共查询到19条相似文献,搜索用时 15 毫秒
1.
Randeep Mandla Karsten Midtvedt Pål-Dag Line ers Hartmann Stein Bergan 《Transplant international》2006,19(1):44-53
Therapeutic drug monitoring of mycophenolic acid (MPA) in combination with cyclosporine 2-h concentration (CsA C2, n = 68) or tacrolimus trough concentration (n = 10) was investigated by repeated measurements of MPA and MPA-glucuronide (MPAG) trough concentrations in renal allograft recipients during the first 3 months post-transplant. The acute rejection rate was lower (19% vs. 43%; P < 0.05) in patients achieving CsA C2 target range during the first week (1600-2000 microg/l), n = 26, compared with those who did not, n = 42. Median MPA concentration was 0.9 and 1.2 microg/ml in patients within or below C2 range, respectively (P = 0.19). CsA C2 correlated with MPAG-to-MPA ratio (P < 0.01, r = 0.91) and gamma-glutamyl-transpeptidase (GGT, P < 0.01, r = 0.86). Total MPA concentration increased during the 3 months, but not in patients on tacrolimus. High CsA C2 lowered the acute rejection rate and plasma MPA. High CsA C2 is associated with elevated GGT, probably because of cholestatic effects, which explain the increased MPAG-to-MPA ratio. Increasing MPA concentration is ascribed to per-protocol CsA C2 reductions. In conclusion, CsA may confound the relationship between MPA and the incidence of rejection, and contribute to the difficulty of obtaining a therapeutic range for MPA in clinical practice. 相似文献
2.
Influence of Co-Medication with Sirolimus or Cyclosporine on Mycophenolic Acid Pharmacokinetics in Kidney Transplantation 总被引:1,自引:0,他引:1
D. Cattaneo S. Merlini S. Zenoni S. Baldelli E. Gotti G. Remuzzi N. Perico 《American journal of transplantation》2005,5(12):2937-2944
The pharmacokinetics of mycophenolic acid (MPA)--the active metabolite of mycophenolate mofetil (MMF)--is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA C(max) and T(max) were comparable in the two groups, while mean MPA AUC(0-12) was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure. 相似文献
3.
Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. 总被引:4,自引:0,他引:4
Ingrid Mai Elke St?rmer Steffen Bauer Hagen Krüger Klemens Budde Ivar Roots 《Nephrology, dialysis, transplantation》2003,18(4):819-822
BACKGROUND: This study investigated the effect of St John's wort (SJW) extract on the pharmacokinetics of the immunosuppressants tacrolimus (TAC) and mycophenolic acid (MPA). METHODS: Ten stable renal transplant patients received 600 mg SJW extract for 14 days in addition to their regular regimen of TAC and mycophenolate mofetil. RESULTS: Dose-corrected AUC((0-12)) of TAC decreased significantly from 180 ng/ml/h at baseline to 75.9 ng/ml/h after 2 weeks of SJW treatment. To maintain therapeutic TAC concentrations, dose adjustments from a median 4.5 mg/day at baseline to 8.0 mg/day under SJW treatment were required. Two weeks after discontinuation of SJW, TAC doses were reduced to a median of 6.5 mg/day. MPA pharmacokinetics remained unaffected by comedication with hypericum extract. CONCLUSIONS: Administration of SJW extract to patients receiving TAC treatment can result in a serious drug interaction leading to markedly reduced TAC blood concentrations associated with the risk of organ rejection. 相似文献
4.
Plasma Concentrations of Mycophenolic Acid Acyl Glucuronide Are Not Associated with Diarrhea in Renal Transplant Recipients 总被引:2,自引:0,他引:2
T. Heller T. van Gelder K. Budde J. W. de Fijter D. Kuypers W. Arns J. Schmidt L. Rostaing S. H. Powis K. Claesson I. A. M. MacPhee E. Pohanka J. Engelmayer G. Brandhorst M. Oellerich V. W. Armstrong 《American journal of transplantation》2007,7(7):1822-1831
The aim of this study was to determine whether plasma concentrations of the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA) were related to diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA, MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of diarrhoea were recorded during 12 months. Significantly more patients on TCL (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the 2 h AUCs of MPAG and AcMPAG did not differ between patients with and without diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in patients on CsA compared with TCL, while MPA-AUC was lower in the former group. These data support the concept that CsA inhibits the biliary excretion of MPAG and AcMPAG, thereby potentially reducing the risk of intestinal injury through enterohepatic recycling of MPA and its metabolites. 相似文献
5.
