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1.
The effect of fluconazole (Fcz) on the cyclosporine (CsA) dosage was investigated in renal transplanted dogs receiving CsA-based immunosuppressive therapy. Initially, CsA was administered orally twice daily to raise the blood trough level between 400 and 600 ng/ml. After the addition of Fcz, the CsA dosage was adjusted to maintain its therapeutic blood concentration. Fcz significantly decreased CsA dosage in both normal and renal transplanted dogs, but a higher dosage of CsA was needed in renal transplanted dogs. In conclusion, Fcz decreases required CsA dosage and thereby reduces the cost of immunosuppressive therapy in canine renal transplantation.  相似文献   

2.
环孢素A对咖啡因刺激下的L6细胞钙蛋白酶活性的影响   总被引：1，自引：1，他引：0  
探究钙调神经磷酸酶抑制剂环孢素A是否调节骨骼肌细胞钙蛋白酶活性.将分化8 d后的L6肌管细胞随机分为4组,即对照组、环孢素组、咖啡因组、环孢素+咖啡因组.急性刺激5 h后收集细胞,提取并定量细胞总蛋白和肌原纤维蛋白,用荧光定量法测定钙蛋白酶的活性.结果显示,咖啡因刺激后肌原纤维蛋白含量下降,同时钙蛋白酶活性明显增加;加...  相似文献   

3.
OBJECTIVE: To determine the effects of ketoconazole (KC) on the pharmacokinetics of cyclosporine A (CsA) elimination in cats. STUDY DESIGN: Research study and prospective clinical trial. ANIMALS: Five healthy adult cats (pharmacokinetic studies) and 6 client-owned cats with chronic renal failure. METHODS: Blood CsA concentrations were measured after CsA (4 mg/kg i.v.) administration with or without concurrent oral KC (10 mg/kg). Subsequently, a combined CsA-KC immunosuppressive regimen was used in cats after kidney transplantation. Blood CsA concentrations were measured using high performance liquid chromatography. CsA elimination was analyzed using a computerized pharmacokinetics program. RESULTS: KC increased blood CsA concentrations 1.8-fold and 2.2-fold at 12 and 24 hours after CsA administration. KC significantly decreased the mean systemic CsA clearance from 2.73 mL/min/kg to 1.22 mL/min/kg resulting in an increase in the terminal phase half-life from 10.7 to 22.2 hours. The volume of distribution of steady-state of CsA was unaffected by KC. In a series of clinical feline kidney transplant patients, a once-a-day CsA-KC regimen was able to be used in most of the cats and was effective for prevention of allograft rejection in all of these cats. CONCLUSION AND CLINICAL RELEVANCE: KC is an effective adjunct treatment for immunosuppression in feline kidney transplant patients. KC suppresses CsA elimination, which reduces the need for CsA and allows once daily administration of CsA.  相似文献   

4.
Randomized crossover studies were performed to determine the effect of coadministration of d-alpha-tocopheryl polyethylene glycol 1,000 succinate (vitamin E TPGS) on the oral bioavailability of cyclosporine A (CsA) formulated as either Sandimmune (Novartis Pharmaceuticals) or Neoral (Novartis Pharmaceuticals). Healthy dogs were given a single oral dose of each cyclosporine formulation with and without vitamin E TPGS. Blood samples were collected from each dog before and at various intervals for 24 hours after drug administration. Whole-blood CsA concentrations were determined by high-pressure liquid chromatography. Noncompartmental pharmacokinetic analysis showed that coadministration of vitamin E TPGS increased the oral bioavailability of Sandimmune. The bioavailability of Neoral was greater than that of cyclosporine. Concurrent administration of vitamin E TPGS had no consistent effect on the bioavailability of Neoral.  相似文献   

5.
Keratoconjunctivitis sicca (KCS) is a prevalent and often vision-threatening condition in dogs. In several reports, 2% cyclosporine (cyclosporin A, CsA) was described as effective in modulating the clinical signs of KCS. This study was designed to compare the efficacy of 1% CsA vs a placebo, using a randomized double-blind clinical trial. Topical administration of 1% CsA significantly improved Schirmer wetting values and subjective markers of corneal health as compared with the placebo. In the dogs treated with topical administration of 1% CsA, the clinical signs of KCS were improved in 81.8% of cases.  相似文献   

