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  • 1
    Electronic Resource
    Electronic Resource
    Uric acid as radical scavenger and antioxidant in the heart (1989)
    Springer
    Pflügers Archiv 415 (1989), S. 127-135 
    Details
    ISSN: 1432-2013
    Keywords: Acetylcholine ; Adenosine ; Allopurinol ; EDRF ; Hydroxyl radical ; Hypochlorite ; Superoxide ; Xanthine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Uric acid (UA) is released from the heart of many species, including man, and its site of formation has been shown to be the microvascular endothelium. Since UA reacts with oxygen radicals in vitro, experiments were conducted on guinea pig hearts perfused with Krebs-Henseleit buffer (KHB) to evaluate whether the formation of UA could afford protection from damage by radicals and oxidants. The following results were obtained: (1) Upon addition of the hydroxyl radical scavenger DMSO to the perfusate, the coronary rate of release of endogenous uric acid was increased relative to the precursor purines. (2) UA was degraded during passage through the coronary system and also in KHB in vitro after addition of substances generating hydroxyl radicals or hypochlorite. Superoxide (O 2 − ) radicals did not seem to react directly with UA, though UA concentration-dependently quenched the chemiluminescence generated from luminol in the presence of O 2 − and OH radicals. (3) Coronary dilatation by acetylcholine (Ach) and sub-μM concentrations of adenosine, induced by both via endothelial mechanisms, was attenuated after prolonged inhibition of endothelial UA formation by allopurinol. Furthermore, the effect of Ach but not of adenosine proved acutely sensitive to methylene blue and O 2 − , substances known to inactivate EDRF. This finding suggests involvement of EDRF in Ach-mediated, but not in adenosine-induced dilatation of the intact coronary system. Exogenously applied UA prevented the impairment of vascular responses to Ach and adenosine caused by allopurinol, and to Ach upon generation of O 2 − .(4) Hearts performed more pressure-volume work and exhibited greater functional stability when perfused with KHB supplemented with UA in a physiological concentration. It is concluded that uric acid can actually serve as a physiologic radical scavenger and antioxidant, maintaining functional responsiveness of the coronary system and of the myocardium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00370582
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  • 2
    Electronic Resource
    Electronic Resource
    Heredity of hexobarbital sleeping time and efficiency of drug metabolism in Wistar and Sprague-Dawley rats (1975)
    Springer
    Archives of toxicology 34 (1975), S. 61-70 
    Details
    ISSN: 1432-0738
    Keywords: Heredity of Drug Metabolism ; Hexobarbital Sleeping Time ; Sexual Differences ; Hexobarbital ; Aminopyrine ; Aniline ; Benzene ; Heridität des Xenobiotika-Metabolismus ; Hexobarbital ; Schlafzeit ; mikrosomaler Metabolismus ; biochemische Genetik ; Rattenselektion ; Hexobarbital ; Aminopyrin ; Anilin ; Benzol ; P-450
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Untersucht wurde das Wesen der beträchtlichen individuellen Variabilität der Hexobarbital-Schlafzeit und des Xenobiotika-Metabolismus. Bei Wistar-und Sprague-Dawley-Ratten mit gegenüber Populationsdurchschnitt verkürzter Hexobarbital-Schlafzeit war auch eine größere Geschwindigkeit des Metabolismus von Hexobarbital, Aminopyrin, Anilin, Benzol in der mikrosomalen Leberfraktion in vitro, ein größeres Lebergewicht, ein höherer Gehalt an mikrosomalem Protein und P-450 in den Lebern und eine schnellere Abnahme des Hexobarbitalspiegels im Blut nach der intraperitonealen Applikation von Hexobarbital nachzuweisen als bei Ratten mit relativ längerer Hexobarbital-Schlafzeit. Die sich hier unterscheidenden Ratten wachten jedoch bei gleichen Konzentrationen von Hexobarbital im Blute auf. Die genannten Unterschiede vererbten sich auf die weitere Generation. Daraus ergibt sich, daß die individuellen Unterschiede in der Dauer der Hexobarbital-Schlafzeit bei Ratten genetisch bedingt sind und vor allem der Geschwindigkeit des Hexobarbital-Metabolismus in der Leber entsprechen. Gleichzeitig bestehen allgemeine Unterschiede in der Geschwindigkeit des Metabolismus mancher Xenobiotika aus. Die Versuche zeigen eine beträchtliche Nichthomogenität üblicher Laborratten, die im Laufe einiger Generationen ermöglicht hatte, zwei Linien zu züchten, die sich hinsichtlich des mikrosomalen Lebermetabolismus unterscheiden. Die Heredität der Hexobarbital-und Aminopyrin-Biotransformation (Substraten von Typ I) könnte durch einen anderen Mechanismus als die von Anilin (Substrat von Typ II) vermittelt werden. Die Wistar-Rattenweibchen wachen bei niedrigerem Hexobarbitalspiegel im Blute auf als Männchen. Ihr Gehirn war also offenbar empfindlicher für die narkotische Wirkung von Hexobarbital.
