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.

AIM To assess antidiabetic and insulin sensitizing effect of a novel thiazolidinedione,neoglitazone, in different animal models of type 2 diabetes. METHODS Neoglitazone combined with low-dose insulin(0.2U·d-1 per mouse,sc)were given in streptozotiocin (STZ)-induced diabetic mice for 7 d to inspect its insulin-sensitive improvement. The antidiabetic effect of chronic oral treatment (8 wk) with neoglitazone on spontaneous diabetes mice (DB/DB mice) was examined. The levels of blood glucose were measured by a One-Touch blood glucose meter and pathology of heart, kidney, and pancreas tissues were observed under a light microscope. The hyperinsulinaemic-euglycaemic clamp technique was applied to measure the increase of glucose infusion rate (GIR) of neoglitazone on the immune insulin-resistant rats induced by Bacillus Calmette-Guerin therapy decreased ( 14±s4)%, (55±24)%,and (28±7)% of blood glucose levels compared with CMC-Na+insulin group, respectively (P < 0.01) . In DB/DB mice, neoglitazone showed better reduction in blood glucose levels than those of model animals (P < 0.01) , and pathological studies indicated that neoglitazone attenuated the diabetic kidney and pancreas lesions. During a hyperinsulinaemic-euglycaemic clamp,neoglitaxone(10,30,and 100mg·kg-1·d-1,ig for 2 wk )-treated groups required significantly higher GIR to maintain basal glucose concentrations than model group (P < 0.01 ). CONCLUSION Neoglitazone could directly enhance insulin sensitivity and ameliorate insulin resistance in different diabetic animal models.

AIM To inVestigate the positiVe transcription elongation factor b(P-TEFb)expressjon and the effect of berberine on diabetic retina of the rat.METHODS Type 2 diabetes mellitus rat models were diabetic control rats(group A)that neither received STZ nor the high-carbohydrate/high-fat diet;16-wk diabetic rats without any drug treatment(group B);diabetic rats treated with berberine at a dose of 75,150 or staining and P-TEFb(cyclin-dependent kinases 9(CDK9)and cyclin T1)protein expression was detected by immunohistochemjstry.RESULTS The retinas of control group were thicker than those of other 6 groups.After thickness but no difference in retinal structure among all groups.Middle-.high-dose berberine and rosiglitazone fenofibrate showed no effect on CDK9 and cyclin T1 expression.CONCLUSION Berberine modulating P-TEFb level in diabetic retina may probably be one of the mechanisms to ameliorate retinopatby induced by STZ and the high-carbohydrate/high-fat diet.

AIM To study the pharmacokinetics of arbidol capsule in Chinese healthy volunteers.METHODS A single oral dose of arbidol capsule 200 mg was given to 20 healthy volunteers respectively.Plasma samples were prepared based on a simple liquid-liquid extraction.The extracted samples were analyzed by HPLC equipped with UV detection.Pharmacokinetic parameters were calculated by 3P87 software. RESULTS The main pharmacokinetic parameters of arbidol were as follows:c(max)(418±s 241)μg·L-1,t(max)(1.3±1.2)h,t(1/2α)(1.9±2.3)h,t1/2β(14±5),hAU0-t(2 633±1 071)μg·L-1,Vc/F(0.7±0.6)L,CL(0.08±0.03)L·h-1,CONLUSION The pharmacokinetics of arbidol capsule in human body accord with two-compartmetn open model.The study will offer the pharmacokinetic parameters for the clinical application of arbidol.

AIM: To study the pharmacokinetics of loratadine in healthy volunteers after single and multiple oral administrations of loratadine, paracetamol and pseudoephedrine (LPP) sustained-release tablets.METHODS: Twenty-four volunteers were randomized into two groups which included six men and six women in each group. In the single dose design, volunteers received either one or two tablet (s) of LPP. After 1 wk wash out period, volunteers of one tablet group participated in multiple dose design in which each volunteer received one tablet of LPP twice per day for six consecutive days. The concentrations of loratadine in plasma were determined by HPLC-MS method and the pharmacokinetic parameters were calculated. RESULTS: In the single dose design, main pharmacokinetic parameters of one and two tablet group were as follow: cmax were ( 1.5 ±groups were similar to each other. The obtained multi-dose pharmacokinetic parameters were as follows: AUCssrespectively. D (F) was (3.3 ± 0.8) %. The pharmacokinetics of loratadine was linear. There were no significant difference in pharmacokinetics between single-dose and multi-dose. CONCLUSION: The release and absorption of loratadine in experimental tablet are close to those in loratadine tablet and not affected by the other two components, pseudoephedrine and paracetamol, in LPP sustained release tablet.

AIM: To develop a simple and sensitive high-performance liquid chromatography (HPLC) for the quantification of zidovudine and to study the pharmacokinetics of two kinds of zidovudine capsules in Chinese healthy volunteers. METHODS :The concentrations of zidovudine in plasma were determined by a validated HPLC method with UV detection. A randomized two-way crossover study was conducted in 18 fasting volunteers to compare plasma pharmacokinetic profile and single-dose tolerability of a new zidovudine capsules. RESULTS: The main pharmacokinetic parameters of two formulations, reference and test capsules, were as follows: cmax were (2 252±s 837) μg·L-1 and (2 300±1 099) μg·L-1; tmax were (0.49±0.19) h and (0.5±0.3) h;t1/2 ke were (0.93±0.19) h and (0.99±0.24) h; AUC0-t were (2 530±452) μg·h·L-1 and (2 467±605) μg·h·L-1;AUC0-∞ were(2 689 ± 414) μg·h·L-1 and (2 583±575) μg·h·L-1. The results of ANOVA and two one-side t test statistical analysis for lg AUC0-t, lg AUC0-∞ and lg cmax showed that two formulations were bioequivalent. CONCLUSION:The method is convenient, sensitive, accurate and reproducible, and could be applied to determining the plasma zidovudine concentration and studying on pharmacokinetics. Two zidovudine capsules are bioequivalent in Chinese healthy volunteers.

