BACKGROUND: How to choose traditional Chinese remedy to treat cerebrovascular disease, not only improving the brain blood supply but also not affecting the blood pressure and heart rate, has been a promising research.OBJECTIVE: To study the role of yangyintongnao granule on average blood pressure and heart rate in anaesthetized dog.DESIGN: Complete grouping design and randomized controlled study based on hybrid dog.SETTING: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University of Chinese PLA and Department of Pharmacology, Faculty of Preclinical Medicine, Fourth Military Medical University of Chinese PLA MATERIALS: The experiment had finished by Cardiovascular Laboratory of Physiology Department in the Fourth Military Medical University of Chinese PLA from March to June 2003. Totally 23 healthy hybrid dogs in either sex were selected. These dogs were divided randomly into 4 groups: high dose group of yangyintongnao( n = 8), moderate dose group of yangyintongnao ( n = 6), low dose group of yangyintongnao( n = 5) and saline group( n = 4).METHODS: Anesthetic dogs in high, moderate and low dose group of yangyintongnao granule were given different doses of yangyintongnao granule: 2 g/kg, 1 g/kg and 0. 5 g/kg respectively. All doses of drug were calculated based on the body mass of dogs, and the drugs were dissolved in 100 mL saline and given through the gastric canal. Dogs in saline group were perfused with equal saline. Aortic average blood pressure was measured by femoral artery intubation via a piezometric transducer. Heart rate was obtained from R-R intervals of a standard Ⅱ lead of electrocardiograph(ECG). The mean blood pressure and heart rate were recorded 0. 5, 1, 1.5, 2.0,3.0, 4. 0, 5.0, 6. 0 hours after treatment.MEAN OUTCOME MEASURES: The changes of blood pressure and heart rate at different time before and after medication.RESULTS: Totally 29 dogs were brought into the final analysis. Blood pressure: The mean blood pressure was reduced -5.4% to -6. 2% respectively in high dose group and moderate dose group after treatment. But in low dose group the average blood pressure sometimes increased sometimes decreased, mainly decreased. It increased by 6.6% ( P ＞ 0. 05) and decreased by -4. 1% ( P ＞ 0.05) at maximum. The average blood pressure in saline group changed by - 9.6% ( P ＞ 0.05). Heart rate: The heart rate in high and medium dose group gradually reduced as time went on. It reduced by - 4. 4%, - 12.2% and - 9.5% respectively in high, moderate and low doses group. The change in each group was not statistically significant as the same in saline group( P ＞ 0.05).CONCLUSION: Yangyintongnao granule has no significant influence on average blood pressure and heart rate.

Objective The combination of vasopressin and epinephrine has long been thought to be more effective then epinephrine alone in cardiopulrnonary resuscitation (CPR), evidence is not enough to make such a clinical recommendation. This meta-analysis compared the efficacy of vasopressin and epinephrine used together versus epinephrine alone in cardiac arrest (ca) in order to verify the truth. Method MEDLINE and EMBASE were searched for the data of randomized trials in comparing the results of co-administration of vasopressin and epinephrine with epinephrine alone in adults with cardiac arrest. The primary outcome was the restoration of spontaneous circulation (ROSC). Results Six randomized trials in 485 articles were analyzed. We failed to get the results supporting the effectiveness of this combination therapy, except for the rate of 24 hours survival (OR: 2.99,95%CI:1.43 ~ 6.28). No evidence supported that vasopressin combined with epinephrine was better than epinephrine alone in ROSC. Conclusions This systematic review indicates the combination of vasopressin and epinephrine is better for the rate of 24 hpurs survival in only 122 patients. Further investigation is needed to support the use of combination therapy for cardiac arrest.