6.
The objective of this study was to compare the efficacy of cyclosporine A (CsA) and prednisolone in feline atopic dermatitis (AD) in a randomised, controlled double blind study. Twenty-nine cats with feline AD were randomly allocated to two groups. Eleven cats were treated orally with prednisolone (1mg/kg SID) and 18 were treated with CsA (5mg/kg/day) for 4 weeks. At day 0 (D0) and D28, skin lesions were graded by means of the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies and intradermal allergy tests were performed at D0 and blood samples for haematology and serum biochemistry were collected at D0 and D28. During the trial the cat owners were asked to evaluate the intensity of the pruritus once weekly on a linear analog scale and to record side effects. Based on the CADESI there was no significant difference between the two groups in the amount of remission (P=0.0562) or in the number of cats that improved by >25% (P=0.0571). The effect of CsA and prednisolone on pruritus as evaluated by the owners was not significantly different (P=0.41) between the two groups. No serious side effects were observed. The conclusion was that CsA is an effective alternative to prednisolone therapy in cats with presumed atopic dermatitis.  相似文献   

7.
Clarithromycin (CLM) has been known to increase the cyclosporine (CsA) trough levels in human transplant patients. However, the interaction of CLM with CsA has not been reported in cats. In this study, the effects of oral dosing of CLM on the pharmacokinetics and dosing of CsA in cats were investigated. Co-administration of CLM with CsA resulted in significant increases of oral bioavailability of CsA. In addition, CLM reduced the CsA dosage required to maintain the therapeutic CsA trough levels to almost 35% of the initial CsA therapy and the dose frequency was successfully replaced from a twice a day schedule to once a day in a feline kidney transplant patient. The addition of CLM to the regular CsA-based immunosuppression could be used as an effective alternative to classical ketoconazole treatment in feline kidney transplant patients and may result in substantial cost saving and convenience for the cat owners.  相似文献   

8.
亲环蛋白(CyP)能与免疫抑制剂环孢霉素A(CsA)结合而作为CsA的胞内受体。在已构建的家蚕蛹cDNA文库中获得了家蚕亲环蛋白A(BmCyPA)基因的cDNA序列。利用生物信息学方法对此序列的开放阅读框(ORF)和序列同源性等进行分析,并以家蚕蛹总RNA反转录的cDNA为材料克隆了BmCyPA,通过原核表达目的蛋白后,将纯化的BmCyPA融合蛋白免疫新西兰兔得到抗血清,Western blotting检测目的蛋白在蚕体中得到表达。利用荧光定量PCR方法检测家蚕5龄幼虫各组织中BmCyPA mRNA的转录水平,由高到低依次为脂肪体、丝腺、中肠、马氏管、表皮、头部、气门、卵巢;Western blotting检测BmCyPA在5龄幼虫各组织中的表达水平,由高到低依次为脂肪体、气门、表皮、马氏管、中肠、丝腺、头部和卵巢。亚细胞定位显示Bm-CyPA在细胞质与细胞核中均有分布。推测BmCyPA与家蚕的生长发育以及促进蛋白质折叠和介导免疫应答等有密切联系。  相似文献   

9.
The aim of this study was to evaluate the efficacy of pimecrolimus oil-based eye drops in alleviating the clinical signs of keratoconjunctivitis sicca (KCS) in dogs and to compare the efficacy with that of cyclosporine A (CsA) ointment. An open-label, multicenter study enrolling 44 dogs previously untreated with CsA was conducted. Dogs were randomly assigned to a treatment group and medicated twice daily for 8 weeks. After that time the mean increase (+/-SEM) in the Schirmer tear test was 9.2+/-1.6 mm/min in the pimecrolimus group and 5.8+/-1.1 mm/min in the CsA group (P=0.085). The improvement in clinical signs of inflammation in eyes treated with pimecrolimus was significantly greater than in eyes treated with CsA (P=0.02). The results show that 1% pimecrolimus oily eye drops are as safe as and more effective than CsA ointment in controlling KCS in dogs.  相似文献   

