bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of benzophenone‐3 after oral exposure in male rats
Authors: Kadry Abdelrazak M. , Okereke Chukwuemeka S. , Abdel‐Rahman Mohamed S. , Friedman Marvin A. , Davis Richard A. 
Published: October 2006

AbstractBenzophenone‐3 (BZ‐3) is one of the UV‐absorbing agents that has been used in industry and medicine for more than 30 years. Millions of consumers are exposed to benzophenones on a daily basis owing to the widespread use of these compounds in many of the products on the market, such as lipsticks, hair sprays, hair dyes, shampoo and detergent bars and sunscreen lotions. This study was performed to investigate the pharmacokinetics of BZ‐3 after oral administration at 100 mg kg−1 body weight in male Sprague‐Dawley rats. Absorption from the gastronintestinal tract was rapid because BZ‐3 was detected in blood 5 min after administration. The peak plasma concentration (Cmax) was 25.6 ± 4.6 μg ml−1 and the time of occurrence (tmax) was 3.0 ± 0.4 h. The half‐life of absorption of BZ‐3 was 0.71 h. The elimination pattern was biphasic with α and β half‐lives of elimination of 0.88 and 15.90 h, respectively. The results of this study indicate the presence of strong binding between the plasma protein and BZ‐3.Tissue distribution studies at 6 h indicate that the liver contained the highest concentration of free (58.9 ± 23.8 μg) and total (free + bound or conjugated) BZ‐3 (2087 ± 60.1 μg), followed by kidney and testes, respectively.Urine and feces analysis indicate that urine was the major route of excretion, followed by feces. Further analysis of urine samples also indicates that conjugation of BZ‐3 with glucuronic acid was the major systemic elimination route for the compound.
Evaluation of the toxicity of several heavy metals by a fluorescent bacterial bioassay
Authors: Mariscal Alberto , García Antonio , Carnero Manuel , Gómez Jorge , Pinedo Alfonso , Fernández‐Crehuet Joaquín 
Published: October 2006

AbstractThis new bioassay determined the toxicity of chemical compounds dissolved in water by measuring the degree of inhibition of the ultraviolet light‐stimulated fluorescence of Escherichia coli in a culture medium in which 4‐methylumbelliferyl β‐D‐glucuronide was the only carbon source. Inhibition produced by one of five heavy‐metal salts (Cd2+, Cr6+, Hg2+, Pb2+ or Zn2+) was the end‐point and comparison standard to determine the EC50 and minimum effective concentration (MEC) that produced a decrease of E. coli growth rate, increased doubling time and percentage inhibition and reduced numbers of generations; all these values were derived from the fluorescence signals. Only Cr6+ and Hg2+ at two concentrations (0.25 and 0.5 mg I−1) almost completely inhibited this E. coli strain. All toxicant concentrations tested produced at least partial inhibitions of growth; Cr6+, Hg2+ and Cd2+, in that order, were most toxic, and Pb2+ the least. Zn2+ gave higher EC50 values at 3 h of incubation than at 4 h. The method was simple, rapid and inexpensive and would permit a large number of samples to be tested quickly.
Reduction of erythema in hairless guinea pigs after cutaneous sulfur mustard vapor exposure by pretreatment with niacinamide, promethazine and indomethacin
Authors: Yourick Jeffrey J. , Dawson Jeffrey S. , Mitcheltree Larry W. 
Published: October 2006

AbstractErythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD‐induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin and promethazine used alone or in all possible combinations on the degree of erythema and histopathologic skin damage after HD exposure in HGP. Niacinamide (750 mg kg−1, i.p.), promethazine (12.5 mg kg−1, i.m.) or indomethacin (4 mg kg−1, p.o.) used singly or in combination was given as a 30‐min pretreatment before an 8‐min HD vapor cup skin exposure. Using a combination pretreatment of niacinamide, promethazine and indomethacin, erythema was reduced at 4 (91%) and 6 (55%) h, but not 24 h after HD. The incidence of histopathological skin changes (microvesicles, follicular involvement, epidermal necrosis, intracellular edema and pustular epidermatitis) 24 h after HD was not reduced. This study indicates that HD‐induced erythema may result from several different mechanisms, including inflammation, histamine release and DNA damage. It is suggested that two phases of inflammation may occur: an early phase sensitive to antihistamines and non‐steroidal antiinflammatory drugs and a late phase of extensive cell damage that was not sensitive to these drug pretreatments.
Topical anesthetic‐induced methemoglobinemia and sulfhemoglobinemia in macaques: A comparison of benzocaine and lidocaine
Authors: Martin Dale G. , Watson Charles E. , Gold Mark B. , Woodard Claude L. , Baskin Steven I. 
Published: October 2006

AbstractBenzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics approved for use in humans. Benzocaine has structural similarities to methemoglobin (MHb)‐forming drugs that are current candidates for cyanide prophylaxis, while LC has been reported to increase MHb in man. In this study, we compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques (Chinese rhesus and Indian rhesus (Macaca mulatta) and pig‐tailed macaques (Macaca nemestrina)) after exposure to BNZ and LC. Formation of SHb, unlike MHb, is not thought to be reversible and therefore is considered to be of greater toxic significance. Both MHb and SHb levels were measured periodically on a CO‐Oximeter. All rhesus macaques (n= 8) were administered an intratracheal/intranasal) dose of 56 mg (low dose) or 280 mg (high dose) of BNZ or 40 mg of LC in a randomized cross‐over design (all animals received all three treatments). Pig‐tailed macaques (n= 6) were given an intranasal dose of 56 mg of BNZ and 40 mg of LC. As no differences in the peak MHb or time to peak (mean ± SD) were observed among the three macaque subspecies, the data were pooled. Lidocaine did not cause MHb or SHb formation above baseline in any monkey. In contrast, all monkeys (n= 14) had a significant elevation in peak MHb formation after 56 mg of BNZ, which ranged from 4.0% to 19.4% with an average of 8.6 ± 4.0% (mean ± SD), with peak MHb levels reached at 30 min. The monkeys given the high dose of BNZ (n= 8) demonstrated higher peak MHb levels (P< 0.05) than the lower dose of BNZ: 14.7 ± 6.5% (mean ± SD) as the time to peak increased to 45 min. Slight increases in SHb levels (0.02–0.04 mm 1−1rise) measured (P< 0.05) after low and high BNZ doses were 54% and 75% higher than baseline SHb levels after LC. This study indicates that benzocaine applied topically in non‐human primates can readily increase MHb concentrations within 30 min to clinically relevant levels required for cyanide prophylaxis, but LC does not. The variability in the peak Hb levels after BNZ is likely to be due to the variability in absorption and/or metabolism of the drug. In addition, the slight increase in SHb seen in BNZ groups should prompt investigators to also evaluate this toxic Hb component when evaluating MHb‐forming drugs.
Factors affecting the bioavailability of benzo[a]pyrene from oils in mouse skin: Oil viscosity, grooming, activity and its prevention
Authors: Ingram A. J. , Lee R. , Phillips J. C. 
Published: October 2006

AbstractIn the main study, tritium‐labelled benzo[a]pyrene ([3H]BaP) was added to oils of a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40°C) and these were applied once to mouse skin under conditions where grooming was either allowed or prevented. The binding of [3H]BaP to epidermal protein and DNA was assessed. In addition, some studies were conducted to investigate the effect of prior oil exposure on binding levels and to compare binding levels following single and multiple application.It was found in the main study that the binding of [3H]BaP to both DNA and protein was increased as the viscosity of the oil vehicle decreased. Whereas only a twofold difference in DNA binding was found between the lowest and highest viscosity oil vehicle if grooming was allowed, a 14‐fold difference was seen if grooming was prevented. This was due to much higher binding levels with low viscosity oils when grooming was prevented. Protein binding showed similar results, although the difference between the grooming and non‐grooming situations was slightly less. Whether grooming was prevented or not, both DNA and protein binding of [3H]BaP were found to be inversely proportional to the logarithm of viscosity of the oil vehicle, but when grooming was prevented, the slope for DNA binding was 10 times steeper than when it was permitted.Exposure of the skin to either high or low viscosity oils prior to the application of [3H]BaP in the same oil inhibited the binding to DNA but not to protein. In experiments where multiple applications of [3]BaP in oil were given, the difference in DNA binding between low and high viscosity oils was similar to that after a single application. This implied that the relative bioavailability of polycyclic aromatic hydrocarbons from oils of differing viscosity, as assessed following single application, is reasonably predictive of that following multiple applications.In considering the relevance of the findings of the main study to long‐term animal studies and to human hazard, it is suggested that the situation where grooming was permitted is likely to be most relevant to animal studies, whereas that where grooming is prevented is more likely to represent human exposure. Hence, borderline positive findings in long‐term mouse skin painting studies with low‐viscosity oils should be regarded more seriously than similar findings with viscous oils. The findings should also be of assistance in making predictions of carcinogenicity from analytical data.
Dermal absorption of polycyclic aromatic hydrocarbons in the blood‐perfused pig ear
Authors: Vanrooij J. G. M. , Vinke E. , De Lange J. , Bruijnzeel P. L. B. , Bodelier‐Bade M. M. , Noordhoek J. , Jongeneelen F. J. 
Published: October 2006