Objective To investigate the variation of biomarker of coagulation, anti-coagulation, fibrinolysis in elderly critical patients and find out whether they are related to the disease severity. Methods Sixty-seven patients were no less than 60 years old. Eligible criteria: coincidence with the diagnostic criteria of systemic inflammatory response syndrome (SIRS) and APACHE Ⅱ score was no less than 10 scores. Blood sample was drawn from the venous for the test of biomarker (APTT, PT, TT, D-D, Fib, AT-Ⅲ , PC, PAI-1). According to the existent status,all the patients were divided into two groups:survival group (43 cases) and death group(24 cases) ,meanwhile,according to the diagnostic criteria of MODSE,all the patients were divided into MODSE group (30 cases) and non-MODSE group (37 cases). Results There were significant differences in APACHE Ⅱ score between MODSE group and non-MODSE group, survival group and death group [(25.83 ± 1.19) scores vs(18.1±20.73) scores and(18.81±0.72) scores vs(26.50 ± 1.42) scores](P <0.01). The PT and D-D in MODSE group anti death group were higher than those in non-MODSE group and survival group, the differences were significant (P <0.05),while the activity of AT-Ⅲand PC in MODSE group and death group were lower than those in non-MODSE group and survival group, the differences were significant (P <0.05). The PT,D-D and PAI-1 were positively correlated to APACHE Ⅱ score (related coefficients were 0.328, 0.308, 0.335,P <0.05). The AT-Ⅲ and PC were negatively correlated to APACHE Ⅱ score (related coefficients were -0.469, -0.559,P <0.01). Conclusions The abnormality of eoagnlation-fibfinolysis system exists in elderly critical patients. The extended PT, elevated D-D and PAI-1 ,descended PC and AT-Ⅲ are the hints of disease severity and poor prognosis.

AIM:To observe the characterization in neural cells derived from the hippocampus of embryonic rats and to examine the effect of myelin-associated glycoprotein(MAG) on the proliferation,differentiation and neurite growth of neural stem cells(NSCs).METHODS:The hippocampus cells of embryonic rats were isolated and cultured in vitro.The expressions of nestin and doublecortin,the marks of NSCs,were observed by immunocytochemical method.The rate of proliferating cells was examined by BrdU immunocytochemistry.The average neuronal neurite length and the percentage of differentiated neurons were detected by immunocytochemistry staining.RESULTS:The hippocampus cells of 16 days old embryonic rats had the characteristics of NSCs.The percentage of differentiated neurons(?-tubulin Ⅲ-positive cells) was 18.17%?2.79% and the average neuronal neurite length was(136.27?33.66)?m,seven days after the differentiation initiated in vitro in control group.After NSCs were treated with MAG-Fc(200 ?g/L),the percentage of differentiated neurons and the average neurite length were decreased,respectively,to 10.05%?3.42%(P0.05).CONCLUSION:MAG-Fc inhibits the differentiation and neurite growth of the NSCs,but has no effect on the proliferation.

