bluuebunny/crossref_metadata_2025 huggingface dataset:
Analogien in Physik und Technik im 19. und 20. Jahrhundert
Authors: Kaiser Walter
Published: October 2006

In this paper the use of analogies in physics and in technology is analysed. First the important role philosophically deep rooted analogies played in romantic physics is discussed. The work of Schelling and Ritter is treated in particular. Second the mechanical analogue models in the kinetic theory of gases and in electrodynamics are examined, as well as the severe philosophical criticism which they received. A sketch of the theory of the electron gas is presented as an example for the success and the shortcomings of analogue models. Finally mechanical and electric analogue models in technology are considered; moreover biological analogies in engineering research, and the principle of similitude as applied to model experiments in shipbuilding are discussed. The analysis of the historical examples shows that in the 19th and 20th century the word “analogy” is no longer a vague notion. It represents a scientific method, which, however, inevitably leads to both an extension of the original theoretical models and to special theories of mapping.
Analogie und mathematisches Denken
Authors: Knobloch Eberhard
Published: October 2006

This article deals with six aspects of analogical thinking in mathematics: 1. Platonism and continuity principle or the “geometric voices of analogy” (as Kepler put it), 2. analogies and the surpassing of limits, 3. analogies and rule stretching, 4. analogies and concept stretching, 5. language and the art of inventing, 6. translation, or constructions instead of discovery. It takes especially into account the works of Kepler, Wallis, Leibniz, Euler, and Laplace who all underlined the importance of analogy in finding out new mathematical truth. But the meaning of analogy varies with the different authors. Isomorphic structures are interpreted as an outcome of analogical thinking.
Neue Wege der Forschung, ihrer Organisation und ihrer Förderung: Friedrich Schmidt‐Ott (4. 6. 1860–24. 4. 1956)
Authors: Treue Wolfgang
Published: October 2006

From 1888–1907 Friedrich Schmidt‐Ott was Althoffs closest collaborator in the Prussian ministry for cultural affairs. It was he whom Althoff let participate in all his endeavours to give German science and scholarship a heading position in the world. After Althoff's death he and Harnack developed further and realized his plans for the foundation of the Kaiser Wilhelm Society – today the Max Planck Society. Schmidt‐Ott had recognized already very early that – after the breakdown in 1918 – Germany would have to mobilize her scientific potential to the utmost. In the completely changed political environment it was his idea to transfer important functions to self‐responsibility and self‐government and hereby keeping them away from the influence of political parties. Following his suggestion, all academic institutions of higher education and academies joined together in the Notgemeinschaft der deutschen Wissenschaft, a self‐governing organization. This organization was supposed to have a central role in research funding and to develop entirely new methods in research promotion and financing. For Schmidt‐Ott, the president of the Notgemeinschaft, the promotion of young academics, interdisciplinary co‐operation and the overcoming of isolation were of foremost importance. The National socialists forced Schmidt‐Ott 1934 to leave office. But his idea, inspite of the short period, had promised good and turned out to be a remarkable success. After the second world war, in 1949, the Notgemeinschaft was refounded. Again the most important tasks were the promotion of young academics, the end of isolation and the development and financing of new research methods. To‐day this institution – since 1951 the Deutsche Forschungsgemeinschaft – is the central self‐governing organization of academic institutions for the promotion of research in the Federal Republik of Germany. It has – with great success – developed further the work of its honorary president Schmidt‐Ott, who died in 1956.
Thesen zur Preußischen Wissenschaftspolitik gegen Ende des Wilhelminischen Zeitalters
Authors: Rasch Manfred
Published: October 2006

Prussian science during the second half of the Wilhelminian Age was confronted with the problem that research in the natural sciences was increasing substantially while at the same time state finances were at a low ebb. In order to finance new academic disciplines and to help German science gain and retain international recognition, the Ministry of Education and the Arts renounced the monopoly it had held so far in the almost exclusively government – supported promotion of science. The novel course adopted by the Prussian Ministry of Education and the Arts, especially by its members Friedrich Althoff and Friedrich Schmidt‐Ott, can most adequately be described as “promotion of the sciences under the control of local authorities” and “central administration of private contributions and donations for scientific purposes”. “Promotion of the sciences under the control of local authorities” signifies the foundation of research institutes and universities, which had taken place under municipal government auspices since the turn of the century. For the purpose of “central administration of private contributions and donations” and channeling these financial means into select projects, the Prussian Ministry of Education and the Arts initiated the foundation of the Kaiser Wilhelm‐Gesellschaft zur Förderung der Wissenschaften.
Wissenschaft — Mathematik — Technik: Ihre Wechselwirkung in der Antike
Authors: Krafft Fritz
Published: October 2006

The question whether there exists an interaction between ‘science’ (foreign text ignored) and ‘technology’ (foreign text ignored, esp. foreign text ignored) in Greek and Roman antiquity is discussed controversially until today. Especially representatives of the philologies strictly deny any form of relation, whereas modern scientists tend to take for granted that the current interaction between (exact) natural sciences and technology has always existed, at least since the beginning of real natural science founded by the ancient Greeks.

