Objective To develop a target-controlled infusion (TCI) system incorporating population pharmacokinetics of propofol for children and evaluate its accuracy. Methods The TCI system was composed of a Samsung Q20 laptop computer, Graseby 3500 infusion pump, Stanpump software (Version 1.0 designed by Shafer et al. Stanford) and pharmacokinetic parameter set for propofol in children reported by Lian et al. Twenty-four ASA Ⅰ children undergoing elective orthopedic or urological surgery under general anesthesia were divided into 2 age groups: group A 3-5 yrs ( n = 12) and group B 5-10 yrs (n = 12). Radial artery and internal jugular vein were cannulated. The pediatric patients were sedated with ketamine 4 mg?kg-1 IM (uncooperative patients) or 2 mg? kg-1 Ⅳ( cooperative patients) . Anesthesia was induced with fentanyl 3 ?g?kg-1, propofol by TCI and vecuronium 0.1 mg?kg-1. Target plasma concentration of propofol was set at 3 ?g?ml-1. TCI of propofol was maintained for 60 min. Arterial blood samples were taken at 1, 3, 5, 10, 20, 30, 40, 50 and 60 min after TCI was started and at 2.5, 5, 10, 20 and 30 min after termination of TCI for determination of blood propofol concentration by HPLC. The median performance error ( MDPE) , MDPE without first five minutes ( MDPE1) , median absolute performance error ( MDAPE), wobble and divergence were calculated. Results During the first 40 minutes of TCI there was a remarkable difference between the measured plasma propofol concentration ( Cm) and the target plasma concentration (Cp). The difference was narrowing gradually until the 50 min of TCI. After the termination of TCI the Cm was significantly lower than Cp. The MDPE was 27% in group A and 26% in group B; MDPE1 was 7% (A) and 12% (B) and MDAPE 27% (A) and 26% (B) during TCI. The wobble was 23 % (A) and 24% (B) and the divergence - 0.75%?h-1 (A) and -0.80%?h-1 respectively. Conclusion The bias and divergence of our TCI system for propofol are small and the accuracy is high and a stable plasma concentration of propofol can be maintained in children.

Objective To investigate the changes in gastric intramucosal pH (pHi) and the effect of propofol on microcirculatory perfusion after myocardial ischemia-reperfusion injury in rabbits. Methods Twenty healthy adult rabbits of both sexes, weighing 2.0-2.7kg were randomly divided into two groups: A control group (n=10) and B propofol group (n = 10) . The animals were anesthetized with 2% sodium pentothal iv. Anesthesia was maintained with intermittent iv boluses of fentanyl and vecuronium. The animals were tracheotomized and mechanically ventilated during fluid and propofol infusion. PaCO2 was maintained at 35-40 mm Hg. Right internal jugular vein was cannulated for fluid and propofol infusion. Left carotid artery was cannulated for BP and HR monitoring and blood sampling. TRIP tonometry catheter (14F) was placed in the stomach. Lactated Ringer's solution was infused at 6-8 ml-kg-1 h-1 during experiment. In group B propofol was infused at 5mg-kg-1-h-1 when BP and HR were stabilized for 10 min, chest was opened and heart exposed. Left anterior descending artery (LAD) was tied for 60 min and then released for reperfusion. Hemodynamics and pHi were measured before myocardial ischemia (T0) , 60 min after myocardial ischemia (T1), 60 min (T2), 90min (T3) and 180min (T4) after reperfusion was started. Results There was no significant difference in BP and HR from T0 to T4 between the two groups. pHi decreased significantly after myocardial ischemia-reperfusion injury in both groups. pHi was significantly lower at T3 in propofol group than that in control group (P

Objective To investigate the pharmacokinetics of propofol in children of different ages after a single dose. Methods Thirty-five ASA Ⅰ or Ⅱ children were divided into 3 age groups: group A

Seven cases scheduled for cesarean section following combined spinal-epidural anesthesia,complicating the premature detachment of placenta,which occurred in the 2nd Affdiated Hospital of Wenzhou Medical College from January 1997 to December 2006,were analyzed to determine the risk factors.The results showed that the supine hypotensive syndrome after combined spinal-epidural anesthesia and anxiety before cesarean section were closely related to the premature detachment of placenta.The incidence rate of the premature detachment of placenta after combined spinal-epidural anesthesia is low,but the prermature of detachment of placenta is severe if it occurs,and the effectively prophylactic measures should be taken,including premedication with midazolam to eliminate anxiety before cesarean section and prevention of supine hypotensive syndrome after combined spinal-epidural anesthesia.

With the development of techniques and methods of medical researches, the ethic review of clinical research has become essential for healthy development of medical research. This article analyseds the practice of ethic reviews of research projects involving human subjects in our hospital and the difficulties in the process are discussed.