    Notes: Abstract Nature of considerable variability of hexobarbital sleeping time and drug metabolism efficiency within a single strain of rats was investigated. Wistar or Sprague-Dawley rats with shorter than average hexobarbital sleeping tune had also higher rates of in vitro hepatic microsomal metabolism of hexobarbital, aminopyrine, aniline and benzene, higher liver weight, microsomal protein content and P-450 level, and faster hexobarbital blood level decline (but similar volumes of distribution) after intraperitoneal hexobarbital sodium than those with relatively longer hexobarbital sleeping time, but awakened with the same hexobarbital blood level. The differences were maintained throughout the life of rats and inherited in their offspring. It indicated a possible genetic control of hexobarbital sleeping time and efficiency of drug metabolisms with apparent differences in selection response for Type I and Type II substrates (hexobarbital and aminopyrine vs aniline): it might indicate different heredity mechanism for these types of substrates. Stronger hexobarbital narcotic effect in females was associated with the rate of hexobarbital metabolism, but also with higher brain sensitivity. Hexobarbital sleeping tune pattern indicated more general pattern of drug metabolism (better for Type I substrates) and success of selection of rats for different efficiency of drug metabolism (up to 8-fold differences in F5 generation) suggested considerable genetic non-homogeneity of two common strains of laboratory rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00353340
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of pregnancy on hepatic microsomal drug metabolism in rabbits and rats (1976)
    Springer
    Archives of toxicology 35 (1976), S. 41-47 
    Details
    ISSN: 1432-0738
    Keywords: Microsomal drug metabolism ; Aminopyrine ; Benzphetamine ; Hexobarbital ; Aniline ; Pregnancy ; In vitro and in vivo ; Species ; Xenobiotik-Metabolismus ; Aminopyrin ; Benzphetamin ; Hexobarbital ; Anilin ; Gravidität ; In vitro und in vivo ; Tierart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei holländischen gestreiften Kaninchen verursachte die Gravidität eine mehrmalige Senkung der mikrosomalen Biotransformation von Aminopyrin, Benzphetamin und Hexobarbital in vitro. Bei graviden Sprague-Dawley-Ratten zeigten verschiedene Bezugspunkte der Umwandlungsgeschwindigkeit von Hexobarbital in vitro (per mg mikrosomal Protein, per g Lebergewicht, 100 g Körpergewicht) eine unveränderte oder eine wenig erhöhte mikrosomale enzymatische Aktivität. Der Konzentrationsverlauf von Hexobarbital im Blut nach einer i. p. Applikation von 100 mg/kg NatriumHexobarbital bewies, daß das Schicksal von Hexobarbital nicht so sehr von kleinen Veränderungen der mikrosomalen enzymatischen Aktivität bestimmt wurde, als vielmehr durch Veränderungen in der Verteilung von Hexobarbital während der Gravidität. Verschiedene Bezugspunkte der Umwandlungsgeschwindigkeit von Anilin in vitro wiesen auf eine gesenkte oder unveränderte enzymatische Aktivität während der Gravidität hin, und Versuche in vivo zeigten, daß diese Veränderungen den Anilinmetabolismus in lebenden Ratten nicht beeinflußten. Die Ergebnisse bewiesen, daß die Gravidität einen signifikant verschiedenen Einfluß bei verschiedenen Tierarten auf den Metabolismus von Fremdstoffen ausübt. Eine Interpretation der Ergebnisse der Biotransformation in vitro auf lebendige Tiere wies darauf hin, daß mikrosomale enzymatische Aktivität oder Verteilung bei verschiedenen Stoffen eine minimale, oder anderseits, eine signifikante Rolle in der Beeinflussung deren Schicksals im Organismus haben kann.
