bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of prior, low‐level cadmium exposure in vivo on metallothionein expression in cultured lymphocytes
Authors: Stennard Fiona A. , Stewart Tim C. , West Adrian K. 
Published: October 2006

AbstractExposure to cadmium (Cd) is currently monitored by measurement of the metal in blood or urine, or by observation of excreted compounds such as β2‐microglobulin or N‐acetyl‐β‐D‐glucose. Whilst these approaches are useful for the detection of acute exposure to Cd, their applicability in the management of long‐term, low‐level exposure is less clear. Metallothioneins are ubiquitous proteins that are synthesized in response to heavy metal ions and may offer themselves as being a biologically sensitive indicator of Cd exposure. We have examined both basal and Cd‐induced metallothionein mRNA levels in cultured lymphocytes from groups with different exposures to Cd, attempting to assess their potential as an indicator of Cd exposure and the suitability of such an assay for routine analysis. We found that induced metallothionein mRNA levels, rather than basal mRNA levels, increased in groups known to have received elevated body burdens of Cd, although these increases were not significant between groups. There was, however, a significant correlation between induced metallothionein mRNA levels and urinary β2‐microglobulin. These results suggest that further work on the in vitro lymphocyte response to Cd as a diagnostic tool is warranted.
Isopropanol: Acute vapor inhalation neurotoxicity study in rats
Authors: Gill Michael W. , Burleigh‐Flayer Heather D. , Strother Dale E. , Masten Lawrence W. , McKee Richard H. , Tyler Tipton R. , Gardiner Thomas H. 
Published: October 2006

AbstractFive groups of 25 Fischer 344 rats of each sex were exposed for 6 h to isopropanol vapor at 0, 500, 1500, 5000 or 10000 ppm. Behavioral observations for 10 rats of each sex were made prior to and 1, 6, and 24 h after exposure. Motor activity was evaluated for 15 rats of each sex prior to and immediately following exposure. Exposure to isopropanol caused a spectrum of transient effects indicative of narcosis at 10000 ppm and sedation at 5000 ppm. Prostration or severe ataxia, decreased arousal, slowed or labored respiration, decreased neuromuscular function, hypothermia and loss of reflex function were observed 1 and 6 h after exposure to 10000 ppm isopropanol vapor. Similar, but less severe, alterations were observed in animals in the 5000 ppm exposure group 1 h after exposure. Exposure concentration‐related decreases in motor activity were observed in males and females in the 5000 and 10000 ppm groups and slight decreases in motor activity were observed in males in the 1500 ppm group. Animals in the 1500 and 5000 ppm exposure groups recovered from these motor activity effects within 5 h. Based on this study, exposure of male and female rats to isopropanol vapor produces transient, concentration‐related narcosis and/or sedation at concentrations of 5000 and 10000 ppm and minor decreases in motor activity in males at a concentration of 1500 ppm. The no‐observed‐effect level (NOEL) for this was 500 ppm isopropanol.
An in vitro method for determination of tissue partition coefficients of non‐volatile chemicals such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and estradiol
Authors: Murphy John E. , Janszen Derek B. , Gargas Michael L. 
Published: October 2006

AbstractThe development of an in vitro vial equilibration technique for determining tissue and liquid partition coefficients for non‐volatile chemicals is described. Radiolabeled chemical dissolved in propylene carbonate is equilibrated with tissues or liquid at 37°C in a vial system. The solvent must be essentially immiscible with the test material. The amount of chemical movement to the tissue or liquid is compared to an appropriate reference vial, and tissue or liquid:solvent partition coefficients are calculated.Tissue:solvent values divided by blood:solvent values provide tissue:blood partition coefficients required for developing physiologically based pharmacokinetic models for chemicals. These models are useful for estimating internal tissue doses to assess human risk from exposure to chemicals. Partition coefficients for various rat tissues, 0.9% saline solution and olive oil were determined in this study for radiolabeled 2,3,7,8‐tetrachloro‐dibenzo‐p‐dioxin (TCDD) and for the less fat‐soluble compound, estradiol. The TCDD tissue:propylene carbonate partition coefficients were found to be: blood, 0.091; fat, 17.02; liver, 0.419; brain, 0.632; kidney, 0.305; muscle, 0.408. For estradiol, the tissue:propylene carbonate partition coefficients were: blood, 0.286; fat, 0.169; liver, 1.032; brain, 0.554. The TCDD results compared well with values reported and estimated from a more protracted in vivo approach. Thus, this current technique offers a simpler and time‐saving alternative to in vivo approaches for determining the partition coefficients of non‐volatile compounds.
Evaluation of coal liquids derived from the eds process in carcinogenesis screening tests
Authors: McKee R. H. , Traul K. A. , Przygoda R. T. 
Published: October 2006

