OBJECTIVE:To evaluate the safety of various high polymer biomaterials to prevent tendon adhesion,and analyze whether the improvement of injured degree,toxic and side effects,and slipping function of tendon can influence tendon healing.METHODS:A computer-based online search of CNKI was undertaken to identify randomized controlled articles about the effect of various high polymer biomaterials on tendon adhesion with the keywords of "tendon adhesion,biomaterials,and barrier" from 1990 to 2005.Retrieval data were then extracted and analyzed.RESULTS:Among 11 tests,there were 571 patients with tendon injury and 7 animal models with tendon injury,according to inclusion criteria.After surgery,high polymer biomaterials were used to prevent from adhesion and reduce exogenous adhesion incidence.Following-up results demonstrated that high polymer biomaterials which affected endogenous and exogenous healing of tendon might prevent from tendon adhesion,provide foundation for early controlling passive activity,reduce exogenous adhesion occurrence,improve moving function of tendon,and promote tendon healing.CONCLUSION:Barrier effect of high polymer biomaterials can well prevent from tendon adhesion in clinic,especially intrathecal injection or local injection of sodium hyaluronate has both trophic and lubricant actions in preventing from tendon adhesion.However,other effective indicators and safety need to be further studied due to less including tests and weak evidences.

BACKGROUND: With wide application of biotechnological substitute materials, pelvic repair and reconstruction develop to a certain degree. Biomaterial patch is a major substitute for repairing injured pelvic fascia tissue, so it is widely used for pelvic reconstruction.OBJECTIVE: To investigate the feasibility, efficacy, and clinical value of biomaterial patch to pelvic reconstruction in the females.METHODS: Articles related to pelvic functional disorder, pelvic reconstruction, and application of patch implant were retrieved from PubMed (http://www.ncbi.nlm.nih.gov/PubMed) and (http://www.wanfangdata.com.cn) with the key words of "reconstruction of whole pelvic floor, mesh, synthetic mesh implants" in both Chinese and English between 1990 and 2008. Duplication studies were excluded. A total of 54 articles were initially retrieved, and 17 ones were included in the final analysis.RESULTS AND CONCLUSION:Pelvic organ prohpse, which was a major symptom of pelvic disorder in the females, caused by defect of pelvic supporting structure, injury, and functional disorder. Traditional operation could not solve fundamental question.At present, substitute materials for pelvic repair and reconstruction mainly include biomaterial patch (self-substitute materials, homogeneity substitute materials, and heterogeneity substitute materials) and artificial patch. All of them could substitute the injured pelvic fascia tissue; therefore, they were major substitute materials of pelvic tissue and widely used for pelvic reconstruction. Patch which was used for pelvic reconstruction realized the recovery of anatomic structure and caused functional recovery, with simple and easy processing. Additionally, patch application did not prolong operative time and cause complication, but induced well tolerance, security and reliability, and remarkable short-term effect on patients. However, the long-term efficacy should be further studied. The modified pelvic reconstruction is clinically valuable for patients with varying prolapsed sites.

Objective To study the neurotoxic effects of acute exposure of methylmercury at low dose and to provide some experimental data for deeply exploring the early mechanism of neurotoxicity of methylmercury. Methods SD rats were administered with methylmercury chloride by intraperitoneal injection with different doses of 0.05, 0.50 and 5.00 mg/kg and different exposure times of 20 min, 1 h, 4 h, 24 h. Mercury, ACh and AChE contents in rat brains were measured. Results Mercury contents in rat brains significantly increased after 20 min-exposure at both 0.50 and 5.00 mg/kg doses. Significant increase occurred after 4 h exposure at dose of 0.05 mg/kg. ACh and AChE in rat brains significantly changed after 20 min at every dose, showing certain dose-response and time-response relations. Conclusion Changes of ACh and AChE in rat brain after administration of low dose(0.05 mg/kg) and short time(20 min) exposure suggested certain modulation of CNS had been initiated. With the increases of exposure dose and time, methylmercury might begin to accumulate in rat brain and induce the significant changes of ACh and AChE.

