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.

Clinical Observation on Treatment of Chronic Aplastic Anemia by Shengxuening (生血宁) and Cyclosporin A

Objective： To explore the therapy to further elevate the efficacy of the treatment of chronic aplastic anemia （CAA）. Methods： Forty-five patients with CCA were assigned into two groups, the 26 patients in the treated group were treated by Shengxuening （ 生血宁, a Chinese herbal preparation） and cyclosporin A （CsA）, and the 19 patients in the control group were treated with androgen alone, with the therapeutic course lasting for over 3 months. Changes of peripheral blood picture, and the colony productivity of burst forming unit-erythroid （BFU-E）, colony forming unit-erythroid （CFU-E） and colony forming unit-granulocyte macrophage （CFU-GM） in bone marrow were observed before and after 3 months treatment. The amount of erythrocyte and platelet infusion, frequency of infection, condition of hemorrhage and relevant death were also observed. The follow-up study was conducted for over half a year. Results： The total effective rate in the treated group was 84.6 %, which was significantly higher than that in the control group （52.6 %, P〈0.05）. Levels of hemoglobin, reticulocyte, neutrophil and platelet increased after treatment in the treated group, as compared with those before treatment, with significant difference （ P〈0.05）, and the colony productivity of BFU-E, CFU-E and CFU-GM in bone marrow also got significantly increased （ P〈0.01 ）, and showed significant difference from those in the control group （P〈0.05）. Conclusion： Shengxuening-assisting CsA therapy is an effective measure for treatment of CAA.

Effects of Cyclosporin A on Proliferation of Cultured Rat Mesangial Cells

The proliferation of mesangial cells on cyclosporin (CsA) test mediumwas studied by MTT assay and TNF-Q in cultured supernatant was examined byusing ELISA. The results showed that cyclosporin A significantly inhibited theproliferation of mesangial cells at the concentration between 0. 25 - 15 μg/ml(IC50 1μg/ml). This action appeared to be dose-dependent. Release of TNF-αfrom mesangial cells stimulated by LPS was also dose-dependently suppressed. It is suggested that cyclosporin A play an important role in antiproliferation mecha-nism of mesangial cells in vitro.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Effect of Cyclosporin a Eye Drop on Keratoconjunctivitis Sicca and Its Mechanism

In this study, the effect of cyclosporin A （CsA） eye drop on keratoconjunctivitis Sicca （KCS） and its mechanism were studied. The KCS models were established by injecting Pertussis vaccine, complete freund＇s adjuvant （CFA） and antigen of conjunctiva from isotype mice. Then the KCS models were treated with cyclosporin A eye drop. Changes in breaking-up time （BUT）, lacrimal secretion in 30 min and diversion in 24 h were measured. The percentage of beaker cells, the lymphocytic infiltration in conjunctiva were observed. The expression levels of Aquaporin-3 （AQP3） in conjunctiva epithelial cells, beaker cells and accessory lacrimal gland were immunohistochemically detected. The results showed that there were significant differences in BUT, the percentage of beaker cells, lacrimal secretion in 30 min, the lymphocytic infiltration and the expression of AQP3 between the experimental group and an control group. It was concluded.that CsA eye drop exerts marked therapeutic effect on KCS by inhibiting T lymph cells, increasing the goblet cells and AQP3 expression in conjunctiva.

Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

Inhibitory effect of cyclosporin A on the immunological rejection of rats with cerebral hemorrhage following transplantation of nerve growth factors transfected glial cells

