Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (-) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized a convergent route using the key and optically pure building block , which was first synthesized asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds and both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.

Association between leptin and postpartum depression / 中国神经精神疾病杂志

Objective This study aims to examine the association between leptin and postpartum depression symptoms. Methods Two hundred pregnant women were enrolled and their prenatal serum leptin levels were measured by using enzyme-linked immunosorbent assay (ELISA). The state of depression was first assessed on the third day after delivery and reassessed by a telephone follow up on the 42nd day using the Edinburg postnatal depression scale (EPDS) after delivery. Patients with postpartum depression symptoms with EPDS score ≥13 points after 3 days postpartum or 42 days postpartum were recruited as the depressive symptom group. Results The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 3rd day) and the control group were 1.36 (1.15, 1.68) μg/L and 1.49 (1.28, 1.91) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P=0.021). The medians and lower and upper quartiles of the prenatal serum leptin levels in the depressive symptom group (the 42nd day) and the control group were 1.17 (1.01, 1.36) μg/L and 1.50 (1.29, 1.90) μg/L, respectively. After normal conversion, the serum leptin level was significantly lower in the depressive symptom group than in the control group (P＜0.001). EPDS scores 3 days postpartum (r=-0.199, P=0.014) and 42 days postpartum (r=-0.254, P=0.002) were negatively correlated with prenatal serum leptin levels. Multiple logistic regression analysis showed that the prenatal leptin levels were associated with depressive symptoms at 42 days postpartum (OR=0.026, P=0.001). Conclusion Prenatal serum leptin levels may be associated with postpartum depressive symptoms, and high levels of leptin are protective factors for postpartum depression.

Colaizzi 7-step analysis in patients with senile cataract eye surgery applications of subjective analysis / 中国实用护理杂志

Objective Explore Colaizzi′s 7-step analysis in patients with senile cataract surgery subjective feelings and provide a basis for formulating targeted interventions. Methods It was a phenomenological study,and a total of 21 cases were recruited and conducted with semi-structural interviews. Results Five themes were found including fear,discomfort,insecurity,eager to communicate,a strong sense of family support. Conclusions Importance to subjective feelings, after entering the operating room to strengthen communication with the patient, increase opponents cognition, is an important measure to reduce the psychological burden of patients. And evidence-based, and scenario training before the increase,using a variety of forms of education,help to reduce patient anxiety and fear and promote patient safety.

Pharmacokinetics of H002, a novel S1PRmodulator, and its metabolites in rat blood using liquid chromatography-tandem mass spectrometry

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2-100 ng/mL for H002 and H002-M, while 0.5-100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from -9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.

Spns 2,a transporter of sphingosine-1-phosphate:research advances / 国际药学研究杂志

Sphingosine 1-phosphate(S1P),a bioactive lipid signaling molecule,plays important roles in diverse cellular functions such as cell proliferation,differentiation and migration,etc. S1P is intracellularly produced from sphingosine and subse?quently released to the extracellular fluid,then specifically binds to S1P receptors on target cells. S1P mainly originates from hemato?poietic cells and vascular endothelial cells. Several findings have revealed that ATP-binding cassette(ABC)transporters in erythro?cytes and platelets and Spinster homologue 2(Spns2)in endothelial cells both function as S1P transporters. Spns2 is proposed to be the first physiologically functional S1P transporter. Based on the amino acid sequence homology,Spns2 is predicted to belong to the major facilitator superfamily(MFS)transporters. Spns2-deficient mice are recently used for the further characterization of Spns2 func?tion. Accumulating results suggest that the S1P concentration in the plasma of Spns2-deficient mice is reduced notably compared with wild-type mice. In addition,lymphocyte egress to the blood stream in Spns2-deficient mice is blocked. Here,we review the research history,enzymatic properties,substrate,physiological functions of Spns2 and the correlation between Spns2 and diseases such as au?toimmune diseases and cancer,which could provide fundamental reference for further study of Spns2.

Survey and Analysis of Label Items in 32 Biological Products Injection for Treatment Instructions / 中国药房

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.

Design and application of ophthalmologic peri-operative information systems / 中国实用护理杂志

Objective To research patients with ophthalmologic perioperative information systems, strengthening the information management of nursing work, achieving consensus and sharing of health care information resources, and then to explore the clinical application effects of this ophthalmologic peri- opera-tive information systems. Methods The convenient sampling method was used in the study. The control group was consisted of 1 740 patients in our hospital from January to March 2013 (before the application of ophthalmologic perioperative information systems). The observation group included 2 078 patients of the same hospital (after the application of ophthalmologic perioperative information systems). The control group adopted routine pre- operative information acquisition method, the observation group applied ophthalmologic perioperative information systems, which included input function, reading function and statistical function. The incidence rate of canceled operation and satisfaction were compared between two groups. Results Ophthalmologic peri- operative information systems provided patients with information gathering, query and analysis in different periods. The rate of the canceled operation reduced in the observation group from 3.74% (65/1 740) to 2.69% (56/2 078) in the control group, χ2=3.91, P<0.05. The satisfaction degree increased from 91.84 % (1 598/1 740) in the observation group to 96.78% (2 011/2 078) in the control group, χ2=44.60, P<0.05, the difference was statistically different. The hospitalization days from April to September in 2013 shortened compared with those of the same period in 2012. Conclusions Ophthalmologic peri- operative information systems promotes the scientific and informatization of nursing information, which is worthy of wide clinic application.

