Canrenone is an important intermediate for the synthesis of eplerenone,a cardiovascular drug.C_ 11 ?-hydroxylation of canrenone is the key reaction,which can be done by microbial transformation.Rhizopus sp.SIPI-0602,kept in our lab,could high selectively transform canrenone to a compound named SIPI-11.By determining and analyzing the MS,UV,NMR etc.spectra of compound SIPI-11,its chemical structure was elucidated to be 11?-hydroxycanrenone.The study on flask transformation technology showed that the transformation ratio exceeded 90% when the substrate concentration was not more than 6g/L.

OBJECTIVETo synthesize venlafaxine with an improved novel method.

METHODSp-methoxypheny lethyl-acid was reacted with SOCl(2) to produce acyl chloride which was reacted with N,N-dimethylamine solution to get amide; then through Ivanov reaction and reduction by KBH(4)/BF(3).Et(2)O to yield venlafaxine.

RESULTVenlafaxine was successfully synthesized by using this method with an yield rate of 50.3%.

CONCLUSIONThe improved method is suitable for industrial production of venlafaxine.

Antidepressive Agents, Second-Generation ; chemical synthesis ; Cyclohexanols ; chemical synthesis ; Venlafaxine Hydrochloride

OBJECTIVETo modify the synthetic method of fluvoxamine.

METHODSFluvoxamine was synthesized from 4-trifluoromethylbenzonitrile by the steps of Grignard reaction, hydrolysis and oximation.

RESULTThe chemical structure of the synthesized product was confirmed by (1)HNMR, and the total yield reached to 36.16%.

CONCLUSIONThe results indicate that the synthetic route is practical.

Fluvoxamine ; chemical synthesis ; Serotonin Uptake Inhibitors ; chemical synthesis

OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.

RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.

CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.

Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits

Objective:To prepare monoclonal antibodies specifically against an immunogenic fragment in ectodomain of prostate-specific membrane antigen ( PSMA ).Methods: An polypeptide immunogenic fragment in the ectodomain of PSMA was predicted by biological information technology,and then it was expressed prokaryotically.BALB/c mice were immunized with the prokar-ytically expressed recombinant polypeptide antigen,to prepare the monoclonal antibodies specifically against an immunogenic fragment in ectodomain of PSMA by hybridoma technology,purification of monoclonal antibody by affinity chromatography,characterization of the monoclonal antibodies by Western blot.The radioimmunoimaging in prostate cancer model was performed by using the labeled McAb.Results:Throught the software analysis,we got the antigen fragment in the ectodomain of PSMA containing 310aa sequences higher specificity, artificially synthesized gene sequence of the region, and constructed a prokaryotic expression vector pET-32a-r-ectodomain-PSMA,by prokaryotic expression we obtained the 50 kD target antigen,after hybridization,the three positive hybridoma cell lines (5E6,4A5 and 4D7) were selected by ELISA using target antigen,the isotypes of 5E6 and 4A5 were IgG2a,the isotypes of 4D7 were IgG1,the titer of three monoclonal antibodies was above 1∶256 000.Western blot results showed that the prepared monoclonal anti-bodies could binding specifically to the antigen in the ectodomain of PSMA.Radioimmunoimaging in prostate cancer animal model results further confirm that the prepared monoclonal antibodies could combinate with the antigen in the ectodomain of PSMA in the animal body, and make the tumor imaging.Conclusion: The prepared monoclonal antibodies can specifically recognizes the PSMA antigen,which laid the foundation for the immunodiagnosis and immunotherapy of prostate cancer.

Objective: To observe the clinical efficacy of sinew-bone balancing manipulation in treating lumbar disc herniation (LDH) and offer clinical evidence to support the concept of paying equal attention to sinew and bone. Methods: Sixty LDH patients were randomized into an observation group and a control group, with 30 cases in each group. The observation group was treated with the sinew-bone balancing manipulation, and the control group received conventional Tuina (Chinese therapeutic massage) manipulation. The clinical efficacy and posterior muscle chain tone effect were compared between the two groups by observing the visual analog scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and posture-associated indicators. Results: The total effective rate was 86.7％ in the observation group, higher than 76.7％ in the control group, but the between-group difference in efficacy was statistically insignificant (P>0.05). After treatment, the VAS and JOA scores, angle-dependent muscle tone indicator of the posterior muscle chain, and lumbar posture symmetry showed significant changes in both groups (P<0.05). The VAS and JOA scores, angle-dependent muscle tone indicator of the posterior muscle chain, and lumbar posture symmetry in the observation group were significantly different from those in the control group after treatment (P<0.05), but the between-group difference in the general posture symmetry was statistically insignificant (P>0.05). Conclusion: Both the sinew-bone balancing and conventional Tuina manipulations can reduce pain in LDH patients, improve lumbar function, and adjust the angle-dependent muscle tone coefficient of the posterior muscle chain and lumbar posture symmetry; except for the general posture symmetry of the posterior muscle chain, the sinew-bone balancing manipulation wins out over the conventional Tuina manipulation.

