The Effect of Cyclosporin A on Aspergillus niger and the Possible Mechanisms Involved.

Aspergillus niger is one of the major pathogenic fungi causing postharvest grape decay. The development of antifungal agents is beneficial to reduce the loss of grapes during storage. The aim of this study was to investigate the antifungal mechanism of cyclosporin A (CsA). It was indicated that the rot development on grapes caused by A. niger was almost completely inhibited with CsA in vivo at a concentration of 200 mg/L. The transcriptomic analysis revealed that the expression levels of genes involved in rRNA processing and ribosome biogenesis were down-regulated, whereas those related to ß-glucosidases and chitinases were up-regulated. The results implied that CsA may disturb rRNA and ribosome formation to obstruct protein synthesis, accelerate chitin and glucan degradation to destruct cell walls, and ultimately reduce postharvest decay caused by A. niger in grapes. This study evaluated the potential of CsA as a grape preservative and provided new insights into the mechanisms underlying the molecular response in A. niger with the treatment of CsA.

Reversal of apoptosis resistance of doxorubicin-resistant human myeloge-nous leukemia cell line K562/DOX by a cyclosporin D analogue PSC833 / 中国病理生理杂志

AIM:To study the reversal effect of a cyclosporin D analogue PSC833 on multidrug resistance of doxorubicin-resistant human myelogenous leukemia ( K562/DOX) cells.METHODS: The reversal effects of PSC833 on resistance to doxorubicin ( DOX)/vincristine ( VCR) in K562/DOX cells were observed by MTT assay.The cell cycle analysis was performed by flow cytometry.Annexin V/PI staining was used to identify PSC833-induced apoptosis in K562/DOX cells.These cells underwent incubation with DCFH-DA, JC-1 and Fluo-3/AM followed by flow cytometry for the measurement of reactive oxygen species ( ROS) , mitochondrial membrane potential (ΔΨm ) , and intracellular calcium, re-spectively.The protein levels of cytochrome C (Cyt C), Bcl-2, Bax, and cleaved caspase-3 were detected by Western blotting.RESULTS:The DOX/VCR-induced cytotoxicity was significantly potentiated by PSC833.PSC833 arrested the cells in G2/M phase and increased the apoptosis induced by DOX in K562/DOX cells.During the apoptosis, the level of ROS and intracellular calcium increased, while the level ofΔΨm decreased.Furthermore, the release of Cyt C, activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2 were observed in K562/DOX cells treated with PSC833 and DOX.CONCLUSION: The reversal effect of PSC833 on multidrug resistance in K562/DOX cells is associated with the induction of apoptosis through a mitochondria-dependent pathway.

The therapeutic efficacy of cyclosporin A in the children with refractory nephrotic syndome / 中国医师杂志

Objective To evaluate the efficacy of cyclosporine A plus prednisone in the treatment of refractory nephrotic syndrome in children.Methods The 26 refractory nephrotic syndrome children were treated with CsA plus prednisone,3 ～6 mg/(kg d),Po.The duration of treatment was 3 to 27 months (12.69 ± 6.44) mos.The 24 h quantitative urinary proteins,serum cholesterol,urea nitrogen,plasma creatinine,N-acetyl beta amino glycosidase enzymes cystatin C were detected before and after treatment,and the adverse drug reactions were accessed.Results Among 26 cases,12 cases of steroid-resistant NS,6 cases of steroid-dependent NS,and 8 cases of frequent relapse NS were included.16 patients (61.54％) were complete remission,8 patients (30.77％) partial remission,2 cases (7.69％) were non-remission,The total remission rate was 92.31％.The 24 hours urine protein was 3.01 g and 0.63 g before treatment and after treatment,respectively,with a statistically significant difference (P ＜0.01); serum cholesterol was (7.72 ± 3.86) mmol/L and (7.15 ± 3.23) mmol/L; nitrogen urea was (3.93 ± 1.44) mmol/L and (4.04 ± 1.27) mmol/L,creatinine (33.38 ± 13.16) μmol/L and (35.64 ± 3.53) μmol/L serum N-acetyl beta amino glycosidase enzymes was (18.96 ±4.86) u/L and (20.45 ±5.85)u/L before treatment and after treatment,respectively,without a statistically significant difference (P ＞ 0.05).The response to CsA was no significant difference in SRNS,SDNS and FRNS.Children complete remission,follow-up to 6 months,9 months,12 months and 18 months of the recurrence rate was 37.5％,31.25％,18.75％ and 12.5％.Eight cases ended treatment 3 ～ 6 months,all cases were not recurrence.The main adverse effects of CsA included hirsutism,tremble,gastrointestinal reaction and so on,and liver kidney toxicity was not obvious during the therapy course.Conclusions The treatment of CsA in combination with prednisone to children refractory nephrotic syndrome had a significant curative effect,which could obviously minimize the dosage of glucocorticoids and reduce the recurrence after at least one year of maintenance treatment of CsA.

