0.01), but the significant difference was found respectively between group C and B and between group C and A (P

Objective To explore the efficiency and safety of sodium valproate intravenous therapy on refractory status epilepsy(RSE)by diazepam in Chinese adult.Methods Twenty-five patients of RSE,consecutively admitted to West China Hospital of Sichuan University from September 1999 to May 2007,received intravenous administration of sodium valproate after being refractory to intravenous diazepam and intramuscular phenobarbitone.The efficiency and side effect of sodium valproate were then evaluated.There were ten males and fifteen females with mean age of fifty-five years.The symptoms of status epilepticus(SE)included generalized tonic-clonic status epilepticus(GTCS)(14 cases),complex partial status epilepticus(CPS)(7 cases),simple partial status epilepticus(SPS)(2 cases)and myoclonic status epielepticus(MS)(2 cases).The primary diseases prior to SE were viral encephalitis(13 cases),withdrawal of antiepilepsy drug(AEDs)(5 cases),cerebral trauma and brain surgery(3 cases),cerebral infarction(2 cases),intoxication(1 case)and cerebral palsy(1 case).Among them nine patients had a history of epilepsy.Results Of all the 25 cases of RSE,twenty-two were controlled with sodium valproate within one hour,and consciousness recovered within next one hour.No significant changes were found in blood pressure,heart rate,respiratory rate and cardiac rhythm,and no encephalopathy occurred.On the other hand,the other three cases who failed to be controlled,frequency and duration of seizure were redured.Conclusions Although intravenous sodium valproate has not been approved to be the drug of first choice for SE therapy,but it is non-sedative anti-convulsion drug that can be safely used to stop different kinds of diazepam resistant SE efficiently without obvious side effect.In addition,a quick recovery of patients' consciousness may be expected within an hour afte RSE being controlled.

Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion (I/R)-induced oncosis of cardiomyocytes and the role of mitochondrial permeability transition pore (MPTP) in it.Methods Sixty male Sprague-Dawley rats,aged 3 months,weighing 280-360 g,were randomly divided into 5 groups (n =12 each):sham operation group (group S),group I/R,sevoflurane postconditioning group (group SP),sevoflurane postconditioning + atractyloside group (group SP + ATR) and atractyloside group (group ATR).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion.2.5 ％ sevoflurane was inhaled for 5 min starting from 27 min of ischemia until 2 min after beginning of reperfusion in SP and SP + ATR groups,while 33 ％ oxygen was inhaled in the other groups.In SP + ATR and ATR groups,atractyloside 5 mg/kg was injected via the internal jugular vein at 15 min before ischemia.HR and systolic pressure were monitored and recorded and rate-pressure product (RPP) was calculated.At the end of reperfusion,the rats were sacrificed and the hearts removed for determination of myocardial infarct size.The myocardial ultrastrncture was observed by electron microscopy.The expression of Porimin (Pro-oncosis receptor inducing membrane injury) was measured by Western blot.Myocardial nicotinamide adenine dinucleotide (NAD+) content was determined by spectrophotometry.Results Compared with group S,the myocardial infarct size was significantly enlarged,the expression of Porimin was up-regulated,and NAD+ content and RPP were decreased in the other four groups (P ＜ 0.05).Compared with groups I/R and SP + ATR,the infarct size was significantly decreased,the expression of Porimin was down-regulated,and NAD+ content was increased in group SP (P ＜ 0.05),and no significant change was found in the indices mentioned above in group ATR (P ＞0.05).Conclusion Sevoflurane postconditioning can mitigate myocardial I/R injury by inhibiting MPTP opening and reducing oncosis of cardiomyocytes.

