A simple, rapid and sensitive method was developed for the quantification of tenofovir in plasma of Beagle dogs using HPLC-MS/MS analysis. The analytes tenofovir and internal standard (IS) adefovir were separated on a Zorbax SB-C18 column (3.5 microm, 100 mm x 2.1 mm, Agilent, USA) with mobile phase of methanol/water containing 0.3% formic acid using a gradient elution mode at a flow rate of 0.2 mL x min(-1). The plasma sample preparation was a simple deproteinization by the addition of 20% trichloroacetic acid followed by centrifugation. The detection was performed in positive selected reaction monitoring (SRM) mode with an electrospray ionization (ESI) source. The reactions monitored were m/z 288.1-176.2 for tenofovir and m/z 274.1-162.2 for adefovir (IS). Linear detection responses were obtained for tenofovir ranging from 10 to 5 000 ng x mL(-1). The intra- and inter-day precisions (RSD%) was no more than 6.3% with high recovery and good stability for the quantification, indicating the present method was specific, fast, accurate and reliable. The method was successfully applied to the pharmacokinetic study of two tenofovir agents. Tenofovir dipivoxil fumarate (BP0018, test agent) and tenofovir disoproxil fumarate (reference agent) were orally administrated to 8 Beagle dogs according to the 2 x 2 crossover design. Comparing with the reference agent, the longer MRT and t1/2 were obtained in the group of BP0018, while no significant difference was observed in AUC(0-t), AUC(0-infinity), C(max) and t(max) between them, suggesting that tenofovir dipivoxil fumarate was bioequivalent to the tenofovir disoproxil fumarate in Beagle dogs.

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

BackgroundThe research of corneal thickness after pars plana vitrectomy in DM patient plays an important role not only theoretically but clinically.Objective Present study was to evaluate the change in corneal thickness after pars plana vitrectomy.Methods A prospective coherent study was designed.Seventy-five eyes of 70 consecutive diabetic retinopathy(DR) patients were collected in Tianjin Medical University Eye Center.Pentacam was used to assess the central and periphery corneal thickness by the same investigator preoperatively and 7 days,1 and 3 months postoperatively,respectively.The thickness values from five corneal zone were obtained,including cornea vertex,the thinnest point of the cornea,periphery cornea near the scleral incision of 4 mm away to vertex of cornea on vertical and 240°,120°,60° meridian ( right eye) or 300°,120°,60° meidian ( left eye ).These results were compared and analyzed with ANOVA of repeated measurement data.Subgroup analysis was performed to evaluate the influence of different corneal positions,the use of conventional 20g or 23g transconjunctival sutureless vitrectomy(TSV) groups,surgery duration,gas or fluid endotamponde on corneal thickness.This study was approved by Ethic Committee of this hospital.Written informed consent was obtained from the subjects before any relative medical procedure.Results The mean corneal thickness was ( 639.9 ± 103.1 ),( 689.5 ± 119.3 ),( 666.5 ±113.7),( 650.8 ± 108.6 ) μm before operation,postperative 7 days,1 and 3 months respectively.As covariates appearing in the model,the corneal thickness change rates were revised as the parameters as following: diabeitc duration =13.0 and age =57.2.The revised corneal thickness was significant different among various time points( F=210.928,P=0.000) and different corneal zones(F=24.843,P=0.000) with the size order in turn P4＞P3＞P1＞P2＞P5.The corneal thickness change rates were less in 23g TSV group compared with conventional 20-g group (F =53.843,P =0.000) and BSS tamponade group compared with gas tamponade group ( F =5.288,P =0.022).But no significant difference was found in the revised corneal thickness among surgery duration ＜ 1 hour group,1-2 hour group and ＞2 hour group( F=1.233,P =0.293).ConclusionsVitrectomy is a safe procedure on the ground of cornea,but TSV and fluid endotamponade appear to be more beneficial to the protection of cornea.Pentacam could offer the reliable data in not only central cornea but also periphery cornea.

