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  • 1
    ISSN: 1432-0843
    Keywords: Key words 7-Hydroxymethotrexate ; Toxicity ; Lethal dose ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To elucidate mechanisms for methotrexate (MTX)-induced renal and hepatic toxicity, we investigated the acute effects of bolus plus continuous infusion of up to 0.4 g/kg 7-hydroxymethotrexate (7-OH-MTX) in the rat. We demonstrate for the first time in any species the occurrence of acute lethal toxicity within a few hours after 7-OH-MTX administration. Serum concentrations of 7-OH-MTX measured at the time of death were 1.4 mM (mean), about one-half of those achieved in some patients after infusion of high-dose MTX (HD-MTX) in the clinic. The data suggest an approximate LD50 (the dose lethal to 50% of the study population) of 0.3 g/kg and a steep dose/lethality curve for 7-OH-MTX. Moreover, acute renal and hepatic toxicity occurred as evidenced by severe morphological findings and increased serum levels of creatinine and liver transaminases. In all rats subjected to continuous infusion of 7-OH-MTX, yellow microscopic precipitations were apparent in the kidney tubules. Crystallization was also seen in bile ducts of the liver in some of the rats. These results further support that the formation of 7-OH-MTX is disadvantageous and that reported attempts to prevent its formation during MTX treatment are warranted.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0878
    Keywords: Key words: Endocardium ; Endothelium ; Collagen ; Catabolism ; Endocytosis ; Reticuloendothelial system ; Cod Gadus morhua ; (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The cells responsible for the clearance of collagen were studied in cod. Cod collagen labelled with the lysosomal trap-label 125I-tyramine cellobiose was cleared from the circulation with a t1/2 of 15 min. 1 h After injection 75%, 17% and 8% of the label were recovered in the heart, liver and blood, respectively. 24 h After administration of collagen labelled conventionally with 125I to allow escape of labelled degradation product from the site of uptake, 80% of the label had left the heart, signifying degradation. When collagen was tagged with 125I-tyramine cellobiose, heart-associated radioactivity did not decrease after 24 h, indicating intralysosomal degradation. Fluorescence microscopy revealed that i.v. injected fluorescently-labelled collagen accumulated in discrete vesicles of cells lining the endocardial blood space of both atrium and ventricle. Conventional and immuno-electron microscopy showed that these cells contained numerous coated pits and vesicles reflecting active endocytosis, and that ligand lined the limiting membrane of early endosomes. Intravenously injected 2 μm latex accumulated mainly in kidney. We conclude that the population of non-macrophagic endocardial cells are important for the turnover of collagen in cod. These cells therefore resemble sinusoidal endothelial cells of salmon kidney and mammalian liver.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    ISSN: 1432-0878
    Keywords: Endocardium ; Endothelium ; Collagen ; Catabolism ; Endocytosis ; Reticuloendothelial system ; Cod Gadus morhua, (Teleostei)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The cells responsible for the clearance of collagen were studied in cod. Cod collagen labelled with the lysosomal trap-label 125I-tyramine cellobiose was cleared from the circulation with a t1/2 of 15 min. 1 h After injection 75%, 17% and 8% of the label were recovered in the heart, liver and blood, respectively. 24 h After administration of collagen labelled conventionally with 125I to allow escape of labelled degradation product from the site of uptake, 80% of the label had left the heart, signifying degradation. When collagen was tagged with 125I-tyramine cellobiose, heart-associated radioactivity did not decrease after 24 h, indicating intralysosomal degradation. Fluorescence microscopy revealed that i.v. injected fluorescently-labelled collagen accumulated in discrete vesicles of cells lining the endocardial blood space of both atrium and ventricle. Conventional and immuno-electron microscopy showed that these cells contained numerous coated pits and vesicles reflecting active endocytosis, and that ligand lined the limiting membrane of early endosomes. Intravenously injected 2 μm latex accumulated mainly in kidney. We conclude that the population of non-macrophagic endocardial cells are important for the turnover of collagen in cod. These cells therefore resemble sinusoidal endothelial cells of salmon kidney and mammalian liver.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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