This paper shows that both parties are right — at least in a certain way. Following current terminology and contents of ‘science’ and ‘technology’ there had been such an interaction — particularly with mathematics as linking element in so far as in antiquity especially foreign text ignored (mechanics) was regarded as applied mathematics and not as science. The strong interaction between pure mathematics and such fields of applied mathematics (namely mechanical technology) based on the fact that technological (mechanical) artefacts were properly constructed mathematically. Some of them are mentioned in this paper (astrolabes and sundials, waterclocks, tools and machines — especially lifting gears, bucket elevators, guns, pneumatic tools —, architecture of temples); in so far the supporters of an interaction between science and technology are right. However, the post‐Aristotelian Greeks and Romans did not consider mathematics to be part of ‘science (of nature)’ as the post‐kantian exact scientists do. Mathematics to them was a mere ‘art’ — consequently, in the mentioned cases there had been an interaction between ‘arts’ and of course not between ‘science’ and ‘art’ (technology); and in so far those are right who deny an interaction between natural science and technology.

This shows that the contrariety of the answers to the question depends on the different terminology chosen. Following the current understanding of ‘exact natural science’ the answer is: yes; following the conception of ‘science’ in the self‐understanding of Greek and Roman antiquity the answer is: no — and this is right as well! The reason for this apparent contrariety are just the different meanings and contents of ‘science (of nature)’ in antiquity and modern times.
Mittlere technische Bildung im deutschen Kaiserreich
Authors: Weber Wolfhard
Published: October 2006

Intermeriate organisations between two extremes tend to have a stressed life because of their adjusting character. Intermediate technical education in Prussia existed from 1821 to 1876 enabling graduates either to go to the Berlin Gewerbeakademie or to start a business on their own. This fell a victim when the bourgoisie striving for emancipation by education (and the association of the German mechanical engineers, VDI) insisted on the highest possible school‐degree as entry for students of technology. Reports on the positive experience in Switzerland, political considerations to integrate the able workers into the middle classes, local and regional economic interests as well as competition between the ministries of education and commerce from 1890 on resulted in a slow and then rapid extension of intermediate technical education, all this against the massive protests of the engineering professions.

Establishing the Landesgewerbeamt and the DATSCH, who embraced all German (and even more German speaking representatives of) technical high schools, who both strongly influenced the shape of technical education in 20th century, mark the successful end of this process of differentiation.
Hat die Geschichtswissenschaft eine Praxis?
Authors: Kerner Maximilian
Published: October 2006

Three examples are given which take into account previous considerations in the twentieth century concerning the theory and science of history as well as concrete studies about practical aspects of the discipline of history and which are intended to put to the test and demonstrate the chances and limits of historiography related to practical experience. On the one hand these examples refer to the role of history during the rediscovery of Europe at the end of our century (cf. note 35), on the other hand they point to the possibility of historical orientation in an era of increasing technical communication (cf. note 38), and also they indicate the significance of history at a time of resurgence of angst and fear caused by expanding technical progress (cf. note 49).
„Der Blick über das ganze Erdenrund”︁ ‐ Deutsche Forschungsreisen und Forschungsreisende im 19. Jahrhundert bis zur Deut‐schen Afrika‐Expedition 1860‐1863
Authors: Rieke‐Müller Annelore
Published: October 2006

The article deals with German scientific overseas travellers in 19th century before the foundation of the Kaiserreich (1871). After considering some political and scientific conditions in Germany it focusses on the expedition to Africa 1860‐1863 which was organized as the first German national enterprise for research in Africa. It was initiated by a group of scientists and journalists to search for the missing scientific traveller Eduard Vogel. The expedition and its popular reception is interpreted as part of forming national identity by scientific work and national solidarity.
Dilthey, Scherer, Erdmannsdörffer, Grimm ‐ ein ‚positivistisches’︁ Zeitschriftenprojekt in den 1860er Jahren
Authors: Kindt Tom , Müller Hans‐Harald
Published: October 2006

Our contribution, which is based on hitherto unanalyzed archive material, traces the plans for an interdisciplinary medium of publication that were pursued in the sixties of the 19th century by a circle of philosophers, philologists, and historians centering around Wilhelm Dilthey and Wilhelm Scherer. The reconstruction of this project brings to light that the members of this circle reflected on the foundations of the historical and philological disciplines and insisted on the development of comprehensive theories and the interdisciplinary cooperation of various fields of study. This case study thus reveals that some widely held assumptions about the role of German “positivism” in the humanities are in need of revision.
Pharmacokinetics of 8‐methoxypsoralen in the dog
Authors: Monbaliu J. G. , Belpaire F. M. , Braeckman R. A. , Bogaert M. G.
Published: October 2006

The pharmacokinetics of 8‐MOP were studied in six dogs following intravenous administration of 2 mg kg−1. In most animals a bi‐exponential decline of the plasma level profile was observed. The calculated pharmacokinetic parameters varied considerably between the different dogs. The mean half‐lives of distribution and of elimination were 0.20 h and 2.17 h, respectively. The average total plasma clearance was 0.51 1 kg−1 h−.

Following both oral and intravenous administration of doses of 1, 3, and 10 mg kg−1, non‐linear kinetics were found. Non‐linearity was confirmed following administration of the substance at increasing infusion rates.

