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[PMID]:29241087
[Au] Autor:Vosough M; Tehrani SM
[Ad] Endereço:Department of Clean Technologies, Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran. Electronic address: vosough@ccerci.ac.ir.
[Ti] Título:Development of a fast HPLC-DAD method for simultaneous quantitation of three immunosuppressant drugs in whole blood samples using intelligent chemometrics resolving of coeluting peaks in the presence of blood interferences.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:69-79, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The present study describes a fast high performance liquid chromatography-diode array detection analytical methodology for quantification of tacrolimus, everolimus and cyclosporine A in whole blood samples, with minimum sample preparation steps. A short isocratic chromatographic elution was coupled with second-order calibration using multivariate curve resolution to stablish a smart and green methodology. Due to presence of matrix effect, a sample-added calibration strategy was used for quantification purposes. The serious issues related to background drift, chromatographic shifts and co-elution of non-calibrated blood components, were resolved by a proper background correction and multivariate curve resolution-alternating least squares (MCR/ALS) methods The main features of this study were based on the fact that the acquired data matrices were handled intelligently and all features of the concerned target analytes were taken into account. Satisfactory resolution and quantification results in the presence of matrix interferences were achieved and the second-order advantage was fully exploited. The average recoveries in therapeutic concentration ranges were 102±10%, 99±11% and 104±12% for TAC, EVR and CsA, with average relative prediction errors of less than 7%. Considering the advantages of the present strategy, such as increased selectivity, sensitivity and sufficiency of lower limit of quantification through multivariate advantage, simplicity of sample treatment steps, a fast elution pattern and also a low-cost instrumentation compared with LC-MS/MS, the proposed method has the significant merits as an alternative for simultaneous therapeutic monitoring of immunosuppressants.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Imunossupressores/sangue
[Mh] Termos MeSH secundário: Biologia Computacional
Ciclosporina/sangue
Everolimo/sangue
Seres Humanos
Análise dos Mínimos Quadrados
Limite de Detecção
Modelos Lineares
Reprodutibilidade dos Testes
Tacrolimo/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 83HN0GTJ6D (Cyclosporine); 9HW64Q8G6G (Everolimus); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE


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[PMID]:29441922
[Au] Autor:Sienkiewicz B; Hurkacz M; Kuriata-Kordek M; Augustyniak-Bartosik H; Wiela-Hojenska A; Klinger M
[Ti] Título:The impact of CYP3A5 on the metabolism of cyclosporine A and tacrolimus in the evaluation of efficiency and safety of immunosuppressive treatment in patients after kidney transplantation.
[So] Source:Pharmazie;71(10):562-565, 2016 Oct 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The aim of the study was to determine the impact of CYP3A5 mutation on the serum levels of immunosuppressive drugs (tacrolimus and cyclosporine A), and on the occurrence of acute rejection episodes among patients after kidney transplantation. A limited number of such research in Polish patients was also an important factor encouraging to perform the study. Fifty-two persons were recruited. The tested patients underwent kidney transplantation and were treated either with cyclosporine A (17 persons) or with tacrolimus (35 persons). The group included 21 women and 31 men. DNA was isolated from whole blood and a modified Van Schaik et al. (2002) PCR-RFLP method was used for genotyping. The serum levels were controlled at the 7th, 14th, 30th, 90th, 180th and 360th day after transplantation. The CYP3A5 genotype had no impact on the concentrations of cyclosporine A and tacrolimus at any investigated time point. No correlation between the rate of acute rejection episodes and different genotypes of the CYP3A5 isoenzyme could be proven.
[Mh] Termos MeSH primário: Ciclosporina/metabolismo
Ciclosporina/uso terapêutico
Citocromo P-450 CYP3A/metabolismo
Imunossupressores/metabolismo
Imunossupressores/uso terapêutico
Transplante de Rim/métodos
Tacrolimo/metabolismo
Tacrolimo/uso terapêutico
[Mh] Termos MeSH secundário: Ciclosporina/efeitos adversos
Citocromo P-450 CYP3A/genética
DNA/genética
Feminino
Genótipo
Rejeição de Enxerto/genética
Rejeição de Enxerto/prevenção & controle
Seres Humanos
Imunossupressores/efeitos adversos
Isoenzimas/genética
Isoenzimas/metabolismo
Masculino
Mutação
Polônia
Reação em Cadeia da Polimerase
Polimorfismo de Fragmento de Restrição/genética
Tacrolimo/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 0 (Isoenzymes); 83HN0GTJ6D (Cyclosporine); 9007-49-2 (DNA); EC 1.14.14.1 (CYP3A5 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6717