BACKGROUND： At present, it has been confirmed that immunological rejection exists in the cell transplantation in brain tissue, the effects of immunosuppressant on the immunological rejection and the survival of grafts in brain cell transplantation are worthy being investigated further. OBJECTIVE： To observe the immunological rejection after transgeneic cell transplantation in treating cerebra hemorrhage in rats, and investigate the interventional effect of cyclosprin. DESIGN ： A randomized controlled study SETTINGS： Second Affiliated Hospital of Xuzhou Medical College; First Affiliated Hospital of Nanjing Medica University. MATERIALS： Thirty-five healthy clean-degree SD rats of 6-8 weeks old were used, weighing 200-250 g, either male or female; The FACSort flow cytometer （American BD Company） and NYD-1000 image analytical system were used, The rat-anti-rat CD4 monoclonal antibody, rat-anti-rat CD8 monoclonal antibody, and rat-anti-rat MHC Ⅱ antigen monoclonal antibody were purchased from Santa Cruz Company; SP and DAB kits were purchased from Beijing Zhongshan Bio-engineering Company. XSP-8C2 light microscope was the product of Shanghai Zousun Optical Instrument, Co.,Ltd, and KYKY-3800B electron microscope was the product of China KYKY Technology Development Co.,Ltd. METHODS ： The experiments were carried out in the animal experimental center of Nanjing Medical University from April to July in 2003. ① Model establishment： The rats were anesthetized, and then the coordinates of left internal capsule were identified, and the needle was withdrawn after 120 μL blood was injected into the internal capsule. Adenoviruses were taken as the carriers, after the astrocytes were successfully transfected by nerve growth factor（NGF） gene, 0.2 mL cell suspension was injected into the sites of cerebral hemorrhage. Thirty successfully established rat models were randomly divided into cyclosporin A group （n=18） and control group, the rats were treated with intraperitoneal injection of cyclosporin A （10 mg/kg per day） intraperitoneal injection of saline of the same dosage from the 1^st day after transplantation, once a day for 7 days continuously.② CD4^＋ and CD4^＋ detection： The CD4^＋ and CD4^＋ T lymphocytes in caudal vein were counted with flow cytometer at 15 days after treatment. ③ Morphological observation in the transplanted sites： The rats were killed and then brain tissues were taken out, the transplanted sites and the structure of the normal brain tissue around the transplanted sites were observed with light and electron microscopes. ④Detections of the infiltration of T lymphocyte subsets and expression of major histocompatibility complex （MHC） Ⅱ antigen in the transplanted sites： The image analysis of immunohistochemical sections was performed with the image analytical system, and the integral optical density （IOD） was taken as the statistical value to observe the infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites, and the normal brain tissue around the transplanted sites were taken as controls. MATN OUTCOME MEASURES： ① Countings of CD4^＋ and CD4^＋ in peripheral blood; ②Results of the morphological observation in the transplanted sites; ③ Infiltration of T lymphocyte subsets and expression of MHC Ⅱ antigen in the transplanted sites RESULTS ： Totally 35 rats were used, and 30 were successfully made into models, 5 died during the treatment, the other 25 were involved in the analysis of results. ① Results of CD4^＋ and CD4^＋ T lymphocytes in pedpherel blood： The percentages of CD4^＋ and CD4^＋ T lymphocytes in the cyclosporin A group were （29.20±3.97）% and （20.65±2,02）%, respectively, which were obviously lower than those in the control group [（47,39±3,01）%, （28.30±2.36）%, t=-4.983, 4.012, P 〈 0.05], and the CDC/CD4^＋ ratio was obviously lower than that in the control group （1,41±0.86, 1,64^＋0.69, t=-3. 871, P〈 0.05）.② Morphological results in the transplanted sites： Under optical and electron microscopes, the survival region of the transplant was round, and it had an unobvious migration region with the normal brain tissues, the grafts had normal cellular form. Infiltrations of lymphocytes and monocytes were observed in both groups, and mainly located in the transplanted sites, and the expression of lymphocytes in the cyclosporin A group was markedly lower than that in the control group, and no above-mentioned changes were observed in the normal brain tissue around the transplanted sites. ③ Results of CD. and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites： The CD4^＋ and CD4^＋ T lymphocytes and expression of MHC Ⅱ antigen in the transplanted sites were observed in both groups. The IOD of CD4^＋ and CD4^＋ antigen positive cells in the cyclosporin A group were obviously lower than those in the control group （1.85±0.38, 1.44^＋0.33; 3.33±0.37, 2.648±0.56, /=-4.122, 4.434, P〈 0.05）, and the IOD of MHC Ⅱantigen positive cells was markedly lower than that in the control group （0.76±0.22, 0.94±0.24, t=3.885, P 〈 0.05）. CONCLUSION： There is immunological rejection in brain tissue after the transplantation of NSC transgeneic glial cells. ② The immunosuppressant of cyclosporin A can reduce the immunological rejection after the cell transplantation.

