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  • 1
    ISSN: 1432-1041
    Keywords: Hypercholesterolaemia ; Pravastatin ; Mevalonate ; cholesterol synthesis ; circadian rhythm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4–8 h after pravastatin administration in the morning (51 vs 19 nmol · h−1) and at 4–16 h after pravastatin administration in the evening (56 vs 27 nmol · h−1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 255 (1998), S. 127-131 
    ISSN: 1434-4726
    Keywords: Key words Cochlea ; Aminoglycoside toxicity ; Hair cell apoptosis ; Nick-end labeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although aminoglycosides have been investigated for their cochleotoxicity, it has still not been determined whether apoptosis or necrosis results in cochlear hair cell death following aminoglycoside treatment. To study possible mechanisms of cell death, we used in situ DNA break-labeling to examine guinea pig cochleae affected by kanamycin ototoxicity. Chronic kanamycin treatment induced DNA fragmentation that was detectable in both outer and inner hair cells, suggesting the occurrence of apoptosis. These findings suggest that apoptosis achieves deletion of affected hair cells without disrupting tissue architecture in the organ of Corti.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European archives of oto-rhino-laryngology and head & neck 254 (1997), S. 153-157 
    ISSN: 1434-4726
    Keywords: Apoptosis ; Labyrinthine vestibule ; Aminoglycoside toxicity ; Zinc toxicity ; Nick-end labeling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We reported that apoptosis occurred in the guinea pig vestibular hair cells after chronic aminoglycoside treatments. In the present study, we used in situ nick-end labeling to determine whether apoptosis was also induced by the acute effects of aminoglycosides in guinea pig ampullar cristae. In addition, we evaluated the effect of zinc supplements upon these ototoxic treatments. After a local application of streptomycin directly to the round window, we found labeled bodies in the vestibular hair cells. The zinc supplement increased the number of labeled bodies resulting in severe hair cell loss. These findings indicate that the acute effects of aminoglycosides also induce apoptosis of the vestibular hair cells, and that zinc enhances aminoglycoside ototoxicity. Consequently, we propose that an interaction with ion channels may play a key mechanism in the processes of apoptosis affecting the vestibular hair cells.
    Type of Medium: Electronic Resource
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