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  • 1965-1969  (104)
  • Psychopharmacology  (37)
  • Insulin  (35)
  • Engineering General
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 325-330 
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; blood sugar ; mice ; rats ; pancreatectomy ; nephrectomy ; hepatectomy (partial) alloxan diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez les rats et les souris le taux du sucre sanguin est abaissé par une proinsuline obtenue à partir de l'insuline bovine (Schmidt et Arens [6]). Chez les rats alimentés et les souris à jeun, le rapport d'activité proinsuline: insuline est de 1∶4, chez les rats à jeun de 1∶2, dans le cas de dose équimolaire et en mesurant l'abaissement maximum du sucre sanguin. L'abaissement du sucre sanguin évolue de façon plus lente après proinsuline qu'après insuline. La proinsuline, incubée in vitro avec la trypsine, agit quantitativement et au point de vue temps, comme l'insuline. Chez les rats pancréatectomisés, chez les rats néphrectomisés ainsi que chez ceux hépatectomisés aux deux tiers, l'action de la proinsuline est la même que chez les animaux normaux. Les souris rendues diabétiques par l'alloxane répondent également à la proinsuline comme les souris intactes. L'action hypoglycémiante de la proinsuline se manifeste de façon retardée probablement parce que l'insuline active doit tout d'abord se former par un processus protéolytique dépendant du facteur temps. Ceci pourrait être aussi la raison pour laquelle, Rubenstein et coll. [5] signalent l'absence d'effet de la proinsuline dans le test de convulsion chez la souris.
    Abstract: Zusammenfassung An Ratten und Mäusen wird der Blutzucker durch ein aus Rinderinsulin gewonnenes Proinsulin (Schmidt und Arens [6]) gesenkt. Bei gefütterten Ratten und nüchternen Mäusen ist das WirkungsVerhältnis Proinsulin: Insulin = 1∶4, bei nüchternen Ratten 1∶2, wenn äquiznolar dosiert und das Maximum der Blutzuckersenkung gewertet wird. Die Blutzuckersenkung verläuft nach Proinsulin protrahierter als nach Insulin. Proinsulin, welches in vitro mit Trypsin inkubiert wurde, wirkt quantitativ und zeitlich wie Insulin. Bei pankreatektomierten, bei nephrektomierten und bei zweidrittelhepatektomierten Ratten wirkt Proinsulin ebenso wie an Normaltieren. Auch alloxandidbetische Mäuse sprechen auf Proinsulin wie intakte Mäuse an. Die hypoglykämische Wirkung des Proinsulins tritt wahrscheinlich deshalb verzögert ein, weil das aktive Insulin in einem zeitabhängigen proteolytischen Prozeß erst entstehen muß. Dies könnte auch die Ursache für eine von Rubenstein et al. [5] zitierte, fehlende Wirkung von Proinsulin im Mäusekrampftest sein.
    Notes: Summary Proinsulin obtained from bovine insulin (Schmidt and Arens [6]) lowered the blood sugar level of rats and mice. The activity ratio proinsulin: insulin was 1∶4 in fed rats and fasted mice, and 1∶2 in fasted rats, based on an equimolar dosage and measuring the effect in terms of maximum lowering of the blood sugar value. After proinsulin the decrease of the blood sugar was more protracted than after insulin. Proinsulin which was incubated with trypsin in vitro, resembled insulin in degree and onset of action. In pancreatectomized, nephrectomized and two-thirds hepatectomized rats proinsulin acted as in normal animals. Alloxan-diabetic mice responded to proinsulin like intact mice. The reason why the onset of the hypoglycaemic action of proinsulin was delayed is probably due to the fact that the active insulin must first be produced by a time-dependent proteolytic process. This may also be the cause of the ineffectiveness of proinsulin in the mouse convulsion test which was quoted by Rubenstein et al. [5].
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 143-145 
    ISSN: 1432-0428
    Keywords: Insulin ; galactose ; galactokinase ; deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez deux adultes souffrant d'une déficience en galactokinase la charge orale de galactose a été suivie d'une hypergalactosémie prolongée sans aucune élevation de l'insuline immunoréactive plasmatique.
    Abstract: Zusammenfassung Orale Belastung mit Galactose führte bei zwei Erwachsenen mit Galactokinasemangel zu einer prolongierten Hypergalactosämie, aber nicht zu einem Anstieg des immunoreaktiven Insulins im Plasma.
    Notes: Summary Oral galactose loading in two galactokinase-deficient adults produced the expected high and prolonged rise of galactose in peripheral blood, but no rise of circulating immunoreactive insulin.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 195-197 
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; adipose tissue ; lipolysis ; FFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé A des concentrations proches de celles qui sont rencontrées dans le plasma humain, le glucagon stimule fortement la lipolyse au niveau de la graisse épididymaire du rat, étudiéein vitro. Les effets de telles concentrations de glucagon sont réduits, voire abolis par l'insuline aux concentrations de 25 et 100μU/ml. Rapprochées de l'effet insulinogénique puissant du glucagon, ces observations peuvent fournir une explication quant au caractère retardé de l'élévation du taux sanguin des acides gras libres observée après injection de glucagonin vivo.
    Abstract: Zusammenfassung Glucagon stimuliert in Konzentrationen, wie sie auch im menschlichen Plasma vorkommen, die Lipolyse im Ratten-Nebenhodenfettgewebein vitro stark. Die Effekte derartiger Glucagonkonzentrationen werden durch Insulin (25–100μE/ml) verringert bis aufgehoben. Unter Berücksichtigung der ausgeprägten Wirkung von Glucagon auf die Insulinfreisetzung können diese Beobachtungen eine Erklärung für die Verzögerung des Anstiegs der freien Fettsäuren im Serum liefern, die man nach Glucagoninjektionenin vivo beobachtet.
    Notes: Summary Glucagon in concentrations similar to those found in human plasma markedly stimulates lipolysis in rat adipose tissuein vitro. The effects of these “physiological” concentrations of glucagon are reduced or abolished by insulin at concentrations of 25 and 100μU/ml. Considering the marked insulinogenic effect of glucagon these observations may provide an explanation for the delayed increase of blood FFA observed after glucagon injectionin vivo.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 61-66 
    ISSN: 1432-0428
    Keywords: Insulin ; islets of Langerhans ; mouse ; collagenase ; glucose ; mannoheptulose ; glucagon ; adrenaline ; phentolamine ; theophylline ; tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La libération de l'insuline pendant l'incubation des îlots de Langerhans de la souris, isolés après digestion du pancréas par la collagénase, a été étudiée, et l'influence de divers facteurs sur la vitesse de libération a été recherchée. Le glucose à 3.0 mg/ml (glucose élevé) stimulait la libération d'insuline, mais n'avait pas d'effet à 0.6 mg/ml (taux bas). Le mannoheptulose bloquait la stimulation provoquée par du glucose élevé, comme le faisait l'adrénaline. L'effet de l'adrénaline était aboli par la phentolamine, un agent bloquant alpha adrénergique. Le glucagon seul, ainsi qu'en pre'sence d'un taux de glucose bas, stimulait la libération d'insuline, mais non de façon constante avec un taux de glucose élevé. L'adrénaline abolissait la stimulation provoquée par le glucagon. La théophylline stimulait la libération lorsque le glucose était bas, mais beaucoup moins lorsque le glucose était élevé et pas du tout avec le glucagon, quelle que soit la concentration de glucose. Le tolbutamide stimulait la libération d'insuline avec une faible concentration de glucose et cet effet n'était pas inhibé par l'adrénaline. La convenance de cette préparation pour des études sur le métabolisme des cellules insulaires et sa relation avec la sécrét ion d'insuline est discutée.
    Abstract: Zusammenfassung Es wurde die Insulinausschüttung aus Langerhans'schen Inseln von Mäusen, die durch Kollagenase-Behandlung des Pankreas gewonnen worden waren, untersucht und der Einfluß verschiedener Faktoren auf die Freisetzungsgeschwindigkeit überprüft. Eine hohe Glucose-Konzentration von 3.0 mg/ml förderte die Insulin-Ausschüttung, während die niedrige Konzentration von 0.6 mg/ml keine Wirkung ergab. Mannoheptulose und Adrenalin blockierten die Stimulation durch die hohe Glucosekonzentration. Der AdrenalinEffekt konnte durch Phentolamin, eine alpha-Rezeptoren blockierende Substanz, wieder aufgehoben werden. Glucagon führte allein und in Gegenwart der niedrigen Glucosekonzentration zu einer verstärkten Insulininkretion: dies war jedoch bei Kombination mit der hohen Glucosekonzentration nicht konstant der Fall. Adrenalin hob die Stimulierung durch Glucagon auf. Theophyllin führte bei Gegenwart der niedrigen Glucosekonzentration zu einer gesteigerten Ausschüttung, dieser Effekt trat unter der höheren Glucosekonzentration in wesentlich geringerem Umfang und bei Zusatz von Glucagon und einer der beiden verwandten Glucosekonzentrationen überhaupt nicht auf. Bei niedriger Glucosekonzentration stimulierte Tolbutamid die Insulinfreisetzung; dieser Effekt ließ sich durch Adrenalin nicht aufheben. Die Aussagefähigkeit dieses Präparates für Untersuchungen des Inselzell-Stoffwechsels und seiner Beziehungen zur Insulininkretion wird diskutiert.
    Notes: Summary The release of insulin during incubation of mouse islets of Langerhans, isolated after digestion of the pancreas with collagenase, has been studied, and the influence of various factors on the rate of release investigated. Glucose at 3.0 mg/ml (high glucose) stimulated insulin release, but had no effect at 0.6 mg/ml (low glucose). Mannoheptulose blocked the stimulation by high glucose, as did adrenaline. The adrenaline effect was abolished by phentolamine, an alpha-adrenergic blocking agent. Glucagon alone, stimulated insulin release, and also with low glucose, but not consistently with high glucose. Adrenaline abolished the stimulation by glucagon. Theophylline stimulated release with low glucose, much less so with high glucose and not at all with glucagon at either glucose concentration. Tolbutamide stimulated release with low glucose, and this effect was not inhibited by adrenaline. The suitability of this preparation for studies of islet cell metabolism and its relationship to secretion of insulin is discussed.
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin ; mouse tissues ; kidney fluorescence microscopy ; microscopy ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La localisation d'insuline marquée avec I125 ou avec de l'isothiocyanate de fluorescéine a été étudiée au moyen d'autohistoradiographie au microscope optique, au microscope électronique et au moyen de microscopie à fluorescence dans les tissus de souris à jeun et de souris alimentées normalement. L'hormone fluorescente a été trouvée dans les cellules des tubules proximaux du rein de souris à jeun seulement, tandis que l'hormone radioactive a été repérée aussi dans le rein de souris alimentées, bien qu'en quantité inférieure à celle trouvée chez les souris à jeun. Au microscope électronique la radioactivité est présente dans le rein dans la bordure en brosse, les vacuoles et les mitochondries apicales et le noyau, mais pas dans l'appareil de Golgi ou dans les lysosomes. —L'hormone radioactive est aussi présente dans les autres tissus mais sans différence quantitative entre les souris à jeun et les souris alimentées. Les auteurs concluent que le procédé de ré-absorption de l'insuline par les cellules des tubules proximaux du rein est spécifique: l'hormone n'est pas dégradée de la même façon que les autres protéines mais probablement stockée afin de contrôler les processus métaboliques relevant des organelles subcellulaires dans lesquelles elle se trouve.
    Abstract: Zusammenfassung Gefütterte und fastende Mäuse erhielten fluoreszierendes oder mit125J markiertes Insulin i.v. Die Lokalisation des Insulins in den Geweben wurde untersucht. Nur bei Tieren im Hungerzustand fand sich das fluoreszierende Hormon in den Nieren, während sich das radioaktive Insulin bei gefütterten und fastenden Tieren in den proximalen Tubulusschlingen der Nieren nachweisen ließ. Die fastenden Tiere schienen dabei mehr Radioaktivität aufzuweisen. Wurden die Nieren unter Verwendung von Techniken mit hohem Auflösungsvermögen untersucht, so fand sich die Radioaktivität im Bürstensaum, in den apikalen Vakuolen und Mitochondrien und dem Kern, jedoch nicht im Golgi-Apparat oder den Lysosomen. Alle anderen Gewebe enthielten Hormon-Radioaktivität, aber weder ihre Menge noch ihre Lokalisation unterschieden sich bei gefütterten und fastenden Tieren. Es wird gefolgert, daß der Prozeß der Insulinabsorption durch die Zellen der proximalen Tubulusschlingen spezifisch ist und daß das Hormon nicht in ähnlicher Weise wie andere Eiweißkörper abgebaut wird. Wahrscheinlich kommt es über eine Speicherung zu einer Steuerung der entsprechenden Stoffwechselprozesse in den subzellulären Organellen, in denen das Hormon sich befindet.
    Notes: Summary Starved and fed mice were injected intravenously with either fluorescent or125I-insulin and the localization of the hormone was investigated in various tissues. The fluorescent hormone was found in the kidney of starved animals only, whereas the radioactive hormone was found in the proximal convoluted tubule cells of the kidney of both fed and fasted animals, although the latter group appeared to contain more radioactivity than the first. With high resolution techniques the radioactivity in the kidney was found in the brush border, the apical vacuoles, the apical mitochondria and the nucleus, and never in the Golgi apparatus or the lysosomes. All other tissues contained radioactivity due to the hormone, but no difference in either the amount or the localization was found between fed an starved animals. It is concluded that the process of absorption of insulin by the cells of the proximal convoluted tubules is specific and that the hormone is not degraded in a way similar to other proteins, but is likely to be stored and to control cellular metabolic processes from its sites of localization.
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin ; 32P incorporation ; adenine nucleotides ; guanine nucleotides ; Na+K+ ATP-ase ; ouabain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le but de ces investigations a été de contribuer à la compréhension du mécanisme d'action de l'insuline, en provoquant un turn-over accru du phosphate inorganique marqué au32P, en ATP et autres mononucléotides, dans le diaphragme du rat. Pendant l'incubation du diaphragme intact de rat dans un milieu bicarbonaté de Krebs Ringer, sans addition de substrat, on n'a pas observé d'effet de l'insuline sur le contenu en adénine-nucléotides, en guanine-nucléotides, y compris le 3′5′ AMP cyclique et le 3′5′ GMP cyclique. Quand du phosphate inorganique radioactif marqué au32P était présent dans le milieu, l'insuline augmentait l'activité spécifique du phosphate inorganique intracellulaire et provoquait une incorporation accrue du32P dans l'ATP et le GTP. L'effet sur l'ADP était moins prononcé. Il a été montré que ces effets de l'insuline dépendent de la composition ionique du milieu et du transport membranaire des ions. L'augmentation due à l'insuline de l'activité spécifique du phosphate inorganique intracellulaire et du marquage accru au32P de l'ATP (et du GTP) était en grande partie inhibée par l'ouabaïne. Pendant l'incubation dans les milieux où le chlorure de sodium a été remplacé isoosmotiquement par le chlorure de potassium ou de choline, les effets de l'insuline décrits ci-dessus étaient abolis. Les résultats indiquent que le marquage accru de l'ATP (et du GTP) provoqué par l'insuline, peut être en premier lieu attribué à des phénomènes survenant au niveau de la membrane cellulaire. L'augmentation de l'activité spécifique du phosphate inorganique intracellulaire en présence d'insuline, peut s'expliquer par une captation accrue du phosphate inorganique marqué au32P, à partir du milieu. Apparemment le marquage accru au32P de l'ATP (et du GTP) est une conséquence secondaire. On suggère que cet effet de l'insuline est d'abord en rapport avec un effet sur les enzymes de la membrane, en particulier sur l'ATP-ase activée par Na+, K+ et Mg2+.
