Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Systemic Amyloidosis Secondary to Psoriasis: A Rare, Autoimmune and Genetically-Determined Disorder That Is Amenable to Treatment with Cyclosporin A—Cyclosporin A for Psoriasis-Induced Amyloidosis

Background: Systemic secondary amyloidosis (SSA) is associated with chronic inflammatory disorders and/or chronic infections. Patients and Methods: Over the past 10 years;a total of 21 patients, with long-term (17 months) and extensive psoriasis (P) with psoriasis area severity index (PASI) >29, were evaluated. Results: Two patients had nephrotic syndrome (proteinuria 3.9 and 3.6 g/day) and decrease creatinine clearance (46 and 62 ml/minute). Their renal biopsy revealed Congo-red (+) nodular glomerulosclerosis that lacked immune-deposits and resisted wash with K-permanganate wash indicating SSA. Three months subsequent to Cyclosporin A (CyA) therapy with 100 mg twice daily;psoriasis improved in all patients with decrease in (PASI) from 29.5 to 3.5 1. In the 2 patients with SSA;proteinuria decreased to 2.1 and 1.8 g/day and creatinine clearance improved to 51 and 69 ml/minute. Such improvement persisted up to 2 years of follow up and up to 78 months in patients with SSA. Conclusion: psoriasis-induced SSA is an autoimmune disease, with genetic predisposition that is amenable to CyA therapy.

Antirejection therapy with Tripterygium woifordii and low-dose cyclosporine in small bowel transplantation in pigs

AIMS Antirejection therapy with tripterygium wolfordii(TW) and low-dose cyclosporine(CsA)was better than treatments with large dosage CsA in small bowel transplantation. METHODS This paper presents the experiment of two step segmental small bowel transplantation with TW,a traditional Chinese medicine and low dose CsA in pigs. RESULTS Rejection was developed in Group I without im- munosuppression as well as in Group Ⅳ treated with low-dose CsA.The mean survival time of grafts was 12.8±2.7days and 12.4±2.6 days respectively.The animals of Group Ⅱ were treated with high-dose CsA for 100 days and then with TW.in which two pigs were killed for severe pneumonia on day 92,97 and two pigs survived more than 348 and 327 days respective- ly.Five animals in Group Ⅲ in which TW and low-dose CsA were administered for 100 days and then TW was the only drug used in living animals,survived 243.2±90.9 days,none of which succumbed to infection. CONCLUSIONS:We are the first to use TW in small bowel transplantation and f Group Ⅰ(n=10):control group,received no immunosuppression.

Studies on in vitro release of cyclosporine A-loaded microspheres

Aim This study was to prepare cyclosporine A （CyA） microspheres （Ms） using 75：25 poly （D, L-lactide-co-glycolide） polymer （PLGA）, and to evaluate the in vitro release of the CyA microspheres. Methods CyA-Ms were prepared by an oil-inwater （o/w） emulsion solvent extraction/evaporation process and characterized for drug content, particle size, surface morphology, and differential scanning calorimeter （DSC）. Accelerated in vitro release of cyclosporine A from the mieropsheres was studied at various conditions, such as temperatures, surfactants, pH values and organic solvents for a short period. Results CyA-Ms were in spherical shape with average particle size of 50 μm and loading efficiency of 13.0%. The results of DSC measurements suggested that at the dry state, CyA did interact very strongly with the hydrophilic PLGA polymer. In vitro release test in various release medium showed slight increase of CyA-Ms release profiles under various conditions of temperatures, surfactants and pH values. However, dramatical increase of CyA-Ms release was seen in the medium containing 30% isopropanol. Conclusion It was demonstrated that CyA could be incorporated into polymeric Ms prepared from PLGA using a solvent evaporation technique. The release medium containing 30% isopropanol might be the ideal condition for CyA-PLGA microspheres in vitro quality control test.

Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation:Effects on virus replication and recurrent hepatitis

AIM： To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus （HCV） replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS： The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS： HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant （P=0.49 at 12 too）. In addition, recurrent hepatitis as determined by serum transarninases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo （P= 0.34）.CONCLUSION： Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV- infected patients after liver transplantation.

