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Objective To assess the influence of different interventional injection routes of raltitrexed on the liver function, histology and pharmacokinetics in experimental rabbits, and to discuss the feasibility, safety and advantages of local application of raltitrexed. Methods A total of 25 New Zealand white rabbits were randomly and equally divided into 5 groups with 5 rabbits in each group: group A (using peripheral intravenous injection), group B (employing hepatic arterial infusion), group C (adopting hepatic artery embolization with Lipiodol), group D (hepatic artery embolization with gelfoam particles), and group E (direct puncture of liver and injection). Clinical equivalent dose (0. 17 mg/kg) raltitrexed injection was given to each experimental rabbit. At 5, 15, 30, 60, 120 and 180 min after the treatment, venous blood sample was collected for pharmacokinetic analysis. At 6 h and one week after administration of drug, liver functions were tested, and histological specimens of liver tissues were made at the same time. Results The peripheral blood drug concentrations at 5 and 60 min in group A were 0. 91 μg/mL and 0 μg/mL respectively, at 5 and 180 min in group B were 1. 73 μg/mL and 0. 37 μg/mL respectively, at 5 and 180 min in group C were 0. 82 μg/mL and 0. 08 μg/mL respectively, at 5 and 180 min in group D were 0. 94 μg/mL and 0. 08 μg/mL, and at 5 and 60 min in group E were 0. 39 μg/mL and 0. 13 μg/mL respectively. Six hours after administration of drug, the serum levels of AST, ALT in group C, group D and group E were significantly increased (P＜0. 0l), which returned to normal levels in one week after the treatment. The severity of liver tissue degeneration and necrosis detected in each group varied, in a severity - decreasing order, from group E, group C, group D, group B and group A. In group E, the surrounding normal liver tissue had no obvious necrosis. Conclusion The rabbit' s liver has no significant first pass elimination effect to raltitrexed. The equivalent dose of raltitrexed administered through the hepatic artery can cause obvious hepatocellular injury. Direct puncture and injection produce limited liver injury. Clinically, the dose of raltitrexed can be adjusted based on the degree of super selective catheterization condition and tumor size. (J Intervent Radiol, 2018, 27:247-251)
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A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.
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Aim To establish depression rat model with kidney-yang deficiency and evaluate the related parameters.Methods A total of 24 adult SD rats were divided into control group,mod-el group and self-healing group by body weight.Model group and self-healing group were injected hydrocortisone for 21 days, meanwhile the control group was injected sodium chloride.After modeling,the related indexs detection were taken out:open-field test,sucrose preference test and forced swim test.Then the orbital blood was taken to detect 5-HT,DA and NE by LC-MS/MS.And liver,kidney,spleen,thymus,adrenal gland,testis and epididymis were taken to calculate organ index.Results Compared with the control group,model rats displayed depres-sion and kidney yang deficiency syndrome such as dry hairs, chills,back arched and so on. Correspondingly, the body weight increased slowly.Immobility in FST was significantly in-creased. Sucrose preference, horizontal scores and vertical scores was significantly decreased.Organ index decreased in liv-er,kidney,spleen,adrenal,testis and epididymis.The level of 5-HT and NE was significantly high.Compared with the model group,5-HT,NE and DA were significantly reduced,5-HT and DA were even lower than those of the control group.Conclusion Depression rat model with kidney-yang deficiency could be in-duced by continuous injection of hydrocortisone.
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Objective To develop an UPLC-MS/MS method for simultaneously determination of five components (adenosine,cytidine,guanosine,mannitol and adenine) in Qiangshenpaidu capsules. Methods The UPLC separation was performed on an Agilent ZOBAX SB-C18(2.1 mm×150 mm,5 μm) column.Isocratic elution was carried out with mobile phase consisting of methanol-0.1%formic acid (5∶95) at a flow rate of 0.2 mL.min-1.The mass spectrometer was operated in the positive ionization electrospray ( ESI) mode using multiple monitoring ( MRM) for analysis of five components. Results Adenosine,cytidine,guanosine,mannitol and adenine were all analyzed with good precision and accuracy. The linear ranges were 35-1 120 ng.mL-1( r=0.998 1) ,10-320 ng.mL-1( r=0.996 4) , 30-980 ng.mL-1( r=0.999 3) , 40-1 280 ng.mL-1( r=0.993 4), 25-800 ng.mL-1(r=0.996 5),respectively.The recoveries of six analytes ranged from 97.4% to 103.6% and the relative standard deviations were all below 4.7%. Conclusion A sensitive,accurate and suitable UPLC-MS/MS method has been developed,and the method could be applied for the determination of adenosine,cytidine,guanosine,mannitol,and adenine in Qiangshenpaidu Capsules.