[Objective] To investigate the inhibitory effect of CTLA-4Ig fusion protein on atherosclerosis in the mice with an apolipoprotein-E gene defect fed on cholesterol diet.[Methods] Twenty-five male 10-week-old ApoE-/- mice were selected and fed on cholesterol diet for 4 weeks,5 out of which were executed at random as control group and their pathological sections were kept to observe the early fatty streaks.The other 20,divided into CTLA-4Ig treatment group,PBS group,IgG1 group,and blank group at random,5 in each.Three groups were given intraperitoneal injection of CTLA-4Ig (10 μg per time),PBS (100 μL per time),Rat-IgG1 (10 μg per time) respectively,twice a week,for 8 weeks.The blank group has no treatment.Followed by 8-week treatment,the whole aorta from the root to crotch of iliac artery was separated after anesthesia with the intraperitoneal injection of 1 % pentobarbital.Subsequently,the area ratio of plaque and lumen,the thickness ratio of endangium and tunica media,the lipid-soaking extent intra-plaque and the content of collagen fibrils and smooth muscle cells intra-plaque were analyzed by image-processing soft.[Results] After fed on cholesterol diet for 4 weeks,there were obviously atherosclerosis in the aorta in the ApoE-/- mice.There were typical atherosclerotic plaque in ApoE-/- mice fed on cholesterol diet after another 8 weeks.The area ratios of plaque and lumen in CTLA-4Ig group,PBS group,IgG1 group,and blank group were 0.27 ± 0.08,0.40 ± 0.08,0.43 ± 0.08,and 0.46 ± 0.10,and obviously increased than those in control group (0.05 ± 0.01,P ＜ 0.05).The thickness ratios of endangium and tunica media in four groups were 2.6 ± 0.6,6.0 ± 0.9,5.7 ± 0.8,and 5.9 ± 0.6 and obviously increased than those in control group (0.5 ± 0.1,P ＜ 0.05).The lipid-soaking extent intra-plaque in experimental groups were 26.0 ± 3.0,40.8 ± 5.7,40.6 ± 3.0,and 43.2 ± 5.7,and were obviously increased than those in control group (7.2 ± 1.4,P ＜ 0.05 ).It was found that the area ratio of plaque and lumen,the thickness ratio of endangium and tunica media,and the lipid-soaking extent intra-plaque in CTLA-4Ig group were significantly lower than those in PBS group,IgG1 group,and blank group (P ＜ 0.05),but there was no significant difference in those between the PBS group,IgG1 group,and blank group (P ＞ 0.05).The content of collagen fibrils in CTLA-4Ig group were 16.0 ± 1.1 and higher than those in PBS group,IgG1 group,and blank group (8.6 ± 1.2,9.2 ± 1.5,and 9.0 ± 1.3,P ＜ 0.05).The content of smooth muscle cells in plaque in CTLA-4Ig group were 11.8 ± 1.0 and higher than those in PBS group,IgG1 group,and blank group (7.8 ± 0.8,7.5 ± 0.9,and 7.3 ± 0.7,P ＜ 0.05).There was no significant difference in content of collagen fibrils and smooth muscle cells between the PBS group,IgG1 group,and blank group (all P ＞ 0.05).[Conclusion] CTLA-4Ig fusion protein could evidently inhibit the atherosclerosis progression and enhance the stability of plaque through increasing the content of collagen fibrils produced by smooth muscle cells intra-plaque in ApoE-/- mice fed on cholesterol diet.

Objective To establish a simple,easily-producible and practical cardiopulmonary cerebral resuscitation model in rabbits.Method Cardiac ventricular fibrillation was induced in 27 New Zealand rabbits by alternating electric current.The rabbits were randomly divided into three groups according to the duration of untreated cardiac arrest(CA):CA-8 min group(n = 9),CA-5 min group(n = 9)and CA-3 min group(n = 9).All animals received cardiopulmonary resuscitation(CPR)until return of spontaneous circulation(ROSC).The sample of vein blood was collected for the measurement troponin I level at 4 hours after ROSC.The animals were sacrificed at 72 hours after ROSC,hippocampus were removed and fixed in 3%formalin,and coronal sections were analyzed by TUNEL staining and N1SSLE staining.The other two animals without ventricular fibrillation or CPR served as sham-operated group.One-way ANOVA or Mann-Whitney rank was used to determine the statistical significance among the three groups.R×C test was used for ROSC,LSD test for multiple comparisons,and t test for comparisons of means between two independent samples.A two-tailed value of P＜0.05 was considered statistically significant.Results There were no differences in rate of ROSC among groups.No animals survived until 72 hours after ROSC in CA-8 min group and CA-5 min group,while three animals in CA-3 min group survived.In group CA-8 min,CA-5 min and CA-3 min,the survival time of animals after ROSC were(1.67 ± 2.55)h,(37.78 ± 30.27)h,(12.0 ± 14.97)h,respectively.There were significant differences in the survival time of animals after ROSC and troponin I level after ROSC 4 h between CA-3 min group and the other two groups(P＜0.05).Compared with animals in CA-3 min group,sham-operated animals(n = 2)did not have neuronal degeneration or TUNEL positive cells in the hippocampus CA1 area.Conclusions CPR initiated as soon as 3 min after CA can give longer survival tome to the rabbits.The rabbits have neuronal degeneration and apoptosis in the hippocampus CA1 area at 72 hours after ROSC.It may be an ideal animal model for investigation on CPCR.

