Objective To investigate the expression pattern and possible function of Nogo-A during neuronal growth. Methods E18 rat hippocampal neurons were primarily cultured both in high-density and low-density conditions. Immunohistochemistry and Western blot were performed to detect Nogo-A expression and distributional changes. Results Nogo-A was found in hippocampal neurons, mainly located in the cytoplasm, plasma membrane and neurites. It was detected at the proximal part of all neurites before axon formation. In axons, Nogo-A was enriched in the distal segment and axonal growth cone. In mature neurons, the fiber net work displayed a large number of Nogo-A immunoreactive varicosities. Conclusion The present results indicate that the neuronal Nogo-A may be involved in the process of neurite outgrowth and axonal projection.

AIM: To compare pharmacokinetics and relative bioavailability of telmisartan capsule (T) and telmisartan tablet(R). METHODS: 20 male healthy Chinese volunteers were enrolled in a randomized two-way crossover designs with a single-oral dose study(80 mg once per day for each preparation). The plasma telmisatan concentration was determined by HPLC- fluorescence detector. Plasma levels of telmisatan were followed up to 96 h. Area under the telmisartan concentration time curve was calculated by variance analysis and the bioequivalent was determined by two one-side t-test. RESULTS: A two-compartment model was adopted in telmisartan plasma concentration-time data analysis. The pharmacokinetic parameters of T and R in single-dose study including Cmax (μg·L-1), Tmax (h), T1/2β (h), MRT(h), AUC0-92(μg·h·L-1) were as following: 456±253 and 760±314, 1.61±0.71 and 1.08±0.36, 22.39±6.29 and 21.08±5.24, 27.02±6.23 and 24.27±5.79, 3454±1050 and 3635±1300, respectively. Statistically significant differences were observed between the parameter values of the two products in Cmax and Tmax; whereas there was no statistically significant difference between AUC0-∞μg·h·L-1 (3601±1095 and 3767±1399). The relative bioavailability for T was 97.28%±12.74%. CONCLUSION: The test telmisartan capsule is bioequivalent to the reference tablet.

Aim To investigate the effects of co-administration of Astragalus Saponin Ⅰ(ASI)and bendazac lysine(BDL)on hypertrophy of cultured rat mesangial cells and its mechanism.Methods The levels of collagen Ⅳ and laminin,the percentages of cells in S phase,the relative quantity of transforming growth factor ?1(TGF-?1) mRNA and indexes of oxidative status were assayed after the cells were incubated in different agents for 36 h.Results The percentage of S phase cells in high glucose group(HG) was greatly decreased while those of vitamin E group(VE) and co-administration groups were increased.The relative quantity of TGF-?1 mRNA and the collagen Ⅳ level in co-administration groups were significantly decreased,and the levels of total anti-oxidative capability(T-AOC),activity of catalase(CAT),GSH-PX,and SOD were greatly increased.Furthermore,the significant differences were found between low ASI(AL)group,low BDL(BL) group and co-administration of low ASI and low BDL(AL+BL) group for TGF-?1 mRNA,T-AOC and GSH-PX;the high ASI group(AH),high BDL group(BH) and co-administration of high ASI and high BDL group(AH+BH) for TGF-?1 mRNA and collagen Ⅳ,respectively. Conclusion Co-administration of ASI and BDL has synergetic effects on regulating TGF-?1,collagen Ⅳ,and radical oxidative stress,therefore,is beneficial to protecting rat mesangial cells against hypertrophy.

AIM: To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I.S.). Six rats were given AGS-Ⅳ 2.0 mg/kg by intravenous infusion for 5 min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR) mode of positive ions by using target ions at m/z 807.5 for AS- Ⅳand at m/z 803.5 for I.S. RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r=0.9992). The intra-and inter-day assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92.8%-98.4% for AGS-Ⅳ and 80.0%-90.9% for digoxin, respectively. The lower limit of quantitation (LLOQ) for AGS-Ⅳ was 0.5 ng/mL. The concentration-time curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t1/2β), clearance rate (CL), distribution volume at steady state (Vss), and AUC0-∞ were (3.46±0.52) h, (0.47±0.02) L/h, (0.76±0.16) L/kg and (4.27±0.19) μg·mL-1·h, respectively. CONCLUSION: These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.

To investigate the protective effects of bendazac lysine (BDL) on diabetic nephropathy (DN) in vitro and in vivo experiments. METHODS: After rat mesangial cells were cultured in 3 concentrations of BDL for 36 h, the percentages of S phase of cells were determined by flowcytometry; the transforming growth factor β1 (TGF-β1) mRNA level was assayed by reverse transcription PCR; and two main components of extracellular matrix (ECM), collagen Ⅳ and laminin, were determined by radioimmunoassay. Streptozotocin (STZ) induced diabetic rats were administered BDL at doses of 100, 200, 400 mg/kg for 8 weeks. The physical behavior and HbAlC levels of rats were observed. RESULTS: In the presence of high glucose and H2O2, the percentages of S phase of cells were lowered, and TGF-β1 mRNA level, collagen Ⅳ and laminin level were significantly increased. When compared with those in the high glucose group, the percentages of S phase of cells were significantly raised, and the levels of TGF-β1 mRNA, collagen Ⅳ and laminin were statistically decreased. The physical behavior of high BDL treated rats restored to be vibrant, vigorous and weight gaining, and the HbAlC level was significantly reduced. CONCLUSION: BDL has the protective effects against damage caused by DN, and is a potential drug candidate worth further study in preventing and treating DN.

