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 ...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.展开更多
Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A(CsA)-induced lung injury in mice.Methods(i) Fifty male BALB/c mice were randomly divided into five groups(10 mice in each group): no...Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A(CsA)-induced lung injury in mice.Methods(i) Fifty male BALB/c mice were randomly divided into five groups(10 mice in each group): normal control(NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide(LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline(PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin(HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin(IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay(ELISA), and those of surfactant protein D(SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry(IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase(MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction(q RT-PCR).(ii) Another 60 BALB/c mice were divided into six groups(10 mice in each group) : NC group,model control(MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinicpolycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection.Detection methods were identical to those described in(i) above.Results(i) CsA(30 mg/kg) increased the lung index of mice(P < 0.001), and decreased the spleen index(P < 0.01), thymus index(P < 0.05), and the serum level of IL-2(P < 0.05). CsA(45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2(P < 0.01) in mice, and increased the serum level of IL-1β(P < 0.05) and the protein level of lung SP-D(P <0.001). CsA(60 mg/kg) increased the lung index of mice(P < 0.01), the serum level of IL-1β(P < 0.05), the protein level of lung SP-D(P < 0.01), and the mRNA levels of lung MPO and SP-D( P < 0.05), and decreased the thymus index of mice(P < 0.01). HE staining showed that 30, 45, and60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice.(ii) After pachymaran intervention in MC mice, the spleen and thymus indexes(P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased(P < 0.05).Moreover, 50 mg/kg pachymaran increased the thymus index(P < 0.05) and decreased the lung index(P < 0.01) in MC group. Pachymaran(50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β(P < 0.001), and the mRNA levels of MPO and SPD in lung tissues(P < 0.05) of mice. Pachymaran(100 mg/kg) increased the protein level of lung IL-2(P < 0.01), decreased the protein level of lung SP-D(P < 0.01), and the mRNA level of IL-1β(P < 0.001) in the lung tissues of mice. Pachymaran(200 mg/kg) increased the serum level of IL-2(P < 0.01) and lung IL-6 of mice(P < 0.05). Pachymaran(50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice(P < 0.05).Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.展开更多
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 mon...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.展开更多
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 t...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.展开更多
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 w...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.展开更多
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...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.展开更多
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...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.展开更多
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 s...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.展开更多
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 infect...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.展开更多
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 i...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.展开更多
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 diag...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.展开更多
文摘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.
基金National Natural Science Foundation of China (8207425)Hunan Provincial Natural Science Foundation(2021JJ30508 and 2020JJ4063)+3 种基金Hunan Provincial Scientific Research Project of Chinese Medicine (2021055)Changsha Outstanding and Innovative Youth Training Program (kq2106060)Key Discipline of Hunan University of Chinese Medicine (Basic Medicine 1)the Excellent Teaching Team of Postgraduates in Hunan Province (Postgraduate Teaching Team of Basic Medicine, 118)。
文摘Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A(CsA)-induced lung injury in mice.Methods(i) Fifty male BALB/c mice were randomly divided into five groups(10 mice in each group): normal control(NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide(LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline(PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin(HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin(IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay(ELISA), and those of surfactant protein D(SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry(IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase(MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction(q RT-PCR).(ii) Another 60 BALB/c mice were divided into six groups(10 mice in each group) : NC group,model control(MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinicpolycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection.Detection methods were identical to those described in(i) above.Results(i) CsA(30 mg/kg) increased the lung index of mice(P < 0.001), and decreased the spleen index(P < 0.01), thymus index(P < 0.05), and the serum level of IL-2(P < 0.05). CsA(45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2(P < 0.01) in mice, and increased the serum level of IL-1β(P < 0.05) and the protein level of lung SP-D(P <0.001). CsA(60 mg/kg) increased the lung index of mice(P < 0.01), the serum level of IL-1β(P < 0.05), the protein level of lung SP-D(P < 0.01), and the mRNA levels of lung MPO and SP-D( P < 0.05), and decreased the thymus index of mice(P < 0.01). HE staining showed that 30, 45, and60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice.(ii) After pachymaran intervention in MC mice, the spleen and thymus indexes(P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased(P < 0.05).Moreover, 50 mg/kg pachymaran increased the thymus index(P < 0.05) and decreased the lung index(P < 0.01) in MC group. Pachymaran(50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β(P < 0.001), and the mRNA levels of MPO and SPD in lung tissues(P < 0.05) of mice. Pachymaran(100 mg/kg) increased the protein level of lung IL-2(P < 0.01), decreased the protein level of lung SP-D(P < 0.01), and the mRNA level of IL-1β(P < 0.001) in the lung tissues of mice. Pachymaran(200 mg/kg) increased the serum level of IL-2(P < 0.01) and lung IL-6 of mice(P < 0.05). Pachymaran(50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice(P < 0.05).Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.
文摘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.
文摘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.
基金Science and Technology Program of Beijing(Grant No. D0205003040621).
文摘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.
文摘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.
基金financially supported by Key Science and Technology Project of Haikou City,with grant number 2011-0142
文摘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.
文摘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.
基金This study was supported by a grant from the National Key Basic ResearchProgram of China (No. 2003CB515501).
文摘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.
基金Supported by Natural Science Foundation of Shaanxi Province(No.S2010JC376)Xi’an Science and Technology Program Funding Project [No.SF1022(1)]
文摘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.
文摘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.