AbstractUrinary 1‐OH‐pyrene, a metabolite of pyrene, is a sensitive biological marker for dermal absorption of pyrene in man. In order to determine whether this metabolite is a reliable biomarker of cutaneous absorption of other polycyclic aromatic hydrocarbons (PAHs), the blood‐perfused pig ear model was used to compare the dermal absorption flux of pyrene with nine other PAHs after coal tar application. Cumulative absorption of PAHs into the perfusion blood, 200 min after application of an overdose of coal tar, ranged between 830 pmol cm−2 for phenanthrene to less than 4 pmol cm−2 for benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[ah]anthracene and indeno[123‐cd]pyrene. The results of this study show that when pyrene is used as a marker compound for PAH absorption through pig skin, the cumulative absorption of PAHs with a lower molecular weight will be underestimated: fluorene, tenfold; phenanthrene, 12‐fold; anthracene and fluoranthene, ca. twofold. The percutaneous absorption of PAHs with a higher molecular weight than pyrene will be overestimated: e.g. benzo[a]pyrene, sevenfold; indeno [123‐cd]pyrene, ca. 100‐fold. It is likely that this conclusion is also valid for dermal PAH absorption in man.
Effect of s‐triazine compounds on testosterone metabolism in the rat prostate
Authors: Kniewald J. , Osredečki V. , Gojmerac T. , Zechner V. , Kniewald Z. 
Published: October 2006

AbstractThe influence of s‐triazine compounds (atrazine, prometryne and deethylatrazine) on testosterone conversion and 5α‐dihydrotestosterone–receptor complex formation was studied in vitro and in vivo in the rat prostate. A marked in vitro influence of atrazine and prometryne (from 0.465 to 1.392 μmol) and their mixtures (in total concentration, 0.928 μmol) on 5α‐dihydrotestosterone formation was detected. 5α‐Dihydrotestosterone‐specific receptor complex formation was inhibited in vitro by ca. 0.5 μmol of atrazine or deethylatrazine and only in vivo by 6 mg of atrazine 100 g−1 body wt. daily during 7 days in the prostate cytosol. The inhibition of the enzymic activities responsible for testosterone conversion and steroid hormone–receptor complex formation was non‐competitive and reversible, and s‐triazine compounds act as antiandrogens.
Disturbances in rat smooth‐muscle induced by a substance with fungicide action
Authors: Milieva E. , Kristev A. , Stoichev N. , Nikolov A. , Nikolov N. 
Published: October 2006

AbstractThe fungicide substance QAS [N, N, N', N'‐tetramethyl‐N,‐N'‐di(8,15‐dichloropentadeca‐5,10‐dien)ethylenediamine methylsulphate] has a biphasic effect on the spontaneous electrical and mechanical activity of smooth‐muscle samples of rat corpus and guinea‐pig taenia coli.During the first phase of QAS application membrane depolarization and increased spontaneous spike frequency were recorded. The tone of the preparations (resting tone) increased transiently. Calcium ion‐entry blockers did not affect the contractile effect of QAS, but K+‐channel blockers and some modulators of the second messenger system abolished or decreased it.During the second phase depolarization increased progressively, spike frequency decreased and the increase in resting tone recorded during the first phase was eliminated.The results reveal that the long‐lasting depolarizing effect of QAS (in concentrations used for plant protection) probably inactivates the entry of Ca2+ into the smooth‐muscle cells and disturbs Ca2+ homeostasis.
Toxicological evaluation of μ‐agonists. Part II: Assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo‐alpha‐noracetylmethadol hcl (norlaam)
Authors: Borzelleca Joseph F. , Egle John L. , Harris Louis S. , Belleville Jo Ann Nuite 
Published: October 2006

