bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of competitive and non‐linear plasma protein binding on the stereoselective disposition and metabolic inversion of ibuprofen in healthy subjects
Authors: Smith David E. , Paliwal Jyoti K. , Cox Steven R. , Berardi Rosemary R. , Dunn‐Kucharski Valerie A. , Elta Grace H.
Published: October 2006

The stereoselective disposition and metabolic inversion of ibuprofen were studied in 12 healthy subjects under conditions of competitive and non‐linear plasma protein binding. Each subject received each of four oral treatments according to a Latin‐square design: 300 mg R(−)‐ibuprofen, 300 mg S(+)‐ibuprofen, 300 mg R(−)‐ + 300mg S(+)‐ibuprofen, and 300 mg R(−)‐ + 600 mg S(+)‐ibuprofen. For a given treatment, the partial clearance of S(+)‐ibuprofen was greater than that of R(−)‐ibuprofen for all stereoisomeric drug species. Likewise, the unbound partial clearances of S(+)‐ibuprofen were greater for most stereoisomeric drug species. There was also less difference among treatment groups when partial clearances were referenced to unbound as opposed to total plasma concentrations of enantiomer. The unbound intrinsic clearance and fractional inversion of R(−)‐ibuprofen were unchanged across the four treatments, and chiral inversion was systemic, averaging 69%. In conclusion, stereoselective differences exist for the partial and composite clearances of R(−)‐ and S(+)‐ibuprofen even when corrected for differences in plasma protein binding. However, differences among treatment groups for a particular elimination pathway are largely due to ibuprofen's non‐linear binding.
Repeated dose pharmacokinetics of pancopride in human volunteers
Authors: Salva P. , Costa J. , Perez‐Campos A. , Martinez‐Tobed A.
Published: October 2006

The aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL−1. The maximum plasma concentration (mean ± SD) after the first dose was 92.5 ± 41.5 ng mL−1 and tmax was 1.7 ± 0.9 h. The elimination half‐life (t1/2) was 14.3 ± 6.9 h. The area under the concentration‐time curve from zero to infinity (AUC) was 997 ± 396 ng h mL−1. The maximum plasma concentration (mean ± SD) at steady state (day 5) was 101.8 ± 36.9 ng mL−1 and tmax was 2.2 ± 1.2 h. The elimination half‐life (t1/2) was 16.3 ± 2.7 h and the minimum plasma concentration (C) was 16.6 ± 6.9 ng mL−1. The area under the concentration‐time curve during the dosing interval (AUC) was 995 ± 389 ng h mL−1. The average plasma concentration at steady state (C) was 43.3 ± 16.1 ng mL−1 and the experimental accumulation ratio (RAUC) was 1.34 ± 0.19, whereas the mean theoretical value (R) was 1.40 ± 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two‐compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration. The safety parameters showed no clinically relevant alterations.
The pharmacokinetics and absolute bioavailability of selegiline in the dog
Authors: Mahmood Iftekhar , Peters David K. , Mason William D.
Published: October 2006

Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. Currently no pharmacokinetic data are available for selegiline in the literature, mainly due to lack of analytical methods that can measure concentrations below 10 ng mL−1 in plasma. A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase‐B (MAO‐B) in vitro has been developed to measure selegiline in plasma as low as 0.25 ng mL−1. The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg kg−1 selegiline in solution via gavage or by an intravenous route separated by one week. The mean terminal half‐life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24 ± 9.56 min, 6.56 ± 0.56 L kg−1, and 159.91 ± 19.28 mL min−1 kg−1, respectively. After oral administration selegiline appeared to be absorbed rapidly with a tmax and Cmax of 25 ± 5.8 min and 5.2 ± 1.36 ng mL−1, respectively. The absolute bioavailability of selegiline in the dog was 8.51 ± 3.31%.
The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis
Authors: Yamamura Yoshikazu , Tanaka Naomi , Santa Tomofumi , Kotaki Hajime , Aikawa Tatsuya , Uchino Katsuyoshi , Osuga Toshiaki , Sawada Yasufumi , Iga Tatsuji
Published: October 2006

The pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half‐life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7–7.6 h and 6.2–40.1 h, and the total body clearance (CLtot) in the range of 2.8–23.2 mL h−1 kg−1 and 1.4–12.9 mL h−1 kg−1, respectively. The t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtot values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtot and hepatic function (asparatate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtot for glycyrrhizin increased from 2.8 ml h−1 kg−1 to 11.4 mL h−1 kg−1, and the t1/2 shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the extent of the liver function.
The bioavailability of cefpodoxime proxetil tablets relative to an oral solution
Authors: Borin Marie T. , Forbes Kristi K. , Hughes George S.
Published: October 2006

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL−1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high‐fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24h period, and urine was collected for 48h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability.
Pharmacokinetics of the antiarrhythmic agent tiracizine: Steady state kinetics in comparison with single‐dose kinetics
Authors: Berndt Annette , Oertel R. , Terhaag B. , Richter K. , Gramatté Th.
Published: October 2006

Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine‐induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1,Cmax,ss= 391.8 ng mL−1againstCmax,sd= 132.8 ng mL−1; M2,Cmax,ss= 143.2 ng mL−1againstCmax,sd= 25.8 ng mL−1). However, significant increases of AUC (AUCτ = 261.9 ng h mL−1against AUC0–∞,sd= 182.9 ng h mL−1),Cmax(Cmax,ss= 75.9 ng mL−1againstCmax,sd= 56.9 ng mL−1) andt1/2β(t1/2β,ss= 4.0 h againstt1/2β,sd= 2.4 h) of the parent compound indicate non‐linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non‐renal tiracizine clearance with repeated dosing led to the assumption that non‐linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at thetmaxof the parent compound, whereas there was no change in any ECG parameter after a single‐dose administration of 50 mg tiracizine.
Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia
Authors: Koopman‐Kimenai Petronella M. , Vree Tom B. , Booij Leo H. D. J. , Hasenbos Marcel A. W. M.
Published: October 2006

After epidural administration of 15 mg 3, 6‐dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6‐mononicotinoylmorphine and morphine. The mean apparent half‐lives (±SD) of elimination were 10 min (0.165 h ± 0.053 h) for 3, 6‐dinicotinoylmorphine and 1.77 h ± 1.23 h for 6‐mononicotinoylmorphine. Morphine is subsequently metabolized into morphine‐3‐glucuronide, and morphine‐6‐glucuronide. The apparent half‐lives of morphine, morphine‐3‐glucuronide, and morphine‐6‐glucuronide are similar: 3.63 h ± 1.63 h, 4.10 h ± 0.57 h, and 4.20 h ± 1.64 h respectively. The possible glucuronide conjugate of 6‐mononicotinoylmorphine was not detected. The prodrug 3, 6‐dinicotinoylmorphine was biotransformed into three active compounds: 6‐mononicotinoylmorphine, morphine, and morphine‐6‐glucuronide.
Factors influencing the protein binding of YH‐439 using an equilibrium dialysis technique. A new hepatoprotective agent
Authors: Lee Woo I. , Yoon Woo H. , Park Joo H. , Lee Jong W. , Shim Chang‐K. , Lee Myung G.
Published: October 2006

Various factors influencing the plasma protein binding of YH‐439 to 4% human serum albumin (HSA) were evaluated using the equilibrium dialysis method at the initial YH‐439 concentration of 2 μg mL−1. It took approximately 12 h of incubation to reach an equilibrium between 4% HSA and isotonic phosphate buffer of pH 7.4 containing 3% of dextran (‘the buffer’) using a Spectra/Por 2 membrane (molecular weight cut‐off, 12 000–14 000) in a water bath shaker kept at 37. C and at a rate of 50 oscillations min−1. YH‐439 was fairly stable both in 4% HSA and in the ‘buffer’ for up to 24 h incubation. The binding of YH‐439 to 4% HSA was constant (97.4 ± 0.55%) at YH‐439 concentrations ranging from 0.5 to 10 μg mL−1. However, the extent of binding was dependent on HSA concentrations: the values were 90.7, 94.7, 96.7, 97.0, 97.0, 97.1, and 97.5% at HSA concentrations of 0.5, 1, 2, 3, 4, 5, and 6%, respectively. The plasma protein binding decreased with increasing incubation temperature: the binding values were 98.2, 97.6, 97.2, and 96.8% when incubated at 10, 21, 26, and 37°C, respectively. The binding of YH‐439 was also influenced by the chloride concentration in the buffer: the binding values were 94.5, 97.0, and 96.8% for the chloride concentrations of 0, 0.249, and 0.546%, respectively. The binding of YH‐439 was also dependent on the buffer pH: the percentages of free fraction were 6.0, 4.1, 3.8, 2.8, 2.7 and 2.8% for the buffer pHs of 5.0, 6.0, 6.5, 7.0, 7.4, and 8.0, respectively. The free fraction of YH‐439 was slightly increased by the addition of heparin (up to 40 U mL−1), sodium azide (NaN3, up to 0.5%), and its metabolites. The protein binding of YH‐439 was influenced neither by AAG, acetylsalicylic acid, or sulphisoxazole, nor by the addition of citrate or EDTA. The free fractions of YH‐439 in rabbit (4.2%) and dog (4.7%) plasma seemed to be higher than in rats (2.9%) and humans (3.1%).
Handschriftliche Funde zu den “verdrängten Wissenschaften” in der frühen Neuzeit
Authors: Schipperges Heinrich
Published: October 2006

A report based on studies in Spanish libraries where about 80 manuscripts have been examined, and concentrating itself on: 1ththe part played by “Astrologia Medica”, 2ndthe importance of “Alchimia Medica”, 3rdthe structure and function of “Magia Naturalis” in the late middle ages.
Folgen der Emigration deutscher und österreichischer Wissenschaftstheoretiker und Logiker zwischen 1933 und 1945
Authors: Thiel Christian
Published: October 2006