    Notes: Abstract In Dutch-belted rabbits, pregnancy caused several-fold decrease of in vitro hepatic microsomal aminopyrine, benzphetamine, and hexobarbital biotransformations. In pregnant Sprague-Dawley rats, various kinds of expressing the in vitro rates of hexobarbital biotransformation (per mg of microsomal protein, g of liver, 100 g of body weight) indicated unchanged or slightly elevated microsomal enzyme activity. In vivo, the course of hexobarbital blood levels after i. p. hexobarbital sodium, 100 mg/kg, indicated that the fate of hexobarbital was not primarily determined by the small changes of microsomal enzyme activity but, rather, by changed hexobarbital distribution. Different ways of expressing in vitro rates of aniline biotransformation showed decreased or unchanged enzyme activity during pregnancy and in vivo experiments indicated that these changes did not affect aniline metabolism in living rats. The results pointed out marked species differences in the effect of pregnancy on drug metabolism. Interpretation of in vitro biotransformation data for living animals suggested that with different substrates, microsomal enzyme activity and distribution, respectively, may exert different effects playing either significant or apparently minor role in drug disposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00333984
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  • 4
    Electronic Resource
    Electronic Resource
    The vascular endothelium: a survey of some newly evolving biochemical and physiological features (1985)
    Springer
    Basic research in cardiology 80 (1985), S. 459-474 
    Details
    ISSN: 1435-1803
    Keywords: adenosine ; antithrombogenic properties ; angiotensin converting enzyme ; cell culture ; EDRF ; ecto-nucleotidases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphological, biochemical and functional characterization of the vascular endothelium has become possible through the broad use of electron microscopic methods, the successful elaboration and application of techniques for the isolation and cultivation of endothelial cells in vitro and through sophisticated studies on vessel and organ preparations, both in vitro and in vivo. In this survey emphasis is placed on certain methodological aspects of endothelial cell culture as well as on biochemical, physiological and pathophysiological features of the vascular endothelium. Endothelial cells can be propagated in culture dishes, the most commonly applied method, on suspended microbeads (dextrane, polyacrylamide), a technique giving large yields, or on thin porous membranes, a procedure suited for the study of transport processes across the endothelial layer. Different structural, biochemical and functional properties of the luminal (apical) and abluminal (basal) cell membrane determine important polarity features of the endothelium. Endothelial cells exhibit a variety of biochemical pathways and are characterized by high metabolic activities. Of particular interest is the large content of ATP in endothelial cells of different vascular origin. The rapid intracellular degradation of adenine nucleotides to nucleosides and bases, which are constantly released, is balanced by synthesis, mainly via salvage pathways. In endothelial cells of microvascular origin uric acid predominates by far as the final purine degradative because of the presence of xanthine dehydrogenase in these cells; in the macrovascular endothelium purine breakdown proceeds only to hypoxanthine, since xanthine dehydrogenase is lacking. In this connection interrelations between nucleotide catabolism in myocardial tissue and in coronary endothelial cells are discussed, also with respect to the participation of endothelial xanthine oxidase in the formation of oxygen radicals during post-ischemic reperfusion of the heart. Vascular endothelial cells of different origin are also capable of a rapid extracellular degradation of ATP, ADP and AMP to adenosine by means of specific ecto-nucleotidases. The subsequent fate of extracellularly formed adenosine appears to be different for endothelial cells of microvascular (preferential adenosine uptake) and macrovascular origin (preferential extracellular adenosine accumulation), thus implying functional consequences for platelet aggregation. Experimentally well supported aspects of endothelial functions under physiological and pathophysiological conditions include: - the involvement of metabolic properties of the endothelium in the separation of the intra-and extravascular space (barrier function, e.g. intraendothelial trapping of adenosine, active participation in leukocyte emigration); - the facilitation of CO2-release in the lung (endothelial carboanhydrases); - the participation in the regulation of vascular resistance (formation of angiotensin II and degradation of bradykinin by means of angiotensin converting enzyme, formation of not yet identified endothelium derived relaxing factor(s) [EDRF] in response to various intraluminally present vasodilating substances); - the establishment of an antithrombogenic luminal surface of the vessel wall (release of PGI2-adenosine, antithrombin III and plasminogen activator, intravascular degradation of adenine nucleotides to adenosine by endothelial ecto-nucleotidases, activation of protein C by endothelial thrombomodulin, heparan and antithrombin III containing endothelial glycocalyx).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01907911
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