K. Budde C. Sommerer T. Becker A. Asderakis F. Pietruck J. M. Grinyo P. Rigotti J. Dantal J. Ng M. J. Barten M. Weber 《American journal of transplantation》2010,10(3):571-581
Sotrastaurin, a novel protein‐kinase‐C inhibitor, blocks early T‐cell activation. In this 12‐month, Phase II study, de novo renal‐transplant patients were randomized to sotrastaurin (200 mg b.i.d.) + standard‐exposure tacrolimus (SET) or reduced‐exposure tacrolimus (RET) (SET: n = 76; RET: n = 66), or control (SET + mycophenolic acid [MPA, 720 mg b.i.d.]; n = 74). In both sotrastaurin groups, patients were converted from tacrolimus to MPA after Month 3, achieving calcineurin inhibitor‐free immunosuppression. The primary endpoint was composite efficacy failure (treated biopsy‐proven acute rejection, graft loss, death or loss to follow‐up). The key secondary endpoint was glomerular filtration rate (GFR). Composite efficacy failure rates were: 4.1%, 5.4% and 1.5% at Month 3 (preconversion) and 7.8%, 44.8% and 34.1% at study end in the control, sotrastaurin + SET and sotrastaurin + RET groups, respectively; these results led to premature study discontinuation. Median GFR at Month 6 was: 57.0, 53.0 and 60.0 mL/min/1.73 m2, respectively. Study‐drug discontinuations due to adverse events occurred in 16.2%, 18.4% and 12.1%, respectively. Leukopenia and neutropenia occurred more frequently preconversion in control versus sotrastaurin groups: 13.7%, 5.6%, and 4.6%; and 11.1%, 4.3% and 3.1%, respectively. The initial sotrastaurin + tacrolimus regimen was efficacious and well tolerated but the postconversion sotrastaurin + MPA regimen showed inadequate efficacy. Longer‐term evaluation of sotrastaurin + tacrolimus is warranted. 相似文献
6.
Jehyun Park Hunjoo Ha Jiyeon Seo Myoung Soo Kim Hae Jin Kim Kyu Ha Huh Kiil Park Yu Seun Kim 《American journal of transplantation》2004,4(12):1982-1990
Vascular smooth muscle cell (VSMC) proliferation is the major pathologic feature associated with chronic allograft nephropathy, and mycophenolic acid (MPA) inhibits VSMC proliferation. Since the role of inosine monophosphate dehydrogenase (IMPDH)-dependent de novo guanosine synthesis is limited in VSMCs, we examined the effects of MPA on platelet-derived growth factor (PDGF)-induced cellular ROS and mitogen-activated protein kinases (MAPK) activation in VSMCs. Primary cultured rat VSMCs were stimulated with PDGF-BB in the presence or absence of MPA. Cell proliferation was assessed by [3H]-thymidine incorporation, ROS by flow cytometry and MAPK activation by Western blot analysis. PDGF increased cell proliferation, cellular ROS and extracellular-regulated protein kinase (ERK) 1/2 and p38 MAPK activation by 3.4-, 1.6-, 3.3- and 3.9-fold, respectively. MPA at above 1 muM inhibited PDGF-induced cellular ROS and ERK 1/2 and p38 MAPK activation, as well as proliferation. Structurally different anti-oxidants and inhibitor of ERK or p38 MAPK blocked PDGF-induced proliferation. Anti-oxidants also inhibited ERK 1/2 and p38 MAPK activation. Exogenous guanosine partially recovered the inhibitory effect of MPA on VSMC proliferation. These results suggest that MPA may inhibit PDGF-induced VSMC proliferation partially through inhibiting cellular ROS, and subsequent ERK 1/2 and p38 MAPK activation in addition to inhibiting IMPDH. 相似文献
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Lionel Rostaing Olivier Puyoo Jean Tkaczuk Christine Peres Anne Rouzaud Jean-Marc Cisterne Claude de Preval Elie Ohayon Dominique Durand & Michel Abbal 《Clinical transplantation》1999,13(5):400-409