Cyclosporin A Enhances Callus Formation in Rabbit Tibia Fractures

Purpose: Drugs that modify the production of cytokines may affect fracture healing.The immunosuppressive drug cyclosporin A is widely used to modify the immune response in transplantations and in treatment of rheumatoid disorders. We wanted to analyze the effect of cyclosporin A on fracture healing and on the development of trauma induced osteopenia.Methods: Experimental tibia fractures were stabilised with intramedullary pins in 26 rabbits. The animals were given 5mg/kg/day of cyclosporin A or placebo for 5 weeks. Bone mineral content, callus volume and biomechanical testing were performed on both tibias and femurs.Results: At 5 weeks cyclosporin A treatment resulted in increased bone mineral content and increased callus volume of the fractured bone. The femora on the operated side had significantly lower bone mineral content compared to the non-operated side. This trauma induced osteopenia was unaffected by cyclosporin A treatment. Failure torque and stiffness of the tibia and femora were similar in both groups.Interpretation: Cyclosporin A stimulates bone formation in fracture repair. The mechanism is unclear, but a direct or cytokine mediated effect on bone forming cells, or enhanced bone induction resulting in increased bone formation, is possible.

Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potas-sium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug in-jection injury. This study aimed to assess the time-dependent efifcacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by cyclosporine-A administration （30 minutes, 8 or 24 hours）. The compound muscle action potentials were recorded pre-injury, early post-injury （within 1 hour） and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant im-provement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury （P 〈 0.05）; at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

Interaction between castanospermine an immunosuppressant and cyclosporin A in rat cardiac transplantation

AIM: To investigate the interaction between castanospermine and cyclosporin A(Cs A) and to provide an explanation for it.METHODS: The alkaloid castanospermine was prepared from the seeds of Castanospermum austral consistently achieving purity. Rat heterotopic cardiac transplantation and mixed lymphocyte reactivity were done using genetically inbred strains of PVG(donor) and DA(recipient). For the mixed lymphocyte reaction stimulator cells were irradiated with 3000 rads using a linear accelerator. Cyclosporin A was administered by gavage and venous blood collected 2 h later(C_2). The blood levels of Cs A(Neoral) were measured by immunoassay which consisted of a homogeneous enzyme assay(EMIT) on Cobas Mira. Statistical analyses of interactions were done by an acceleratedfailure time model with Weibull distribution for allograft survival and logistic regression for the mixed lymphocyte reactivity.RESULTS: Castanospermine prolonged transplant survival times as a function of dose even at relatively low doses. Cyclosporin A also prolonged transplant survival times as a function of dose particularly at doses above 2 mg/kg. There were synergistic interactions between castanospermine and Cs A in the prolongation of cardiac allograft survival for dose ranges of Cs A by castanospermine of(0 to 2) mg/kg by(0 to 200) mg/kg(HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) and(0 to 3) mg/kg by(0 to 100) mg/kg(HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) respectively. The addition of castanospermine did not significantly increase the levels of cyclosporin A on day 3 or day 6 for all doses of Cs A. On the contrary, cessation of castanospermine in the presence of Cs A at 2 mg/kg significantly increased the Cs A level(P = 0.002). Castanospermine inhibited mixed lymphocyte reactivity in a dose dependent manner but without synergistic interaction. CONCLUSION: There is synergistic interaction between castanospermine and Cs A in rat cardiac transplantation. Neither the mixed lymphocyte reaction nor the metabolism of Cs A provides an explanation.

