bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals
Authors: Kararli Tugrul T. 
Published: October 2006

AbstractIn addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier‐mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter.While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human.This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.
The acetylcholinesterase oxime reactivator HI‐6 in man: Pharmacokinetics and tolerability in combination with atropine
Authors: Clement John G. , Bailey David G. , Madill Herbert D. , Tran Lan T. , Spence J. David 
Published: October 2006

AbstractIn a double‐blind, placebo‐controlled, single‐dose ascending pharmacokinetics and tolerance study, we evaluated the bispyridinium oxime HI‐6 dichloride monohydrate (62.5, 125, 250, and 500 mg), administered intramuscularly with atropine sulphate, 2 mg, in 24 healthy male volunteers. The plasma HI‐6 peak concentration (Cmax) and area under the concentration—time curve (AUC) demonstrated linear pharmacokinetics with low intradose variability, suggestive of uniformity of effect among subjects. HI‐6 (500 mg) attained plasma drug concentrations that appeared adequate for practical use as an antidote. The mean ± SD time to maximum plasma HI‐6 concentration (tmax = 0.69 ± 0.21 h, n = 16), and absorption half‐life (t/2a = 0.17 ± 0.05 h) indicated rapid onset of effect. The volume of distribution (Vd = 0.25 ± 0.04 L kg−1 TBW) approximated the extracellular fluid volume. A high total body clearance (CL = 252 ± 52 mL min−1) and short apparent elimination half‐life (t/2e = 1.15 ± 0.19 h) were expected for this polar quaternary ammonium drug. The renal clearance (CLr = 137 ± 33 mL min−1), which approximated the expected glomerular filtration rate, and 24 h urinary excretion of unchanged drug (55 ± 10%) indicated substantial non‐renal elimination. Blood pressure, heart rate, respiratory rate, electrocardiographic parameters, mental acuity, and vision were not altered. Adverse events and changes in serum, urine and semen laboratory tests were mild. The pharmacokinetics, safety, and apparent efficacy of HI‐6 suggest it may be a superior oxime antidote against nerve agent poisoning.
Pharmacokinetics and antitumour activity of a new anthracycline, DA‐125, after intravenous administration to subcutaneously implanted Lewis‐lung‐carcinoma‐bearing mice
Authors: Lee Sang D. , Park Jeong B. , Lee Woo I. , Shim Hyun J. , Lee Eung D. , Lee Jong J. , Kim Won B. , Yang Junnick , Kim Chong K. , Lee Myung G. 
Published: October 2006

AbstractThe pharmacokinetics and tissue distribution of M1–M4 were compared after intravenous (IV) administration of DA‐125, 25 mg kg−1, to BDF1 mice (n = 5 at each sampling time) and subcutaneously implanted Lewis‐lung‐carcinoma‐bearing BDF1 mice (n = 10 at each sampling time). The mean plasma concentrations of M1–M4 were not significantly different between the two groups of mice, and hence similar pharmacokinetic parameters for M1–M4 were obtained. The amount of M1 in the lung was significantly greater in the tumour‐bearing mice than in the control mice, resulting in a greater AUA, in the tumour‐bearing mice (18 600 against 8940 μg min g−1), and vice versa in the liver (962 against 3840 μg min g−1). However, the corresponding values for other tissues were comparable between the control and tumour‐bearing mice. The amount of M1 was greatest in the lung for up to 2 h in the tumour‐bearing mice. M2 was the predominant metabolite among M1–M4 excreted in 24 h urine by both groups of mice; 8.36 and 10.7% of the IV dose were excreted in 24 h urine as M2–expressed in terms of DA‐125—by the control and tumour‐bearing mice, respectively. The amount of M1 in the tumour mass reached a mean Cmax of 3.75 μg g−1 immediately after IV administration of DA‐125 to the tumour‐bearing mice, then declined very slowly to an amount that remained almost constant for up to 24 h. This suggested that M1 has high affinity for the subcutaneously implanted Lewis lung carcinoma. The antitumour activity, such as the increase in life span (ILS) and tumour growth inhibition (TGI) of DA‐125, 6–48 mg kg−1, and adriamycin (ADM), 3–18 mg kg−1, were also compared in subcutaneously implanted Lewis‐lung‐carcinoma‐bearing BDF1 mice after four weekly IV administrations of the drugs on days 1, 8, 15, and 22 following tumour implantation. More than three out of six mice survived as tumour‐free for longer than 70 d at a DA‐125 dose range of 6–24 mg kg−1, but there were no tumour‐free mice at any dose of ADM. Assuming ILS values higher than 30% to be effective, DA‐125 doses ranging from 6 to 24 mg kg−1 were effective in increasing the life span, which ADM dose only within the dose range of 6–12 mg kg−1.
Pharmcokinetics of HI‐6 and atropine in anaesthetized pigs after administration by a new autoinjector
Authors: Nyberg Ann Göransson , Cassel Gudrun , Jeneskog Torgny , Karlsson Lena , Larsson Roland , Lundström Marlene , Palmer Lena , Persson Sven‐Åke 
Published: October 2006

