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Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C18 col-umn(4.6 mm×50 mm,5 μm)under gradient conditions with eluents of methanol:acetonitrile(1∶1,V/V)and 5mM ammonium formate:methanol(9∶1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30 → 437.30 for RA and m/z 256.10 → 227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40 mg/kg)and intravenous(10 mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20 mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1％to 19.4％.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.
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Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of me-thanol and 10 mM ammonium formate (containing 0.1%of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4-191.2 for TY501 and m/z 473.3-143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra-and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within 71.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.
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OBJECTIVE To explore the drug-resistant situation and patients′ basis condition of clinical isolated Enterococcus from Jan to Dec in 2008 to offer evidence for drug-resistant monitoring and clinical antibiotics usage.METHODS All clinical specimens were isolated and cultured and identification conform to Standard′ Operation.The bacteria were identified by using the automatic microorganism analyzer VITEK-2,and bacteria′s drug susceptibility tests were performed using counterparts panel.RESULTS 273 strains Enterococci were isolated,of which E.faecalis were 158 strains,E.faecium were 109 strains,the others were 6 strains.The isolated HLAR E.faecalis were 80 strains and HLAR E.faecium were 10 strains,the isolated.ratio of HLAR was different(P
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Objective To establish a mouse model of acute necrotizing pancreatitis.Methods Thirty six male ICR mice were randomly divided into control group ( n =6) and experimental group ( n =30). Each of the animals in the experimental group received 7 intraperitoneal injections of caerulein (50 ?g/kg body weight) in 0.9% NaCl at hourly intervals over 6 hours. The animals in the experimental group were killed at 9,18,24,48 and 72 hours respectively after the first caerulein injection. The control animals received the same volume of 0.9% NaCl without caerulein. The animals in the control group were killed at the 18th hour after the first intraperitoneal injection. The severity of acute necrotizing pancreatitis was evaluated in terms of amylase level, pancreatic weight/body weight and the histological changes. Variance analysis was employed in the processing of these data. Results Both amylase level and pancreatic weight elevated 9 hours after the first caerulein injection, and correlated with the course of pancreatitis. The maximums of both alterations were observed at the same time point (18 hours after the first injection of caerulein). Prominent interstitial inflammation and acinar cell necrosis occurred at the 18th hour, and the histological score for pancreatitis reached a maximum ( P
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OBJECTIVE:To gain clear idea of influence of multiorigins of Cordyc ep s on quality and nature of this drug.METHODS:The mannitol contents in the Cordy ceps samples collected from different growing areas were determined and compared ,and their MDR(Mutual Different Rate)was analyzed.RESULTS:The MDRs among specim ens from Sichuan,Tibet and Yunnan were 0.012～0.32 and the MDRs among the Cordyc eps samples from different micro-ecological environment were 0.037～1.36.CONCLU SION:On the mannitol content in Cordyceps,the effect of the species diversity a nd the micro-ecological environment might exceed that of district and climate d ifference.
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ObjectiveTo classify chronic pancreatitis (CP) based on pathological features and evaluate the benefits of different surgical procedures according to the pathological forms. Methods Forty CP cases during recent 9 years who underwent surgical therapy were retrospectively reviewed in association with clinicopathological analysis. Results Postoperative pain-relief rate was 79.16% in patients treated with longitudinal pancreaticojejunostomy(LPJ). In cases without enlarged pancreatic head or diverticulum of duodenum, postoperative pain-relief rate was 86%.Postoperative pain-relief rate was high by Whipple′s procedure, pylorus-preserving pancreaticoduodenectomy or Beger duodenum-preserving pancreatic head resection,while postoperative diabetes mellitus developed in 22%.Conclusions Both pathological form and operative procedure were factors influencing outcomes of CP.LPJ is still a main surgery for most CP patients with pancreatic fibrosis and dilated pancreatic duct and pancreatic stone.Some patients of CP with enlarged pancreatic head, hyperplasia of pancreatic parenchyma and pancreatic duct epithelia or complicated with diverticulum of the duodenum should be treated with resections targeting at the head of the pancreas.
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brain and fatty. The accumulation excretion ratios within 96 h were 70.16% in urine and only 1.35% in feces after iv administration in rats, while within 24 h was 3.46% in bile. Conclusion The results of pharmacokinetics of novel r-hirudin in rats given by iv determined by RA are different from those determined by TCA-RA, but the trends indicated by the two methods are the same; urine excretion is the major excretion pathway.