Objective To study the effects of mild hypothermia (MH) on blood coagulation and cerebral microcirculation in rabbits after cardiopulmonary resuscitation (CPR). Method A total of 24 New Zealand rabbits were randomly (random number) divided equally into normothermic group (NT) and MH group. CPR model was established by ventricular fibrillation induced by using alternating current. The rabbits of NT group were observed for 12 h in room temperature after restoration of spontaneous circulation (ROSC). The mild hypothermia was induced in the rabbits of group MH by surface cooling after ROSC, and maintained for 12 h after the aimed low temperature reached. The PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio of prothrombin), D-dimmer (DD) , blood platelet count (BPC) , anti-thrombin Ⅲ activity (AT-Ⅲ) and protein C activity (PC) were measured before CPR and 4 h, 8 h and 12 h after ROSC, and at the same time the cerebral microcirculation was measured by using PERIMED Multichannel Laser Doppler system. One-way ANOVA or Mann-Whitney rank was used to determine the statistical significance between two groups. LSD-t test was used for multiple comparisons,t test for comparisons of means between two independent samples, and Pearson correlation test for correlation analysis. Results The PT, APTT and INR showed a trend of gradually shortening during the course. The APTT in 12 h after ROSC was significantly shorter than that before CPR (23.32 ±5.19 vs. 29.53 ±5.10,P = 0.025), and the activity of AT- Ⅲ and PC were decreased significantly. Compared with the group NT,the PT, APTT and INR in group MH were increased significantly, while there were no differences in the activity of AT- Ⅲ, PC and D-D between two groups. The rates of cerebral microcirculation in group NT before CPR and 4 h, 8 h and 12 h after ROSC were 401.60 ± 11.76 mL/min, 258.86 ± 34. 58 mL/min,317.59 ± 23.36 mL/min and 371.98 ± 5.79 mL/min, respectively, and those in group MT were 398.18 ±12.91 mL/min, 336.19 ± 19.27 mL/min, 347.76 ± 13.80 mL/min and 383.78 ± 3.29 mL/min, respectively. There were significant differences between two groups at each interval after ROSC (4 h: t = - 6.025,df=16, P=0.000;8 h: t= -2.942, df=12, P=0.012;12 h: t= -3.959, df=8, P=0.004). The Pearson correlation test showed that the rate of cerebral microcirculation was positive correlated with APTT after ROSC (4 h:R =0.503,P=0.033;8 h:R=0. 565,P=0. 035;12 h:R=0. 774,P=0. 009), and was not correlated with the other blood coagulants. Conclusions The mild hypothermia led to the inhibition of blood coagulation and improved the cerebral microcirculation concomitantly, which may be one of the mechanism of cerebral protection.

Objective To investigate the changes of brain edma and expression of blood high mobil-ity group box 1(HMGB1) and calcium binding protein S100B after traumatic brain injury (TBI) in IL-4 knockout (IL-4 KO) mice,and to explore the effects of IL-4 on traumatic brain injury. Methods Twenty male wild type ( WT) or twenty male IL-4 KO BALB/cJ mice were randomly divided into WT sham TBI group,WT TBI group,IL-4 KO sham TBI group and IL-4 KO TBI group(n=10 in each group).The model of traumatic brain injury was established by the free falling body epidural impact method,then the brain water content was measured. The expression of aquaporin-4 ( APQ4) and HMGB1 in injured brain of each group was detected by Western blot,and the concentration of HMGB1 and S100B in serum was detected by ELISA assay. Results ( 1 ) The brain water content of injured lateral brain of BALB/cJ mice with IL-4 gene knockout was significantly higher than that of wild type mice with brain injury model (WT group: (80.03± 0.35)％;IL-4 KO group:(81.93±0.41)％;P<0.05).(2) The Western blot showed that the expression of AQP4 and HMGB1 in brain tissue of BALB/cJ mice with IL-4 gene knockout was significantly higher than those in wild type mice after traumatic brain injury. ( 3) The results of ELISA showed that the levels of HMGB1 and S100B in the serum of IL-4 knockout BALB/cJ mice were significantly higher than those of wild type mice (HMGB1:WT group:(9.21±0.74)ng/ml;IL-4 gene knock-out group:(13.39±1.33)ng/ml,P<0.05;S100B protein:WT group:(11.11±0.84)pg/ml;IL-4 KO group: (18.11±2.02)pg/ml,P<0.05 ). Conclusion The brain tissue water content and the expression of APQ4 are increased in IL-4 KO TBI mice.The expression of HMGB1 in brain issue and serum and S100B in serum are also up-regulated.

