35 results on '"Xiao Jin-shi"'
Search Results
2. Chemical profiling of San-Huang decoction by UPLC–ESI-Q-TOF-MS
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Li Zhongdong, Xiao-jin Shi, Mingkang Zhong, Zheng Jiao, Qing-Feng Liu, Wang Wenjian, Bin Wang, and Liu Yi
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Flavonoids ,Spectrometry, Mass, Electrospray Ionization ,Chromatography ,010405 organic chemistry ,Chemistry ,Electrospray ionization ,010401 analytical chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Decoction ,Tandem mass spectrometry ,Mass spectrometry ,01 natural sciences ,High-performance liquid chromatography ,0104 chemical sciences ,Analytical Chemistry ,Alkaloids ,Triterpenoid ,Tandem Mass Spectrometry ,Drug Discovery ,Uplc esi q tof ms ,Ultra high performance ,Chromatography, High Pressure Liquid ,Spectroscopy ,Drugs, Chinese Herbal - Abstract
San-Huang decoction (SHD), a traditional Chinese medical (TCM) formula, is made from five chinese herbs and has been widely used for centuries to treat metabolic syndrome, such as abdominal obesity and nonalcoholic fatty liver disease. In this work, an ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS) method in both positive and negative ion mode was first employed to rapidly survey the major constituents in SHD. The analysis was performed on a Waters Acquity UPLC BEH C18 column at 45°C within 17min. 56 compounds in SHD including alkaloids, flavonoids, protostane triterpenoids, coumarins, triterpenoid saponins, organic acids, lignans, lactones and chromones were identified and tentatively characterized by comparison with retention times, accurate mass within 5ppm error and MS fragmentation ions. Among them, twenty-two compounds were clearly identified mainly by the reference standards. Moreover, this method was respectively applied to determine five batches of SHD and the decoctions of relative individual herbs. These results provide a helpful basic chemical profile for further research of SHD in vivo and exploitation of new drug to treat metabolic syndrome.
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- 2016
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3. Antiproliferative activity of Farnesol in HeLa cervical cancer cells is mediated via apoptosis induction, loss of mitochondrial membrane potential (ΛΨm) and PI3K/Akt signalling pathway
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Yao-Lei, Wang, Hai-Fang, Liu, Xiao-Jin, Shi, and Yi, Wang
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Membrane Potential, Mitochondrial ,Cell Survival ,Down-Regulation ,Uterine Cervical Neoplasms ,Apoptosis ,Farnesol ,Phosphatidylinositol 3-Kinases ,Cell Line, Tumor ,Humans ,Female ,Proto-Oncogene Proteins c-akt ,Cell Proliferation ,HeLa Cells ,Signal Transduction - Abstract
Cervical cancer remains the most gruesome health problem in women worldwide as it ranks third in incidence. Despite recent developments in the treatment options of cervical cancer, the survival of patients not fit for surgical treatment rather remains poor. The main purpose of the current research was to determine the anticancer effect of farnesol in HeLa human cervical cancer cells together with studying its impact on apoptosis induction, mitochondrial membrane potential (MMP) and PI3K/Akt signalling cascade.Cell viability was estimated by MTT assay while clonogenic assay was used to assess the effects on colony formation tendency in these cells. Fluorescence microscopy indicated apoptosis induction while flow cytometry showed the farnesol effects on the loss of MMP.Farnesol exerted both dose and time-dependent antiproliferative effects on cervical cancer cells with IC50 values of 33.5, 23.8 and 17.6 μM at 24, 48 and 72 hrs time intervals, respectively. Colony formation of HeLa cells was considerably affected in a dose-dependent manner with the addition of farnesol to the cell culture. Farnesol-treated cells mostly emitted orange fluorescence indicating apoptotic cell death and this effect increased with increasing dose of the compound. Furthermore, farnesol induced considerable reduction in the number of cells with depolarized mitochondria corresponding to a reduction of MMP. With increase in the dosage of farnesol, there was a noticeable decrease in the expression levels of PI3K, p-PI3K and p-Akt proteins.In brief, this study showed that farnesol -a naturally occurring sesquiterpene- exerts powerful antiproliferative activity via apoptosis induction, loss of MMP and downregulation of the expression levels of PI3K, p-PI3K and p-Akt proteins.
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- 2018
4. Determination of telbivudine in the plasma of chronic hepatitis B patients in long-term treatment by high-performance liquid chromatographic-tandem mass spectrometry
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Jiming Zhang, Bin Wang, Bicui Chen, Cai Cheng, Xiao-jin Shi, Li Chen, and Mingkang Zhong
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0301 basic medicine ,Adult ,Male ,Bioanalysis ,030106 microbiology ,Clinical Biochemistry ,Pharmacology ,Creatine ,Tandem mass spectrometry ,030226 pharmacology & pharmacy ,Biochemistry ,Antiviral Agents ,Sensitivity and Specificity ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Hepatitis B, Chronic ,Pharmacokinetics ,Tandem Mass Spectrometry ,Telbivudine ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,Creatine Kinase ,Chromatography, High Pressure Liquid ,Chromatography ,biology ,medicine.diagnostic_test ,Reproducibility of Results ,General Medicine ,Middle Aged ,medicine.disease ,Mitochondrial toxicity ,chemistry ,Therapeutic drug monitoring ,biology.protein ,Linear Models ,Creatine kinase ,Female ,Drug Monitoring ,medicine.drug ,Thymidine - Abstract
Creatine kinase elevation is commonly reported in telbivudine-treated patients. However, little is known about the relationship between this adverse drug reaction and plasma concentration. In this study, a sensitive, rapid and safe quantitative bioanalytical method has been established by using LC-MS/MS for the determination of telbivudine in a clinical study of chronic hepatitis B patients. The assay was linear in a dynamic 10-10,000 ng/mL range (r2 > 0.999) and total analysis time was 6 min in this method. The validated method was applied to quantitatively determine plasma concentration in chronic hepatitis B patients during long-term telbivudine treatment. The results revealed that telbivudine concentration in the creatine kinase-elevated group (707.92-2788.78 ng/mL) was significantly higher than those with normal creatine kinase (412.63-1108.32 ng/mL). This method was adapted for therapeutic drug monitoring.
