OBJECTIVE:To determine the concentration of dehydroisoandrosterone sulfate (DHEAS) in human plasma by LC-MS.METHODS:With estrogen sulfate (ES) served as an internal standard,the plasma samples were deproteinized with acetonitrile,extracted by solid phase,hydrolyzed and derivatized.Then the concentration of DHEAS was determined by HPLC-MSD on Agilent SB C18 with column temperature kept at 40℃.The mobile phase consisted of acetonitrile-water (in gradient elution).Atmosphere pressure chemical ion source in negative ion detection model was employed.The ions selected for SIM (selected ion monitoring) quantitative analysis included m/z 490.0 (DHEAS ) and m/z 472.1(ES)[M-H]-.RESULTS:The linear range of DHEAS was 250.0～320.0 ng?mL-1(r=0.999 4).The extraction recovery of the simulated human albumin samples ranged from 71.1%～78.9% and its relative recovery ranged from 98.3%～101.4%.Both the intra-day RSD and inter-day RSD were less than 10%.The mean concentration of DHEAS in 15 health aged male volunteers was (981.6?353.4) ng?mL-1.CONCLUSION:The method is simple,practical,accurate and sensitive,and it is applicable for the determination of plasma concentration of DHEAS.

OBJECTIVE:To investigate the compatible stability of Voriconazole for injection after mixed with Fructose injec-tion or Invert sugar injection. METHODS:Referring to package inserts,Voriconazole for injection 200 mg was dissolved with Wa-ter for injection to 20 mL,and then combined with Fructose injection 250 mL and Invert sugar injection 250 mL,respectively. At room temperature,the appearance of mixtures were observed 0,1,2,3,4,5 h after mixing,and pH value and the number of in-soluble particles were determined;the content of voriconazole was determined by HPLC. RESULTS:Under above condition,the appearance and pH value of mixtures had no significant change within 5 h;the number of particles ≥10 μm and ≥25 μm were all in line with the standard of Chinese Pharmacopoeia (2015 edition);the relative content of voriconazole was decreasing (95.28%-100%),but it changed within ±5%(RSD<2%,n=6). CONCLUSIONS:Voriconazole for injection could keep stable within 5 h after mixed with Fructose injection or Invert sugar injection.

OBJECTIVE:To evaluate the bioavailability of two nimesulide preparations.METHODS:A total of 20 healthy male volunteers were enrolled in a randomized crossover study in which the subjects were randomly assigned to receive single dose of 200 mg nimesulide orally disintegrating tablets(test)or nimesulide tablets(reference).The plasma concentrations of nimesulide were determined by RP-HPLC,and the pharmacokinetic parameters and bioavailability were calculated with DAS program.RESULTS:The main pharmacokinetic parameters of nimesulide test and reference preparations were as follow:AUC0～24:(54.67?18.25)vs.(56.15?15.54)?g?h?mL-1;AUC0～∞:(56.38?18.03)vs.(57.63?15.26)?g?h?mL-1;Cmax:(7.61?2.72)vs.(7.50?2.19)?g?mL-1;tmax:(3.83?1.39)and(3.80?1.28)h.The relative bioavailability of nimesulide or-ally disintegrating tablets as against nimesulide tablet was(98.7?22.9)%.CONCLUSION:Nimesulide test and reference preparations were bioequivalent.

OBJECTIVE:Using in vitro studies,we evaluated the antibacterial activity of amoxicillin/tazobactam against 128 strains of pathogens isolated from patients and compared with amoxicillin/clavulanic acid and amoxicillin/sulbactam.METHODS:To detect the minimum inhibitory concentrations (MIC)of four ?-lactams against 128 clinically isolated strains with agar dilution method.RESULTS:The results indicated that the in vitro antibacterial activity of amoxicillin/tazobactam(2∶1) was the best.The MIC50 of amoxicillin/tazobactam(2∶1) is 1/4～1/8 times than those of amoxicillin/sulbutam and amoxicillin/clavulanic acid.The MIC90 of amoxicillin/tazobactam(2∶1) was 1/2～1/4 of those of amoxicillin/sulbutam and amoxicillin/clavulanic acid.The combination ratio 2∶1(amoxicillin/tazobactam)of the two compounds was more suitable than other combination ratios(4∶1 and 8∶1)for inactivating ?-lactamase.CONCLUSION:The in vitro antibacterial activities of amoxicillin/tazobactam(2∶1) against MRSA,MRSE,MSSA and E.coli are high.It showed that amoxicillin/tazobactam(2∶1)is stable to ?-lactamase and is an effective bactericidal agent.