    Abstract: Zusammenfassung Ziel dieser Untersuchungen war es, zu einem besseren Verständnis der stimulierenden Wirkung von Insulin auf den Einbau von anorganischem32P Phosphat in ATP und andere Mononucleotide im Rattenzwerchfell beizutragen. Während der Inkubation intakter Rattenzwerchfelle in Krebs-Ringer-Bicarbonat Puffer ohne Substratzusatz konnte kein Insulineffekt auf den Gehalt an Adenonucleotiden und Guaninnucleotiden, sowie von cyclischem 3′,5′ AMP und cyclischem 3′,5′ GMP beobachtet werden. In Gegenwart von anorganischem32P Phosphat steigerte Insulin die spezifische Aktivität von intrazellulärem anorganischen Phosphat und bewirkte einen verstärkten Einbau von32P in ATP und GTP. Die Wirkung auf ADP war weniger ausgeprägt. Es konnte gezeigt werden, daß diese Insulineffekte von dem IonenGehalt des Mediums und dem Membrantransport der Ionen abhängen. Die Steigerung der spezifischen Aktivität des anorganischen Phosphates und der Markierung von ATP (und GTP) mit32P ließ sich weitgehend durch Ouabain wieder aufheben. Bei Inkubation in Pufferlösungen, die statt NaCl isoosmolare Mengen von KCl oder Cholinchlorid enthielten, waren die oben erwähnten Insulineffekte nicht mehr nachweisbar. Die Resultate sprechen dafür, daß die verstärkte Markierung von ATP (und GTP) unter Insulin in erster Linie auf Vorgängen an der Zellmembran beruht. Die erhöhte spezifische Aktivität des intrazellulären anorganischen Phosphates in Gegenwart von Insulin läßt sich durch einen verstärkten Einstrom von32P Phosphat aus dem Medium erklären. Augenscheinlich kommt es dadurch sekundär zu einer gesteigerten32P Markierung von ATP (und GTP). Wir möchten annehmen, daß dieser Insulineffekt vorwiegend über die Membranenzyme erfolgt und sich vor allem auf die Na+, K+ und Mg++ aktivierbare ATPase erstreckt.
    Notes: Summary The aim of these investigations has been to contribute to an understanding of the mechanism of action of insulin in promoting increased turn over of32P inorganic phosphate into ATP and other mononucleotides in the rat diaphragm. During incubation of the intact rat diaphragm in Krebs Ringer bicarbonate medium without addition of substrate, no effect of insulin on the content of adenine nucleotides and guanine nucleotides including cyclic 3′,5′ AMP and cyclic 3′,5′ GMP has been observed. When32P radioactive inorganic phosphate was present in the medium, insulin increased the specific activity of intracellular inorganic phosphate and promoted an increased incorporation of32P into ATP and GTP. The effect on ADP was less pronounced. It has been shown that these effects of insulin depend upon the ionic composition of the medium and on ion membrane-transport. The insulin-promoted increase of specific activity of intracellular inorganic phosphate and of increased32P labelling of ATP (and GTP) was to a great extent inhibited by ouabain. During incubation in media where sodium chloride had been iso-osmotically replaced by potassium chloride or choline chloride, the above mentioned effects by insulin were abolished. The results indicate that the increased labelling of ATP (and GTP) promoted by insulin can be primarily attributed to events occuring at the cell membrane. The increased specific activity of intracellular inorganic phosphate in the presence of insulin can be explained by increased uptake of32P inorganic phosphate from the medium. Apparently the increased32P labelling of ATP (and GTP) occur as a secondary consequence. It is suggested that this insulin effect is primarily concerned with an effect on membrane enzymes, particularly the Na+, K+, Mg2+ activated ATP-ase.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 5 (1969), S. 304-308 
    ISSN: 1432-0428
    Keywords: Insulin ; bile ; rabbit ; 125I-insulin ; glucose ; galactose ; fructose ; tolbutamide ; phenformin ; liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On trouve de l'insuline immunoréactive dans la bile hépatique de lapins normaux. Moins de 1% d'une dose injectée d'insuline bovine atteint la bile. Quand de l'insuline bovine 125I, seule ou liée à l'anticorps, est administrée par voie intraveineuse, seulement 40% de la radioactivité retrouvée dans la bile est précipitable avec l'acide trichloracétique et moins de 10% réagit avec le sérum anti-insuline de cobaye. Le glucose, le fructose le galactose, le tolbutamide et la phenformine provoquent tous une élévation de l'insuline dans la bile, qui atteint son maximum 40 à 50 min après l'injection. L'alloxane atténue ou abolie ces réponses.
    Abstract: Zusammenfassung Immunoreaktives Insulin wird in der Leber-Galle normaler Kaninchen gefunden. Weniger als 1% einer injizierten Dosis von Rinder-Insulin erreicht die Galle. Wenn man reines oder an Antikörper gebundenes 125I-Rinderinsulin intravenös verabreicht, lassen sich mit Hilfe von Trichloressigsäure nur 40% der Radioaktivität ausfällen, die in der Galle gefunden wird, und weniger als 10% reagieren mit Meerschweinchen-Anti-Insulinserum. Glucose, Fructose, Galaktose, Tolbutamide und Phenformin verursachen ein Ansteigen von Insulin in der Galle, welches ein Maximum innerhalb von 40 bis 50 Min. nach der Injektion erreicht. Alloxan vermindert oder hebt diese Effekte auf.
    Notes: Summary Immuno-reactive insulin is found in the hepatic bile of normal rabbits. Less than 1% of an injected dose of bovine insulin reached the bile. When 125I-bovine insulin alone or complexed with antibody was given intravenously, only 40% of the radioactivity recovered in the bile was precipitable with trichloracetic acid, and less than 10% reacted with guinea pig anti-insulin serum. Glucose, fructose, galactose, tolbutamide and phenformin all caused an elevation in bile insulin, which reached a maximum 40 to 50 min after the injection. Alloxan attenuated or abolished these responses.
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  • 8
    ISSN: 1432-1912
    Keywords: Amiloride ; Insulin ; Glucose Transport ; Leucine Incorporation ; Isolated Adipose Tissue ; Amilorid ; Insulin ; Glucosetransport ; Leucineinbau ; isoliertes Fettgewebe
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Die Aufnahme von Glucose ins isolierte epididymale Fettgewebe und die Bildung von 14CO2 aus [1-14C]-Glucose wurde als Maß von Transportvorgängen, die Incorporation von [1-14C]-Leucin ins Fettgewebsprotein als Maß der Proteinsynthese vor und nach Zusatz von Amilorid in vitro verwendet. 2. Amilorid setzt den Transport durch die Membran sowohl ohne als auch mit Stimulierung durch Insulin halbmaximal in 10−4 M-Konzentration herab. Aus der Kinetik des Transportes kann geschlossen werden, daß Amilorid die maximale Geschwindigkeit des gesamten Vorganges verlangsamt, ohne die Transportkonstante zu verändern. 3. Der Einbau von Leucin ins Fettgewebsprotein wird durch Amilorid in 3 · 10−4 M-Konzentration auf ein Zehntel herabgesetzt. Das Verhalten von [1-14C]-α-Aminoisobuttersäure läßt den Schluß zu, daß der Aminosäuretransport durch die Membran des Fettgewebes nicht beeinflußt wird. 4. Die Wirkungen des Amilorids am Fettgewebe entsprechen im Prinzip denjenigen des Triamterens und des 6-Aminonicotinsäureamids. Ebenso ist allen gemeinsam, daß sie den renalen Natrium- und Kaliumtransport im distalen Abschnitt des Nephrons hemmen. 5. Es ist möglich, daß ein Zusammenhang zwischen den hemmenden Wirkungen dieser Pharmaka auf den Leucin-Einbau in das Fettgewebsprotein und der Störung von Transportvorgängen durch biologische Membranen besteht.
    Notes: Summary 1. The uptake of glucose and the formation of 14CO2 from [1-14C]-glucose were used as a measure of transport processes, and the incorporation of [1-14C]-leucine into the protein of adipose tissue served as a measure of protein synthesis before and after the addition of amiloride to the isolated epididymal adipose tissue of the rat in vitro. 2. In a concentration of 10−4 M, amiloride decreases the glucose transport through tissue membranes by 50% with and without stimulation by insulin. It can be deduced from the kinetics of the transport that amiloride slows down the maximal velocity of the complete process without influencing the transport constant. 3. The incorporation of leucine into adipose tissue protein was diminished to 10% by amiloride in a concentration of 3 × 10−4 M. Experiments with [1-14C]-α-aminoisobutyric acid allow the conclusion that the amino acid transport through the membrane of the adipose tissue remains uninfluenced. 4. The effects of amiloride on the adipose tissue are similar to those of triamterene and of 6-aminonicotinamide. In addition, they all inhibit renal sodium and potassium transport in the distal part of the nephron. 5. It is possible, that there is a connection between the inhibiting effects of these drugs on the incorporation of leucine into the protein of adipose tissue and the disturbance of transport processes through biological membranes.
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  • 9
    ISSN: 1432-2013
    Keywords: Toad Bladder ; Sodium Transport Pool ; Aldosterone ; Insulin ; Vasopressin ; Krötenblase ; Natrium-Transport-Pool ; Aldosteron ; Insulin ; Vasopressin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The size of toad bladder sodium transport pool, defined as that amount of sodium of apical origin and recovered in tissue at equilibrium, was compared with sodium transport rate, derived from short-circuit current read immediately before tissue analysis. Provided certain precautions be taken, the relationship between both variables can be described by a curve starting at the intersect ofX (pool, in μEq) andY (transport, in μEq/hr) axes, with a tendency forX to increase faster thanY. Assuming sodium transport pool forms one compartment, its calculated half-life averages 2–3 min. sodium transport pool measurements are thought to shed light on mechanism of sodium transport by toad bladder because pool size was large with respect to transport rate when tissue was exposed to several inhibitors of sodium transport. Conversely, upon stimulation of activity of (substrate — depleted) preparations by glucose, a relative reduction of pool size was observed. Aldosterone, vasopressin (and adenosine 3′,5′-phosphate) increased sodium pool size and transport rate, proportionately; insulin stimulated sodium transport more than it increased pool size. Thus, insulin presumably exerts its effect at the sodium “pump” while such a site of action need not be postulated for aldosterone and vasopressin: these 2 hormones would instead induce, permeability changes faciliting sodium movement at the apical border of toad bladder epithelial cells.
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  • 10
    ISSN: 1432-2072
    Keywords: Lysergic Acid Diethylamide or LSD ; Methylphenidate or Ritalin ; Chlordiazepoxide or Librium ; Psychopharmacology ; Alcoholism and Drug Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Through the retrospective use of the 156 item DWM Card Sort, the experiences from a single intravenous dose of 200 mcg of LSD, 75 mg of methylphenidate (Ritalin) and 75 mg of chlordiazepoxide (Librium) were compared in a population of 99 chronic male alcoholics treated in an “LSD setting” in a double-blind study. Surprisingly, 96 of the 156 items proved significantly different among the 3 groups. LSD was unique in producing Sensory and Perceptual Distortions (including Hallucinations or Illusions), and Mystical, Religious or Paranormal Sensations. However, contrary to expectation, LSD did not uniquely produce the traditional “therapeutic” experience, but appeared to be surpassed in that area by methylphenidate. Both drugs also produced some anxiety, while chlordiazepoxide produced relaxation, and enhanced music appreciation.
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  • 11
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    Psychopharmacology 14 (1969), S. 18-22 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behaviour ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice were stained with pulverized charcoal and the resulting grooming behaviour observed. From 119 controls, the typical patterns indicated a late cleaning of the tail, the sacrum and the region between the ears. The following substances were tested: Imipramine, Desipramine, Trimeprimine, Amitriptyline, Nortriptyline, Chlordiazepoxide, Iproniazide, d-Amphetamine, Chlorpromazine, Haloperidol, Acetylsalicylic acid, Metronidazole. Of these Amitriptyline, Chlorpromazine, Haloperidol and Metronidazole were effective in doses less than 1/10 of LD 5.
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  • 12
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    Psychopharmacology 14 (1969), S. 62-73 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Hallucinogens ; Drug Addiction ; Psychopharmacology ; Phenylethylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The amphetamine analog, 2,5-dimethoxy-4-methylamphetamine (DOM), was studied in 18 volunteer subjects given single doses ranging from 2 to 14 mg. The former was a threshold dose, with definite psychotomimetic effects being evident from doses over 5 mg. The clinical syndrome greatly resembled that of the LSD-mescaline-psilocybin series of drugs, including its time-course. Somewhat more sedation was produced by DOM than would have been expected from the others, despite concomitant evidence of peripheral sympathetic stimulation. Just as with the other drugs, DOM increased plasma free fatty acids, decreased phosphorus and creatinine clearance, decreased circulating eosinophils and had little effect on catecholamine excretion. Performance of psychometric tests was impaired. Chlorpromazine treatment concurrently was found to attenuate the reaction. Tolerance rapidly developed when the drug was used chronically by patients.
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  • 13
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Doxepin ; Diazepam ; Anti-Anxiety ; Antidepressant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Doxepin and diazepam were evaluated for therapeutic effectiveness in a double blind study carried out with 69 primarily anxious neurotic outpatients attending either a municipal hospital clinic or a general practitioner's office. Doxepin produced more clinical improvement than diazepam in several questionnaire clusters measuring depressive symptomatology, but not in clusters measuring anxious symptomatology. According to several outcome criteria, doxepin tended to produce more clinical improvement in general practice than in clinic patients, while diazepam produced either equal improvement in both populations or slightly more improvement in the clinic. Possibly contributing to the present results are low daily dosage of diazepam, differential pharmacological drug effects, population differences in levels of anxiety and depression, and differences in population characteristics, primarily as related to social class.
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  • 14
    ISSN: 1432-2072
    Keywords: Nicotine ; Antimuscarinic Drugs ; Ganglion-Blocking Drugs ; Operant Conditioning ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of nicotine on bar-pressing behaviour in the rat are blocked by mecamylamine. The depressant phase of the effect is blocked by atropine, supporting the conclusion that this depression is mediated by released acetylcholine. The quaternary compounds chlorisondamine and atropine methylnitrate also antagonise the behavioural effects of nicotine but the doses required for this are far in excess of those which are effective peripherally, suggesting that the sites of interaction are central.
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  • 15
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    Psychopharmacology 15 (1969), S. 1-8 
    ISSN: 1432-2072
    Keywords: Cannabis (Marihuana) ; Lysergic Acid Diethylamide ; Hallucinogens (Psychopharmacology) ; Visual Perception ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four pigeons were trained on a visual discrimination task which required conditional responding along the independent dimensions of form and color. High doses of Cannabis sativa (marihuana) extract and lysergic acid diethylamide (LSD), which were equated on the basis of their effectiveness in suppressing responding, increased responding on a color dimension but not on a form dimension. High doses of LSD produced a decrement in discrimination performance while comparable doses of Cannabis did not effect accuracy. Treatment with Bromolysergic acid diethylamide, saline, and pentobarbital did not produce significant changes in performance. Results are discussed in terms of a break-down in stimulus control and central hallucinogenic activity.
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  • 16
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    Psychopharmacology 14 (1969), S. 394-403 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Morphine ; Skin Conductance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin conductance changes during periods of stress induced by hypercapnia were studied during a cycle of addiction to morphine. Conductance changes were found to be dose dependent in both tolerant and non-tolerant states. The effects of morphine on skin conductance changes induced by hypercapnia were similar to those effects previously observed on changes induced by electric shock.
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  • 17
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    Psychopharmacology 14 (1969), S. 417-425 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Psychoses ; Reflex, Abnormal ; Chlorpromazine ; Trifluopromazine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary According to our results in 117 subjects, recently taken medications, age and sex must be considered when duration of the Achilles-tendon reflex is used as a clinical test to assess thyroid status. Males have a shorter ATR than females. In older subjects the ATR lasts longer than in those below age 27. Fifty-two psychiatric patients before medication did not differ in ATR duration from 65 controls. However, after 28 patients took chlorpromazine and 24 received trifluoperazine, ATR was prolonged in the chlorpromazine group and shortened in the trifluoperazine group. Neither chlorpromazine concentrate, 1,800 mg, nor trifluoperazine concentrate, 180 mg, given during the first six days, affected ATR, but an additional 6,000 mg of chlorpromazine, or an additional 420 mg of trifluoperazine over the next six days, did significantly alter ATR-duration.