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- 2017
5. 6-Hydroxydaidzein Enhances Adipocyte Differentiation and Glucose Uptake in 3T3-L1 Cells
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Shi-Long Mao, Li Chen, Yongli Du, Qunyi Li, and Xiao-Jin Shi
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medicine.medical_specialty ,medicine.medical_treatment ,Glucose uptake ,Carbohydrate metabolism ,Biology ,Mice ,chemistry.chemical_compound ,3T3-L1 Cells ,Internal medicine ,Adipocyte ,Gene expression ,Adipocytes ,medicine ,Animals ,Hypoglycemic Agents ,Plant Extracts ,Binding protein ,Insulin ,Glucose transporter ,Soy Foods ,Biological Transport ,Cell Differentiation ,General Chemistry ,Isoflavones ,Glucose ,Endocrinology ,chemistry ,biology.protein ,General Agricultural and Biological Sciences ,GLUT4 - Abstract
Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARγ) gene expression and PPARγ transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPα) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPα and facilitating the translocation of GLUT4 via the activation of PPARγ, suggesting that 6-HD can be promising in diabetes management.
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- 2013
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6. Genetic association of FOXP3 gene polymorphisms with allograft rejection in renal transplant patients
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Ming Zhang, Xiaoyan Qiu, Jian-Ping Chen, Mingkang Zhong, Zheng Jiao, and Xiao-jin Shi
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medicine.medical_specialty ,business.industry ,Proportional hazards model ,Hazard ratio ,General Medicine ,Odds ratio ,Gastroenterology ,Confidence interval ,Genotype frequency ,Transplantation ,Nephrology ,Internal medicine ,Genotype ,Immunology ,Medicine ,business ,Allele frequency - Abstract
Aim: FOXP3 gene is known to be important for regulatory T cell development and function, and is associated with the rejection of human kidney transplants. The present study was therefore conducted to determine the effect of FOXP3 polymorphisms on allograft rejection in renal transplant recipients. Methods: A total of 166 adult patients were categorized into either a Rejection group (65 patients) or a No rejection group (101 patients). Rs3761547, rs3761548 and rs2232365 variant alleles in the FOXP3 gene were genotyped using a TaqMan probe technique, and their relationships with rejection were investigated. Results: There was no significant difference in the genotype frequencies of rs3761547 and rs2232365 variants between patients with and without rejection history (P > 0.05). Binary logistic regression analysis showed that the rs3761548 AA genotype carriers were associated with about a fourfold greater risk for rejection compared with CC genotype (5 years post-transplant: odds ratio 3.95, 95% confidence interval 1.27–12.29, P = 0.018). Kaplan–Meier analysis revealed a lower mean time to the first rejection in rs3761548 AA compared with CC genotype patients (Log rank = 4.303, P = 0.038). Multivariate Cox regression analysis indicated that rs3761548 AA genotype carriers have up to about a twofold (hazard ratio 2.37, 95% confidence interval 1.17–4.80, P = 0.017) higher risk for rejection than CC carriers. Conclusion: Our study suggests an association between FOXP3 rs3761548 polymorphisms and allograft rejection in renal transplantation. This association should be further proven in large prospective studies because of the small sample size and confounding factors in this retrospective study.
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- 2012
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7. Association of ABCB1, CYP3A4*18B and CYP3A5*3 genotypes with the pharmacokinetics of tacrolimus in healthy Chinese subjects: a population pharmacokinetic analysis
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Xiaoyan Qiu, Fang Geng, Xue-yan Cui, Zheng Jiao, Mingkang Zhong, and Xiao-jin Shi
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Pharmacology ,education.field_of_study ,CYP3A4 ,CYP3A ,Population ,Biology ,NONMEM ,Pharmacokinetics ,Genotype ,Pharmacology (medical) ,Allele ,education ,CYP3A5 - Abstract
Summary What is known and Objective: Tacrolimus (TAC) is metabolized mainly by the CYP3A subfamily and extruded into the intestine by P-glycoprotein, which is encoded by the ABCB1 gene. Several studies have suggested that the CYP3A5*3 genotype influenced the pharmacokinetics (PK) of TAC. The CYP3A4*18B and CYP3A5*3 alleles are clinically important in Chinese subjects because of their relatively high frequency. The present study aimed at evaluating the effects of ABCB1 (C1236T-G2677T/A-C3435T), CYP3A4*18B and CYP3A5*3 genetic polymorphisms on TAC PK in healthy Chinese subjects. Methods: Data were obtained from a comparative bioavailability study of oral TAC formulations (n = 22). TAC whole blood concentrations were measured by LC-MS/MS. Genetic polymorphisms were determined using a direct sequencing method. Nonlinear mixed-effects modelling (NONMEM) was performed to assess the effect of genotypes and demographics on TAC PKs. Results and Discussion: Both CYP3A4*18B and CYP3A5*3 polymorphisms affected the TAC PK, whereas ABCB1 genetic polymorphisms and other demographic characteristics did not. The combined genotypes of CYP3A4*18B and CYP3A5*3 had a greater impact than either genotype alone, and they were estimated to account for 28·4% of the inter-subject variability of apparent clearance (CL/F) by NONMEM. The CL/F in subjects with CYP3A4*1/*1-CYP3A5*3/*3 was 10·3 L/h and was 48·5% in those not carrying CYP3A4*1/*1-CYP3A5*3/*3. What is new and Conclusion: This is the first study to extensively explore the influence of CYP3A4*18B, CYP3A5*3 and ABCB1 genetic polymorphisms on TAC PK in healthy Chinese subjects. The results demonstrated that subjects with a combined genotype of CYP3A4*1/*1-CYP3A5*3/*3 may require lower TAC doses to achieve target concentration levels and further investigation is needed in larger populations to confirm the clinical benefits.
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- 2010
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8. Simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine in human plasma by high-performance liquid chromatography
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Wei-wei Qin, Li Zhongdong, Xue-yan Cui, Zheng Jiao, Mingkang Zhong, Jun Zhang, and Xiao-jin Shi
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Tetracaine ,Lidocaine ,medicine.drug_class ,Clinical Biochemistry ,Sensitivity and Specificity ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Procaine ,chemistry.chemical_compound ,Drug Stability ,medicine ,Humans ,Ropivacaine ,Least-Squares Analysis ,Phosphoric acid ,Chromatography, High Pressure Liquid ,Bupivacaine ,Chromatography ,Chemistry ,Local anesthetic ,Reproducibility of Results ,Cell Biology ,General Medicine ,Amides ,medicine.drug - Abstract
A simple and sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method has been developed and validated for simultaneous quantification of five local anesthetics in human plasma: procaine, lidocaine, ropivacaine, tetracaine and bupivacaine. In an ice-water bath, 500 microL plasma sample, containing 100 microg/mL neostigmine methylsulfate as anticholinesterase, was spiked with carbamazepine as internal standard and alkalized by sodium hydroxide. Liquid-liquid extraction with ethyl ether was used for plasma sample preparation. The chromatographic separation was achieved on a Kromosil ODS C18 column with a mobile phase consisting of 30 mM potassium dihydrogen phosphate buffer (0.16% triethylamine, pH adjusted to 4.9 with phosphoric acid) and acetonitrile (63/37, v/v). The detection was performed simultaneously at wavelengths of 210 and 290 nm. The chromatographic analysis time was 13 min per sample. The calibration curves of all five analytes were linear between 0.05 and 5.0 microg/mL (r(2) > or = 0.998). Precision ranged from 1.4% to 7.9% and accuracy was between 91.7% and 106.5%. The validated method is applicable for simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine for therapeutic drug monitoring and pharmacokinetic study.