BACKGROUND:The mechanical properties of monkeys are the closest to the human body.Monkey is the ideal animal model of osteoporosis research.OBJECTIVE:To explore the biomechanical properties of the long bones and vertebrae in rhesus monkeys.DESIGN.TIME AND SETTING:The mechanics experiment for the study was based on monkeys,which was completed in the South Medical University,Key Laboratory of Medical Biomechanics in Octobor 2006.MATERIALS:Four male macaca mulattas aged 17.5 years on average and three female crab-eating monkeys aged 9 years on average.METHODS:Long bones(femur,tibia,fibula,humerus,radius and ulna)and the third and fourth lumbar vertebrae of three adult crab-eating monkeys and four old macaca mulattes were teken to do four-point bending test,torsion test,indentation test and compression test respectively.MAIN OUTCOME MEASURES:①The results of compression experiments and indentation experiments in monkey vertebrae.②The maximum load and the rigidity factor in left side of long bone of monkeys.③The maximum torque(N·m)in the right side of long bone of monkeys.RESULTS:①In the four-point bending tests,the maximum Ioad of the left ulna,fibula,humerus,femur,tibia and radius in macaca mulattas were(574.16±163.53),(179.98±38.32),(1487.9±965.12),(1928.60±336.23),(1303.23±969.35),(559.92±1.12)N,respectively.While the rigidity factor of the left femur,tibia,fibula,humerus,radius and ulna in macaca mulattas were (53.49±14.22),(28.41±5.86),(114.22±13.24),(142.16±18.56).(101.11±15.46),(69.13±5.54)N/mm,respectively.The maximum load of the left femur,tibia.fibula,humerus,radius and ulna in crab-eating monkeys were(179.93±19.38),(53.82±5.31),(631.61±225.81),(726.07±245.69),(424.52±49.s0),(1 91.97±67.73)N,respectively;however,the rigidity factor of the left femur,tibia,fibula,humerus,radius and ulna in crab-eating monkeys were(21.45±2.63),(16.25±6.66),(68.5±12.22),(76.79±14.01),(41.80±2.79),(64.31±15.89)N/mm,respectively.②In the torsion test,the maximum torque of the right fibula,humerus,femur and tibia in macaca mulattas were(1.55±0.82),(22.26±4.26),(30.93±6.54),(17.49±4.04)N·m,respectively.The maximum torqua of the right fibula,humerus,femur,tibia in crab-eating monkeys were(0.81±0.15),(10.34±2.06),(11.58±0.76),(6.68±1.34)N·m,respectively;③In the compression test,the maximal compression load and the rigidity factor of L4 in macaca mulattas were (2811.21±403.90)N,and(69.47±8.92)N/mm,respectively;the maximal compression load and the rigidity factor of L4 in crab-eating monkeys were(1659.90±339.08)N,and(36.29±6.61)N/mm,respectively.④In the indentation test,the maximal indentation and the maximal anti-pressure of L_3 in macaca mulattas were(521.90±38.94)N,and(699.16±43.46)MPa,respectively;the maximal indentation and the maximal anti-pressure of L_3 in crab-eating monkeys were(614±145.94)N,and (815.92±193.69)MPa,respectively.CONCLUSION:Experimental data derived from the experiments demonstrated that rhesus monkeys as a kind of nonhuman primate animals have an important reference value in the animal studies of osteoporosis.

OBJECTIVE:To study the pharmacokinetics and relative bioavailability of clindamycin phosphate capsules in healthy volunteers METHODS:A single oral dose of 300mg domestic clindamycin phosphate capsules or imported Dalacin C was given to 18 healthy male volunteers in an open randomized crossover study Clindamycin concentrations in plasma were determined by microbiologic assay The pharmacokinetic parmameters as well as relative bioavailability were calculated with 3p97 software and bioequivalence was analysed with NDST software RESULTS:The concentration-time curves of domestic clindamycin phosphate capsules or imported Dalacin C were well fitted for one-compartment open model The pharmacokinetic parameters of domestic and imported products were:Tmax(0 94?0 51) and(0 75?0 35)h;Cmax(3 86?0 62)?g/ml and (4 08?0 60)?g/ml;AUC0～12(14 88?3 64)?g/(ml?h)and(16 07?3 68)?g/(ml?h)respectively There were no significant differences in AUC0～12 and Cmax between two products CONCLUSION:The relative bioavailability of clindamycin phosphate capsules was(93 4?14 9)% compared with imported Dalacin C The results showed that the two formulations were bioequivalent

Angiogenesis, a process by which the preexisting blood vasculature gives rise to new capillary vessels, is associated with a variety of physiologic and pathologic conditions. However, the molecular mechanism underlying this important process remains poorly understood. Here we show that histone deacetylase 6 (HDAC6), a microtubule-associated enzyme critical for cell motility, contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells. Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice. The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting. Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization. In addition, microtubule end binding protein 1 (EB1) is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures. These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.
Anilides ; pharmacology ; Animals ; Cell Movement ; Cell Polarity ; Cells, Cultured ; Chick Embryo ; Chickens ; Endothelial Cells ; cytology ; Histone Deacetylase 6 ; Histone Deacetylases ; metabolism ; physiology ; Humans ; Hydroxamic Acids ; pharmacology ; Mice ; Microtubule-Associated Proteins ; metabolism ; physiology ; Neovascularization, Physiologic