BACKGROUND:Cyclosporine A has shown its immunosuppressive effects and has been widely used in clinical organ transplantation.OBJECTIVE:To review the recent studies on the immunosuppressive mechanisms and the active pathway of cyclosporine A.RETRIEVAL STRATEGY:A compute-based online search of ScienceDirect Onsite,ProQuest,Springer and Ovid,based on the data from Peking University Medical Library,was undertaken for the English articles concerning with the immunosuppressive mechanism of cyclosporine A from January 1990 to December 2006,with the keywords of "cyclosporine A,mechanism/action,immunosuppression".Totally 68 articles were collected after the first trial,and the preliminary screening was conducted for the titles and abstracts.Inclusion criteria:articles related with the immunosuppressive mechanisms of cyclosporine A.Repetitive studies were excluded.Fifty accorded with the inclusive criteria,and 46 of them regarding tracheal transplantation were selected for the full-texts as the references.LITERATURE EVALUATION:Forty-six included articles included 6 ones about the clinical use and effects of cyclosporine A,and 40 involving the related studies on the molecular mechanisms of cyclosporine A.DATA SYNTHESIS:The review of literatures indicates that,the immunosuppressive mechanisms of cyclosporine A consist of:① the calcineurin/nuclear factor of activated T-cells pathway,②the activation of JNK and P38 signaling pathways,③other effects.CONCLUSION:Cyclosporine A selectively regulates the function of peripheral blood lymphocytes subgroup,blocks the activation of cytotoxic T-cells,and possibly inhibits the formation or reaction of memory T-cells.But it doesn't affect activation and proliferation of suppressive T-cells,or expression of interleukin-2 receptors,which may induce selective immunosuppression.

Objective To study the effects of vascular endothelial growth factor(VEGF) in early stage diabetic retinopathy and their mechanisms,so as to guide the clinical work theoretically.Methods Thirty-six SD rats were randomly divided into four groups.Nine rats were used as normal controls(M Group).Streptozocin were injected intraperitoneally to induce diabetes for 1 month(M1 Group),2 months(M2 Group),and 3 months(M3 group).At the experimental ends of each group,the rats were over anesthetized and their eyeballs were extracted to make digest preparation.Immunofluorescence were used to investigate the expression of VEGF on retinal blood vessels.Transmission electromicroscopy was used to observe the histology of the retinal vessels.Results VEGF immunofluorescence showed an expression rate of 56% in M2 group and 89% in M3 group.Transmission electromicroscopy showed no change in M Group.However,it showed swelling of endothelial cells,finger like process into the capillary cavity,uneven distribution of heterochromatin in pericytes in M1 Group.Obvious fragmental thickening and splitting of basement membrane,swelling and deformation,finger like process to the capillary cavity,and concentration and margination of heterochromatin in endothelial cells,and swelling and deformation of rough surfaced endoplasmic reticulum and mitochondrion in pericytes were observed in M2 and M3 groups,especially in the latter.Conclusion The expression of VEGF proteins in the retinas of diabetic rats increases with the progression of diabetes.It proves that VEGF plays an important role in the occurrence and development of early diabetic retinopathy.

The action of BTHP on a-adrenoceptor was studied in anococcy-geus muscles, vas deferens and cell membrane of cerebral cortex of rats and aortic strips, saphenous vein of rabbit. BTHP produced parallel shifts to the right of dose-response curves for phenylephrine in rat anococcygeus muscle and rabbit aortic strips without change in the maximal responses. Their pA2 values were 5.8 and 5.86 respectively. BTHP was also a competitive antagonist for presynaptic and postsynaptic ?2-adrenoceptors on prostatic portion of rat vas deferens( pA2 against clonidine=5.2 ) and on rabbit saphenous vein ( pA2 against B-HT920=5.3 ) . BTHP decreased in dose-dependent manner 〔8H〕 prazosin and 〔3H〕 clonidine specific binding to ?1- and ?2- adrenoceptors on cell membrane of cerebral cortex in rats with IC50 of4 and 9.5 ?mol/L and with Ki ( apparent dissociation constant ) of 3.5 and 8.1?mol/L respectively, suggeating that BTHP has affinity for both ?1 and ?2- adrenoceptors of rat cerebrance.

