Schiefer H. B. 
Published: October 2006

AbstractThe subacute toxic effects of dietary T‐2 toxin were compared in young male Wistar rats, young male Swiss mice and juvenile Swiss mice. Purified T‐2 toxin was fed in the diet at levels of 10 or 20 ppm for 2 or 4 weeks. Dose‐related depressions in food consumption and weight gain consistently occurred in all animals fed T‐2 toxin. Hyperkeratosis of the squamous gastric mucosa, atrophy of the thymus and thymusdependent lymphoid tissues, and lymphopenia occurred in all animals exposed to T‐2 toxin. These effects were most severe in juvenile mice, and least severe in rats. In addition, juvenile mice fed the 20‐ppm level developed erythroid hypoplasia and became severely anemic by 4 weeks. These results demonstrate that dietary T‐2 toxin at levels up to 20 ppm cause similar effects attributable to food refusal and alimentary irritation in both species. However, mice and rats were relatively resistant to hematopoietic suppression. Only the juvenile mice fed 20 ppm developed this potentially lethal toxic effect.
Urinary excretion of 5‐hydroxyindolacetic acid in occupational exposure to polyvinyl chloride and polyurethane foams
Authors: Korićanac Z. , Stanković B. , Milovanović J. L. , Dugandžić M. , Trpković D. 
Published: October 2006

AbstractThe effect of plastics as polyurethane foams and polyvinyl chloride on the metabolism of tryptophan was investigated by determining the concentration of 5‐hydroxyindolacetic acid (5‐HIAA) as its metabolic end product excreted in the urine. Investigation of persons occupationally exposed to polyurethane and polyvinyl chloride showed that these plastics inhibit the metabolism of tryptophan, causing increased excretion of its easily measurable metabolite 5‐HIAA. This fact points to the possibility of practical use of this laboratory test which, together with other biological parameters, could improve methods for early detection of occupational exposure to polyurethanes and polyvinyl chloride.
Iodine in diet increases mercury absorption in rats
Authors: Kostial Krista , Kargačin Biserka , čimonović Ivan 
Published: October 2006

AbstractIncreasing the iodine content of rats diets caused an increase in the whole‐body retention of 203Hg after oral, but not after intraperitoneal, administration. That iodine increases gastrointestinal absorption of inorganic mercury might be of interest in conditions of simultaneous environmental exposure to both elements, and therefore deserves further investigations.
Evaluation of the skin uptake of mercuric chloride in man
Authors: Baranowska‐dutkiewicz Bożena 
Published: October 2006

AbstractSkin on the forearms of male human volunteers was exposed to aqueous HgCl2 solutions. It was assumed that loss of mercury from the test solution was equivalent to percutaneous absorption. Two parameters important for influencing uptake considered as the rate of absorption were investigated: the concentration of HgCl2 solutions (0.01, 0.1 and 0.2 M) and the time of exposure (5, 10, 15, 30 and 60 min). The absorption rate from 0.1 M HgCl2 solution decreased from 9.3 μg cm−2 min−1 during a 5 min exposure to 2.5 μg cm−2 min−1 during a 1 h exposure. A ten‐fold decrease of HgCl2 concentration resulted in an approximately ten‐fold decrease of the absorption rate, from 4.6 to 0.4 μg cm−2 min−1 during a 30 min exposure. The results indicate that the absorption rate is a directly related function of concentration and an indirectly related function of time of exposure.
Inhibition of mixed‐function oxidase activities in vitro and in vivo: Comparisons between kidney and liver
Authors: Kluwe W. M. , Herrmann‐kluwe C. L. , Hook J. B. 
Published: October 2006

AbstractThe concentration‐dependent abilities of SKF 525‐A, metyrapone (MET), piperonyl butoxide (PB), allyl‐isopropylacetamide (AIA) and α‐napthoflavone (7.8‐benzoflavone; ANF) to inhibit the activities of p‐chloro‐N‐methylaniline‐N‐demethylase (PCNMA) and aryl hydrocarbon hydroxylase (AHH) in vitro were determined in microsomal and postmitochondrial supernatant (PMS) fractions of homogenates prepared from kidneys and livers of rats and mice. Renal microsomal AHH was less sensitive to modulation by SKF 525‐A, MET and ANF in vitro than was hepatic microsomal AHH, but renal and hepatic microsomal AHH were equisensitive to inhibition by PB. AIA did not inhibit AHH activities in vitro. Renal AHH and PCNMA activities in PMS fractions were less sensitive to inhibition by SKF 525‐A, MET and PB than were hepatic AHH and PCNMA activities. The temporal characteristics of enzyme inhibition in vivo were studied in kidneys and livers removed 1, 2, 4 or 12 h after treatment of the animals with 75 mg kg−1 SKF 525‐A or 600 mg kg−1 PB. The degree of inhibition of AHH and PCNMA activities produced by i.p. administration of the inhibitors were greater quantitatively in liver PMS than in kidney PMS, and the degree of inhibition of PCNMA activity in both organs was much less than that of AHH activitiy. The differences in sensitivity of renal and hepatic AHH and PCNMA activities to the inhibitors may have been due to organ‐specific differences in the affinities of the inhibitors for interaction with the active site(s) on cytochrome P‐450.
MS/MS analysis of diesel emissions and fuels treated with NO2
Authors: Henderson Thomas R. , Royer Robert E. , Clark Charles R. , Harvey T. M. , Hunt D. F. 
Published: October 2006

AbstractCorrelations between direct‐acting mutagens in diesel emissions and the activity of nitroaromatic compounds have been noted, but detection and identification of nitro‐compounds in diesel particulates has remained an elusive problem. In the results reported here, MS/MS (tandem mass spectrometry) was found to detect nitroaromatic compounds in fractionated and unfractionated diesel soot extracts. The nitro‐compounds detected ranged from two‐ to four‐ring polynuclear aromatic hydrocarbon derivatives and were primarily mono‐nitroderivatives. An aromatic fraction from diesel fuel reacted with NO2 resembled diesel exhaust extracts from an engine operating on the same fuel. Therefore, it is possible that nitroaromatic derivatives in diesel exhaust may be in part due to unburned fuel residues reacting with NOx formed in the combustion process. The utility of MS/MS in comparing complex mixtures from different sources or subfractions thereof is discussed.
Isotoxic oral and inhalation exposure of carbon tetrachloride in Porton–Wistar and Fischer rats
Authors: Magos L. , Snowden R. , White I. N. H. , Butler W. H. , Tuffery A. A. 
Published: October 2006

AbstractMale Fischer or Porton–Wistar rats were exposed for 4 h to different atmospheric concentrations of CCl4 or were given increasing oral doses of CCl4 in order to estimate isotoxic exposures or doses. Animals were killed 20 h after treatment, their serum glutamic–pyruvic transaminase activities were measured and their livers were processed for histological examination. It has been found that the equitoxic oral dose in Wistars is 1.5 times that in Fischer rats and more than 3 times after inhalation. Therefore, the conversion factors from inhalation exposure to oral dose were much higher for Fischer than for Porton–Wistar rats. After oral dosing, the extent of centrilobular damage in Fischer rats was approximately twice that in Porton–Wistar rats. After inhalation exposure, the extent of damage was the same in the two strains, but at least at the two lower exposure levels hydropic degeneration definitely contributed to the size of the damaged areas more in Porton‐Wistar than in Fischer rats.