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- 2010
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9. Development of a liquid chromatography-isotope dilution mass spectrometry method for quantification of fentanyl in human plasma
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Yu-zhou Gui, Xiao-jin Shi, Gangyi Liu, Chen Yu, Jingying Jia, Shuijun Li, and Chuan Lu
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Pharmacology ,Chromatography ,Chemistry ,Calibration curve ,Electrospray ionization ,Clinical Biochemistry ,Pain ,General Medicine ,Isotope dilution ,Bioequivalence ,Biochemistry ,Analytical Chemistry ,Fentanyl ,Triple quadrupole mass spectrometer ,Analgesics, Opioid ,Tandem Mass Spectrometry ,Human plasma ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,Chromatography, Liquid ,Transdermal ,medicine.drug - Abstract
Fentanyl is a potent analgesic drug in relieving chronic pain in patients. In this report, we present a simple, reliable and sensitive LC–ID/MS method for the quantification of fentanyl in human plasma. LC-ID/MS analysis was carried out on a triple quadrupole mass spectrometer operated in positive electrospray ionization multiple-reaction-monitoring using the transitions m/z 337.6 187.9 for fentanyl and m/z 342.6 187.9 for the internal standard (D5-fentanyl). The calibration curve covered the range 0.02–10 ng/mL. The intra- and inter-batch precision were less than 6.739 and 3.126% for fentanyl and IS, with accuracy from 94.16 to 102.0%. The lower limit of quantification was identifiable and reproducible at 0.02 ng/mL. The validated method offered increased sensitivity and wide linear concentration range. This method was successfully adopted for the evaluation of bioequivalence of two fentanyl transdermal preparations after single dose administration to 20 Chinese pain-patients. Copyright © 2009 John Wiley & Sons, Ltd.
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- 2009
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10. Simple and Sensitive Determination of Metformin in Human Plasma Using an Ion-Pair LC Method
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Mingkang Zhong, Xiao-jin Shi, Li Zhongdong, Zheng Jiao, and Qing-Feng Liu
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Chromatography ,Elution ,Chemistry ,Calibration curve ,Organic Chemistry ,Clinical Biochemistry ,Analytical chemistry ,Reversed-phase chromatography ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Blood plasma ,Perchloric acid ,Sodium dodecyl sulfate ,Quantitative analysis (chemistry) - Abstract
A simple, selective and sensitive ion-pair liquid chromatography method was described for the determination of metformin in human plasma. Plasma samples (200 μL) were deproteinated with 10% (v/v) perchloric acid followed by LC analysis using a Symmetry C18 column and a mobile phase of 29% acetonitrile—71% 2 mM sodium dodecyl sulfate (with 350 μL 0.1 M HCl) operated at a flow rate of 1.5 mL min−1. Metformin and the internal standard (sodium phenytoin) were detected at 232 nm and eluted at 6.8 and 7.9 min, respectively. Calibration curves were linear (r > 0.9990) between 9 and 2,000 ng mL−1. The quantitation limit was 9 ng mL−1, intra- and inter-day precision (CV) were 5.26% or less, and accuracy values were found to be within 5.95% of the nominal concentration.
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- 2009
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11. Isocratic Reversed-Phase HPLC for Simultaneous Separation and Determination of Seven Antiepileptic Drugs and Two of their Active Metabolites in Human Plasma
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Zheng Jiao, Chun-Lai Ma, Yang Jie, and Xiao-jin Shi
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Chromatography ,Chemistry ,Metabolite ,medicine.medical_treatment ,Organic Chemistry ,Clinical Biochemistry ,Carbamazepine ,Reversed-phase chromatography ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Anticonvulsant ,medicine ,Quantitative analysis (chemistry) ,Primidone ,Active metabolite ,medicine.drug - Abstract
A simple reversed-phase high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of the antiepileptic drugs (AEDs) zonisamide (ZNS), primidone (PRI), lamotrigine (LTG), phenobarbital (PB), phenytoin (PHT), oxcarbazepine (OXC), and carbamazepine (CBZ) and two of their active metabolites, monohydroxycarbamazepine (MHD) and carbamazepine 10,11-epoxide (CBZE) in human plasma. Plasma (100 μL) was pretreated by deproteinization with 300 μL methanol containing 20 μg mL−1 propranolol hydrochloride as internal standard. HPLC was performed on a C8 column (4.6 mm × 250 mm; particle size 5 μm) with methanol–acetonitrile–0.1% trifluoroacetic acid, 235:120:645 (v/v), as mobile phase at a flow rate of 1.5 mL min−1. ZNS, OXC, and CBZ were monitored by UV detection at 235 nm, and PRI, LTG, MHD, PB, PHT, and CBZE by UV detection at 215 nm. Relationships between response and concentration were linear over the concentration ranges 1–80 μg mL−1 for ZNS, 5–50 μg mL−1 for PRI, 1–25 μg mL−1 for LTG, 1–50 μg mL−1 for MHD, 5–100 μg mL−1 for PB, 1–10 μg mL−1 for CBZE, 0.5–25 μg mL−1 for OXC, 1–50 μg mL−1 for PHT, and 1–25 μg mL−1 for CBZ. Intra-day and inter-day reproducibility were adequate (coefficients of variation were ≤11.6%) and absolute recovery ranged from 95.2 ± 6.13 to 107.7 ± 7.76% for all the analytes; for the IS recovery was 98.69 ± 1.12%. The method was proved to be accurate, reproducible, convenient, and suitable for therapeutic monitoring of the nine analytes.
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- 2007
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12. The neuropharmacokinetics of valproate in pentylenetetrazol-kindled conscious epileptic rat hippocampus
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Yong-Hua Ji, Zhi-Ping Li, Ming-Kang Zhong, Xu-Ying Zhang, and Xiao-Jin Shi
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business.industry ,Dosing regimen ,Hippocampus ,Drug administration ,General Medicine ,Pharmacology ,Rat brain ,Epileptogenesis ,General Biochemistry, Genetics and Molecular Biology ,Pharmacokinetics ,medicine ,Valproate level ,Pentylenetetrazol ,business ,medicine.drug - Abstract
In the present communication, the neuropharmacokinetics of valproate in pentylenetetrazol-kindled epileptogenesis rat hippocampus have been examined by micordialysis. It was found that the maximum concentration and the area under the hippocampus concentration-time curve of valproate in pathological rats were significantly higher than those in the control group. Time to maximum concentration of valproate appeared at 45 min after drug administration, and then the concentration of valproate gradually declined. The results suggest that the pathological damages of rat brain induced by pentylenetetrazol may result in the increase of the valproate level in epileptic rat hippocampus, and the neuropharmacokinetic research of valproate in a chronic kindled conscious animal model with acute administration may help the clinic in the pharmacokinetic optimization of the valproate dosage schedule in epileptic patients.