AIM: To access the difference of the efficacy between terbinafine and itraconazole in the treatment of dermatophyte onychomycosis. METHODS: The Medline, Science Direct On Site (SDOS), and Springer database were searched in detail on the data of the mycological cure rates of the two antifungal agents for treatment of dermaphyte onychomycosis occourring in patients aged from 18 a to 60 a with the published double blind randomized clinical trials and then pooled. The odds ratio (OR) and its 95 % confidence interval (CI) were calculated. RESULTS: Six treatises of double blind randomized clinical trials were selected for this analysis according to the screening criteria. The mycological cure rate of continuous terbinafine 250 mg per day was higher than that of either therapeutic effect of itraconazole pulse 400 mg per day (OR = 5.01, 95 % CI (3.42 - 7.33)) or continuous itraconazole 200 mg per day (OR = 2.58, 95 % CI (1.91 - 3.49)) . CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of dermatophyte onychomycosis.

AIM: A new HPLC-MS method was developed to determine finasteride in human plasma. METHODS: Two formulations of finasteride tablets were given to 20 healthy male volunteers according to a randomized 2-way cross-over design. The samples were extracted by ethyl acetate under basic conditions, then were separated by C18 column and determined by mass detector. RESULTS: The calibration curve of finasteride was linear and intra-day and inter-day RSD were less than 10 %. The pharmacokinetics parameters of the two formulations (4.5 ± 0.5) h for t1/2; (3.0 ± 0.7) and (2.8 ± 0.9) h for tmax, respectively. The results indicated that there was no significant difference on cmax, A UC0-24, t1/2 or tmax values between the two formulations. CONCLUTION: The relative bioavailability of tablets I with respect to tablets Ⅱ is (99.3 ± 9.2) % by the A UC0-24 measurement, and bioe quivalence is observed between the two tablets.

AIM: To determine the distribution and frequency of functionally important allelic variants in the cytochromes P450 (CYP) 2C19, arylamine N-acetyltransferase 2 (NAT2), and thiopurine S-methyltransferase (TPMT) genes in the Han Chinese population and compare them with those of other ethnic populations.METHODS: Genotyping was carried out in a total of 210 unrelated Han Chinese volunteers derived from He-nan area. CYP2C19 variants ( * 2 and * 3), NAT2 variants ( * 6 and * 7), and TPMT variants ( * 3A, * 3B, and * 3C) were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP)assays. Detection of NA T2 * 5 and TPMT * 2 were performed using allele-specific polymerase chain reaction assays. RESULTS: Allele frequencies of CYP2C19 * 2 and * 3 occurred with 34.76 % and 6.4 %, respectively.Thirty-one persons ( 14.8 % ) carried two of these CYP2C19 alleles responsible for poor metabolizing activity.The frequencies of specif ic NAT2 alleles were 59.1%, 4.1%, 26.4 %, and 9.5 % for * 4 (wild-type), * 5(341C), * 6 (590A), and * 7 (857A), respectively. Genotyping of three different single nucleotide polymorphisms in the NA T2 gene revealed that the frequency of slow acetylators was 19.5 %. TPMT * 3C had an allelic frequency of 1.2 %. TPMT* 2, TPMT * 3A, or TPMT* 3B was not detected in the analysed samples. CONCLUSION: The overview of allele distribution for drug-metabolizing enzymes CYP2C19, NAT2, and TPMT among a Han Chinese population shows obvious difference to Caucasians. The data will be useful for clinical pharmacokinetic investigation and drug dosage administration to Han Chinese population.

AIM: To discuss the effects of phytoestrogenic-genistein on cathepsin K (CK) expression stimulated by interleukin-1α (IL-1α) in osteoclast-like cells (OCLs) . METHODS: The OCLs were isolated from tissue of human giant cell tumor of bone (GCT) . The cells treated with reagents were divided into 7 groups including control (treated with phenol red-free-DMEM), vehicle (treated with 1.2 nmol· L-1 IL- 1α), 10-10-10-6genistein, genistein+ ICI 182.780, and 17[β-estrodiol (17β-E2) group. The cells were treated with 1.2 nmol· L-1IL-1α after pre-treated with genistein or 17β-E2 for 48 h (excluded the control group) . Expression of CK wasdetermined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot in OCLs stimulated by IL-1α in the presence of genistein or 17[β-E2. RESULTS: The obvious increase of expression of CK by IL1α in vehicle group was noted in comparing with control group (P ＜ 0.01 ) . Genistein down-regulated CK gene expression stimulated by IL-1α at the transcription level in a dose-dependent manner (r = 0.68, P ＜ 0.01 ) .Genistein down-regulated CK protein expression stimulated by IL-1α also in a dose-dependent manner (r = 0.61,P ＜ 0.01 ). The effects of genistein were abrogated partly after treatment with the estrogen receptor antagonist ICI 182.780. CONCLUSION: Genistein inhibits CK expression stimulated by IL-1α partly through estrogen receptor in OCLs.