The paper begins by delimiting the scope of ‘logic’ and ‘philosophy of science’ and goes on to present the biographies and select bibliographies of 36 émigré scholars from Germany and Austria working in these fields. An evaluation of this material, and of data on societies, congresses, lecture series, books and periodicals on logic and philosophy of science, is then undertaken. Against the rich background of activity in the 20s and 30s of our century, there is manifest a rapid decline of high‐ranking research in the philosophy of science and (to a lesser degree) in logic in Germany and Austria. Since, with one exception, émigré logicians and philosophers of science did not return after the breakdown of the Third Reich, recovery in these fields has been extremely slow. Pertinent knowledge had to be re‐imported, and a satisfactory level has been reached only with the coming of a new generation.
Die Idee einer historischen Entwicklung der Krankheiten des Menschengeschlechts und ihre Bedeutung für die empirische Medizin des frühen 19. Jahrhunderts
Authors: Bleker Johanna
Published: October 2006

In early 19th‐century German medicine many doctors had a strong interest in historical pathology. They investigated the historical records of fevers and epidemics in detail, trying to find out how the changing influence of the epidemic constitution worked and hoping that history would help them to define specific disease entities. The underlying theory of this endeavour was that diseases undergo a historical development similar to the evolution of plants and animals. This paper tries to show that historical pathology was, in its time, a legitimate attempt to solve the most urgent problems of empirical medicine.
Von der „Natur der Sache”︁ zur Geschichte der Sprache Der Übergang von der Sprachforschung zur Sprachwissenschaft zu Beginn des 19. Jahrhunderts
Authors: Grotsch Klaus
Published: October 2006

From the “nature of things” to the history of language: The transition from the study of language to historico‐comparative linguistics. This brief essay deals with a somewhat problematic phase in the history of linguistics and tries to investigate the process by which language could be understood as a historical phenomenon with a history of its own. This new understanding of language turned out to be the starting condition for a new and very prolific way in the study of language. The conjecture is that this is due to certain alterations in the semantic field of some important notions relating to language and its study. The process of alteration began by the end of the eighteenth century with conceptual achievements which could adequately be termed as temporalization of aspects of language and the notions related to these aspects. In connection with the so called discovery of the Sanskrit language and the gradual reception of its grammatical structure, looking upon language as an organic entity with autonomous and internal structures of developpement became possible after the German romantic language philosophy had developped a strictly abstract concept of language as a notion of form. This essentially metaphorical mode of speaking nevertheless inaugurated that languages were concieved of as having their own history totally independent of their speakers. With language as an autonomous object the study of language rapidly became the science of language.
Geschlecht und Gesellschaft: Die ersten Ärztinnen und sozialpolitische Vorurteile
Authors: Geyer‐Kordesch Johanna
Published: October 2006

The objective mode of scientific inquiry has increasingly been called into question especially within feminist theory. I have tried to introduce two methodological approaches in examing a small area of medical opinion‐making in the medical press at a period in which the question of women doctors was being discussed, but very few women doctors were actually practicing in Germany. Methodologically feminist history sees gender as a structural component used to ascribe sexual division of labour and to form concepts of “masculinity” and “femininity” in a society. It does not define “women's history” as a separate sphere additive to other traditional areas of historical writing including history of science. The second methodological approach is that of deconstruction: “objective” statements in medicine and the biological sciences are part of social and cultural preconceptions. I have examined the pattern of unreflected scientific statements about women's claims to want to become doctors. The pattern is one of preventive prejudice: representative doctors wrote about women in physiological and biological terms of being “weak” and “unfit”. This was an effective strategy for maintaining a status quo of dequalification. The historical examination of women entering the professions has not so much to do with their own capacities, but rather with socially conceived forms of argumentation indirectly applied: preventive statements in medicine about biological function, the “weaker” sex, intellectual denigration, physiological determinism. Some of the statements I found are amusing, but the humour becomes bitter when the consequences enter our social consciousness.
Theologische Wissenschaft und Frömmigkeit im Konflikt: Ferdinand Christian Baur und seine Schüler
Authors: Köpf Ulrich
Published: October 2006

The Tübingen School has essentially effected the formation of historical theology in the 19th century. But F. Chr. Baur, the founder of the school, had to overcome great resistances, and all his pupils (D. F. Strauß, E. Zeller etc.) were prevented from a career in a theological faculty.
“Die wissenschaftliche Ausbildung des Arztes ist eine Culturfrage …”. Über das Verhältnis von Wissenschaftsanspruch, Bildungsprogramm und Praxis der Medizin
Authors: Toellner Richard
Published: October 2006

