Objective To explore the feasibility of the applicatoin of readout-segmented echo-planar imaging (RS-EPI) at 3.0T MR of the orbit DWI and compared with single-shot echo-planar imaging (SS-EPI).Methods Forty-two volunteers underwent both standard SS-EPI and RS-EPI DWI of the orbit at a 3.0T MR unit.Two sets of DWI images were independently qualitatively scored in the number of distinguishable normal structures,fat suppression,ghosting artifact and overall image quality.SNR of the vitreous body,geometric distortion ratio (GDR) in both anterior-posterior (AP) and right-left (RL) direction,and ADC value of the vitreous body and pons were also quantitatively calculated and compared between two sets of DWI images.The statistical analysis was performed.Results For qualitative assessment,the RS-EPI was superior to SS-EPI on the number of distinguishable normal structures (P=0.009 0),ghosting artifact (P＜0.000 1),and overall image quality (P＜0.000 1),while no significant difference was found on fat suppression (P=0.753 9).For quantitative assessment,RS-EPI had significantly lower GDR than the SS-EPI in both AP and RL direction (P=0.001 4,0.001 7).The SNR in RS-EPI was significantly lower than that of SS-EPI (P=0.004 0).Meanwhile,there was no significant difference of ADC on vitreous body and pons between RS-EPI and SS-EPI (P=0.143 8,0.126 2).Conclusion The RS-EPI can provide better image quality than SS-EPI protocol in orbital DWI at 3.0T MR imaging.

Objective To investigate the effect of xenon intervention on delayed neuropsychologic sequelae (DNS)in acute carbon monoxide(CO)poisoning.Method Adult Wistar rats were randomly divided into sustained group,early intervention group,and control group.CO(150 ml/kg)was infused by intraperitoneal injection to produce DNS model.In sustained intervention group(S-group),xenon(150 ml/kg/d)was infilsed by intraperitoneal injection for 2 weeks;in control group(C-group),xenon was replaced by equal volume air;and in early intervention group(E-tvoup),xenon(150 ml/kg/d)was,employed in the first 3 days and air(150 ml/kg/d)was substituted for xenon in the following days until 2 weeks after CO poisoning.Morris maze test was used to evaluate the intelligence of rats.The long-term potentiation(LTP)of hippocampus Was detected by neuroelectricity recording.The apoptosis rates in brain was detected by TUNEL staining.The data were expressed as(x±s)and analyzed with student's test and analysis of variance.A P value less than 0.05 indicated statisfical significance.Results After exposure to CO,poisoned rats showed intelligence decline,demyeliation ofwater matler and cell apoptosis increased,which were consistent with DNS.In S-group and E-group,the rates of DNS and apoptosis were significantly lower than those in C-group,whereas the rote of LTP in S-group and E-group Was significantly higher than those in C-group.Conclusions Early xenon intervention can effectively decrease the rates of DNS occurred after acute CO poisoning.

AIM　This study was conducted to identify the human CYP isoforms responsible for the biotransformation of clivorine in human liver microsomes and the mechanism of metabolism-induced hepatotoxicity of clivorine. METHODS　Human liver microsomes were used to investigate the metabolism of clivorine in vitro. Selective CYP-450 inhibitors and cDNA expressed human CYPs were used to study their effects on the formation of hepatotoxic metabolites and the metabolism of clivorine and the principal CYP-450 isoform involved in the formation of hepatotoxic metabolite. RESULTS　Four metabolites, namely dehydroretronecine(DHR), 7-glutathionyl-dehydroretronecine(7-GSH-DHR), 7,9-diglutathionyl-dehydroretronecine(7,9-diGSH-DHR) and clivoric acid were found in the microsomal incubations. Chemical inhibition studies indicated that the metabolism of clivorine and the formation of pyrrolic metabolites as well as the bound pyrroles were strongly inhibited by CYP3A inhibitor ketoconazole(Ket). Whereas α-naphthoflavone(Nap), sulfaphenazole(Sulp), quinidine(Qui), diethyldithiocarbamate(DDC) have no significant effects on the metabolism of clivorine and the formation of pyrrolic metabolites in human liver microsomes. The results of metabolism of clivorine by cDNA expressed human CYPs showed that only CYP3A4 was found to be capable of catalyzing the metabolism of clivorine, while CYP1A2, CYP2C9, CYP2D6 and CYP2E1 did not play significant roles in the metabolism of clivorine and the formation of pyrrolic metabolites. CONCLUSION　The resultsdemonstrated that the pyrrolic metabolites were the major in vitro metabolites of clivorine and CYP3A4 was the major CYP isoform involved in clivorine metabolism and the formation of hepatotoxic pyrrolic metabolites in human liver microsomes. CYP3A4 plays a key role in the clivorine induced hepatotoxicity.

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.

The fourth generation poly( amidoamine) dendrimers ( G4. 0 PAMAM) functionalized multiwalled carbon nanotube ( G4 . 0-MWCNTs ) was prepared by amidation between carboxylated multiwalled carbon nanotube (MWCNTs) and G4. 0 PAMAM. Then a novel hydrogen peroxide (H2O2) sensor was fabricated by electrodepositing Pd nanoparticles (NPs) on a glassy carbon electrode (GCE) modified with G4. 0-MWCNTs composites. The modified electrode was characterized by field emission scanning electron microscopy ( FESEM) , cyclic voltammetry ( CV) and electrochemical impedance spectroscopy ( EIS) . A large amounts of highly dispersion PdNPs could be well loaded on the surface of the G4. 0-MWCNTs, and the modified electrode exhibited excellent electrocatalytic activity towards the reduction of H2 O2 . Under the optimized conditions, the reduction peak currents of H2 O2 were linear to their concentrations in the range from 1. 0 × 10-9 mol/L to 1. 0×10-3 mol/L and the limit of detection of 2. 3×10-8 mol/L was obtained. The recovery of standard addition for human serum samples was 96 . 7%-103 . 1%.