IMMUNOSUPPRESSIVE TREATMENT OF CHILDHOOD APLASTIC ANEMIA WITH ANTITHYMOCYTE GLOBULIN (ATG) AND CYCLOSPORIN A (CSA)

This paper described the therapeutic efficacy of immunosuppressive (IS) treatment agents (ATG and CSA) and androgens in the treatment of childhood aplastic anemia (AA). The results showed that the overall curative rate was 52.4% in the ATG therapy group (21 cases) and 58.3% in the CSA therapy group (12 cases) respectively. The effective rate of all patients (SAA and CAA) was 58.1% in the IS group (18/31) and 40.4% in the androgens group (42/104), P】0.05. But, in the childhood patients with SAA, the clinical effective rate was 68.4% in the IS group and 7.9% in the androgens group, P【0.01. The laboratory tests revealed that the majority of the AA patients displalyed abnormal immunological states: inversed CD4/ CD8 ratio and increased IL-2 activity. These abnormal immunological states could be normalized in several patients when clinical response was abtained following IS therapy with ATG and CSA.

Rapid Separation of Five Cyclosporin Analogs by Supercritical Fluid Chromatography

Recently there has been a resurgence of interest in cyclic peptides due to their therapeutic advantages in terms of potency, permeability, proteolytic stability, and unique selectivity relative to traditional smaller drug molecules. Cyclosporin is a family of cyclic peptides widely used as autoimmune suppression agents. Cyclosporin analogs consist of eleven amino acids with the main difference lying at the side chain of its amino acid residues. In this study, a single step separation method was developed utilizing Supercritical Fluid Chromatography (SFC) to resolve five naturally occurring cyclosporin analogs (Cyclosporin A, B, C, D, and H) on a bare silica-packed column. The optimized method involved use of ethanol-modified carbon dioxide as mobile phase on a bare silica column at 80 °C and UV detection at 220 nm. Although column temperature and back pressure generally had insignificant effect on SFC separation, it was found in our study that increasing temperature and pressure greatly improved peak shape and resolution.

Adding cyclosporin A to eltrombopag for aplastic anemia secondary to chemotherapy for solid cancers

To the Editor:Myelosuppression is one of the most common side effects of chemotherapy.Some patients would develop long-lasting aplastic anemia(AA)even after stopping chemotherapy for over three months,due to persistent destruction of the bone marrow.As a thrombopoietin-receptor agonist,eltrombopag(EPAG)has been widely used in patients with thrombocytopenia from various origins,[1]including those with AA secondary to chemotherapy.However,both EPAG and cyclosporin A(CsA)have been reported to possibly induce the expansion of abnormal clones or controversially increase the risk of neoplasms.[2]Thus,the challenge was to treat severe cytopenia while preventing cancer relapse.Our study reported the efficacy and safety of EPAG with or without CsA for patients with AA secondary to chemotherapy,in an attempt to find solutions to these difficulties.

Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment.Serum creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function.Here,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney function.We used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 m2.We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum creatinine.The estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all equations.Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 m2.We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients.Therefore,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Recombinant human thrombopoietin in combination with cyclosporin A as a novel therapy in corticosteroid-resistant primary immune thrombocytopenia

Background The management of patients with refractory immune thrombocytopenia （ITP） is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin （rhTPO） in combination with cyclosporin A （CsA） for the management of patients with corticosteroid-resistant primary ITP.

The clinical value of enzyme-multiplied immunoassay technique monitoring the plasma concentrations of cyclosporine A after renal transplantation

The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.

Cyclophilin D-induced mitochondrial impairment confers axonal injury after intracerebral hemorrhage in mice

The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.

Size-controlled/Surface-Fu nctionalized Polystyrene Nanospheres with Good Biocompatibility and High Encapsulation Efficiency of Cyclosporin A via Miniemulsion Polymerization in One Step

In this paper, size-controlled and surface-functionalized RhB-labeled and Cyclosporin A （CsA）-loaded polysty- rene （PS） nanospheres were successfully synthesized via miniemulsion polymerization. The biophysical properties of PEG functionalized PS nanospheres from protein adsorption, blood compatibility, cell compatibility and cell penetrability showed the nanoparticles with high biocompatibility. These results indicated that PEG modified PS nanospheres showed outstanding properties as low size distribution （0.164）, high encapsulation efficiency （98.3%）, long re-calcification time （50% than positive control）, low hemolysis ratio （3.19%） and high cell viability （95.3%）. This work could be used as a good drug delivery system for CsA.

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.

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.