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111.
Sahni-Arya B Flynn MJ Bergeron L Salyan ME Pedicord DL Golla R Ma Z Wang H Seethala R Wu SC Li JJ Nayeem A Gates C Hamann LG Gordon DA Blat Y 《Biochimica et biophysica acta》2007,1774(9):1184-1191
11beta-hydroxysteroid dehydrogenase 1 regulates the tissue availability of cortisol by interconverting cortisone and cortisol. It is capable of functioning as both a reductase and a dehydrogenase depending upon the surrounding milieu. In this work, we have studied the reaction mechanism of a soluble form of human 11beta-hydroxysteroid dehydrogenase 1 and its mode of inhibition by potent and selective inhibitors belonging to three different structural classes. We found that catalysis follows an ordered addition with NADP(H) binding preceding the binding of the steroid. While all three inhibitors tested bound to the steroid binding pocket, they differed in their interactions with the cofactor NADP(H). Compound A, a pyridyl amide bound more efficiently to the NADPH-bound form of 11beta-hydroxysteroid dehydrogenase 1. Compound B, an adamantyl triazole, was unaffected by NADP(H) binding and the sulfonamide, Compound C, showed preferential binding to the NADP+ -bound form of 11beta-hydroxysteroid dehydrogenase 1. These differences were found to augment significant selectivity towards inhibition of the reductase reaction versus the dehydrogenase reaction. This selectivity may translate to differences in the in vivo effects of 11beta-hydroxysteroid dehydrogenase 1 inhibitors. 相似文献
112.
Srinivas Mutalik Krishnan Manoj Meka Sreenivasa Reddy Pralhad Kushtagi Achutha Nayak Usha Parambil Anju Averineni Kumar Ranjith Nayanabhirama Udupa 《AAPS PharmSciTech》2008,9(2)
The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug–excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results.Key words: aceclofenac, chitosan, matrix tablet, pharmacokinetics, sustained release 相似文献
113.
Imaizumi Nobuyuki; Usuda Hideaki; Nakamoto Hitoshi; Ishihara Kuni 《Plant & cell physiology》1990,31(6):835-844
Photosynthesis is known to occur in rice panicles, but littlehas been reported about the photosynthetic or biochemical characteristicsof such panicles. The estimated gross amount of photo-syntheticallyassimilated CO2 in a panicle is 30% of that in a flag leaf.This result and the good light-intercepting characteristicsof the panicle in the canopy suggest that photosynthesis inthe panicle may contribute significantly to grain filling. Therice panicle is composed of spikelets and of rachis-branchesincluding rachis which have estimated gross rates of photosynthesisduring the 30-day period after anthesis of 130 to 180 and 50to 100 µmol CO2.(mg Chl)1.h1, respectively.The corresponding rate for the flag leaf is 180 to 230 µmolCO2.(mg Chl).h. On the basis of Chl, spikeletshave a high photosynthetic capability which is similar to thatof the flag leaf. The activities of ribulose-l,5-bisphosphate carboxylase (RuBPCase),phosphoenolpyruvate carboxylase (PEPCase), and pyruvate.Pi dikinase(PPDK) in spikelets were 129, 220, and 87 µmol.(mg Chl).h,respectively. The activities of PEPCase and PPDK in spikeletswere considerably higher than those in the flag leaf or rachis-branches.Oxygen-insensitive photosynthesis was found only in spikelets.The Km of NaHCO3 for photosynthesis by slices of spikelets inan aqueous solution (0.6 mM) was considerably lower than thatfor slices of flag leaf (4.2 mM). All these results indicatethat spikelets have different photosynthetic characteristicsfrom those of the flag leaf and rachis-branches. The possibilityof C3C4 intermediate photosynthesis or C4-like photosynthesisin spikelets is discussed.
4Present address: Department of Biochemistry, Faculty of Science,Saitama University, Urawa, 338 Japan (Received February 14, 1990; Accepted June 12, 1990) 相似文献
114.
Antimycobacterial drugs such as isoniazid; ethionamide and thiocarlide are inhibitors of mycolic acid synthesis in Mycobacterium tuberculosis. Isoniazid in particular appears to block the formation of a Δ5−C24:1 fatty acid which could be a precursor of mycolic acids. 相似文献
115.
116.
James O. Kilburn Kuni Takayama Emma Lee Armstrong 《Biochemical and biophysical research communications》1982,108(1):132-139
A 105,000 x g residue fraction of contains an enzyme (acyl transferase) that transfers endogenous mycolic acid to trehalose monomycolate to yield trehalose dimycolate. This enzyme activity is stable to repeated freezing and thawing and is unaffected by the antimycobacterial drug, ethambutol. These results show that trehalose monomycolate is a direct precursor of trehalose dimycolate and suggest the presence of activated mycolic acids (acyl donor) in the cell-free system. 相似文献
117.