Aim The pharmacokinetic parameters and relative bioavailability of capsule A(Maiwei Pharmaceutical Co Ltd, Beijing, China) and capsule B (Xianjing Pharmaceu-tical, Hunan, China) were studied. Methods A single oral dose of 600 mg gemfibrozilof these two kinds of capsules was given to 12 chinese healthy male volunteers in anopen, randomized crossover study. Plasma levels were determined with HPLC-UVmethod. Results The plasma concentration-time curve was fitted to 1-compartmentopen model with a first order and lag time absorption and the major pharmacokineticparameters of capsules A and B were shown respectively as following: C max(32. 69?5. 67 )and (29. 41?2. 60) mg?L-1; Tmax (1. 01?0. 14) and (1. 13?0. 37) h, t1/2ka(0. 46 ? 0. 18) and (0. 62 ? 0. 20) h; C max (1. 11 ? 0. 32) and (1. 32 ? 0. 26) h; MRT(2. 14 ? 0.27) and (2. 37 ? 0.26) h; AUC (91.7 ? 13.2) and (82.2 ? 7. 38) mg?h? L-1. There were no significantly differences between the pharmacokinetic parame-ters of capsule A and B. The relative bioavailability of the capsule A was (110 ? 9) % ascompared to the capsule B. Conclusion The two kinds of capsules have the equivalentbiological effects.

Objective To evaluate the role of the expression of protein kinase Cγ and Cα in spinal dorsal horn in the metabotropic glutamate receptor subtype 5 (mGluR5)'s participation in the development of morphine tolerance in rats. Methods Thirty-two male SD rats in which the intrathecal (IT) catheter was successfully placed were randomly divided into 4 groups (n = 8 each): control group (group C), morphine tolerance group (group M), antisense oligodeoxynucleotide (ODN) plus morphine group (group ANT) and mismatch ODN plus morphine group (group MIS). Rats in group M received 0.9% normal saline (NS) 5 μl twice a day for 8 days, and IT morphine 15 μg was injected simultaneously at 6, 7 and 8 days twice a day. Rats in group ANT and MIS received IT antisense and mismatch ODN 30 nmol (in 0.9% NS 5 μl) twice a day for 8 days respectively and IT morphine 15 μg was injected simultaneously at 6, 7 and 8 days twice a day. Rats in group C received NS instead twice a day for 8 days. Paw-withdrawl threshold (PWT) to thermal and mechanical stimulation was measured at 6, 7 and 8 days after ODN injection (T1-3). The animals were killed on 9th day (T4) and the lumbar segment of the spinal cord was removed for determination of the expression of mGluR5, PKCα and PKCγ mRNA (by RT-PCR), PKCαand PKCγ ( by Western blot). Results PWT to thermal and mechanical stimulation was significantly higher at T1.2in group M and MIS and at T1.3 in group ANT, the expression of mGluR5 mRNA, PKCα and PKCγ was significantly higher at T4 in group M and MIS, and mGluR5 mRNA expression was significantly lower at T4 in group ANT than in group C ( P ＜ 0.05). PWT to thermal and mechanical stimulation was significantly higher at T2.3, while the expression of mGluR5 mRNA, PKCα and PKCγ lower at T4 in group ANT than in group M ( P ＜ 0.05). Conclusion The expression of protein kinase C in spinal dorsal horn plays an important role in the mGluR5's participation in the development of morphine tolerance in rats.

Objective To investigate the effects of recombinant human erythropeietin(rh-EPO)on Bid mRNA and caspase-3 activity in the brain after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the possible mechanism of the neuroprotective effect of rh-EPO.Methods Ninety 7 day old male SD rats weighing 12-18 g were randomly divided into 3 groups(n=30 each):group Ⅰ sham operation(S);group Ⅱ hypoxia-ischemia group(HI)and group Ⅲ rh-EPO.The animals were anesthetized with ether.Left common carotid artery was ligated with 4-0 silk and 3 days later the animals were placed in a 2 L airtisht vessel filled with 8%O2-92%N2 at 2-3 L/min for 2 h in group Ⅱ and Ⅲ.rh-EPO 3 000 IU/kg in 4 ml/kg normal saline(NS)was administered intraperitoneally after induction of hypoxia-ischemia(HI)in group Ⅲ while in group Ⅱ NS 4 ml/kg was given IP instead.Six animals in each group were killed at 6,12,24,48 and 72 h(T1-5)respectively after IP NS or rh-EPO.Their brains were removed for determination of Bid mRNA expression(by RT-PCR)and caspase-3 activity(by colorimetric method).Results The expression of Bid mRNA was up-regulated and caspase-3 activity was significantly increased in the brain at T1-5 in HIBD group(group Ⅱ)as compared with sham operation group.rh-EPO administration significantly reduced the increase in Bid mRNA expression and caspase-3 activity in the brain induced by hypoxia-ischemia.The expression of Bid mRNA was positively correlated with the caspase-3 activity.Conclusion rh-EPO has protective effects on the brain against hypoxia and ischemia by decreasing the expression of Bid mRNA and caspase-3 activity in the brain.