BACKGROUND:The laser applied in the clinical oral medicine is mainly for early diagnosis of caries, removal of carious tissue, pulpotomy for pulp bleeding, dentin hypersensitivity treatment, disinfection of infected root canals, and periodontitis treatment. OBJECTIVE:To explore the changes of basic fibroblast growth factor in inflammatory pulp after laser treatment. METHODS:Five healthy adult beagle dogs were enroled, and six teeth were randomly selected from each dog. Then, these teeth were randomly divided into three groups, 10 teeth in a group, and they were treated with laser irradiation, saline and gentamicin irrigation respectively. At days 1, 2, 3 after operation, exudates from the pulp were colected for detection of basic fibroblast growth factor expression. Meanwhile, the dental pulp was detected by hematoxylin-eosin staining and immunohistochemistry method. RESULTS AND CONCLUSION:In the al three groups, the expression of basic fibroblast growth factor at day 3 was significantly higher than that at days 1 and 2, and there were no differences between days 1 and 2. Moreover, these three groups also showed no significant differences. Under hematoxylin-eosin and immunohistochemical staining, blood vessels in the pulp cavity were in good condition and the pulp arranged tightly. These findings suggest that the laser is safe, convenient and effective for oral clinical application, and has no injury to the inflammatory pulp.

Aim: To study the pharmacokinetic effects of salvianolic acid B( Sal B) on danshensu( DSS) in Danshen injection in rats. MGthod: Following the intravenous administration of Danshen injection and Danshen injection added with Sal B to rats, the plasma kinetic study, tissue distribution and urine excretion were studied. The plasma kinetic study was also investigated by giving DSS and DSS in combination with Sal B to rats. Plasma, tissue and urine drug levels of danshensu were analyzed by LC-MS. Results: Compared with danshensu given alone, no significant difference of the pharmacokinetic behavior of danshensu was found when danshensu was given in combination with salvianolic acid B. However, compared with Danshen injection given alone, the pharmacokinetic behavior of danshensu changed remarkably when Danshen injection was given in combination with salvianolic acid B which might be caused by the decrease of DSS in kidney distribution and urine excretion. Conclusion: The pharmacokinetic effects of salvianolic acid B on danshensu depend on the existence of multiple components in Danshen injection. Results suggest that the pharmacokinetic interactions of the multiple components are closely related to the integrity of herbal medicines.

Aim: To determine the uptake characteristics of salvianolic acid B(Sal B) in myocardial cells and blood vessel endothelial cells. Method: The effects of various factors, such as time, temperature, drug concentration, pH of the medium, on the uptake of Sal B in myocardial cells and aorta endothelial cells were investigated. LC/MS was employed to determine the intracellular concentration of Sal B. Results: Uptake kinetics of Sal B in the myocardial cells and aorta endothelial cells fitted well to the logarithmic model at 37 ℃ and 4 ℃. The a-mount of uptake was in direct proportion to the extracellular concentration of Sal B in the experimental concentration range. Uptake of Sal B both in the myocardial cells and blood vessel endothelial cells would significantly increase while the medium pH decreased, and some water-soluble components extracted from danshen would also facilitate the uptake of Sal B both in the myocardial cells and blood vessel endothelial cells obviously. The energy metabolism inhibitors would significantly inhibit the uptake of Sal B in the myocardial cells and blood vessel endothelial cells. When lactic acid and fatty acid were added to the incubation solution, the uptake of Sal B both in the myocardial cells and aorta endothelial cells increased more than 20%. Conclusion: pH is the most important factor influencing the cellular uptake of Sal B, and the amount of uptake tends to increase in acidic medium. Results suggest that the uptake of Sal B would increase in the acidified internal environment induced by myocardial ischemia, thus exerting better cardiovascular activities.

The purpose of this study was to investigate the pharmacokinetic interaction between sunitinib and ramipril in rats. Eighteen male SD rats were divided into three groups, with each group being assigned to orally receive sunitinib, ramipril, sunitinib and ramipril, respectively, for ten days. Blood samples were collected at dif-ferent times after first-day and tenth-day administration. The concentrations of ramiprilat and sunitinib in rat plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated and statistically analyzed. Compared with the administration of ramipril alone, after a single-dose combined administration, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ remained unchanged. These results indicated that the ab-sorption rate of ramiprilat increased and the elimination rate decreased, but total absorption degree was not changed. After multiple-dose administrations, CL of ramiprilat decreased and AUC0-∞ increased obviously. It sug-gested that accumulation of ramiprilat occurred in body and the drug elimination became slower. No obvious difference of sunitinib pharmacokinetic behavior was found when it was given in combination with ramipril after a single-dose administration or multiple-dose administration. Sunitinib decreased the elimination of ramiprilat after co-administration in company with drug accumulation in body after multiple-dose co-administration. The study showed that there were pharmacokinetic interactions between sunitinib and ramipril in SD rats.