BACKGROUND:Studies have shown that Weilingxian can maintain and promote the synthesis of proteoglycan and collagen Ⅱ of chondrocyte,and protect artlcular cartilage and postpone the development of osteoarthdtis by inhibiting the level of intedeukin-1(1L-1)possibly.OBJECTIVE:Based on the previous studies,to observe the effect of Weilingxian on the proliferation of rabbit knee articular chondrocyte and transforming growth factor-β1 mRNA expression,and then to explore the role and possible mechanism of Weilingxian in the treatment of osteoarthdtis.METHODS:Knee cartilage was shredded after harvested from New Zealand white rabbits under sterile conditions,and chondrocytes were isolated and cultured by the way Of enzymatic digestion.After identifying by toluidine blue staining,the third-passage calls in the logarithmic growth phase were cultured in vitro and randomly divided into two groups after adherence.The experimental groups were cultured in DMEM with 0.01,0.05,0.1,0.5,and 1.0 mg/mL Weilingxian,while the control group was given with normal medium alone.Chondrecytes morphology was observed under an inverted phase contrast microscope,and the phenotype was identified by toluidine blue staining;Methyl Thiazolyl Tetrazolium(MTT)assay method was adopted to observe the influenca of Weilingxian with difierent concentrations on the proliferation of chondrocytes,and anti-transcription-polymerase chain-type reaction(RT-PCR)was used to assay the expression changes of transforming growth factor-β1 mRNA.RESULTS AND CONCLUSlON:Primary cultured chondrocyte was round-shaped,and most of It adhered after 24 hours,the appearance was polygonal and irregular-shaped;after passage,cell growth was faster than before,the typical appearance was slabstone-like;long spindle-shaped chondrocytes appeared after four generations;after six generations,most cells showed long spindle-shaped fibroblast-like appearance,the rate of growth also slowed down.Extracellular matrix of chondrocytes was stained to be blue by toluidine blue staining,and the nucleus was dark blue.Different concentrations of Weilingxian could promote the proliferation of chondrocytes,effect of 0.5 mg/mL group was significantly,and the peak of proliferation was on the third day.0.05,0.1,0.5,and 1.0 mg/mL Weilingxian group could promote the expression of transforming growth factor-β1 mRNA.and there was no significant difference between four groups(P＞0.05),but the peak was at 0.5 mg/mL group.Weilingxian can promote proliferation of chondrocyte and transfonlling growth factor-β1 mRNA expression,and these may be one of the possible mechanisms that Weilingxian can work in the treatment of osteoarthritis.

Objective:To compare the efficacy of individualized PEEP determined by lung electrical impedance tomography (EIT) and dynamic lung compliance (Cdyn) during lung-protective ventilation strategies in the patients undergoing general anesthesia.Methods:Sixty patients of both sexes, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18.5-28.0 kg/m 2, undergoing elective surgery with general anesthesia and endotracheal intubation in the Second Affiliated Hospital of Soochow University, were selected.Lung-protective ventilation strategy was applied in supine position after general anesthesia.The peak value of PEEP did not exceed 10 cmH 2O, with an increment/decrement of 2 cmH 2O for titration.The corresponding Cdyn value and lung EIT data were collected during titration.The patients were divided into 2 groups ( n=30 each) using a random number table method: titration first increased and then decreased group (group A) and titration first decreased and then increased group (group B). The determination method of individualized PEEP: Cdyn method was the PEEP corresponding to the maximum Cdyn value; EIT method was obtained through PV500 PC software analysis.The level and success rate of individualized PEEP determined by the Cdyn and EIT methods were compared, and the ICC consistency analysis of the determined individualized PEEP was performed. Results:Compared with the Cdyn method, the success rate of individualized PEEP determined by EIT method was significantly increased, and the level of individualized PEEP was decreased in the two group ( P<0.05). In group A, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.761, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.763, P<0.05). In group B, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.809, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.797, P<0.05). Conclusion:The agreement between the individualized PEEP determined by lung EIT method and Cdyn method during lung-protective ventilation is good in the patients undergoing general anesthesia, and the success rate of EIT method is higher, and the level of individualized PEEP is lower.