The article shows that the elite, nationalistic and imperial mentality of German medicine in the second half of the nineteenth century was closely connected to its aim to be understodd as a natural science. With this in view leading representatives of German medicine propagated a scientific approach to man and nature instead of the traditional values of humanistic education (“Bildung”). One of the most important consequences of the new scientific ideal in medicine — integration in governmental planning, the change in professionel status of doctors, the increasing tendeny to recognize biologistic ideologies — was the loss of the medical ideal of the ars medica, a subject which has not received sufficient thematic attention. This theme is explored in the third part of the article.
Frühe Fälle der “Verwendung” von Analogien in der altgriechischen Medizin
Authors: Langholf Volker
Published: October 2006

Analogy in ancient Greek medical texts may be either explicit or implicit. Greek physicians of the fifth and fourth centuries B.C. often used explicit analogy, e.g. when trying to explain unobservable processes within the body by comparing them to observable processes in common objects. Such explicit analogies served several purposes: illustration, exemplification, confirmation, or a combination thereof. ‐ Other analogies are implicit, particularly those originating in metaphors, i. e. in language. While explicit analogies were intended to support only marginal details of medical doctrines, analogies implicit in metaphors occasionally became the nuclei of comprehensive and therapeutically important doctrines, particularly with reference to the crisis of a disease. ‐ Explicit and implicit analogies occur already very early (Homer, eighth century B. C.) and with characteristics which make it possible to assess the specific function of analogy in Greek medical texts of the fifth and fourth centuries B.C.
Gesellschaftsstruktur als Analogie: Genetiker stellen sich die Zelle vor
Authors: Harwood Jonathan
Published: October 2006

In den 1920er und 1930er Jahren entstand eine heftige Diskussion unter deutschen Genetikern, inwieweit das Zytoplasma eine wichtige Rolle bei der Vererbung spiele. Für Vertreter des sogenannten ‘Kernmonopols’ waren es lediglich die Gene in den Chromosomen des Zellkerns, die den entscheidenden Einfluß auf die Entwicklung jeder Zelle hätten, während das Zytoplasma bloße Rohstoffe für die Gen‐Wirkung liefere. Für die Vertreter der ‘Plasmontheorie’ dagegen war die zeitliche und räumliche Ordnung der genbedingten Entwicklungsvorgänge ohne die regulierende Wirkung einer ganzheitlichen genetischen Struktur im Zytoplasma (‘Plasmon’) nicht denkbar. Weder die Argumente der Plasmontheoretiker noch diejenigen der Kernmonopolisten waren allein empirisch begründet; beide setzten gewisse Annahmen voraus.
Ernst Haeckel, Zoologie und Jugendstil
Authors: Mann Rosemarie
Published: October 2006

Au début du 19e siècle, à la suite des tours du monde en voiliers à but scientifique, commença l'époque de l'exploration maritime. Une faune inconnue retint l'attention des scientifiques. Surtout de nombreuses espèces nouvelles de méduses occupèrent les chercheurs. Une littérature specialisée se developpa rapidement, cependant une étude systematique et unitaire faisait défaut. Ernst Haeckel essaya de combler ce manque en 1879/80 avec son ouvrage «System der Medusen». Pas un ouvrage classique, comme l'écrivit Thilo Krumbach, mais pour tous ceux qui sont les adeptes d'une recherche biologique systématique, cet ouvrage est indéniablement une pierre angulaire. Les descriptions critiques de toutes les espèces connues et les excellents tableaux recueillirent approbation et admiration. Le principe artificiel de classification et les efforts trop forces de rapports d'ontogénie suscitèrent la critique. — Les tableaux zoologiques ultérieurs de Haeckel furent beaucoup appréciés par les artistes, surtout les «Kunstformen der Natur». Le mouvement Art Nouveau — Jugendstil, d'inspiration naturaliste, qui débuta en Angleterre et en France dans les années 1880, trouva en eux des modèles idéaux. L'abondance des formes et la beauté des animaux marins — jusqu'alors inconnus — fascinèrent les artistes.

Une influence directe est évidente pour Hermann Obrist, August Endell, René Binet, Karl Gross et bien d'autres et dans beaucoup de traités de l'histoire de l'art au sujet du style des années de 1900, les tableaux de Haeckel représentent une source importante de l'inspiration.
Zur Geschichte des Kaiser‐Wilhelm‐Instituts für physikalische Chemie und Elektrochemie. Zur geplanten Veränderung des Instituts in eine Forschungs‐ und Entwicklungsstätte des Heeres für den Gaskampf und Gasschutz auch in Friedenszeiten 1916 und nach 1933
Authors: Stoltzenberg Dietrich J.
Published: October 2006

A Contribution to the History of the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry: On Projected Changes of the Institute into a Research and Development Center of the Army for Chemical Warfare also in Times of Peace 1916 and after 1933. — The Kaiser Wilhelm Institute for Physics and Electrochemistry, today named after its first director Fritz‐Haber‐Institut, was in the first World War a place of research on chemical warfare. Evidences in the Archive for the History of the Max‐Planck‐Gesellschaft show that it was planned during the war to continue research in this area in peacetime. To realize this Fritz Haber proposed to found a special Kaiser Wilhelm Institute. As this could not be accomplished the war ministry founded 6 million marks to establish an extra department in the KWI of Physical Chemistry and Electrochemistry just before the end of the war. After Germany lost the war these were used for other research areas while work on chemical warfare was carried out elsewhere.