Recent multicenter, randomized clinical trials have shown that in renal transplant patients tacrolimus (FK506) was more efficient than cyclosporine A (CsA) at preventing acute rejection. In order to try and evaluate whether this difference was related to a different in vivo T-cell suppression we assessed, in a prospective study, the frequencies of interleukin (IL)-2-, IL-4-, IL-5-, IL-6-, IL-10-, interferon-gamma (IFN-gamma)- and double-positive IL-2/IFN-gamma-producing whole T cells, CD4 + and CD8 + T-cell subsets by means of cytokine flow cytometry. This was performed after in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with phorbol myristate acetate (PMA) and ionomycin, in the presence of monensin, in 14 healthy volunteers (controls) and in 14 renal transplant patients. The immunosuppression of the latter was based either on CsA (n = 7) or on FK506 (n = 7). Cytokine-expressing T-cell frequencies were assessed immediately pretransplantation (DO), and subsequently 3 months (M3) and 6 months (M6) afterwards in fasting patients prior to the morning intake of the immunosuppressive drug. We found that at DO the frequencies of IL-2-(22 +/- 2% vs. 22.2 +/- 2%), IFN-gamma-(26 +/- 3% vs. 29 + 3.4%) and IL-4-(0.8 +/- 0.2% vs. 1.4 +/- 0.2%)-expressing T lymphocytes were not significantly different between the controls and the patients, respectively. Conversely, the frequency of IL-2/IFN-gamma double positive cells was higher in the latter (9.3 +/- 1.6%) than in the controls (5.6 +/- 0.8); p = 0.06. Finally, on D0 the frequencies of IL-5-, IL-6-, and IL-10-producing T lymphocytes were lower than 1%, in both groups, as well as after grafting, i.e. on M3 and M6. As compared to baseline (DO): (a) chronic immunosuppression significantly decreased the frequencies of IL-2-, IL-4- and IL-2/IFN-gamma-expressing T cells, whereas those of IFN-gamma, IL-5, IL-6, and IL-10 were not significantly affected; (b) the frequencies of cytokine-expressing T cells were not statistically different between M3 and M6; (c) the decrease in the frequencies of IL-2- and IL-2/IFN-gamma-expressing T cells affected CD4 + and CD8 + cells equally; (d) there was a marginal decrease in the frequency of IFN-gamma-expressing cells only in the CD4 + subset but not in the CD8 population; and (e) for CsA, but not for FK506, the frequency of the IL-2-expressing T cells was negatively correlated with the whole blood trough levels. When we compared the frequencies of cytokine-expressing cells in FK506- and CsA-treated patients, we found that the frequency of IL-2-expressing T cells was significantly lower with FK506 (10.9+/-1.61%) than with CsA (16.3 +/- 1.8%; p = 0.03), whereas the frequencies of the other cytokine-expressing cells were not statistically different between the two groups. In conclusion, our study clearly demonstrated that studied ex vivo, FK506 and CsA decrease the frequencies of cells expressing IL-2, IL-4 and IL-2/IFN-gamma in vivo but do not affect those expressing IFN-gamma. Meanwhile, the frequency of IL-2-producing T cells was more affected with FK506 than with CsA and was negatively correlated with the CsA trough level. Finally, our results regarding IL-2 might explain to some extent the higher efficiency of FK506 in vivo than CsA. 相似文献
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富集低丰度蛋白的人类精子全蛋白二维电泳整合图的建立 总被引:3,自引:0,他引:3
目的:运用二维电泳(2-DE)技术分离人类正常精子低丰度蛋白并建立全精子蛋白的2-DE整合图。方法:30例精子标本混匀后一次性进行蛋白提取,分别使用0.8、0.6、0.5、0.3 mg的蛋白上样量进行2-DE。运用MALD I-TOF法对确定2个恒定蛋白点的等位点(PI)和相对分子质量(Mr)作为图像的内参照点,对不同上样量的2-DE图进行比较分析,最后合成1张富集低丰度蛋白的整合图。结果:在0.5 mg图中分离出(1 080±23)个蛋白点,并合成具889个匹配点的整合图A。在上样量为0.8、0.6及0.3 mg的2-DE图中,分别新检测到381、50、32个在0.5 mg图中未检测到的蛋白点。最后合成具1 352个蛋白点的整合图B。结论:通过改变上样量的方法促进低丰度蛋白分离并合成具1 352个蛋白点富集低丰度蛋白的2-DE整合图。 相似文献
11.