Objective To explore the relations between pulse pressure and LDL-C for elderly patients with hyperten-sion. Methods A total of 451 elderly patients with hypertension were selected and divided into four groups. Group A was 65 to 69 years of age, group B was 70 to74 years of age, group C was 75 to 79 years of age, and group D was ≥80 years of age. They were also divided into four groups according to PP levels: PP1 group ≤40 mm Hg, PP2 group 41 to 60 mm Hg, PP3 group 61 to 80 mm Hg, and PP4 group>80 mm Hg. They were divided into LDL-C group 1 (≥2.6 mmol/L) and LDL-C group 2 (<2.6 mmol/L) according to their LDL-C levels. Distribution of different age groups in four PP groups and the effects of different levels of LDL-C on pulse pressure were analyzed. Results (1) The propor-tions of PP2 group among the four age groups were 59.41%, 48.84%, 55.45% and 51.67%. The proportions of PP4 a-mong the four age groups were 4.95%, 3.88%, 3.96% and 7.50%. (2) Compared with PP1 group, the proportion of LDL-C ≥2.6 mmol/L in PP2 group, PP3 group and PP4 group was significantly increased. Conclusion (1) PP levels in different ages groups are concentrated on 41-60 mmHg. Among elderly patients with hypertension>80 mmHg, the pro-portion of patients with advanced age (≥years of age) is relatively higher. (2) LDL-C is the risk factor of increased pulse pressure for elderly patients with hypertension.

Objective To evaluate the role of the mitochondrial ATP-sensitive potassium (mito-KATP)channel in sevoflurane preconditioning-induced delayed cardioprotection against ischemia-reperfusion (I/R) injury in isolated rat hearts.Methods Seventy-two adult male Sprague-Dawley rats were randomly divided into 6 groups (n =12 each):control group (group CON),I/R group,sevoflurane control group (group SEVO),sevoflurane preconditioning group (group SWO P),5-hydroxydeconoate (5-HD) + sevoflurane preconditioning group (group 5-HD+ SWOP) and 5-HD control group (group 5-HD).The rats were exposed to 33％ pure oxygen for 1 h in groups CON and I/R.The rats were exposed to 2.5％ sevoflurane for 1 h in groups SEVO and SWOP.5-HD (a mito-KATP channel inhibitor) 10 mg/kg was injected intraperitoneally 30 min before sevoflurane preconditioning in group 5-HD + SWOP.5-HD 10 mg/kg was injected intraperitoneally in group 5-HD.The hearts were immediately removed and perfused in a Langendorff apparatus.The hearts were made globally ischemic for 30 min followed by 120 min reperfusion in groups I/R,SWOP,5-HD + SWOP and 5-HD.The expression of phosphorylated protein kinase C-epsilon (p-PKC-ε) and caspase-8 was measured by Western blot immediately before ischemia (T0) and at 120 min of reperfusion (T1).The myocardial infarct volume was measured by TTC staining.Results Compared with group CON,the myocardial infarct volume was significantly increased at T1 in groups I/R,SWOP,5-HD +SWOP and 5-HD,p-PKC-ε expression was up-regulated at T0 in groups SEVO and SWOP and at T1 in groups I/R,SWOP,5-HD + SWOP and 5-HD,and caspase-8 expression was down-regulated at T1 in group SEVO (P ＜0.05).Compared with group I/R,the myocardial infarct volume was significantly decreased at T1 in groups SWOP and 5-HD + SWOP,p-PKC-ε expression was up-regulated at T0 in groups SEVO and SWOP,and caspase-8 expression was down-regulated at T1 in group SWOP (P ＜ 0.05).Compared with group SWOP,the myocardial infarct volume was significantly increased,p-PKC-ε expression was down-regulated at T0,and caspase-8 expression was up-regulated at T1 in group 5-HD + SWOP (P ＜ 0.05).Conclusion The mito-KATP channel is involved in sevoflurane preconditioning-induced delayed cardioprotection against I/R injury in isolated rat hearts through upregulation of p-PKC-ε expression before ischemia and inhibition of cell apoptosis during reperfusion.