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This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
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Aim To establish a LC-MS/MS method for determination of 5-HT, NE, DA and observe the con-centration of 5-HT, NE, DA in rat plasma of CUMS. Methods Twenty-two male SD rats were divided into control group and model group. Model group was given 9 kinds chronic unpredictable mild stimulating factors every day. 21 days later, behavior and orbital blood were measured before and after modeling. Using benzo-yl chloride as a pre-column derivatization reagent, three analytes and IS were derivatized before LC-MS/MS detection. Change in three kinds of neurotransmit-ter concentration was measured in rat plasma before and after modeling. Results After modeling, com-pared with control group, the weight of rats in model group was declined significantly ( P<0. 05 ) . Horizon-tal scores, vertical scores and sugar consumption were declined significantly ( P <0. 01 ) . Calibration curves of 5-HT, NE, DA were linear between 1. 47 ~752, 1. 75 ~898 , 2. 05 ~1 053 μg · L-1 and LOQ were 1. 47, 1. 75, 2. 046μg·L-1 ,respectively. The recov-ery of 5-HT, NE, DA from plasma was over than 70%, and RSD of inter-day and intra-day assay was limited in 15%. Compared with control group, the con-centration of 5-HT, NE, DA in rat plasma of model group was declined to ( 3. 99 ± 1. 21 ) , ( 6. 24 ± 1. 94), (6. 07 ± 1. 98) μg·L-1(P <0. 01). Con-clusion After making CUMS model of depression, three kinds of neurotransmitters in rat plasma are de-creased.
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Objective To investigate hemostatic effect of uterine tamponade in dealing with postpartum hem -orrhage due to uterine inertia during caesarean section .Methods 72 patients treated with conservative treatment due to bleeding uterine contraction weakness during cesarean section were chosen ,who were dealed with sterile gauze close packing of uterine bleeding ( uterine packing group ) .43 patients underwent conservative therapy of uterine contraction weakness resulted in postpartum hemorrhage were selected to carry out B -Lynch suture hemostasis ( B-Lynch suture group).Bleeding volume,operation time,bleeding efficiency of two groups were calculated .Results The uterine packing group had shorter operation time ,less bleeding,immediate hemostasis rate.The B-Lynch suture group had a tad longer operation time , bleeding more , immediate hemostasis rate low , low efficiency .Immediate hemostasis rate (95%VS 82%)between two groups had statistically significant (χ2 =4.02,P0.05).Conclusion Uterine packing for postpartum hemorrhage due to uterine inertia during caesarean section has simple operation ,rapid,hemostatic effect,postoperative body without foreign body removal.
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Aim To establish a LC-MS/MS method for the determination of hydroxysafflor yellow A ( QA ) in human plasma. Methods After being added into 0. 2M ammonium acetate (1∶1,V/V), QA was extrac-ted using solid-phase extraction technique, and the eluent was directly injected into LC-MS/MS systems. Agilent ZORBAX SB C18 (3. 0 × 100 mm, 3. 5 μm) column and isocratic elution system composing of meth-anol and 0. 2 mM ammonium acetate (70 ∶ 30, V/V) provided chromatographic separation of QA and internal standard isorhamnetin-3-O-neohespeidoside ( SLS) fol-lowed by detection with mass spectrometry. The mass transition ion-pair was followed as m/z 611 . 131→490. 900 for QA and m/z 623. 032→298. 800 for SLS. Results The retention time of QA and SLS was 2. 7 min and 3. 9 min respectively, with no interference in human blank plasma. The proposed method showed good linearity over the concentration range of 8. 57 ~4185 μg·L-1 for QA with a correlation coefficient≥ 0 . 9949 . The lower limit of quantitation was 8. 570 μg ·L-1 . The intra-batch and inter-batch precision and accuracy were within 7%. The average matrix effect ranged from 115. 72% to 119. 06% with RSD less than 5%. The average extraction recovery ranged from 77. 75% to 80. 76% with RSD less than 5%. Stability of human samples after 4 h at room temperature, after the three freeze-thaw cycles and after 31 days at -70℃, and post-preparative stability of the processed sam-ples after 24 h was acceptable. Plasma samples with the concentration beyond the upper quantitation limit could be accurately determined after being diluted using 6. 25 times ( V/V ) of human blank plasma. Conclusion Our current LC-MS/MS method is sensitive, accurate and convenient, and is proved to be suitable for the sys-tematic study on clinical pharmacokinetics of QA.
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Aim To investigate the pharmacokinetic effect of aspirin on caffeic acid in dengzhanxixin injec-tion( DI) . Methods Concentration of caffeic acid in rat plasma was detected by LC-MS/MS after rats were given intravenous administration of DI or DI combined with aspirin by gavage. Pharmacokinetic parameters were calculated by DAS 1. 0 pharmacokinetic software. Results In vivo pharmacokinetic models of caffeic acid were two-compartment open models in both the caffeic acid group and the caffeic acid combined with aspirin group. After compatibility, caffeic acid showed a significant increase in T 12β, with a slight decrease in CL. Conclusions Aspirin can reduce metabolic process of caffeic acid in vivo.