观察果酸联合二氧化碳点阵激光治疗面部毛孔粗大新方案的临床效果及安全性。方法 选取
2021年4月-2022年8月佛山市第二人民医院收治的60例面部毛孔粗大患者为研究对象,按随机数字表法分
为点阵组、果酸组及联合组三组,每组20例。点阵组给予二氧化碳点阵激光治疗,果酸组给予果酸活肤套
包治疗,联合组给予二氧化碳点阵激光联合果酸活肤套包治疗,分别比较治疗前、治疗后4周VISIA面部分
析仪的毛孔计数分值变化、毛孔标准照片评分,统计不良反应发生情况。结果 三组治疗后4周VISIA面部
分析仪检测毛孔计数分值及部毛孔标准照片评分低于治疗前,且联合组低于果酸组、点阵组,差异有统计
学意义(P <0.05);果酸治组不良反应发生率低于联合组及点阵组,联合组不良反应发生率低于点阵组
(P <0.05)。结论 对面部毛孔粗大患者采用果酸联合二氧化碳点阵激光治疗效果确切,较单一使用二氧
化碳点阵治疗或果酸治疗更能改善毛孔,且安全性更高。 相似文献
12.
Nelly E. Avissar Liana Toia Yingchuan Hu Thomas J. Watson Carolyn Jones Daniel P. Raymond Alexi Matousek Jeffrey H. Peters 《Journal of gastrointestinal surgery》2009,13(2):212-222
Objectives Bile acids and acid are implicated in the development of Barrett’s esophagus. Evidence suggests that Barrett’s esophagus intestinal
metaplasia may occur via induction of caudal homeobox gene 2 (CDX2). We hypothesized that induction of CDX2 by bile acids
may be due to ligand-dependent transactivation of epidermal growth factor receptor (EGFR).
Methods Human mucosal epithelial cells (SEG-1) were treated for 0 to 24 h with up to 300 μM deoxycholic acid (DCA) at pH 7 or 5 with
or without (w/wo) antibodies against EGFR ligand-binding site (Mab528, 3–5 μg/ml). Treatment with 100 ng/ml EGF served as
control. CDX2 mRNA expression was determined by real-time polymerase chain reaction. EGFR activation was analyzed by Westerns
of phosphorylated EGFR tyrosines.
Results Acid (pH 5) increased the induction of CDX2 mRNA expression caused by DCA. CDX2 mRNA induction was markedly reduced by EGFR
blockade with Mab528. Each treatment (pH 5, DCA or pH 5 plus DCA) activated the EGFR on all tyrosines tested but in different
time courses. Phosphorylation by DCA was inhibited by Mab528. Activation of EGFR by DCA at pH 5 resulted in EGFR degradation,
while that by DCA alone did not.
Conclusion Thus, CDX2 induction by DCA w/wo acid occurs through ligand-dependent transactivation of the EGFR. The variations in EGFR
degradation pattern with DCA or DCA at pH 5 indicate differential transactivation pathways. The molecular pathogenesis of
Barrett’s esophagus may occur via bile-stimulated cell signaling through the EGFR.
