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Studies on the metabolism of perhexiline in man (1987)

Cooper, R. G. ; Evans, D. A. P. ; Price, A. H.

Springer

European journal of clinical pharmacology 32 (1987), S. 569-576

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ISSN: 1432-1041

Keywords: perhexiline ; polymorphic oxidation ; stereoselectivity ; P450 ; enterohepatic circulation

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology , Medicine

Notes: Summary We have studied the disposition of perhexiline and its two major metabolites, M1 and M3, in healthy volunteers and in patients with biliary T-tube drains after cholecystectomy. In healthy volunteers the genetic control for impaired hepatic oxidation is identical for debrisoquine, sparteine, and perhexiline. Poor metabolizers demonstrate markedly reduced production and excretion of the major metabolite, M1. Their production of M3 is also reduced, but to a lesser degree than for M1, confirming substrate stereoselectivity by hepatic oxidases. Biphasic urinary elimination of M1 and M3 is seen in intact extensive oxidizers, whereas only the first phase is apparent in patients with biliary T-tube drainage. This suggests the possibility of enterohepatic recycling of these compounds, which may account for their prolonged elimination More than 90% of an ingested dose of perhexiline maleate remains unaccounted for at 24h after ingestion, even in extensive metabolizers. A careful, radiolabelled tissue-distribution study is warranted to elucidate the complicated metabolic fate of perhexiline.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF02455990

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Multiple roles of the Dcdc42 GTPase during wing development in Drosophila melanogaster (2000)

Baron, M. ; O'Leary, V. ; Evans, D. A. P. ; [et al.]

Springer

Molecular genetics and genomics 264 (2000), S. 98-104

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ISSN: 1617-4623

Keywords: Drosophila GTPase Cdc42 Cell polarity Notch

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Abstract. The Rho sub-family of GTPases, comprising Rho, Rac and Cdc42, regulates many biological processes, including morphogenesis, cell polarity, migration, the cell cycle and gene expression. It is important to develop genetic approaches to allow the dissection, in vivo, of the mechanisms of GTPase regulation and signal transmission, and their biological consequences. In this regard, wing development in Drosophila melanogaster is an excellent model system. To investigate the functions of the Drosophila Cdc42 GTPase (Dcdc42), we generated phenotypes during wing development, by expression of the dominant-negative N17 and L89 mutants of Dcdc42. We have identified roles for Dcdc42 in wing growth, and in cell fate choice during the development of the wing veins and the peripheral nervous system. Reduction of Dcdc42 signalling following over-expression of Dcdc42N17 resulted in a broader but more diffuse domain characterised by wing-margin sensory bristles. This was correlated with a broadened stripe of wingless expression along the dorsal-ventral boundary of third-instar wing imaginal discs. Together with genetic interactions with loss- and gain-of-function Notch alleles, these data support a role for wild-type Dcdc42 as a negative regulator of Notch signalling.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/s004380000287

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