OBJECTIVE:To provide reference for the further standardization of biological products injection for treatment in-structions. METHODS:32 biological products injection for treatment instructions collected from Ma’anshan Center for Disease Control and Prevention and Ma’anshan Central Hospital during Jan. to Jun. in 2015. The information of marked item was summa-rized and analyzed. RESULTS & CONCLUSIONS:Among 32 biological products injection for treatment instructions, the mark rates of drug names,main ingredients,character,indications,specification,usage and dosage,package,term of validity,opera-tive norm,license number,manufacturing enterprise and other items all reached 100%. Although the mark rates of ADR,contrain-dication,precaution,drug use of pregnant women and nursing mothers,drug interactions,pharmacokinetics,drug use of the elder-ly,storage and other items were relatively high,but some items lacked the specific description of the content. The mark rates of drug use of children,drug overdose,toxicology,warnings,clinical trial were 56.25%,62.50%,59.38%,37.50% and 18.75%. Some biological products injection for treatment instructions are not revised timely and not complete in content and non-standard in writing,which can not meet the needs that clinical pharmacists and patients get enough drug safety information from instructions. Manufacturing enterprise is suggested to label the content of package inserts completely,verify and supplement related content, standardize and improve the instructions.

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.

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.

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.

Effects of constituents from Schisandra chinensis (Wuweizi) on six liver microsomal CYP450 isozymes (CYP1A2, CYP2C6, CYP2C11, CYP2D2, CYP2E1 and CYP3A1/2) were studied in rats in vivo and in vitro. The in vitro incubation was conducted using liver microsomes of rats after multiple dosing of alcoholic/water extract from Schisandra chinensis. A HPLC-MS method was applied to determine the metabolites formation of six CYP450s probe substrates (phenacetin-CYP1A2, dextromethorphan-CYP2D2, diclofenac sodium-CYP2C6, mephenytoin-CYP2C11, chlorzoxazone-CYP2E1 and midazolam-CYP3A1/2) in rat liver microsomal incubations. The activity of CYP450 isozymes were represented by the formation of metabolites. Alcoholic extract of Schisandra chinensis (28-120 microg x mL(-1)) showed significant inhibitory effect on six CYP450 isozymes to a certain extent in vitro. Multiple dosing of Schisandra chinensis alcoholic extract (1.5 g x kg(-1), qd x 7d) had significant induction on CYP2E1 and CYP3A1/2, inhibition on CYP2D2 and CYP2C11, and no effect on CYP2C6 and CYP1A2. Water extract of Schisandra chinensis (100-500 microg x mL(-1)) also exhibited inhibition on the activity of CYP450 isozymes in vitro, whereas multiple administrations (1.5 g x kg(-1), qd x 7d) had significant induction of CYP2E1 and inhibition on CYP2D2, no effect on CYP2C6, CYP3A1/2, CYP1A2 or CYP2C11. The results suggested that the constituents from Schisandra chinensis exhibited the inhibition and induction on six rat liver microsomal CYP450 isozymes to a certain extent in vivo and in vitro. The possibility of interaction between Schisandra chinensis and coadministrative drugs will be considered base on the levels and subtype of CYP450 involved in the drug metabolism.

Objective:To study the positive expression rate of M2 subtype of macrophage cell surface molecules and the inflammatory factors of PPS in IL-4-induced M2 macrophage.Methods:The experiment was divided into 5 groups:blank control group, Model group,PPS groups(50 μg/ml,100 μg/ml and 200 μg/ml).The expression of CD206 and CD23 was used as bio-maker to confirm IL-4 induced macrophages by treating RAW264.7 with 20ng/ml of IL-4.IL-4 induced RAW264.7 cells were treated with PPS of 50μg/ml,100μg/ml and 200μg/ml for 24 h.Then the expression of CD206,CD16/32 and CD40 were analyzed by flow cytometry, and the mRNA expression of IL-1β,TNF-α,IL-10 and iNOS were detect by qRT-PCR.Results: After treated with IL-4,the positive rate of CD206 of RAW264.7 were high.After treated with PPS ,the rate of CD16/32 and CD40 in IL-4 induced RAW264.7 cells were high ,the expression of CD206 decreased,and the mRNA level of IL-1βand TNF-αincreased.Conclusion:RAW264.7 cells can be polarlized to M2 subtype macrophage by using 20 ng/ml IL-4.PPS enhances the mRNA of IL-1β,TNF-αand the expression of CD40, CD16/32 in IL-4-induced RAW264.7 cells .These results indicate that PPS can induce the M2 subtype to become M1 macrophages, can improve immune function of macrophages.