AbstractThis study evaluated levo‐alpha‐noracetylmethadol (NorLAAM), the first N‐demethylated metabolite of levo‐alpha‐acetylmethadol (LAAM), a long‐acting morphine‐like (μ) agonist, approved in 1993 to treat opiate dependence. After acute and 7‐day pilot studies to define dose levels appropriate for use in longer term evaluations, Sprague‐Dawley rats (20 of each sex per group) were gavaged with doses of 4.4–25.9 mg kg−1 day−1 for 30 days followed by a 14‐day recovery period. Treatment‐related effects included dose‐dependent CNS depression paralleled by changes in food consumption, body weight gain and fecal output, as well as reddish urine and abdominal staining. Tolerance developed by day 7. The spectrum of activity observed differed from the parent compound primarily in its time course. Cage‐biting and gnawing behavior were observed only with NorLAAM. Mortality was dose‐dependent, with deaths occurring predominantly during the first week. At day 30, all male‐treated groups exhibited statistically significant, dose‐dependent decreases in body weight gain and increases in serum cholesterol that returned to the control range following recovery. Increases in brain/body weight and testes/body weight ratios and decreases in kidney/brain, liver/brain, spleen/brain and heart/brain ratios, as well as decreases in kidney, liver, spleen and heart absolute weights, achieved statistical significance only for males. At terminal sacrifice, histological findings in the kidneys included increased incidences of tubular mineral deposition in mid‐ and high‐dose groups of both sexes and of corticomedullary mineral deposition in females. Hepatic centrilobular hypertrophy was evident in male and female mid‐ and high‐dose groups. Histopathological changes abated following the recovery period. In summary, acute and repeated administration of NorLAAM produced a pharmacodynamic profile commensurate with its role as the primary N‐demethylated metabolite of LAAM, which is more potent and less lipophilic than the parent compound; this was reflected in the toxicological outcomes observed. Like LAAM, NorLAAM's overall pattern of activity is consistent with its activity as a μ‐agonist, which stimulates hepatic microsomal enzymes in rodents.
Altered activation/detoxication enzymology following neonatal diethylstilbestrol treatment
Authors: Lamartiniere Coral A. , Pardo Guillermo A. 
Published: October 2006

AbstractThe effects of neonatal exposure to diethylstilbestrol (DES) on hepatic activation/detoxication enzyme levels in the adult rat were investigated. Neonatal exposure of male rats to DES (DES males) decreased the endogenous levels of UDP‐glucuronyltransferase as compared to control males. Female rats exposed neonatally to DES (DES females) had higher endogenous epoxide hydrolase and glutathione transferase activity levels than control females. Adult animals treated neonatally with DES also had altered metabolic potential following exposure to 3‐methylcholanthrene and phenobarbital. The DES males treated in adulthood with 3‐methylcholanthrene had higher benzo(a)pyrene hydroxylase activities and lower UDP‐glucuronyltransferase activity levels than did control males treated in adulthood with 3‐methylcholanthrene. The DES males exposed in adulthood to phenobarbital had reduced cytochrome P‐450 and glutathione transferase activity levels as compared with respective controls. The DES females treated in adulthood with 3‐methylcholanthrene had lower benzo(a)pyrene hydroxylase and epoxide hydrolase activity levels than control females receiving 3‐methylcholanthrene. The DES females challenged in adulthood with phenobarbital also had decreased benzo(a)pyrene hydroxylase, epoxide hydrolase, UDP‐ glucuronyltransferase, and glutathione transferase activity levels as compared with respective controls. Our results demonstrated that neonatal exposure to DES changed the endogenous levels of specific hepatic enzymes and altered the metabolic response of these adult animals to a carcinogen and a drug.
Germ cell depletion does not alter the morphogenesis of the fetal testis or ovary in the red‐eared slider turtle (Trachemys scripta)
Authors: Dinapoli Leo , Capel Blanche 
Published: October 2006