The phytase was extracted from solid state leavening of Trichoderma Viride LH374.The crude product was purified by(NH_4)_2SO_4 precipitation,gel filtration and ion exchange chromatography.The purified phyatse was 13.3 times of the raw products,and the extraction ration was 27.1%.The study on the enzymology of phyatse showed that the optimal temperature and pH were 55℃ and 6.0,respectively.The Km value of the phytase was 0.15mmol/L.

The rat single-pass intestinal perfusion model was applied to study the effect of CYP3A and P-glycoprotein on the absorption of buagafuran in lumen of rats. Buagafuran concentrations in intestinal perfusate and blood in vena mesenterica collected at different time points after perfusion were determined by GC-MS. Permeability coefficient of buagafuran was calculated by the equation [P(lumen) = -(Q/2pirl)Ln(C(out)/C(in)) and P(blood) = (deltaM(B)/deltat)/(2pirl)]. The effects of troleandomycin (TAO, CYP3A inhibitor), cyclosporin A (CYP3A/p-glycoprotein inhibitor) on the absorption of buagafuran in lumen were observed. After rat single-pass intestinal perfusion, the cumulative amount of buagafuran in mesenteric vein of rat was 73.4, 82.9, and 98.3 pmol x cm(-2) and were increased 3.9, 4.6, and 5.6 fold by addition of inhibitor of P-gp (LSN335984), CYP3A (TAO) or P-gp and CYP3A (CsA), respectively. Moreover, the metabolized fraction of buagafuran was decreased by 12%, 11% and 21% with inhibitors. The results suggested that the poor bioavailability of buagafuran was mostly due to the interplay of P-gp and CYP3A on the absorption, transport and metabolism of buagafuran in intestine of rats.

Objective To identify the effect of blood pool 18F-FDG activity on liver SUV and to investigate the optimal normalization method.Methods PET/CT and common serological examination items from 1 018 subjects were retrospectively collected.Mean SUV of liver and blood were recorded as SUVmean(L) and SUVmean (B),respectively.The difference and quotient of SUVmean(L) and SUV mean (B) were calculated as SUVmean (L-B) and SUVmean (L/B),respectively.CV of SUVmean (L),SUVmean (L-B) and SUVmean(L/B) were calculated to assess their inter-individual variations.Pearson correlation analysis was used to evaluate the relationship of SUVmean(L),SUVmean(L-B),SUVmean(L/B) with SUVmean(B).Multiple linear stepwise regression was performed to identify their vulnerability to common serological examination items.Results CV of SUVmean(L/B) (15.1％) was less than that of SUmean(L) (23.2％) and SUVmean(L-B) (40.6％).Correlation between SUVmean(L) and SUVmean(B) (r =0.820,P＜0.001) was more significant than that between SUVmean(L-B) and SUVmean(B) (r =0.205,P＜0.001) as well as between SUVmean (L/B) and SUVmean (B) (r=-0.376,P＜0.001).Blood glucose and BMI correlated with SUVmean(L) and SUVmean(L/B),but not with SUV (B).Age and HDL correlated with SUVmean(L) and SUVmean(B),but not with SUV (L/B).Fatty liver was significantly associated with SUV mean (L/B) (β =-0.047,P ＜0.001),but not with SUVmean(L) and SUVmean (B).Conclusions 18 F-FDG activity of blood pool affects liver SUV.SUV mean (L/B) is a simple and reliable normalization method since its inter-individual variation and vulnerability to common serological examination items are relatively lower than liver SUV.

Objective To observed the clinical effect of vidarabine and interferonα-2b aerosol inhalation in the treatment of children with infantile herpangina.Methods 58 children with infantile herpangina were divided ran-domly into the observation group and control group,29 cases in each group.All children were given theroutine nursing and general supportive therapy.The patients in the control group were treated by ribavirin and those in the observation group treated by vidarabine and interferon aerosol inhalation.The fever clearance time,the disappearance time of her-pes,the days of hospitalization and cases of adverse reaction was observed and recorded.Results The cooling time, bleb disappear time and hospital stay of the observation group were lower than those of the control group,the difference were statistically significant(P <0.05).Comparation of the clinical effects of the two groups showed that the test group were significantly better than those in the control group(P <0.05).The total effective rate in the observation group was 96.6%,which was higher than 75.9% in the control group(χ2 =5.22,P <0.05).No obvious adverse e-vents took place in both groups.Conclusion Vidarabine and interferon aerosol inhalation in treating infantile herpan-gina takes a good effect,no obviously adverse reaction and is worth being widely applied in clinic.