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  • 18
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    Psychopharmacology 14 (1969), S. 142-149 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Amphetamine ; Cholinergics ; Drug Interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amphetamine was administered to a group of rats trained on a nondiscriminated avoidance procedure. An intraperitoneal dose of 2.0 mg/kg caused about a 75% increase in response rate for the three-hour session. Doses of atropine, Tremorine, eserine, and 4-(1-naphthylvinyl)-pyridine (NVP), an inhibitor of the enzyme choline acetylase, which were ineffective in themselves, markedly affected the increase in rate observed after amphetamine. The quarternary amine of NVP was without effect on the amphetamine response. Those agents that decreased cholinergic function, either by blocking the effect of acetylcholine or by preventing its synthesis, augmented the stimulating effect of amphetamine. Cholinergic stimulants, on the other hand, significantly antagonized the behavioral effects of amphetamine.
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  • 19
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    Psychopharmacology 14 (1969), S. 221-232 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behaviour ; Nicotine ; Punishment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of nicotine, amphetamine, chlordiazepoxide and caffeine were studied in rats trained on a VI 2 crf schedule of water reward with all rewards accompanied by electric shock. Responding, partially suppressed by the shock, was restored by chlordiazepoxide and further suppressed by amphetamine. Nicotine resembled amphetamine in its effects on most rats but occasionally increased responding. Caffeine also increased responding in some rats indicating that this property is not always confined to tranquillising drugs.
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  • 20
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    Psychopharmacology 15 (1969), S. 109-115 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Hallucinogens ; Drug Effects ; Behavior Exploratory ; Monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of Psilocybin on the behavior of the baboon Papiopapio has been studied. Animal watchfulness, as estimated from the E.E.G., is enhanced within the first five minutes after injection and then is not further modified. Psilocybin induces a decrease of spontaneous motility. Conversely, the frequency of eye movements is considerably increased. This pattern might be explained by alterations of visual perception.
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  • 21
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    Psychopharmacology 15 (1969), S. 134-143 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Anti-Anxiety ; Controlled Trial ; Doxepin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six patients with persistent anxiety symptoms were used in a preliminary assessment of a new anti-anxiety compound-Doxepin (Sinequan) with placebo. The factorial design is discussed as a potentially useful way of conducting a first-stage test of anti-anxiety compounds. Analysis of the results showed that Doxepin at 25 mg t.d.s. and 50 mg t.d.s. was associated with improvement in the patient's self ratings of anxiety symptoms.
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  • 22
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    Psychopharmacology 15 (1969), S. 144-152 
    ISSN: 1432-2072
    Keywords: Niacin ; Nicotinamide Adenine Dinucleotide ; Schizophrenia ; Phenothiazines ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two grams of NAD were administered orally to ten chronic schizophrenic patients for twenty-one days. Five of the patients were also receiving thioridazine. There was no gross clinical improvement noted in any of the patients despite the fact that related experiments suggested that the NAD was absorbed. In those patients who were not also receiving phenothiazines there was a distinct tendency towards increased hostility, aggressiveness and irritability beginning one week after the initiation of NAD treatment and lasting for nearly two weeks after the NAD was discontinued.
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  • 23
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    Psychopharmacology 15 (1969), S. 245-254 
    ISSN: 1432-2072
    Keywords: Aggression ; Lithium ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of lithium on aggressive behavior was studied in Siamese fighting fish, mice and golden hamsters. The fish stopped fighting when exposed to concentrations of 10 to 30 meq/l LiCl in the surrounding water. Also in mice and hamsters which ingested LiCl with the drinking fluid lithium abolished intraspecific aggression. Measurements of plasma and brain lithium levels revealed astonishing individual differences in the concentrations which were necessary for the antiaggressive effect. In all species normal aggressive behavior reappeared after lithium treatment was discontinued.
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  • 24
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Antidepressants ; Reserpine Emesis ; Apomorphine Pecking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Seven psychic energizers have been quantitatively evaluated for their antidepressant and tranquillizing activity using antagonism of reserpine induced emesis and apomorphine induced pecking in pigeons as test procedures for the two activities respectively. Pheniprazine and deanol possess anti-reserpine activity only whereas imipramine, desmethylimipramine, amitriptyline, opipramol and orphenadrine possess both anti-reserpine as well as anti-apomorphine activity. It is suggested that the two tests form a simple and reliable combination for evaluating potential antidepressants.
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  • 25
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    Psychopharmacology 15 (1969), S. 351-360 
    ISSN: 1432-2072
    Keywords: Nicotine ; Conditioned Stimulus ; Discrimination Learning ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to respond for water rewards on different bars in a Skinner box depending on whether they had previously been injected with nicotine or with saline. No other drug tested could consistently elicit responses on the “nicotine correct” bar. Pre-treatment with mecamylamine abolished the rats' ability to distinguish between nicotine and saline but pretreatment with chlorisondamine did not.
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  • 26
    ISSN: 1432-5233
    Keywords: Glybenclamide ; Insulin ; Insulin secretion ; Sulfonylureas ; Tolbutamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les effets métaboliques de la glybenclamide et de la tolbutamide ont été étudiés chez deux groupes de sujets normaux traités avec des doses comparables des deux sulphanylurées. En rapport aussi à la dose de 1:400, la glybenclamide a démontré une activité insuline-sécrétive bien majeure de celle de la tolbutamide. La réponse insulinique a été suivie par une rapide et prolongée diminution des NEFA sériques et par un moins persistant effet hypoglycémique. Les effets métaboliques de l'HB 419 sont encore évidents 10–12 heures après l'administration du médicament, tandis que l'activité de la tolbutamide est terminée géneralement entre 4–6 heures. Quand l'administration des médicaments a été pratiquée en concomitance avec une charge veineuse de glucose, le coéfficient de Conard était élevé d'une façon significative par toutes les deux sulphanylurées.
    Abstract: Resumen Los efectos metabólicos de la glibenclamida y de la tolbutamida han sido investigados en dos grupos de sujetos normales tratados con dosis comparables de las dos sulfanilúreas. Inclusive en una relación de dosificación de 1:400, la glibenclamida ha demostrado una actividad insulinosecretora mucho mayor de la tolbutamida. La respuesta insulínica ha sido seguida de una disminución pronta y prolongada de los NEFA séricos y de un efecto hipoglucemiante menos persistente. Los efectos metabólicos del HB 419 son aún evidentes a las 10–12 horas después de la administración del medicamento, mientras la actividad de la tolbutamida es anulada por lo general dentro de 4–6 horas. Cuando la suministración de los medicamentos ha sido practicada en coincidencia con una carga venosa de glucosa, el coeficiente de Conard apareció significativamente elevado por ambas sulfanilúreas.
    Notes: Riassunto Gli effetti metabolici della glibenclamide e della tolbutamide sono stati indagati in 2 gruppi di soggetti normali trattati con dosi comparabili delle due sulfaniluree. Anche in un rapporto di dosaggio di 1:400, la glibenclamide ha mostrato un'attività insulino-secretiva assai maggiore di quella della tolbutamide. La risposta insulinica è stata seguita da una pronta e prolungata diminuzione dei NEFA serici e da un meno persistente effetto ipoglicemico. Gli effetti metabolici del-l'HB 419 sono ancora evidenti 10–12 h dopo la somministrazione del farmaco mentre l'attività della tolbutamide si annulla generalmente entro 4–6 h. Quando la somministrazione dei farmaci è stata praticata in coincidenza con un carico venoso di glucosio, il coefficiente di Conard è apparso significativamente innalzato da entrambe le sulfaniluree.
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  • 27
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    Acta diabetologica 6 (1969), S. 371-388 
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Insulin assay ; Laboratory technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 28
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Islets of Langerhans ; Placenta ; Transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Ce travail est la continuation des communications préliminaires sur la résistance insulinique des nouveaux-nés de mères insuline-résistantes. Les recherches ont été conduites sur cobayes et sur sujets humains. Les AA. ont démontré que les anticorps anti-insuline passent dans la circulation fœtale et provoquent l'apparition d'une insuline-résistance passive qui va disparaître dans les premières semaines de la vie. Les anticorps contre l'insuline bovine lient en partie l'insuline endogène des cobayes, ce qui est mis en evidence par l'hyperglycémie élevée des cobayes jeunes nées de mères insuline-résistantes. Les anticorps anti-insuline n'ont aucun effet important sur la structure du pancréas des cobayes dans la période périnatale.
    Abstract: Resumen Este trabajo representa la continuación de las comunicaciones preliminares sobre la resistencia insulínica que presentan las personas nacidas de madres insulino-resistentes. Las investigaciones han sido efectuadas en cobayas y hombres. Se ha demostrado que los anticuerpos anti-insulina pasan al círculo fetal, provocando la aparición de insulino-resistencia pasiva, que desaparece durante las primeras semanas de vida. Los anticuerpos contra la insulina bovina ligan en parte la insulina endógena de cobayas, como lo demuestra la hiperglucemia elevada de las cobayas jóvenes nacidas de madres insulino-resistentes. Los anticuerpos anti-insulina no ejercen ningún efecto apreciable sobre la estructura del páncreas de las cobayas durante el período peri-natal.
    Notes: Riassunto Questo lavoro rappresenta la continuazione delle comunicazioni preliminari sulla resistenza insulinica dei nati di madri insulino-resistenti. Le ricerche sono state condotte su cavie e su uomini. E' stato dimostrato che gli anticorpi anti-insulina passano nel circolo fetale inducendovi la comparsa di una insulino-resistenza passiva che scompare nelle prime settimane di vita. Gli anticorpi contro l'insulina bovina legano in parte l'insulina endogena di cavie, come è evidenziato dall'elevata iperglicemia delle cavie giovani nate da madri insulino-resistenti. Gli anticorpi anti-insulina non esercitano alcun effetto di rilievo sulla struttura del pancreas delle cavie nel periodo perinatale.
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  • 29
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    Acta diabetologica 6 (1969), S. 197-205 
    ISSN: 1432-5233
    Keywords: Diurnal variations ; Food intake ; Glucose load ; Insulin ; Tolbutamide test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume On a étudié l'effet de la lumière et de la période d'ingestion des aliments sur l'élimination d'insuline par les urines. On peut démontrer l'existence d'un rythme circadien et la présence de deux facteurs de régulation pour cette élimination. On présente quelques hypothèses concernant ces phénomènes.
    Abstract: Resumen Se estudió el efecto que sobre la eliminación de insulina urinaria ejercen los períodos de luzoscuridad y el horario de administración del alimento. Se demuestra la existencia de un ritmo circadiano de eliminación de dicha hormona, describiéndose dos reguladores del mismo. Se hacen especulaciones fisiopatológicas acerca de su significado.
    Notes: Riassunto E' stato studiato l'effetto della luce e del periodo di ingestione del cibo sull'eliminazione di insulina nelle urine. Si può dimostrare l'esistenza di un ritmo circadiano e la presenza di due fattori di regolazione per questa eliminazione. Vengono presentate alcune ipotesi concernenti questi fenomeni.
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  • 30
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    Acta diabetologica 6 (1969), S. 796-808 
    ISSN: 1432-5233
    Keywords: Desensitization ; Immunoglobulins ; Insensitivity ; Insulin ; Insulin allergy ; Insulin antibodies ; Macroglobulins ; Porcine insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Cinq patients atteints d'allergie à l'insuline ont été désensibilisés par de l'insuline de porc selon la méthode d'Urbach et Gotlieb. Le diagnostic d'allergie à l'insuline a été posé sur la base des manifestations cliniques, de la positivité des réactions cutanées et, dans 2 cas, des réactions de Prausnitz-Küstner (P.K.). On a obtenu dans 3 cas une désensibilisation. La présence d'anticorps anti-insuline a été révélée par la méthode immunoautoradiographique en employant de l'insuline131J. Avant la désensibilisation la présence d'anticorps IgG a été enregistrée chez 3 patients tandis que chez 2 on a démontré également des anticorps IgA. Une réaction de P.K. positive a été observée chez des patients dont les sérums contenaient des anticorps IgA. Pendant la désensibilisation on a observé une apparition transitoire de macroglobulines capables de lier l'insuline131J. Après la désensibilisation on a constaté la persistance de la positivité aux réactions cutanées immédiates à l'insuline de porc et de boeuf. En même temps les réactions retardées et la réaction de P.K. à l'insuline de porc étaient interverties, bien que les mêmes réactions à l'insuline bovine restaient positives.
    Abstract: Resumen Cinco pacientes que padecían de alergia a la insulina han sido desensibilizados con insulina porcina según el método de Urbach y Gotlieb. El diagnóstico de alergia a la insulina ha sido puesto teniendo en cuenta las manifestaciones clínicas, el positivismo de las reacciones cutáneas, y, en 2 casos, las reacciones de Prausnitz-Küstner (P.K.). En 3 casos se ha obtenido desensibilización. La presencia de anticuerpos anti-insulina ha sido puesta en evidencia con el método inmunoautoradiográfico, empleando insulina131J. Antes de la desensibilización, la presencia de anticuerpos IgG ha sido hallada en 3 pacientes, mientras que en 2 han sido demostrados también anticuerpos IgA. Una reacción de P.K. positiva ha sido observada en pacientes cuyos sueros contenían anticuerpos IgA. Durante la desensibilización se ha observado aparición transitoria de macroglobulinas capaces de ligar la insulina131J. Al cabo de la desensibilización se ha notado la persistencia del positivismo a las respuestas cutáneas inmediatas a la insulina porcina y bovina. Al mismo tiempo, las respuestas retardadas y la reacción de P.K. a la insulina porcina cstaban invertidas, no obstante que las mismas reacciones a la insulina bovina hubieran quedado positivas.
    Notes: Riassunto Cinque pazienti con allergia all'insulina sono stati desensibilizzati con insulina suina secondo il metodo di Urbach e Gotlieb. La diagnosi di allergia all'insulina è stata posta sulla base delle manifestazioni cliniche, della positività delle reazioni cutanee e, in 2 casi, delle reazioni di Prausnitz-Küstner (P.K.). In 3 casi si è ottenuta una desensibilizzazione. La presenza di anticorpi anti-insulina è stata rivelata con il metodo immunoautoradiografico impiegando insulina131J. Prima della desensibilizzazione la presenza di anticorpi IgG è stata riscontrata in 3 pazienti mentre in 2 sono stati dimostrati anche anticorpi IgA. Una reazione di P.K. positiva è stata osservata in pazienti i cui sieri contenevano anticorpi IgA. Durante la desensibilizzazione si è osservata una comparsa transitoria di macroglobuline capaci di legare l'insulina131J. Dopo la desensibilizzazione si è riscontrata la persistenza della positività delle risposte cutanee immediate all'insulina suina e bovina. Al tempo stesso le risposte ritardate e la reazione di P.K. all'insulina suina erano invertite, sebbene le stesse reazioni all'insulina bovina rimanessero positive.
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  • 31
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    Psychopharmacology 14 (1969), S. 200-210 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Hashish ; Cannabinoids ; Monkeys Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The psychopharmacological activity of Δ 1-tetrahydrocannabinol, (I); Δ 1(6)-tetrahydrocannabinol (4′ hexyl), (II); Δ 1(6)-tetrahydrocannabinol, (III); 1-ethoxyhexahydrocannabinol, (IV); 8-ethoxy-iso-hexahydrocannabinol, (V); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer I, (VI); Δ 1(6)-tetrahydrocannabinolic acid Me ester, Isomer II, (VII); cannabigerol, (VIII); Δ 1(6)-tetrahydrocannabinol (3′ hexyl), (IX); cannabichromene, (X); has been examined in a variety of animal species. 2. Compounds (I) and (III) caused severe motor disturbances and a stuporous state in dogs and ptosis, “tameness” and peculiar postural changes in monkeys. In the latter animal, compound (II) elicited similar effects. 3. Compounds (I) and (III) after intraperitoneal but not subcutaneous administration, suppressed the gerbil digging activity; reduced the rat conditioned avoidance response and induced a cataleptoid reaction in mice, rats and gerbils. In addition, compound (I) reduced the performance of mice on the rotating-rod. Both compounds, administered subcutaneously, induced a measurable ataxic gait in rats. 4. Amphetamine reversed the behavioural changes elicited by compounds (I) and (III) in monkeys, as well as the cataleptoid reaction in rats. 5. None of the other compounds provoked observable changes in any of the species studied. 6. It is suggested that Rhesus monkeys might serve as a suitable model for assessing the psychopharmacological activity of active cannabinoids.