Finally in four dogs, extraction by the liver was calculated by measuring 8‐MOP concentration in the femoral artery and in a hepatic vein after intravenous administration of 1 mg kg−1. The extraction varied from animal to animal (18 per cent to nearly 100 per cent). Administration of an additional dose of 3 mg kg−1 in two of the dogs led to a decreased extraction.
Influence of high‐fat meal on the absorption of a silicon — containing amide, an inhibitor of acyl — coa: Cholesterol acyltransferase, in man
Authors: Tse F. L. S. , Jaffe J. M.
Published: October 2006

The pharmacokinetics of 3‐(decyldimethylsilyl)‐N‐[2‐(4‐methylphenyl)‐l‐phenylethyl] propanamide (DMPP), an inhibitor of acyl‐CoA: cholesterol acyltransferase, have been examined in 18 healthy male volunteers who received an oral dose of either 14C‐DMPP or 3H‐DMPP immediately following a high‐fat meal, or 3H‐DMPP in the fasting state. DMPP was poorly absorbed in the fasting subjects. Administration with a high‐fat meal significantly increased the extent of absorption to 15 per cent of the dose. Simultaneous fitting of the blood levels and excretion data to a pharmacokinetic model showed that ca. 64 per cent of the absorbed DMPP was metabolized while the remainder was excreted intact via the bile. The routes of biotransformation included hydrolysis of the amide bond and oxidation of the phenyl ring. The apparent volumes of distribution for DMPP and its 14C and 3H labelled metabolites were 0.89,0.95, and 1.61kg−1, respectively, suggesting that these materials were distributed into extravascular spaces. The metabolites of DMPP were partially excreted in urine, accounting for 1.2 per cent and 3.8 per cent of the postprandial 14C and 3H labelled doses, respectively. The elimination half‐lives of DMPP and its 14C and 3H labelled metabolites were 2.8, 5.3, and 6.9 h, respectively.
Comparative bioavailability of furosemide from solution and 40 mg tablets with different dissolution characteristics following oral administration in normal men
Authors: Waller Elaine S. , Crismon M. Lynn , Bauza Micheal T. , Doluisio James T. , Smith Robert V.
Published: October 2006

Furosemide tablets, with markedly different dissolution characteristics, and solution were orally administered to 21 healthy adult males to determine the effect of in vitro dissolution rate on in vivo bioavailability profiles. Furosemide 40 mg was given as Tablet A (fast dissolution characteristics), Tablet B (slow dissolution characteristics), and an aqueous solution. Both batches of tablets had identical formulae and were produced by a common process. The dissolution rate of the slower Tablet B was probably retarded by extension of the wet granulation time. Blood was collected for 12 h postdose and urine for 24 h. Peak plasma furosemide concentrations after the solution were significantly greater than after the tablets; there was no significant difference between the tablets. The time to peak occurred significantly earlier with the solution, with no significant difference between the tablets. Relative bioavailabilities of Tablet A and B were 89 per cent and 101 per cent, respectively, as determined by AUC, and 79 per cent and 84 per cent, respectively, as determined by urine recovery. These differences are not statistically significant. These results indicate that dissolution rate profiles of furosemide tablets may not be predictive of in vivo bioavailability.
The non‐linear pharmacokinetics of prednisone and prednisolone
Authors: Ferry James J. , Wagner John G.
Published: October 2006

Intravenous zero order infusions were administered to New Zealand white rabbits. In a pilot study using one rabbit, prednisone and prednisolone clearance values increased with increase in either prednisone or prednisolone infusion rates. In the second study, prednisone was infused until both prednisone and prednisolone achieved steady‐state concentrations. In the third study, prednisone was infused until only prednisone achieved steady‐state concentrations. The results of the three experiments support the use of a non‐linear reversible metabolism model to describe the pharmacokinetic relationship between prednisone and prednisolone.
Clinical pharmacokinetics of etintidine
Authors: Huang Shiew‐Mei , Weintraub Howard S. , Abels Robert , Harris William , Marriott Thomas B. , Arnold John D. , Boccagno Joseph
Published: October 2006

The pharmacokinetics of etintidine (E), a potent H2 blocker, were studied in 12 normal, fasted subjects. The subjects received five ascending doses of E HCI in capsules at 72‐h intervals. Blood and urine samples were collected and the plasma and urine levels of E were determined by HPLC. Following oral administration, plasma E levels showed double peaks in half of the subjects. Mean Cmax., (0.42, 2.11, 3.82, 4.50, and 7.15 μg ml−1), AUC0‐∞ (0.96, 4.94, 11.3, 17.5, and 24.5 h μg ml−1), and the amount of E excreted unchanged in 72 h (20, 54.8, 170, 320, and 371 mg) were determined. These parameters indicate the amount of E absorbed increased linearly with dose for each individual. Renal clearance was independent of the dose and the mean value (16.6 lh−1) was about twice that of the creatinine clearance (which did not significantly change as a result of E treatment), indicating that E is actively secreted into the renal tubules. As E was eliminated rapidly from the body (t½<2 h), no substantial accumulation of E is expected after multiple dose treatment.
Pharmacokinetics and bioavailability of methocarbamol in rats
Authors: Obach R. , Pruñonosa J. , Menargues A. , Nomen M. , Vallès J.
Published: October 2006

In a pharmacokinetic study, 15, 30, 60, and 150 mg kg−1 intravenous and oral doses of methocarbamol were administered to rats. Differences observed in plasma clearance values, i.e. 0.0203, 0.0156, 0.0123, and 0.0085 1 kg−1 min−1 for 15, 30,60, and 150 mg kg−1, respectively, suggested a dose‐dependent pharmacokinetic behaviour of the drug. Elimination according to a biocompartmental open model and Michaelis‐Menten kinetics fits the plasma level data. Estimated Km and Vmax values were 38.49 ± 3.71 mg l−1 and 1.24 ± 0.06 mg l−1 min−1, respectively. After oral administration of 15, 30, and 60 mg kg−1 the peak plasma levels were reached earlier. The tmax values were 6, 6, and 10 min, respectively. After 150 mg kg−1 oral doses, peak plasma levels were reached later (tmax = 150 min). Estimated bioavailability ranged between 77 and 112 per cent.
Ocular absorption and disposition of phenylephrine and phenylephrine oxazolidine
Authors: Schoenwald R. D. , Chien D. S.
Published: October 2006