Benzyltetrahydropalmatine ( BTHP ) which is a derivative of tet-rahydropalmatine, induced concentration-dependent decreases of the APA & dV/dt max and prolongation of conduction delay (CD) in toad sciatic neural action potential while it has little effect on APD.Bloocking action of Na+ -channel was measured with the dose required to produce 50% diminution of the value of APA, ie,EC50. EC50 of BTHP was 2.8 folds less than that of lidocaine and 11.9 folds more than that of quinidine, reflecting blocking action of Na+ -channel by BTHP, lidocaine, quinidine respectively.

The objective of this experiment was to study the sequential pathologic changes in the remodeling of the internal structure of the tibia, caused by controlled excessive jumping and running. Eighteen rabbits were exercised separately in two electrical cages with high voltage and low current. They were forced to jump and run in a manner which simulated athletic activity. Two additional rabbits served as controls. The rabbits were sacrificed periodically to obtain the required specimens. Radiographic and histologic methods were applied to observe the development of the pathologic changes of the tibia throughout the sixty-day experimental period.Vascular changes and circulatory disturbances within the cortical bone occurred before osteoclastic resorption. Degeneration and necrosis of osteocytes due to circulatory disturbances also occurred. Periosteal new bone formation found on and after 14 days of the experiment was a compensatory reaction to support the tibia which was weakened by the accelerated ostoclastic resorption. A Small crack appeared at the cement line and propagated through the neighboring cement line of the Haversian systems. After 21 days, incomplete fracture of the tibial cortex was found in two rabbits. Complete fracture on one side of the cortex was seen in 1 animal on the 50th day of the experiment. In addition, degeneration and necrosis of the surrounding muscles were also observed microscopically. In this study, however, most of the tibias did not have visible fracture lines after a period of strenuous exercise. This result suggests that most tibias can adapt to changes under stress through proper internal remodeling, so that a complete fracture rarely occurs.

Objective To investigate the fatigue properties of bone cement specimens prepared with different monomer storing temperatures and polymerization environment temperatures; to find out the combination of the storing temperature of bone cement monomer and the mixing temperature of bone cement. Methods Bone cement monomer was stored under 21 ℃ or 4 ℃ environment. They were mixed with the powder under partial vacuum at room temperature of 21 ℃ for 1 minute, followed by 3 minutes' rest. The cement was then injected into metal molds with different temperatures of 21 ℃ or 50 ℃. Finally, the polymerized cement specimens were removed from the molds for mechanical tests. The bone cement specimens were divided into four groups. Group 1(control group): monomer temperature 21 ℃, metal mold temperature 21 ℃. Group 2: monomer 21 ℃, mold 50 ℃. Group 3: monomer 4 ℃, mold 21 ℃. Group 4: monomer 4 ℃, mold 50 ℃. Each group consisted of 21 specimens. All specimens were soaked in 37 ℃ water bath, and were tested with MTS mechanical test machine. Completely reversed tension-compression cycling loading was applied. Testing strength exerted was 15 MPa and the frequency was 2 Hz. This strength was approximately 3.5 times of the force that cement received in vivo. The cycles to failure was recorded. Specimens that failed in less than 5000 cycles were excluded. Comparisons of cycles to failure among different groups were performed using independent sample t tests. Results The cycles to failure of the control group(group 1) were lower compared with those of group 2, 3 and 4. The differences were all statistically significant(P≤0.001). Conclusion 1) The combination of monomer temperature of 21 ℃ and metal mold (polymerization environment) temperature of 21 ℃ produced the worst bone cement specimens in terms of their fatigue property. 2) The fatigue property was obviously improved when the monomer and the mold temperatures differed by 20 ℃ to 30 ℃.

Objective To evaluate the clinical efficacy of retroperitoneoscopic nephrectomy for tuberculous nonfunctioning kidneys.Methods From October 2003 to November 2006,retroperitoneoscopic nephrectomy was performed in nine cases of tuberculous nonfunctioning kidneys in our hospital.Dissecting kidney and ureter with ultrasound scalpel,blocking kidney pedicle with Endo-GIA(n=4) or Hem-o-lok(n=5),kidney was put into kidney bags and taken out.Results All nine cases were performed nephrectomy successfully without conversions to open surgery.The mean of operative time was 110 min(range,90-180 min);the mean of blood loss was 94.4 ml(range,20-200 ml);the mean of postoperative hospital stay was 5.5 days(range,3-8 days).One case had a little cheese-like pura extravasation induced by laceration of kidney capsule.Peritoneum damage occurred in one case.The nine patients showed a primary healing of the wound.Follow-up of 1-38 months in nine cases showed normal function of contralateral kidney.Conclusions Retroperitoneoscopic nephrectomy for renal tuberculosis has advantages of minimal invasion,less blood loss and quicker recovery,therefore it is a fairly safe and reliable procedure for tuberculous nonfunctioning kidneys.