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  • 32
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    Psychopharmacology 14 (1969), S. 248-254 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Appetite Depressants ; Psychopharmacology ; Sympathomimetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method is described with which it is possible to measure locomotor activity and food intake simultaneously in the same rat or other small animal. From a study of a number of psychomotorstimulant drugs and anorectic agents it may be concluded that locomotorstimulation and appetite-suppression are two different effects that may or may not characterize the same drug. Methamphetamine and phenmetrazine are stimulants in doses that do not inhibit food intake. Amphepramon reduced food intake in low doses but acts as a stimulant in higher doses. Chlorphemternine and phenfluramine are anorectic agents that are not stimulants, even in high doses.
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    Psychopharmacology 15 (1969), S. 28-38 
    ISSN: 1432-2072
    Keywords: Drugs ; Sleep ; Electroencephalography ; Psychophysiology ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sleep physiological patterns were examined following a single oral dose (500 mg) of the hypnotic drug alpha chloralose. The drug increased SW sleep and decreased REM sleep without affecting total sleep time or the amount of stage 2. These changes were accompanied by a shift to slower frequencies and greater EEG synchrony, as well as a decrease in the number of spontaneous arousals in all stages of sleep, and throughout the night of medication. Except for a slight decrease in eye movement density, the drug had no systematic effects on phasic phenomena such as electrodermal or cardio-respiratory fluctuations, nor was there a systematic change in basal heart and breathing rates. On the night following medication a “rebound” increase in percent stage REM was associated with a sharp decrease in SW sleep, and increases in spontaneous arousals and waking time. Such findings suggest that sleep stages are controlled by homeostatic mechanisms whose function is to maintain equilibrium. A comparison of the effects of alpha chloralose with those of the barbiturate secobarbital revealed some striking differences. Although both alpha chloralose and the barbiturate reduced the amount of stage REM and the frequency of brief arousals, the latter compound enhanced EEG fast activity and desynchrony, and suppressed such phasic phenomena as rapid eye movements during stage REM, sigma spindles in stage 2, nonspecific electrodermal responses during SW sleep and cardio-respiratory variability in all sleep stages. For secobarbital, the decrease in percent stage REM was compensated by an increase in stage 2 rather than SW sleep. Several studies in the cat suggest that in subanesthetic doses, alpha chloralose acts primarily on cortical inhibitory processes, causing release of the reticular activating system from inhibitory influences. The results of this study show that moderate doses in man probably act on both cortical and subcortical systems involved in the mediation of SW sleep, REM sleep and arousal.
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    Psychopharmacology 15 (1969), S. 64-72 
    ISSN: 1432-2072
    Keywords: Amphetamine ; Dextro Amphetamine ; Psychopharmacology ; Conditioning, Operant ; Pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bar pressing was maintained by food reinforcement of each fiftieth response (FR50 schedule). Rats were tested at 3 levels of food deprivation (60, 80 and 100% of ad libitum body weight) under three drug conditions (0, 0.2 and 0.4 mg of D-amphetamine per rat). Overall response rate was reduced by increasing doses of drug, but not significantly by deprivation, within the range studied. The components of response rate were analysed separately into the starting speed (latency of the first response of each ratio run of 50 responses) and running rate. Drug level affected running rate and first latency of the session, whereas body weight affected only first latency of the session. Only the first latency of the session showed an interaction of drug level and body weight. The lack of interaction raises the question, whether amphetamine is more properly administered as total dose per rat, rather than proportional to body weight.
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    Psychopharmacology 15 (1969), S. 196-206 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behavior ; Alcohol ; Atropine ; Discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two operant procedures were used for training albino rats to make differential responses on the basis of their drug or nondrug condition. In the Conflict procedure, every fifth lever press was rewarded by a food pellet in one condition (drug for half the animals, saline for the other half) and was punished by electric shock in the other condition. For 6 animals the drug condition was ethyl alcohol (1200 mg/kg of a 10% v/v solution in isotonic saline, injected i.p. 5 min before the start of the session); for 4 animals the drug condition was atropine sulfate (10 mg/kg in 1 ml/kg saline injected i.p. 30 min before the start of the session). In the Choice procedure, food reward was obtained by the first press on one of two levers at a variable time interval, averaging one minute, after the prior food reward. The rewarded lever depended on the animal's drug or saline condition (alcohol for 7 animals, atropine for 5 animals, administered as in the Conflict procedure); the same right-hand or left left-hand lever was rewarded in the drug condition for half the animals and in the saline condition for the other half. The response associated with 1200 mg/kg alcohol was generally elicited in tests with sufficiently high doses of pentobarbital sodium (10–20 mg/kg), chlordiazepoxide hydrochloride (10–15 mg/kg) and chloral hydrate (90–120 mg/kg, administered orally). Lower doses of these compounds, and of alcohol, were perceived as less similar to the alcohol and therefore more similar to the saline condition. Substantial doses of chlorpromazine hydrochloride (2 mg/kg) and d-amphetamine sulfate (1 mg/kg) also were perceived as similar to the saline condition. The response associated with a centrally acting anticholinergic (10 mg/kg atropine) was generally elicited in tests with several doses of scopolamine hydrobromide (0.06 to 1.0 mg/kg) and of atropine (2.5–5.0 mg/kg). The saline response was elicited by a lower dose of scopolamine (0.03 mg/kg) and by a peripherally-acting anticholinergic, atropine methyl bromide, at a dose (5 mg/kg) equimolar with 10 mg/kg atropine sulfate. The same results, including closely similar ED50 doses, were generally found with the Conflict and Choice procedures, despite the differences between them in the motivational basis for the differential drug and nondrug responses. The similarities and dissimilarities among these compounds in perceived stimulus characteristics also correspond closely with those reported by Overton (1966) with a locomotor shock-escape procedure in tests which were generally limited to a single high dose of each drug.
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    Psychopharmacology 15 (1969), S. 425-429 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Methysergide ; Mania ; Lithium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Six manic patients were studied in an open sequential drug trial of placebo and the serotonin antagonist methysergide; lithium was then substituted double-blind. No dramatic change occurred in individual manic item scores or in mean daily mania ratings after 48 hours or seven days of methysergide, although several of the patients showed slight trends toward improvement. However, after a mean duration of 10.3 days of lithium treatment, all manic item scores improved dramatically and significantly, so that complete clinical remission was evident in all patients. In view of the discrepancy between these essentially negative findings and several recent positive reports on the efficacy of methysergide in the treatment of mania, the authors feel that the indolealkylamine hypothesis of affective disorders should be further investigated.
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    Psychopharmacology 15 (1969), S. 19-27 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behavior ; Nicotine-Physical Performance ; Motivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In sessions of ten runs each, swimming time of rats through a 4 m long water alley was measured. Four doses of nicotine (0.05; 0.1; 0.2; 0.4 mg/kg given intraperitoneally 30 minutes before testing) were tested in sessions with a braking load on the tails of the animals either in all 10 runs of a session, or in every second run, or in none of the 10 runs. Regardless of the swimming condition, nicotine produced a considerable, and at doses of 0.1 mg/kg and over, significant decrease of performance in the first two runs. From the third to the 10th run, the changes caused by nicotine were smaller and differed depending on the swimming conditions. A dose of 0.1 mg nicotine/kg improved performance in the “without-load-sessions” and the “without-load-runs” of the alternating sessions, while both 0.1 and 0.2 mg/kg improved performance of the “with-load-runs” of the alternating sessions. Performance in the “without-load-sessions” and the “without-load-runs” was depressed by 0.4 mg/kg and that in the “with-load-sessions” by 0.2 and 0.4 mg/kg.
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    International Journal for Numerical Methods in Engineering 1 (1969) 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 1-2 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 40
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 3-28 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Finite element methods can be formulated from the variational principles in solid mechanics by relaxing the continuity requirements along the interelement boundaries. The combination of different variational principles and different boundary continuity conditions yields numerous types of approximate methods. This paper reviews and reinterprets the existing finite element methods and indicates other alternative schemes. Plate bending problems are used to compare the relative merits of the various methods.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 47-66 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Three methods for finding natural frequencies and modes of complex structures composed of beam elements are described and compared. The analysis is extended to include hysteretic damping for the determination of response and transmissibility without a modal analysis. Experimental comparison is given for the response of a simple engineering structure.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 29-45 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The theory, function generator routine and testing procedures are given for a six-node 18 degree of freedom triangular element. At corner nodes the variables are the displacement and the two slopes. At midside nodes the variables are the displacement, the slope normal to the side, and the rate of change of this along the side - i.e., the rate of torsion. Of two options, one divides the triangle into three and takes different quartic displacements in the three regions, and the other uses displacement functions with singularities at the vertices. According to a test which compares the energies of the two formulations by eigenvalues, the second is the better if the integration is accurate. The same test, together with others based on finite differences and on nodal values, etc. checks the correctness of the routine decisively.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 67-73 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Finite difference treatment of two-dimensional problems in elastostatics is usually based on the differential equations for the displacement vector or the Airy stress function, depending on whether boundary conditions are on displacement or stress. In either case, determination of stresses requires numerical differentiation and therefore use of a rather fine grid. Moreover, neither method is suited to the treatment of mixed boundary conditions. The alternative method developed in this paper uses the first derivatives of the displacement components at the grid points as basic variables and hence does not require numerical differentiation in the evaluation of stresses. Appropriate finite difference equations are established, and their use is discussed in connection with a specific example with known explicit solution.
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    International Journal for Numerical Methods in Engineering 1 (1969) 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 45
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 279-299 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: When calculating complex interconnected systems (electrical, power, water supply, gas systems, etc.) by digital computer, a number of common problems arise, connected both with the mathematically correct formulation of the problem under investigation, and with the algorithms of the solution, the programming of which makes it possible to reduce the computing time, the store capacity and the volume of input data required. The present article is devoted to the solution of these problems. The procedure is illustrated by formulating and manipulating the equations relating to complex interconnected mine ventilation networks.
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  • 46
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 301-310 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Solution of plane elastic problems by piecewise linear approximation is outlined. This method is based upon Galerkin error distribution technique, which leads to simultaneous algebraic equations identical to those associated with the Finite Element Method. In addition, this method permits definition of the discretization error, which can be computed once the displacement components are known. Properties of the interpolation functions are discussed, and a sequence of internally compatible plane elastic elements is defined.
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  • 47
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 311-331 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A review is given of some mathematical programming methods suitable for optimization of structures needing matrix methods for analysis. An application is presented for elastic flat grillages made of straight orthogonal beams normally loaded. Empirical relationships are used to relate beam section properties so that each beam element has only one design variable. Optimization results are obtained by methods of stress-ratio, linear programming-cutting plane and usable-feasible gradient directions. A comparison of the efficiency of these methods is given for the grillage designs which are shown to have non-convex stress constraints and numerous relative optima. Instances are given of non-fully stressed global optima and fully stressed designs which are not local optima for cases with only stress constraints. Discussions include locating the global optima for grillage designs and extensions of the methods presented to other structural design problems.
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  • 48
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 379-394 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A completely numerical method for steady state linear viscoelastic stress analysis is presented by means of the finite element approach. Numerical representations of the measured viscoelastic constitutive relations are used. This method is developed to obtain steady state solutions to mixed boundary value problems in which the character of the boundary conditions at a point changes with time. Such problems cannot be handled by direct application of the correspondence theorem. A numerical example of viscoelastic sheet rolling is presented along with an experimental verification of the solution by photo-viscoelastic observations.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 351-378 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The application of non-linear programming methods for the optimum design of statically indeterminate structures is discussed, with special emphasis on the design of elastic grillages loaded laterally and in plane. Some features of SUMT (sequential unconstrained minimization technique) are demonstrated by means of numerous examples of varying complexity. The Variable Metric method of search is discussed and compared to Powell's Direct Method. It is shown that non-convex sets of design variables are often encountered in structural problems of the grillage type. SUMT may still be used, but the choice of starting value and initial response factor decisively influences the chance of finding the global optimum.It is demonstrated that a fully stressed design may not necessarily correspond to the minimum weight design. Optimum design of grillages which are simultaneously subjected to lateral and in-plane loads may be performed efficiently by means of non-linear programming.
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  • 50
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 395-395 
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    Keywords: Engineering ; Engineering General
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  • 51
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 275-277 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 75-100 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The paper presents first a general formulation of the elasto-plastic matrix for evaluating stress increments from those of stresses for any yield surface with an associated flow rule. A new ‘initial stress’ computational process is proposed which is shown (1) to yield more rapid convergence than alternative approaches (2) to permit large load increments without violating the yield criteria and thus simply to establish lower bound solutions. Several solutions showing stress distribution, strain development and growth of plastic enclaves are given both for the von Mises and for Coulomb (Drucker) type yield surfaces. Load reversal and thermoplastic behaviour are dealt with.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 135-149 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The assumed stress distribution approach is used to derive the stiffness matrix of a plate-bending element of general polygonal shape having any number of nodes. The effect of assuming various numbers of unknown coefficients in the stress distributions is examined and the convergence properties of the resulting elements compared with others derived form assumed displacements.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 163-167 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Deformation functions which, in addition to satisfying the continuity conditions at nodes. Also satisfy. Approximately, the governing differential equation within the element allow system eigenvalues to be found more accurately, with a given number of elements, than is possible with previously published deformation functions. This is illustrated for the case of beams.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 169-175 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: A numerical method for obtaining the Green's functions for Laplace's, Poisson's, and the transient heat diffusion equations is presented. The Green's functions thus obtained are then employed to rapidly obtain numerical solutions of the above equations by matrix multiplication, with subsequent considerable savings in machine time.
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  • 56
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 151-162 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The direct Finite Element Analysis which was successfully employed in the solution of dynamic flexural traveling wave problems is extended herein to provide the transient behaviour of finite beams and plates in which shear deformation and rotatory inertia are considered. The particle and angular velocities are exponentially damped so that the static solutions for these problems are obtained with the same analysis which provided the dynamic and transient cases. Three special cases are chosen as examples. In the first, a sinusoidally varying shear force is applied at the tip of a cantilever beam. The resonant characteristics of this beam for both the undamped and damped cases are studied. In the second, a step shear loading is applied to a cantilever beam and its damped dynamic history is studied. Finally, a circular plate whose outer edge is simply supported is impacted at its inner edge by a step moment and its damped transient behaviour is determined. The idea of the methods is potentially applicable to dynamic problems in general.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 177-180 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The solution of the large numbers of non-linear algebraic equations occurring in analyses of non-linear structural systems using finite differences or finite elements is time consuming even for the fastest computers. This paper presents a method of solution based on a Taylor's expansion technique which is an aid in the solution of such systems of equations.Examples presented show that in the finite element analysis of moderately non-linear structural systems the technique provides sufficiently accurate solutions. For more non-linear systems the technique provides excellent starting values for the Newton-Raphson method.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 201-203 
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    Keywords: Engineering ; Engineering General
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  • 59
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 181-200 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Surface displacements at the end of a semi-infinite, circular cylinder due to an axisymmetric ring of forces on the end are examined. The solution which has been found may then be used to find surface displacements for general axisymmetric loadings by convolution. The solution, in tabular form, is given as corrections to the counter-part half-space solution.The method of solution involves a three step superposition process. First, the displacement due to a ring of forces on a half-space is found by using the Boussinesq solution. Then, the excess tractions on the half-space, over that of the cylinder, are removed. This is done in two parts. The problem of an infinite cylinder with linearly varying pressure and shear over a short length of the lateral surface is solved by using Fourier integrals. This is used for the removal of the pressure and shear on the lateral surface of the cylinder by convolution. Next, the stresses at the mid-section of the infinite cylinder are removed. This is done by finding a set of boundary conditions for the end which yields zero tractions on the lateral surface. Then a series of these boundary conditions is used to approximate the tractions which must be removed.With the solution thus obtained, two sample problems are shown: 1. an elastic cylinder in contact with a half-space; 2. a rigid punch in contact with an elastic cylinder.
