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.

Objective To investigate the correlation of the middle cerebral artery stenosis (MCAS) and the mild cognitive function impairment (MCI),and the clinical efficacy of statins in patients with MCI. Methods Six hundred and thirty-six patientse,who received transcranial color doppler ultrasound (TCD)assay, were enrolled in our hospital hospitalization or outpatients. The simple mental state examination (MMSE) and clinical dementia rating scale (CDR) were used as cognitive function assessment indexes. Forty-four cases of MCI with MCAS and 58 cases of MCI with NMCAS were used as the treatment group , who received the atorvastatin 20 mg every day , 56 cases of MCI with NMCAS were used as the control group , who only received the routine and basic diseases treatment. One yearlater,we determined the changes of MMSE and CDRagain. Results We detected 124 patients with MCAS, 512 patients with NMCAS, and 44 cases of MCAS patients with MCI, the prevalence was 35.5%,114 cases of NMCAS in patients with MCI, with the prevalence of 22.3%, the prevalence between the two groups was statistically different. One year later, the patients in the treatment group, MMSE score was improved, the score of MCI of the MCAS group improved more significantly. Conclusion The middle cerebral artery stenosis correlated with the occurrence of MCI. Atorvastatin could improve cognitive function in patients with MCI, especially for MCI which was caused by middle cerebral artery stenosis.

Objective To investigate the correlation between cerebral artery stenosis (MCAS) and mild cognitive impairment (MCI).Methods Continuous selected 636 cases of 50-80 years old inpatients or outpatients who examined by transcranial color Doppler ultrasound (TCD) in April 2012 to April 2013 in our hospital.Keep the mini-mental state examination (MMSE) and clinical dementia rating (CDR) as the evaluation of cognitive function.Results Detected 124 cases of MCAS patients (MCAS group) and 512 cases of non-MCAS patients (non-MCAS group).Forty-four cases MCI were detected in MCAS group with the prevalence rate was 35.5％(44/124),and 114 cases of patients with MCI were detected in non-MCAS group with the prevalence rate was 22.3％ (114/512),the difference was statistically significant (P ＜ 0.05).Single factor analysis showed that there were no significant difference between two groups in waist circumference,hypertension,coronary heart disease,hyperlipidemia,smoking,diastolic blood pressure and total cholesterol,uric acid,fasting glucose,C-reactive protein (P ＞ 0.05); There were significantly different between two groups in age,gender,education level,MCAS,history of diabetes,systolic blood pressure and triglyceride,low density lipoprotein-cholesterol,high-density lipoprotein-cholesterol(P ＜ 0.05).Multiple factors analysis showed that the MCAS (OR =1.899,95％ CI 1.224-2.946),history of diabetes (OR =1.764,95％ CI 1.191-2.612),systolic blood pressure(OR =1.012,95％ CI 1.003-1.022),gender (OR =0.558,95％ CI 0.380-0.821),and age (OR =1.029,95％ CI 1.010-1.049) was the independent risk factor for MCI.Conclusion The MCAS related with MCI occurrence and development.

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.

Objective: To observe the effect of Weiyanyin on Motilin (MOT) in blood plasma of experiment bile reflux gastritis rats. Methods: To make the model of experiment bile reflux gastritis by drinking reflux liquid, compared with Domperidone.The effect of Weiyanyin on Pathological histology and MOT in blood plasma of bile reflux gastritis rats was observed. Results: The mucosal of rats in model group was damaged, amotic, and a lot of inflammatory cell could be seen, glandular organ hyperplasy and intestinal metaplasia in most of rats; At the same time the content of the MOT was decreased; Compared with model group, Weiyanyin could improve pathological histology of experiment bile reflux gastritis rats, and increase the content of MOT(P