AbstractFour process streams derived from the EDSEDS is a designaiton for a direct coal liquefation process and was descriptive of an early stage in process development.
direct coal liquefaction process were evaluated in two in vitro assays to screen for carcinogenic potential: the Salmonella/mammalian microsome mutagenicity assay and the Syrian hamster embryo morphologic transformation assay. Three high boiling liquids (two recycle solvents, nominal boiling range 200–425°C; and a fuel oil blend, nominal boiling range 200–538°C) were active in both assays. A hydrotreated naphtha sample (<200°C) was not active in either. The Salmonella data agreed qualitatively with results of dermal carcinogenesis studies; however, quantitative differences as measured by the estimation of mutagenic potency were apparent. The lack of quantitative agreement may have been related to the fact that the dermal carcinogenic activity of coal‐derived synthetic fuels is predominantly associated with neutral polycyclic aromatic hydrocarbons, whereas activity in the Salmonella assay is strongly influenced by the presence of aromatic amines and nitroaromatic compounds.Two modifications of the Salmonella assay—detergent disperson and hamster S9 activation—were examined. These techniques improved assay performance for some but not all of the coal liquids. The differences in response may have been related to compositional differences in the various liquids.
Ecological hazard assessment of aqueous soil extracts using fetax
Authors: Fort Douglas J. , Stover Enos L. , Norton Dale 
Published: October 2006

AbstractFrog Embryo Teratogenesis Assay—Xenopus (FETAX) testing of a series of diverse hazardous waste‐site soil samples was performed to evaluate the efficacy of FETAX as a rapid developmental toxicity screening tool for environmental hazard assessment. Soil samples were collected from six different hazardous waste sites, three from eastern and three from western Washington State. The type of waste site samples studied, based on the contaminants identified, included: heavy metals (2), polymnuclear aromatic hydrocarbons, petroleum products (2) and organochlorine pesticides. Three to five samples from each site representing baseline and increasing levels of contamination were collected. Aqueous extracts of the soil samples were prepared and used for FETAX studies. Samples collected from the polynuclear aromatic hydrocarbon‐ and petroleum product‐contaminated sites induced greater levels of embryolethal effects, although embryonic malformation was also observed. The metal‐contaminated sites induced greater levels of embryonic malformation, but induced less embryolethality than the other samples evaluated. The organochlorine pesticide‐contaminated site samples caused significant levels of embryonic deformities but failed to induce embryolethal effects. Results from these studies suggested that FETAX was sensitive enough to detect low levels of developmental toxicants but robust enough to be suitable for aqueous soil extract testing. FETAX may be used as a component of a battery of tests designed to assess potential ecological hazard.
Serum biochemical and histopathological changes related to the hepatic function in pigs following atrazine treatment
Authors: Gojmerac T. , Kartal B. , Žurić M. , Ćurić S. , Mitak M. 
Published: October 2006

AbstractBiochemical and histopathological parameters of the hepatic function were used to quantify the hepatotoxic effects of atrazine in female pigs (gilts) undergoing intensive breeding. Female pigs (cross‐bred Swedish and German landrace) received 2 mg atrazine kg−1 body wt. in feed daily during 19 days of the oestrous cycle. The last treatment day corresponded to day ‐3 of the onset of the next expected oestrus: Blood samples were collected three times daily at 3‐h intervals on the first four post‐treatment days. Serum activities of γ‐glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) were determined. Serum activity of GGT was significantly increased throughout the four post‐treatment days. In comparison with the control values, a slight but not significant decrease was observed in the serum activities of ALT, AST and AP. Histopathological examination of the liver of exposed pigs showed mild centrolobular parenchymatous degeneration. Interstitial connective tissue proliferation resulted in narrow and irregular bile canaliculi.
Effect of 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin on the Hepatic Distribution of Iron, Copper, Zinc, and Magnesium in Rats
Authors: Wahba Z. Z. , Al‐Bayati Z. A. F , Stohs S. J. 
Published: October 2006