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    International Journal for Numerical Methods in Engineering 1 (1969) 
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 205-221 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: This paper presents a general theory of finite elements. The concept of finite elements is cast in a general topological framework valid for spaces of finite dimension. It is shown that the idea of finite element models can be developed in higher-dimensional spaces, independent of specific co-ordinate systems, for any type of continuous abstract function defined on the space. Generalizations of the familiar Lagrange and Hermite interpolation functions are presented as well as a general statement of the notion of generalized variables and conjugate fields. It is also shown that admissible finite elements can be developed for non-Euclidean spaces of finite dimension. Topological properties of finite element models are examined in Part I of the paper. Part II is devoted to certain applications.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 224-224 
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 247-259 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: In Part I of the this paper, topological properties of finite element models of functions defined on spaces of finite dimension were examined. In this part, a number of applications of the general theory are presented. These include the generation of finite element models in the time domain and certain problems in wave propagation, kinetic theory of gases, non-linear partial differential equations, non-linear continuum mechanics, and fluid dynamics.
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 225-245 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A method is presented based on matrix algebra for the dynamic analysis of a mixed rotating and non-rotating vibration system. Such systems occur in practice when turbo-alternator sets are mounted on flexible steel foundations.The mathematical model considered consists of a rotating non-uniform, bi-symmetric shaft connected via three or more flexible-film bearings to a flexible structure throughout which mass is distributed. The shaft, which is assumed to rotate at constant speed, is heavy, flexible and carries several rigid axi-symmetric discs. Viscous damping is assumed to act in all parts of the system and gravitational effects are ignored.
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  • 65
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 261-274 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A presentation is made of a rectangular plate bending element, the use of which corresponds to the finite difference method. The element stiffness matrix is arrived at by approximation of the strain energy of the element by suitably selected finite difference expressions which contain not only values in respect of the deflection, but also values of its first derivatives. On the basis of the connection found between the two methods, some changes are suggested in the finite difference method, which involve a more realistic way of considering the detailed distribution of the loading. The effect of these modifications is illustrated in two applications.
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  • 66
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 101-122 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The derivation of the stiffness matrix for a refined, fully compatible triangular plate bending finite element is presented. The Kirchhoff plate bending theory is assumed. Six parameters or degrees of freedom are introduced at each of the three corner nodes resulting in an 18 degree of freedom element. This refined element is found to give better results for displacements and particularly for internal moments than any plate bending element, regardless of shape, previously reported in the literature.
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  • 67
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 123-133 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The large deflection problem of a rectangular plate is analysed by using the finite element method and employing the iteration technique. In the present study, the stiffness matrix of a rectangular plate element for bending proposed by Greene is employed, and results of numerical examples duly justifies applicability of the present method.
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  • 68
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    International Journal for Numerical Methods in Engineering 1 (1969) 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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  • 69
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    International Journal for Numerical Methods in Engineering 1 (1969), S. 333-349 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The paper presents a method for reducing the size of a vibration analysis by generating an inertia matrix referred to a limited set of ‘master’ vibrational freedoms. In designing a computer program to perform this mass condensation process, the emphasis has been on providing a two way interface between structural analysis and vibration analysis programs. The transformation from the full set of degrees of freedom to the master set makes extensive vibration calculations economically feasible giving solutions in terms of the amplitudes of the master freedoms. However, by reversing the transformation after completion of a vibration analysis, it is possible to restore the full set of freedoms, allowing automatic plotting of mode shapes in full detail, and re-entry to the structural analysis program for the purpose of computing dynamic stresses.A worked example is given. This is a realistic machine tool structure rather than the simple plates or beams which are usually used for illustration purposes. Natural frequencies and mode shapes, calculated with various degrees of condensation, are compared with those obtained by using all possible freedoms. A comparison is also made with an intuitive selection of ‘lumped masses’.
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    Diabetologia 4 (1968), S. 111-117 
    ISSN: 1432-0428
    Keywords: Insulin ; diabetes ; insulinase ; rat diaphragm ; glycogen synthesis ; RNA turnover ; cell culture ; anti-insulin serum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Peu de progrès conduisant à la compréhension du diabète en termes moléculaires ont été réalisés. La possibilité qu'il existe une modification dans la structure de l'insuline des diabétiques, aussi bien circulante que pancréatique, s'appuie sur trois arguments expérimentaux obtenus au laboratoire des auteurs. — La purification immunochimique de l'insuline circulante de diabétiques jeunes non traités par l'insuline a d'abord conduit à la constatation que cette insuline est relativement résistante à l'action réductrice et protéolytique d'une préparation d'insulinase musculaire. De plus, l'insuline pancréatique, isolée à partir de cinq pancréas diabétiques, s'est avérée d'activité biologique diminuée quant à son pouvoir d'augmenter la synthèse du glycogènein vivo et à sa capacité d'accélérer le “turnover” du R.N.A. en culture tissulaire. — La nature de cette „insuline anormale” et son rôle possible dans la physiopathologie du diabète sont examinés à la lumière de la nécessité de donner une définition spécifique de la modification moléculaire précise.
    Abstract: Zusammenfassung Unsere Kenntnisse über den Diabetes in molekularbiologischer Sicht haben kaum Fortschritte gemacht. Die Möglichkeit, daß das zirkulierende und das Pankreas-Insulin des Diabetikers strukturelle Unterschiede aufweisen, wird durch die Ergebnisse von drei verschiedenen Untersuchungsreihen gestützt, die im Laboratorium der Verfasser durchgeführt wurden. — Immunologisch gereinigtes zirkulierendes Insulin von Diabetikern, die noch kein Insulin erhalten hatten, erwies sich als recht widerstandsfähig gegenüber dem Abbau durch ein Insulinase-Rohextrakt aus Muskelgewebe. Aus den Bauchspeicheldrüsen von 5 Diabetikern gewonnenes Insulin zeigte sowohl in seiner Fähigkeit, die Glycogen-Synthesein vivo, als auch den Ribonucleinsäuren-Umsatz in der Gewebskultur zu stimulieren, eine herabgesetzte biologische Aktivität. — Bei der Diskussion der Natur dieses „abnormen” Insulins und seiner hypothetischen Rolle in der Physiopathologie des Diabetes ergibt sich besonders deutlich, wie dringend erforderlich eine genauere Klärung des in diesem Falle vorliegenden molekularen Umbaus ist.
    Notes: Summary Understanding of diabetes in molecular terms has advanced very little. The possibility that a structural difference exists in the circulating and pancreatic insulin moiety of diabetics is supported by three lines of evidence obtained in the authors' laboratory. — Immunologically purified circulating insulin from diabetic subjects untreated with insulin was noted to be relatively resistant to degradation by a crude muscle insulinase preparation. The pancreatic insulin of five diabetic pancreases was found to have a decreased biological activity in its ability to enhance glycogen synthesisin vivo and in its capacity to stimulate RNA turnover in tissue culture. — The nature of this “abnormal insulin” and its hypothetical role in the physiopathology of diabetes are discussed in the light of the need for a specific definition of the precise molecular change.
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    Diabetologia 4 (1968), S. 1-9 
    ISSN: 1432-0428
    Keywords: Human growth hormone ; Growth hormone ; Insulin ; Diabetes mellitus ; Experimental diabetes ; Acromegaly ; Pathogenesis of diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Il a été démontré récemment que l'hormone de croissance humaine (HGH) joue un rôle prééminent dans la régulation normale de la glycémie. De plus, il est bien connu que l'hormone de croissance peut créer un état semblable au diabète chez l'animal. Chez l'homme, l'injection de HGH ou l'hypersécrétion de l'hormone endogène dans l'acromégalie est suivie d'intolérance au glucose seulement dans 25% des cas. — Dans ce travail nous présentons des données qui mettent l'action dite diabétogène de HGH dans un contexte plus nuancé. Nous suggérons que HGH, bien que diminuant l'utilisation du glucose par les tissus périphériques, n'est pas une substance primairement diabétogène, car l'effet insulinotrope de l'hormone cause une hyperinsulinémie compensatrice, qui à son tour normalise la tolérance au glucose. HGH est diabétogène exclusivement chez les sujets prédiabétiques dont le pancréas est incapable de répondre à l'effet insulinotrope de l'hormone. Chez ces sujets, la diabétogénicité de HGH n'étant pas surmontée par une hyperinsulinémie compensatrice, la tolérance au glucose sera anormale. Ainsi, HGH peut être considérée comme unfacteur additif pour la pathogénèse du diabète sucré, la condition essentielle et primaire étant un état préexistant de prédiabète.
    Abstract: Zusammenfassung Wie kürzlich gezeigt wurde, spielt das menschliche Wachstumshormon (HGH) eine wichtige Rolle bei der Kontrolle der Blutzucker-Homöostase. Ferner ist schon lange bekannt, daß die Verabreichung von Wachstumshormon an Tiere zu einem diabetesähnlichen Zustand führen kann. Beim Menschen löst die Gabe der Substanz oder die Überproduktion des endogenen Hormons bei der Akromegalie nur in etwa 25 % der Fälle eine Glucosetoleranzstörung aus. — In dieser Arbeit werden Resultate beschrieben, die ein detaillierteres Bild der sogenannten diabetogenen Wirkung des HGH vermitteln. Wir möchten annehmen, daß das HGH, obwohl es den peripheren Glucoseverbraueh herabsetzt, kein primär diabetogener Faktor ist, da es über eine Insulin-mehrausschüttung zu einem Hyperinsulinismus führt, der eine normale Glucosetoleranz bewirkt. HGH zeigt Scine diabetogene Wirkung nur bei Prädiabetikern, deren Pankreas den stimulierenden Effekt des Hormons auf die Insulinausschüttung nicht beantworten kann. Bei diesen Personen kann eine Störung der Glucosetoleranz dadurch entstehen, daß die diabetogene Wirkung des HGH nicht durch einen kompensatorischen Hyperinsulinismus ausgeglichen wird. HGH kann daher als ein Zusatzfaktor bei der Diabetesentstehung angesehen werden, deren Hauptvorbedingung jedoch eine schon vorher bestehende prädiabetische Stoffwechselsituation darstellt.
    Notes: Summary Human growth hormone (HGH) has recently been shown to play a prominent role in the control of blood glucose homeostasis. Furthermore, it has long been known that administration of growth hormone in animals can induce a diabetes-like state. In human subjects, exogenous administration of HGH or hypersecretion of the endogenous hormone in acromegaly is accompanied by glucose intolerance in only about 25 per cent of the cases. — In this paper, data are presented which give a more diversified picture of the so-called diabetogenic action of HGH. It is suggested that HGH, although decreasing the peripheral utilization of glucose, is not a primary diabetogenic factor, since its insulinogenic action causes a compensatory hyperinsulinism, with normal glucose tolerance as the result. HGH is diabetogenic only in prediabetic subjects whose pancreas is unable to respond to the insulinogenic effect of the hormone. In such subjects, the diabetogenic action of HGH not being counterbalanced by a compensatory hyperinsulinism, glucose intolerance may result. Thus, HGH may be regarded as anadditional factor for the development of diabetes, the major prerequisite being a preëxisting prediabetic state.
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    Diabetologia 4 (1968), S. 281-285 
    ISSN: 1432-0428
    Keywords: Insulin ; radioimmunoassay ; bile ; bile acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'effet des acides biliaires sur le dosage radioimmunologique de l'insuline a été examiné et les résultats ont montré que les acides biliaires en concentrations physiologiques nuisent à la liaison de l'insuline avec le sérum anti-insulinique. La courbe de dilution de l'insuline immunoréaetive dans la bile de la vésicule biliaire porcine n'était pas parallèle à celle de l'insuline porcine standard. Après extraction de la bile porcine par du sérum antiinsulinique et après dosage de l'extrait, des taux d'insuline plus bas ont été trouvés. Les résultats suggèrent qu'une partie seulement de «l'insuline immunoreactive» de la bile de la vésicule biliaire représente de l'insuline véritable.
    Abstract: Zusammenfassung Die Wirkung von Gallensäuren auf die radio-immunologische Insulinbestimmung wurde untersucht. Aus den Resultaten geht hervor, daß Gallensäuren in physiologischen Konzentrationen zu einer Störung der Insulinbindung an Anti-Insulinserum führen. Die Verdünnungskurve von immunoreaktivem Insulin im Gallensaft aus Schweinegallenblasen verlief nicht parallel zur Standard-Eichkurve von Schweineinsulin. Nach Extraktion der Schweinegalle mit Anti-Insulinserum fanden sich im Extrakt niedrigere Insulinkonzentrationen. Die Ergebnisse deuten darauf hin, daß nur ein Teil des „immunoreaktiven Insulins” in der Blasengalle echtes Insulin ist.
    Notes: Summary The effect of bile acids on the radioimmunoassay of insulin has been investigated, and the results show that bile acids in physiological concentrations interfere with the binding of insulin by anti-insulin serum. The dilution curve of immunoreactive insulin in pig gall-bladder bile was not parallel to that of standard pig insulin. After extraction of pig bile with anti-insulin serum and assay of the extract, lower insulin levels were found. The results suggest that only a part of the “immunoreactive insulin” in gall-bladder bile is genuine insulin.
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  • 73
    ISSN: 1432-0428
    Keywords: Insulin ; 3′,5′-AMP phosphodiesterase ; glycogen metabolism ; lipolysis ; insulin secretion ; antilipolytic action of insulin ; glycogen synthesis and insulin ; cyclic adenosine 3′,5′-monophosphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'influence de l'insuline sur le métabolisme du glycogène hépatique et sur la lipolyse semble s'exercer par l'intermédiaire d'une diminution de la concentration de 3,′5′-AMP intracellulaire. Onamontré une diminution de la formation de 3′5′-AMP dans le tissu adipeux incubé avec de l'insuline. L'influence de l'insuline sur la dégradation du 3,′5′-AMP est étudiée. — L'activité de la 3,′5′-AMP-phos-phodiestérase (PDE) est diminuée dans le foie, le tissu adipeux et, de façon non-significative, dans le muscle strié des rats qui manquent d'insuline, c-à-d les rats rendus diabétiques par l'alloxane ou les rats privés de nourriture. L'injection intraveineuse d'une faible dose d'insuline (0.5 U/kg) ou la stimulation de la sécrétion d'insuline endogène par une injection de glucose provoquent une augmentation rapide de l'activité de la phosphodiestérase dans ces tissus. 15 min après l'injection d'insuline, l'activité de la phosphodiesterase du foie est augmentée. L'effet maximum est atteint après 30–45 min. L'activité de la phosphodiestérase rénale n'est pas diminuée dans le diabète alloxanique, l'injection d'insuline s'est avérée inefficace.In vitro, l'insuline cristalline a un effet activant sur la phosphodiestérase purifiée du coeur de boeuf. La concentration d'insuline requise pour doubler l'activité de l'enzyme est de l'ordre de 2 · 10−5 M. Le traitement avec actinomycin D empêche la stimulation par l'insuline de la PDE dans le foie. Ceci peut indiquer que l'action de l'insuline sur l'activité de la phosphodiestérase est essentiellement basée sur une synthèse accrue de l'enzyme. A cause de l'influence de la sécrétion d'insuline sur la concentration en 3,′5′-AMP du foie et du tissu adipeux, le métabolisme du glycogène et la lipolyse peuvent s'adapter rapidement à la prise de nourriture.
    Abstract: Zusammenfassung An der Steigerung der Glykogensynthese der Leber und der Verminderung der Lipolyse durch Insulin ist eine Abnahme der 3′,5′-AMP-Konzentration wesentlich beteiligt. Die 3′,5′-AMP-Bildung ist in Fettgewebe, das mit Insulin inkubiert wird, vermindert. Insulin beeinflußt jedoch auch den 3′,5′-AMP-Abbau. -Die 3′,5′-AMP-Phosphodiesterase (PDE)-Aktivität des Fettgewebes, der Leber und, in geringerem Grade, der Skeletmuskulatur ist im Insulinmangel vermindert, d.h. bei alloxandiabetischen oder hungernden Ratten. I.v. Injektion von 0,5 E/kg Insulin oder eine erhöhte Abgabe von Insulin aus dem Pankreas nach Glucoseinjektion führen in diesen Geweben zu einem raschen Anstieg der PDE-Aktivität. Dieser ist in der Leber schon 15 min nach Insulingabe nachweisbar und erreicht nach 30–45 min sein Maximum. In der Niere ist kein Einfluß von Insulin auf die PDE-Aktivität nachweisbar. — Aus Rinderherz isolierte PDE wirdin vitro durch Insulin aktiviert, jedoch werden2 · 10−5 M zur Verdopplung der Aktivität benötigt. Actinomycin D verhindert die Steigerung der Leber-PDE-Aktivität nach Insulininjektion. So kann die Wirkung des Hormons im wesentlichen auf eine gesteigerte PDE-Synthese zurückgeführt werden. — Durch diesen Einfluß der Insulininkretion auf die 3′,5′-AMP-Konzentration in Leber und Fettgewebe können Glykogenstoffwechsel und Lipolyse rasch an die Nahrungsaufnahme angepaßt werden.