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- 2004
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13. Population Pharmacokinetics of Carbamazepine in Chinese Epilepsy Patients
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Jing-hua Zhang, Mingkang Zhong, Min Hu, Xiao-jin Shi, and Zheng Jiao
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Adult ,Male ,China ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Population pharmacokinetics ,Epilepsy ,Pharmacokinetics ,Internal medicine ,Confidence Intervals ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Clinical care ,Child ,Prospective cohort study ,Aged ,Aged, 80 and over ,Pharmacology ,Chi-Square Distribution ,business.industry ,Infant ,Reproducibility of Results ,Carbamazepine ,Middle Aged ,medicine.disease ,Anticonvulsant ,Nonlinear Dynamics ,Child, Preschool ,Anesthesia ,Female ,business ,medicine.drug - Abstract
To investigate the pharmacokinetic profile of carbamazepine (CBZ) in Chinese epilepsy patients.Serum samples through concentrations at steady state (n = 687) were collected prospectively from 585 patients during routine clinical care. Data were analyzed by the non-linear mixed-effect modeling (NONMEM) technique with a one-compartment model of first-order absorption and elimination.The important determinants of clearance (CL) were total body weight (TBW); dose; patient age over 65 years (E); and comedication with phenytoin (PHT), phenobarbital (PB), or valproic acid (VPA) when VPA daily dose was greater than 18 mg/kg. The final pharmacokinetic model for relative CL and apparent distribution volume (V) were: EquationA population pharmacokinetic model was proposed to estimate the individual CL for Chinese patients receiving CBZ in terms of patient's dose, TBW, and comedications to establish a priori dosage regimens.
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- 2003
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14. [XCT790 inhibits rat vascular smooth muscle cells proliferation through down-regulating the expression of estrogen-related receptor alpha]
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Yun-Hong, Lu, Qun-Yi, Li, Li, Chen, and Xiao-Jin, Shi
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Male ,Vascular Endothelial Growth Factor A ,Dose-Response Relationship, Drug ,MAP Kinase Signaling System ,GTPase-Activating Proteins ,Myocytes, Smooth Muscle ,Nuclear Proteins ,Cadherins ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Muscle, Smooth, Vascular ,Rats ,Rats, Sprague-Dawley ,Cytoskeletal Proteins ,Thiazoles ,Receptors, Estrogen ,Nitriles ,Animals ,RNA, Messenger ,Phosphorylation ,Cells, Cultured ,Cell Proliferation ,Transcription Factors - Abstract
Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in several pathological processes of cardiovascular diseases. In this study, the effects of XCT790, a potent and selective inverse agonist of estrogen-related receptor alpha (ERRalpha), on rat VSMCs proliferation and related signal pathways were investigated. The proliferative activity of VSMCs was determined by CCK-8 assay. The mRNA levels of ERRalpha, PGC-1alpha, OPN and MCAD were assayed by RT-PCR. The protein levels of ERRalpha, ERK2 and p-ERK1/2 were evaluated by Western blotting. ELISA was used to assess the protein expression of VEGF. The results showed that XCT790 (5-20 micromol x L(-1)) inhibited rat VSMCs proliferation, and the expression of ERRalpha and its target genes, as well as p-ERK1/2, were also inhibited. XCT790 inhibited VSMCs proliferation in a dose-dependent manner at the dose range from 5 to 20 micromol x L(-1) and in a time-dependent manner at the dose range from 10 to 20 micromol x L(-1). These findings demonstrate that XCT790 inhibits rat VSMCs proliferation by down-regulating the gene level of ERRalpha and thus inhibiting the ERK signal pathway, suggesting that ERRalpha may be a novel potential target for therapeutic approaches to inhibit VSMCs proliferation, which plays an important role in several cardiovascular diseases.
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- 2014
15. Pharmacokinetic comparisons of berberine and palmatine in normal and metabolic syndrome rats
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Mingkang Zhong, Li Zhongdong, Xiao-jin Shi, Qing-Feng Liu, Bin Wang, and Zheng Jiao
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Male ,Berberine ,Berberine Alkaloids ,Administration, Oral ,Blood stasis ,Traditional Chinese medicine ,Pharmacology ,chemistry.chemical_compound ,Random Allocation ,Pharmacokinetics ,Oral administration ,Drug Discovery ,Medicine ,Animals ,Metabolic Syndrome ,Molecular Structure ,business.industry ,Palmatine ,medicine.disease ,Rats ,chemistry ,Area Under Curve ,Metabolic syndrome ,business ,Drug metabolism ,Drugs, Chinese Herbal ,Half-Life - Abstract
Ethnopharmacological relevance San-Huang formula is a popular traditional Chinese medicine (TCM) preparation to replenish Qi, resolve phlegm, dissipate blood stasis, and therapy metabolic syndrome in China. Metabolic syndrome, which is accompanied by Qi and blood stasis, mainly arises from spleen deficiency in essence. There is limited information available for differences of pharmacokinetic properties of San-Huang formula between normal and metabolic syndrome rats. The present study was conducted to compare the pharmacokinetics of berberine as well as palmatine in normal and metabolic syndrome rats following oral administration of San-Huang formula extract. Materials and methods The animals were orally administered with San-Huang formula extract with the equivalent dose of 60.4 and 12.5 mg/kg for berberine and palmatine, respectively. The blood samples were collected according to the time schedule. The concentrations of berberine and palmatine in rat plasma were determined by LC–ESI/MS. Various pharmacokinetic parameters were estimated from the plasma concentration versus time data using non-compartmental methods. Results It was found that AUC 0− t , C max , Vd and CL of berberine and palmatine in metabolic syndrome rats were significantly different ( P Conclusions The results indicated that berberine and palmatine have higher uptake and slower elimination in the rats with metabolic syndrome, which suggests that the rate and extent of drug metabolism were altered in metabolic syndrome rats.