Interaction of butylphthalide with rat and human liver CYP450 isoenzymes / 药学学报

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.

Transformation of PPS induce M2 subtype to M1 macrophages / 中国免疫学杂志

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.

Resistance reversal effect of a novel taxane compound NPB304 and its collaboration with verapamil / 药学学报

The tumor multidrug resistance reversal effect of NPB304, a novel taxane, was studied. MTT assay was used to determine the IC50 of chemotherapy drugs. Western blotting assay was applied to analyze the expression of P-glycoprotein (P-gp). The effect of compounds on the P-gp function and P-gp ATPase activity was determined by rhodamine 123 (Rh123) accumulation assay and analysis kit, respectively. Molecular docking was employed to predict the binding force between compounds and P-gp. Transmembrane transport of NPB304 was analyzed using MDCK II and MDR1-MDCK II cell model. NPB304 displayed multidrug resistance reversal effect on KBV cells and MCF-7/paclitaxel cells, NPB304 collaborative with P-glycoprotein (P-gp) inhibitors verapamil enhanced the reversal activity, specifically, 10 μmol x L(-1) verapamil in combination with paclitaxel reversed resistance by 56.5-fold, while combined with NPB304 increased the reversal fold; NPB304 synergistically increased Rh123 accumulation in the resistant cells when combined with verapamil, and NPB304 at 0-1 μmol x L(-1) enhanced the ATPase activity activated by verapamil was observed. NPB304 existed the hydrophobic interactions with the TM regions of P-gp, and the binding force between NPB304 and the A chain of the TM region was stronger. P-gp ATPase activity assay demonstrated NPB304 at lower concentrations (0-1.5 μmol x L(-1)) could activate the P-gp ATPase, playing a role on inhibition of P-gp function. However, NPB304 did not have an obvious feature of P-gp substrate. NPB304 exerted itself and synergy with verapamil activity on reversing tumor resistance via inhibiting the P-gp function.

Anti-rejection study in mice skin transplantation of a novel immunosuppressant SYL934 / 中国药理学通报

Aim To determine the effect of SYL934 , a novel immunosuppressant, on skin allograft rejec-tion. Methods HTRF-IP1 assay was used to evaluate the agonistic activity of SYL934-P, the active form of SYL934 in vivo, on S1P1 and S1P3 in vitro. SD rat peripheral blood lymphocytes ( PBL ) test and heart rate test was used to assess the in vivo immunosuppres-sive effect and heart rate effect of SYL934 . Mice skin graft transplantation experiment was used to observe the effect of SYL934 on skin allograft refection. ResultsSYL934-P selectively activated S1 P1 but not S1 P3 in vitro. Single orally administration of SD rats with SYL934 decreased the PBL significantly and played an obviously immunosuppressant role, but did not affect the heart rate. Daily orally administration of mice with SYL934 significantly increased the survival rate of al-lografts of skin slice in mice. Conclusion SYL934 has great selectivity in vitro and good activity in vivo, which indicated it potential use as an anti-rejection drug in skin transplantation.

Chemical-pharmacokinetic-pharmacodynamic fingerprints of Schisandra chinensis alcoholic extract / 药学学报

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.

Pharmacokinetics of tenofovir in Beagle dogs after oral dosing of tenofovir dipivoxil fumarate using HPLC-MS/MS analysis / 药学学报

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.

Effects of Schisandra chinensis (Wuweizi) constituents on the activity of hepatic microsomal CYP450 isozymes in rats detected by using a cocktail probe substrates method / 药学学报

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.

Effect of CYP3A and P-glycoprotein on the absorption of buagafuran in rat intestinal lumen / 药学学报

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.

Clinical characteristics of pelvic reconstruction using biomaterial patch in females / 中国组织工程研究

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.

Barrier effects of various high polymer biomaterials on prevention of tendon adhesionA systemic evaluation / 中国组织工程研究

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.

Improved synthesis and pharmacological evaluation of racemic 11-demethylcalanolide A / 药学学报

An improved and practical synthesis of racemic 11-demethylcalanolide A [(±)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5, 7,-dihydroxy-4-n-propylcoumarin(3). Poly phosphoric acid (PPA) catalyzed acylation of compound(3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone(4). A microwave assisted synthetic method preparing chromene(6) using chromenynation of chromanone(4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene(6) using NaBH<,4> with CeCl3·7H2O preferably gave (±)-1. The overall yield of this four step synthesis of (±)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (±)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65mg·kg-1 and 525.10mg·kg-1, respectively. The C<,max> and AUC<,0-∞> were 0.54μg·mL-1 and 1.08(μg·mL-1)·h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100mg·kg-1 (±)-1 once intraperitoneally were similar to that of 5mg·kg-1 of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (±)-1 was warranted.