OBJECTIVE:To provide reference for promoting the priority use of essential medicines. METHODS:The use amount ratio of essential medicines in 2 third-level grade-A hospitals in Beijing from 2011 to 2013 was statistically investigated. And the literatures related to policies of essential medicines and application were retrieved for in-depth analysis. RESULTS:The use amount ratios of essential medicines in the outpatient and emergency departments in Beijing Hospital of Ministry of Health from 2011 to 2013 were respectively 24.04%,23.10% and 22.76%;and the use amount ratios of essential medicines of inpatients were respectively 16.56%,14.52% and 12.04%. The use amount ratios of essential medicines in the outpatient and emergency depart-ments in Beijing Friendship Hospital(a pilot hospitals of cancelling drug addition medical reform)in the 3 years were respectively 21.59%,19.85% and 22.93%;the use amount ratios of essential medicines of inpatients were respectively 17.70%,17.62% and 15.89%. The use amount ratios of essential medicines did not meet 25%-30% of the requirements. CONCLUSIONS:Cancelling the drug addition and adjusting the types and quantity of essential medicine list had no obvious effects on the use amount ratios of gen-eral third-level grade-A hospitals. It is suggested to promote the priority use of essential medicines by systems of medical insurance total amount prepayment,single disease payment or diagnosis related groups-based prepayment and the free policy of essential medi-cines,rather than administrative order.

Objective To study the relationship between the genetic polymorphisms of carboxylesterase 1 gene (CESI) and the susceptibility to antituberculosis drug-induced hepatotoxicity (ATBDIH).Methods Genetic polymorphisms of CES1 in 473 tuberculosis patients with or without hepatotoxicity (200∶ 273) after antituberculosis chemotherapy were analyzed by PCR-MassArray.Results In4 tags of CES1 single nucleotide polymorphism (SNP),the frequency of the rs1968753 allele had statistical difference between the hepatotoxicity group and the no-hepatotoxicity group ( P =0.0236 ).The characteristics of anti-hepatotoxicity had been shown relationship with rs8192950 ( P =0.044,OR =0.649,95％ CI =0.426-0.989,AC/AA ) and rs1968753 ( P =0.048,OR =0.556,95％ CI =0.311-0.995,GG/AA).The diplotypes with ‘ CGC' haplotype exhibited significant protection against hepatotoxicity at one copy (P=0.048,OR=0.654,95％CI=0.430-0.996).Conclusions The genetic polymorphisms of CESI might have significant association with ATBDIH.SNP rs8192950 AC genotype and rs1968753 GG genotype might be the candidates for risk prediction of ATBDIH.

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 study the therapeutic effects of Ag85A plasmid DNA vaccines in a mouse model of multi-drug resistant-(MDR-) Mycobacterium tuberculosis infection. Methods BALB/c mice were infected with Mycobacterium tuberculosis clinical strain HB361 with isoniazid and rifampin resist-ance by intratail-vein injection and were subsequently divided into 6 groups. At the third day after infection, the mice were treated with saline (group A), vector pVAX1 (greup B), rifampin (group C), vaccae (group D), Ag85A plasmid DNA vaccines (group E),rifampin and Ag85A plasmid DNA vaccines (group F) for 60 d. The lungs and spleens from the mice were taken and their pathological changes, weight and number of myeobacterial colony were examined at the third week after the end of treatment. Results At third week af-ter the end of treatment, the gross pathological observation and histopathological examination in lung showed that the lung lesions were limited, the profile of the alveoli was relatively clear, and normal structure could be seen in 2/3 areas of the lung sections in group D, E and F. The extent of lung lesion was 50% in group D,20% in group E and F. The pathological changes in group A, B, and C were more severer than those in group D, E and F. Compared with group A, the colony-forming units (CFU) in the lungs from mice in group D,E and F decreased 52%, 68%, 78%, respectively. The CFU in the spleens from mice in group D,E and F decreased 48%, 65%, 79%, respectively. Conclusion Ag85A plasmid DNA vaccines alone or Ag85A plasmid DNA vaccines along with chemotherapy have significant therapeutic effects on the mouse model of MDR-Mycobacterium tuberculosis infection.