AbstractIn the red‐eared slider turtle, Trachemys scripta, both prospective male and female gonads contain primitive cord structures at the time when the gonad first forms. Primordial germ cells arrive in the gonad and accumulate on the coelomic surface. If testis development is initiated, these cords develop further at the same time that germ cells migrate from the coelomic surface and become sequestered in the interior of the cords. In contrast, in the developing ovary germ cells proliferate in a defined cortical domain, while the primitive cords regress and form flattened lacunae in the medulla. Because of their intimate association with these developmental processes, we investigated whether germ cells were required in turtles to establish the morphology of the fetal testis and ovary. We present evidence that normal morphological development of the fetal gonad occurs in both sexes in T. scripta after germ cell depletion, suggesting a conservation of developmental mechanisms across vertebrates. J. Exp. Zool. (Mol. Dev. Evol.) 308B:236–241, 2007. © 2006 Wiley‐Liss, Inc.
Managers on flexibility and innovation: are Porter's assumptions on leadership right? An empirical exploration
Authors: Kasper Helmut , Mühlbacher Jürgen 
Published: October 2006

Abstract

This paper is based on an empirical test of Porter's strategic model of role allocation between top and middle management. The empirical results show that in future both hierarchy levels favour flexibility instead of innovation. Although this tendency makes sense from a practitioner's point of view, it is completely inconsistent with the sustainable development of a company. Only a balance between flexibility and sufficient stability makes a company successful. Therefore managers have to find a fit between creativity, innovation and speed with clarity of focus, co‐ordination and control.
The authors recommend putting the anticipated change on a company's agenda as soon as possible. Only this will ensure the development of targeted qualification programmes and a future‐oriented distribution of competencies and responsibilities, within the framework of strategic HRM well before the first conflicts within companies occur.

Copyright © 2006 John Wiley & Sons, Ltd.
A rational elasto‐plastic spatially curved thin‐walled beam element
Authors: Pi Yong‐Lin , Bradford Mark Andrew , Uy Brian 
Published: October 2006

AbstractTorsion is one of the primary actions in members curved in space, and so an accurate spatially curved‐beam element needs to be able to predict the elasto‐plastic torsional behaviour of such members correctly. However, there are two major difficulties in most existing finite thin‐walled beam elements, such as in ABAQUS and ANSYS, which may lead to incorrect predictions of the elasto‐plastic behaviour of members curved in space. Firstly, the integration sample point scheme cannot capture the shear strain and stress information resulting from uniform torsion. Secondly, the higher‐order twists are ignored which leads to loss of the significant effects of Wagner moments on the large twist torsional behaviour. In addition, the initial geometric imperfections and residual stresses are significant for the elasto‐plastic behaviour of members curved in space. Many existing finite thin‐walled beam element models do not provide facilities to deal with initial geometric imperfections. Although ABAQUS and ANSYS have facilities for the input of residual stresses as initial stresses, they cannot describe the complicated distribution patterns of residual stresses in thin‐walled members. Furthermore, external loads and elastic restraints may be applied remote from shear centres or centroids. The effects of the load (and restraint) positions are important, but are not considered in many beam elements. This paper presents an elasto‐plastic spatially curved element with arbitrary thin‐walled cross‐sections that can correctly capture the uniform shear strain and stress information for integration, and includes initial geometric imperfections, residual stresses and the effects of the load and restraint positions. The element also includes elastic restraints and supports, which have to be modelled separately as spring elements in some other finite thin‐walled beam elements. Comparisons with existing experimental and analytical results show that the elasto‐plastic spatially curved‐beam element is accurate and efficient. Copyright © 2006 John Wiley & Sons, Ltd.
A fast high‐resolution algorithm for linear convection problems: particle transport method
Authors: Smolianski A. , Shipilova O. , Haario H. 
Published: October 2006

AbstractThe paper is devoted to a novel explicit technique, the particle transport method (PTM), for solving linear convection problems. While being a Lagrangian (characteristic based) method, PTM has the advantage of Eulerian methods to represent the solution on a fixed mesh. The proposed approach belongs to the class of monotone high‐resolution numerical schemes, possesses the property of unconditional stability and works with structured and unstructured meshes. It is also demonstrated that the method has a linear computational complexity. The performance of the presented algorithm is tested on one‐ and two‐dimensional benchmark problems. The numerical results confirm that the method has the 2nd‐order spatial accuracy and can be significantly faster than the grid‐based methods of the same order. Copyright © 2006 John Wiley & Sons, Ltd.