AbstractA newly developed autoinjector (Astra Tech, Sweden) containing 500 mg HI‐6 and 2 mg atropine sulphate was tested in anaesthetized normal pigs. The pharmacokinetics and pharmacodynamics of the drugs after administration by the autoinjector were compared with those after conventional needle and syringe delivery intramuscularly and intravenously. Cardiopulmonary parameters were monitored and serum concentrations of oxime, atropine, and acetylcholinesterase were determined in blood samples taken at intervals over a 6h period postinjection. After injection in anaesthetized pigs, both HI‐6 and atropine were absorbed rapidly and completely from the injection site. Therapeutic serum concentrations of HI‐6, arbitrarily taken as 4 μg mL−1, were reached within 1 min of intravenous and autoinjector administration, and within 5 min of intramuscular injection. The concentrations remained above this level for 3–4h. There were no significant changes in acetylcholinesterase activity, mean arterial blood pressure, or respiration frequency after injection of HI‐6 and atropine sulphate. The heart rates increased significantly after administration of the two drugs (cardioacceleration defined as ⩾ 5% increase in heart rate), regardless of the technique employed. Our results show that HI‐6 and atropine sulphate can be given intramuscularly by the new autoinjector with the same effectiveness and speed as when given intravenously. Irrespective of the injection technique, no overt signs of toxicity were observed at the drug concentrations used.
The effect of aging on the pharmacokinetics of nalbuphine in rabbits
Authors: Ho Shung‐Tai , Wang Jhi‐Joung , Hu Oliver Yoa‐Pu , Hu Teh‐Min 
Published: October 2006

AbstractFor the purpose of selecting an animal model for the study of the aging effect on the pharmacokinetics of nalbuphine, the pharmacokinetic properties in young and in aged rabbits were reported. Thirty‐one healthy New Zealand white rabbits ranging in ages (mean) from three months to 43 months (six three months old, group I; nine eight months old, group II; nine 18 months old, group III; and seven 43 months old, group IV) were included in the study. After intravenous bolus injection of nalbuphine (10 mg kg−1) to each rabbit, plasma samples were collected and analysed for nalbuphine by a high‐performance liquid chromatography method. The plasma concentration—time data regarding nalbuphine were successfully fitted to a linear two‐compartment open model. The elimination half‐life of nalbuphine in rabbits increased significantly with age. Consequently, clearance decreased significantly with age. The parameter AUC0‐∞, which is derived from dose/clearance, increased significantly with age. The effect of aging on the pharmacokinetics of nalbuphine in rabbits is quite similar to that in humans. From the present study, it is concluded that rabbits may be suitable for the study of aging effects on the pharmacokinetics of nalbuphine.
The effect of three H2 receptor antagonists on the disposition of cyclosporin a in the in situ perfused rat liver model
Authors: Hughes C. M. , Swanton J. G. , Collier P. S. 
Published: October 2006