When Fritz Haber resigned 1933 because of the race‐laws of the nationalsocialists the war ministry in cooperation with the ministery for culture nominated an obliging scientist as director of the institute with the aim to take up again research in the area of chemical warfare despite of the opposition of the president of the Kaiser‐Wilhelm‐Gesellschaft and the ministery of the interior. After that time until the end of the second world war 1945 a good part of the work carried out in the institute was done for the war ministry.
Hilbert, Zermelo und die Institutionalisierung der mathematischen Logik in Deutschland
Authors: Peckhaus Volker
Published: October 2006

This paper presents the history of the first German lectureship for mathematical logic based on a ministerial commission, to which the Göttingen mathematician Ernst Zermelo was appointed in 1907. The lectureship is shown as imbedded in the intellectual history of mathematical logic which was at that time determined by the discussion of the set theoretical and logical paradoxes. Although Zermelo's early set theoretic papers can be regarded, and were in fact regarded in the Göttingen mathematicians' application for the lectureship, as contributions to mathematical logic, the close connection between set theory and logic was at that time not evident. It is shown, however, that such “internal” motives were not the only reasons for proposing the lectureship, since the application was also highly influenced by personal and institutional factors and the attempt to find a paid position for Zermelo at the University of Göttingen. In addition, Zermelo's lectureship is presented in the context of the history of academic teaching in mathematical and symbolic logic with an overview of German lecture courses in this topic in the period between 1830 and 1915. The results are correlated with the reception of George Boole's algebra of logic and other symbolic logical systems in Germany at that time. Zermelo's lectureship is regarded as the first step towards an institutionalization of mathematical logic as a subdiscipline of mathematics. This step is interpreted by critically applying the results of Hubert Laitko's and Martin Guntau's considerations on the genesis of scientific disciplines.
(29. Symposium der Gesellschaft für Wissenschaftsgeschichte an der RWTH Aachen, 28. bis 30. Mai 1992). Bemerkungen zur Fragestellung und zu den Ergebnissen der Tagung
Authors: Kaiser Walter
Published: October 2006

The subject of the 29th conference of the Gesellschaft für Wissenschaftsgeschichte was the “Problem of Interaction of Science and Technology”. At issue at the conference was the difficult relationship between the theoretical concepts and the data of science and the practical devices and processes of technology. Although the interplay of science and technology is a well established field of research in the History of Science and Technology, there are still no solutions to the problem, especially with regard to the continuous discussions in the realm of science policy and technology policy. So the conference aimed both at a contribution to the historiographic problems of the science‐technology relationship and at a historical foundation for the discussion in technology policy.
Professoren als Gutachter für die Kälteindustrie 1870–1930. Ein Beitrag zum Verhältnis von Hochschule und Industrie in Deutschland
Authors: Dienel Hans‐Luidger
Published: October 2006

German professors at Polytechnic Institutes (Technische Hochschulen) were successfully consulting refrigeration industry after 1870. Besides of the tremendous output of graduates and of the results of scientific research itself, the expertise was a third important function of Polytechnic Institutes for the industrial development in Germany. The article analyzes the functions of consulting for industry by presenting five types of expertise: Expertise in behalf of the government, expertise for patent‐cases, expertise as machine‐description and test, expertise for the acceptance of machines, and expertise for investment‐credits. Carl von Linde, Moritz Schröter, Hans Lorenz Theodor Ganzenmüller and Rudolf Plank are examined as case studies. The article argues that German Professors could fulfill this highly demanded function because they were accepted both as competent and neutral.
Theoretische Ansätze und praktische Erfahrung in der Nationalökonomie unter besonderer Berücksichtigung Joseph A. Schumpeters
Authors: Winkel Harald
Published: October 2006

The paper presents in a short survey the development of economic thought from mercantilism to Keynes, where specially the connections between economic reality and thinking were pointed out. New ideas as well as the re‐examination of those of the past depend on real development of the economy. So, for instance, the ideas of Keynes and the conviction that business cycles could be managed failed and were followed by a return to Schumpeter and his ideas which seem to be very attractive nowadays.
Die Nachfolge von August Kundt und Hermann von Helmholtz im Spiegel der Korrespondenz zwischen Emil Fischer und Friedrich Kohlrausch
Authors: Stoltzenberg Dietrich
Published: October 2006