The ocular bioavailability of phenylephrine oxazolidine (PO), a prodrug intended for rapid corneal penetration, was micronized and suspended in sesame oil (1 and 10 per cent) and compared in bioavailability to phenylephrine HCl (PE) dissolved (10 per cent) in a buffered (pH 5.75), viscous (30 centipoise) vehicle. Cornea and aqueous humor of New Zealand rabbits were measured over time following 10 μl instillation to the eye. Based upon AUC measurements, corneal and aqueous humor levels were approximately 6 and 8 times greater for 10 per cent PO versus 10 per cent PE, respectively. In addition, the ocular pharmacokinetic values were determined for PE applied in a constant concentration (1 per cent) to the cornea over 180 min to anesthetized rabbits. Cornea and aqueous humor were measured for drug content over time. Using moment analysis and an initial slope method, the absorption rate constant, Ka, the steady state volume of distribution in the eye, Vss and ocular clearance, Qe, were calculated. Values obtained for PE were 4–15 × 10−5 min−1, 0.423ml and 14.6 μl min−1, respectively. The half‐life for drug elimination ranged from 63‐83 min depending on the tissue or route of administration.
The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis
Authors: Usui Yoshihiko , Akiba Hisaya , Takeuchi Masaru , Kezuka Takeshi , Takeuchi Aya , Hattori Takaaki , Okunuki Yoko , Yamazaki Tomohide , Yagita Hideo , Usui Masahiko , Okumura Ko
Published: October 2006

ICOS/B7RP‐1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP‐1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4+ T cells in the region of the retina in EAU‐induced mice. The anti‐B7RP‐1 monoclonal antibody (mAb)‐treated or ICOS‐deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP‐1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti‐B7RP‐1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti‐B7RP‐1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN‐γ production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP‐1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS‐mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.
In vivo CD44‐CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance
Authors: Marhaba Rachid , Freyschmidt‐Paul Pia , Zöller Margot
Published: October 2006

CD44 is involved in leukocyte migration and activation and has recently been reported to contribute to leukocyte extravasation by associating with CD49d. We explored whether similar changes in CD44 activity are seen in vivo using murine alopecia areata (AA) as a chronic, organ‐related autoimmune disease model system. Expression of the activated, hyaluronan‐binding form of CD44, and of CD49d, was elevated in draining lymph node cells (LNC) of AA‐affected mice as compared to control mice. LNC of AA mice displayed increased motility, proliferative activity and apoptosis resistance, which were equally well inhibited by anti‐CD44 and anti‐CD49d. The latter is the sequelae of the association between CD44 and CD49d that is seen in activated lymphocytes. Significantly, due to CD44‐CD49d complex formation, CD44 gains access to focal adhesion kinase and CD49d gains access to CD44‐associated lck and ezrin, such that downstream kinases become activated via CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually avail themselves of the partner's signaling pathways and the ligand binding of each one triggers signaling pathways of both. This strongly influences the lymphocytes’ activation state and function.
Spontaneous class switching and B cell hyperactivity increase autoimmunity against intracellular self antigen in Lyn‐deficient mice
Authors: Silver Karlee , Bouriez‐Jones Tiphaine , Crockford Tanya , Ferry Helen , Tang H. Lucy , Cyster Jason G. , Cornall Richard J.
Published: October 2006

IgG autoantibodies cause pathology due to their ability to bind self antigens. However, the extent to which the initial B cell activation and isotype switching is antigen‐driven is unclear and it has been widely proposed that intrinsic B cell hyperactivity may be a contributing factor. To explore this issue we generated mice with B cell hyperactivity secondary to deficiency in the src kinase Lyn that also expressed a gene‐targeted anti‐hen egg lysozyme Ig construct (VDJκ) capable of class switching to all isotypes. The B cell hyperactivity caused spontaneous hypersecretion of antibodies and class switching to IgM, IgA, IgG1 and IgG3 isotypes in the absence of self antigen, and this persisted as an autoimmune phenomenon in the presence of intracellularly expressed hen egg lysozyme. Exaggerated class switching was also unaffected by antigen in vitro. These findings show that systemic high‐avidity intracellular self antigens do not induce self tolerance in the face of B cell hyperactivity. Under these circumstances, spontaneous activation of hyperactive B cells leads to isotype switching and the development of high titres of IgG autoantibodies against intracellular proteins.
Grafting of 4‐Hydroxybenzenesulfonic Acid onto Commercially Available Poly(VDF‐co‐HFP) Copolymers for the Preparation of Membranes
Authors: Taguet A. , Ameduri B. , Boutevin B.
Published: October 2006

