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Sense and nonsense in bacterial taxonomy 总被引:1,自引:0,他引:1
S T Cowan 《Journal of general microbiology》1971,67(1):1-8
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The efficacies and dissociation constants of proposed mu and kappa receptor agonists (morphine and ethylketocyclazocine, respectively) were compared using the method of partial irreversible blockade (with buprenorphine) and Stephenson's theory of drug action. While there was good agreement between the dissociation constant (KA) of morphine in analgesia (3.3 x 10(-5) M) and in inhibition of gastrointestinal transit (1.1 x 10(-5) M), the KA of ethylketocyclazocine differed by an order of magnitude in these endpoints (3.2 x 10(-6) M and 6.7 x 10(-5) M, respectively). The efficacies of morphine were found to be similar for the two effects studied (4.23 and 5.26), while those for ethylketocyclazocine differed markedly (2.06 and 10.39). The fraction of receptors remaining unblocked after buprenorphine was consistent for the test but not for the agonist, indicating a different distribution of receptors for the two endpoints. Our results strongly suggest that morphine induces analgesia, and slows transit in the small intestine, through the same type of receptor. The same conclusion cannot be drawn for ethylketocyclazocine. 相似文献
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Steroid metabolites in urine from neonates with 21-hydroxylase deficiency are predominantly polyhydroxylated 17-hydroxyprogesterone and androgen metabolites, and most have incompletely defined structure. This study forms part of a comprehensive project to characterize and identify these in order to enhance diagnosis and to further elucidate neonatal types of steroid metabolism.Steroids were analyzed, after extraction and enzymatic conjugate hydrolysis, as methyloxime-trimethylsilyl ether derivatives on gas-chromatographs coupled to quadrupole and ion-trap mass-spectrometers. GC-MS and GC-MS/MS spectra, obtained with constant excitation conditions, were used together to determine the structure of the D-ring and the side chain of 20-oxo and 20-hydroxy pregnane(ene)s without oxo groups on the A-, B-, and C-ring.All possible combinations of D-ring and side chain configuration were considered. Most fragmentations could be interpreted as partial or complete D-ring cleavages with loss of the side chain, aided by comparison with spectra of deuterated derivatives and of borohydride reduced metabolites. Possible rearrangement ions are also discussed. More than 140 endogenous metabolites were characterized.GC-MS/MS was especially beneficial for characterization of compounds with 16,17-dihydroxy-20-oxo structure, interpreted as markers of intra-uterine enzyme induction. It also assisted the differentiation of 16-hydroxy-20-oxo metabolites, present in urine of non-affected neonates, from the diagnostic 17-hydroxy-20-oxosteroids and enabled the detection of 15,17-dihydroxy-20-oxo compounds in low concentrations. The presence of 17,21-dihydroxylated pregnane(ene)s despite the deficit in CYP21A2 is discussed.We conclude that GC-MS combined with GC-MS/MS allows reliable identification of the structure of the D-ring and side chain of pregnane(ene)s without prior isolation, even when in low concentrations in urine. 相似文献
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