Clinical study of recombinant human interleukin-11 combined with ciclosporin in treatment of glucocorticoid invalid idiopathic thrombocytopenic purpura / 中国医师进修杂志

ObjectiveTo observe the effect of recombinant human interleukin-11 combined with ciclosporin in treatment of giucocorticoid invalid idiopathic thrombocytopenic purpura.MethodsFrom August 2009 to August 2011,35 cases with glucocorticoid invalid idiopathic thrombocytopenic purpura patients were divided into two groups according to the treatment method:13 cases in control group were treated with ciclosporin and 22 cases in observation group were treated with recombinant human interleukin-11 at basis of above method.The clinical effect and platelet counts between two groups were compared.Results The total effective rate in observation group was 90.9％ (20/22),which was significantly higher than that in control group [53.8％ (7/13)] (P ＜0.05).After treatment,the platelet counts in both two groups were significantly increased [control group:( 112.5 ± 15.4) × 109/t vs.(13.2 ± 1.8 ) × 109/L; observation group:( 132.7 ± 22.3 ) × 109/L vs.(12.9 ± 1.6) × 109/L] (P ＜ 0.05 ).Moreover,the platelet counts after treatment in observation group was significantly more than that in control group (P ＜ 0.05).ConclusionRecombinant human interleukin-11combined with ciclosporin in treatment of glucocorticoid invalid idiopathic thrombocytopenic purpura is a good treatment scheme,which can be applied in clinic.

Comparison of the kinetics of 99Tcm-MIBI in tumor cells with or without MDR and the changes after MDR reversing agents / 中华核医学杂志

Objective Overexpression of multidrug resistance(MDR)is one of the mechanisms that will lead to chemotherapy failure.Of the MDR pathways in tumor cells,P-glycoprotein (P-gp) encoded by MDR genes is one of the key points.99Tcm-methoxyisobutylisonitrile(MIBI) is an imaging agent that can detect overexpression of MDR in tumor cells.The aim of this study was to observe the relationship between 99Tcm.MIBI uptake kinetics and P-gp levels in tumor cells,with or without MDR reversing agents.Methods A totle of 2×106 cells of human myelogeneous leukemia cell line K562 and its resistant subline(K562/D) were incubated with 8 MBq 99Tcm-MIBI respectively.99Tcm-MIBl accumulation and emux at various time inter-vats and the uptake difference with the presence of different cyclosporin A(O.1-O.4 ug/ml)were also ob-served.Comparison of different cell lines or without and with cyclosporin A were performed with the t-test, and the daa of different groups were compared by q-test.Results 99Tcm-MIBI uptake in K562 and K562/D cell line were 1.559±0.529 and 0.107±0.036,99Tcm-MIBI uptake in k562 was flitleon times higher than k562/D.As compared with K562 cell line with no expression of P-gp,significantly increased the 99Tcm-MIBI uptake of K562/D to 106%,148% and 163%after treated with cyclosporin A(0.1,0.2.0.4ug/ml)was ob-served(t=4.35,4.83,5.88,P<0.05).Conclusiom 99Tcm-MIBI uptake can reflect the P-gP level and multidrug-resistance inhibitor may impact 99Tcm-MIBI uptake in P-gP overexpressing cells.