10.
The effects of the calcineurin inhibitors cyclosporine A (CsA) and FK506 on the mRNA expressions of various cytokines were evaluated in dogs to determine whether the effects of CsA and FK506 in dogs were similar to those in humans. The mRNA expression levels of the cytokines IL-2, IL-4, IFN-gamma and TNF-alpha were measured in PHA-stimulated canine PBMC using real-time RT-PCR after incubation with CsA or FK506 for 5 hr. Both reagents inhibited IL-2, IL-4 and IFN-gamma mRNA expressions in a dose-dependent manner. However, CsA hardly inhibited the mRNA expression of TNF-alpha. These findings are important for assessing the indications of CsA treatment in dogs.  相似文献   

11.
OBJECTIVE: To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. ANIMALS: 8 juvenile 8-week-old Landrace X Large White crossbred pigs. PROCEDURE: CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma C-peptide and insulin concentrations were measured in response to i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. RESULTS: Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following i.v. administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. CONCLUSIONS AND CLINICAL RELEVANCE: In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.  相似文献   

12.
OBJECTIVE: To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. ANIMALS: 24 dogs with bilateral KCS. PROCEDURE: Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. RESULTS: Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. CONCLUSIONS AND CLINICAL RELEVANCE: Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.  相似文献   

13.
To clarify the interaction between St John's wort (SJW) and cyclosporine (CsA) in dogs, the pharmacokinetics of CsA before and during the repeated administration of SJW were analyzed. In the SJW group, SJW (300 mg) was given orally to four dogs every 24 h for 14 days. A single dose of CsA (5 mg/kg) was given orally 7 days before and 7 and 14 days after the initiation of the repeated administration of SJW. In the Control group, a single dose of CsA (5 mg/kg) was given orally to four other dogs in accordance with that in the SJW group. Blood samples from both groups were collected, and whole-blood concentrations of CsA were determined using high-performance liquid chromatography with UV detection. The maximum whole-blood concentration and AUC(0-∞) of the SJW group were significantly lower and the CL(tot) /F and V(d) /F were significantly higher than those in the Control group 7 and 14 days after the initiation of repeated SJW. Thus, repeated administrations of SJW affect the pharmacokinetic profiles of CsA in dogs. Further studies are necessary to elucidate the mechanisms of interaction between SJW and CsA in dogs.  相似文献   

14.
Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a four-period crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC(0-12) and C(max) values for treatment B were significantly higher than those for the other treatments. In particular, the AUC(0-12) of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.  相似文献   

15.
Acute systemic toxoplasmosis was diagnosed in a 4-5-year-old, male, Domestic Short Hair cat, which had been on cyclosporine A immunomodulatory therapy for feline atopy, over an 8-month period. Cyclosporin A (CsA) has shown promising results as a immunosuppressive agent in the cat for the treatment of eosinophilic plaque and granulomas, allergic cervico-facial pruritus, feline atopy and other immune-mediated dermatoses. However, inhibition of T-lymphocyte function by CsA is believed to have predisposed this cat to the development of a newly acquired, acute Toxoplasma gondii infection, as characterized by severe hepatic and pancreatic pathology in conjunction with the heavy parasite load demonstrated on immunohistochemical (IHC) stains for T. gondii. Cats on CsA therapy appear to be at risk of developing fatal systemic toxoplasmosis.  相似文献   

16.
This retrospective study of 51 dogs with atopic dermatitis (AD) treated with cyclosporine (CsA) for a minimum of 6 months assessed the frequency of dosing and the need for continual treatment to control clinical signs. The study evaluated both medical records and information supplied by the owners in the form of written questionnaires and telephone follow-up. Laboratory parameters, possible adverse effects and owner satisfaction were assessed. The dose of CsA was 5 mg/kg orally per day and dogs received CsA for 6-30 months. At the conclusion of the study period, 28 dogs (55%) needed ongoing CsA to control clinical signs of AD: 8 (15%) received CsA 2-3 days per week, 10 (20%) 4-5 days per week, and 10 (20%) daily. CsA was discontinued in 23 dogs (45%) after 6-24 months due to either a limited response (22%) or after achieving a clinical response (24%). The results suggest that some dogs with AD treated with CsA may not require daily or even ongoing treatment to control clinical signs. Laboratory abnormalities were detected in 13 dogs (25%) during their CsA treatment. Two dogs developed oral growths and three developed hirsuitism. Forty owners (78%) reported no adverse events in their dogs during the treatment period. Thirty-six owners (71%) were satisfied with CsA as treatment for their atopic dog.  相似文献   

