Promotion effect of cartilage regenerated scaffolds combined with exosomes derived from mutant type of HIF-1α modified BMSCs in repairing advanced cartilage defects / 吉林大学学报(医学版)

Objective:To explore the protective effect of exosomes secreted from bone mesenchymal stem cells (BMSCs)modified by hypoxia inducible factor-1α(HIF-1α)on the chondrocytes,and to elucidate the possible mechanism of its combination with cartilage regenerated scaffolds in promoting the repair of advanced cartilage defects.Methods:The exosomes(BMSCs-ExoWTand BMSCs-ExoMU)were extracted from the BMSCs modified by wild type of HIF-1α and mutant type of HIF-1α by ultracentrifugation method and identified in the meantime.In vitro the inflammatory response of chondrocytes were induced by interleukin-1β(IL-1β),the same amount of PBS, BMSCs-ExoWT(80 μg · mL-1),BMSCs-ExoMU(80 μg · mL-1)were respectively cultivated with the chondrocytes under the inflammatory reaction and blank group,inflammation group,BMSCs-ExoWTgroup and BMSCs-ExoMUgroup were set up;Hoechst33342 staining was used to detect the number of apoptotic bodies of chondrocytes in various groups.The Western blotting method was used to detect the expression levels of AKT/p-AKT,ERK/p-ERK and p38/p-p38 in the chondrocytes in various groups.Twelve New Zealand white rabbits were randomly divided into 4 groups and the models of rabbit knee cartilage defects were consructed;the equal volume of physiological saline,scaffold +physiological saline,scaffold +BMSCs-ExoWTand scaffold +BMSCs-ExoMUwere respectively injected into the cartilage defects of rabbits.Six weeks after operation,gross conference, HE and safranin O staining were used to observe and compare the repair effects of cartilage defects in each group. Results:BMSCs-ExoWTand BMSCs-ExoMUwere successfully extracted and identified,and the exosomes were observed to be nearly circular with diameter of about 40-100 nm;the Western blotting results showed that they expressed special proteins CD63 and CD81,respectively.In vitro,the number of apoptotic bodies of chondrocytes in BMSCs-ExoMUgroup was lower than those in inflammation group and BMSCs-ExoWTgroup(P<0.01).The Western blotting results revealed that the expression levels of p-ERK1/2 in BMSCs-ExoMUand BMSCs-ExoWT groups were lower than that in inflammation group(P<0.05);the expression levels of p-AKT and p-p38 were higher(P<0.05);the effect in BMSCs-ExoMUgroup was stronger than BMSCs-ExoWTgroup,and the difference was statistically significant(P<0.05).In the advanced cartilage defect models of rabbit knee joint,the repair effect in scaffold+ BMSCs-ExoMUgroup was better than those in blank group,scaffold group and scaffold+BMSCs-ExoWTgroup.Conclusion:Cartilage scaffold combined with BMSCs-ExoMUcan promote the repair of cartilage defects.

The correlation between heart rate turbulence of pediatric viral myocarditis and other indexes / 中国基层医药

Objective To study the value of heart rate turbulence(HRT) of acute pediatric viral myocarditis (VMC) ,and the relationship between HRT and other indexes. Methods We randomly assigned 75 acute pediatric VMC and 77 health enfant those all received holter. We calculated the heart rate turbulence(To) and turbulence slope (Ts) respectively,and compared the difference between them. Simultaneously, record the number of ventricular pre-mature complex(VPC) ,whether with ventricular tachycardia(VT) and the SDNN index of HRV. Then we analyzed the association between them and To,Ts. Results The difference of To between pediatric VMC and control group is significant in statistics, as follows [ (1.47±2.03 ) %, (-0.78±2.55) %, P<0.01; (3.05±2.12) ms/RR, (8.82±3.42) ms/RR,P<0.01]. There are no correlation between To and the number of VPC. And the number of VPC is interrelated to Ts. To and Ts are not correlative with whether with VT and heart rate variability(HRV). Conclusions The HRT of pediatric VMC is significanty reduced,so HRT can be a new index that to evaluate the heart parasym-pathetic function state in pediatric VMC and it is independent from traditional HRV. Therefore we can evaluate the heart parasympathetic function state of the sufferers after analyzed their HRT. This technique can help to discover pathological changes of heart parasympathetic system in forepart and guide clinical therapy in time,and avoid heart ill event.

Determination of finasteride in human plasma and its pharmacokinetics and relative bioavailability by HPLC-electrospray mass spectrometry / 中国新药与临床杂志

AIM: A new HPLC-MS method was developed to determine finasteride in human plasma. METHODS: Two formulations of finasteride tablets were given to 20 healthy male volunteers according to a randomized 2-way cross-over design. The samples were extracted by ethyl acetate under basic conditions, then were separated by C18 column and determined by mass detector. RESULTS: The calibration curve of finasteride was linear and intra-day and inter-day RSD were less than 10 %. The pharmacokinetics parameters of the two formulations (4.5 ± 0.5) h for t1/2; (3.0 ± 0.7) and (2.8 ± 0.9) h for tmax, respectively. The results indicated that there was no significant difference on cmax, A UC0-24, t1/2 or tmax values between the two formulations. CONCLUTION: The relative bioavailability of tablets I with respect to tablets Ⅱ is (99.3 ± 9.2) % by the A UC0-24 measurement, and bioe quivalence is observed between the two tablets.