Exposição de fibroblastos da cápsula de Tenon de pterígios à ciclosporina 0.05 por cento / Exposure of Tenon's capsule fibroblasts of pterygium to cyclosporin 0.05 percent

OBJETIVO: Avaliar o comportamento dos fibroblastos da cápsula de Tenon de pterígios e normais em cultura, quando expostos a ciclosporina 0,05 por cento. MÉTODOS: Estudo prospectivo, controlado, do qual participaram 20 portadores de pterígio primário. Foram colhidas amostras da cápsula de Tenon normal e proveniente do pterígio, ambas do mesmo indivíduo, colocadas para crescimento em cultura e expostas a ciclosporina 0,05 por cento. As avaliações foram feitas aos 3, 6, 12 e 17 dias após a exposição. RESULTADOS: Das amostras colhidas, 7 foram utilizadas para exposição a ciclosporina - 6 provenientes de pterígios e 1 da Tenon normal. Houve redução significativa na proliferação celular das culturas de fibroblastos expostos a ciclosporina (p<0,05). CONCLUSÃO: A ciclosporina 0,05 por cento é capaz de inibir a proliferação de fibroblastos provenientes da cápsula de Tenon de pterígio e também da Tenon normal. Novos estudos devem ser providenciados para definir o papel da ciclosporina no tratamento do pterígio.

PURPOSE: To evaluate normal Tenon capsule fibroblasts and from pterygia in culture when exposed to cyclosporin 0.05 percent. METHODS: A prospective, randomized study was done, involving 20 patients with primary pterygium. Samples of normal and pterygium Tenon's capsule from the same individual were collected, cultured and exposed to cyclosporin 0.05 percent. RESULTS: Only 7 samples could be exposed to cyclosporin - 6 from pterygial Tenon's capsule and 1 from normal Tenon's capsule. There was a significant reduction of cellular proliferation in the cyclosporin exposed cultures (p<0.05). CONCLUSION: Cyclosporin 0.05 percent is effective to inhibit the proliferation of pterygia and normal Tenon's capsule fibroblasts. Further studies should be performed to define the role of cyclosporin in pterygium treatment.

Pharmacological and clinical observation on Implanta / 中华器官移植杂志

In order to observe the pharmacological action and clinical effects of Implanta (from Hanmi Pharm. Co. Ltd) on renal transplantation, 30 patients receiving renal transplantation were treated with Implanta. Among the 30 patients, 12 patients (group A) just underwent renal transplantation, the remaining 18 cases underwent the operation 0.5 to 4 years ago and administered Sundimin or Cyspin. The results showed that the blood concentration, the effcets of inhibiting the rejection, the function recovery of transplanted kidney and side effects of Implanta were the same as those of Sundimin or Cyspin. It was conlcuded that Implanta was safe and effective.

Histological observation of the effects of cyclosporine A on laryngeal allograft in the rat / 中华器官移植杂志

Objective To study the inhibitory effects of cyclosporine A (CsA) on the laryngeal allograft rejection and corresponding histological changes,and the relation to the CsA dose.Methods The Wistar rats as recipients were divided into control group(without CsA)and two experimental groups:group Ⅰ and group Ⅱ receiving CsA 15 mg/kg and 25 mg/kg daily for 2 weeks respectively.Topographic anatomically and histologically,the survival of the laryngeal allografts was evaluated.Results Obvious histologic evidence of acute rejection of the laryngeal allografts was found in the control group.In the two experimental groups,the histological changes was obviously lessened 7 days after operation as compared with those in the control group,and the tissue structure of the laryngeal allografts was kept intact 14 days after transplantation.In the group Ⅱ,2 allografts histologically showed an increase in inflammatory cells in the lamina propria,predominantly polymorphonuclear leukocytes,with associated edema.surface epithelium and minor salivary gland acini were damaged,with focal ulceration and acinar micro-abscesses.The other case only exhibited slight rejection.Conclusion CsA can effectively prevent rejection of laryngeal allografts and block the development of injury of allografts from SD rat donors to Wistar recipients.The dosage and the pattern of administration of CsA may be closely related to its efficacy.The increased infection rate of the allografts may possibly be contributed to the higher CsA doses employed.