Objective To evaluate the clinical efficacy of retroperitoneoscopic surgery for adrenal cyst.Methods From May 2002 to December 2006,retroperitoneoscopic surgery was performed in 12 cases of adrenal cyst.The diameter of cyst was ranged from 3.6 cm?2.2 cm-10.0 cm?8.0 cm.After the retroperitoneal space was dilated,the perinephric fascia was opened.The adipose tissues around the upper polar of the kidney and the adrenal gland were dissected.Then the upper polar of the kidney and the cyst of adrenal gland were separated along the renal surface with a ultrasound scalpel.The cysts and normal adrenal tissue 1 cm away from the cysts were resected.Results The operation was successful in all of 12 patients without conversion to open surgery.The mean operative time was 65 min(range,50-120 min);the mean blood loss was 45 ml(range,10-150 ml);the mean hospital stay was 4.5 days(range,3-7 days).Intraoperative cyst rupture occurred in 2 cases of larger cysts,then the cystic fluid was drawn out and the cyst wall was fully excised.No incision infections occurred.A follow-up period of 2-55 months(mean,32 months) in 12 patients showed no cysts recurrence.Conclusions Retroperitoneoscopic surgery for adrenal cyst has the advantages of minimal invasion,less blood loss,quicker recovery,and shorter hospital stay,therefore it provides the first choice for adrenal cyst.

Objective To investigate the main causes and strategies for the difficulties in ureteroscopic lithotripsy.Methods From March 2004 to December 2006,19 cases of ureteral calculi,who experienced difficulties during holmium laser lithotripsy or pneumatic lithotripsy under a rigid ureteroscope,were analyzed retrospectively.Among the cases,3 had difficulties in ureteroscope placement due to the narrow ureteral ingress,6 owing to calculus obstruction complicated with ureteral inflammatory polypi,4 resulted from twisted ureter,and 6 because of stenosis of the ureter.Results In 15 of the patients,the operation was successfully performed by changing surgical approach,controlling the hydraulic irrigation,and incising the stenotic segments,etc.Two patients,who had stenotic ureter,received ESWL with double-J catheter dwelling.Lithotripsy failed in 2 cases,and PCNL was used to remove the calculi.The postoperative complications occurred in 4 cases,including 2 with mucosal laceration and 2 ureteral perforations.One of the 4 cases was transferred to an open surgery,and the other 3 were cured by conservative treatments.Conclusions Holmium Laser lithotripsy and pneumatic lithotripsy under a rigid ureteroscope are safe and effective in treating ureteral calculi.

Objective To investigate the change of glucose metabolism in warm ischemia/reperfusion injured kidney of rabbits in vivo by microdialysis and real-time electrochemical detection.Methods A total of 20 New Zealand rabbits were divided into experiment and control groups(10 in each).After anesthesia by intravenous injection of barbitone,an oblique incision under the 12th rid was made in the animals to expose the right kidney and the right renal artery and vein.Afterwards,a microdialysis probe was placed into the dorsal renal cortex along the long axle of the kidney.After 60 minutes to equilibrate,an electrochemical detection system was used to continuously determine the concentration of glucose in the renal cortex before ischemia.Then,ischemia/reperfusion injury model was established by clamping the renal pedicle for 60 minutes followed by perfusion for 60 minutes.The control group received the same intervention without clamping the renal pedicle.The glucose concentration of the microdialysis samples were analyzed before,during,and after the ischemia.Results The reaction of the glucose electrode to the electric current was linearly correlated with the concentrations of glucose,and the rate of microdialysis probe recycling was(63.6?2.1)%.The concentration of glucose in the renal cortical interstitial samples were(1.89?0.37),(0.69?0.12),and(0.62?0.14)mmol/L respectively before,during,and after the warm ischemia.During the ischemia phase,the mean concentration of glucose decreased by(36.7?2.4)% from the base level(LSD test,P=0.000).The glucose concentration of the experimental group was significantly lower than that in the control at both ischemia and reperfusion phases(t=-11.975,P=0.000;t=-11.993,P=0.000,respectively).Conclusions In vivo microdialysis combined with electrochemical detection provides a sensitive and real-time method for measuring the glucose concentration in warm ischemia/reperfusion injured kidney,which can suggest the ischemic condition of the renal cortex.