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- 2013
16. Genetic association of FOXP3 gene polymorphisms with allograft rejection in renal transplant patients
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Xiao-Yan, Qiu, Zheng, Jiao, Ming, Zhang, Jian-Ping, Chen, Xiao-Jin, Shi, and Ming-Kang, Zhong
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Adult ,Graft Rejection ,Male ,China ,Chi-Square Distribution ,Time Factors ,Graft Survival ,Forkhead Transcription Factors ,Kaplan-Meier Estimate ,Middle Aged ,Kidney Transplantation ,Polymorphism, Single Nucleotide ,Risk Assessment ,Logistic Models ,Phenotype ,Treatment Outcome ,Gene Frequency ,Risk Factors ,Multivariate Analysis ,Humans ,Female ,Genetic Predisposition to Disease ,Immunosuppressive Agents ,Proportional Hazards Models ,Retrospective Studies - Abstract
FOXP3 gene is known to be important for regulatory T cell development and function, and is associated with the rejection of human kidney transplants. The present study was therefore conducted to determine the effect of FOXP3 polymorphisms on allograft rejection in renal transplant recipients.A total of 166 adult patients were categorized into either a Rejection group (65 patients) or a No rejection group (101 patients). Rs3761547, rs3761548 and rs2232365 variant alleles in the FOXP3 gene were genotyped using a TaqMan probe technique, and their relationships with rejection were investigated.There was no significant difference in the genotype frequencies of rs3761547 and rs2232365 variants between patients with and without rejection history (P0.05). Binary logistic regression analysis showed that the rs3761548 AA genotype carriers were associated with about a fourfold greater risk for rejection compared with CC genotype (5 years post-transplant: odds ratio 3.95, 95% confidence interval 1.27-12.29, P = 0.018). Kaplan-Meier analysis revealed a lower mean time to the first rejection in rs3761548 AA compared with CC genotype patients (Log rank = 4.303, P = 0.038). Multivariate Cox regression analysis indicated that rs3761548 AA genotype carriers have up to about a twofold (hazard ratio 2.37, 95% confidence interval 1.17-4.80, P = 0.017) higher risk for rejection than CC carriers.Our study suggests an association between FOXP3 rs3761548 polymorphisms and allograft rejection in renal transplantation. This association should be further proven in large prospective studies because of the small sample size and confounding factors in this retrospective study.
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- 2012
17. Ginsenoside Rb1 inhibits proliferation and inflammatory responses in rat aortic smooth muscle cells
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Wang Bin, Li Zhongdong, Li Chen, Zhong Mingkang, Wen-Huan Fu, Xiao-Jin Shi, and Qunyi Li
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medicine.medical_specialty ,Ginsenosides ,Cell ,Myocytes, Smooth Muscle ,Down-Regulation ,Inflammation ,Biology ,Rats, Sprague-Dawley ,Ginseng ,Downregulation and upregulation ,Internal medicine ,medicine.artery ,medicine ,Animals ,Aorta ,Cells, Cultured ,Cell Proliferation ,Cell growth ,Plant Extracts ,Cell Cycle ,food and beverages ,General Chemistry ,Cell cycle ,eye diseases ,Rats ,medicine.anatomical_structure ,Endocrinology ,Female ,medicine.symptom ,General Agricultural and Biological Sciences ,Fetal bovine serum - Abstract
Ginsenoside Rb1, a known phytoestrogen, is a major pharmacologically active component in ginseng. The present study was designed to investigate the effect of ginsenoside Rb1 on fetal bovine serum (FBS)-induced proliferation and tumor necrosis factor-α (TNF-α)-evoked inflammatory responses in cultured rat aortic vascular smooth muscle cells (VSMCs). The data showed that Rb1 potently inhibited VSMC proliferation and cell growth induced by 5% FBS. These inhibitory effects were associated with G(1) cell cycle arrest and down-regulation of cell cycle proteins. Treatment with Rb1 reduced FBS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Furthermore, TNF-α-evoked inflammatory responses were inhibited by Rb1. Reporter gene assay indicated that Rb1 could transactivate ERβ especially. Moreover, Rb1-mediated inhibition of VSMCs proliferation was greatly blocked by transfection of ERβ siRNA. These results suggest that Rb1 inhibits FBS-induced proliferation and TNF-α-evoked inflammatory responses in VSMCs. The findings presented here highlight the possible therapeutic use of Rb1 in cardiovascular disease.
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- 2011
18. Determination of berberine, palmatine and jatrorrhizine in rabbit plasma by liquid chromatography-electrospray ionization-mass spectrometry
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Mingkang Zhong, Fengqing Liu, Xiao-jin Shi, and Li Zhongdong
- Subjects
Jatrorrhizine ,Male ,Quality Control ,Spectrometry, Mass, Electrospray Ionization ,Berberine ,Formic acid ,Electrospray ionization ,Clinical Biochemistry ,Berberine Alkaloids ,Pharmaceutical Science ,Administration, Oral ,Mass spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Limit of Detection ,Drug Discovery ,Protein precipitation ,Animals ,Spectroscopy ,Detection limit ,Chromatography ,Selected reaction monitoring ,Reproducibility of Results ,Palmatine ,chemistry ,Calibration ,Rabbits ,Chromatography, Liquid ,Drugs, Chinese Herbal - Abstract
Incurred rabbit plasmas samples were utilized for method quality assessment in this study, where an optimized protein precipitation method for the preparation of rabbit plasma samples and a rapid and sensitive liquid chromatography-electrospray ionization-mass spectrometry for the simultaneous determination of berberine, palmatine and jatrorrhizine was described. Plasma samples (100 μl) were pretreated by protein precipitation with the mixture of 3% formic acid and 50 ng/ml clozapine (internal standard) in acetonitrile followed by LC analysis using a C(18) column and a mobile phase composed of 0.4% formic acid solution and 0.2% formic acid solution of methanol (60:40, v/v) operated at a flow rate of 0.4 ml/min. The analysis was performed in the multiple reaction monitoring mode via electrospray ionization source operating in the positive ionization mode. The method was linear over the concentration range of 0.1-400 ng/ml for all target components. The lower limits of quantification were 0.1 ng/ml for all analytes, all intra- and inter-day precision values were less than 7.10%, and accuracy (bias, %) was within ±7.11%. The mean absolute recovery was more than 72% for all analytes. The validated method has been successfully applied to the pharmacokinetic study of berberine, palmatine and jatrorrhizine in rabbit plasma after oral administration of San-Huang decoction to rabbits.
- Published
- 2011
19. Calculation of the thin line electromagnetic effects in a cavity
- Author
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Zhang Shiying, Xiao Jin-shi, and Liu Wenhua
- Subjects
Engineering ,genetic structures ,urogenital system ,business.industry ,Shell (structure) ,Finite difference method ,Electromagnetic radiation ,Thin line ,Power (physics) ,Optics ,sense organs ,Rectangle ,business ,Current density ,Electromagnetic pulse - Abstract
The cables in the inner of equipments will also be damaged by high power EMP, because the electromagnetic energy can couple into the inner structure through slots in the shell of equipments. The electromagnetic effects on the thin line in a cubic cavity with a rectangle slot are simulated using thin line FDTD algorithm. The little slot is divided into many thin grids, and the transitional area is divided using sub-gridding technique. The influence of different length, different directions and different location in the cavity of the thin line on electromagnetic effects is studied. Some useful results are gotten.
