Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).

BACKGROUND: As a common anticoagulant, heparin is widely used in clinic, but it has remarkable side effects such as severe bleeding and heparin-induced thrombocytopenia, and it cannot inactivate fibrin-bound thrombin. Annexin Ⅴ derivative (AND) is inosculated with C-terminal of hirudin and annexin Ⅴ, and its anticoagulation and anti-thrombosis effects are compared with those of heparin. OBJECTIVE: To investigate the relationship between quantitative effectiveness and time effectiveness of AND on coagulation and thrombosis, and study its reliability. DESIGN: Completely randomized grouping design and controlled study. SETTING: Cardiac Department of amunicipal hospital. MATERIALS: The experiment was conducted at the Animal Laboratory of Jiangsu Provincial People's Hospital from July 2000 to April 2001. Totally 32 male New Zealand white rabbits were randomly divided into 4groups, namely, high dosage AND group, low dosage AND group, common heparin group and saline group with 8 in each group. METHODS: Heparin and AND were diluted with saline.①High dosage AND group: 0.7 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.35mg/(kg ·h)for 2 hours.Low dosage AND group: 0.3 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.15 mg/(kg·h) for 2 hours. Heparin group: 75 IU/kg heparin was injected intravenously and followed by intravenous dripping of 37.5 IU/(kg·h) for 2 hours. Saline group: The same volume of saline and medication were used as those in drug groups.② Blood sample was collected from the femoral vein before administration so as to test blood routine, activated partial thromboplastin time(APTT)and prothrombin time (PT) after 15-, 30- and 60-minute administration and 2-hour withdrawal.③Saccule was separated from endothelium of femoral artery to measure blood pressure of distal femoral artery at 15 minutes after administration.Time of pulse pressure equal to 0 mmHg was recorded when the vessel was occluded completely by a thrombus.Finally the injured femoral arteries whose vessel was stripped were collected to measure its length, wet weight and dry weight. ④Observation of AND toxicity and sideeffects:During the experiment,vital signs of the animals were measured,such as blood pressure,heart rate and breath;in addition,bowelhemorrhage was observed and the number of leucocytes was counted after dissection of some of the animals. MAIN OUTCOME MEASURES:①Effect of AND on blood coagulation system and arterial thrombosis.②AND toxicity and side effects. RESULTS: All the 32 white rabbits entered the final analysis. ① Anticoagulant effect: APTT: Fifteen minutes after administration, APTT in AND group was the longest,which was(136.86±39.46)s in high dosage AND group and (122.90±34.19) s in low dosage ANDgroup.Moreover, APTT was longer than that in saline group [(95.14±24.64) s], but shorter than that in common heparin group [(180.00±0.00) s, P ＜ 0.05, 0.01]. At 30 minutes after administration,AND in high dosage group still had coagulation,and APTT was (124.61±40.19) s in high dosage group, which was longer than that in saline group [(85.57±27.67) s], but APTT was (112.94±43.17) sin low dosage group,which was shorter than that in common heparin group [(85.57±27.67)s,P ＜ 0.05].APTT was shorter in high and low dosage groups than in common heparin group at 60 minutes after administration (P ＜ 0.05),and longer than that in saline group 2 hours after drug withdrawal,but there was not significant difference(P ＞ 0.05).PT:PT in common heparin group was longer than that in high and low dosage groups at 15,30 and 60 minutes after administration (P ＜ 0.05).② Effect on arterial thrombosis:Wet weight of thrombus:It was lighter in AND group than in common heparin group(P ＜ 0.05). Dry weight of thrombus:Thrombus was lighter in high and low dosage groups than in common heparin group, and was lighter in high dosage group than in low dosage group (P ＜ 0.05).Thrombus length:It was shorter in low dosage group than in saline group (P ＜ 0.05), and shorter in high dosage groupthan in common heparin group (P ＜ 0.05). Time of complete occlusion: It was longer in high and low dosage groups than in saline group(P ＜ 0.05).③ AND toxicity and side effects:The behavior of rabbits in high and low dosage groups was similar to that in other two groups. Obvious hemodynamic changes were not found, and bowel hemorrhage was not observed, either. CONCLUSION: AND is an effective anticoagulant and anti-thrombosis agent; the highest anticoagulation effect occurs at 15 minutes afteradminis tration. However, the anticoagulant effect is poor as compared to heparin.The effect is poorer after 60-minute administration. Effect of AND on thrombus is stronger than that of heparin,but the size of thrombus is smaller than that of heparin, and the dosage-dependence manner was found. In addition, the anti-thrombus effect of AND is stronger in high dosage group than in low dosage group.