Cyclosporin A通过MEK/ERK1/2信号通路调节滋养细胞titin表达

探讨MEK/ERK1/2信号通路在Cyclosporin A(CsA)诱导滋养细胞表达titin中的作用。应用RT-PCR、Western blot检测CsA诱导的滋养细胞titin的表达水平,Western blot检测CsA作用于滋养细胞后ERK1/2的活化程度,并观察MEK特异性抑制剂U0126对其mRNA转录的影响。发现CsA以时间和剂量依赖方式诱导titin表达,并刺激滋养细胞ERK1/2的活化,U0126以剂量依赖方式抑制CsA诱导的titin表达。结果表明CsA通过活化MEK/ERK1/2信号通路诱导滋养细胞titin 的表达,改变其生物学行为,从而有利于胚胎着床及早期发育。

Comparative analysis of different cyclosporine A doses on protection after myocardial ischemia/reperfusion injury in rat

Objective:To investigate the protective effect of different cyclosporin A(CsA)doses on myocardial ischemia/reperfusion injury in rat models.Methods:A rat model of myocardial ischemia/reperfusion injury was established in vivo and the rats were randomly divided into four groups:placebo(PBS;T1),low-dose(CsA dose:1.0 mg/kg:T2),medium-dose(CsA dose:2.5 mg/kg:T3),and high-dose(CsA dose:5.0 mg/kg;T4)groups.Heart function indexes were monitored at different time points,the extent of myocardial infarction was assessed by Evans Blue-TTC staining,and creatine kinase MB mass and cardiac troponin 1 values were measured by biochemical assays.Results:Compared with the T1 and T2 groups,both the creatine kinase MB mass and cardiac troponin 1 were significantly lower in the T3 and T4 groups(P<0.05).The mean arterial pressure(MAP)and left ventricular systolic pressure(LVSP)decreased sequentially in each group,with the extending reperfusion time.Significant decreases in LVSP and MAP were observed in the T3 and T4 groups as compared to the T1 and T2 group(P<0.05)and the T2 group showed a significantly lower LVSP and MAP decline than the T1 group(P<0.05).Compared with the Tl group,the rats from the T2.T3,and T4 groups suffered from a significantly lower extent of myocardial infarction(P<0.05).Also,the a animals in the T3 and T4 groups had a significantly smaller extent of myocardial infarction than those in the T2 group(P<0.05).Conclusions:Various CsA doses exert different degrees of protection against ischemia/reperfusion injury,and this protective effect peaks at approximately 2.5 mg/kg in rat models.

Cytomegalovirus infection in severe ulcerative colitis patients undergoing continuous intravenous cyclosporine treatment in Japan

AIM： TO investigate active cytomegalovirus （CMV） infection following the cydosporine A （CyA） treatment of steroid-refractory ulcerative colitis （UC）. METHODS： Twenty-three patients with severe UC not responding to steroid therapy （male 14, and female 9） enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA （average 4 mg/kg per day） for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology （IgM antibody by ELISA）, quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin （HE）-stained colonic biopsies. CMV infection was indicated by positive results in any test. RESULTS： No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV （IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%）. There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection （83.3%） required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION： Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy.

Production of cyclosporin C by Gliomastix luzulae isolated from different areas of the P.R.China

本文调查了１５株粘鞭菌属Ｇｌｉｏｍａｓｔｉｘｌｕｚｕｌａｅ菌种产生环孢菌素Ｃ的能力。分离自中国１１省１５个不同地区的菌种在葡萄糖－麦芽汁－蛋白胨液体培养基中于２４～２６℃发酵１０ｄ。代谢产物经ＨＰＬＣ分析，其中１１株菌株除能产生环孢菌素Ｃ外不产生任何已知的环孢菌素，另４株菌虽然不产生已知的环孢菌素，但全部都产生一未知的环孢菌素。对产生环孢菌素Ｃ的两株具有不同液体培养性状的菌株用Ｌ－丙氨酸、Ｄ－丙氨酸、Ｌ－缬氨酸、ＤＬ－α－氨基丁酸、ＤＬ－原缬氨酸和Ｌ－苏氨酸进行氨基酸前体掺入实验，发现所有氨基酸前体均只能调节菌株合成环孢菌素Ｃ的能力，而不能使其合成相应的其它环孢菌素，其中Ｌ－丙氨酸和Ｄ－丙氨酸具有相近但比其他氨基酸更强的提高菌株合成环孢菌素Ｃ的能力，提示该类菌的合成机制与已知环孢菌素Ａ产生菌的合成机制明显不同。

Protective effects of cyclosporine A on T-cell dependent ConA-induced liver injury in Kunming mice

INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.

Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline

AIM: To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints.METHODS: One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups: nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline.RESULTS: Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes(P 【0.001). Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs(P =0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group(P 【0.05).CONCLUSION: Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease

· AIM: To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. · METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age: 66.8 years, interquartile range: 61 -73.2 years) with moderate -severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow- up period was 12 months. Before treatment and at 3 and 12 months post -treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed. ·RESULTS: The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm 2 (inter- quartile range, 2 178 -2548.5), 2 364/mm 2 (interquartile range, 2 174.25 -2 657.5), and 2 366 cells/mm 2 (inter - quartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post -treatment were 34.5 (interquartile range, 30 -37), 35 (interquartile range, 30 -38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre - treatment and at 3 and 12 months post -treatment were 53 (interquartile range, 47 -58), 54 (interquartile range, 45.75 -59), and 50.5 (interquartile range, 45.75 -58), respectively (P=0.824, one way ANOVA). · CONCLUSION: Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.

Effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. METHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. RESULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight gain.CONCLUSION: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

Effect of topical 0.05% cyclosporine A on the tear protein lacritin in a rat model of dry eye

AIM: To observe the effect of topical 0.05% cyclosporine A(CsA) on the ocular surface and tear protein lacritin in a botulinum B-induced dry eye rat model. METHODS: A total of 36 female SD rats were randomly divided into 3 groups, botulinum B was injected into the right lacrimal gland of all rats. Group A and group B were treated with 0.05% CsA and 0.1% sodium hyaluronate, respectively, 3 times daily. The control group was not treated. Basal tear flow, corneal epithelial defects, and lacritin levels were measured. RESULTS: Tear secretion in all rats was reduced on day 3 and was even lower on day 7 postoperation(P<0.05). Tear secretion in group A increased by day 14 and was at the preoperative level on day 42. Tear secretion in group B and control rats was lower on days 14 and 42 compared with preoperative level(P<0.05). Corneal fluorescein staining in group A was higher on day 3, peaked on day 7, and then decreased gradually from day 7 until day 14, returning to normal by day 42 post-procedure. However, in group B, corneal fluorescein staining had improved, but was not fully recovered by day 42. Corneal fluorescein staining was more intense than before the operation and then in the control group at all time points. Tear protein lacritin levels reached the lowest levels on day 7 in all groups. In group A, tear protein lacritin levels began to increase on day 14 and were normal on day 42. In group B, tear protein lacritin levels began to increase on day 14, but had not completely recovered on day 42. In the control group, tear protein lacritin levels remained low post-procedure. CONCLUSION: CsA 0.05% prompts tear protein lacritin expression in a rat model of dry eye and improves the signs and symptoms of dry eye disease.

Cyclosporine玻璃体腔内注射对异种视网膜色素上皮移植的排异抑制作用

目的 观察兔眼视网膜下腔植入人胚眼视网膜色素上皮 (retinal pigm ent epithe-lium,RPE)后不同时期的眼底和组织学改变。研究环胞菌素 A (Cyclosporines,Cs A )玻璃体腔内注射能否抑制人胚眼 RPE在兔眼视网膜下腔中诱导的异种移植排异反应。方法 人胚眼色素上皮片和浓缩色素上皮细胞悬液植入 36只兔眼的视网膜下腔 ,其中 16眼为对照组 ,用于观察排异的自然转规。分别于 7d(8眼 )和 30 d(8眼 )后获取组织标本。另 2 0眼为实验组。RPE移植后 ,每周一次玻璃体腔内注射 Cs A1mg(12眼 )或 Cs A0 .1mg(8眼 )。视网膜和视神经的毒性反应使用 ERG进行检查。结果 人胚眼 RPE片和浓缩的 RPE细胞均能在视网膜下腔短期存活。移植的 RPE与视细胞结合良好并显示吞噬功能。排异反应发生时间约在术后 10～ 30 d。对照组中 7d的排异发生率为 0 /8;30 d排异发生率为 7/8。排异发生后荧光造影中移植区为高荧光区 ,组织切片中显示有大量的组织细胞积聚。 Cs A1mg组 30 d排异发生率为 0 /12 ,0 .1mg组为 5 /8。ERG波幅的下降与 Cs A剂量和注射次数呈正相关。结论 异种 RPE视网膜下腔移植在无免疫抑制剂的条件下 ,只能短期存活。Cs A玻璃体腔中注射能抑制异种 RPE移植的排异反应但易引起明显的视网膜毒性反应。

