A modified CZ-1 preserving solution for organ transplantation: comparative study with UW preserving solution / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution.</p><p><b>METHODS</b>A series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied.</p><p><b>RESULTS</b>There was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22 - 31 hours were transplanted successfully and the mean renal function recovery time was (3.83 +/- 1.68) days.</p><p><b>CONCLUSIONS</b>CZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.</p>

CTLA-4Ig combined with ICAM-1 mAb promotes immune tolerance induced by donor-derived immature dendritic cells in recipient mice / 第二军医大学学报

Objective: To investigate the mechanism of CTIL-4Ig combined with Anti-ICAM-1 mAb in promoting immune tolerance induced by donor-derived immature dendritic cells (imDC) in recipient mice. Methods: Male mice were divided into 4 groups: control group (receiving only imDC), CTLA-4Ig group, ICAM-1 mAb group and CTLA-4Ig + ICAM-1 group. Mice were transfused with donor-derived imDC 7 days before they received heart transplantation in company with daily injection of ICAM-1 mAb, CTLA-4Ig or both for the following 2 weeks. Immunological analysis was performed in mice 7 days and 21 days after heart transplantation. Results: CTLA-4Ig alone or in combination with ICAM-1 mAb significantly inhibited T cells proliferation to alloantigen stimulation, impaired lymphocyte cytotoxicity, suppressed production of IL-2, IFN-γ by Th1, increased production of IL-10, and obviously decreased the production of alloantibody IgG in recipient mice treated with donor-derived imDC. ICAM-1 mAb alone had no significant effects on T cells proliferation and production of Th-derived cytokines except for IL-2. Conclusion: ICAM-1 mAb combined with CTLA-4Ig can enhance immune tolerance induced by donor-derived imDC in recipient mice through induction of T cells hypo-responsiveness, inhibition of lymphocyte cytotoxicity and B cell immunoreation, and promotion of Th2 polarization in vivo.

Dynamic changes of chemokines Mig, IP10, and ITAC in early diagnosis of acute rejection after liver transplantation / 第二军医大学学报

Objective: To investigate the dynamic expression of chemokines Mig, IP10, and ITAC after liver transplantation and to study its role in early diagnosis of acute rejection in humans. Methods: Thirty patients receiving liver transplantation (April 2005 to September 2005) were divided into acute rejection (AR) group (n=9) and non-acute rejection (NAR) group (n=18) based on the clinical symptoms and pathological examination. Three patients were excluded due to post-operation infection. The chemokines expression was determined in all patients 1 day before and day 1, 3, 5, 7 after transplantation. Sixteen patients with liver cirrhosis (cancer) and 16 normal adults were also examined as control in this study. Patients in AR group received pulse glucocorticoid treatment from the onset of AR and the expression of chemokines was determined on the day of AR diagnosis and day 3, 7 after glucocorticoid treatment. The relationship between Banff rejection activity index (RAI) and 3 chemokines expression on the day of AR onset was analyzed. Results: Chemokines expression was not significantly different between transplantation group and liver cirrhosis (cancer) group one day before transplantation; however, it was significantly higher than that of the normal control group (P<0.01). The expression of Mig, IP10 and ITAC was increased markedly in AR and NAR group day 3 after transplantation (P<0.05). AR was confirmed in 9 patients on day 11, 12 and 14 after transplantation. The serum contents of Mig, IP10 and ITAC in AR group were higher than those in NAR group at all defined time points after transplantation. There was a positive relationship between RAI and the expression of Mig, IP10 and ITAC on the day of AR onset (r=0.88, 0.94, 0.80, respectively). In AR patients, the expression of Mig, IP10 and ITAC decreased after pulse treatment with glucocorticoid (P<0.01). Conclusion: Serum level of Mig, IP10 and ITAC can serve as a sensitive, specific marker for early predication of AR in liver transplant patients.

Expression of heparanase mRNA and its clinical significance in primary hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of heparanase mRNA and its relation with the clinicopathological features and angiogenesis in primary hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Expression of heparanase mRNA was detected by RT-PCR in 51 HCC lesions, and microvessel density (MVD) was detected by immunohistochemical stain with a factor VIII-related monoclonal antibody.</p><p><b>RESULTS</b>Expression of heparanase mRNA was shown in 49.0% (25/51) HCC lesions. The positive rate of heparanase expression in tumors larger than 3 cm (63.6%, 21/33) was significantly higher than those in smaller tumors (22.2%, 4/18; P < 0.01). Heparanase expression was more frequent in highly invasive tumors (70.0%, 14/20) compared with moderately invasive tumors (46.7%, 7/15) and low invasive ones (25.0%, 4/16; P < 0.05). Moreover, heparanase expression in tumors with high MVD (62.5%, 20/32) was significantly higher than those in tumors with low MVD (26.3%, 5/19; P < 0.05).</p><p><b>CONCLUSION</b>Heparanase mRNA expression may be important for the growth, invasion and angiogenesis of hepatocellular carcinoma.</p>

A meta-analysis of therapeutic effect of cyclosporine microemulsion and tacrolimus for patients undergoing liver transplantation / 第二军医大学学报

Objective:To evaluate the efficacy and safety of microemulsified cyclosporine(Neoral)and tacrolimus(FK506) for immunodepression after Iiver transplantation.Methods:According to the including criteria,fifteen randomized controlled trials were enrolled in this analysis.The data of trial design,characteristics of the subjects,and findings of the studies were reviewed and analyzed by RevMan 4.2.8 software.Results:The patient survival rate,graft survival rate,incidence of nephrotoxicity,and incidence of infection were not significantly different between Neoral and FK506 groups,with the relative risk and(95% CI,P)being 0.99(0.96-1.02,0.37),0.97(0.92-1.03,0.30),0.99(0.87-1.13,0.86)and 1.08(0.97-1.20, 0.16),respectively.The incidences of hypertension(1.34[1.15-1.55,0.000 1])and acute rejection(1.15[1.06-1.25,0.001]) were significantly lower in the FK506 group,with no significant difference found in the degree of acute rejection(1.00[0.92- 1.22],0.98).Interestingly,the incidence of diabetes was significantly higher in the FK506 group within 1 year after the operation,but was similar to that of the Neoral group thereafter,with relative risk(95%CI,P)being 0.72(0.62-0.83,

Expression of chemokines and chemokine receptors in organ-graft rejection:recent progress / 第二军医大学学报

Acute and chronic graft rejection are the major factors leading to graft non-function.There is an active expression of chemokines early after transplantation.They recruit T cells and antigen presenting cells selectively to the graft, leading to inflammatory reaction and finally to graft non-function.Accordingly,monitoring the expression status of chemokines and their receptors regularly may help to the diagnose rejection.To determine one or more chemokines or their receptors as the new targets for anti-rejection therapy will be of great clinical significance.This review focuses on the research progression in the above areas.