- Published
- 2010
- Full Text
- View/download PDF
20. Simulation of high power EMP effects on a cylinder object with openings using FDTD method
- Author
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Xiao Jin-shi, Zhang Shiying, Liu Wenhua, and Zhang Jinhua
- Subjects
Electromagnetic field ,Physics ,Coupling ,Optics ,business.industry ,Frequency domain ,Finite-difference time-domain method ,Double exponential function ,Cylinder ,business ,Astrophysics::Galaxy Astrophysics ,Electromagnetic pulse ,Pulse (physics) - Abstract
High power electromagnetic pulse (EMP) can easily couple into the inner of targets via lots of slots. To calculate the EMP coupling effects on a cylinder object with openings, the coupling course is simulated using FDTD method in this paper. Gauss pulse and double exponential pulse are selected as the incident pulse source. The coupling EM field strength E inside the object and the current density J on the surface are calculated. Several rules about EMP coupling effects are gotten both in time and frequency domain. The results can help us to understand the damage effects of high power EMP.
- Published
- 2010
- Full Text
- View/download PDF
21. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients
- Author
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Xiao-jin Shi, Zheng Jiao, Li Zhongdong, and Mingkang Zhong
- Subjects
Oncology ,Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Adolescent ,Urinary system ,Young Adult ,Pharmacokinetics ,Asian People ,Adrenal Cortex Hormones ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Young adult ,Kidney transplantation ,Aged ,Retrospective Studies ,Pharmacology ,Aged, 80 and over ,Sirolimus ,Kidney ,business.industry ,Retrospective cohort study ,Middle Aged ,equipment and supplies ,medicine.disease ,Kidney Transplantation ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Endocrinology ,Cyclosporine ,Drug Therapy, Combination ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients.Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of cyclosporin dose reduction and cyclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with cyclosporin, sirolimus and corticosteroids during the first 3 months followed by either cyclosporin dose reduction or cyclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations (C(0)) from 112 patients were used to develop a population pharmacokinetic model using the NONMEM program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, cyclosporin daily dose, cyclosporin C(0) as well as other commonly used co-medications were explored.The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 10.1 l h(-1) (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or cyclosporin C(0). Moreover, CL/F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates from NONMEM.These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients.
- Published
- 2009
22. Modeling and Calculation of High Power Electromagnetic Pulse Interference on Radar
- Author
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Xiao Jin-shi, Zhang Jinhua, Liu Wenhua, Xing Chang-feng, and Zhang Shiying
- Subjects
Engineering ,business.industry ,Pulse-Doppler radar ,Main lobe ,law.invention ,Continuous-wave radar ,Bistatic radar ,Optics ,Radar engineering details ,Side lobe ,law ,Electronic engineering ,Radar ,Radar display ,business - Abstract
The high power electromagnetic pulse (EMP) with sufficient radiating energy can penetrate and interfere on all kinds of radars. This paper studies the interference effect of high power EMP on paraboloid radar and AESA radar respectively. The coupling EMP (5us duration) energy via main lobe and side lobe into a paraboloid radar antenna is calculated. The distance and other parameters at which the sensitive component in radar front end can be damaged are presented. The coupling probability of EMP (single pulse and pulse trains) into the radar antenna in scanning state via main lobe or side lobe is studied and modeled. Finally, high power EMP hazard on the AESA radar is investigated, and some results about the needed values for 10 percent of T/R units destruction are presented.
- Published
- 2008
- Full Text
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23. Study of Damage Mechanism of High Power Microwave on Electronic Equipments
- Author
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Zhang Jinhua, Xing Chang-feng, Liu Wenhua, Xiao Jin-shi, and Zhang Shiying
- Subjects
Coupling ,Engineering ,business.industry ,Rise time ,Electronic engineering ,Electrical engineering ,Waveform ,Electronics ,business ,Microwave ,Coupling coefficient of resonators ,Power density ,Power (physics) - Abstract
Currently, damage effect of high power microwave (HPM) on electronic equipments is of increasing interest. HPM can disturb, damage, or destroy many military or civil electronic equipments. In this paper, the representative HPM waveform is investigated in time and frequency field respectively, and the main characteristics (peak power, rise time, power density, etc) are analyzed and listed. HPM generation devices and radiation are also discussed. Coupling energy into electronic devices via front door and back door, as a function of coupling coefficient and the effective area, is modeled. By presenting lots of kinds of coupling modes and paths, damage effects are divided into five different classes, and damage mechanism of HPM on electronic equipments is proven in the paper.
- Published
- 2008
- Full Text
- View/download PDF
24. [Development and identifiability analysis of parent-metabolite pharmacokinetic model for risperidone and its main active metabolite 9-hydroxyrisperidone]
- Author
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Jun-Jie, Ding, Zheng, Jiao, Yun-Qiu, Yu, and Xiao-Jin, Shi
- Subjects
Adult ,Male ,Pyrimidines ,Cytochrome P-450 CYP2D6 ,Paliperidone Palmitate ,Humans ,Isoxazoles ,Risperidone ,Models, Biological ,Monte Carlo Method - Abstract
To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
- Published
- 2007
25. [Simultaneous determination of the inhibitory potency of compounds on the activity of five cytochrome P-450 enzymes using a cocktail probe substrates method]
- Author
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Zhi-Wei, Gao, Xiao-Jin, Shi, Chen, Yu, Shui-Jun, Li, and Ming-Kang, Zhong
- Subjects
Inhibitory Concentration 50 ,Tandem Mass Spectrometry ,Cytochrome P-450 Enzyme Inhibitors ,Humans ,Enzyme Inhibitors ,Chromatography, Liquid - Abstract
This study developed a method for simultaneously assessing the inhibitory potency of compounds on five major cytochrome P-450 ( CYP450) enzymes using a cocktail of probe substrates. A cocktail selective substrates consisting of the phenacetin (PN, CYP1A2), dextromethorphan (DM, CYP2D6), tolbutamide (TB, CYP2C9), omeprazole (OPZ, CYP2C19) and midazolam (MPZ, CYP3A4) was incubated with human liver microsomes. The concentrations of the substrate metabolites paracetamol, dextrorphan, 4-hydroxytolbutamide, 5-hydroxyomeprazole and 1'-hydroxymidazolam were determined by LC/MS/MS in a single assay sample. The method was validated by incubating known CYP inhibitors--alpha-naphthoflavone (ANF, CYP1A2), quinidine (QND, CYP2D6), sulfaphenazole (SUL, CYP2C9), fluconazole (FLU, CYP2C19) and ketoconazole (KET, CYP3A4) with the individual substrates and with the substrate cocktail. The IC50 values were then determined. The IC50s (micromol x L(-1)) were in good agreement with those obtained with individual substrates (alpha-naphthoflavone, 0.18 vs 0.26; quinidine, 0.058 5 vs 0.058 4; sulfaphenazole, 0.48 vs 0.45; fluconazol, 17.5 vs 11.4; ketoconazole, 0.22 vs 0.24) and with previously reported values in the literature. This cocktail probe substrate method can be utilized for the rapid simultaneous determination of the inhibition potential of compounds on the five CYP450 enzymes.