The grafting of a phenate bearing sulfonate group in solution onto commercially available poly(VDF‐co‐HFP) copolymers, where VDF and HFP stand for vinylidene fluoride and hexafluoropropene, respectively, is presented. This reaction leads to novel fluoropolymers, bearing aryl sulfonic acid side functions, which are fuel cell membrane precursors. A mechanism similar to the grafting of bisphenol onto VDF‐containing copolymers is discussed. First, the sulfonate phenate is modified to give the didecyldimethylammonium bromide sulfonate phenate salt, in order to promote the substitution onto a fluorine atom in VDF unit adjacent to one HFP unit onto a fluorine atom in the copolymer. The substitution of this salt onto the fluorinated copolymer yields low molar percentages of grafted phenate, ranging from 1.8 to 5.1 mol‐%, whereas it reaches values up to 13 mol‐% grafting when the NH2‐CH2‐CH2‐S‐CH2‐CH2‐C6H4‐SO3Na amine is used as the grafting agent. NMR characterization is used to monitor the grafting process. The electrochemical properties of the resulting phenate grafted‐poly(VDF‐co‐HFP) copolymer are studied. The theoretical ion exchange capacities are half that of Nafion®. The proton conductivities are also lower than that of Nafion®, although one conductivity measurement reached a value of 5.1 mS cm–1, showing a non‐negligible conductivity. The water uptake is lower than these noted for a sulfonated amine‐grafted copolymer, and is of the same order as that for Nafion®. Finally, it is shown that these novel materials start to decompose above 200 °C, showing a similar thermostability as that of an amino‐containing aryl sulfonate‐grafted poly(VDF‐co‐HFP) copolymer.
A note on cointegration of health expenditures and income
Authors: Wang Zijun , Rettenmaier Andrew J.
Published: October 2006

Utilizing a panel data set of 50 US states, this note investigates nonstationarity and cointegration of health care expenditures and gross state products (GSP). Both the individual state‐based method and the recent panel data method are applied. Allowing for structural breaks in the test, we find that health care expenditures and GSP are both nonstationary. The evidence also suggests that the two series form a cointegrating relationship. The income elasticities of health spending vary over states and became smaller in the 1990s. Copyright © 2006 John Wiley & Sons, Ltd.
Chemical form and distribution of mercury and selenium in canned tuna
Authors: Cappon Chris J. , Smith J. Crispin
Published: October 2006

The content, chemical form and distribution of mercury and selenium were determined for several samples of canned tuna. Samples represented albacore, bluefin, skipjack and yellowfin species, and were packed in either water or vegetable oil. Recently‐processed samples (less than one year old) and much older samples (8–29 years old) were examined. Methylmercury was the predominant mercury form in all samples, comprising 57.4–94.7% of the total mercury content. For these samples, 7.6–44.8% of the total selenium content was present as selenate. There was no apparent effect of packing medium, species or sample age on the methylmercury and selenate percentages. Although the total selenium content exceeded that of total mercury, there was no apparent correlation between the total levels of both elements. Sample age influenced the level of water‐extractable mercury and selenium in canned tuna. For recently canned samples, an average of 27.0% of the total mercury and 55.6% of the total selenium content were water‐extractable. However, for the older samples, the corresponding respective average extractable levels were 46.4 and 48.2%. For both categories, inorganic mercury and selenate were more extractable, on an average percentage basis. In addition, an average of 7.2% of the total mercury content was benzene‐extractable.
Teratogenicity, fetal toxicity and tissue concentration of cadmium administered to female rats during organogenesis
Authors: Barański B. , Stetkiewicz I. , Trzcinka‐ochocka M. , Sitarek K. , Szymczak W.
Published: October 2006

Cadmium chloride was administered by gavage to pregnant rats from day 7 to day 16 of gestation. Cadmium, when administered at a dose of 40 mg Cd per kg per day, was associated with significant maternal toxicity, placental injury and an increased fetal burden of cadmium. At lower dose levels (2–20 mg Cd per kg per day), fetal development was retarded. Teratogenic effects were not observed and the fetal cadmium concentrations did not differ significantly from the controls, despite the marked cadmium accumulation in the placenta and maternal tissues. The body‐weight gain during gestation of all cadmium‐treated females was reduced and an absolute weight of adrenals in females given cadmium at doses 4 mg kg−1 and higher was significantly increased. The obtained results indicate that cadmium‐induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.
Whole body and liver distribution of inhaled mercury vapor in the mouse: Influence of ethanol and aminotriazole pretreatment
Authors: Khayat Amir , Dencker Lennart
Published: October 2006

Inhalation of radioactive metallic mercury vapor (203H°) in the mouse resulted in an accumulation of mercury in several organs where no specific uptake was observed after i.v. injection of inorganic mercury (203Hg2+). This was true for the whole respiratory epithelium (including the lung parenchyma), myocardium, brain, retina of the eye, adrenal cortex, corpora lutea of the ovary, epididymis, brown fat and thyroid gland. It is assumed that these organs have a high capacity for oxidizing Hg° to Hg2+, which will then be retained in the tissues. Ethanol and aminotriazole (catalase inhibitors) decreased the concentration in several of these organs, although not in an exactly similar pattern. In the livers of non‐treated animals, most of the inhaled mercury accumulated in the hepatocytes in the periphery of the lobuli (periportal region), close to where the blood vessels enter the liver parenchyma. Treatment with ethanol or aminotriazole increased the liver mercury content, with more or less all the hepatocytes apparently engaged in the oxidation of Hg°.
Influence of alcohol, dithiocarb and (+)‐catechin on the hepatotoxicity and metabolism of vinylidene chloride in rats
Authors: Siegers C.‐P. , Heidbüchel K. , Younes M.
Published: October 2006

