The absorption of oral drug in the intestine is an important factor to determine the drug bioavailability. There are many intestinal transporters mediating drug absorption, distribution, excretion and drug-drug interaction. Understanding the transport mechanism can improve the effectiveness and safety of drug and guide clinical rational use of drugs. The in vivo and in vitro methods are used to predict the transport mechanism of drugs by intestinal transporters in the intestine. The purposes of this article are to introduce the main transporters in the intestinal tract, to explain the transport mechanism and to summarize the advantages and disadvantages of the research methods of them.

PXR, CAR and PPAR, widely distributed in the body, are important members of the nuclear receptors (NRs) family. The activities and gene expressions of drug-metabolizing enzymes (DMEs) and transporters can be regulated by the activation of NRs, which effect the drug disposition. Multidrug resistance (MDR) is the leading cause of failure in cancer therapy. NRs, including PXR, CAR and PPAR, were shown to regulate the expressions of DMEs and transporters involved in the drug metabolism and clearance, suggesting that the modulation of NRs can be considered as a new target to overcome MDR. This review described the research progress of NR family members PXR, CAR, PPAR and their transcriptional activation mechanism, the regulation of DMEs and transporters by NRs, which may provide a valuable reference for clinical medication and overcome of MDR.

Objective To evaluate the myocardial protective effect of hyperpolarized heart arrest at different temperature during cardiopulmonary bypass CPB.Methods Eighteen dogs were randomly allocated to be infused with St.Thomas solution containing 50?mol/L pinacidil and 5mmol/L K + at 37℃ (group A) or 4℃ (group B), or the standard St.Thomas solution containing K + 16mmol/L at 4℃ (group C) respectively, through aortic root after aortic clamping . The global surgical ischemia lasted 60min with the declamping of 20min .The activities of serum myocardial enzymes, and levels of lipid peroxide and adenine nucleotide of myocardium were measured.Results All paramaters showed to occur serious ischemic and reperfusion damages during the whole procedures in group C, while there were the mild damages in two hyperpolarized groups, especially in group B.Conclusions Myocardial protective effect of hyperpolarized arrest induced with pinacidil, an ATP sensitive potassium channel opener, is superior to that of traditional hyperkalemic cardioplegia , which is much more prominent in hypothermic state.

Objective To evaluate the myocardial protective effect of hyperpolarized arrest induced with ATP-sensitive potassium channel opener ,pinacidil in vitroMethods Twenty-four rabbit hearts were randomly divided into three groups : hypothermic hyperpolarized group (LH group), normothermic hyperpolarized group ( WH group), and hyperkalemic control group (group C) The isolated rabbit hearts with a Langendorff apparatus were perfused oxygenated Krebs-Henseleit's solution (K-H) for 10 min and followed by cardioplegia The cardioplegia consisted of StThomas solution with either traditional high potassium (16mmol/L KCl, 4 ℃, group C), or pinacidil 50?mol/L (4 ℃ in LH group or 37 ℃ in WH group ) with 5mmol/L KCl The hearts were subjected to 40 min perfusional occlusion and followed by 20 min reperfusionResults Hearts were arrested quickly in LH group, and a little slowly in WH group, but rebeated quickly , which were different significantly from those in group C ; Recovery of LVP and left ventricle contracility in LH group and WH group were remarkedly faster than those in group C (P

Objective To discuss Buyang-huanwu decoction preventing the formation of lower limb deep vein thrombosis (DVT) after major orthopedic surgery.Methods 60 patients were randomly divided into a treatment group and a control group.The treatment group was treated with oral liquid of Buyang-huanwu,twice a day; while the control group was treated with 5000IU of low molecular heparin through subcutaneous injection,once daily.Prothrombin time (PT),activated partial thromboplatin time (APTT),fibrinogen (FIB),D-dimer,lower limb deep vein color B ultrasonic and the wound flow changes after 48 hours were observed at 1st,7th,and 14th day after medication.Results ①)Comparison on the incidence of DVT:The incidence of DVT in the treatment group was higher than the control group at 7th day after medication,this incidence turn to equal in the two groups at the 14th day after medication,while at the end of therapy,the incidence of DVT in the treatment group was lower than the control group with significant difference (P＜0.05).②Comparison on D-dimer changes:D-dimer at the 1st and 14th day were (0.782 ± 0.472) mg/1 and (0.320 ± 0.102) mg/1 in the treatment group and (0.720±0.421)mg/1 and (0.417 ± 0.217) mg/l in the control group.Comparing with the same group before treatment [the treatment group was(0.548±0.245)mg/1; the control group was (0.560±0.195) mg/l],D-dimer was increased at the 1 st day with obvious difference (P＜ 0.05),but reduced at the 14th day,without statistical difference (P＞0.05).Conclusion Buyang-huanwu decoction did not show good effects as low molecular heparin at the beginning of the treatment,but the its whole therapeutic effects and safety was better in treating lower limb deep vein thrombosis after major orthopedic surgery.

Objective To explore the clinical effect of renal artery embolization for renal graft dysfunction.Methods A total of 17 patients with renal graft dysfunction were treated by embolizing the renal graft artery.Coil embolization was performed on 7 of the cases,and gelfoam combined with coil was used in the other 10.Results Among the 17 patients,14 discontinued immunosuppressant in 3 weeks after the embolization,and 2 discontinued after receiving low-dose cortisones for about 6 months,and showed good recovery during follow-up.The other patient underwent resection of the renal graft because of continuous fever and graft pain.After the embolization,14 cases developed 'post-embolization syndrome'.Coil migration occurred in 1 case during the procedure.One patient experienced angina during the operation,and developed myocardial infraction the day after the embolization.Conclusions Renal artery embolization is safe and effective for patients with renal graft dysfunction.By using the method,open surgery can be avoided.Attention should be paid to potential complications.