- Published
- 2007
26. [Bioequivalence assessment of pioglitazone hydrochloride oral preparation by limited sampling strategy]
- Author
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Jun-jie, Ding, Zheng, Jiao, Zhong-dong, Li, and Xiao-jin, Shi
- Subjects
Adult ,Male ,Pioglitazone ,Therapeutic Equivalency ,Area Under Curve ,Sample Size ,Administration, Oral ,Humans ,Hypoglycemic Agents ,Thiazolidinediones ,Models, Biological ,Monte Carlo Method ,Chromatography, High Pressure Liquid - Abstract
To develop limited sampling strategy (LSS) for estimation of C(max) and AUC(0-t) and assessing the bioequivalence of two pioglitazone hydrochloride (PGT) preparations.Healthy subjects (n = 20), enrolled in a bioequivalence study, were received 30 mg PGT po of reference or test formulation. The plasma concentration of PGT was determined by the validated HPLC method. A multiple linear regression analysis of the Cmax and AUC(0-t) against the PGT concentration for the reference formulation was carried out to develop LSS models to estimate these parameters. The models were internally validated by the Jackknife method and externally validated using simulated sets generated by Monte Carlo method. The best model was employed to assess bioequivalence of the two PGT formulations.The linear relationship between pharmacokinetics parameters and single concentration point was poor. Several models for these parameters estimation met the predefined criteria (r20.9). The Jackknife validation procedure revealed that LSS models based on two sampling times (C1, C2.5 and C1.5, C2.5 for C(max); C1.5, C9 and C2.5, C9 for AUC(0-t) predict accurately. Mean prediction errors (MPE) were less than 3%, and mean absolute prediction error (MAE) were less than 9%. The prediction error (PE) beyond 20% was less than 5% of total samples. Model external validation by Monte Carlo simulated data indicated that the most informative sampling combinations were C1.5, C2.5 for C(max), and C1.5, C9 for AUC(0-t), respectively. MPE and MAE of the proposed models were less than 5% , and 9% respectively. The PE beyond 20% was less than 5% of the total. Bioequivalence assessment of the two PGT formulations, based on the best LSS models, provided results similar to those obtained using all the observed concentration-time data points, and indicated that the two PGT formulations were bioequivalent.The LSS method for bioequivalence assessment of PGT formulations was established and proved to be applicable and accurate. Thus, it could be considered appropriate for PGT bioequivalence study with inexpensive cost of sampling acquisition and analysis. Key words: pioglitazone hydrochloride; limited sampling strategy; Monte Carlo simulation; bioequivalence
- Published
- 2006
27. Total and free mycophenolic acid and its 7-O-glucuronide metabolite in Chinese adult renal transplant patients: pharmacokinetics and application of limited sampling strategies
- Author
-
Jian-yong Zhong, Yunqiu Yu, Zheng Jiao, Xiao-jin Shi, Wei-yue Lu, and Ming Zhang
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Metabolite ,Urology ,Mycophenolate ,High-performance liquid chromatography ,Mycophenolic acid ,chemistry.chemical_compound ,Glucuronides ,Pharmacokinetics ,Asian People ,medicine ,Humans ,Pharmacology (medical) ,Prodrugs ,Chromatography, High Pressure Liquid ,Pharmacology ,business.industry ,General Medicine ,Blood Proteins ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Surgery ,Transplantation ,chemistry ,Free fraction ,Area Under Curve ,Female ,business ,Glucuronide ,Immunosuppressive Agents ,medicine.drug ,Protein Binding - Abstract
This study aimed to investigate the pharmacokinetic characteristics of total and free mycophnolic acid (MPA) and its 7-O-glucuronide metabolite (MPAG) in Chinese renal transplant recipients. In addition, limited sampling strategies were developed to estimate the individual area under concentration curve (AUC) of total and free MPA. Total and free MPA and MPAG concentrations were determined by high performance liquid chromatography. Whole 12-h pharmacokinetic profiles were obtained on the 10th day after operation in 12 adult Chinese de novo renal transplant recipients administrated with mycophenolate mofetil (MMF, 750 mg bid), cyclosporine and corticosteroids. Limited sampling strategies with jackknife technique, a resampling method, and Bland-Altman analysis were employed to develop equations to estimate total and free MPA AUC. The pattern of total and free MPA and MPAG plasma concentration-time curves in the cohort of patients taking lower doses of MMF was consistent with previous reports of Caucasian patients taking MMF 1 g bid, except that dose-normalized exposure of total and free MPAG was much lower in the current study than in those of the Caucasians. The mean C max and AUC0–12h of total and free MPA were 9.4 ± 3.4 mg/L, 20.2 ± 6.5 mg·h/L and 0.4 ± 0.4 mg/L, 0.7 ± 0.5 mg·h/L, respectively, whereas mean C max and AUC0–12h of total and free MPAG were 97.3 ± 32.6 mg/L, 656.0 ± 148.0 mg·h/L and 29.9 ± 8.5 mg/L, 222.0 ± 58.1 mg·h/L respectively. The mean fractions of free MPA and MPAG were 3.5 ± 2.0 and 34.6 ± 8.0%, respectively. No determinant was identified to influence the pharmacokinetics of total and free MPA and MPAG or the free fraction of MPA and MPAG. The combinations of C 2h−C 4h and C 1h-C 2h-C 3h were the best to estimate free and total MPA AUC0–12h respectively, whereas the combination of C 2h-C 3h-C 4h and C 1h-C 2h-C 4h was the best to estimate both simultaneously. This is the first time that the pharmacokinetics profile of total and free MPA and its main metabolite MPAG has been examined in Chinese adult renal transplant patients. The limited sampling strategies proposed to estimate individual free and total MPA AUC could be useful in optimizing patient care.