Neoral C_2 predicting drug hepatic toxicity following renal transplantation in hepatitis patients / 中华器官移植杂志

Objective To investigate the clinical implication of Neoral C 2 in evaluating drug hepatic toxicity following renal transplantation in hepatitis patients. Methods 162 cases receving renal transplantation were divided into two groups: positive group with positive hepatitis B and(or) C viral antigens or de finite hepatitis history before renal transplantation ( n =51) and the remaining 111 cases served as normal control group. One week posttransplantation, the blood concentrations of cyclosporins at 0 (C 0) and 2 (C 2) h after administration were determined. Results In the positive group, C 2, not C 0 one week postoperation was higher than normal control group ( P

Adult-onset Still's Disease with Disseminated Intravascular Coagulation and Multiple Organ Dysfunctions Dramatically Treated with Cyclosporine A

Severe systemic manifestations of adult onset Still's disease (AOSD) are often fatal and occasionally related to hemophagocytic syndrome (HS). We describe the case of a 49-yr-old woman with AOSD presenting with non-remitting high fever, confusion, jaundice, hepatosplenomegaly, serositis, azotemia, pancytopenia, coagulopathy with disseminated intravascular coagulation (DIC), hyperferritinemia, acute acalculous cholecystitis and ileocolitis noted in computed tomographic images. The patient had a history of herpes zoster developed prior to the admission, but there is no history of diarrhea or abdominal pain. Although bone marrow examination was not performed due to hemorrhagic diathesis, we suspected AOSD-associated HS on the basis of clinical course without detectable infectious agents in cultures or serologic studies. Intravenous immunoglobulin, pulse methylprednisolone, oral cyclosporine A (CsA) and ceftriaxone brought about transient improvement of fever and confusion, but the disease progressed. After increasing CsA dose, all previously mentioned abnormalities disappeared rapidly. Accordingly, we believe that DIC and multiple organ dysfunctions might have been the complications of HS but not that of sepsis, and that CsA can be used as a first-line therapy in case of life-threatening situations.

Osteoporosis after cardiac transplantation / 中华器官移植杂志

Objective To study the prevalence of osteoporosis in patients undergoing cardiac transplantation.Methods By using dual-energy X-ray absorptiometry,bone mineral density(BMD) in lumbar spine and femoral neck was measured in 53 adult patients after cardiac transplantation and 22 patients prior to heart transplantation.Results Mean BMD in lumbar spine and femoral neck was roughly one standard deviation below the mean for age-matched and sex-matched subjects both for men and women.Eight patients(15.1%)had densitometric evidence of osteopenia defined as a Z score of -2.0 SD or less.The mean BMD in lumbar spine and femoral neck was normal in 22 patients without undergoing cardiac transplantation.The most rapid drop in vertebral BMD occurred during the first 2 years following cardiac transplantation.Conclusion Osteopenia are Commnon in the patients after cardiac transplantation,which might be related to the immunosuppressive therapy-glucocorticoid and cyclosporine A.

Effect of Immunomodulators on experimental herpes simplex keratitis in mice / 眼科

TP5 and CsA were injected-intraperitoneally into groups of experimental mice, and NS was used for the contral group. Herpes simplex keratitis models were made subsequently by inoculation of the virus on the cornea. On the 4～6th day after inoculation, slit lamp examination showed that the corneal epithelial and stromal lesions in the TP5 group were significantly more severe than those in the NS group, whereas the group of CsA manifested no such differences. Among the 3 groups of mice, no differences were evident in the formation of corneal neovascularization, which all peaked on the 8th day. The conjuctival and palpebral lesions in the TP5 and CsA groups were also more severe than in NS group. Therefore, immunomodulators should be clinically used with care in accordance with the morbid varieties and conditions.

Acute graft-versus-host disease in thalassaemic marrow transplantation with low-dose antithymocyte globulin

Our unit performed transplantations on 21 classes II and III thalassaemic patients [class II patients had either hepatomegaly or portal fibrosis and class III patients had both]. We used busulfan [15 mg/kg] and cyclophosphamide [200 mg/kg]. Graft-versus-host disease [GVHD] prophylaxis was cyclosporin, prednisolone and low-dose antithymocyte globulin. Our patient data showed a low incidence of acute GVHD following transplantation. We offer this regimen as an acceptable therapy for thalassaemic patients undergoing allogeneic marrow transplantation as a safe clinical procedure, irrespective of the class of patient