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 evaluate the efficacy and safety of neurotropin in the treatment of neuropathic pain.METHODS: A systematic literature search was performed in biomedical database including MEDLINE,EMBASE, Cochrane Central Register of Controlled Trials, CBM and CNKI. All studies focused on the clinical controlled trials, especially randomized controlled trials (RCTs) . The outcome measures included efficacy,life quality, cost of the treatment and adverse reactions. Quality assessments of clinical trials were evaluated with Jadad Score. Meta-analysis of included studies was performed with Revman software. RESULTS: Twenty-six clinical trials were included. Jadad Score of 24 trials was less than 3, which indicated the poor quality of the trials. None of the clinical trials evaluated the changes in life quality and cost related to neurotropin treatment.Meta analysis of 11 trials indicated neurotropin was more effective than placebo or blank, and the odds ratio of efficacy was 3.84 [2.68, 5.50] . The combining effect of 6 RCTs showed that neurotropin decreased the pain scores measured by Visual Analog Scale significantly compared with placebo or blank, the weighted mean difference (WMD) was -1.76 [-2.31, -1.21] . The pooled effects of the trials comparing neurotropin with other pain relieving drugs such as earbamazepine or NSAIDs also showed positive effect favored neurotropin.Neurotropin had no more adverse reactions than placebo, carbamazepine or NSAIDs, and the pooled risk difference was -0.01 [-0.04, 0.02] . CONCLUSION: According to present evidence, neurotropin may be effective and safe in the treatment of neuropathic pain. However, the poor quality of the studies decreases the persuasion of the results. Large-scale and well-designed RCTs with enough follow-ups should be carried out to provide further evidence for the use of neurotropin in neuropathie pain.

AIM: To investigate the effects of metallothionein (MT) induced by zinc on doxorubicin (DOX)-treated mice and to explore the potential mechanisms. METHODS: Male C57BL/6J mice were divided randomly into 4 groups (n = 6) following control, DOX, Zn and Zn plus DOX. Mice were pretreated with eikg-1, ip) or equal volume of saline, and were killed on d 4 after the last injection. Serum and hearts were collected for examination. RESULTS: Zinc pretreatment elevated cardiac MT levels significantly while other antioxidants in heart including glutathione (GSH), glutathione peroxidase (GSHpx) , superoxide dismutase (SOD), and catalase (CAT) were not altered. Severe oxidative injury occurred in the mice treated with DOX as myocardial lipid peroxidation and morphological changes manifested by myocardial fibers swelling and vacuolization and nuclear condensation or dissolution, with increased activities of serum creatine kinase and lactate dehydrogenase and depletion of GSH, GSHpx, and SOD while CAT activity was increased in compensation. However, pre-induction of MT with zinc attenuated all of these toxic changes significantly. Furthermore, DOX induced elevation of hydrogen peroxide in heart tissues was greatly inhibited by zinc pretreatment. CONCLUSION: Preinduction of MT by zinc protects the heart from DOX-induced cardiotoxicity, and this effect is possibly correlated with the property of MT on scavenging free radicals in vivo.

AIM: To examine the pharmacodynamics of a self-developed oral colon-specific delivery coated tablets of 4-aminosalicylic acid (4-ASA) on rats. METHODS: Ulcerative colitis rat model was developed by intrarectal administration of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in alcohol. Rats were divided randomly into healthy control group, TNBS control group, TNBS + lower dose (coated tablets) group, TNBS +medium dose (coated tablets) group, TNBS + higher dose (coated tablets) group, TNBS + sulfasalazine (SASP) group, TNBS + medium dose non-coated tablet group. Several indices including macroscopic change,histological damage, and tissue myeloperoxidase (MPO) activity were examined after 5 consecutive oral drug administration to assess pharmacodynamics of the coated tablets. RESULTS: An experimental ulcerative colitis in rats was induced by TNBS. Compared with 4-ASA non-coated tablet group, decreased macroscopic and histological damage score and lower MPO activity were observed after the oral administration of 4-ASA coated tablets or SASP. There was no significant difference between the effects on the indices of higher dose of coated tablets and SASP (P ＞ 0.05) CONCLUSION: The self-made 4-ASA oral colon-specific delivery coated tablet showes higher effect than non-coated tablets to treat ulcerative colitis in rats.

AIM: To study the protective effects of baicalin on myocardial ischemia-reperfusion injury in rats. METHODS: The models of myocardial ischemia-reperfusion injury were established by occluding left anterior descending coronary artery (LAD) for 30 min, followed by reperfusion for 120 min. The rate of rise and decline of left ventricular pressure (±dp/dtmax) and end-diastolic pressure of left ventricle (LVEDP) were monitored continuously with polygraph. After reperfusion, the blood and myocardium samples were taken for determination of malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, Ca2+-ATPase activities in myocardium, creatine kinase (CK) and lactate dehydrogenase (LDH) in serum with spectrophotometer. The ultrastructural changes in ischemic myocardium were assessed by transmission electron microscope. RESULTS:dtmax and LVEDP, decreased plasma CK and LDH levels, reduced myocardial MDA content, and increased the activities of SOD, Na+-K+-ATPase, and Ca2+-ATPase in myocardium following ischemia-reperfusion. The ultrastructural injury in reperfused myocardium was relieved. CONCLUSION: Baicalin possesses a protective effect against myocardial ischnemia-reperfusion injury through scavenging oxide radicals and improving Na+-K+-ATPase and Ca2+-ATPase activities.

AIM: To investigate the effect of soybean isoflavones (SI) on ventricular remodeling induced by myocardial infarction (MI). METHODS: MI was induced by permanent ligation of the left anterior descending coronary artery (LAD) in male Sprague-Dawley (SD)rats. Rats were randomly divided into six groups: shamThree hours after the operation, the drugs or solvent were administrated ig qd for 35 d. Twenty-four hours after the last administration, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), peak systolic left ventricular pressure (Peak), maximal rate of left ventricular pressure rising (+dp/dtmax), maximal rate of left ventricular pressure declining (-dp/dtmax) and myocardial maximal shortening velocity (Vmax) were measured. After above hemodynamic parameters were measured, hearts were extracted. The ratio of total ventricle weight to body weight(TVW/BW) was calculated. Myocardial collagen was shown with the collagen-specific picrosirius red stain,myocardial interstitial collagen volume fraction(ICVF), perivascular collagen volume fraction(PCVF), infarct size,septal thickness (ST) and left ventricular diameter (LVD) were measured by image analysis system. RESULTS:(31 ± 5) %, respectively, all of which were significantly smaller than that in MI group (( 38.9 ± 2.9) %, P ＜ 0.01 ).In MI group, TVW/BW, LVD, ICVF and PCVF were remarkably increased compared with those in sham group (P ＜ 0.01 ). The increased TVW/BW, LVD, ICVF and PCVF were significantly reduced by treatment with eaprats in MI group was significantly decreased than that in sham group (P ＜ 0.01 ). The reduced ST could be in-dp/dtmax and Vmax were decreased (P ＜ 0.01 ), while LVEDP was increased (P ＜ 0.01 ), significantly. The reSION: SI can improve cardiac function and ventricular remodeling induced by myocardial infarction in the rat.