OBJECTIVETo evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in murine liver tissue.

METHODSFulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intraperitoneally (ip) in galactosamine (GalN) sensitized mice. Two separate experiments were designed, including saline control group, fulminant hepatitis group and oxymatrine pretreated group (50 mg/kg, intraperitoneally, bid x 3 days). The levels of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysaccharide. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells under transmission electron microscope (TEM). Liver samples at 7.5-hour time point were taken for hematoxylin-eosin (HE) staining and immunohistochemical staining of Fas and its ligand (FasL).

RESULTSAs compared with the fulminant hepatitis group, the levels of serum tumor necrosis factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour time point were all significantly decreased (P < 0.05 and P < 0.01 respectively). Hepatocyte apoptosis in mice at 5-hour time point was significantly inhibited (P < 0.01). Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably (P < 0.01 and 0.05 respectively) when compared with the saline control group.

CONCLUSIONSOxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may block hepatocyte apoptosis and subsequent necrosis through downregulating the production of serum tumor necrosis factor alpha and the expression of Fas and Fas ligand in liver tissue.

Alkaloids ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; Apoptosis ; drug effects ; Fas Ligand Protein ; Hepatitis, Animal ; blood ; drug therapy ; mortality ; Hepatocytes ; drug effects ; pathology ; ultrastructure ; Liver ; drug effects ; metabolism ; pathology ; Membrane Glycoproteins ; biosynthesis ; drug effects ; Mice ; Microscopy, Electron ; Quinolizines ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; drug effects ; metabolism ; fas Receptor ; biosynthesis ; drug effects

Objective To explore the effect of long-term enhanced external counterpulsation(EECP)on endothelium-dependent and endothelium-independent vasorelaxation in the carotid arteries of atherosclerotic piss. Method Totally 18 20-day-old male infant pigs were randomly divided into 3 groups according to feeding given: the normal[control group(n=6),the hypercholesterolemic control group(n=6)and the hypereholesterolemic +EECP group(n=6).Porcine model of hypercholesterolemia was made by feeding high-cholesterol diet.After EECP for 36 hours in the hypercholesterolemic+EECP group(n=6),carotid arterial rings were harvested from all animals and their vaso-relaxation response to different dose of Acetylchofine(Ach)and Sodium nitroprusside (SNP)were detected,respectively.Results As the dose of Ach varying between 10-8 mol/L and 10-5mol/L, endothelium-dependent vasorelaxation ratio of hypereholesterolemic piss with or without EECP treatment was significantly lower than that of the normal control group(P＜0.05),however,endothehum-dependent vasorelax- ation ratio in pigs with EECP treatment was obviously higher compared with hypereholesterolemic pigs without EECP treatment(P＜0.05)as the Ach ranged from 10-7 mol/L to 10-5mol/L.Similarly,as the concentration of SNP ranged fiun 10-8 mol/L to 10-5 mol/L.endothelium-independent vasorelaxafion ratio of both the hypercholesterolemic control group and the hypercholesterolemic+EECP group were significantly lower than that of the normal control group(P＜0.05),and end othelium-independent vasorelaxation ratio of the hypercholesterolemic+EECP group was significantly higher than that of the hypercholesterolemic control group (P＜0.05).Condusions Long-term EECP improves the impaired endothelium-dependent and endothelium independent vasorelaxalion function resulting from atherosclerosis.