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91.
Burdan F 《Birth defects research. Part B, Developmental and reproductive toxicology》2004,71(5):321-330
BACKGROUND: Ibuprofen and tolmetin are popular non-steroidal anti-inflammatory drugs. Previous animal studies taken with single daily doses showed their good prenatal tolerability. However, since both cyclooxygenase (COX) inhibitors have a short half-life, the current report presents drug developmental effects after triple daily doses administration, as they are used in human. METHODS: Drugs were separately, orally dosed to pregnant rats triple daily 8 hr apart from day 8 to 21 (GD=1-plug day). The total daily doses were set at 25.5, 255.0, and 600.0 mg/kg for ibuprofen and 25.5, 255.0, and 2550.0 mg/kg for tolmetin. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. RESULTS: Maternal toxicity and intrauterine growth retardation were found in groups exposed to the highest doses of both drugs. An increase of external variations was reported in groups exposed to the middle and highest dose of ibuprofen and to the highest dose of tolmetin. Skeletal variations were significantly different only in litters treated with the highest doses of the drugs. Pooled statistical analysis showed a higher incidence of midline and ventricular septal (VSD) defect in rat fetuses exposed to COX inhibitors when compared with historical control data. For ibuprofen, the influence on VSD was similar to aspirin. CONCLUSION: Both COX inhibitors were toxic to dams in the highest doses evaluated, which caused a significantly greater incidence of intrauterine growth retardation and developmental variations. 相似文献
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Saczewski J Hudson A Scheinin M Rybczynska A Ma D Saczewski F Laird S Laurila JM Boblewski K Lehmann A Gu J Watts H 《Bioorganic & medicinal chemistry》2012,20(1):108-116
A series of 2-[(heteroaryl)methyl]imidazolines was synthesized and tested for their activities at α(1)- and α(2)-adrenoceptors and imidazoline I(1) and I(2) receptors. The most active 2-[(indazol-1-yl)methyl]imidazolines showed high or moderate affinities for α(1)- and α(2)-adrenoceptors. However, their intrinsic activities at α(2A)-adrenoceptors proved to be negligible. A selected 7-chloro derivative behaved as a potent α(1)-adrenoceptor antagonist and exhibited peripherally mediated hypotensive effects in rats. 相似文献
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Saczewski F Sławiński J Kornicka A Brzozowski Z Pomarnacka E Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry letters》2006,16(18):4846-4851
Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I and II (cytosolic enzymes), and the tumor-associated CA IX and XII. Some mercaptans led to a consistent increase of inhibitory power (52.8- to 243-fold) over the corresponding oxidized (S-S type) derivatives, acting as potential hypoxia-activatable drugs. 相似文献
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Główka FK Karaźniewicz M Lipnicka E 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,839(1-2):54-61
A new indirect RP-HPLC method was developed for determination of small, ng/ml, concentrations of triamcinolone (TMC) in human plasma, in presence of endogenous corticosteroids: cortisol (hydrocortisone, F), cortisone (E) and their metabolites, after administration of TMC in a free alcohol form. After solid phase extraction (SPE) in cartridges with octadecyl phase, TMC and prednisolone (I.S.) were derivatized by treatment with 9-anthroyl nitrile (9-AN) in a basic mixture, consisting of triethanolamine and quinuclidine, to receive fluorescent esters at 21-hydroxyl group of the steroid chain. Optimal conditions were also established to purify fluorescent TMC and I.S. derivatives before injection into HPLC column. The fluorescent esters were determined using an isocratic RP-HPLC technique in a C18 column. The mobile phase consisted of acetonitrile and 0.3 mM ortho-phoshoric acid. The method was validated before using to pharmacokinetic studies. Calibration curve of TMC was linear in the range of 2.5-100.0 ng/ml. Intra- and inter-day measurement precision and accuracy were equal to or lower than 15%. Percent recovery, and limits of detection (LOD) and quantification (LOQ) of TMC were also determined. The method was applied for in vivo conditions after administration of tablets containing TMC to healthy volunteers. Moreover, the method provided potential to determine TMC and, simultaneously, other glucocorticoids: E, F and their metabolites in one analytical run. Column interactions were observed between endogenous metabolites of E. Usefulness of the elaborated method was confirmed in pharmacokinetic studies following administration of a small (4 mg) dose of TMC to human volunteers. The method can provide an alternative to HPLC coupled with RIA in determination of small quantities of TMC. 相似文献
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Iwona Żur Ewa Dubas Elżbieta Golemiec Magdalena Szechyńska-Hebda Franciszek Janowiak Maria Wędzony 《Plant Cell, Tissue and Organ Culture》2008,94(3):319-328
The accumulation of abscisic acid (ABA) and the activities of antioxidative enzymes along with cell metabolic activity were
monitored during androgenesis induction in triticale (×Triticosecale Wittm.). Tested cultivars ‘Mieszko’ and ‘Wanad’ were selected due to their significantly different responses to androgenic
induction. Significant variation was observed in respect of superoxide dismutase activity and endogenous ABA content in anthers
isolated from freshly cut tillers. For both cultivars, tillers pretreatment with low temperature decreased peroxidase activity
by 36%, highly accelerated respiration rate and reduced heat production. At the same time, the level of ABA in ‘Mieszko’ was
increased to the level measured in ‘Wanad’. This effect was associated with higher microspore culture viability and increased
stress tolerance in ‘Mieszko’. Low temperature and metabolic starvation during 4-day anther preculture did not influence activities
of antioxidative enzymes, while it resulted in slight decrease in respiration rate and heat emission. The importance of these
changes for effective androgenesis induction is discussed. 相似文献