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  • 1
    ISSN: 1432-0738
    Keywords: Chlorphentermine ; RMI 10.393 ; Ro 4-4318 ; Drug-induced lipidosis ; Foam cell reaction ; Palmitate-1-14C incorporation and turnover ; Lung phospholipid metabolism ; Chlorphentermin ; RMI 10.393 ; Ro 4-4318 ; Arzneimittelbedingte Lipidose ; Schaumzellreaktion ; Palmitat-1-14C-Einbau und Turnover ; Phospholipidmetabolismus der Lunge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An Ratten wurden die Wirkung von 3 Lipidose-erzeugenden Medikamenten auf den Einbau und den Turnover von Palmitinsäure-1-14C in Phospholipiden der Lunge untersucht. Nach 1 Dosis Chlorphentermin und RMI 10.393 war der Einbau von Palmitinsäure-1-14C in die Lungenphospholipide leicht reduziert. Eine Dosis Ro 4-4318 dagegen führte zu stark vermindertem Palmitateinbau. Acht Dosen Chlorphentermin und RMI 10.393 hemmten den Einbau von Palmitinsäure in die Lungenphospholipide deutlich. Acht Dosen Ro 4-4318 dagegen steigerten den Einbau von Palmitat in die einzelnen Phospholipidfraktionen. Dreißig Stunden nach der letzten von 3 Palmitat-Injektionen war der Turnover der meisten Phospholipide in Chlorphentermin und RMI 10.393-behandelten Ratten niedriger als in Kontrollratten. Im Gegensatz dazu erhöhte Ro 4-4318 den Turnover der meisten Lungenphospholipide. Nach 54 Std hatte sich der Phospholipid-Turnover in den Rattenlungen weitgehend normalisiert. Unsere Untersuchungen zeigten, daß die Phospholipidspeicherung, die durch Chlorphentermin und RMI 10.393 ausgelöst wird, auf einer Hemmung des Phospholipidabbaus zurückgeführt werden kann. Dagegen beruht die Phospholipidose, die durch Ro 4-4318 induziert wird, auf einer Aktivierung der Phospholipidsynthese.
    Notes: Abstract The effects of 3 lipidosis-inducing drugs on the incorporation and turnover of palmitic acid-1-14C in lung phospholipids was studied. In rats treated with 1 dose of chlorphentermine or RMI 10.393, the incorporation of palmitate-1-14C into most lung phospholipid fractions was moderately decreased, but markedly lowered after 1 dose of Ro 4-4318. Eight doses of chlorphentermine and RMI 10.393 strongly inhibited the incorporation of palmitate-1-14C into lung phospholipids, whereas with 8 doses of Ro 4-4318 the incorporation was highly increased. Thirty hours after the last of 3 injections of the labeled palmitic acid the turnover of most lung phospholipids was considerably lower in chlorphentermine and RMI 10.393-treated rats than in controls. Ro 4-4318, however, induced a highly increased turnover of most phospholipids. After 54 h, this effect had practically disappeared. Our studies showed that phospholipid storage after treatment with chlorphentermine and RMI 10.393 is mainly due to decreased degradation of phospholipids, whereas increased synthesis accounts for the effect of Ro 4-4318.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 48 (1981), S. 69-88 
    ISSN: 1432-0738
    Keywords: Behavioral teratogens ; Reflex development ; Operant conditioning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possibility that the exposure of the embryo to certain chemical substances can lead to behavioral disturbances is known from human epidemiological studies, e.g., in chronic poisoning with mercury and ethanol. Therefore, efforts are made to develop toxicological techniques with which new behavioral teratogens can be recognized. The review describes the most important experimental methods which are presently explored, and which are based on a rich body of knowledge accumulated by experimental psychologists. Most of the tests were developed with small animals, mostly with rats. They range from a rather straightforward determination of various reflexes to complex behavioral situations involving mechanical devices, operant conditioning techniques and procedures evaluating social behavior. In applying these methods in routine toxicology, it is important to remember, that many behavioral effects determined in newborn and adult animals are subtle. Moreover, they are influenced by a large variety of environmental factors affecting the health and the behavior of the mothers and of the offspring in the early and later phases of development. Therefore, the experiments must be conducted under highly standardized conditions and must be controlled rigorously. It is concluded that the best experimental strategy for the evaluation of potential behavioral teratogens is not yet established. Therefore, it would be premature to decide on a fixed protocol to be included in routine animal safety experiments for drugs and other chemical substances.
    Type of Medium: Electronic Resource
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