Objective: To evaluate the effect of nicotinamide adenine dinucleotide phosphate (NADPH) on myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Fifty-six SPF adult male Sprague-Dawley rats, weighing 220-320 g, aged 1-2 months, were divided into 4 groups (n=14 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), NADPH group (N group) and diltiazem group (D group). The model of myocardial I/R injury was established by ligation of the left anterior descending branch for 30 min followed by 2-h reperfusion in anesthetized rats.NADPH 16 mg/kg was intravenously infused over 5 min starting from 5 min of reperfusion in N group.Diltiazem 5 mg/kg was infused through the internal jugular vein starting from 10 min before ischemia until the end of ischemia.At 2 h of reperfusion, blood samples were taken from the internal jugular vein for measurement of serum LDH and cTnI concentrations, and myocardial tissues were taken for determination of infarct size and ROS level. Results: Compared with Sham group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly increased in I/R group (P<0.05). Compared with I/R group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly decreased in N and D groups (P<0.05). Compared with N group, the LDH concentration was significantly decreased (P<0.05), and no significant change was found in the cTnI concentration, myocardial infarction size or ROS level in D group (P>0.05). Conclusion NADPH can reduce myocardial I/R injury through antioxidant effect in rats.

OBJECTIVETo investigate the effects of mitochondrial membrane permeability transition pore (MPT)-opened agent diamide and MPT-closed agent cyclosporin A on arsenic trioxide (As(2)O(3))-induced apoptosis in acute promyelocytic leukemia (APL) cell line NB4.

METHODSNB4 cells were treated with As(2)O(3) alone or in combination with diamide or cyclosporin A in different concentrations. Cell apoptosis was assessed by the morphological observation, Annexin-V assay, distribution of cellular DNA contents and genomic DNA electrophoresis. The mitochondrial transmembrane potentials (DeltaPsim) were detected by flow cytometry according to the intensity of rhodamine 123 uptake in cells.

RESULTSBoth diamide and cyclosporin A significantly enhanced As(2)O(3)-induced apoptosis in NB4 cells. The DeltaPsim collapse induced by As(2)O(3) was also enforced by combined treatment with diamide or cyclospo-rin A. 1 micromol/L As(2)O(3) alone treatment for 72 hours led to DeltaPsim disruption in 27.9% of cells, while combined treatment of As(2)O(3) and diamide or cyclosporin A increased DeltaPsim disruption cells to 59.7% and 42.2%, respectively.

CONCLUSIONSAs(2)O(3)-induced DeltaPsim disruption possibly involves with thiol oxidation or crosslink of important components especially ANT-related molecules.

Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Arsenicals ; pharmacology ; therapeutic use ; Cyclosporine ; pharmacology ; Diamide ; pharmacology ; Drug Synergism ; Enzyme Inhibitors ; pharmacology ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; pathology ; Membrane Potentials ; drug effects ; physiology ; Mitochondria ; physiology ; Oxides ; pharmacology ; therapeutic use ; Sulfhydryl Reagents ; pharmacology ; Tumor Cells, Cultured

Objective To evaluate the efficacy and tolerability of zonisamide (ZNS) as add-on therapy in patients with refractory partial seizures.Methods In this Chinese muiticenter, double-blind, randomized, placebo-contrclled trial, ZNS was compared with placebo add-on therapy in 217 patients (intent-to treat (ITT) population) with uncontrolled partial-onset seizures.All patients entered a 3-month baseline period followed by a 4-week titration interval and a 12-week maintenance period.The starting dose of ZNS group was 100 mg/d, increased by 100 mg/d every week and reached the goal of 400 mg/d.The main outcome was measured by the median of the percentage of decreased seizure frequency.The secondary ouwomes points included the percentage of patients who had seizure attacks decreased by more than 50%,and adverse events.Results The median of the percentage of decreased seizure frequency in ZNS group was 33.33%, and the placebo group was 0.Thirty-eight patients (34.23%) experienced more than 50% reduction in the seizure frequency in ZNS group, compared with 19.81% of patients (21 cases) in the placebo group (χ2 =5.7159,P =0.0168) ; Moreover, 13 (11.71%) patients in ZNS group and 5 patients in placebo group were seizure free, 25 patients in ZNS group and 16 patients in placebo group who had seizure attacks decreased by more than 50%.The availability rate in ZNS group was higher than placebo group (34.23% vs 19.81%, U=2.4701, P=0.0135).The most common adverse events in ZNS group were drowsiness, fatigue, decreased appetite, gastrointestinal complaints, insomnia and constipation.Conclusion Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency as adjunctive treatment for partial-onset seizures.