Objective：To study anatomic basis of ligaments factors in carpal radial instability. Methods:The length, width, thickness and maximum length of radial scaphoid capitate ligament(RSCL) , radial lunate ligament(RLL) , radial scaphoid lunate ligament(RSLL),radial scaphoid ligament(RSL), scaphoid trapezium ligament(STmL), scaphoid lunate interosseous ligament(SLIL), scaphoid triangular ligament(STgL) and radial ulnar triangular ligament(RUTgL)were measured in the neutral position. The length of RSCL, RLL, RSLL, RSL and RUTgL in the maximum position of radial deviation, ulnardeviation, palmarflexes and dorsiflexes were also measured. The normal and maximal distance of scaphoid lunate gap(SLG) , scaphoid trapezium gap(STmG), radial scaphoid gap(RSG) and capitate lunate gap(CLG) were measured,especially for variation of SLG in the condition of different ligament lesions. Results:Volar carpal radial ligaments were thicker than dorsal ones. The injuries of SLIL, STmL, RSL and CLL were considered generally when SLG>4.78±0.54mm, STmG>3.71±0.32mm, RSG>5.77±0.79mm, CLG>4.62±79mm; when SLIL was incised completely, SLG>5mm. Keeping anatomic structure of SLIL and incising other ligaments, there existed no obvious variation in SLG. Keeping dorsal part and incising proximal and palmar ones, no obvious variation of SLG can be observed. Conclusions: There were no effects on SLG when carpal radial ligaments (except dorsal part of SLIL) were injuried .Dorsal part of SLIL played a very important role in keeping SLG normal.

α-Galactosidase A (α-Gal A ) activities in plasma and peripheral blood granulocytes of 100healthy subjects and one patient with Fabry disease was determined by means of fluorogenic substrate.The results showed that the enzymatic activities of peripheral blood granulocytes and plasma in 100 subjects were (51.97 ± 15.24)and(148.08±26.30) nmol · h-1 · ml-1 respectively.The α-Gal A activities in plasma and granulocytes were positively correlated( r=0.533,P＜0.01 ).The enzymatic activities in peripheral blood granulocytes and plasma of the patients with Fabry disease were 1.05 and 10.06 nmol · h-1 · ml-1 respectively,both much lower than those of 100healthy subjects.These results suggest that α-Gal A activity in plasma and peripheral blood granulocytes can be used for diagnosis and screening of Fabry disease.

BACKGROUND: Studies have found that chondroitin sulfate proteoglycans degradation with chondroitinase canpromote the migration of Müller cells on the retina, but whether it could promote the migration of adipose-derivedmesenchymal stem cells in retinal degeneration rats is unclear.OBJECTIVE: To investigate the effect of chondroitin sulfate proteoglycans degradation with chondroitinase on adipose-derived mesenchymal stem cell treatment for retinal degeneration in rats.METHODS: Human adipose-derived mesenchymal stem cells were isolated and cultured. A retinal degeneration ratmodel was established followed by administration of adipose-derived mesenchymal stem cells+chondroitinase into thesubretinal space. The migration of adipose-derived mesenchymal stem cells and retinal cell apoptosis in rats aftertransplantation were observed.RESULTS AND CONCLUSION: The human adipose-derived mesenchymal stem cells could be successfully cultured.The labeling rate of BrdU to the human adipose-derived mesenchymal stem cells was more than 90.0%. At 7 days aftermodeling, the outer nuclear layer of the retina was collapsed, and a large amount of photoreceptor cells were dissected.The outer nuclear layer was attached to the Bruch''s membrane, and the retina was arched. The central retina andperipheral retina were damaged. In normal rats, the retinal layers were clear, and the photoreceptor cells arrangedregularly; and the retinal pigment epithelium was complete. The migration rate of adipose-derived mesenchymal stemcells in adipose-derived mesenchymal stem cells+chondroitinase group was higher than that in adipose-derivedmesenchymal stem cells group (P < 0.05). There was no significant difference in the apoptotic rate of retinal cellsbetween the two groups (P > 0.05). These experimental findings show that chondroitin sulfate proteoglycans degradationwith chondroitinase can enhance the migration ability of human adipose-derived mesenchymal stem cells on the retina.