OBJECTIVETo investigate the clinical value of Paroxetine combined with mid-frequency electrical pulse acupoint stimulation (EPAS) in the treatment of premature ejaculation (PE).

METHODSTotally 69 PE patients were equally assigned to receive oral Paroxetine 20 mg/d, mid-frequency EPAS, or oral Paroxetine 10 mg/d combined with mid-frequency EPAS (P + EPAS) , all for 8 weeks. We obtained the intravaginal ejaculation latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE-5) scores of the patients before and after treatment, and compared adverse reactions among the three groups of patients.

RESULTSOne patient of the Paroxetine group gave up treatment because of abdominal pain and nausea. Compared with the baseline, the patients in the Paroxetine, EPAS, and P + EPAS groups all showed markedly increased IELT ([0.92 ± 0.11] vs [4.07 ± 0.11] min, P < 0.01; [0.92 ± 0.12] VS [2.78 ± 0.17] min P < 0.05; [0.91 ± 0.09] vs [5.31 ± 0.13], P < 0.01) and decreased CIPE-5 scores (12.5 ± 3.0 vs 22.0 ± 2.1, P < 0.01; 12.8 ± 2.9 vs 19.5 ± 1.9, P > 0.05; 13.1 ± 2.8 vs 25.2 ± 2.1, P 0.01), with statistically significant differences between the P + EPAS group and the other two (P < 0.05). The total effectiveness rate was 95.7% in the P + EPAS group, remarkably higher than in the Paroxetine (72.7%, P < 0.05) and the EPAS group (47.8, P < 0.01).

CONCLUSIONOral Paroxetine combined with mid-frequency EPAS has a higher safety and efficacy than either Paroxetine or EPAS alone in the treatment of PE.

Acupuncture Points ; Aged ; Combined Modality Therapy ; methods ; Ejaculation ; Electroacupuncture ; methods ; Humans ; Male ; Paroxetine ; therapeutic use ; Premature Ejaculation ; therapy ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome

OBJECTIVETo synthesize epalrestat and to improve the method of synthesis.

METHODSGlycine reacted with carbondisulfide,then with ClCH(2)COONa to give 3-carboxymethylrhodanine. PhCHO reacted with CH(3)CH(2)CHO in NaOH/EtOH solution to produce 2-methylcinnamaldehyde.3-carboxymethylrhodanine and 2-methylcinnamaldehyde were treated with NH(3).H(2)O to obtain epalrestat.

RESULTThe described method was effective in synthesis of Epalrestat and the yield was higher than that of in references.

CONCLUSIONThe results suggest that this method is suitable for industrial production.

Aldehyde Reductase ; antagonists & inhibitors ; Enzyme Inhibitors ; chemical synthesis ; Rhodanine ; analogs & derivatives ; chemical synthesis ; Thiazolidines

Objective To study the effects of vascular endothelial growth factor(VEGF)on production of pulmonary surfactants.Method Fetal rat lungs were obtained at 19-day gestation.Primary culture of typeⅡalveolar epithelial cells(AECⅡ)was performed using IgG panning technique.The rats was divided into groups: VEGF,Dexamethasone,VEGF plus Dexamethasone and a control.Total phospholipids,phosphatidylcholine (PC),phosphatidyl glycerol(PG)and sphingornyelin(SM)were determined.Results expressed as mean?SEM. Comparison between groups were made with LSD-t test and one -way ANOVA.Result VEGF,Dexamethasone and VEGF plus Dexamethasone groups showed increased amount of total phospholipids and its compositions on the first day of culture.Conclusions VEGF-165 promotes the production and secretion of pulmonary surfactant. VEGF and Dexamethason may go through different mechanism for enhancement of synthesis of pulmonary surfactant,thereby improve biological function of AECⅡ.

Objective To explore a better method for treatment atrophic rhinitis.Methods 56 patients with atrophic rhinitis(96 lateral)were treated by nasal submucou pediculated bone-suberiosteal muscle flap extracted from anterior wall of sinus maxillaries.Results All patients were followed 2 to 10 years,total effective rate was 100 %, with 49 cases(87.5 %)showing prominent effect.Conclusion The grafted flap cannot be assimilated,felled off and necrosis,because the flap has rich blood supply.This methods has obvious short-term effective and stable long-term effective.No complications were found.