Objective To evaluate the effects of curcumin on the activity of NR2B and NR1 in the spinal dorsal horn in a rat model of diabetic neuropathic pain (DNP).Methods Diabetes mellitus was induced by high-sucrose and high-fat diet and intraperitoneal streptozotocin 35 mg/kg,then confirmed by fasting blood glucose level ≥ 16.7 mmol/L 3 days later in male Sprague-Dawley rats.DNP was confirmed by the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) measured on day 14 after streptozotocin administration ＜ 80％ of the baseline value.The rats were then randomly divided into 3 groups (n =27 each) using a random number table:DNP,DNP+ curcumin group (group DCur)and DNP + solvent control group (group DSC).Curcumin 100 mg· kg-1 · d-1 and corn oil 4 ml· kg-1 · d-1 were injected intraperitoneally for 14 consecutive days starting from 14 days after administration of streptozotocin in DCur and DSC groups,respectively.Another 27 normal male Sprague-Dawley rats served as control group (group C) and were fed with normal forage.At 3,7 and 14 days after curcumin injection,MWT and TWL were measured and the lumbar segments (L4-6) of the spinal cord were removed.The expression of pTyr1472-NR2B and pSer896-NR1 in the spinal dorsal horn was determined by immunohistochemistry and Western blot.Results Compared with group C,MWT was significantly decreased,TWL was shortened,and the expression of pTyr1472-NR2B was up-regulated at each time point in group DNP.Compared with group DNP,MWT was significantly increased,and TWL was prolonged at 7 days after curcumin injection,and the expression of pTyr1472-NR2B was down-regulated at 3 days after curcumin injection in group DCur.There was no significant difference in each parameter between DNP and DSC groups,and in the expression of pSer896-NR1 between the four groups.Conclusion The mechanism by which curcumin mitigates neuropathic pain in type 2 diabetic rats may be related to inhibition of up-regulation of pTyr1472-NR2B expression,while unrelated to pSer896-NR1 expression in the spinal dorsal horn.

Objective To evaluate the effect of resveratrol on the cognitive function after isoflurane anesthesia in obese rats.Methods Sixty SPF healthy male Sprague-Dawley rats,aged 4 weeks,weighing 70-80 g,were divided into 4 groups (n=15 each) using a random number table:normal diet plus 30％ O2 group (group N+O),high-fat diet plus 30％ O2 group (group H+O),high-fat diet plus 2％ isoflurane group (group H+I),and reveratrol plus high-fat diet plus 2％ isoflurane group (group R+H+I).Rats were fed a normal diet for 8 weeks in N+O group,while animals were fed a high-fat diet for 8 weeks in H+O,H+I,and R+H+I groups.Starting from 9th week,reveratrol 40 mg · kg-1 · d-1 was given into the stomach through a gastric tube for 7 consecutive days in group R+H+I,while the equal volume of 1％ carboxymethyl cellulose sodium was given instead of reveratrol in the other groups.After the end of drug intervention,animals were exposed to the mixture of 70％ nitrogen and 30％ oxygen for 4 h in N+O and H+O groups or to 2％ isoflurane for 4 h in H+I and R+H+I groups.Ten rats were randomly selected on 2nd day after inhaling isoflurane,and Morris water maze test was performed to assess the cognitive function.Five rats were randomly sacrificed on 3rd day after inhaling isoflurane,brains were removed,and hippocampi were isolated for determination of the expression of brain-derived neurotrophic factor (BDNF),tyrosine kinase B receptor (TrkB) and phosphorylated TrkB (p-TrkB) in hippocampal tissues by Western blot.The p-TrkB/TrkB ratio was calculated.Results Compared with group N+O,the escape latency was significantly prolonged on 3rd and 4th days,the exploration time spent on the original target quadrant was shortened,the expression of BDNF and p-TrkB in hippocampal tissues was down-regulated,and the p-TrkB/TrkB ratio was decreased in group-H+O (P＜0.05).Compared with group H+O,the escape latency was significantly prolonged on 2nd-5th days,the exploration time spent on the original target quadrant was shortened,the expression of BDNF and p-TrkB in hippocampal tissues was down-regulated,and the p-TrkB/TrkB ratio was decreased in group H+I (P＜0.05).Compared with group H+I,the escape latency was significantly shortened on 2nd-5th days,the exploration time spent on the original target quadrant was prolonged,the expression of BDNF and p-TrkB in hippocampal tissues was up-regulated,and the p-TrkB/TrkB ratio was increased in group R+H+I (P＜0.05).Conclusion Resveratrol can mitigates the cognitive dysfunction after isoflurane anesthesia in obese rats,and the mechanism may be related to promoting the activation of BDNF/TrKB signaling pathway.

