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AIM: To compare the pharmacokinetics and relative bioavailability of the domestic and imported sustained-release tablets of gliclazide in healthy volunteers. METHODS:The study was performed by an four-period crossover design with singledose and multiple-dose administration. The plasmadrug concentrations of twenty male healthy volunteers were determined by liquid chromatography with mass spectrum detector method (LC-MS). RESULTS:The pharmacokinetic parameters after a single oral dose of the domestic and imported gliclazide tablets were (7.2+s 1.5) h and (6.9 +1.4) h for tmax, (13.4 ±1.2) h and (13.7 +1.3) h for t1/2, (2.4 +0.8) mg ·L-1and (2.3 ±0.6) mg· L-1 forcmax, (48 ±14)mg · h · L-1 and (48 +14) mg· h · L-1 forAUC0-60,(51+15) mg· h· L-1 and (50±14) mg· h· L-1for AUC0-∞, (22.4 ± 1.9 ) h and (22.8 ± 1.9 ) h for MRT, respectively. The steady state pharmacokinetic parameters after multiple doses of the domestic and imported gliclazide tablets were (6. 1 ± 1.4) h and (6.5+1.4) h for tmax, (4.6±0.9) mg· L-1 and (4.7±1.1) mg· L-1 for cmax, (0.23 ±0.08) mg ·L-1and (0.26±0.08) mg· L-1 forcmin, (1.6±0.3) mg·L-1 and (1.6±0.3) mg · L-1 for mean value of steady plasma-drug concentration (cav),(94±19) mg· h · L-1 and (95 ±20) mg · h · L-1forAUCss, (282 ±33)% and (283 ±43)% for degree of fluctuation DF ), respectively. The relative bioavailability of the domestic gliclazide tablet to the imported gliclazide tablet following a single and multiple dose were ( 102 ± 9) % and (99 ± 10 ) %, respectively. Main pharmacokinetic parameters between the two formulations in both single and multiples dose studies showed no statistical difference ( P >0.05 ). CONCLUSION: The result of two one side t-test shows that the two formulations are bioequivalent.

AIM: To study inhibitory effect on proliferation of docetaxel on murine angiosarcoma cell line (ISOS-1) and compare with etoposide. METH ODS: In vitro, the inhibitory effect on proliferation of docetaxel and etoposide on ISOS-1 cells were carried out by Alamar Blue assay. In vivo study, after murine angiosarcoma model establishment, seventy mice were divided into trial and control group with 5 mice for each group. The dosages of docetaxel and etoposide were 5, 10, 20 mg · kg-1 respectively through administration by intravenous (iv) or intraperitoneal (ip) injection. The iv injection was performed once a week and total 4 times as one course. The ip injection was taken once a day, keeping for 5 d as a course and then repeated once more after 2 wk. The control group was injected with the normal saline. The volumes of the tumors and the survival days were calculated. RESULTS: In vitro study, the IC5o of docetaxel for ISOS-1 cells was 15.8 μg · L-1 showing obviously lower than that of et oposide group ( 1. 175 mg · L-1 ). In vivo study, the anti-tumor effect of docetaxel was better than that of et oposide at three different doses by iv, and all the in hibitory rates of tumor volume were more than 70 %. The life prolonging effect of 5 mg · kg- 1 docetaxel was similar to that of etoposide 10 mg · kg-1. The adverse reactions of ip injection were stronger than those of ivinjection. The dosage of etoposide 20 mg · kg-1 almost reached the lethal dose. CONCLUSION: Docetaxel shows obviously inhibitory effects on proliferation of murine angiosarcoma cell line (ISOS-1), which is superior to that of etoposide. It is safe and effective with low dosage once a week by iv.

AIM: To study the pharmacokinetics of magnesium isoglycyrrhizinate (MgIG),which was diluted by 5%glucose injection in a total volume of 250 mL, after a single and multiple intravenous dose in 10 healthy volunteers.　METHODS: MgIG 100 mg once daily for 9 d in the multiple-dose regiment. Plasma MgIG concentrations are measured using high performance liquid chromatography (HPLC). Waters HPLC instrument was used with the Hypersil ODS2 C18 (5 μm, 300 mm×4.6 mm) column. The mobile phase was composed of 0.23 mol·L-1 phosphate buffer (pH=7.4):acetonitrile (79∶21).Flow rate was 1.0 mL·min-1 and column temperature was maintained at 40°C. The UV detector was set at 250 nm. The concentration time curves of MgIG were fitted to a two-compartment open model.　RESULTS: The pharmacokinetic parameters obtained from the single-dose study were as follows: cmax=(29±s 4) mg·L-1;t(1)/(2)α=(1.72±0.27) h;t(1)/(2)α=(23±3) h and AUC0-72=(448±75) mg·h·L-1. The steady-state pharmacokinetic parameters were: cssmin=(13±3) mg·L-1;cssmax=(42±6) mg·L-1;cav=(21±4) mg·L-1;t(1)/(2)α=(1.6±0.4) h;t(1)/(2)β=(24±4) h and AUCss0-24=(513±108) mg·h·L-1.CONCLUSION:The distribution and elimination rate of MgIG were not changed after multiple intravenous administration.