AbstractThe in situ, perfused rat liver model was used to investigate the effect of three H2 receptor antagonists on the disposition of cyclosporin A (CyA) and the major human metabolite, AM1. Perfusion experiments, using standard techniques, were carried out on four groups (one control and three H2‐receptor antagonist‐treated groups) of male Sprague‐Dawley rats (300–350 g). All animals received CyA, 2.5 mg; the three treated groups received cimetidine (8 mg), ranitidine (3 mg), or famotidine (0.4 mg). Perfusated and bile samples were collected and assayed for CyA, AM1, and the H2 receptor antagonists by HPLC. Results indicated that CyA perfusate concentrations in the controls and cimetidine and ranitidine‐treated groups were not significantly different, although levels in the famotidine group were significantly higher at all times (p<0.05), except 30 min, compared to the controls. However, examination of the AM1 perfusate and bile data and the apparent metabolic clearance data indicated that CyA metabolism was still occurring, despite the presence of the H2 receptor antagonist. It is suggested that the absence of a interaction may be attributed to a lack of specificity of the H2 receptor antagonists for CYP3A, the isoenzyme responsible for CyA metabolism.
Eschatologische Wissenschaft und wissenschaftliche Eschatologik
Authors: Sternberger Dolf 
Published: October 2006

AbstractEschatological science and scientific eschatology. ‐ The science which this speech is dealing with is almost extinct. Far apart from modern intellectual life it is surviving only in certain adventist sects, in religious subculture as it were, and thus, under the ban of both modern science and official churches as well. Through all of the Christian middle‐ages, however, eschatological science stood in full bloom and high esteem. The case of Joachim de Fiore, the Calabrian abbot (ca. 1135‐1202), is taken as a paradigm ‐ although he was concerned not so much with the apocalyptic Last Events than with a “trinitarian” construction of history and with the advent of the aeon of the Holy Ghost. Eschatological science proper is based on canonic and other authentic prophecies but it is not prophecy itself. It aims at revealing the revelation once more, taking biblical texts as secrets which are still to be decoded. ‐ The paper goes on describing some more characteristics of eschatological science: The tendency of stating definite periods within the history of salvation which is understood to form a coherent body and a definable mass of years; furthermore, the scholarly art of more or less precisely determining the time‐table of apocalyptic events which requires, of course, a good deal of numerical and chronological experimentation. In addition, the eschatological scientist has always been eager to read the ominous “signs of the time” out of or into current history of his own days, and this capacity particularly makes for his public prestige and influence.While eschatological science has always started from undoubted prophetic and apocalytic premises the other phenomenon which the present speaker terms “scientific eschatology” is, quite reversely, parading as an authentic independent science in the modern meaning of the word not realizing their own hidden eschatological schemes. This is briefly illustrated by the “Communist manifest” and Lenin's statements on the “world revolution”.
Der Höhepunkt der Iatromathematik
Authors: Müller‐Jahncke Wolf‐Dieter 
Published: October 2006

AbstractThe science of “Iatromathematic” and “Iatroastrology” evolved during Antiquity and not unknown in the Middle Ages reached its prime in the 15th century. Their theories fortified by the re‐discovery of Newplatonism and Hermetism were also applied by physicians at the sick‐bed. Due to the outbreak of the syphilis in 1496 a violent discussion arose among physicians, whether or not this new epidemic was caused by the prevailing constellation. Contradictory statements about the epidemic's first appearance caused competend opponents to take action. But they failed to succeed since the idea about the constellation's influence on the sublunar ruled within widest circles of physicians up to the 17th century.
Der Ausklang der wissenschaftlichen Iatromagie
Authors: Rothschuh Karl E. 
Published: October 2006