- Published
- 2006
28. [Effect of MDR1 polymorphic expression on oral disposition of cyclosporine A]
- Author
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Zheng, Jiao, Hui-qi, Liang, Jun-jie, Ding, Zhong-dong, Li, Xiao-jin, Shi, and Ming-kang, Zhong
- Subjects
Adult ,Male ,Mouth ,Genetics, Population ,Polymorphism, Genetic ,Genotype ,Cyclosporine ,Administration, Oral ,Biological Availability ,Humans ,Exons ,Genes, MDR - Abstract
To determine the relationship between C3435T mutation in exon 26 of the human multidrug resistant 1 gene and cyclosporine (CsA) pharmacokinetic (PK) parameters among healthy Chinese volunteers by nonlinear mixed effect model (NONMEM).Twenty healthy subjects were given orally a single dose of 500 mg CsA in microemulsion solution. Blood CsA concentrations were measured with HPLC and the genotype for the C3435T polymorphism of MDR1 gene was determined with the PCR and restriction fragment length polymorphism. The results were further confirmed by sequencing. NONMEM was performed to assess the effect of genotype on CsA PK profile.MDR1 C3435T genotype was identified as the best predictor of CsA systemic exposure. The relative bioavailability of CsA was 40% higher in subjects who carried at least one 3435C allele compared to that of TT type individuals in the study population.The MDR1 C3435T genotype offers a potential basis of mechanism to explain inter-subject differences in CsA oral bioavailability.
- Published
- 2005
29. Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data
- Author
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Z.-G. Zhao, Zheng Jiao, Xiao-jin Shi, and Mingkang Zhong
- Subjects
Phenytoin ,Adult ,Male ,Adolescent ,Metabolic Clearance Rate ,medicine.medical_treatment ,Metabolite ,Population ,Administration, Oral ,Pharmacology ,Models, Biological ,Drug Administration Schedule ,chemistry.chemical_compound ,Pharmacokinetics ,Asian People ,medicine ,Methods ,Humans ,Pharmacology (medical) ,education ,Chromatography, High Pressure Liquid ,Valproic Acid ,education.field_of_study ,Chemistry ,Body Weight ,Carbamazepine ,NONMEM ,Anticonvulsant ,Phenobarbital ,Regression Analysis ,Anticonvulsants ,Drug Therapy, Combination ,Female ,medicine.drug - Abstract
Objective: To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine-10, 11-epoxide (CBZE) in Chinese population. Methods: Serum samples at steady trough state (n = 459) were collected prospectively from 408 compliant outpatients during their routine clinical care. CBZ and CBZE concentrations were simultaneously determined by high performance liquid chromatography. Population clearance (CL) of CBZ and CBZE were estimated by nonlinear mixed effect modeling and NONMEM program with a one-compartment model of first-order absorption and elimination. Results: Total body weight (TBW), dose and concomitant medication were all important determinants of CL of CBZ and CBZE. The final regression model for CBZ was: CL(CL/F)(L/h)=0.141 x Dose(mg/d) 0.406 x TBW(kg) 0.117 ×1.23 VPA ×1.44 PHT ×1.26 PB Vd(CL/F)(L)=72.0 where VPA = 1 for patients comedicated with valproic acid and its dose greater than 18 mg/kg, otherwise VPA = 0; PHT = 1 for patients comedicated with phenytoin, otherwise PHT = 0; PB = 1 for patients comedicated with phenytoin, otherwise PB = 0.The final regression CL model for the CBZE was: CL(CL/F)(L/h)=0.686 x Dose(mg/d) 0.311 VPA x TBW(kg) 0.440 x 0.693 Vd(CL/F)(L)=175 where VPA = 1 for patients comedicated with valproic acid, otherwise VPA = 0. Conclusion: The current models, which describe CL of CBZ and CBZE in terms of patient specific details, can be used as a reference to optimize CBZ therapy in Chinese epilepsy patients.
- Published
- 2004
30. The Pharmacokinetics of Ropivacaine in Elderly Patients Undergoing Nerve Stimulator–Guided Thoracic Paravertebral Block
- Author
-
Wei Zhou, Zheng Jiao, Jun Zhang, Wei-min Liang, Wei-wei Qin, Jianghui Xu, and Xiao-jin Shi
- Subjects
medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Pharmacokinetics ,business.industry ,Ropivacaine ,Anesthesia ,medicine ,Paravertebral Block ,Cardiology and Cardiovascular Medicine ,business ,Nerve stimulator ,Surgery ,medicine.drug - Published
- 2011
- Full Text
- View/download PDF
31. Simulation of Transient EMP Effects Coupling through Apertures Using Sub-Gridding FDTD Algorithm
- Author
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Xiao, Jin Shi, primary and Ren, Xiong Wei, additional
- Published
- 2012
- Full Text
- View/download PDF
32. Calculation of the thin line electromagnetic effects in a cavity.
- Author
-
Xiao Jin-shi, Liu Wen-hua, and Zhang Shi-ying
- Published
- 2010
- Full Text
- View/download PDF
33. 6-Hydroxydaidzein Enhances Adipocyte Differentiation and Glucose Uptake in 3T3-L1 Cells.
- Author
-
Li Chen, Qun-Yi Li, Xiao-Jin Shi, Shi-Long Mao, and Yong-Li Du
- Published
- 2013
- Full Text
- View/download PDF
34. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients.
- Author
-
Zheng Jiao, Xiao-jin Shi, Zhong-dong Li, and Ming-kang Zhong
- Subjects
- *
PHARMACOKINETICS , *RAPAMYCIN , *IMMUNOSUPPRESSIVE agents , *HOMOGRAFTS , *HERBAL medicine - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? • Sirolimus is an immunosuppressive agent used for the prophylaxis of renal allograft rejection. • Several conventional pharmacokinetic and population pharmacokinetic studies have been conducted to assess the pharmacokinetic characteristics of sirolimus in White or African-American recipients. WHAT THIS STUDY ADDS? • The population pharmacokinetics of sirolimus in Chinese adult renal transplant recipients was characterized for the first time. • New drug–drug interactions between herbal medicines and sirolimus were identified as the covariates on sirolimus clearance. AIMS This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients. METHODS Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of ciclosporin dose reduction and ciclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with ciclosporin, sirolimus and corticosteroids during the first 3 months followed by either ciclosporin dose reduction or ciclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations ( C0) from 112 patients were used to develop a population pharmacokinetic model using thenonmem program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, ciclosporin daily dose, ciclosporin C0 as well as other commonly used co-medications were explored. RESULTS The typical values with interindividual variability for apparent clearance (CL/ F) and apparent volume of distribution ( V/ F) were 10.1 l h−1 (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/ F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or ciclosporin C0. Moreover, CL/ F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates fromnonmem. CONCLUSIONS These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
35. Population Pharmacokinetics of Carbamazepine in Chinese Epilepsy Patients.
- Author
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Zheng Jiao, Ming-kang Zhong, Xiao-jin Shi, Min Hu, and Jing-hua Zhang
- Published
- 2003
- Full Text
- View/download PDF
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