BACKGROUND:Dragon’s blood is the main ingredient of traditional medicine prescription for promoting granulation, which has been used in clinical treatment of a variety of refractory wounds and achieved the exact effects. But the Dragon’s blood effect on colagen secretion from normal fibroblasts has not been reported. OBJECTIVE: To investigate the effects of Dragon’s blood extract on the proliferation and secret function of fibroblastsin vitro. METHODS: Dragon’s blood was extracted by extracts chloroform, acetoacetic ester, and alcohol in turn. Normal human fibroblasts were respectively cultured in Dragon’s blood extracts of chloroform, acetoacetic ester, and alcohol, DMEM containing 1% dimethyl sulfoxide, and normal culture medium. Then, the fibroblasts were cultured in vitro in different media containing gradient dilutions of Dragon’s blood extracts (0.002, 0.02, 0.2, 2, 20 g/L), which was folowed by cel proliferation determination assessed with MTT assay. Under the optimal concentration, the cel growth curves were drawn and the flow cytometry was used to determine the changes of cel cycle. The concentration of procolagen type III in the supernatant of the fibroblast culture systems was measured by radioimmunoassay. RESULTS AND CONCLUSION:0.2 g/L-2 g/L dilution of Dragon’s blood extracted by acetoacetic ester enhanced the proliferation of fibroblasts in a dose-dependent manner. The 2 g/L was the optimal dilution of Dragon’s blood extracted by acetoacetic ester, and it increased the ratio of S cels in cel cycle than control group and decreased procolagen type III. These findings indicate that Dragon’s blood acetoacetic ester extract can improve the proliferation of cultured human fibroblastsin vitro, and decrease the secretion of procolagen type III of fibroblasts, and it can be beneficial to improve wound healing and inhibit hypertrophic scar.

Objective To explore the relationship among idiopathic thrombocytopenic purpura(ITP),human cytomegalovirus(HCMV) infection,and immunological function in infants.Methods HCMV-Ab were tested by ELISA;HCMV DNA were tested by PCR for the case groups (n=54) and the controls(n=30).At the same time,T cell subgroups were tested by direct IF staining for the case groups.Results In the case group,the positive infants of HCMV Ab and HCMV-DNA were more than those in the controls(P

Objective To compare the effect and safety of arthroscopic debridement enmbined with intercondylar fossa angioplasty in the elder with knee osteoarthritis.Methods Six-eight elderly with knee osteoarthritis were selected from June 2012 to December 2014 in this hospital and they were averagely and randomly divided into group A and B.Patients in group A were given arthroscopic debridement,while in group B were given and arthroscopic debridement,intercondylar fossa angioplasty.The levels of VAS scores,Lysholm scores,WOMAC scores and joint range of motion were measured and compared between the two groups after 3 months,6 months and 12 months of operation.The adverse events of the two groups were supervised and compared as well.Results All elder in the two groups had apparently decreasing in VAS scores and WOMAC scores (P＜0.05) after operation.Compared with group A,patients in group B had lower levels of VAS scores and WOMAC scores(P＜0.05) at 12 months after operation.The level of Lysholm score was significantly increased in the two groups after treatment(P＜0.05),while group B had a higher level at 12 months after treatment than group A (P＜0.05).The joint range of motion in the two groups were improved after treatment(P＜0.05).The elder patients in group B had better joint range of motion than group A at 6 and 12 months after operation (P＜0.05).Early postoperative swelling in the joints was the adverse event after operation,but there was no statistically difference between two groups.Conclusion The combination of arthroscopic debridement and intercondylar fossa angioplasty is effective to release knee pain,increase the clinical efficacy and improve the knee function.