In 1894, three great German physicists died: Heinrich Hertz in Bonn, August Kundt and Hermann von Helmholtz in Berlin. As their successor Friedrich Kohlrausch, director of the Institute of Physics in Straßburg, was nominated. He denied to go to Bonn and at first accepted the call to Berlin as director of Kundt's former Institute of experimental physics, but he took for granted that the chair should be devided, declaring that it would be impossible to take the burden of teaching, research and the whole administration. After some months of negotiation the philosophical faculty refused this condition. In the meantime the director of the Physikalisch‐Technische Reichsanstalt Helmholtz died, and the Prussian Cultural Ministry offered this position to Kohlrausch, who accepted it. These proceedings which were kept secret by the faculty were openly discussed and commented in the correspondence between Emil Fischer and Friedrich Kohlrausch.
Neue Dimensionen wissenschaftlicher Reisen im 18. Jahrhundert Maupertuis' Lapplandexpedition
Authors: Hecht Hartmut
Published: October 2006

The Lapland‐expedition of Maupertuis and his group of young academics is known as one of the most decisive and most impressive experimental determinations of the figure of the earth which will be obviously discussed against the background of the fundamental antagonism of 18th century philosophy, i.e. the struggle of Cartesianism against Newtonianism and vice versa. Following such an interpretation, the historian is only interested in one aspect of the voyage. Nevertheless, there are other ones which, taken into account, modify the inherited perspective on the expedition enormously. In this paper the experimental proof of the Newtonian theory as well as the ethnographic observations, the investigation of the inscriptions from Windso etc. will be studied. The argumentation tries to give an explication of the Lapland‐expedition as a whole and develops it in comparison with Leibniz' grand tour to Southern Germany, Austria and Italy. Its dominating point is to stress that the new dimensions of scientific voyages in the 18th century are to be understood as elements of a new philosophical paradigm, i. e. an all‐embracing historical world‐view.
‚Reise der Aufklärung’︁: Selbstverortung, Empirie und epistemischer Diskurs bei Herder, Lessing, Lichtenberg und anderen
Authors: Kleinknecht Thomas
Published: October 2006

The »journey of enlightenment« (Lea Ritter Santini) should denote an ideal type of explorative events that produced the twin effect of shedding new light on any given topic and, simultaneously, of representing a modern scientific, yet humane outlook to the world. This outlook depended on a higly reflective approach of viewing the world, granting the self an original, even pivotal position (Herder is a case in point). It could involve self‐delusion and could have melancholy or pathological results. The successive phases of a journey, (a) the discovery of unfamiliar surroundings and (b) its legitimatory aftermath, should therefore be linked to the biographical setting of the travellers involved. The journey often left a lifelong impact on their lives; Lichtenberg is exemplary in this respect.

Recent research into eminent figures of the Enlightenment period, e. g. into Lessing, have enabled us to follow quite closely the learning and filtering process, by which the gradual acquisition of knowledge and judgement took place. A lively face‐to‐face and/or epistolary intercourse in most cases accompanied the interpretation of data culled from observation. Furthermore, discussion (vis‐à‐vis mere registration or sketching) proved essential for reaching an understanding of a fairly intersubjective standing. Lichtenberg's two visits to England provide a minute protocol of a variety of steps that ‐ more in a zigzag than in a direct fashion ‐ eventually form the growth and the style of our (preliminary) knowledge ‐ by taking journeys.
„Gehet hin in alle Welt …”︁ Die Aneignung fremder Sprachen und die Sprachwissenschaft des 18. und 19. Jahrhunderts
Authors: Nowak Elke
Published: October 2006

“The appropriation of foreign tongues and eighteenth and nineteenth centuries linguistics”. ‐ Until well into the nineteenth century the documentation of hitherto unknown languages was but a by‐product of other activities: samples of languages were gathered on expeditions as anthropological specimen, and missionaries did their best to come to grips with the alien tongues they encountered. Although a large number of languages was known by the beginning of the nineteenth century, the number of printed grammars was very small and their reception by the European scientific community was ambiguous. Most of these grammars were composed by missionaries to facilitate the acquisition of the respective language. Most of them show serious deficiencies. From a historiographic perspective the exclusively practical purpose of these grammars highlights two characteristics of the science of language of the time. The actual process of composing a grammar was not a part of investigations into language or languages. There was nothing close to what might be called “empirical research” with respect to the investigation of languages. It was only in the nineteenth century that the importance of language data was advocated by American scholars and the investigation of non‐literate languages was subsequently introduced into linguistic research.
Messen und Zählen. Die Herstellung des normalen Menschen als Maß der Gesundheit
Authors: Hess Volker
Published: October 2006

The emergence of a ‘norm of normalcy’ in 19th century laboratories and hospitals was in no way simply a byproduct of the scientific search for knowledge. It was instead closely associated with expectations of social egalitarianism which merged with the moral economy of a new scientific objectivity. The establishment of normal people as a valid measure for a population socially divided and segregated in estates was thus an essential element of the processes of social formation which created our modern society.
Recruitment pharmacophore for interleukin 5 receptor α antagonism
Authors: Bhattacharya Madhushree , Pillalamari Udaya , Sarkhel Sanjay , Ishino Tetsuya , Urbina Cecilia , Jameson Bradford , Chaiken Irwin
Published: October 2006

