AIM: To evaluate the effect of simvastatin on the left ventricular mass in patients with essential hypertension (EH). METHODS: 50 patients with hypertension without severe complication were randomly divided into two treatment groups: combination treatment group and hydragogue group, and 25 normal subjects without any treatment were taken as the control. The 25 patients in combination treatment group were given simvastatin and hydragogue for 12 weeks while the other patients in hydragogue group were given hydragogue during the same time. The left ventricular mass was examined from ultrasonography in all patients before and after treatment. RESULTS: The left ventricular mass index (LVMI) was higher in the two treatment groups of patients (133.61±31.02, 118.04±39.62 g·m-2) than that in the control group (88.79±22.73 g·m-2) before treatment (P<0.01, 0.0001, respectively) while the blood pressure was higher. There was no significantly difference in age, serum concentrations of total cholesterol or triglyceride, sugar and blood pressure between the two treatment groups and the control group (P>0.05). There was no significant difference in all variables between the two treatment groups before treatment. After treatment, the LVMI was decreased (133.61±31.02 vs 91.07±16.01 g·m-2, P<0.01) in the combination treatment group while there was no significant change in LVMI in the hydragogue group compared with the control group. The blood pressure in the two treatment groups was decreased to the normal. Compared with hydragogue group, the change of LVMI was higher in the combination group though the serum concentrations of total cholesterol, triglyceride or sugar were not significantly different. No significant change in serum concentrations of total cholesterol, triglyceride or sugar was found during treatment in the two groups. The change of LVMI did not correlate with the change of blood pressure, serum concentrations of total cholesterol , triglyceride or sugar in the combination treatment group(P>0.05). CONCLUSION: Being independent of the changes of serum concentrations of total cholesterol, triglyceride or sugar and blood pressure, simvastatin can inhibit the increase of left ventricular mass in patients with essential hypertension.

AIM: To investigate the effects and mechanisms of swainsonine-induced apoptosis on SGC-7901 cells. METHODES: After being treated with swainsonine, effective dose and median inhibition concentration (IC50) of swainsonine to SGC-7901 cells were examined by MTT assay. Cell cycle distribution and apoptotic rates were analyzed by flow cytometry. Expression of p53, c-myc and Bcl-2 were determined by immunocyto- chemical method, and the concentration of Ca2+ intra-cellular ([Ca2+]i ) was measured by the laser scanning confocal microscope (LSCM). RESULTS: Swainsonine inhibited cell growth of SGC-7901 in vitro, IC50 of 24 h was 0.84 μg·ml-l, and complete inhibition concentration of swainsonine was 6.2 μg·ml-l. Treated with swainsonine at the concentrations of 0.5, 1.5 and 4.5 μg·ml-l for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreased, and apoptotic trigger gene c-myc increased (P<0.05), as well as [Ca2+]i overloading, SGC-7901 cell was induced to apoptosis in the end. The percentage of S phase were 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group), the percentage of G2/M phase were 4.5%, 1.7% and 5.3%, respectively (5.5% in control group and 9.0% in 5-Fu group), and the percentage of G1/M phase was not altered. SGC-7901 cells were treated by swainsonine at the concentrations of 0.5, 1.5 and 4.5 μg·ml-l for 24 h. Compared with the control group, the percentage of S phase were increased and that of G2/M cells were decreased significantly in treatment groups (P<0.01). CONCLUSION: Swainsonine can inhibit the cell proliferation and induce apoptosis of SGC-7901 cells, the mechanisms of swainsonine-induced apoptosis may related with [Ca2+]i overloading and expression of apoptosis-related genes.

AIM: To establish a new sensitive microplate-based method to determine alpha-glucosidase inhibiting activity and provide a reliable high-throughput way for screening alpha-glucosidase inhibitors in vitro.METHODS: The fitting combination of enzyme and substrate in a certain reaction was tested.Acarbose,the most popular alpha-glucosidase inhibitor in clinical use was used to validate the established method.Calibration curve,wavelength fidelity and kinetic analysis,together with the effect of altered incubation time,temperature and pH were then studied.RESULTS:The details of assay procedure and evaluation of factors affecting the measurement are described.As little as 160 μl assay system was performed in a 96-well plate.The optimal action was finally achieved by incubated at 37 ℃,pH 7.0 for 15 min and measured at 400 nm.Results from the validation exercises by Acarbose strongly demonstrated the accuracy and reliability of the proposed approach.CONCLUSION: This method reported in the current paper makes it possible to rapidly examine large numbers of samples for the presence of alpha-glucosidase inhibitors in very small sample volumes.Such action may help to pace the development of potential oral medications from natural products protecting patients against postprandial hyperglycemic toxicity and therefore treating diabetes mellitus and the related complications.

