1.Alemtuzumab induction therapy in highly sensitized kidney transplant recipients.
Tie-Ming LÜ ; Shun-Liang YANG ; Wei-Zhen WU ; Jian-Ming TAN
Chinese Medical Journal 2011;124(5):664-668
BACKGROUNDImmunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.
METHODSIn this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.
RESULTSMedian follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05).
CONCLUSIONAlemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.
Adult ; Aged ; Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antilymphocyte Serum ; therapeutic use ; Female ; Graft Rejection ; immunology ; Graft Survival ; immunology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Treatment Outcome ; Young Adult
2.Effects of D1 and D2 dopamine receptor agonists and antagonists on cerebral ischemia/reperfusion injury.
Xue-Mei ZONG ; Yin-Ming ZENG ; Tie XU ; Jian-Nong LÜ
Acta Physiologica Sinica 2003;55(5):565-570
Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
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pharmacology
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Animals
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Apoptosis
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Brain
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physiopathology
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Brain Ischemia
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physiopathology
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Dopamine Agonists
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pharmacology
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Dopamine Antagonists
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pharmacology
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Gerbillinae
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Hippocampus
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physiopathology
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Ischemic Attack, Transient
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physiopathology
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Male
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Neurons
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physiology
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Neuroprotective Agents
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pharmacology
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Pergolide
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pharmacology
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Prosencephalon
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physiopathology
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Proto-Oncogene Proteins
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biosynthesis
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genetics
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Proto-Oncogene Proteins c-bcl-2
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biosynthesis
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genetics
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Reperfusion Injury
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physiopathology
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bcl-2-Associated X Protein
3.Rosiglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice.
Quan-ming ZHAO ; Dong YAN ; Ai-li SONG ; Wei WANG ; Qiang SHI ; Lü-ya WANG ; Dong CHEN ; Wei FANG ; Ying WU ; Jin-peng XU ; Xin CHEN ; Tie-jun CHEN ; Shu-hua MI ; Shu-zheng LÜ
Chinese Journal of Cardiology 2005;33(5):399-404
OBJECTIVETo study the effect of rosiglitazone on atherosclerosis and potential mechanism in ApoE-knockout mice.
METHODSThirty-two 6-week-old ApoE-knockout mice were used as atherosclerosis model in two groups: rosiglitazone group (n = 18) and control group (n = 14). Each group contained equal numbers of male and female mice. All mice were fed with normal chow diet. In addition to normal diet, rosiglitazone group received rosiglitazone 17 mg/kg of body weight/day. Venous bloods were collected for plasma glucose and lipid analysis, and aorta were prepared for morphologic and immunohistochemical analysis after 14 weeks. Aortic root (1 cm) was cut and prepared for paraffin slice. The histomorphometric analysis of atherosclerotic lesion was performed by means of HE; positive percentage of macrophage cell and tumor necrosis factor-alpha were measured by means of immunohistochemistry in cross section. The ratio of lesion/aortic wall surface in the rest aorta was measured by means of Sudan IV staining in longitudinal section.
RESULTSThe amount of fatty streak in rosiglitazone group was significantly greater than that of control group; the gross number of lesions and the number of fibrous plaque and atheromatous plaque were similar in two groups. There were no differences in percentage of lesions in cross section in two groups. Rosiglitazone could significantly reduce the extend of atherosclerosis of longitudinal section, decrease the amount of macrophage cell and the level of tumor necrosis factor-alpha in lesions. The plasma glucose was normal and similar in two groups, and total cholesterol, LDL-cholesterol and triglyceride were significantly higher in rosiglitazone group.
CONCLUSIONRosiglitazone suppresses the expression of tumor necrosis factor-alpha, reduces the number of macrophage cell in lesion, and inhibits the development of atherosclerosis.
Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; physiology ; Atherosclerosis ; blood ; pathology ; prevention & control ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Female ; Hypoglycemic Agents ; therapeutic use ; Macrophages ; pathology ; Male ; Mice ; Mice, Knockout ; Thiazolidinediones ; therapeutic use ; Tumor Necrosis Factor-alpha ; biosynthesis