Study on Bioequiavailability in Human Body between Domestic and Imported Roxithromycin / 中国药房

OBJECTIVE:To study the bioequiavailability of domestic roxithromycin tablets and imported ones.METH?ODS:20male healthy volunteers took single dose of150mg roxithromycin tablet orally in a random crossover design,blood concentrations were determined by LC-MS.RESULTS:The main pharmacokinetic parameters of domestic and imported tablets were determined respectively as follows,AUC 0～72 were(72.81?23.85)(mg?n)/L and(72.63?20.86)(mg?h)/L,AUC 0～∞ were(74.41?24.45)(mg?h)/L and(74.42?24.45)(mg?h)/L,C max were(6.46?1.51)mg/L and(6.58?1.55)mg/L,t max were(1.9?0.5)h and(1.8?0.5)h,t 1/2 were(13.56?1.35)h and(14.18?1.50)h,the relative bioavailability of the homemade tablet to imported one was(99.8?11.2)%.CONCLUSIONS:Domestic and imported roxithromycin are bioequivalent.

Pharmacokinetics and bioavailability of two kinds of gliclazide sustained release tablets following a single and multiple dose in healthy volunteers / 中国新药与临床杂志

AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained-release tablets of gliclazide in healthy volunteers. METHODS:The study was performed by an four-period crossover design with singledose and multiple-dose administration. The plasmadrug concentrations of twenty male healthy volunteers were determined by liquid chromatography with mass spectrum detector method (LC-MS). RESULTS:The pharmacokinetic parameters after a single oral dose of the domestic and imported gliclazide tablets were (7.2+s 1.5) h and (6.9 +1.4) h for tmax, (13.4 ±1.2) h and (13.7 +1.3) h for t1/2, (2.4 +0.8) mg ·L-1and (2.3 ±0.6) mg· L-1 forcmax, (48 ±14)mg · h · L-1 and (48 +14) mg· h · L-1 forAUC0-60,(51+15) mg· h· L-1 and (50±14) mg· h· L-1for AUC0-∞, (22.4 ± 1.9 ) h and (22.8 ± 1.9 ) h for MRT, respectively. The steady state pharmacokinetic parameters after multiple doses of the domestic and imported gliclazide tablets were (6. 1 ± 1.4) h and (6.5+1.4) h for tmax, (4.6±0.9) mg· L-1 and (4.7±1.1) mg· L-1 for cmax, (0.23 ±0.08) mg ·L-1and (0.26±0.08) mg· L-1 forcmin, (1.6±0.3) mg·L-1 and (1.6±0.3) mg · L-1 for mean value of steady plasma-drug concentration (cav),(94±19) mg· h · L-1 and (95 ±20) mg · h · L-1forAUCss, (282 ±33)% and (283 ±43)% for degree of fluctuation DF ), respectively. The relative bioavailability of the domestic gliclazide tablet to the imported gliclazide tablet following a single and multiple dose were ( 102 ± 9) % and (99 ± 10 ) %, respectively. Main pharmacokinetic parameters between the two formulations in both single and multiples dose studies showed no statistical difference ( P >0.05 ). CONCLUSION: The result of two one side t-test shows that the two formulations are bioequivalent.

Different impact on echocardiography in assessment of cardiac function of mouse under anesthetic or unanesthetic condition / 中华超声影像学杂志

Objective To compare echocardiographic parameters of left ventricular function in mice under anaesthesia with those in conscious condition.Methods Forty mice were randomized to anesthetic group and nonanesthetic group,all mice were examined in conscious state at baseline,then anesthetic group had intraperitoneal injection of ketamine and xylazine,the non-anesthetic group received intraperitoneal injection of the same volume of saline.Echocardiography was performed every 10min and every 15min after 30min time point until 60min.ResultsAnesthetic agent strikingly brought down heart function of mice.The nadir of heart rate,fractional shortening(FS),cardiac output(CO) occurred during 10-20min period and could not be restored to normal value at baseline even after 60min.Left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter(LVESD) increased to maximum at 20min point,then decreased to value at baseline until 60min.LVEDD could be restored to baseline value while LVESD remained larger than baseline at 60min.Coefficient of variation of echocardiographic measurement in non-anesthetic group was smaller than those in anethetic group.FS and heart rate of all mice were highly corrrelated by regression analysis(r=(0.884),P

Bioequivalence of Ambroxol Hydrochloride Orally Disintegrating Tablets in Healthy Volunteers / 中国药房

OBJECTIVE:To study the time-concentration curves of single dose of ambroxol hydrochloride orally integrating tablets in healthy volunteers and to evaluate its bioequivalence.METHODS:A single oral dose of 90mg ambroxol hydrochloride orally dissolving tablets and 90 mg ambroxol hydrochloride tablets were given to 18 healthy volunteers by a randomized crossover design.The concentrations of ambroxol hydrochloride in plasma were determined by HPLC.RESULTS:The main pharmacokinetic parameters of the test and references preparations of ambroxol hydrochloride were as follows:Cmax were(169.58?39.43)ng?mL-1 and(170.28?43.26)ng?mL-1;tmax were(1.6?0.5)h and(2.2?0.6)h;t1/2 were(6.77?2.04)h and(6.50?1.27)h;AUC0～24 were(1 131.26?289.36)ng?h?mL-1 and(1 191.54?270.17)ng?h?mL-1;AUC0～∞ were(1 215.27?306.56)ng?h?mL-1 and(1 281.44?291.51)ng?h?mL-1,respectively.The relative bioavailability of the test preparation was(95.5?15.6)%.CONCLUSION:The result demonstrated that the two preparatioins were bioequivalent in absorption degree,suggesting the rapid release characteristics of the preparation.