Hepatotoxicity of vinylidene chloride (1,1‐dichloroethylene, VDC) in rats was evidenced by increases of serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH). Simultaneous treatment with ethanol (4.8 g kg−1 p.o.) totally inhibited these hepatotoxic effects, whereas pretreatment with the same ethanol dose 24h prior to VDC had no effect. Dithiocarb or (+)‐catechin (0.2 g kg−1;p.o.), administered simultaneously with VDC, significantly reduced the VDC‐induced increments of serum enzyme activities. Pretreatment with 5% ethanol for 7 days instead of drinking water increased the hepatotoxicity of a single dose of VDC. The combined treatment with VDC (0.125–0.2 g kg−1, twice weekly) and 5% ethanol for 4 weeks led to only small increases of serum enzyme activities as compared with controls treated with VDC alone. However, 60% lethality occurred in the VDC‐ethanol group. Administration of either dithiocarb or (+)‐catechin with VDC totally antagonized the observed lethality. Metabolic studies with VDC in a closed exposure system indicated that simultaneous treatment with ethanol or dithiocarb totally depressed the metabolic removal of VDC, whereas (+)‐catechin had no effect.
Mutagenic effects of aqueous extracts of Symphytum officinale L. and of its alkaloidal fractions
Authors: Fumanowa Mirosława , Guzewska Joanna , Bełdowska Bożena
Published: October 2006

Symphytum officinale L. (Boraginaceae) is a medicinal plant widely used in therapy. Its roots, described in the Polish Pharmacopoeia1 as Radix symphyti, are recommended as expectorants, especially for children. Aqueous solutions of three alkaloid fractions obtained from infusions of Symphytum officinale L. root were tested for their antimitotic and mutagenic activity in meristematic cells of the lateral roots of Vicia faba L., var minor. Lasiocarpine, a proven carcinogen, served as a positive control. Mutagenic effects were induced by lasiocarpine, by the alkaloidal fraction I and by diluted infusions from Radix symphyti. Fraction III had only antimitotic effect. The biological activity of the tested solutions is discussed in relation to the relevant literature.
Increased urinary excretion of selenium among workers exposed to elemental mercury vapor
Authors: Alexander J. , Thomassen Y. , Aaseth J.
Published: October 2006

The content of selenium and mercury in urine was measured in 28 male workers exposed to Hg° and in 21 unexposed male controls. The first group excreted significantly more selenium into urine as compared with the control group. No significant correlation between mercury and selenium excretion was found.
Tissue origin of MDH isozymes in blood serum of rats exposed to alkylmercurials
Authors: Brzeźnicka Elżbieta A. , Chmielnicka Jadwiga , Wójcikiewicz‐Herma Łucja
Published: October 2006

Wistar rats were dosed with Hg at 2.5 mg kg−1 intragastrically as methylmercuric chloride (MeHg) or ethylmercuric chloride (EtHg) on alternate days for 6 weeks. Activities of the mitochondrial (m‐MDH) and cytosol (c‐MDH) isozymes of malate dehydrogenase (MDH; E.C. 1.1.1.37) were studied in the serum, liver and kidneys of rats at 2‐week intervals using agar gel electrophoresis. In order to determine the tissue of origin of the MDH isozymes in rat serum, studies were also made on changes in their activities after poisoning the animals with a hepatotoxic (CCl4) or nephrotoxic(HgCl2) agent. The results indicate that the kidneys are responsible for the increase of the c‐MDH activity in the serum of rats poisoned with EtHg, while in the case of MeHg this increase results from damage initially to the liver and then also to the kidneys.
High‐performance liquid chromatographic analysis of MTX, 7‐OH‐MTX and MTX derivatives: Application to intracellular metabolism in tumor cells (HT 29)
Authors: Durand R. , Fabre G. , Cano J. P. , Catalin J. , Ahmed O. Ait , Just S.
Published: October 2006

In order to study the intracellular metabolism of Methotrexate (MTX) and the cytotoxicity of the antifolates, a specific paired‐ion HPLC method has been developed which permits the simultaneous determination of DAMPA, MTX, 7‐OH‐MTX, MTX‐G1, MTX‐G2 and MTX‐G3. Cells were incubated with 3H‐MTX. The MTX metabolites were extracted, purified on SEP‐PAK cartridges and further analysed by high‐performance liquid chromatography (HPLC). The stationary phase was constituted by a C18 μBondapak and the mobile phase by 5 mM phosphate buffer (pH 7.4) containing 2.5 mM tetrabutylammonium nitrate. The elution was performed with a linear methanol gradient (20–30%). HPLC fractions were collected and radioactivity evaluated by β counting (retention times: DAMPA = 12.93 min; MTX = 18.29 min; 7‐OH‐MTX = 21.13 min; MTX‐G1 = 22.69 min; MTX‐G2 = 26.81 min; MTX‐G3 = 30.61 min). This analytical procedure was applied to separate and characterize multiple forms of MTX polyglutamate derivatives in HT 29, a human adenocarcinoma cell line varying the incubation time (4–18 h) and MTX concentration (0.6‐10.6 μM). The incorporation process seems to be characteristic of a cell line resistant to MTX. The incorporation were very low and after a 4‐h exposure time only 5% of the MTX was converted to polyglutamates. Between 1.6 and 10.6 μM MTX, no difference was observed in the polyglutamization. The defect in the incorporation of the drug and in the metabolization process in vitro could partially explain the failure of the MTX treatment in colorectal cancer.
In vitro and in vivo studies on the potential mutagenicity of alclofenac, dihydroxyalclofenac and alclofenac epoxide
Authors: Mercier M. , Poncelet F. , de Meester C. , McGregor D. B. , Willins M. J. , Léonard A. , Fabry L.
Published: October 2006