AbstractThe distribution of iron, copper, zinc, and magnesium in hepatic subcellular fractions of male and female rats treated with 2,3,7,8‐tetrachloro‐dibenzo‐p‐dioxin (TCDD) was determined. Animals received 40 μg TCDD per kilogram per day for three days by mouth (PO) or the vehicle and were killed seven or nine days posttreatment. Iron, copper, zinc, and magnesium were determined by atomic absorption spectroscopy. The iron content of liver from female animals was twofold higher than male animals. The administration of TCDD increased the iron content of mitochondria in female and male rats and decreased iron content of microsomes of both sexes. Significant increases occurred in the copper content of whole liver, mitochondria, and cytosol of male rats and in whole liver and cytosol of female rats. Decreases in the copper content of the microsomes of male rats were observed following TCDD treatment; however, TCDD produced no changes in the zinc content of hepatic subcellular fractions of either sex. The magnesium content of female TCDD‐treated rats increased in whole liver, mitochondria, and cytosol, while the magnesium content of microsomes was not altered. With respect to the subcellular distribution of iron, copper, zinc, and magnesium, TCDD produces differential effects. The altered distribution of some cations may contribute to the broad range of effects of TCDD.
Purification of rat liver microsomal cytochrome P‐450b without the use of nonionic detergent
Authors: Dutton David R. , McMillen Susan K. , Parkinson Andrew 
Published: October 2006

AbstractSodium cholate, Emulgen 911, and (3‐[(‐cholamidopropyl)‐dimethyl‐ ammonio]‐1‐propanesulfonate) (CHAPS) were selected to examine the effects of ionic, nonionic, and zwitterionic detergents on testosterone hydroxylation catalyzed by four purified isozymes of rat liver microsomal cytochrome P‐450, namely P‐450a, P‐450b, P‐450c, and P‐450h, in reconstituted systems containing optimal amounts of dilauroylphosphatidylcholine and saturating amounts of NADPH‐ cytochrome P‐450 reductase (reductase). The major phenobarbital‐inducible form of rat liver microsomal cytochrome P‐450, designated P‐450b, was extremely sensitive to the inhibitory effects of Emulgen 911, which is used in several procedures to purify this and other forms of cytochrome P‐450. In contrast, sodium cholate and CHAPS had little effect on the catalytic activity of cytochrome P‐450b, even at ten times the concentration of Emulgen 911 effecting 50% inhibition (IC‐50). By substituting the zwitterionic detergent CHAPS for Emulgen 911, we purified cytochrome P‐450b without the use of nonionic detergent. The protein is designated cytochrome P‐450b* to distinguish it from cytochrome P‐450b purified with the use of Emulgen 911. NADPH‐cytochrome P‐450 reductase was also purified both with and without the use of nonionic detergent.The absolute spectra of cytochrome P‐450b and P‐450b* were indistinguishable, as were the carbon monoxide (CO)‐ and metyrapone‐difference spectra of the dithionite‐reduced hemoproteins. When reconstituted with NADPH‐cytochrome P‐450 reductase and dilauroylphosphatidylcholine, cytochromes P‐450b and P‐450b* catalyzed the N‐demethylation of benzphetamine and aminopyrine, the 4‐hydroxylation of aniline, the O‐dealkylation of 7‐ethoxycoumarin, the 3‐hydroxylation of hexobarbital, and the 6‐hydroxylation of zoxazolamine. Both hemo‐proteins catalyzed the 16α‐ and 16β‐hydroxylation of testosterone, as well as the 17‐oxidation of testosterone to androstenedione. Both hemoproteins were poor catalysts of erythromycin demethylation and benzo[a]pyrene 3‐/9‐hydroxylation. The rate of biotransformation catalyzed by cytochrome P‐450b* was up to 50% greater than the rate catalyzed by cytochrome P‐450b when reconstituted with either reductase or reductase*. The activity of cytochrome P‐450b and P‐450b* increased up to 50% when reconstituted with reductase* instead of reductase. In addition to establishing the feasibility of purifying an isozyme of rat liver microsomal cytochrome P‐450 without the use of nonionic detergent, these results indicate that the catalytic activity of cytochrome P‐450 is not unduly compromised by residual contamination with the nonionic detergent Emulgen 911.
A study on the recovery of xylitol by batch adsorption and crystallization from fermented sugarcane bagasse hydrolysate
Authors: Mussatto Solange I , Santos Júlio C , Ricardo Filho Walter C , Silva Silvio S 
Published: October 2006