Presented at the annual meeting of the Western Surgical Association, Colorado Springs, CO, USA, November 6, 2007 and in Digestive
Disease Week, San Diego, CA, USA, May 19, 2008. 相似文献
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目的 分析CO2点阵激光联合水杨酸在痤疮后凹陷性瘢痕中的临床治疗效果。方法 选取我院 2021年1月-2022年6月收治的60例痤疮后凹陷性瘢痕患者为研究对象,按照随机数字表法分为对照组与观察 组,每组30例。对照组使用CO2点阵激光治疗,观察组在对照组基础上联合博乐达水杨酸,比较两组皮肤 状态(皮肤纹理值及皮肤毛孔值)、临床疗效、生活质量及不良反应发生情况。结果 观察组生活质量各项 评分高于对照组(P<0.05);观察组不良反应发生率为6.67%,低于对照组的33.33%(P<0.05);观察组治 疗总有效率为90.00%,高于对照组的66.67%(P<0.05);观察组皮肤纹理值及皮肤毛孔值评分低于对照组 (P<0.05)。结论 CO2点阵激光是临床上治疗痤疮疤痕常用且有效的方法,选择点阵激光联合水杨酸疗法治 疗凹陷性痤疮疤痕,能够取得较好的临床疗效,改善患者皮肤状态,提高患者生活质量,且不良反应较少。 相似文献
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目的 探究痤疮后凹陷性瘢痕患者采用果酸联合CO2点阵激光治疗的效果。方法 选取2023年
2月-2024年2月我院收治的痤疮后凹陷性瘢痕患者70例作为研究对象,以随机抽签法分为对照组和研究组,每
组35例。对照组采用CO2点阵激光治疗,研究组采用果酸联合CO2点阵激光治疗,比较两组治疗效果、不良反
应发生率、GAGS评分。结果 研究组治疗总有效率为97.14%,高于对照组的80.00%(P<0.05);研究组治疗
后GAGS评分低于对照组(P<0.05);研究组不良反应发生率为5.71%,低于对照组的22.86%(P<0.05)。
结论 果酸联合CO2点阵激光治疗痤疮后凹陷性瘢痕的效果良好,能避免患者出现皮疹、皮肤红肿、色素
沉着等情况,减轻患者痤疮后凹陷性瘢痕症状。 相似文献
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目的探讨珊瑚羟基磷灰石负载含骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)纳米缓释微球体系在促进人间充质干细胞(human mesenchymal stem cells,hMSCs)骨形成中的作用。方法从骨移植患者中收集hMSCs,分离培养后使用BMP-2纳米微球作为载体,装载到珊瑚羟基磷灰石(coral hydroxyapatite,CHA)支架上。将CHA-BMP-2-hMSCs与CHA-hMSCs分别植入两组小鼠的L4和L5横向软组织中,10周后检测小鼠碱性磷酸酶(alkaline phosphatase,ALP)活性,通过Western blot检测Runx2蛋白与骨桥蛋白表达水平,通过显微镜观察骨质生长情况。结果 CHA-BMP-2-hMSCs小鼠的支架上骨组织覆盖面积显著大于CHA-hMSCs小鼠,ALP活性显著高于非缓释组小鼠,骨钙素、Runx2蛋白与骨桥蛋白表达水平高于非缓释组小鼠。结论 CHA-BMP-2-hMSCs缓释系统有利于在较长时间内诱导骨形成。 相似文献
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尼卡地平与低剂量艾司洛尔联合控制性降压对血液儿茶酚胺、β2-微球蛋白和血乳酸的影响 总被引:10,自引:1,他引:9
目的研究尼卡地平与低剂量艾司洛尔联合控制性降压方法的可行性及对血液儿茶酚胺、&2-微球蛋白(β2-mG)和组织氧代谢的影响.方法择30例择期手术的骨肿瘤病人,随机分为三组对照组(C组,n=10),不实施控制性降压,仅泵入生理盐水;尼卡地平组(N组,n=10),尼卡地平、艾司洛尔联合15组(N+E组,n=10),N组和N+E组尼卡地平起始药物速率为2.5μg@kg-1@min-1,艾司洛尔速率12.5μg@kg-1@min-1(NE=15).降至目标血压后(MAP 60~70mm Hg),调整药物剂量使MAP维持在此范围.分别于降压前、降至目标血压时、降至目标血压后30min、降压停止时以及术毕,采集动脉血分别测定血液儿茶酚胺水平、血清β2-mG含量、血乳酸含量和血红蛋白,同时记录各时间点的HR、MAP、CVP和降压期间的尿量.结果 C组与N组降压期间血去甲肾上腺素(NE)水平明显增加且呈递增趋势(P<0.05),N+E组病人NE水平虽有升高但保持在低水平(P>0.05);而其它两组病人则无明显改变.三组病人降压期间β2-mG含量均无明显升高,但降压期间的血乳酸含量升高显著(P<0.05).结论尼卡地平控制性降压不会造成组织无氧代谢发生及潜在肾损害,其与低剂量艾司洛尔联合(15)可作为一种控制性降压方法,且具有部分抗应激作用,有助于降压期间内脏血流的维护. 相似文献
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