Objective To investigate the incidence and distribution of aberrational karyotype in acute myeloid leukemia (AML), and study the significance of the grouping by Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) in the prognosis of AML Methods The chromosome was prepared with brief culture of bone marrow, and the karyotype was analysed by G banding technique. All the patients were grouped according to the criterion of SWOG/ECOG, and the survival function of different groups was observed by the Kaplan-Meier method.Results 56 (67.47 %) out of 83 patients had clonal chromosome aberrations. Among those 56 patients, AML with translocation (15;17) and with translocation (8;21) presented in 30 patients(53.57 %), and the other kinds of aberrational karyotypes shared the left proportion. Among the 74 followed-up patients, 42 patients were dead. Among three groups with favorable, intermediate and adverse prognosis respectively, there is a significant difference (P <0.001). The complete remission rate of favorable group is higher than that of both intermediate and adverse (P <0.05). There is no difference between intermediate and adverse groups(P>0.05). Conclusion Cytogenetic aberration is one of the important factors affecting the effect on prognosis. The criterion of SWOG/ECOG can predict prognosis objectively.

Objective To analyze the efficacy and safety of DCF and XELOX regimens in the treatment of advanced gastric cancer and to explore the appropriate chemotherapy regimen for advanced gastric cancer.Methods 63 patients with advanced gastric cancer were divided into two groups.Group A (31 patients) was administered with DCF regimen,with docetaxel 60-75 mg/m2 on day 1,5-fluorouracil 500 mg/m2 on day 1 to day 5,cisplatin 75 mg/m2 on day 1,a total cycle of 21 days.Group B (32 patients) was performed with XELOX regimen,with oxaliplatin 130 mg/m2 on day 1,capecitabine 100 mg/m2 twice a day on day 1 to day 14.Results 63 cases were eligible to analyze the efficacy and adverse reactions.The efficient rate (PR+CR) of group A and B were 58.1％ and 62.5 ％,respectively.The median survival time were 10.9 months and 11.5 months,but there were no significant difference between the two groups (P ＞ 0.05).The patients in both groups showed the similar tolerance of adverse reaction.Bone marrow suppression above level 3 in group A (16.1％) was higher than that in group B (9.3 ％).Hair loss above level 2-3 in group A was higher (77.4 ％).Hand-foot syndrome in group B (68.8 ％) was higher than that in group A (9.6 ％).Mild liver function damage in group B (37.5 ％) was higher than that in group A (16.1％).Conclusion The DCF and XELOX schemes have the similar effect in the treatment of advanced gastric cancer with the tolerate side effect.

Plasmid DNA (pDNA) is used as an important vector for gene therapy, and its wide application is restricted by the purity and yield. To obtain high-purity pDNA, a chromatographic method based on anion-exchange supermacroporous cryogel was explored. The anion-exchange cryogel was prepared by grafting diethylaminoethyl-dextran to the epoxide groups of polyacrylamide-based matrix and pUC19 plasmid was used as a target to test the method. The plasmid was transferred into Escherichia coli DH5alpha, cultivated, harvested and lysed. The obtained culture was centrifuged and the supernatant was used as the plasmid feedstock, which was loaded into the anion-exchange cryogel bed for chromatographic separation. By optimizing the pH of running buffer and the elution conditions, high-purity pDNA was obtained by elution with 0.5 mol/L sodium chloride solution at pH 6.6. Compared to the traditional methods for purification of pDNA, animal source enzymes and toxic reagents were not involved in the present separation process, ensuring the safety of both the purification operations and the obtained pDNA.
Anions ; Chromatography, Ion Exchange ; methods ; Cryogels ; chemical synthesis ; DNA ; isolation & purification ; Genetic Vectors ; isolation & purification ; Plasmids ; isolation & purification ; Porosity

OBJECTIVETo investigate the efficacy and adverse effect of DCF regimen with subsequent S-1 maintenance chemotherapy in patients with advanced gastric cancer (AGC).

METHODSSixty AGC patients without disease progression after 4 to 6 cycles of DCF regimen as the first-line chemotherapy were randomized into maintenance group and control group (30 patients each). The patients in the maintenance group received maintenance chemotherapy with S-1 (40 mg/m(2), twice daily for 14 days; 21 days for a treatment cycle) until disease progression or with intolerant toxicity, and those in the control group received optimal supportive care.

RESULTSThe response rate (CR+PR) was 33.3% in the maintenance group, significantly higher than that in the control group (3.33%, P<0.05), and the disease control rate (CR+PR+SD) also differed significantly between the two groups (73.3% vs 46.7%, P<0.05). The median time to progression was 7.9 months in the maintenance group and 6.8 months in the control group, with median overall survival time of 13.8 and 11.7 months, respectively (P>0.05). The most common adverse effect in the maintenance group included nausea, vomiting, leucocytopenia, and hand-foot syndrome; no death occurred in relation to the therapy.

CONCLUSIONS-1 maintenance chemotherapy, with a tolerable toxicity profile, can improve the RR, DCR and median time to progression in AGC patients who respond to DCF regimen, but its efficacy still awaits further evaluation.