AbstractXylitol was recovered from fermented sugarcane bagasse hemicellulosic hydrolysate by adsorption and crystallization procedures. Silica gel adsorption was employed to purify the broth containing xylitol. In this step, different mixtures of the solvents ethyl acetate, ethanol and acetone were used as eluent, and different proportions of fermented broth volume incorporated per gram of silica gel (Vb/Msg, varying from 1.0 to 2.0 cm3 g−1) were used to pack the column employed as stationary phase bed. The xylitol purification efficiency varied for each mixture of solvent, and for each Vb/Msg ratio used. The purified broth was submitted to different crystallization procedures (cooling, concentration and supplementation with commercial xylitol) aiming to recover xylitol crystals. The best result (60% crystallization yield and 33% total recovery of xylitol from fermented broth) was obtained when the column was packed with a Vb/Msg ratio of 2 cm3 g−1, and the broth was purified with a mixture of ethyl acetate and ethanol, concentrated 6.5‐fold, and supplemented with commercial xylitol to force the precipitation. Copyright © 2006 Society of Chemical Industry
Novel Molecular Resist Based on a First Generation Dendrimer Possessing Furan Rings
Authors: Mori Hajime , Nomura Eisaku , Hosoda Asao , Miyake Yasuhito , Taniguchi Hisaji 
Published: October 2006

AbstractSummary: A novel chemically amplified negative‐tone molecular resist for electron‐beam (EB) lithography was developed. The base matrix had six furan rings as a reactive functional group at its terminal. The resist containing the matrix, a crosslinker and a photoacid generator worked well as a negative‐tone resist with high sensitivity (3 µC · cm−2). Line and space patterns (1:2) of 200 nm could be fabricated.SEM image of negative‐tone line and space patterns for the resist film formulated with G1‐dendrimer 5.magnified imageSEM image of negative‐tone line and space patterns for the resist film formulated with G1‐dendrimer 5.
Modelling and numerical analysis of heat treatments on aluminium parts
Authors: Andrade‐Campos A. , Neto da Silva F. , Teixeira‐Dias F. 
Published: October 2006

AbstractA theoretical model suitable for the modelling and analysis of heat treatment problems is described. The presented formulations are implemented incrementally with a non‐linear rate‐dependent constitutive model, adequate to the simulation of a wide range temperature processes. The large deformation model is based on the additive decomposition of the strain rate tensor in elastic, thermal and viscoplastic parts. The flow rule is a function of the equivalent stress and the deviatoric stress tensor of the temperature field and of a set of internal state variables. The thermal problem is solved by a prediction/correction algorithm. The prediction, which uses a semi‐implicit integration, provides a first estimation of the temperature field. The correction stage, performed with a Newton–Raphson implicit scheme, improves the solution until a satisfactory result is found. The thermomechanical coupled problem is solved with a staggered approach. The finite element formulations for coupled analysis of deformation and heat transfer given in this article are validated and applied to the process of quenching of aluminium parts into boiling water. Copyright © 2006 John Wiley & Sons, Ltd.
Experience of a premarketing alert
Authors: East M. O. 
Published: October 2006

