Ciclosporin does not attenuate intracranial hypertension in rats with acute hyperammonaemia

AIM:To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia.METHODS:Twenty-four male Wistar rats with portacaval anastomosis were randomised into four groups receiving ciclosporin or vehicle and ammonia or saline infusion. Ciclosporin or vehicle was given intrathecally prior to the ammonia or saline infusion. The ammonia or saline infusion was given intravenously for 4 h,while intracranial pressure and arterial pressure was recorded. At the end of the experiment, cerebral cortex and cerebellar brain tissue was analysed for water and aquaporin-4 content.RESULTS:The following intracranial pressures were found at the end of the experiment:ammonia + ciclosporin:10.0±1.7 mmHg, ammonia + vehicle:6.8±1.0mmHg, saline + ciclosporin:3.1±0.5 mmHg, saline +vehicle:3.3 ± 0.6 mmHg. Ammonia infusion had a significant effect on intracranial pressure and brain water content, which both were higher in the groups receiving ammonia(P<0.001, two-way analysis of variance). Treatment with ciclosporin resulted in relevant tissue concentrations of ciclosporin(>0.2 micromolar)but did not reduce intracranial pressure after 4 h. Furthermore, ciclosporin did not attenuate the increase in cerebral water content, and did not affect aquaporin-4expression.CONCLUSION:Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.

Ciclosporin在重症激素依赖型支气管哮喘中的应用

全身应用及局部吸入糖皮质激素是支气管哮喘的主要治疗措施,但对少数重症患者,尽管应用较大剂量的激素仍不能完全控制症状,并产生不能耐受的副作用。慢性支气管哮喘者支气管灌洗液及支气管粘膜中 T 辅助细胞及其介质活性增加。

A Case of Fungal Keratitis Secondary to Cylindrocarpon Destructans

Purpose: To report the first human case of fungal keratitis caused by Cylindrocarpon destructans and to highlight the issues with the use of topical steroids, the duration of antifungal treatment and the potential role of topical ciclosporin. Methods: A patient presented following being injured in the left eye by a fuchsia plant. Data was collected by slit lamp examination and review of the case notes and microbiology reports. Results: No organisms were cultured from a corneal scrape however cultures from a corneal biopsy identified cylindrocarpon species morphologically resembling Cylindrocarpon destructans. The patient responded well to topical amphotericin and clotrimazole and oral voriconazole but, developed a corneal perforation, which required an urgent tectonic penetrating keratoplasty (PKP). Despite being on topical dexamethasone and natamycin, the patient presented two months post-operatively with a corneal epithelial defect and a large hypopyon. Subsequently, the patient developed a deep corneal infiltrate and corneal vascularisation with a persistent epithelial defect. Conclusion: This is the first reported case of keratitis caused by Cylindrocarpon destructans. The case highlights: the contentious issues in the use of topical steroids following PKP and the duration of antifungal treatment both in primary infection and following PKP. Furthermore, the case accentuates a potential role for ciclosporin as an alternative to steroids following PKP.

Randomized Trial of Ciclosporin with 2-h Monitoring vs.Tacrolimus with Trough Monitoring in Liver Transplantation:DELTA Study

Background and Aims:Previous trials comparing cyclosporine and tacrolimus after liver transplantation(LT)showed conflicting results.Most used trough monitoring for cyclosporine(C0),leading to less accurate dosing than with 2-h monitoring(C2).Only one larger trial compared C2 with tacrolimus based on trough level(T0)after LT,with similar treated biopsy-proven acute rejection(tBPAR)and graft loss,while a smaller trial had less tBPAR with C2 compared to T0.Therefore,it is still unclear which calcineurin inhibitor is preferred after LT.We aimed to demonstrate superior efficacy(tBPAR),tolerability,and safety of C2 or T0 after first LT.Methods:Patients after first LT were randomized to C2 or T0.tBPAR,patient-and graft survival,safety and tolerability were the main endpoints,with analysis by Fisher test,Kaplan-Meier survival analysis and log-rank test.Results:In intention-totreat analysis 84 patients on C2 and 85 on T0 were included.Cumulative incidence of tBPAR C2 vs.T0 was 17.7%vs.8.4%at 3 months(p=0.104),and 21.9%vs.9.7%at 6 and 12 months(p=0.049).One-year cumulative mortality C2 vs.T0 was 15.5%vs.5.9%(p=0.049)and graft loss 23.8%vs.9.4%(p=0.015).Serum triglyceride and LDL-cholesterol was lower with T0 than with C2.Incidence of diarrhea in T0 vs,C2 was 64%vs.31%(p≤0.001),with no other differences in safety and tolerability.Conclusions:In the first year after LT immunosuppression with T0 leads to less tBPAR and better patient-/re-transplant-free survival as compared to C2.

Mesenchymal stem cells transplantation mildly ameliorates experimental diabetic nephropathy in rats

Background Diabetic nephropathy is a common complication of diabetes mellitus. This study aimed to explore whether mesenchymal stem cells （MSCs） transplantation could attenuate diabetic nephropathy in experimental diabetic rats. Methods Sprague-Dawley rats received a single intraperitoneal injection of streptozotocin （STZ） （60 mg/kg）. Diabetic rats were randomized to four groups： diabetes control group （DC）, ciclosporin A group （CsA）, MSC group, and MSC＋CsA group （MSCA）. Bone marrow mesenchymal stem cells were cultured, identified and labeled by 5-bromo-2＇-deoxyuridine （BrdU） in vitro. Then they were transplanted to diabetic rats via introcardiac infusion. Ciclosporin A was administered daily at 5 mg/kg. At 1,2, 4, 8 weeks after transplantation, random blood glucose, urine albumin/creatinine ratio （AIb/Cr）, endogenous creatinine clearance rate and renal mass index were tested. Renal morphology and labeled cells were examined. Results Cultured MSCs expressed mesenchymal cell phenotype, and could be multidifferentiated to osteogenic and adipogenic cells. Labeled MSCs could be detected in the kidney of nephropathic rats, mainly in renal interstitium, but they did not propagate after engrafting in kidney. Over the course of the experiment, MSCA group showed a significant decrease in blood glucose compared with MSC group, CsA group and DC group （P 〈0.05, respectively）. The AIb/Cr in MSCA group and MSC group were significantly lower than CsA group and DC group （P〈0.05）. And the AIb/Cr in MSCA group showed a significant decrease compared with MSC group （0.74 vs 0.84, P 〈0.05）. There was a significant difference in renal mass index between the MSCA group and DC group （5.66 vs 6.37, P 〈0.05）. No significant difference was found in creatinine clearance rate among 4 groups （P 〉0.05）. Treatment with MSC＋CsA significantly ameliorated the morphology of diabetic kidney. Conclusion MSC could mildly ameliorate diabetic nephropathy by decreasing blood glucose, AIb/Cr ratio and renal mass index.