Objective To explore the single point target concentration for Neoral at 2 h postdose (C2) in Chinese renal transplantation recipients for the first 3 months following surgical procedures. Methods Neoral trough levels (C0) and C2 monitoring were measured by fluorescence polarization immunoassay (TDX) in 114 cases of cadaver renal transplants treated with Neoral (6～7 mg?kg -1 ?d -1 ), mycopherolate mofetil (MMF,1.0～1.5 g/d) and steroids for the first 3 months after renal transplantation.The effectiveness of the new monitoring method in predicting the acute rejection and side effects was retrospectively analyzed. Results The acute rejection rate of 114 transplants for the first 3 months was 15.8%(18/114).The incidence of side effects was 30.7% (35/114),including hepatoxicity(26.3%) and nephrotoxicity(7.0%).The results of 234 pairs of Neoral C0, C2 monitoring showed that the difference was not statistically significant between C0 levels of rejection and non rejection,while the difference between C2 levels [(921.55 ?431.31) vs (1 185.17?358.86)ng/ml) ] was significant.There was also no statistically significant between C0 levels of the recipients with side effects and those without side effects,but statistically significant difference was found between C2 levels [(1 302.59?450.21) vs (1 105.23? 371.64 )ng/ml].Analysis of the relationships between C2 levels and the incidences of acute rejection and side effects showed that no acute rejection and side effects rate of 4.3% were observed in the Neoral C2 interval from 1 250 ng/ml to 1 500 ng/ml. Conclusions Neoral C2 monitoring is a more sensitive predictor not only for acute rejection but also for side effect rate.The optimal C2 target level of Chinese renal transplantation recipients is 1 250 ～1 500 ng/ml for the first 3 months post transplantation.

Objective To study the effect of genomic HLA-DR compatibility on long-term survival in renal transplantation.Methods A retrospective study was performed on 518 first-cadaver renal transplants by using genotyping technique.Results More than 10%recipients shared HLA-DR matching at DNA level.half of 1 DR mismatches.The recipients with HLA-DR matched transplants showed a significant decrease of acute rejection episodes and a smooth recovery of early renal function as compared with those of DR mismatching kidneys.The 1 to 5 year-person survival rate was increased by 17%to 37.7% (P＜0.01)respectively.Multivariate analysis of 10 variables by Cox regression model revealed that DR mismatching was the most important factors influencing the long-term graft survival.Conclusion Genomic HLA-DR compatibility had a significant impact on long-term survival of first-cadaver kidney transplantation.

Objective To determine whether altered expression of apoptosis pathway genes is related to different apoptosis susceptibility of prostate cancer cells. Methods Androgen sensitive and insensitive prostate cancer cell lines LNCaP and PC 3 were cultured and treated by etoposide,and apoptosis were determined using Hoechst 33258 staining.The cells were harvested and the total RNA was extracted.cDNA probes were prepared and labeled with biotin 16 dUTP,then hybridized to commercially available cDNA arrays including apoptosis pathway specific genes. Results Apoptosis were induced in both PC 3 and LNCaP cells by etoposide,however,PC 3 was more resistant than LNCaP.Compared with LNCaP cells,the 4 fold down regulated genes in PC 3 cells were Bcl10,CIDE A,GADD45a,RIP2,caspase 4,5 and 6,while the 4 fold up regulated gene in PC 3 cells was TRAF4.Caspase 14 and TNFR2 were most strongly expressed genes in the 2 cell lines. Conclusions The altered expressions of apoptosis pathway specific genes are related to the different apoptosis susceptibility,and this may make an important contribution to androgen insensitive state of prostate cancer cells.

Objective To compare the efficacy and safety of Tacrolimus(FK506)and Neoral CsA in conjunction with MMF(2.0g/d)and steroid in preventing renal allograft rejection.Methods 98 cases of renal transplant recipients were randomly divided into two groups:FK506 group(n=40),receiving tacrollimus,MMF and prednison(Pred);CsA group(n=58),receiving CsA,MMFand Pred.Results The mean follow-up time in both two groups Was 12.5 months.Acute transplanted renal rejection occurred in 2 cases in FK506 group and 9 cases in CsA group respectively.The one-year person/kidney survival rate was 100%/100%in FK506 group and 100%/94.8%in CsA group respectively.The dosage of Pred in FK506 group was lower than in CsA group.12 cases in FK506 group had stopped using Pred.Hypergly cermia occurred in 7 cases in FK-506 group.Polytricosis,gingival hyperplasia and liver function disorder dominantly occurred in CsA group.Infection Was found in 9 cases of FK506 group and 11 cases of CsA group respectively.Conclusion FK506 combined with MMF could decrease the occurrence of acute trans planted renal rejection and the dosage of Pred.The good adjustment of the dose of FK506 iS helpful for re ducing the side effects and preventing rejection.

The effect of HLA-DR matching was retrospectively examined at DNA level on rejection and graft survival of cadaver renal transplantation. HLA-DR matching was typed by PCR-SSP technique in 318 cyclosporine-treated primary cadaveric renal recipients. The recipients were divided into three groups:no DR mismatching (0MM), one DR mismatching (1MM) and two DR mismatching (2MM). The effect of genomic HLA-DR compatibility on early kidney function, acute rejection, steroid pulses and 1 year graft survival was retrospectively analyzed. HLA-DR alleles in all samples were successfully genotyped by PCR-SSP. The overall time of DNA typing was 4 hours. The patients well-matched(0MM),moderately-matched(1MM) and poorly-matched(2MM) were 11.6%, 51.9% and 36.5%, respectively. The total rejection rate, 1 year patient survival and graft survival in 318 recipients were 49.1%, 94.3% and 90.3%. Early graft function, acute rejection episodes, steroid pulses and graft survival in well-matched recipients were better than those in poorly-matched patients. In particular, significant difference was found in acute rejection episodes and 1 year graft survival,suggesting genomic compatibility of HLA-DR has effect on acute rejection and graft survival in cadaver kidney transplantation.