Objective To investigate the effect of ultrasound-guided transversus abdominis plane (TAP)block on the efficacy of postoperative analgesia in parturients undergoing selective cesar-ean delivery.Methods Eighty ASA Ⅰ or Ⅱ parturients recruited for selective cesarean delivery under combined spinal-epidural anesthesia were randomly divided into two groups(n =40 each):TAP group (group T)and control group(group C).After cesarean delivery,bilateral of ultrasound-guided TAP block were performed,20 ml of 0.5% ropivacaine was injected in each side in group T,while TAP was not done in group C.Both groups received patient-controlled intravenous analgesia (PCIA)after cesarean delivery.The resting and exercise visual analogue scale (VAS)scores,Ramsay sedation score and the Bruggrmann comfort scale(BCS)score were evaluated at 2,4,6,8 and 24 h after operation. The consumption of sufentanil within 24 h after operation,the number of successfully delivered doses (D1 )and the number of attempts (D2 )within 24 hr after operation were recorded.D1/D2 was calculated.The parturients satisfaction and the adverse reactions were also recorded.Each parturient was assessed postoperatively by a blinded investigator.Results The consumption of sufentanil within 24 hr after operation,the resting and exercise VAS scores at 2,4,6 hr after surgery were significant-ly lower,while the BCS score,the value of Dl/D2 and the degree of satisfaction were higher in group T than those in group C (P <0.05).There were no adverse reactions in both groups.Conclusion Ultra-sound-guided TAP block reduces the postoperative sufentanil consumption,enhances the efficacy of post-cesarean analgesia of the parturients.Comfort and satisfaction are achieved in the parturients of the group T.

Phospholipase A_2 (PLA_2) inhibitor quinacrine was used to explore protective effect on multiple organ dysfunction (MOD) caused by intestinal ischemia-reperfusion (I/R) in rats. Gut I/R caused the increase of gut PLA_2 activity and induced endotoxemia and bacteriemia. Pretreatment with intravenous quinacrine 10mg?kg~(-1) attenuated bacteria and endotoxin translocation,markedly lowered the levels of thromboxane A_2 and prostacyclin I_2 in blood,and provided protection from the development of vital organs dysfunction. As a result,the survival rate in pretreatment group increased by 25%. The results demonstrate that gut I/R promotes gut barrier failure,then contributes to the development of MOD by allowing bacteria or endotoxin reaching the circulation. PLA_2 and PLA_2-dependent lipid mediators play an important role in the development of gut I/R injury and MOD. Intravenous quinacrine has protection against MOD resulting from gut I/R.

Objective: We investigated experimentally the changes of intestinal immunity following shock and resuscitation after trauma. Method:The experimental model was made in rats, which underwent laparotomy, then bleeding and reinfusing through the right fetmoral artery. Result: The concentration of IgA following shock and resuscitation were significantly higher than that before shock.. The concentration of IgA 24 h following resuscitation was the lowest, and was significantly lower than that at the end of shock.. The endotoxin in portal vein following shock and resuscitation were higher than that before shock.. The endotoxin level 24 h following resuscitation was the highest, and markedly higher than that at the end of shock. Conclusion: The traumatic shock and resuscitation are capable of causing intestinal immunosuppression and endotoxemia.

Objective:To determine the pharmacokinetics of continuously infused midazolam in patients during intensive care. Method: The study involved six critically ill patients who required sedation to facilitate controlled ventilatory support. The infusion rate of midazolam was adjusted individually to achieve an appropriate level of sedation. Blood samples were taken during and after the continuous infusion of midazolam to measure plasma concentration of midazolain with high performance liquid chromatography,and pharmacokinetic parameters were calculated. Result:The mean value of elimination half-life was 5.09 h(range: 3.19-7.30h), and the volume of distribution was 64.45L(range: 10.41-135.25L). The clearance was 7.29L/h, Conclusion:Clinical pharmacokinetics of midazolam in critically ill patients is highly variable. The increased volume of distribution in the patients is the major determinant for the slower elimination of midazolam.

Objective: To investigate the effects of pentoxifylline (PTX) on oxygen free radicals induced myocardial injury. Method: An in vivo myocardial impairment model was developed in SD rat with exogenous oxygen free radicals. The changes cardiac performance and serum malonylaldehyde (MDA), lactic acid, cretine phosphokinase (CK) levels were tested before and at different interval after I. V. administration of oxygen free redieal. Result: Myocardial performance after oxygen free radicals administration was significantly depressed compared to the baseline values (P

0.05 ),the O- 2 production increased significantly (P

Objective To evaluate the efficacy of PTX on the global cerebral ischemia reperfusion injuryMethods The global cerebral ischemia of gerbils was induced by clamping bilateral carotid arteries for 30 min , then declamping with the reperfusion lasting 90 min At the beginning of ischemia , PTX 25mg?kg -1 or 50mg?kg -1 was administered intravenously by mini infusion pump In another group , PTX 25mg?kg -1 was infused at the beginning of reperfusion In sham operated and control groups the same volume of 0 9% NaCl were infused 0 2% Even's blue 1ml?100g -1 was injected intraperitoneally At the end of experiment , The gerbils were decapitated to be preserved at -70℃ for measurement of water contents of whole hemispheres , cerebral superoxide dimutase (SOD) activity, malonyldialdehyde (MDA) content and Even's blue content Results As compared with those in control group, at the beginning of ischemia or reperfusion ,the administration with PTX 25mg?kg -1 significantly reduced the cerebral water content (P