Objectives It was constructed that the replication defective adenoviral vectors carried the short hairpin sequences of mouse SCP2.And we will make a further study of mechanism between SCP2 gene and cholesterol stone in gallbladder.Methods The short hairpin sequences of mouse SCP2 were cloned by two-step PCR,and connected together with the plasmid pDC312.The Admax Adenoviral Vector System was used to generate the replication defective adenoviral vectors,which were purified by CsCl method.The processes of TCID50 were applied to detect the titers of the adenoviral vectors.Furthermore,Protein levels of SCP2 were determined by Western blot analysis,and the levels of SCP2、CYP7A1、HMGCR mRNA from the hepa1-6 cell of mouse were measured by the usage of RT-PCR.Results SCP2mRNA and SCP2 protein were down-regulated by the replication defective adenoviral vectors carried the SCP2-shRNA.With the decreasing SCP2mRNA,the levels of HMGCRmRNA were down-regulated at same the time,while CYP7A1mRNA were up-regulated.Conclusions The replication defective adenoviral vectors carried SCP2-shRNA were constructed successfully.The lower levels of SCP2 could affect the activities of HMG-CoA reductase and CYP7-a enzyme,which caused the variations of cholesterol metabolism and then decreased the formation of cholesterol stone.

Objective:To explore the effect of Naoshuning on the protein expression of Matrix metalloproteinases(MMPs) in experimental injuried brain tissue of rats. Methods:Immunohistochemistry was used to determine the changes of protein expression of MMPs. Brain tissue water content,permeability and ultramicrostructure of blood-brain barrier(BBB) were also observed. Results:Compared with the sham group,the brain tissue water and EB content of injured side and the level of MMP-2 and MMP-9 protein expression in brain tissue around contusion in model group increased obviously(all P

0.05).Conclusion The results suggested that the polymorphism of CCR2-64I was not associated with hypertension in Han Chinese elders.

Objective To study the changes of serum free triiodothyronine (FT3), free tetraiodothyronine (FT4) and the relation between free thyroxine levels and serum tumor necrosis factor (TNK), albumin (ALB), urinary protein in children with primary nephrotic syndrome(PNS). Methods There were sixty children who were suffered from nephrotic syndrome in study group Serum FT3,FT4,TNF, Alb and urinary protein were detected. In the meantime compared with 25 health,cases. Results The levels of FT3, FT4 of the children who were suffered from nephrotic syndrome were lower. The difference between nephrotic syndrome and health cases were significantly (P

Objective To observe the effect of circadian rhythm on hypnotic median effective dose( ED50) of ketamine. Methods Sixty mice were randomly divided into 4 groups which had 15 mice in each group. They were intraperitoneally injected with ketamine at different times of 2 Am,8 Am,2 Pm and 8 Pm, respectively. Righting reflex was recorded and the value of ED50 was measured with sequential experimental method. Results The hypnotic ED50 of ketamine at 2 Am was(54.57?0.82) mg/kg, with 95% confidence limit of ED50 38.06-78.22 mg/kg;ED50 was(49. 27?0. 12) mg/kg at 8 Am, with 95% confidence limit of ED50 40. 21-60. 37 mg/kg;ED50 at 2 Pm was (42.28?0.21) mg/kg, with 95% confidence limit 37.35 - 47 83 mg/kg;and ED50 at 8 Pm was(57.42?0.14) mg/kg, with 95% confidence limit 37.51-73 72 mg/kg,respectively. The ED50 were significant different at 2 Pm and 8 Pm. However, there were no significant difference in ED50 value among other groups. Conclusion The hypnotic effect of ketamine has circadian rhythm - dependent.