17.
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18.
本研究旨在探索免疫抑制剂环孢菌素A（CsA）对LPS诱导的子宫内膜基质细胞中促炎症细胞因子白细胞介素1β（IL-1β）和白细胞介素6（IL-6）表达的影响。母兔子宫内膜基质细胞经过体外培养和鉴定后,用1 μg/mL脂多糖（lipopolysaccharide,LPS）诱导构建子宫内膜基质细胞炎症模型,0 μg/mL LPS处理作对照组。用0、50、100、200和500 ng/mL CsA处理后,分别检测IL-1β和IL-6的表达水平。结果显示,与对照组相比,添加LPS显著诱导IL-1β和IL-6在子宫内膜基质细胞中的表达（P<0.05）,CsA对子宫内膜基质细胞IL-1β和IL-6的表达无影响,但50、100、200和500 ng/mL CsA均极显著地抑制1 μg/mL LPS诱导的IL-1β和IL-6表达的上调（P<0.01）。因此,在子宫内膜基质细胞中,一定剂量的CsA能够有效抑制LPS诱导的子宫内膜基质细胞的免疫应激。本研究为雌性生殖道遭受革兰氏阴性菌感染引起免疫应激后用CsA治疗的可行性提供了依据,但在临床上的应用及其机制尚需进行深入研究。  相似文献   

19.
The aim of this study was to investigate the effect of immunosuppressant cyclosporine A (CsA) on the expression of proinflammatory cytokines interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in LPS-induced uterine endometrial stromas cells (ESCs).After cultured and identified in vitro,the inflammation model of the ESCs of female rabbits were successfully constructed by 1 μg/mL lipopolysaccharide (LPS),and 0 μg/mL LPS was used as the control.Then the expression levels of IL-1β and IL-6 were detected after treatment with 0,50,100,200 and 500 ng/mL CsA.The results showed that LPS significantly induced the expression of IL-1β and IL-6 in ESCs (P<0.05).Although CsA had no effect on the expression of IL-1β and IL-6,but 50,100,200 and 500 ng/mL CsA extremely significantly inhibited the upregulation of IL-1β and IL-6 induced by 1 μg/mL LPS (P<0.01).It suggested that a certain dose of CsA could effectively inhibit the LPS-induced immune stress in ESCs.This study provided a basis for the feasibility of CsA treatment after the genital tract of female infected by gram-negative bacteria,but its clinical application and mechanism still need to be further studied.  相似文献   

20.
Objective —To compare two methods of whole blood cyclosporine A (CsA) measurement in cats.
Study Design —Whole blood samples were analyzed for CsA concentrations with use of high performance liquid chromatography (HPLC) and monoclonal immunoassay methods.
Animals —Blood (n = 36 samples) was obtained from six cats after renal transplantation.
Methods —Results were compared by linear regression analysis using both pooled and individual patient data. Eight samples were off-scale on the immunoassay and were excluded.
Results —There was significant correlation between CsA measured using HPLC and immunoassay methods ( P < .001; r = .942; r2= .887). However, individuals varied nonrandomly from the mean pooled patient data. Correlation between the assay methods was higher for individual patients using data only from that specific individual (mean r value = .976; r2= .955). Clinical utility of the immunoassay (ie, results would prompt an appropriate CsA dosage adjustment) was good when based on individually derived conversion factors (27 of 28 [96.5%] of decision events).
Conclusion—HPLC is superior for measurement of blood CsA concentrations in cats after kidney transplantation. However, an immunoassay may provide reliable information for CsA management if a comparative database (HPLC v immunoassay) has been previously determined in a specific patient.
Clinical Relevance —Locally available monitoring of CsA by immunoassay in cats may provide significant advantages when shipping of blood samples to distant locations is required to obtain analysis by HPLC. These advantages may include cost and timeliness of results in circumstances where daily blood CsA concentrations may be desired, such as when managing an acute rejection reaction.  相似文献   

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