Alclofenac (A) and two of its metabolites, dihydroxyalclofenac (DHA) and alclofenac epoxide (AE), were tested for their mutagenic potential. Alclofenac and DHA showed no mutagenic, transforming or clastogenic potential in any in vitro experiment. The addition of a supplementary metabolic activation system did not change the response of those two compounds in any test procedures in vitro. AE, an intermediary metabolite between A and DHA, was mutagenic by itself in the Ames test, but in the presence of a liver post‐mitochondrial fraction its activity of Salmonella typhimurium was greatly decreased. Dominant lethal mutations were not induced in male rats given alclofenac, and AE had no effect in the micronucleus test. In human volunteers given alclofenac at therapeutic dose levels, no mutagenic activity was found in the urine and no significant increase in the incidence of structural chromosome aberrations was observed in peripheral blood lymphocytes.
Cadmium‐metallothionein‐induced nephropathy: A morphological and autoradiographic study of cadmium distribution, the development of tubular damage and subsequent cell regeneration
Authors: Murakami M. , Cain K. , Webb M.
Published: October 2006

A single intravenous dose of 0.8 mg thionein‐bound cadmium (Cd) per kg body weight, as the isolated (Cd, Zn)‐metallothionein (MT) from rat liver, in rats of the same strain is nephrotoxic, but not lethal. Apical vesiculation in epithelial cells of the renal proximal convoluted tubules is apparent within 1 h of dosing and, by 4 h, is extensive in some of these cells that surround the larger arteries in the cortex. The membranes of these cells appear undamaged. The lesion at first progresses with time; by 24 h, the initially affected cells show extensive necrosis and most proximal convoluted tubular epithelia in other regions of the cortex are hydropically or vacuolarly degenerated. The inner stripe of the outer zone of the medulla and other portions of the nephron (glomerulus, distal tubule and collecting duct), however, appear essentially unaffected. The necrotic changes are maximal at 48 h but, after this time, regeneration begins. By seven days, much of the cell debris has been eliminated and cells of the regenerating or regenerated epithelia are similar in morphology to those of the normal kidney. Electron microscopic autoradiography of kidney sections from rats after administration of 109Cd‐metallothionein of high specific activity shows that Cd is not concentrated in endocytotic vesicles, lysosomes, or any other cellular organelle, even at early times after dosing, but is distributed evenly throughout the epithelial cell. Thus, although Cd‐MT appears to be taken up endocytotically in the kidney tubules, it appears that liberation of Cd from the metalloprotein must occur very early in the reabsorptive process.
Induction of microsomal epoxide hydrolase by tienilic acid in the rat
Authors: Sellman R. , Parkki M. G.
Published: October 2006

The effects of tienilic acid [2,3‐dichloro‐4‐(2‐thienylcarbonyl)phenoxy acetic acid] on drug‐metabolizing enzymes in the rat liver and kidneys were studied. Short‐term treatment for 2 weeks (450 mg per kg per day) increased the activity of microsomal epoxide hydrolase at least two‐fold in both rat liver and kidneys. The effect of tienilic acid on the activity of microsomal epoxide hydrolase in the rat liver correlated with the dose at levels of 20–450 mg per kg per day for 14 days (r = 0.92). Tienilic acid had only marginal effects on cytochrome‐P‐450‐mediated mono‐oxygenases. Tienilic acid caused an approximately two‐fold increase in glucuronide conjugation of 4‐methylumbelliferone in the liver. No increase in the activity of rat hepatic microsomal UDP—glucuronosyltransferase toward O‐aminophenol was detected. According to these results, tienilic acid can be regarded as one of the most specific inducers of microsomal epoxide hydrolase.
Skin‐tumor initiation activity of coal liquids with different boiling‐point ranges
Authors: Mahlum D. Dennis
Published: October 2006

High‐boiling coal liquids from the solvent‐refined coal‐I and ‐II (SRC‐I, ‐II) processes, respectively, were fractionally distilled. In the case of SRC‐I process solvent (PS), 50°F distillation cuts were obtained between 550 and 850°F, while for the SRC‐II material, the 50°F cuts were only obtained between 700 and 850°F. These cuts, as well as the parent material, were tested for their ability to initiate skin tumors by applying a single dose (25 mg) to the shaved backs of Charles River female CD‐1 mice. After 2 weeks, the mice received twice weekly applications of 5 μg of the promoter, phorbol myristate acetate. Only a few tumors were found for SRC‐I fractions boiling below 700°F; tumor‐initiating activity increased as the boiling point increased. A similar increase in response with increasing boiling point was seen for the SRC‐II cuts. The initiating activities for the parent materials were similar to those observed for their respective 800 to 850°F cuts.
Acute toxicity study of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorine‐1‐oxide (a new antitumor agent with an inorganic ring) in mice, rats and dogs
Authors: Nakano Shigeki , Yamashita Kazumasa , Kirihara Yoshinobu , Kuwata Masahiko , Morita Ken'ichi
Published: October 2006