Interleukin‐5 receptor α is a therapeutic target for hypereosinophilic diseases including allergic inflammations and asthma. The cyclic peptide AF17121 (Ac‐VDE[CWRIIASHTWFC]AEE‐CONH2) has been identified as a submicromolar inhibitor of interleukin 5 (IL5)‐interleukin 5 receptor α (IL5Rα) interaction from a random peptide screen. However, this inhibitor has limitations as a drug lead because of its relatively large size. We used chemical synthesis of peptides with natural and non‐natural amino acids along with kinetic binding and cell proliferation competition assays to expand definition of structural elements in the peptide that are important for receptor antagonism and to elucidate the underlying pharmacophore. We found that the specific steric array of hydrogen bonding groups in the Arg 6 guanido side chain is critical for receptor inhibition. We also investigated noncharged structural elements in AF17121. Screening a set of five hydrophobic residues showed that peptide function is strongly sensitive to variations in several of these residues, most prominently Ile 7 and Trp 13. We postulate that presentation of charged, hydrogen bonding and hydrophobic structural elements within the disulfide‐constrained peptide drives IL5Rα recruitment by AF17121. We hypothesize from these results and previous receptor mutagenesis studies that Arg 6 recruitment of IL5Rα occurs through hydrogen bonding as well as charge–charge interactions with Asp 55 in site one of domain 1 of IL5Rα, and that this interaction is complemented by additional charged and hydrophobic interactions around the Asp 55 locus. Scaffolding a limited set of structural elements in the inhibitor pharmacophore may be useful for small molecule antagonist design inspired by the peptide. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88:83–93, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.
Laparoscopic incisional hernia repair with a self-centring suture
Authors: Motson R W , Engledow A H , Medhurst C , Adib R , Warren S J
Published: October 2006

Background

Open incisional hernia repair is associated with high morbidity and recurrence rates. Laparoscopic approaches offer improved long-term results with low complication rates.

Methods

Laparoscopic repair was attempted in 117 consecutive patients (median age 68 (range 31–91) years, 50 men) undergoing 122 operations. A novel mesh centralization technique was employed. Data were recorded prospectively. Follow-up was by clinical review or telephone consultation.

Results

One hundred and eighteen procedures (96·7 per cent) were completed laparoscopically; four required conversion. Forty-one patients (35·0 per cent) had additional, unsuspected defects. The median mesh size was 225 (range 42–600) cm2. Median follow-up was 42 months. Small bowel enterotomy occurred in six patients. Fourteen postoperative seromas were successfully aspirated. Recurrence was detected in nine patients (7·7 per cent). One patient was readmitted with small bowel obstruction that settled with conservative management. There were no enterocutaneous fistulas. One patient died after operation from myocardial infarction.

Conclusion

Laparoscopic incisional hernia repair using a self-centring suture provides good long-term results with low complication rates.
Study of the bioavailability of different formulations of 8‐methoxypsoralen in the dog
Authors: Monbaliu J. G. , Belpaire F. M. , Bogaert M. G.
Published: October 2006

The absolute bioavailability of 8‐methoxypsoralen in gelatin capsules and as a solution was studied in dogs. A dose of 2 mg kg−1 was given. Both for the solution and the gelatin capsules, a large variation in bioavailability was found between the different dogs. For the gelatin capsules in 1 dog out of 4 an absolute bioavailability of more than 100 per cent was found; for the solution a bioavailability of more than 100 per cent was found in all 4 dogs. Resorption was more rapid and bioavailability higher for the solution than for the gelatin capsules.

Relative bioavailability of an emulsion and of a solution of 8‐methoxypsoralen was studied in 2 dogs. A faster resorption and a higher bioavailability were found for the solution.
Influence of food on the absorption of theophylline administered in the form of sustained release tablet and microgranules
Authors: Delhotal‐Landes Brigitte , Flouvat Bernard , Karpouzas Ianis , Prinseau Jacques , Boutin Marie‐Sylvie
Published: October 2006

Two sustained‐release formulations of theophylline, tablets (T) and microgranules (MG) forms, were administered in a randomized order to 8 healthy subjects in fasting or with a high‐protein test meal (50 per cent). Blood was collected for 32h post‐dose. In fasting subjects, absorption of theophylline was significantly faster for T (tmax 5 h) as compared with MG (tmax 8 h, p<0‐05), but Cmax and AUC were comparable; intersubject variability was higher with T. Administration of a high‐protein test meal with T produced a significant decrease of the zero‐order absorption rate constant of theophylline (Ko 37·8±9 1 mgh−1 after meal versus 58·8±13mgh−1 in fasting, p=0·01), tmax was doubled to 10 h, and Cmax increased by 25 per cent (6·33±2·16 mgl−1 versus 504±1·28 mgl−1p <0 02); with MG, tmax were the same (8 h), Cmax were not significantly increased (4·79±0·84 mgl−1 versus 4·55±0·67 mgl−1), absorption was delayed (lag‐time 1·28±0·58 h) and the absorption was slightly accelerated (Ko 50·4±10·4 mgh−1 versus 42·3±11·9 mgh−1, NS). For each form bioavailability was not significantly modified by food. This study demonstrated that food rich in protein modifies the absorption rate of theophylline in a sustained‐release tablet formulation but is without influence in a pH‐independent, sustained‐release microgranule formulation.
Dose‐dependent pharmacokinetics of probenecid in the rat
Authors: Emanuelsson B‐M. , Paalzow L. K.
Published: October 2006