AbstractIatromagic is the use of magic in medical thought and in treatment. It is rooted in the theory of life based on magic and between approx. 1500 and approx. 1680 it presented a widespread, well‐found, i.e. ‘scientific’, concept of medicine. Its origin lay in the supposition that there exist hermetical forces ‐ sympathies and antipathies ‐ relating human beings to the spheres of nature. This idea, elaborated in Neoplatonism to Scientia Magica, lead to the Praxis Magica in medicine, i.e. to medical application of inclinations and disinclinations, correspondances, similarities between plants, animals and human beings on the sick‐bed, for example in the form of signature doctrine. Medicinal magic did not treat according to visible, cause‐and‐effect relationships, but according to inner relating forces as recommended the writings of Agrippa von Nettesheim, Oswald Croll, Wolfgang Hildebrand and many others. In this talk two writings in particular, one of Kenelm Digby, the other of Sylvester Rattray (1658) will be more closely looked at as to their evidence of iatromagical connections. Digby is concerned with a corpuscular interpretation of the hermetically effective weapon salve. Rattray attempts another explanation for magical cures, which propagates [fermentation] as the basic principle of treatment. According to him there are two kinds of fermentation, one causing, the other curing sickness. Neither of the two authors doubts the reality of magical connections, but both seek new explanations deviating from the neoplatonic system. In the final third of the 17th century there is an increase of voices raised in criticism. With reference to this two writings published in 1673/74 are analysed. The authors are Thomas Bartholinus († 1680), an excellent anatomist and polyhistorian in Copenhagen, and Hermann Grube († 1698), a doctor in Hadersleben, Schleswig. Thomas Bartholinus defended magical practices, for example those using the transplantatio morborum, the amulet and the signature doctrine. Grube is much more critical and sceptical; he doubts all aspects of magical healing, for example the weapon salve, transference of disease, amulets, the choice of treatment according to similarity. Grube also makes his own experiments on the effectiveness of magical healing. He cannot confirm it. The credibility of Iatromagic decreased in the final third of the 17th century, the search for new interpretations shows that the neoplatonic system of thought has lost its validity. Iatromagic becomes pure practice, at the end of the 17th century it loses the character of being a scientific concept and in the 18th and 19th centuries it sinks to the level of household‐ and folk‐medicine. Around 1680 it met its end as a science.
Der Herausbildungsprozeß moderner wissenschaftlicher Disziplinen und ihre stadiale Entwicklung in der Geschichte
Authors: Guntau Martin 
Published: October 2006

AbstractResearch on the emergence of scientific disciplines has become a current topic of scientific historical work in recent years. Scientific disciplines are structures of cognitive social character whose geneses represent cornerstones in the history of scientific knowledge. As to the initial history of a science, such stages may be distinguished as its prehistory, emergence and consolidation. This development is dertermined above all by qualitative changes of the knowledge about a particular subject‐matter (1) against the background of concrete material and ideational needs of society (2), and the foundation of specific institutions forming the basis of existance of a scientific discipline (3). Geology is taken as an example to illustrate the emergence of a natural science at the turn from the 18th to the 19th century.
Ein gravierender Fehler in der Übersetzung und Interpretation der Akten des Galileischen Inquisitionsprozesses
Authors: Kurig Thomas 
Published: October 2006

AbstractErroneous translation of a crucial document from the Inquisition file on the trial of Galileo Galilei: In 1616 Galileo was forbidden to propagate the doctrine that the earth revolves around the sun. This injunction, by order of the pope, was only to be implemented if Galileo actually refused when asked to abandon his stance. Galileo was asked and did refuse. This fact has remained hitherto unknown because of an error in translation. The words in question are “successive, ac incontinenti”, which must be rendered as “then (following the order of the pope) because Galileo did not agree”. The document makes sense if translated in this manner.
Der Ort des rhetorischen Wissens Kunst und Natur bei Isokrates
Authors: Cahn Michael 
Published: October 2006