    Notes: Summary Influence of insulin on liver glycogen metabolism and on lipolysis appears to be mediated by a decreased intracellular 3′,5′-AMP concentration. Reduced formation of 3′,5′-AMP had been shown in adipose tissue incubated with insulin. The influence of insulin on 3′,5′-AMP degradation has been investigated. — 3′,5′-AMP phosphodiesterase (PDE) activity was reduced in liver, adipose tissue and, insignificantly, in skeletal muscle of insulin deficient, i.e. alloxan diabetic or starved rats. I.V. injection of a low dose of insulin (0.5 U/kg) or stimulation of endogenous insulin secretion by injection of glucose led to a rapid increase of PDE activity in these tissues. 15 min after insulin injection liver PDE activity was increased. The maximal effect occurred after 30–45 min. Renal PDE activity was not decreased in alloxan diabetes, insulin injection has been found ineffective. —In vitro, there was an activating effect of crystalline insulin on PDE purified from beef heart. Insulin concentration required for duplication of enzyme activity was of the order of 2 · 10−5 M. Treatment with actinomycin D nearly prevented stimulation of liver PDE by insulin. This may indicate that the action of insulin on PDE activity is essentially based on an increased enzyme synthesis. — Owing to the influence of insulin secretion on liver and adipose tissue 3′,5′-AMP concentration, glycogen metabolism and lipolysis can be quickly adapted to food intake.
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    Diabetologia 4 (1968), S. 68-70 
    ISSN: 1432-0428
    Keywords: Insulin ; proinsulin ; biosynthesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Après incubation de tranches de pancréas d'embryon de veau, la leucine-H3 est incorporée dans une fraction protéique qui semble avoir les propriétés d'une “proinsuline”. Cette fraction protéique est de taille supérieure à l'insuline, possède l'immunoréactivité propre à l'insuline, et après traitement limité par la trypsine elle est transformée en un peptide semblable à l'insuline.
    Abstract: Zusammenfassung Die Inkubierung von Dünnschnitten des fötalen Rinder-Pankreas in Gegenwart vom H3- Leucin ergab einen Einbau dieser Amminosäure in eine Eiweißfraktion, die die Eigenschaften eines, Pro-Insulins' aufwies. Das Molekulargewicht dieser Eiweißfraktion war größer als dasjenige des Insulins; sie besaß die Immunreaktivität des Insulins und konnte durch teilweisen Abbau mit Trypsin in ein insulinähnliches Peptid umgewandelt werden.
    Notes: Summary Incubation of fœtal bovine pancreas slices resulted in the incorporation of3H-leucine into a protein fraction which appeared to have the properties of a ‘proinsulin’. This protein fraction was larger in size than insulin, possessed the immunoreactivity of insulin and was converted by limited trypsin treatment to a peptide similar to insulin.
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  • 75
    ISSN: 1591-9528
    Keywords: Insulin ; Monosaccharide ; Hormones ; Mammals ; Amphibians ; Insulinsekretion ; Monosaccharide ; Hormone ; Säugetiere ; Amphibien
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Stimulierung der Insulinsekretion durch Monosaccharide und Hormone wurde mit der Technik der Inkubation von isolierten Pankreasstückchen untersucht. Der Insulingehalt der Inkubationsmedien und der Pankreasgewebe wurde mit der biologischen (Oxydation von14C-Glucose durch das epidydemale Fettgewebe der Ratte) und der radioimmunologischen Bestimmungsmethode mit Trennung des freien und gebundenen Insulins durch Amberlite ermittelt. Das Kaninchenpankreas reagierte auf Glucose, Fructose, Ribose, Xylose, STH und Sekretin mit gleichbleibender Insulinausschüttung, nicht dagegen auf Galaktose, D- und L-Arabinose und ACTH. Die Gewebe anderer Säugetiere (Hund und Kalb, nicht aber Ratten) und einer Amphibienart (Grasfrosch) zeigten eine übereinstimmende Insulinfreisetzung nach Gabe von Glucose, wobei die Säugetiere etwa 1%, das Amphibium etwa 10% des Insulingehalts abgaben. Das Froschpankreas wies in seiner Reaktion eine jahreszeitliche Abhängigkeit auf, indem es im Winter nicht, im Sommer am stärksten auf die Stimulationsreize ansprach.
    Notes: Summary The stimulation of insulin-secretion by monosaccharides and hormones was studied with the technique of incubation of isolated pieces of pancreas. The insulin content of the incubation medium and of the pancreatic tissue was measured using both biological (oxidation of 14-C-glucose by epidydimal fat tissue of rats) and radio-immunological methods (separation of free and bound insulin with amberlite). The rabbit pancreas was stimulated by glucose, fructose, ribose, xylose (with constant insulin release), STH, and secretin, but not by galactose,d- andl-arabinose, and ACTH. The pancreatic tissue of other mammals (dog and calf, not rats) and one amphibian species (gras frog) showed the same insulin release after glucose which was 1% by mammals and 10% by amphibian of the insulin content of the tissue. The reaction of the frog pancreas depended upon the time of the year. In summer it reacted strongly to stimulants but in the winter it did not.
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    Naunyn-Schmiedeberg's archives of pharmacology 260 (1968), S. 254-268 
    ISSN: 1432-1912
    Keywords: Bilirubin ; Glucuronates ; Insulin ; Liver ; Tolbutamide ; Bilirubin ; Glucuronidsynthese ; Insulin ; Leber ; Tolbutamid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Lebergewebe von Ratten, die mit Tolbutamid, mit anderen blutzuckerwirksamen Sulfonylharnstoffderivaten oder mit Insulin behandelt worden waren, bildet bei Inkubation in vitro mehr Bilirubinglucuronid als das Gewebe unbehandelter Kontrolltiere. Dieser Effekt wurde 2 Std nach der intraperitonealen Injektion der blutzuckersenkenden Stoffe nachgewiesen, er tritt dosisabhängig auf und ist mit der blutzuckersenkenden Wirkung gut korreliert. Ein dem Tolbutamid chemisch verwandtes, jedoch blutzuckerunwirksames Methylsulfonylharnstoffderivat hatte diese Wirkung nicht. Die Steigerung der Glucuronidsynthese ist dadurch bedingt, daß in der Leberzelle während einer Insulin- oder Sulfonylharnstoffhypoglykämie vermehrt aktivierte Glucuronsäure (UDPGA) für die Konjugation bereitgestellt wird. Die Aktivität des für die Konjugationsreaktion verantwortlichen Enzyms, der UDP-Glucuronyltransferase, war unter unseren Versuchsbedingungen nicht verändert. Es fanden sich keine Anhaltspunkte dafür, daß in der Insulin- oder Sulfonylharnstoffhypoglykämie die Bildung von UDPGA aus UDPG beschleunigt erfolgt. Die Aktivität der UDPG-Dehydrogenase war nicht verändert, auch Faktoren, die eine Bildung von UDPGA begünstigen könnten, wie ein erhöhter NAD+/NADH-Quotient und eine gesteigerte ATP-Konzentration im Gewebe, waren nach Tolbutamid nicht nachzuweisen.
    Notes: Summary Liver tissue of rats pretreated with tolbutamide, with other hypoglycaemic sulfonylurea compounds, or with insulin formed more bilirubinglucuronide when incubated in vitro than the tissue of untreated controls. The effect was present two hours after the blood sugar lowering agents had been injected intraperitoneally. It was dose-dependent and well correlated to the hypoglycaemic response. A methylated sulfonylurea compound, which is chemically closely related to tolbutamide but devoid of blood sugar lowering activity failed to show this effect. Glucuronide formation in hypoglycaemia induced by insulin or tolbutamide is increased as more activated glucuronic acid (UDPGA) is made available to the conjugation reaction. There was no change in the activity of the enzyme responsible for glucuronide synthesis, the UDP-glucuronyl-transferase, in our experiments. There was no indication that the formation of UDPGA from UDPG was accelerated by insulin or sulfonylureas. There was no change in the activity of the hepatic UDPG-dehydrogenase. Factors which could favour the formation of UDPGA such as an increased NAD+/NADH ratio or an elevated ATP concentration in the tissue were not present following tolbutamide.
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    Pflügers Archiv 301 (1968), S. 254-258 
    ISSN: 1432-2013
    Keywords: Insulin ; Potassium Deficiency ; Membrane Potential ; Rat Diaphragm ; Insulin ; Kaliummangel ; Membranpotential ; Rattenzwerchfell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An 102 Zellen des Zwerchfells von insgesamt 7 Ratten mit alimentärem Kaliummangel fanden wir unter dem Einfluß von Insulin (0,1 I.E./ml) eine Depolarisation um 11,2 mV, nämlich von −94,6 (s=±6,4) mV bei insgesamt 100 Zellen auf −83,4 (s=±6,8)mV (p 〈 0,001). Die Kaliumkonzentration in der Inkubationslösung betrug 4,7 (s=±0,29) mval/l. — Ferner steigt die bei kaliumverarmten Tieren erniedrigte intracelluläre Kaliumkonzentration unter Insulineinfluß von 107 (s=±12) mval/lH2O IZR auf 130 (s=±19,8) mval/lH2O IZR an (p〈0,05). Die Befunde sprechen dafür, daß Insulin bei kaliumverarmten Tieren einen Netto-Kaliumeinstrom bewirkt, der eine Abnahme des Membranpotentials zur Folge hat.
    Notes: Summary In 102 single muscle cells of 7 rats with alimentary potassium depletion we found under influence of insulin (0.1 I.U./ml) a depolarisation of 11.2 mV, i.e. from −94.6 (s=±6.4)mV (100 cells) to −83.4 (s=±6.8)mV (p〈0.001). The potassium concentration in the incubation medium was 4.7 (s=±0.29) mequ/l. — In addition we measured under influence of insulin (0.1 I.U./ml) an intracellular potassium concentration of 130 mval/lH2O IZR, which is probably higher than in potassium deficient animals without insulin (p〈0.05). These findings suggest that insulin produces a netto potassium influx in potassium deficient animals, which could explain the depolarisation.
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  • 78
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    Psychopharmacology 12 (1968), S. 384-399 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Tranquilizing Agents ; Chlordiazepoxide ; Frustration ; Animal Behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This experiment investigated the possibility that chlordiazepoxide (CDP) has unique properties that account for state dependent learning, and prevention of conflict-induced behavior fixations. One group of rats were given a discrimination problem on a Lashley jumping stand, but on even days all responses were punished. Another group were treated the same way except than on even days all responses were rewarded. Each of these groups were subdivided, half of the Ss were given CDP on even days, the other half no drug. The results showed that punishment on even days for the response to be learned disrupted learning more than reward for responses that were to be avoided. CDP practically eliminated these disruptive effects and aided learning for the punishment group, but led to a slower rate of learning for the reward group. These findings confirmed the hypothesis that CDP attenuates the effects of negative incentives, and that this property accounts for the drug's cue value in discrimination learning and for its fixation prevention characteristics.
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  • 79
    ISSN: 1432-2072
    Keywords: Central Nervous System ; Psychopharmacology ; DDT ; Parathion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The offspring of female mice treated with 2.5 mg/kg DDT during the second or third trimester of pregnancy showed a delayed acquisition of the conditioned avoidance response. If DDT was given in the first trimester, or if 3 mg/kg of Parathion was given during the pregnancy, no effect on the conditioned avoidance response of the off-spring was seen.
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  • 80
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Psychopharmacology ; Antianxiety ; Drug Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oxazepam has two opposing actions on behavior: a responsedecreasing or depressant action and a response-increasing or disinhibitory action. The course of the two actions in chronic dosing was determined in rats in a test in which punished and unpunished schedules of reinforcement were alternated. The depressant action (measured by a decrease in the rate of unpunished behavior) was observed to undergo tolerance after 3–4 doses, while the disinhibitory action (measured by an increase in the rate of punished behavior) failed to show tolerance and even increased throughout the chronic series. The selective tolerance of the depressant action is probably due to neuronal adaptation, but changes in metabolism also may be involved. The increase in the rate of punished behavior is attributed, at least in part, to a progressive unmasking of the disinhibitory action as tolerance to the depressive action develops.
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  • 81
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Electrophysiology ; Arousal ; Animal Behavior ; Brain Biogenic Amines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the interactions of reserpine and the monoamine oxidase inhibitors, nialamide and isocarboxazid, in rabbits. EEG recordings were made from animals with acute and chronically implanted electrodes. Gross behavioral observations were made in freely moving rabbits and brain amine concentrations of norepinephrine and serotonin were also determined. Emphasis was placed on observing drug effects over periods of time ranging up to 13 days. Rabbits given isocarboxazid or nialamide alone exhibit a phenomenon rarely seen in the control animals, namely partial activation, an EEG pattern in which slow waves of high amplitude are maintained in the cortex while fast activity appears in subcortical structures. This effect was also observed in rabbits treated with nialamide and reserpine in combination. By appropriate dosage schedules in which reserpine was administered to animals pretreated with monoamine oxidase inhibitors it was possible to maintain extended periods of frank arousal or EEG activation over a period of several days. The absolute concentrations of brain amines bore little or no relationship to the EEG effects observed, however, increased ratios of serotonin to norepinephrine were observed in conjunction with EEG activation and signs of behavioral excitement.
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  • 82
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    Psychopharmacology 12 (1968), S. 428-432 
    ISSN: 1432-2072
    Keywords: Ganglia, Basal ; Psychopharmacology ; Chlorpromazine ; Amphetamine ; Dopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In rats micro-injections in corpus striatum of quaternary chlorpromazine and related drugs give rise to highly characteristic neuroleptic effects: antagonism of amphetamine-induced stereotyped behaviour and development of catalepsy. There is no effect of injections in hippocampus or septum. Dopaminergic mechanisms in corpus striatum seem to play a central role in neuroleptic action.
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  • 83
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    Psychopharmacology 13 (1968), S. 118-128 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Diagnosis ; Sampling Studies ; Statistics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Theoretical models for sample selection by diagnosis using one, one-out-of-two, two, two-out-of-three, and three concurring opinions are illustrated. These models are then applied to two categories, schizophrenia and depressive disorders, for an actual sample of patients diagnosed by multiple observers. The conclusion is reached that sample selection by a single opinion is not sufficiently reliable for research studies. The choice of alternative methods of selection depends on the needs of a particular study. Samples chosen on the basis of two-out-of-three concurring opinions provide the least total error. When erroneous inclusions are particularly undesirable, higher degrees of consensus—e.g. agreeing pairs or triplets—are necessary.
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  • 84
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    Psychopharmacology 13 (1968), S. 129-139 
    ISSN: 1432-2072
    Keywords: Electroencephalography ; Psychopharmacology ; Imipramine ; Amphetamine ; Physostigmine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The results of the interaction of imipramine, physostigmine and d/l amphetamine in various intravenously administered dosages were studied on the cortical and subcortical electrical activity of cats. Imipramine was shown to cause a cortical synchronization, hippocampal desynchronization, rise in the threshold of electrocortical arousal and limbic convulsive activity which was potentiated by amphetamine. Imipramine increased the amount of physostigmine, but decreased the amount of amphetamine needed for cortical desynchronization. The possible significance of these findings for the neuropsychopharmacological action of imipramine is briefly discussed.
