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OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.
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Objective:To evaluate the inhibitory effect of 5 Chinese herbal medicinal ingredients baicalin, andrographolide, hes-peridin, polyphenols and daidzein on the activity of carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). Methods: The spe-cial probes respectively for CES1 and CES2, namely imidapril and CPT-11, imidaprilat and SN-38, were used to investigate the poten-tial effect of the above drugs on CES1 and CES2 in rat liver microsomes incubation system. Results:Compared with that in the control group, the activity of CES1 and CES2 was not significantly influenced by the above 5 Chinese herbal medicinal ingredients ( P <0. 05). Conclusion:Baicalin, andrographolide, hesperidin, polyphenols and daidzein exhibit no inhibitory effect against CES1 and CES2, and further studies should be conducted to confirm the effect in vivo.
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Objective To investigate the compatible stability of alanylglutamine by using continuous series infusion device,and provide experimental evidence for reasonable clinical use of alanylglutamine. Methods pH,osmolality and quantity of insoluble particles were measured by using pH meter, automatic freezing osmometer and intelligent particle detector respectively.A HPLC method was built for the determination of the content of alanylglutamine. Results pH and quantity of insoluble particles of the two tested groups did not change significantly over time. Osmolality and the content of alanylglutamine fluctuated greatly in the first half an hour. Conclusion Continuous series infusion device may not mix each bottle of solution very well.It is suggested to premix these solutions to ensure the stability of the dilution ratio and the osmotic pressure of the mixture in the process of the infusion.
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With the advent of bezoar substitutes, bezoar compound has been widely used in clinics. Bezoar is commonly applied in the traditional prescriptions for emergency. Due to the complex compositions and difficult soluble constituents, the prescriptions show the disadvantages of low bioavailability and slow onset in clinical application, and the effectiveness is usually related with the adminis-tration route and characteristics of dosage form of the preparations. The exiting bezoar compound and its new dosage forms were summa-rized in the paper, and the existing bezoar compound preparations were stated according to the characteristics of dosage forms and com-pound clinical application in order to promote the development and application of bezoar new dosage forms.
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Objective To explore the influence of different administration time on antidepressant effect of seven clinical common antidepressants. Methods Male mice were randomly divided into eight groups:venlafaxine (75 mg/kg), sertraline (20 mg/kg), fluoxetine (20 mg/kg), doxepin (15 mg/kg), mirtazapine (15 mg/kg), citalopram (40 mg/kg), trazodo?ne (50 mg/kg) and control (saline) groups. Each group contained 36 mice. Drugs were administered to 6 mice per group 30 min before forced swimming test at the 6 time points (9:00, 13:00 and 17:00 as light phase and 21:00, 1:00 and 5:00 as dark phase). Forced swimming test was applied to determine the influence of dosing time on anti-immobility effect of seven antidepressants at each time point. Results Immobility time in venlafaxine group and sertraline group significant?ly decreased compared with that of control group at all time points(all P<0.05). Moreover, anti-immobility effects of ven?lafaxine, fluoxetine, mirtazapine and doxepin were better during the dark phase than during the light phase (all P<0.05). In addition, immobility time in sertraline group decreased at the late part of dark phase (5:00) and the early part of light phase (9:00) compared with other phases (P<0.05). Conclusions Most antidepressants show 24-h rhythm dependent an?ti-immobility effects, but rhythmic patterns are not completely consistent among different antidepressants. Further study is needed to explore the chronopharmacological mechanism and clinical applications of these antidepressants.
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Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially regulate CES1 and CES2.
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Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially regulate CES1 and CES2.
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Animals , Male , Rats , Carboxylic Ester Hydrolases , Genetics , Dexamethasone , Pharmacology , Gene Expression , Allergy and Immunology , Rats, Sprague-Dawley , Receptors, Cytoplasmic and Nuclear , MetabolismABSTRACT
Anti-HER2 monoclonal antibody (Sc7301)-paclitaxel (TAX) immunoconjugate was prepared and its specific binding to tumor cells was investigated in this study. Sc7301 was conjugated to TAX by the active ester method and then the TAX-Sc7301 immunoconjugate was obtained. After purification and labeling by Cyano-fluorescein isothiocyanate (FITC), the specific binding of TAX-Sc7301 to HER2-positive tumor cells (SKOV3) and HER2-negative tumor cells (HepG2) was evaluated respectively. TAX-Sc7301 (20 nmol/L) showed distinct specific binding to SKOV3 cells rather than HepG2 cells. And the uptake of the immunoconjugate by SKOV3 cells was increased with the TAX-Sc7301 concentration (3-48 nmol/L) and the incubation time (P<0.05). It was concluded that the TAX-Sc7301 immunoconjugate is potentially applicable as a targeted agent against HER2-positive tumor cells.
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Objective To investigate the effect of predictive nursing on the living donor liver transplantation.Methods Forty patients undergoing living donor liver transplantation were divided into the intervention group and the control group with 20 patients in each group randomly.We gave routine nursing cooperation to the control group while predictive nursing besides routine nursing cooperation to the intervention group.The operation time,cold ischemia time of donor liver,nursing complication,cost of surgery and satisfaction degree of surgery cooperation were recorded.Results Compared with the control group,the operation time,cold ischemia time of donor liver,nursing complication,cost of surgery were all decreased,and the satisfaction degree of surgery cooperation was improved.Conclusions Predictive nursing can improve nursing operation quality,raise the efficiency of nursing and surgery,reduce the incidence of complication,which is beneficial to smooth progress of operation and increase satisfaction degree of doctors and nurses to nursing cooperation.
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OBJECTIVE To explore the application of hydrogen dioxide hypothermic plasma sterilizing system(STERRAD 100S) in operating room,and study the cost.METHODS The cost of sterilizing endoscopic instruments in operating room was analyzed.And the method of using medical material was improved as follows: use the non-woven fabrics and transparent packing bags repeatly to increase the utilization efficiency of medical material.RESULTS Compared with the traditional method,the cost of sterilizing instruments by STERRAD 100S decreased 2-3 times,which brought much economic benefit.CONCLUSIONS 100S Can improve the working efficiency,reduce inventory level of endoscopic instruments and sterilizing cost,which can relief patient economic burden and ensure patient interest.