AIM: To study pharmacokinetics and relative bioavailability of pantoprazole sodium enteric-coated test and reference tablets in healthy volunteers. METHODS: A single oral dose of 40 mg pantoprazole sodium enteric-coated test and reference tablets were given to 20 male healthy volunteers in a randomized two-way crossover design. Plasma concentrations of pantoprazole were determined by HPLC method. Pharmacokinetic parameters and relative bioavailability were calculated with DAS program to evaluate the bioequivalence of the two preparations. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The main pharmacokinetic parameters of pantoprazole sodium test and reference tablets were as follow: The values of Tmax were (3.18±0.54) and (3.30±0.47) h, Cmax were (2.98±0.83) and (2.91±0.87) mg·L-1, T1/2β were (1.86±0.41) and (1.72±0.48) h, AUC0-t were (9.51±3.71) and (9.77±4.55) mg·h·L-1, respectively. The relative bioavailability of test tablets was (102.3±19.6)%. CONCLUSION: The two preparations of pantoprazole sodium are bioequivalent.

AIM: To evaluate myocardial relaxation function changes in an adriamycin-induced cardiomyopathy model using the transmitral flow velocity to mitral annular velocity ratio (E/E'), a strong positive relationship with left ventricular filling pressure and a good indicator for evaluating left ventricular diastolic relaxation abnormality. METHODS: Twenty-eight Japanese rabbits were divided into two groups. Adriamycin was administered at cardiomyopathy model. 8 rabbits served as controls receiving the same amount of saline once a week for a total of 8 weeks. Conventional and tissue Doppler echocardiography (TDE) were performed at baseline, 4th, 6th,8th, 10th and 12th week. RESULTS: In the adriamycin-treated group, LV chamber diameter significantly increased, while ejection fraction and fraction shortening significantly decreased in 10th and 12th week (P ＜0.05). The significant changes were firstly found in 10th week. Mitral annulus systolic peak velocity (S') by TDE significantly decreased in 8th, 10th and 12th week ( P ＜0.05). The significant changes were firstly found in 8th week. The ratio of E/E' significantly increased in 6th,8th, 10th and 12th week (P ＜ 0.05). The significant changes were firstly found in 6th week. In the control group, no significant changes were found in all parameter by tissue Doppler conventional echocardiography (P ＞0.05). CONCLUSION: Myocardial function is reduced in adriamycin-induced rabbit model of dilated cardiomyopathy. The relaxation parameter (E/E') by TDE changes is earlier than contraction indices S' by TDE and conventional echocardiography in adriamycin-induced cardiomyopathy rabbits, which provides a new sensitive and reliable method to evaluate LV relaxation function.

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 compare the expression of three cyclooxygenase (COX) isoforms in the process of inflammatory pain and evaluate the analgesic effects of different protocols about usage of COX inhibitors on inflammatory pain. METHODS: Formalin was injected subplantarly to mice to induce inflammatory pain. The expression of COX-1, COX-2 and COX-3 was evaluated by radioimmunoassay and RT-PCR, respectively. For the analgesic effect assay, animals were divided into 5 groups including control, SC, NS, IN and NS + SC group. The former 4 spectively. In the NS + SC group, animals received NS398 during the first 1 month and SC-560 during the second month in the NS + SC group. RESULTS: The expression of COX-1 was higher at the late phase while that of COX-2 was higher at the early phase of inflammatory pain. The expression of COX-3 did not significantly change in the process of inflammatory pain. Additionally,behavioral assessment showed that using COX-2 inhibitors at the early phase followed by COX-1 inhibitors at the late phase could get better analgesic effect on inflammatory pain compared with single using COX-1 selective or COX-2 selective inhibitors. CONCLUSION: In brain, the expression of COX-2 increases rapidly in the inflammatory pain process while COX-1 expression does not increase till the late phase. Brain COX-3 is poorly involved in the inflammatory process. Combined use of COX-1 and COX-2 selective inhibitors may be a better protocol in inflammatory pain treatment.