In order to study the safety of 1,3,3,5,5‐pentaziridino‐1‐thia‐2,4,6‐triaza‐3,5‐diphosphorme‐1‐oxide(SOAz), a new antitumor agent, acute toxicity studies by intravenous administration were performed in ddY mice, Wistar rats and beagle dogs. The LD50 values in rodents were 325 mg kg−1 for male mice, 450 mg kg−1 for female mice, 100 mg kg−1 for male rats and 82 mg kg−1 for female rats. In dogs, the LD50 values were 12 mg kg−1 for males and 18 mg/kg−1 for females. The dosed animals showed diarrhoea and decreased movement in the three species, and emaciation and loss of body weight in mice and rats. Dogs also showed signs of pneumonia. Histopathological examination revealed bone marrow suppression, atrophy of lymphoid organs and testes, and damage to the digestive tract mucosa in the three species. The main causes of death from single‐dose administration were bone marrow aplasia and atrophy of lymphoid tissue in all species, together with gastro‐intestinal ulceration in rats and dogs, and infection in mice and dogs.
The subchronic oral toxicity of polyphenylene sulfide
Authors: Thomas W. C. , Kirwin C. J. , Wazeter F. X. , Jessup D. C.
Published: October 2006

Polyphenylene sulfide was offered to Charles River CD® rats for 6 months in the diet at concentrations of 0.00, 0.50, 2.75 and 5.00% (w/w). In this study, animals of both sexes consumed polyphenylene sulfide for 6 months without exhibiting compound‐related effects. Parameters studied were: body weight, hematology, clinical chemistry, urinalysis, organ weights, gross pathology and histopathology.
Relaxation of rabbit aorta by chlordimeform
Authors: Robinson Casey P.
Published: October 2006

Chlordimeform N′‐(4‐choro‐O‐tolyl)‐N, N‐dimethyl‐formamidine; CDF), an acaracide‐insecticide, relaxed helically cut strips of rabbit thoracic aorta and deadventitiated aorta strips. Relaxations by CDF of aorta strips contracted by 5 × 10−7M prostaglandin F2α were not altered by the antimuscarinic agent atropine (10−5M), the beta‐adrenergic antagonist propranolol (10−5M), the histamine H2 antagonist cimetidine (2 × 10−4M), the dopamine antagonist haloperidol (10−5M) or the Na+‐K+‐ATPase inhibitor ouabain (5 × 10−6M). CDF further relaxed deadventitiated strips contracted by 10−6M NE or 40 mM potassium and then partially relaxed by 10−5M verapamil. CDF (10−5M) potentiated contractions caused by the addition of calcium to potassium depolarized strips in zero calcium media, but higher concentrations reduced calcium‐induced contractions. The highest CDF concentration (10−2M) not only prevented tension increase on calcium addition, but also progressively decreased tension to below baseline levels. The addition of 10−2M CDF to aorta strips not contracted by a vasoactive agent decreased resting tension. This relaxation was usually maximal at 10−3M and less at 10−2M. Thus, CDF relaxes vascular smooth muscle, not by antagonism at the usual vascular relaxant receptors, but by interference with calcium utilization.
Developmental toxicity following oral administration of a high‐boiling coal liquid to pregnant rats
Authors: Hackett P. L. , Rommereim D. N. , Sikov M. R.
Published: October 2006

Heavy distillate (HD), the highest‐boiling coal liquid from the solvent‐refined coal‐II process (SRC‐II), was administered by intragastric (IG) intubation to pregnant rats. Five dose levels of HD (0.09, 0.14, 0.18, 0.36 and 0.74 g kg−1), were given daily from 12 to 16 days of gestation and the rats were killed at 20 days of gestation. Maternal body weights and weights of the liver, kidneys, spleen, adrenals, thymus, ovaries and the gravid uterus were obtained. Gravid uteri were evaluated for prenatal mortality. Live fetuses were examined for malformations and weighed; fetal lungs were excised and weighed. Maternal (extragestational) weight gains and thymic weights diminished in all groups that received the SRC material. Adrenal weights were increased in all treated animals, except for those in the lowest‐dose group (0.9 g kg−1). There was significant maternal mortality at 0.74 g kg−1 and increased intrauterine mortality at doses of 0.37 and 0.74 g kg−1. Placental weight was depressed, and the incidence of fetal anomalies was increased at 0.14 g kg−1 and all higher dose levels.
A survey of genetic toxicology testing in industry, contract laboratories and government
Authors: McCarroll N. E. , Farrow M. G. , McCarthy K. L. , Scribner H. E.
Published: October 2006

Genetic Toxicology Association members from governmental, contract and industrial laboratories were surveyed to determine the status of 28 recognized genetic toxicology assays in their laboratories. Compiled results of the 1982 questionnaire indicate that the Ames test, in vitro cytogenetics, in vitro sister chromatid exchange, unscheduled DNA synthesis, mutation in Chinese hamster ovary cells at the HGPRT locus, and in vivo bone marrow assays were the most frequently performed routine tests by the majority of laboratory affiliations. Investigation of the number of transformation assays performed indicated a high routine use. However, their use was largely confined to contract laboratories. Volume analysis of chemicals tested for 1982 indicated: (i) contract laboratories studied the largest number of compounds over the broadest spectrum of assays; (ii) industrial laboratories processed more compounds in the Ames test than any other laboratory group; and (iii) governmental laboratories ranked lowest in numbers of compounds evaluated both in‐house and/or subcontracted.