AIM: To investigate the efficacy and safety of low-dose leflunomide (Lef) combined with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). METHODS: Sixty-four RA patients were randomly divided into two groups, with 32 patients in each group. All the patients were required to stop the treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for 1 wk before entering the trial. Patients in the Lef+MTX group received Lef 20 mg, po, qd in the first 4 wk, followed by 10 mg,po, qd for next 20 wk. Patients also received MTX 7.5 mg,po, qw during the trial. Patients in the MTX group received MTX 15 mg,po, qw for 24 wk. Physical and laboratory examinations were performed at the beginning of the trial, after 12 wk treatment and 24 wk treatment. Entopic X-ray examination of both hands was performed before and after the treatment. RESULTS: The rate of remarkable improvement was 88% (28/32) in Lef+MTX group and 38% in MTX group (12/32). Adverse reactions were reported in 12% (4/32) patients in Lef+MTX group and 43% (14/32) patients in MTX group. The reported adverse reactions were rash and nausea in Lef+MTX group and nausea, vomiting, oral ulcer, alopecia, ALT elevation, palpitation and menoxenia in MTX group. CONCLUSION: Combination of Lef with MTX is safe and effective in treatment of RA with less adverse reactions.

AIM: To evaluate the safety and efficacy of loteprednol for controlling of ocular inflammation. METHODS: Data from 8 relevant monographs were retrieved by means of computerized and manual search. The combined analysis of the data was assessed in terms of clinical and statistical criteria, and the data were extracted and synthesized by using the statistical techniques of meta-analysis. Treatment effects and safety of loteprednol were through counting as risk difference between treatment and control groups. The estimates of pooled risk differences were computed according to a random-effects model. RESULTS: A total of 1 660 patients were included in this meta-analysis. Pooled risk differences of intraocular pressure elevation were 1 % (95 % CI, -1 %, 3 %) compared with placebo, -5 % (95 % CI, -9 %, 0 %) compared with prednisolone, respectively. Compared with placebo, pooled risk differences of inflammation improvement were: 31 % (95 % CI, 22 %, 40 %) of postoperative inflammation, 28 % (95 % CI, 19 %, 37 %) of seasonal allergic conjunctivitis, and 26 % (95 % CI, 18 %, 35 %) of giant papillary conjunctivitis, respectively. Compared with prednisolone, pooled risk differences of inflammation improvement of acute anterior uveitis was -15 % (95 % CI, -25 %, -4 %). CONCLUSION: Loteprednol is a safe and effective corticosteroid in controlling ocular inflammation such as postoperative inflammation, seasonal allergic conjunctivitis, giant papillary conjunctivitis, and acute anterior uveitis.

AIM: To analyse quantitatively the interactions among ethanol, chloral hydrate and naloxone with isobologram, Q-test and multiple logistic regression methods. METHODS: The hypnotic effects of the three drugs on Kunming mice were observed. In two drugs interaction study, chloral hydrate and ethanol were given at different ratios (25∶75, 50∶50, 78∶22 and 80∶20). In three drugs interactions study, 15 min after treatment of naloxone at fixed dose (0.5 mg*kg-1 and 0.2 mg*kg-1) the mixture of chloral hydrate and ethanol (at 1∶1 and 1∶3 ratio) was given to induce sleep. The ED50 for hypnotic action (righting reflex loss) of chloral hydrate, ethanol, naloxone and their mixtures were calculated by use of isobologram, interaction Q-index test and multivariate logistic regression analysis. RESULTS: The mixtures of ethanol and chloral hydrate in all ratios revealed partial but significant synergism. But in addition with naloxone the three agents showed different natures of interactions according to different naloxone levels. CONCLUSION: There are synergistic interactions in hypnotic ED50s between ethanol and chloral hydrate at different ratios and antagonistic interaction in adding a fixed dose of naloxone. The results coincide with the pharmacologistic mechanism discussed in this paper.

AIM: To study the effect of genistein on c-myc mRNA expression induced by oxidized low density lipoprotein (ox-LDL) in human vascular endothelial cells (ECV304). METHODS: LDL were isolated from healthy human plasma by gradient ultracentrifugation and oxidized by CuSO4. ECV304 cells were exposed to ox-LDL 200 mg*L-1 in the presence or absence of genistein 100 μmol*L-1 for 1, 2, and 4 h in vitro. Northern blot was employed to measure c-myc mRNA levels of ECV304. RESULTS: In response to ox-LDL 200 mg*L-1, c-myc mRNA expression in ECV304 increased by 3 fold for 1h and 3.3 fold for 2 h and decreased below the control level at 4 h. Expressions of c-myc stimulated by ox-LDL in the presence of genistein 100 μmol*L-1 for 1 h and 2 h were separately 80 percent and 60 percent of that in the absence of genistein 100 μmol*L-1. CONCLUSION: Genistein can effectively inhibit c-myc mRNA expression in ECV304 induced by ox-LDL.

