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1.
目的: 评估液相色谱-电喷雾串联质谱(LC-ESI-MS/MS)分析人全血中环孢素的基质效应,并探究其发生机理。方法: 全血裂解物的蛋白沉淀上清液用作全血基质。分别用乙腈水溶液和全血基质配制等浓度环孢素A(CyA)、环孢素C(CyC)的质控样品。分别在添加H+、NH4+和Na+的流动相中,用LC-ESI-MS/MS的MRM模式检测质控样品中CyA,CyC的[M+H]+、[M+NH4]+和[M+Na]+(M=CyA,CyC)峰面积,以其计算基质效应因子;用MS Scan模式检查质控样品中CyA、CyC色谱流出峰的质谱离子组成情况,用于判断基质效应原因。结果: 在添加H+、NH4+和Na+的流动相中,全血基质中CyA、CyC基质效应因子分别为-76.6%~-54.0%、-86.0%~-55.3%和-42.8%~-34.1%。在加H+、加NH4+流动相中,标准液加全血基质的CyA、CyC色谱峰的质谱中出现丰度很高的[M+Na]+和[M+K]+,在加Na+流动相中它们出现丰度很高的[M+K]+,而对应的定量离子[M+H]+、[M+NH4]+或[M+Na]+的丰度显著降低。结论: 全血基质对环孢素的LC-ESI-MS/MS分析产生明显的基质效应,其原因与基质中Na+、K+同添加在流动相中用于辅助电离的H+、NH4+或Na+竞争与环孢素加合,导致定量目标加合离子丰度显著降低有关。 相似文献
2.
环孢菌素A和1,2 5(OH)2D3防治实验性自身免疫性甲状腺炎的研究 总被引:1,自引:0,他引:1
将猪的甲状腺球蛋白(pTG)100μg/只分别于第0d,第14d皮下注入CBA小鼠体内,制作实验性自身免疫性甲状腺炎(EAT)的动物模型。免免疫干预组从0-28d,治疗组从10-38d单独或者联合应用环孢菌素A(CsA,10mg/kg)灌胃和(或)1,25(OH)2D3(0.2μg/kg)腹腔注射,pTG免疫后第28d,第38d处死小鼠,取甲状腺组织作病理学检查,并检测血清中猪的甲状腺球蛋白抗体(pTGAb)、猪的甲状腺微粒体抗体(pTMAb)。免疫干预组和治疗组联合应用小剂量CsA和1,25(OH)2D3分别使EAT发病率降低44.44%和37.50%。严重病例分别降低71.43%和60.32%,免疫干预组的血清pTGAb,pTMAb的值均降低。提示:小剂量免疫抑制剂CsA和1,25(OH)2D2联合防治EAT有效,并具有协同作用。 相似文献
3.
Efstathios ALEXOPOULOS Aikaterini PAPAGIANNI Dominiki ECONOMIDOU Andreas VAINAS Dimitrios MEMMOS Menelaos PAPADIMITRIOU 《Nephrology (Carlton, Vic.)》2002,7(2):51-55
SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency. 相似文献
4.
Manish Gautam Santanu Saha Sarang Bani A. Kaul Sanjay Mishra Dada Patil N.K. Satti K.A. Suri Sunil Gairola K. Suresh Suresh Jadhav G.N. Qazi Bhushan Patwardhan 《Journal of ethnopharmacology》2009
Ethnopharmacological relevance
Roots of Asparagus racemosus Willd (Shatavari in vernacular) are widely used in Ayurveda as Rasayana for immunostimulation, galactogogue as also in treatment of conditions like ulcers and cancer. Various studies have indicated immunomodulatory properties of Shatavari root extracts and formulations.Aim of the study
To study the effect of standardized Asparagus racemosus root aqueous extract (ARE) on systemic Th1/Th2 immunity of SRBC sensitized animals.Materials and methods
We used HPTLC to quantify steroidal saponins (Shatavarin IV, Immunoside®) and flow cytometry to study effects of ARE on Th1/Th2 immunity. SRBC specific antibody titres and DTH responses were also monitored as markers of Th2 and Th1 responses, respectively. We also studied lymphocyte proliferation. Cyclosporin, cyclophosphamide and levamisole were used as controls.Results
Treatment with ARE (100 mg/(kg b.w. p.o.)) resulted in significant increase of CD3+ and CD4/CD8+ percentages suggesting its effect on T cell activation. ARE treated animals showed significant up-regulation of Th1 (IL-2, IFN-g) and Th2 (IL-4) cytokines suggesting its mixed Th1/Th2 adjuvant activity. Consistent to this, ARE also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes.Conclusion
The study suggests mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential. 相似文献5.
Michael Robson Isabelle Côte Ian Abbs Geoffrey Koffman David Goldsmith 《American journal of transplantation》2003,3(3):324-327
Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration. 相似文献
6.
Angel J. Amante Herwig-Ulf Meier-Kriesche Linda Schoenberg B. D. Kahan 《Transplant international》1997,10(3):217-222
The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use
for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose
to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations
after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling
from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor
the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly
greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (Cav) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de
novo administration of CyA-ME than with CyA-GC.
Received: 13 September 1996 Accepted: 7 January 1997 相似文献
7.
K. Hamano Hiroshi Ito Andrew Bushell Kathryn J. Wood Kensuke Esato 《Transplant international》1997,10(4):293-298
In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation
was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival.
The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose
treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant
effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level
of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence
of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced
by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined
use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were
used concurrently at the time of transplantation.
Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997 相似文献
8.
Hilary Eadon Marlene Rose Richard O'Neill Neil Leaver Magdi Yacoub 《Transplant international》1995,8(1):35-40
Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, Cmax, Cmin and tmax) showed that there were no significant differences between the two formulations except for the tmax, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London 相似文献
9.
L. G. Krivoshchapov E. M. Pal'tseva 《Bulletin of experimental biology and medicine》1998,126(5):1160-1163
Methylprednisolone increased the content of laminine, cyclosporin increased the content of fibronectin, and cyclophosphamide
suppressed the extracellular matrix production in experimental nephrotoxic nephritis and puromycin aminonucleoside nephrosis.
Therapy should be chosen with due consideration of the extracellular matrix structure in different morphological variants
of chronic glomerulonephritis.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 584–587, November, 1998 相似文献
10.
K. A. Rolls P. A. Phillips K. Aldred K. J. Hardy 《Clinical and experimental pharmacology & physiology》1994,21(3):227-230
1. Since plasma renin activity is increased in cyclosporin A (CsA)-induced hypertension in the rat, the role of the vascular renin-angiotensin system (RAS) in CsA-induced hypertension was investigated in rat mesenteric resistance vessels. 2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail-cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001). 3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration-response curves to tetradecapeptide renin substrate (10-11-10?6 mol/L), angiotensin I (10-l1-10?6 mol/L) and angiotensin II (10-12-10?6 mol/L) showed no differences between CsA-treated and control groups. 4. Mesenteric vascular angiotensin-converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA-treated and control rats. 5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA-induced hypertension in the rat. 相似文献