AIM:To investigate molecular regulatory mechanism of K-ras to girdin protein in COS7 cells and expression of K-ras and girdin in colorectal carcinoma tissues .METHODS:The lentiviral vector carrying K-ras gene was constructed and transfected in the COS 7 cells.The expression of K-ras, girdin proteins and other related proteins in COS 7 cells and colorectal carcinoma tissues was observed by Western blot .RESULTS:The COS7 cells with K-ras over-expres-sion showed an irregular cell morphology .The results of Western blot indicated that the downstream signal protein levels of p-ERK1/2, p-Stat3 and girdin were significantly increased in the COS 7 cells with K-ras over-expression.Transfection with the K-ras siRNA into the COS7 cells significantly reduced the protein levels of p-ERK1/2, p-Stat3 and girdin.In the color-ectal carcinoma tissues (7 cases), 5 cases had higher expression of K-ras and girdin compared with pericarcinous tissues . CONCLUSION:K-ras regulates girdin expression through the signal pathway of K-ras-ERK1/2-Stat3-girdin.

OBJECTIVE:To establish a method for determining the concentration of vinorelbine bitartrate in human plasma, and study the pharmacokinetic process of vinorelbine in human plasma. METHODS:The samples were extracted with Solid-phase extraction(SPE). LC-MS/MS was performed on the column of Agilent Extend C18 with the mobile phase of 5 mmol/L ammonium ac-etate solution(pH10.5)-acetonitrile-methano1(18∶10∶72,V/V/V)at the flow rate of 0.4 ml/min,the ion source was ESI and MRM mode was used to scan positive ion detection. The ion reaction of quantitative analysis was m/z 779.50→m/z 122.10 (vinorelbine) and m/z 811.60→m/z 224.50 (internal standard, vinblastine). 3p97 was used to calculate the pharmacokinetic parameters. RE-SULTS:The determination was not interfered by endogenous impurities,and there was no matrix effect;the lowest limit of quantita-tive analysis was 2.0 ng/ml with the linear range of 2.0-4 000.0 ng/ml(r=0.997 8);the linear range of vinorelbine in plasma was. The intra-day and inter-day precisions and accuracy results were all in line with the acceptable limit across all concentrations. t1/2γ of 30 mg/m2,40 mg/m2 Vinorelbine Emulsion for Injection groups and 30 mg/m2 Vinorelbine for Injection group were(37.958 ± 34.256)、(47.835±54.231)、(76.873±40.537)h respectively,cmax were(1 426.250±397.562)、(1 700.125±624.669)、(2 187.500± 828.040)ng/ml respectively,AUC0-48 h were(75 839±19 551)、(82 088±14 207)、(95 318±18 208)mg·h/L respectively. CONCLU-SIONS:The method is rapid,sensitive and specific,and suitable for the determination of vinorelbine and pharmacokinetic study. Metabolic processes of vinorelbine can be described as first order process of three-compartment model in cancer patients.

BACKGROUND:Silk fibroin/mesoporous glass ceramic composites have been reported to exert satisfactory repair outcomes in bone defects and hold good biocompatibility. However, the biosafety and preparation methods are rarely reported. OBJECTIVE:To investigate the preparation method and treatment outcomes of silk fibroin/mesoporous bioactive glass ceramic in skul repair. METHODS:Thirty-two Sprague-Dawley rats were enrol ed to establish the skul defect models and were thenrandomized into two groups:fibroin/mesoporous glass ceramic materials and silk fibroin were respectively implanted into the defect region in experimental and control groups. At 4 and 8 weeks after implantation, the CT examination and histological observation were performed. RESULTS AND CONCLUSION:CT examination showed that at 4 weeks after implantation, the defect area in the experimental group diminished in size, showing more dense new bones. The defect area of the control group was reduced, and a smal amount of new bones were observed. At 8 weeks after implantation, bone defect repair was completed in the experimental group, but not in the control group. The bone volume in the experimental group was significantly larger than that in the control group at different time points after implantation (P<0.05). Hematoxylin-eosin staining found that at 4 weeks after implantation, in the experimental group, there was new bone between the implant and the bone, which did not cause inflammation;there were few new bones and fibrous tissues in the control group. At 8 weeks after implantation, many new bones formed in the experimental group, with similar morphology to the host bone and the scaffold was degraded completely. Conversely, the implant material stil existed in the control group. In conclusion, the silk fibroin/mesoporous glass ceramic composite can promote bone repair.

Lactate and succinate were produced by Corynebacterium acetoacidophilum from glucose under oxygen deprivation conditions. To construct knockout mutant, lactate dehydrogenase gene (ldh) of C. acetoacidophilum was deleted by double-crossover chromosome replacement with sacB gene. Comparing with the wild strain ATCC13870, ldhA-deficent mutant produced no lactate with glucose consumption rate decreased by 29.3%, while succinate and acetate concentrations were increased by 45.6% and 182%, respectively. Moreover, the NADH/NAD+ rate was less than 1 (about 0.7), and the activities of phosphoenolpyruvate carboxylase and acetate kinase of the ldhA-deficent mutant were enhanced by 84% and 12 times, respectively. Our studies show that succinicate and acetate production pathways are strengthened by blocking lactate synthesis. It also suggests that improving NADH supply and eliminating acetate generation are alternative strategies to get high succinate-producer.
Corynebacterium glutamicum ; genetics ; metabolism ; Glucose ; Industrial Microbiology ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Lactic Acid ; metabolism ; Oxygen ; metabolism ; Phosphoenolpyruvate Carboxylase ; Succinic Acid ; metabolism