Objective To investigate the expression and clinical implication of CC chemokines and receptor in long surviving kidney grafted patients of different immune states. Methods 73 cases of recipients surviving more than 3 years were divided into three groups: control group of normal renal function(C group,n=32), group under low dosage of immunosuppressants(L group,n=20) and group with chronic allograft dysfounction(D group,n=21). The plasma RANTES、MCP 1 and MIP 1?were detected by sandwich ELISA.The expression of CCR5 was determined by flow cytometry(FACS). Results Concentrations of RANTES and MIP 1? as well as expression rate of CCR5 in L group were lower than those of C group ( P 0.05).Plasma level of MCP 1 was significantly higher in group D than that in group C( P 0.05). Conclusions Expression of CC chemokines and receptor closely correlated with the immune state of renal transplant recipients and could be valuable to estimate and monitor the immune state of patients.

Objective To evaluate the efficacy and safety of Prostant TM in the treatment of chronic prostatitis. Methods A multi center, randomized, double blinded, placebo controlled trial was carried out during March 2001 and May 2001. 72 cases of patients who had been diagnosed as chronic prostatitis were separated into tow groups: 36 cases in the trial group treated with Prostant TM and the other 36 cases in the controlled group using placebo. The efficacy was evaluated by the WBC in EPS and NIH Chronic Prostatitis Symptom Index after a one month follow up. The efficacy of the therapy was divided into four levels:cure,the symptom index score being reduced over 90%, and the number of WBC in the EPS less than 10/HP; effective, the symptom index score being reduced 60%～89% and the number of WBC in the EPS lowered over 50% or less than 15/HP;improved,the symptom index score being reduced 30%～59% and the number of WBC in the EPS lowered over 25%; no effect, the symptom index score being reduced less than 30% or the number of WBC in the EPS lowered no more than 25%. Results All but two cases had completed the follow up.One case (2.8%) was completely cured,remarkable effective in 7 cases (20.0%) of the trial group;and improred in 16 cases (45.7%).Only 2 cases (5.7%)seemed effective and 8 cases (22.8%) improved in the controlled group. The efficacy showed significant difference between these two groups ( P

Objective To investigate the effect of nuclear factor ?B(NF-?B)decoy on the chemokine expression in bladder cancer cell line. Methods Human bladder cancer cell line EJ,NF-?B decoy ODN were used as a NF-?B inhibitor(scrambled NF-?B decoy was used as control).NF-?B DNA binding activity was detected by electrophoretic mobility shift assay (EMSA);and p65 subunit of NF-?B was detected by RT-PCR and Western blot.Chemokines including IL-8,MCP-1,RANTES were detected by RT-PCR. Results EMSA showed that NF-?B decoy inhibited NF-?B activation induced by TNF-?.RT-PCR or Western blot test suggested that p65,IL-8,MCP-1 and RANTES were upregulated by TNF-? and downregulated by NF-?B decoy.However,mutated decoy ODN had no effect on them. Conclusions Chemokines can be detected in bladder cancer.They are activated by TNF-? and inhibited by NF-?B decoy.

Objective To observe the dynamic change of cytokines and effect of different stimulating combinations on dominant regulation, and describe the microenviroment character of local immune response. Methods PBMCs were separated from peripheral blood of healthy donors with density gradient centrifugation. The expression levels of cytokine genes under different stimulating combinations, including IL-2, IFN-?, IL-12, IL-4, IL-10 and TGF-?1, were detected by ELISA and RT-PCR. Results ELISA results indicated that secretion level of IL-2, IL-4, IL-12 and IFN-? were inhibited by IL-10. There were significant differences in IL-4 and IL-12 between control group and stimulating groups under the stimulation by anti-CD3 monoclonal antibody (McAb) or anti-CD3 McAb + anti-CD28 McAb combination. Significant differences in IL-2 only appeared in anti-CD3 antibody stimulating group. The concentrations of IFN-? were decreased moderately. At the mean time, IL-10 significantly promoted the secretion of TGF-?1 under the anti-CD3 McAb stimulation. There were similar results on the genes level for the studied cytokines. Conclusion The induction and maintenance of dominant regulation were dependent mainly on IL-10, which inhibits the overexpression of IL-4 and IL-12. It is the vital step for dominant regulation to avoid the mono-polarization development at the beginning of immune response.

Objective To explore the mechanisms of protective effect of benazepril in the treatment of experimental cyclosporin- induced chronic nephrotoxicity. Methods Rats were on low-salt diet and cyclosporine A (CsA) was administered by gastric gavage at a dose of 30?mg/kg once daily for 28 days. The expression of mRNA for intrarenal transforming growth factor-?1 (TGF-?1) and renin was detected by reverse transcription-polymerase chain reaction (RT-PCR). Intrarenal expression of TGF-?1 and Collagen Ⅳ was determined by immunohistochemistry. The effects of benazepril on these changes were also evaluated. Results Chronic cyclosporine-induced nephropathy may be related to TGF-?1 and renin mRNA up-regulation as well as matrix proteins accumulation in interstitium. Benazepril could reduce TGF-?1 mRNA up- regulation and decrease intrarenal matrix proteins accumulation. Conclusion Decreased CsA-related TGF-?1 up-regulation expression and accumulation of matrix proteins in the kidney may be related to mechanisms of protective effect of benazepril in the treatment of cyclosporin-induced chronic nephrotoxicity.