The basic pharmacokinetics of probenecid was studied by administration of three different i.v. bolus doses (50, 75, and 100 mg kg−1) to rats. The protein binding of probenecid in pooled rat serum was estimated by equilibrium dialysis. The unbound fraction was found to increase non‐linearly with increasing total concentration, yielding a maximum free fraction of 49 per cent. The plasma concentration data obtained were described by a two‐compartment model with Michaelis‐Menten elimination. The maximal rate of elimination (Vm) remained unchanged between different doses irrespective of whether it was calculated in total or free concentrations (mean 187·2±8·3 (SD) μg min−1). The Michaelis‐Menten constant (Km) decreased slightly with increasing dose, while the unbound Michaelis‐Menten constant (Km, u) did not change between the doses (mean 37·1±1·3 (SD) μg ml−1 ). The volume of distribution of the central compartment (Vc, u) did not alter when the dose was increased from 50 to 100 mg kg−1 (mean 56·5±4·3 (SD) ml), but the unbound volume of distribution of the central compartment (Vc, u) decreased from 186·5±15·6 (SD) to 89·8±6·9 (SD) ml, which is in accordance with the reduction to be expected for drugs that only distribute in the extracellular fluid.
Pharmacokinetics and bioavailability of etintidine in beagle dogs: Effects of routes of administration, doses, dosage forms, and chronic dosing
Authors: Huang Shiew‐Mei , Abrams Larry S. , Marriott Thomas B. , Weintraub Howard S.
Published: October 2006

Etintidine HCl is an H2 receptor antagonist which has been under clinical trial for the treatment of duodenal ulcer diseases. Our studies are to determine the effects of routes of administration, doses, dosage forms, and chronic dosing on the bioavailability and pharmacokinetics of etintidine (E) in the beagle dog. Salient findings are:

Plasma levels of etintidine after i.v. administration of 200mg of E followed a 3‐exponential decay with a terminal t½ of 1.7 h.

Following oral administration of 200mg of E in capsules, tablets, or a solution dosage form to dogs, etintidine was rapidly and nearly completely absorbed with no significant first‐pass elimination.

A proportional increase in the amount of etintidine absorbed in the dogs occurred as the administered doses increased from 30 to 180 mg kg−1 and this relationship did not change with repeated dosing.

Some accumulation of etintidine took place during the 52 weeks of chronic dosing.
Bioequivalence study of two liquid formulations of benzydamine
Authors: Catanese B. , Del Bosco M. , Lagana A. , Curini L. , Colloca A.
Published: October 2006

A bioequivalence study of two liquid formulations containing benzydamine hydrochloride was carried out to evaluate the influence of a change of the excipients and the addition of a flavouring agent, ICEBERG AR 84/05/15, on the absorption of benzydamine.

No statistically significant differences were observed suggesting that the two formulations are bioequivalent.
On the absorption of clavulanic acid
Authors: Allen G. D. , Coates P. E. , Davies B. E.
Published: October 2006

It was not possible to computer fit oral clavulanic acid data using exponential or model equations incorporating a single exponential defining the absorption phase. Using the Loo‐Riegelman method three phases of the absorption process became apparent, an initial slow phase, a more rapid phase and a final slow phase, contributing approximately 20, 70, and 5%, respectively, to the overall absorption process. Statistical moment analysis of clavulanic acid data following intravenous and oral solution administration gave mean values for the mean residence time, mean absorption time, and volume of distribution steady‐state of 56 min, 43 min, and 14.01, respectively. Weibull analysis of the oral solution data gave mean values for lag‐time and mean absorption time of 8 min and 46.8 min, respectively. Administration of clavulanic acid in a capsule formulation increased the lag‐time before absorption but had no significant effect on the mean absorption time.
Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease
Authors: Eradiri Okponanabofa , Jamali Fakhreddin , Thomson Alan B. R.
Published: October 2006

The influence of prednisone( PR ), sulfasalazine( SZ ), cimetidine( CM ), and pheno‐barbital(PB) on the pharmacokinetics of metronidazole was investigated in six Chrohn's patients. Metronidazole was first administered alone ( 250 mg bid, po ) and then with prednisone ( 10mg bid, po), sulfasalazine (lg bid, po), cimetidine ( 600mg bid ) or phenobarbital ( 60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole‐1‐acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 ± 0.15 1kg−1, a half‐life of 9.7 ± 3.1 h and an oral clearance of 0.852 ± 0.23 ( ml−1min ) kg−1. The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half‐life, and urinary excretion of the parent drug.