环孢霉素A(Cyclosporin A,CsA)对穿透性异种角膜移植的影响——免疫学检测与形态学观察

以鸡→兔穿透性角膜移植为实验模型,运用ELISA 技术和微量全血~3H—TdR 掺入法、光镜和扫描电镜进行检测和观察。结果:术后3～4周血清中抗角膜抗体水平和外周血淋巴细胞转化程度达峰值,而CsA 治疗组与对照组比,上述二项免疫指标水平都有明显下降。组织病理学检查:在对照组的移植片内出现明显的炎性细胞浸润和新生血管,而CsA 治疗组,异种植片基本正常,没有出现炎性细胞浸润和新生血管。

Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits

AIM:To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction. ·METHODS:Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy. · RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P 】0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P =0.025). In addition, the cornealultrastructure showed no differences between CsA-MS and MS injected eyes. CONCLUSION:CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.

Inhibitory effect of cyclosporine A on hepatitis B virus replication in vitro and its possible mechanisms

BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT). However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in Chi- na. Cyclosporine A (CsA), which is routinely used to pre- vent the allograft rejection, is reported to have the inhibito- ry activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possi- ble mechanisms of CsA on HBV replication in vitro. DATA RESOURCES: An English-language literature search was conducted using MEDLINE (1990-2004) on cyclospo- rine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles. RESULTS: Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cy- clophilin D, then blocking the mitochondria-mediated cy- tosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro. CONCLUSIONS; By interacting with mitochondria, pre- venting the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.

Azathioprine is essential following cyclosporine for patients with steroid-refractory ulcerative colitis

AIM: To evaluate long-term prognosis following cyclosporine treatment by examining the rate of surgery avoidance among cyclosporine responders.METHODS: We retrospectively reviewed clinical records for 29 patients diagnosed with severe steroid-refractory ulcerative colitis in our hospital from August 1997 to August 2008 and treated with cyclosporine by continuous intravenous infusion.All patients were treated with intravenous corticosteroids for more than 5 d prior to cyclosporine therapy.Administration was continued for up to 21 d under serum monitoring to maintain cyclosporine levels between 400 and 600 ng/mL.Clinical activity was assessed before and after cyclosporine therapy using the clinical activity index score,with a reduction of ≥ 5 considered to indicate a response.Among responders,we defined cases not requiring surgery for more than 5 years as exhibiting long-term efficacy of cyclosporine.Factors considered to be possibly predictive of long-term efficacy of cyclosporine were sex,age,disease duration,clinical activity index score,C-reactive protein level,hemoglobin level,disease extent,endoscopic findings,and clinical course.RESULTS: Cyclosporine was not discontinued due to side effects in any patient.Nineteen(65.5%) of 29 patients were considered responders.A statistically significant(P = 0.004) inverseas sociation wa s observed between an endoscopic finding of "mucosal bleeding" and responsive cases.Fifteen(9 males,6 females) of these 19 patients were followed for 5 years or more,of whom 9(60%) exhibited long-termefficacy of cyclosporine.Of the 10 non-responders,9(90%) underwent surgery within 6 mo of cyclosporine therapy.None of the following factors had a significant impact on the long-term efficacy of cyclosporine: sex,age,duration of disease,clinical activity index score,C-reactive protein level,hemoglobin level,extent of disease,endoscopic findings,or clinical course.In contrast,a significant association was observed for maintenance therapy with azathioprine after cyclosporine therapy(P = 0.0014).CONCLUSION: Maintenance therapy with azathioprine might improve the long-term efficacy of continuously infused cyclosporine for severe steroid-refractory ulcerative colitis patients.

Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

AIM： To investigate the effect of cyclosporine A （CsA）, FK-506, and mycophenolate mofetil （MMF） and 40-0-[2- hydroxyethyl]rapamycin （RAD） on proliferation of human intrahepatic biliary epithelial cells （BECs） in vitro.METHODS： BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-S06, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot.RESULTS： Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs （P〈0.05） was 500, 100, 0.25, and 100 pg/L, respectively. However, the expression of CK19 by BECs was not changed.CONCLUSION： CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.