AIM: To investigate the efficacy and safety of leflunomide (Lef) in long-term treatm ent of rheumatoid arthritis (RA).　METHODS: Twenty-one patients ［M 2,F 19; age (45±s 9)a］ with RA were s elected. Disease duration was (59±48) mo. All patients enrolled in double-blin d or single-blind trials with Lef 20 mg, po, qd for 6 mo at first. Doses of leflunomide in nine patients were reduced down to 10 mg, qd and all the others c ontinued the treatment with Lef at 20 mg, qd. 　RESULTS: All twenty-one patient s we re followed up for 1.5 a. The results showed that twenty patients had remarkable improvement and one patient had clinical remission. Ni neteen patients had been followed up for more than 2 a and twelve patients had r emarkable improvement while seven patients had clinical remission. Twelve pati ents had been followed up for 3 a and three of them had remarkable improvement while nine patients had clinical remission. Total rate of adverse reactions was 19 %( 4/21). 　CONCLUSION: This study shows that long-term treatment of RA with Lef is effec tive and safe.

Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival.However,chronic allograft failure,antibody mediated rejection,recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life.New immunosuppressive agents and protocols are being evaluated to combat these problems.Importantly,clinicians must work to manage post-transplant complications and avoid complex medication regimens,which will potentiate drug interactions and non.compliance.Different organs have different immunogenicities and each recipient has a unique clinical and immunologic profile.The clinician must recognize these variations and customize the immunosuppressive regimens and treatment protocols based on the individual condition.The general principles of an individualized immunosuppressive protocol should take the following factors into account:organ type,donor and recipient characteristics,quality of the donor organ,recipienVs medical history,recipient's undedying disease,immunologic risk for acute rejection,potential co-morbidity related to immunosuppression,significant druginteractions,medication costs and patient compliance.In addition,the combination of immunosuppressive drugs must have a pharmacologic rationale to achieve the desired goal of suppressing the individual's immune system to render the patient tolerant to the allograft while minimizing co-morbidities.For the past few years,many clinical strategies have been applied in an attempt to improve graft survival or to reduce immunsuppressants induced side-effects.Specific protocols include steroid or CNI avoidance,minimization or withdraw,desensitization,and treatment for antibody mediated rejection,disease specific,and pediatric specific.The short-term outcomes from these different strategies are promising but the long-term results remain to be determined.Unfortunately,current immunosuppressive agents or strategies have failed to adequately control chronic rejection in most of solid organ transplantation except liver transplantation.Eady post-transplant complications aye generally related to the operation,the severity of pre-operative illness,immunologic status,and the quality of the donor organ.Careful recipient and donor selection is paramount to minimize severity of disease and medical comorbidities.These early complications include allograft dysfunction,cardiovascular and hemodynamic instability,and immunosuppressive drug-induced adverse effects.Acute infection remains a common and serious early complication despite new and effective drug therapies,placing the responsibility on the clinician for early recognition and treatment.Emerging resistant bacteria and fungi require early and aggressive intervention.Unlike infection,early aUograft rejection is usually limited and manageable with the newer immunosuppressive agents.However,it must be distinguished from other causes of allograft dysfunction(ie.recurrent hepatitis C,ealcineurin induced nephrotoxicity,or infection).Recently approved Cylex@immune cell function assay allows clinicians to tailor and individualize immunosuppression to prevent organ rejection while minimizing infection and complications.Improved patient and allograft survival has enabled transplant recipients to reach milestones and return to productive lives provided they are compliant. It was also challenged the clinician to manage the long-term complications of immunosuppression therapy, adverse drug interaction, recurrent diseases and chronic allograft failure. Long-term immunosuppressive therapy places transplant recipients at risk for renal insufficiency, cardiovascular and metabolic diseases, de novo malignancies, and psychosocial challenges. The management of viral hepatitis C re-infection, chronic allograft nephropathy, vasculopathy, and obliterative bronchiolitis is currently the greatest challenges facing the transplant specialist. The management of immunosuppressants induced adverse effects/drug interactions, chronic allograft failure and recurrent disease is dependent on regular clinical follow-up, an accurate diagnosis and appropriate treatment.Our challenge for the future will be to develop strategies to determine the best, cost-effective regimens for an individual patient to prevent long-term graft loss. I believe the management of immunosuppression and posttransplant complications is best met with a multidisciplinary team approach. This presentation will discuss the current immunosuppressive strategies and the common post-transplant complications. It is designed to help the clinician recognize individual risk factors and provide appropriate management.