AbstractThis paper poses the question of the place of rhetoric as a discipline. It addresses the topical demand that nature, art, and exercise have to be combined by way of an analysis of Isocrates' Against the Sophists. Its thesis is that the call for a “combination” of art and nature solves the disciplinary problems of rhetoric, even though such a synthesis is in fact inconceivable. Rhetoric is not a science, and does not have access to a methodical correlation of rhetorical strategies and their effects upon the audience. Isocrates' criticism of those rhetoricians who assume that their art could be taught in much the same way as the art of writing is of paramount importance here. The case of Isocrates is instructive because it shows how rhetorical success depends on re‐designing the institutional structure of rhetoric and on the capacity to cope with its lack of methodical knowledge. As a result of its para‐scientific nature, rhetoric refers to various models and metaphors to present itself as a discipline. Of these the orator perfectus, the orator imperfectus, and the sophist model of the art of writing as criticized by Isocrates are discussed. This paper attempts a rhetorical reading of the discourse of rhetoric by exploring the implications of these metaphors. At the same time it argues for a history of science which does not shrink away from an analysis of such para‐sciences as rhetoric. It is precisely the lacking scientificity of rhetoric as a discipline which warrants increased attention from the point of view of the history of science.
Der quantitative Beitrag der nach 1933 emigrierten Naturwissenschaftler zur deutschsprachigen physikalischen Forschung
Authors: Fischer Klaus 
Published: October 2006

By scientiometrically analyzing the physics‐literature produced between 1925 and 1933 it is shown that the purely quantitative contribution of physicists subsequently emigrating from Germany to the literature produced by the physics community in this country was much lower than hitherto estimated. The actual figure is not in the range of 30%, as is generally assumed, but much nearer to 11%. Control analysis of three leading German physics journals and of memberships in the Deutsche Physikalische Gesellschaft confirms this result. Further investigation of university calendars shows that transferring these results to purely academic physics would amount to committing a “universalistic fallacy”. In academic physics emigré‐physicists held a total of 15,5% of all teaching postitions.Differentiating the physics literature into various specialties allows further insights into the cognitive and social structure of the German physics community before 1933. Works of emigré‐physicists are not randomly distributed over specialities; instead, the distribution reveals a nearly perfect correlation with what could be called “the specialty's paradigmatic age”. The spectrum begins with quantum theory, where future emigrants produced more than 25% of the literature, and fades away with acoustics, where their contribution amounts to less than 4%. The commonly accepted explanation of this phenomenon, which is based on the assumption that time of institutionalization of a specialty, “prestige” of that specialty, and entrance barriers for Jewish scientists are correlated, is falsified by two cases of non‐ or zero‐correlation: by the very old specialties and by the technical disciplines. A new explanans is proposed which is based on the hypothesis of cognitive and social marginality being correlated and on a certain amount of cognitive marginality enhancing the disposition to innovative behavior and creativity.
Die Mathematisierung der Naturwissenschaften vor dem Hinter‐grund der Bildungsvorstellungen des 19. Jahrhunderts
Authors: Schneider Ivo H. 
Published: October 2006

Both, astronomy in the first half of the 19th century and physics in the second half of the 19th century functioned as models and paradigms for the other sciences. The paradigmatic character of a theoretical, mathematical astronomy was due mainly to its capability to predict future events. According to the influence of the Romantische Naturphilosophie the mathematization of physics in Germany took place belatedly compared to France. A modified Newtonian research program with its mathematical implications was adopted by German physicists only after the establishment of the principle of energy conservation. German physicists of the late 19th century claimed over and above the results of physicists the successes of German technology for physics and interpreted these achievements as “cultural” achievements.They combined this claim with a request for a better representation of physics in the curricula of secondary schools so as to be comparable to that of mathematics. The resistance of the most prestigious secondary schools, the Humanistische Gymnasien, against this request meant that the concept of Bildung as propagated by physicists was not accepted generally in Germany.
Deutsch‐schwedische Wissenschaftsbeziehungen an der Universität Greifswald zwischen 1770 und 1850 unter besonderer Berücksichtigung von Chemie und Pharmazie
Authors: Friedrich Christoph 
Published: October 2006

AbstractThe aim of the article is to trace the German‐Swedish relations at the University Greifswald in the 18th and 19th centuries. Ch. E. Weigel translated many books and papers of famous Swedish chemists. During the periode from 1775–1815 many Swedish students staid in Greifswald. An other professor of chemistry in Greifswald, F. L. Hünefeld, was as a student by J. J. Berzelius. This paper analyzes the letters of these two scientists.