AIM: To validate the alternations of flow velocity patterns in the infarct-related artery (IRA) during no-reflow phenomenon in a canine model of acute myocardial ischemia and reperfusion by transthoracic Doppler echocardiography (TTDE) combined with myocardial contrast echocardiography (MCE) by means of administration of Albunex. METHODS: Nineteen dogs first underwent 60 min myocardial ischemia and then followed by 60 min,120 min and 180 min reperfusion ( n = 6, 6 and 7, respectively). The perfusion defect area determined by MCE at 60 min myocardial ischemia was regarded as risk area (RAMCE). The perfusion defect area defined by MCE after reperfusion was considered as no-reflow area (NRAMCE). The ratio between NRAMCE and RAMCE ≥ 25 %was regarded as the development of no-reflow phenomenon and the ratio of NRAMCE to RAMCE＜25% was considered as the myocardial reflow. The coronary flow velocity parameters in IRA were determined through TTDE. RESULTS: Two dogs died during experiment and the remaining seventeen dogs completed throughout the procedure.There were seven dogs in reflow group and ten dogs in noreflow group. No significant difference was present in reflow group between at baseline and at 60 min reperfusion in systolic peak velocity (PVs), systolic velocity time integral (VT Is), corrected systolic flow duration (cFDs),diastolic peak velocity (PVd), diastolic velocity time integral (VT Id), corrected diastolic flow duration (cFDd),diastolic deceleration rate (DDR), corrected diastolic deceleration duration (cDDD) (P＞0.05), however, a significant difference was found in no-reflow group between at baseline and at 60 min reperfusion in PVs,VTIs, cFDs, PVd, VTId and cFDd (P＜0.05). The most marked alterations during diastolic phase were the increase of DDR and reduction of cDDD. CONCLUSION: The impaired microvasculature may profoundly affect the coronary flow velocity pattern in the IRA. The increase in microvascular resistance and decrease in coronary perfused pressure can contribute to the changes.Transthoracic Doppler echocardiography combined with MCE has the capability of noninvasive assessment of coronary flow velocity pattern in the IRA during no-reflow phenomenon.

AIM: To investigate the dynamic changes of ATPases and NOS activities and NO production at different anesthesia phases using thiopental and propofol andifferent anesthetic phases (induction, anesthesia, restoration, and awake), the activities of NOS and ATPase and NO production in cortex and brain stem were meagroup. RESULTS: Ca2+ -ATPase and Na+ ,K+ -ATPase activities in the cortex and brain stem were significantly decreased after administration ofthiopental and propofol,especially at induction, anesthesia, or even restoration phase of thiopental group (P＜0.05, P＜0.01) and at anesthesia phase of propofol group (P＜0.05). NOS activities and NO production decreased from induction to restoration phase with thiopental and propofol anesthesia (P＜0.01). The parameters were returned near to the normal at awaken phase. CONCLUSION: Activities of ATPases and NOS and the production of NO may mediate the anesthesia effects of thiopental and propofol in the rat cortex and brain stem.

AIM: To investigate the efficacy and safety of liduofen in the treatment of patients with osteoarthritis of the knee joint. METHODS: A randomized, double-blind, parallel-controlled, multi-centre study was adapted to compare the efficacy and safety between liduofen and Olfen-75 in 136 patients. Patients were randomly assigned into two groups: liduofen group which was received 75 mg (diclofenac) Liduofen injection (n=69) once a day for seven days and Olfen group which was received 75 mg (diclofenac) Olfen-75 injection (n=67) once a day for seven days. RESULTS: After the treatment, similar improvements for rest pain, pain on exercise, swelling of joint, pressing pain of joint, knee joint bend extend function measured using a 10 cm visual analogue scale was performed in two groups. In Olfen-75 group, the rate of efficacy was 62.69% in the 3rd day, 95.76% in the 5th day and 97.88% in the 7th day. While in liduofen group, the rate of efficacy was 57.97% in the 3rd day, 93.87% in the 5th day and 96.94% in the 7th day. In liduofen and Olfen-75 groups, the progressive rates were 56.72% and 55.07%, respectively. The total improvement rates were 89.85% and 92.54% respectively (P＞0.05), and the rates of side effects were 0% and 1.49%, respectively (P＞0.05). CONCLUSION: Liduofen is an effective and safty drug inthe treatment of patients with osteoarthritis of the knee joint. There is no significant difference on efficacy and safety between the two groups using liduofen and Olfen-75.