AbstractA very effective and well‐tolerated beta‐blocking agent was withdrawn from preregistration clinical development because a pattern of endocrine‐related tumours was observed in high‐dose, long‐term studies in rodents. The use of doses of up to 90 times the maximum dose in man was the result of regulatory agency insistence at that time that the maximum dose tolerated by the rodents must be used. In addition, the relevance of the differences between genotoxic and non‐genotoxic carcinogenicity to man was not fully understood or accepted. More appropriate criteria are now used to select dose levels in long‐term rodent studies, and the relevance of the differences in carcinogenicity is accepted.
Nomifensine and hemolytic anemia — experience of a post‐marketing alert
Authors: Stonier Peter D. 
Published: October 2006

AbstractThe antidepressant nomifensine was withdrawn worldwide by the manufacturer in January 1986 following a rising incidence of reports of acute immune hemolytic anemia with serious clinical sequelae, including a number of fatalities. This short report describes the chronology of events leading up to the drug's withdrawal in one country, the United Kingdom, 9 years after it was first made available. The known incidence of hemolytic anemia reports was related to prescription data and showed that the risk‐benefit ratio was tipped against continued availability of the drug only in the latter part of 1985, shortly before the drug was withdrawn. Factors related to the increased reporting of the adverse events are discussed, but increased awareness by prescribers of drug‐related events and their willingness to report them as a result of medical literature and media reports, including publications by the Committee on Safety of Medicines of Yellow Card data, are thought to have been major contributors.
The determinants of warfarin requirements in Chinese patients
Authors: Chan Thomas Y. K. , Tsoi W. C. , Critchley Julian A. J. H. 
Published: October 2006

AbstractThe warfarin requirements of 33 Chinese patients presenting with deep vein thrombosis and/or pulmonary thromboembolism were studied. The mean daily maintenance dosage was considerably lower in Chinese (3 mg) than in Caucasian subjects (4–6 mg) and, as in Caucasian subjects, the age of the patient rather than body weight was an important determinant of warfarin requirements (r = 0.4, p < 0.05).
PEM report number 6. Paroxetine
Authors: Inman William , Kubota Kiyoshi , Pearce Gillian , Wilton Lynda 
Published: October 2006

AbstractPatients (13,741) who had been treated with paroxetine between March 1991 and March 1992 have been, studied by Prescription‐Event Monitoring (PEM). The events were compared with those recorded in studies of two other selective serotonin re‐uptake inhibitors (SSRIs) and with data from 31 PEM studies of unrelated drugs.The most frequent indication was depression (94%). A daily dose of 20 mg was prescribed most frequently (93%). Benzodiazepines had been co‐prescribed for 9% of the patients. Treatment was considered to have been effective in 62% of patients.The rates of events occurring during the first‐month of treatment were compared with the mean rates recorded during the second to the sixth month of treatment. The analysis was restricted to those events which had been experienced by 14 or more patients during the first month of treatment (rates in excess of one per 1000). A ‘signal’ was noted when this rate exceeded the second‐to‐sixth‐month rate by a factor of three or more or when the first‐month rate exceeded a pooled base‐rate for other drugs by a similar amount. All the data were compared with those obtained in earlier studies of the two SSRIs fluoxetine and fluvoxamine.Although a number of class effects were signalled, the only noteworthy difference between paroxetine and the other two SSRIs was the rate of male sexual dysfunction which was higher for paroxetine. Several psychiatric events were recorded with greater than average frequency than in the population of 350,000 patients used for comparison, but these are all commonly associated with depressive illness. Drowsiness, insomnia and tremor were prominent side‐effects with all three drugs.Particular attention was paid to events occurring shortly after withdrawal of paroxetine, but again, no obvious difference was detectable between these events in the three groups. This supports the view that more frequent use of the word ‘withdrawal’ may have resulted from recent publicity given to dependence, especially to benzodiazepines.Small numbers of events of potential interest such as of disturbances of liver function, hyponatraemia, extrapyramidal signs or symptoms or convulsions were reviewed individually but no unacceptable hazards were detected.One hundred and thirty‐seven pregnancies were followed up and no attributable abnormalities were noted.There were 416 deaths (3%) at any time during the course of the study, of which 224 occurred during the six‐month period used in comparisons with other drugs. No deaths were atttributable to paroxetine.