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  • 85
    ISSN: 1432-2072
    Keywords: Indoleamine Metabolism ; Psychopharmacology ; Antidepressive Drugs ; Amphetamine Derivatives (Chlorinated) ; Depression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary CMA (p-chloro-N-methylamphetamine) lowers the cerebral 5-HT concentration in test animals but has virtually no effect on the catecholamine concentrations. Moreover, this compound was found to behave in depressive patients like an antidepressive drug, not like a central stimulant of the amphetmine type. The study described was conducted in order to establish whether CMA influences the overall metabolism of indoleamines in man. Such an influence was clearly demonstrable. Our findings are consistent with the hypothesis that CMA releases 5-HT from its depots. It has not been explained why a considerable proportion of the released 5-HT is excreted unchanged and why the increase in 5-HIAA excretion is so small: the overall activity of MAO was found not to be inhibited. No indications of abnormal 5-HT degradation were found at this time. Patients with vital depressions who improved on CMA medication showed a lower 5-HIAA excretion before treatment than did patients who were refractory to CMA treatment. This is consistent with earlier observations. The possible cause of this phenomenon is discussed. Among the various possibilities considered, an abnormal 5-HT metabolism is regarded as the most plausible. Pertinent investigations are being continued.
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  • 86
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    Psychopharmacology 13 (1968), S. 161-169 
    ISSN: 1432-2072
    Keywords: Sleep-wakefulness Cycle ; Amphetamine ; Psychopharmacology ; Growing Animals ; Electrencephalography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of amphetamine on the sleep-wakefulness cycle were studied in 48 kittens during the growth period of 1–28 days of age. Recordings of EEG, EMG of the posterior neck muscles and respiratory rhythms were made as well as observations of gross behavior. 2. Percent time of wakefulness was increased with amphetamine (0.3 mg/kg). This effect became more marked with age, i.e., being more significant after 16 to 18 days of age (P〈0.005) than before (P〈0.05). These increases in the intensity of the effect during growth may be related to the postnatal development of the structures responsible for wakefulness. 3. Percent time of “activated” sleep was diminished significantly at all ages including the newborns (P〈0.005). This lack of the influence of age suggests that the structures responsible for “activated” sleep are well developed at birth. 4. The increase of percent time of slow wave sleep was observed. This increase is regarded as a “passive” manifestation of time left available after a severe diminution of “activated” sleep time and relatively slight increase of wakefulness time during amphetamine medication.
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  • 87
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    Psychopharmacology 13 (1968), S. 287-298 
    ISSN: 1432-2072
    Keywords: Motion Pictures ; Motor Skills ; Eye Movements ; Psychopharmacology ; Psychological Tests
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Measures of skilled motor performances, both of a task-oriented (tests of eye-hand coordination) and incidental (control of facial and ocular muscles) nature were recorded for a sample of 20 healthy young adults before and after single administrations of perphenazine, opipramol, imipramine and placebo at doselevels commonly supposed to produce mood or behavioral effects. It was anticipated that such performances would be sensitive even to slight changes in the subjects' physiological and psychological state; the aim was to test the power of tests of subtle skills in providing indices of slight to moderate behavioral effects. The performance measures remained surprisingly little affected by all drugs, despite their sensitivity to drug-independent improvement in performance throughout the experimental day, and despite evidences of drug-related effects, especially for imipramine and opipramol, in simple objective physiological measures, and for imipramine alone in subjective measures taken concurrently. There may be a class of skilled sensory-motor acts, particularly those related to well-learned daily activities, which, rather than being vulnerable to adverse effect, remain efficient even in the presence of signs of disturbance of bodily function.
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  • 88
    ISSN: 1432-2072
    Keywords: Cannabis ; Lysergic Acid Diethylamide ; Mescaline ; Hallucinogens ; Psychopharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using climbing rope and bar-pressing behavior methods, rats were rendered tolerant to Δ 9-THC, cannabis extract, mescaline and LSD-25. Cross-tolerance experiments showed that rats refractory to Δ 9-THC and cannabis extract were still sensitive to mescaline and LSD-25, and vice-versa. These results suggest that, in spite of the similarity of the clinical symptoms produced in man by the 3 drugs, Δ 9-THC may have its psychotomimetic effects produced by different mechanisms from those of LSD-25 and mescaline.
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  • 89
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    Psychopharmacology 12 (1968), S. 371-383 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Cholinergic Blocking Drugs ; Animal Behavior ; Scopolamine ; Conditioned Reflex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Atropine or scopolamine improved conditioned avoidance behavior for most rats which performed poorly, in spite of extensive training, in a shuttle-box procedure. As previously reported, d-amphetamine also improved performance in many of these animals, but there was no particular relationship between a rat's responses to the cholinergic blocking agents and to d-amphetamine. The effect of any one of the 3 agents was, for the most part, reversible after the drug effect had dissipated. Physostigmine was quite potent in disrupting avoidance behavior in rats that performed well in the shuttle-box, even in animals that were overtrained. This impairment was antagonized by atropine or scopolamine, partly antagonized by d-amphetamine, and not antagonized by methyl atropine. Poor performers were found to be very sensitive to the disruptive effects of physostigmine, losing much of their escape behavior after relatively small doses. The results are interpreted as evidence for a central cholinergic system with inhibitory influences for modulating stimulus-response patterns. Under normal circumstances this inhibitory system probably functions in an integrated manner with the adrenergic mobilizing system for the central control of learned behavior. Centrally-active anticholinergic drugs of the muscarinic type appear to influence behavioral responses by inducing a response disinhibition.
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  • 90
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    Psychopharmacology 13 (1968), S. 210-221 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Animal Behaviour ; Nicotine ; Physostigmine ; Motor Activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats of 3 strains were observed at regular intervals and their activity was recorded using four categories of behaviour-rearing, moving, grooming and immobile. Strain differences in control activity were found. Nicotine and physostigmine reduced the activity of the more active rats and increased that of the less active animals. Rearing behaviour was particularly susceptible to depression by both drugs. The similarity of effect of the two drugs supports the hypothesis that one of the actions of nicotine in the brain is the release of acetylcholine.
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  • 91
    ISSN: 1432-5233
    Keywords: Insulin ; Insulin antibodies ; Insulin binding properties of serum ; Insulin therapy ; Serum proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les AA. ont observé que le sérum d'un sujet normal et celui d'un diabétique, jamais traité avec insuline, ont la possibilité de lier l'insuline dans la même mesure. Dans certains sérums, soit du sujet normal soit du diabétique, est présente une activité de liaison de l'insuline supérieure aux taux normaux plus élevés; cette activité diminue après administration de µU 500 d'insuline bovine. Les AA. présentent leurs considérations à propos de ce phénomène.
    Abstract: Resumen Los AA. observan que los sueros del individuo normal y del diabético nunca tratado con insulina poseen propiedades insulino-ligantes de entidad análoga. En algunos sueros — ya del sujeto normal, ya del diabético — está presente una actividad insulino-ligante superior a los valores máximos normales, que disminuye luego de haber agregado µU 500 de insulina bovina. Los AA. hacen algunas consideraciones interpretativas de tal fenómeno.
    Notes: Riassunto Gli AA. rilevano che i sieri dell'individuo normale e del diabetico mai trattato con insulina sono provvisti di proprietà insulino-legante di entità analoga. In alcuni sieri, sia del soggetto normale che del diabetico, è presente un'attività insulino-legante superiore ai valori massimi normali, che diminuisce dopo aggiunta di µU 500 di insulina bovina. Gli AA. fanno alcune considerazioni interpretative su tale fenomeno.
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    Acta diabetologica 5 (1968), S. 347-363 
    ISSN: 1432-5233
    Keywords: Diabetes mellitus ; Gel-filtration ; Insulin ; 125J-insulin-plasma complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les AA. ont étudié la capacité des protéines plasmatiques de lier l'insuline125J avec la méthode de filtration surgel. Le fractionnement parSephadex G-100 a démontré que seulement le 10 % de l'insuline marquée était lié par le protéines plasmatiques des sujets sains, des femmes gravides et des diabétiques non traités. Un pourcentage d'insuline beaucoup plus élevé était liée par les protéines plasmatiques dans des sujets que étaient traités precédemment avec de l'insuline bovine, tandis que le degrée de la liason était tres élevé dans les diabétiques insulino-résistants. De recherches avecSephadex G-200 ont demontré que, après une courte période d'insulinothérapie, le complexe insuline-protéine migrait avec les globulines 19 S. Après une insulinothérapie prolongée et dans les cas insulino-résistants la plus grande partie de l'insuline marquée liée aux protéines était élui avec les globulines 7 S. Le phénomène est attribué à l'action des anticorps anti-insuline bovine.
    Abstract: Resumen La capacidad que poseen las proteínas para ligar la insulina marcada con125J se estudió mediante el método de filtración engel. El fraccionamiento medianteSephadex G-100 demostró que solamente el 10 % de la insulina marcada estaba ligada por las proteínas plasmáticas de sujetos sanos, de mujeres embarazadas y de pacientes diabéticos no tratados. Un porcentaje de insulina notablemente superior estaba ligado por las proteínas plasmáticas en pacientes que anteriormente habían sido tratados con insulina bovina, mientras el grado de enlace se volvía muy elevado en los diabéticos resistentes a la insulina. Experimentos realizados conSephadex G-200 demostraron que después de un breve tratamiento insulínico, el complejo insulina-proteína migraba con las globulinas 19 S. Después de un prolongado tratamiento insulínico y en los casos resistentes a la insulina, la mayor parte de la insulina marcada con las proteínas resultaba eluida con las globulinas 7 S. El fenómeno, discutido detalladamente, se atribuye a la acción de los anticuerpos anti-insulina bovina.
    Notes: Riassunto La capacità delle proteine plasmatiche di legare l'insulina marcata con125J è stata studiata mediante il metodo di filtrazione sugel. Il frazionamento medianteSephadex G-100 ha dimostrato che soltanto il 10% dell'insulina marcata era legato dalle proteine plasmatiche di soggetti sani, di donne gravide e di pazienti diabetici non trattati. Una percentuale di insulina notevolmente superiore era legata dalle proteine plasmatiche in pazienti che erano stati precedentemente trattati con insulina bovina, mentre il grado di legame diveniva molto elevato nei diabetici insulino-resistenti. Esperimenti eseguiti conSephadex G-200 hanno dimostrato che, dopo una breve terapia insulinica, il complesso insulina-proteina migrava con le globuline 19 S. Dopo prolungata terapia insulinica e nei casi insulino-resistenti la maggior parte dell'insulina marcata legata alle proteine era eluita con le globuline 7 S. Il fenomeno, discusso nei particolari, è attribuito all'azione degli anticorpi anti-insulina bovina.
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    Acta diabetologica 5 (1968), S. 499-512 
    ISSN: 1432-5233
    Keywords: Entero-insular axis ; Gastrin ; Glucagon ; Gut hormones ; Insulin ; Pancreozymin ; Secretin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Des préparations hautement purifiées de gastrine, sécrétine et pancréozymine ont été injectées par voie endoportale chez des chiens anesthésiés, en vue d'examiner les influences possibles des hormones gastro-intestinales sur la sécrétion des îlots de Langerhans. On a vu que les trois hormones provoquent une augmentation immédiate de la concentration d'insuline dans la veine pancréatico-duodénale. L'effet de la gastrine sur la libération d'insuline était insignificant quantitativement, tandis que celui de la sécrétine était plus important et de plus grande durée; cependant la pancréozymine semblait être le stimulant le plus puissant et déterminer en outre une augmentation parallèle de la sécrétion pancréatique de glucagon. On a démontré de plus que la pancréozymine augmentait la réponse tant de l'insuline que du glucagon à l'hyperaminoacidémie. On a observé que l'administration intraduodénale d'acides aminés, qui représente notoirement la stimulation la plus puissante de la pancréozymine endogène, est en mesure de déterminer une libération plus grande et plus rapide d'insuline et de glucagon par rapport à l'administration intraveineuse d'acides aminés, ce qui fait supposer que la pancréozymine endogène joue un rôle physiologique lorsque la réponse de l'hormone des cellules insulaires aux acides aminés ingérés est augmentée. Le facteur physiologique qui augmente la réponse insulaire au glucose ingéré reste toutefois inconnu.
    Abstract: Resumen Medicamentos altamente purificados de gastrina, secretina y pancreozimina han sido inyectados por via intraportal a perros anestesiados, con el fin de examinar las posibles influencias de las hormonas gastro-intestinales sobre la secreción de las hormonas de las islas de Langerhans. Se ha notado que las tres hormonas producen aumento inmediato de la concentración de insulina en la vena pancreática-duodenal. El efecto de la gastrina sobre la liberación de insulina era insignificante cuantitativamente, mientras el de la secretina era apreciable y de mayor duración; sin embargo, parecía que la pancreozimina fuese el estimulante más potente y que además determinava aumento paralelo de la secreción pancreática de glucagón. Además se ha demostrado que la pancreozimina aumentava la respuesta, ya de la insulina, ya del glucagón, a la hiperaminoacidemia. La administración intraduodenal de aminoácidos, que representa notoriamente el más potente estímulo de la pancreozimina endógena, está en grado de provocar una liberación mayor y más rápida de insulina y glucagón, que la administración intravenosa de aminoácidos; cosa que hace pensar que la pancreozimina endógena ejerce un papel fisiológico cuando aumenta la respuesta de la hormona de las células de las islas a los aminoácidos ingeridos. Sin embargo, el factor fisiológico que aumenta la respuesta insular a la glucosa ingerida, queda desconocido.
    Notes: Riassunto Preparati altamente purificati di gastrina, secretina e pancreozimina sono stati iniettati per via endoportale in cani anestetizzati, allo scopo di esaminare le possibili influenze degli ormoni gastro-intestinali sulla secrezione degli ormoni delle isole di Langerhans. Si è riscontrato che tutti e tre gli ormoni provocano un immediato aumento della concentrazione di insulina nella vena pancreatico-duodenale. L'effetto della gastrina sulla liberazione di insulina era quantitativamente insignificante, mentre quello della secretina era più rilevante e di maggiore durata; tuttavia sembrava che la pancreozimina fosse il più potente stimolatore e che inoltre determinasse un aumento parallelo della secrezione pancreatica di glucagone. Per di più si è dimostrato che la pancreozimina aumentava la risposta sia dell'insulina che del glucagone alla iperaminoacidemia. La somministrazione intraduodenale di aminoacidi, che rappresenta notoriamente la più potente stimolazione della pancreozimina endogena, è stata riscontrata in grado di determinare una liberazione maggiore e più rapida di insulina e di glucagone rispetto alla somministrazione endovenosa di aminoacidi, il che fa pensare che la pancreozimina endogena svolga un ruolo fisiologico nell'aumentare la risposta dell'ormone delle cellule insulari agli aminoacidi ingeriti. Tuttavia il fattore fisiologico che aumenta la risposta insulare al glucosio ingerito rimane sconosciuto.
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  • 94
    ISSN: 1432-5233
    Keywords: Bovine insulin ; Insulin ; Insulin antibodies ; Insulin resistance ; Pork insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Les AA. présentent les résultats obtenus avec une méthode très simple pour la recherche des anticorps anti-insuline, basée sur l'emploi d'insuline I125 ou I131 et sur la précipitation avec alcool absolu du complexe antigène-anticorp. Les anticorps anti-insuline ont été fréquemment observés seulement dans des sujets diabétiques déjà soumis à traitement avec insuline. Un taux élevé d'anticorps anti-insuline s'accompagne à une diminution de la sensibilité à l'insuline (0,1 U/kg i.v.).
    Abstract: Resumen Se expresan los resultados obtenidos con el empleo de un método que puede ser ejecutado en forma my simple, para la investigación de anticuerpos anti-insulina; el método se basa sobre el empleo de insulina I125 o I131; y sobre la precipitación sucesiva con alcohol absoluto del complejo antígeno-anticuerpo. Los anticuerpos anti-insulina han sido hallados con mucha frecuencia solamente en pacientes diabéticos, que recibían tratamiento insulínico. Un título elevado de anticuerpos antiinsulina se asocia a una disminución sensible de la sensibilidad a la insulina (0,1 U/kg i.v.).
    Notes: Riassunto Vengono presentati i risultati ottenuti con l'impiego di una metodica di semplice esecuzione per la ricerca di anticorpi anti-insulina, basata sull'impiego di insulina I125 o I131 e sulla successiva precipitazione con alcool assoluto del complesso antigene-anticorpo. Gli anticorpi anti-insulina sono stati riscontrati con grande frequenza solo in pazienti diabetici già sottoposti a trattamento insulinico. Un elevato titolo di anticorpi anti-insulina si associa ad una diminuzione marcata della sensibilità all'insulina (0,1 U/kg i.v.).