Objective To evaluate the role of adenosine A1 receptors in hippocampal neurons in the cognitive dysfunction caused by isoflurane anesthesia in aged mice.Methods Sixteen male adenosine A1 receptor gene knockout homozygote mice (gene knockout mice) and 16 male wild-type mice,aged 18-22 months,weighing 27-32 g,were studied.Each type of mice was randomly divided into 2 groups (n=8 each) using a random number table:control group (group C) and isoflurane anesthesia group (group Ⅰ).Mice inhaled 1.4％ isoflurane in 100％ O2 for 2 h in group Ⅰ,and 100％ O2 for 2 h in group C.All the mice underwent Morris water maze test at 24 h after isoflurane or O2 inhalation.After the test,the mice were sacrificed and the hippocampal tissues were harvested to determine the number of β-amyloid1-42 (Aβ1-42) plaques (using immunohistochemistry) and expression of phosphorylated tau (p-tau) protein,and 2B subunit-containing N-methyl-D-aspartate receptors (NR2B) (by Western blot analysis).Results Compared with group C of wild type mice,the escape latency was significantly prolonged,the number of Aβ1-42 plaques was enlarged,the expression of p-tau protein was up-regulated,and the expression of N R2B was down-regulated in group Ⅰ of wild type mice.Compared with group Ⅰ of wild type mice,the escape latency was significantly shortened,the number of Aβ1-42 plaques was decreased,the expression of p-tau protein was down-regulated,and the expression of NR2B was up-regulated in group Ⅰ of gene knockout mice.There was no significant difference in the parameters mentioned above between group Ⅰ and group C of gene knockout mice.Conclusion Adenosine A1 receptors in hippocampal neurons mediate isoflurane anesthesia-induced cognitive dysfunction in aged mice,and the mechanism may be related to promotion of deposition of Aβ,phosphorylation of tau protein and inhibition of activities of NR2B.

Objective To evaluate the effects of curcumin on the expression of phosphorylated extracellular signal-related kinase (p-ERK) and phosphorylated cAMP response element binding protein (p-CREB) in the spinal dorsal horn and dorsal root ganglion (DRG) in type 2 diabetic neuropathic pain (DNP) in rats.Methods Type 2 diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin (STZ) 35mg/kg,and confirmed by fasting blood glucose level≥ 16.7 mmol/L in male Sprague-Dawley rats.Type 2 DNP was confirmed by the mechanical withdrawal threshold (MWT) and thermal withdraw latency (TWL) measured on day 14 after STZ administration ＜ 80％ of the baseline value,and the rats with type 2 DNP were randomly divided into 3 groups (n =27 each):type 2 DNP group (group DNP),curcumin group (group Cur) and solvent control group (group SC).Curcumin and corn oil 100 mg/kg (25 mg/ml) were injected intraperitoneally once a day for 14consecutive days starting from 14 days after administration of streptozocin in Cur and SC groups,respectively.Another 27 normal rats were served as control group (group C) and were fed with common forage.MWT and TWL were measured at 3,7 and 14 days after curcumin injection (T1 3),and the lumbar segment 4-6 of the spinal cord and DRGs were removed at the same time for determination of the expression of p-ERK and p-CREB (by Western blot).Results Compared with group C,MWT was significantly decreased,TWL was shortened,and the expression of p-ERK and p-CREB in spinal dorsal horn and DRGs was up-regulated at T1-3 in DNP and SC groups,and at T1 in Cur group (P ＜ 0.05).Compared with group DNP,MWT was significantly increased,TWL was prolonged,and the expression of p-ERK and p-CREB in spinal dorsal horn and DRGs was down-regulated at T2,3 in Cur group (P ＜0.05).There was no significant difference in the MWT,TWL and expression of p-ERK and p-CREB between DNP and SC groups (P ＞ 0.05).Conclusion Curcumin can attenuate type 2 diabetic DNP by inhibiting up-regulation of the expression of p-ERK and p-CREB in the spinal dorsal horn and DRG in rats.

Objective To evaluate the effects of different concentrations of parecoxib sodium on the rat sperm motility,capacitation and acrosome reaction in vitro.Methods The sperm samples from Sprague-Dawley rat epididymis were collected by Klinefelter diffusion method and randomly divided into 4 groups (n =18 each) using a random number table:control group (group C),and parecoxib sodium 100,500,1 000 μmol/L groups (P1-3 groups).Parecoxib sodium with the final concentrations of 100,500 and 1 000 μmol/L was added to the culture medium.The samples were then incubated for 5 h in an airtight container filled with 5 ％ CO2 at 37 ℃.Then sperm motility was examined in vitro at 37 ℃ and analyzed by the computer-assisted sperm analysis,including the sperm motility ((a + b)％),average path velocity (VAP),straight line velocity (VSL),curvilinear velocity (VCL) and amplitude of lateral head displacement (ALH).The capacitation effect was assessed by using the chlortetracycline staining and phase-contract microscopy.The acrosome reaction was evaluated by coomassie brilliant blue staining.Results The VAP,VSL,VCL and capacitation ability of the sperm were gradually decreased in C and P1-3 groups (P ＜ 0.05).Compared with group C,(a + b)％ in P2,3 groups and ALH in P2 group were significantly decreased (P ＜ 0.05).There was no significant difference in the acrosome reaction between groups (P ＞ 0.05).Conclusion Parecoxib sodium has significant inhibitory effects on the rat sperm motility and capacitation in a dose-dependent manner,while has no effect on the acrosome reaction in vitro.