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    Acta diabetologica 5 (1968), S. 279-298 
    ISSN: 1432-5233
    Keywords: Choline ; Clinical situation (diabetes) ; Glucagon ; Growth hormone ; Heparin ; Histamine ; Insulin ; Insulinemia ; Night vision ; Pro-insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Resume Alors que mon intérêt pour l'insuline a été pratiquement continu depuis déjà sa découverte, il y a eu des périodes pendant lesquelles mon attention s'est concentrée sur la coline, l'histamine et l'héparine. Pendant les années de guerre, les sujets de recherche ont été naturellement très différents. Les points importants dans le développement de l'insuline, du point de vue chimique, ont été sa purification, cristallisation, détermination de la structure et synthèse. Les physiologistes ont été fascinés par les études regardant le point et le mécanisme d'action de l'insuline. On a appris beaucoup quant à l'action sur grand nombre de tissus différents et l'insuline se montra être la principale hormone anabolique. Les développements cliniques ne sont mentionnés que brièvement car mes intérêts personnels de recherche ont été exclusivement expérimentaux.
    Abstract: Resumen Mientras mi interés para insulina fue prácticamente continuo desde su descubrimiento, hubo períodos en que mi atención se concentró sobre colina, histamina y heparina. Durante los años de la guerra, los temas de investigación fueron naturalmente muy diferentes. Los puntos fundamentales en el desarrollo de la insulina desde el punto de vista químico, fueron su purificación, cristalización, determinación de la estructura y síntesis. Los fisiólogos fueron cautivados por los estudios sobre el punto y el mecanismo de acción de la insulina. Mucho se aprendió acerca de la acción sobre muchos tejidos diferentes y la insulina demostró ser la hormona anabólica principal. Los desarrollos clínicos se mencionan sólo brevemente pues mis intereses personales de investigación han sido exclusivamente experimentales.
    Notes: Riassunto Mentre il mio interesse per l'insulina è stato praticamente continuo sin dalla sua scoperta, ci sono stati periodi nei quali la mia attenzione si concentrò sulla colina, istamina ed eparina. Durante gli anni della guerra, i temi di ricerca furono naturalmente molto diversi. I momenti culminanti nello sviluppo dell'insulina, dal punto di vista chimico, furono la sua purificazione, cristallizzazione, determinazione della struttura e sintesi. I fisiologi sono stati affascinati dagli studi circa il punto ed il meccanismo di azione dell'insulina. Molto è stato appreso intorno all'azione su molti tessuti differenti e l'insulina dimostrò di essere l'ormone anabolico principale. Gli sviluppi clinici sono menzionati solo brevemente poichè i miei personali interessi di ricerca sono stati esclusivamente sperimentali.
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  • 96
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    Psychopharmacology 12 (1968), S. 414-423 
    ISSN: 1432-2072
    Keywords: Psychopharmacology ; Barbiturates ; Phenothiazines ; Animal Behavior ; Motor Coordination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The rotarod test of motor coordination in mice was modified by increasing the rotation speed every 30 sec until the animals fell off. This procedure yielded a stable, proficient level of performance within four brief trials; the approximately normal distribution of performance times provided an equivalent measure of either improvement or impairment caused by drugs and permitted the use of parametric statistical tests. A total of 240 mice were assigned to 20 different groups of 12 each, administered oral doses of placebo or different drugs, prior to trial 4. The use of a ratio score (performance time in trial 4 divided by the same animal's time in trial 3) provided a measure of drug-induced changes, controlling for individual differences among animals in over-all level of performance. Two phenothiazines (chlorpromazine and perphenazine) impaired performance at low doses, with a progressively greater decrement at increasing doses (4, 8, 16 mg/kg); 2 barbiturates (pentobarbital and amobarbital) showed an all-or-none effect, with no significant decrement at the lower doses (20 and 40 mg/kg) but almost complete incapacitation at the highest dose of 80 mg/kg. Performance superior to the placebo condition was found with the 2 lower doses of pentobarbital and with 3 d-amphet-amine doses (4, 8, 16 mg/kg). An analysis of individual differences gave evidence that the animals which were inferior in prior performance were more susceptible to both improvement and impairment of performance under the influence of drugs.
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  • 97
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    Clinical and experimental medicine 148 (1968), S. 22-27 
    ISSN: 1591-9528
    Keywords: Insulin ; Hypoglycemia ; Xylitol ; Insulin ; Hypoglykämie ; Xylit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei Kaninchen, Meerschweinchen, Mäusen und Ratten wurde der Einfluß von Xylit auf die Insulinhypoglykämie untersucht. Es zeigte sich, daß Xylit die durch große intravenöse Insulindosen hervorgerufenen neurogenen Störungen (Lähmungserscheinungen, Krämpfe) zu beseitigen bzw. zu verhüten vermag. Gleichzeitig kommt es zu einem Wiederanstieg der Glucosekonzentration im Blut. Die möglichen Mechanismen dieser Wirkung werden diskutiert.
    Notes: Summary The influence of xylitol on insulin-induced hypoglycemia was studied in rabbits, guinea pigs, mice, and rats. Relief of hypoglycemia and the concomitant disturbances of the nervous system was observed following the injection of xylitol. The possible mechanisms of this action are discussed.
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  • 98
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    Clinical and experimental medicine 144 (1967), S. 285-299 
    ISSN: 1591-9528
    Keywords: Prostaglandin ; Insulin ; Lipoproteidlipase ; Prostaglandin ; Insulin ; Lipoproteidlipase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die intraaortale Injektion von 3μg PGE1/kg senkte bei Kaninchen im Hungerzustand und unter dem Einfluß des operativen Vorgehens (Sympathicusstimulierung) innerhalb von 10 min die unveresterten Fettsäuren, die veresterten Fettsäuren und Acetonkörper des Blutes in ähnlicher Weise wie die i.v. Injektion von 0,1 E Insulin/kg. Während Insulin außerdem eine passagere Verminderung des freien Serumglycerins und eine geringe Abnahme des Blutzuckers verursachte, wurde durch PGE1 der Glycerinspiegel nicht beeinflußt und eine Hyperglykämie ausgelöst. Die PGE1-abhängige Senkung der unveresterten Fettsäuren und der Acetonkörper muß als Ergebnis einer gesteigerten Reveresterung der Säuren im Fettgewebe angesehen werden. Die Insulinwirkung dürfte zusätzlich noch durch eine kurzfristige Lipolysehemmung zustande kommen. Die durch Injektion von 100 E Heparin/kg hervorgerufenen blutchemischen Veränderungen ließen sich durch PGE1 in Abhängigkeit vom Zeitpunkt der Injektion des Wirkstoffes mehr oder weniger deutlich beeinflussen. Durch gleichzeitige Verabfolgung von PGE1 und Heparin ebenso wie durch eine PGE1-Dauertropfinfusion (0,3μg/kg/mval) konnte die heparinbedingte Hyperlipacidämie und Hyperketonämie abgeschwächt bzw. unterdrückt werden. Ähnliche Verhältnisse ergaben sich bei der gemeinsamen Injektion von Heparin und 0,1 E/kg Insulin. Der heparinbedingte Anstieg des freien Serumglycerins blieb dagegen in allen Fällen weitgehend unbeeinflußt. Die In-vitro-Aktivität der Lipoproteidlipase von humanem Postheparinplasma erfuhr weder durch PGE1 noch durch Insulin in verschiedenen Konzentrationen eine Änderung. Auch der Aktivitätsanstieg der Lipoproteidlipase im Kaninchenplasma nach 100 E/kg Heparin mit einem Maximum nach 5 min wurde bei gleichzeitiger Injektion von PGE1 und Heparin bzw. Insulin und Heparin nicht verändert. PGE1 und Insulin beeinflussen demnach nicht die heparininduzierte Freisetzung bzw. die Aktivierung der Lipoproteidlipase, sondern verstärken unter den Bedingungen einer gesteigerten intravasalen Triglyceridspaltung die Aufnahme und Reveresterung von unveresterten Fettsäuren in das Depotfett.
    Notes: Summary In animal experiments it was proved that the injection of 3 μg of PGE1/kg into the aorta of starving rabbits under operative conditions (stimulation of the sympathetic system) lowered the level of non-esterified and esterified fatty acids and ketones in blood within 10 min in a similar manner as did the i.v. injection of 0.1 U of insulin/kg. While insulin also caused a transient diminution of free serum glycerol and a slight decrease in blood sugar there was no influence of PGE1 on the glycerol level, and a hyperglycemia was caused. The PGE1-depending decrease in non-esterified fatty acids and ketones in blood should be considered as the result of increased re-esterification of the acids in adipose tissue. The additional activity of insulin may be caused by a short-lasting inhibition of lipolysis. The biochemical changes in blood induced by injecting 100 U of heparin/kg could be influenced more or less by PGE1, depending upon the injection time. The heparin-induced hyperlipacidemia and hyperketonemia could be decreased or suppressed by simultaneous injection of PGE1 and heparin as well as by a PGE1-infusion (0.3 μg/kg/min). Similar results were obtained with simultaneous injections of heparin and 0.1 U of insulin/kg. However, in most cases the heparin-induced increase in free serum glycerol was not influenced. There was no change in thein vitro activity of lipoprotein-lipase of human postheparin plasma, neither by PGE1 nor by insulin at various concentrations. Also, the increase in the activity of lipoprotein-lipase in the plasma of rabbits after administration of 100 U of heparin/kg — with a maximum after 5 min — was not changed by simultaneous injection of PGE1 and heparin or insulin and heparin, respectively. In conclusion, PGE1 does not influence the heparin-induced release or activation of the lipoprotein-lipase but causes an enhanced uptake and re-esterification of non-esterified fatty acids into adipose tissue under conditions of an increased intravasal cleavage of triglycerides.
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  • 99
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    Diabetologia 3 (1967), S. 47-49 
    ISSN: 1432-0428
    Keywords: Calcium ; Magnesium ; Insulin ; Secretion Rabbit ; Pancreas ; Foetus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Le glucose, le glucagon, le tolbutamide et la L-leucine stimulent la libération d'insuline par le pancréas de lapin étudié in vitro. Cette stimulation n'a pas lieu lorsque le milieu d'incubation est préparé sans calcium. L'absence de magnésium n'a pas d'effet sur la sécrétion insulinique stimulée par le glucose, alors que le magnésium à la concentration de 10mM exerce un effet inhibiteur. La concentration optimale du calcium extracellulaire pour la sécrétion insulinique est de 2.64 mM. La stimulation de la sécrétion insulinique par le glucose est également supprimée par l'absence de calcium pour le pancréas de foetus de lapin âgé de 27 jours.
    Abstract: Zusammenfassung Die Freisetzung von Insulin aus Kaninchen-Pankreas in vitro wird durch Glucose, Glucagon, Tolbutamid oder L-Leucin stimuliert. In allen diesen Fällen bleibt die Stimulation in Abwesenheit von Calcium in Inkubationsmedium aus. In Abwesenheit von Magnesium stimulierte Glucose die Insulinsekretion weiter, währenddem eine Erhöhung der Magnesiumkonzentration auf 10 mM deutlich hemmend wirkte. Die optimale Sekretion von Insulin erfolgte bei einer Calciumkonzentration von 2.64 mM. In Abwesenheit von Calcium wurde die Freisetzung von Insulin auch aus dem Pankreas von 27 Tage alten Foeten gehemmt.
    Notes: Summary Glucose, glucagon, tolbutamide and L-leucine stimulated insulin secretion from rabbit pancreas studiedin vitro. In each case stimulation was inhibited by omitting calcium from the incubation medium. The omission of magnesium had no effect on glucose stimulated insulin secretion but 10 mM magnesium inhibited secretion. Optimal secretion of insulin occurred at an extracellular calcium concentration of 2.64 mM. The omission of calcium inhibited glucose-stimulated insulin secretion from pancreas of 27 day rabbit foetuses.
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  • 100
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    Diabetologia 3 (1967), S. 382-388 
    ISSN: 1432-0428
    Keywords: Isolated fat cells ; Insulin ; Glucose metabolism ; in vitro incubation ; CO2 collection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé On a étudié les conditions de réponse optimale à l'insuline en ce qui concerne la transformation du glucose-1-14C en14CO2 par les cellules adipeuses isolées. On a trouvé que les cellules adipeuses libres étaient sensibles à 0.25–1.0μU d'insuline par ml. L'effet maximum était obtenu avec 20–30μU d'insuline par ml. Celui-ci se traduisait par une augmentation de la transformation du glucose de 8–30 fois, quand la concentration de glucose du milieu était de 0.1 mg par ml. L'effet maximum de l'insuline diminuait quand les concentrations de glucose extracellulaire augmentaient, tandis que la sensibilité à l'insuline demeurait inchangée. Un certain nombre de facteurs causait une augmentation de l'oxydation basale du glucose et, par conséquent, une diminution de la réponse à l'insuline: manque d'albumine dans le milieu de préparation, incubation prolongée et traitement mécanique trop vigoureux des cellules. Des préparations de cellules insuffisamment lavées contenaient assez de collagénase pour inactiver de petites quantités d'insuline. Des insulines préparées à partir de 11 espèces animales différentes présentaient des activités biologiques semblables sur les cellules de rat (60–100 pour cent du standard d'insuline de boeuf). Le sérum de cobaye anti-insuline de boeuf neutralisait les activités à des degrés variables. Les activités des insulines provenant de 2 poissons différents n'étaient pas — ou étaient seulement légèrement — diminuées par ces anticorps anti-insuline.
    Abstract: Zusammenfassung Es werden die Bedingungen für eine optimale Insulinwirkung auf die Bildung von14CO2 aus Glucose-1-14C an isolierten Fettzellen untersucht. Freie Fettzellen zeigten eine Insulinempfindlichkeit bis zu einer Konzentration von 0.25–1.0μE/ml. Der Maximaleffekt wurde mit einer Insulinkonzentration von 20–30μE/ml erreicht. Der Anstieg des Glucoseabbaues war also 8–30-fach, wobei die Glucosekonzentration des Medium 0.1 mg/ ml war. Der maximale Insulineffekt fiel mit steigender extrazellulärer Glucosekonzentration ab, während die Insulinempfindlichkeit unverändert blieb. Eine Reihe von Faktoren führte zu einem Anstieg der Basaloxydation von Glucose und somit zu einem Abfall des Insulin-effektes: Fehlen von Albumin im Medium während der Preparation, verlängerte Inkubation und zu brüske mechanische Behandlung der Zellen. Ungenügend gewaschene Zellpräparate enthielten genügend Kollagenese, um kleine Mengen Insulin zu aktivieren. Insulin von 11 verschiedenen Tierspezies hatten an Rattenfettzellen ähnliche biologische Aktivität (60–100% des Rinder-insulinstandards). Serum mit Anti-Rinderinsulin vom Meerschweinchen neutralisierte die Aktivität in verschiedenem Ausmaß. Die Aktivität zweier verschiedener Fischinsuline wurde nicht — oder nur gering — durch diese Insulinantikörper gehemmt.
    Notes: Summary The conditions for the optimal response of isolated fat cells to insulin in terms of the conversion of glucose 1-14C to14CO2 were studied. Free fat cells were found to be sensitive to 0.25–1.0μU of insulin per ml. The maximum effect was obtained with 20–30μU of insulin per ml. This was an 8–30 fold increase in the glucose conversion when the glucose concentration of the medium was 0.1 mg per ml. The maximal effect of insulin decreased with increasing extracellular glucose concentrations, whereas the sensitivity to insulin appeared unchanged. A number of factors caused an increase in the basal oxidation of glucose, and consequently a decrease in the response to insulin: lack of albumin in the preparation medium, prolonged incubation and a too vigorous mechanical treatment of the cells. Insufficiently washed cell preparations contained enough collagenase to inactivate small amounts of insulin. Insulins prepared from 11 different animal species had similar biological activities on rat cells (60–100 per cent of the beef insulin standard). Guinea pig anti-beef-insulin serum neutralized the activities to varying degrees. The activities of 2 different fish insulins were not — or only slightly — depressed by these insulin antibodies.
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