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[PMID]:29367529
[Au] Autor:Tamura M; Kitano M; Azuma K; Tsuboi K; Abe T; Ogita C; Yokoyama Y; Furukawa T; Yoshikawa T; Saito A; Nishioka A; Sekiguchi M; Azuma N; Tsunoda S; Hosono Y; Nakashima R; Ohmura K; Matsui K; Mimori T; Sano H
[Ad] Endereço:Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine.
[Ti] Título:[A case of anti-PL-7 antibody positive polymyositis with thrombotic microangiopathy].
[So] Source:Nihon Rinsho Meneki Gakkai Kaishi;40(6):450-455, 2017.
[Is] ISSN:1349-7413
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:  A 65-year-old woman with a 17-year history of polymyositis and 8-year history of rheumatoid arthritis who was treated with a low dose of prednisolone and tacrolimus (Tac) was admitted to our hospital because of general malaise and hypertension. Blood tests showed thrombocytopenia, hemolytic anemia with fragmented erythrocytes, and hypercreatinemia. Based on these clinical features, she was diagnosed with thrombotic micro-angiopathy (TMA). Thrombocytopenia and hemolytic anemia with fragmented erythrocytes improved with the discontinuation of Tac and plasma exchange; however, hypertension and renal dysfunction persisted. TMA due to calcineurin inhibitor (CNI) nephropathy was suspected based on the histopathological findings of renal biopsy. However, the condition was atypical of a CNI nephropathy because the trough level of Tac was lower than that reported previously and renal dysfunction persisted after drug discontinuation. She had mild sclerodactylia and Raynaud's symptoms, although the diagnostic criteria for systemic sclerosis (SSc) were not satisfied. Moreover, the patient tested positive for anti PL-7 antibody. The relationship between anti PL-7 antibody and pathogenesis of SSc has been reported. In this case, it was suspected that CNI nephropathy worsened because of the potential basic factors of SSc. These findings indicate that TMA may occur in patients testing positive for anti PL-7 antibody who are treated with Tac.
[Mh] Termos MeSH primário: Aminoacil-tRNA Sintetases/imunologia
Autoanticorpos/sangue
Polimiosite/complicações
Microangiopatias Trombóticas/etiologia
[Mh] Termos MeSH secundário: Idoso
Artrite Reumatoide/complicações
Artrite Reumatoide/terapia
Biomarcadores/sangue
Inibidores de Calcineurina/administração & dosagem
Inibidores de Calcineurina/efeitos adversos
Feminino
Seres Humanos
Troca Plasmática
Polimiosite/diagnóstico
Polimiosite/terapia
Tacrolimo/administração & dosagem
Tacrolimo/efeitos adversos
Microangiopatias Trombóticas/diagnóstico
Suspensão de Tratamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Biomarkers); 0 (Calcineurin Inhibitors); EC 6.1.1.- (Amino Acyl-tRNA Synthetases); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.2177/jsci.40.450


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[PMID]:29279557
[Au] Autor:Kaneko T; Arai M; Watanabe A; Tsuruoka S
[Ad] Endereço:Divisions of Nephrology, Nippon Medical School Tama Nagayama Hospital.
[Ti] Título:Effectiveness of Measuring Genetic Polymorphisms in Metabolizing Enzymes of Tacrolimus within One Medical Facility.
[So] Source:J Nippon Med Sch;84(6):274-279, 2017.
[Is] ISSN:1347-3409
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Because genetic polymorphisms cause diverse activity in drug metabolizing enzymes, drug concentrations in the blood may be variable among patients. We analyzed the genotypes of CYP3A5 and MDR1, and investigated their relationship with whole blood drug concentrations. METHODS: Eight patients were administered an oral dose of tacrolimus for one week or longer prior to enrollment in this study. Whole blood concentrations for tacrolimus were measured 12 hours post oral administration, on the same day as genotyping, within our hospital using a fully automated gene analyzer. The procedures became so rapid that collection of blood samples could be completed within the same day (approximately one hour). RESULTS: The genotype frequency of CYP3A5 was 3/ 3 in five patients, 1/ 3 in two patients, and 1/ 1 in one patient. All five patients with 3/ 3 showed favorable increases in tacrolimus blood concentrations. In the two patients with 1/ 3, an increase in tacrolimus blood concentration was not readily achieved in one patient, but increased favorably in the other patient. In the patient with 1/ 1, tacrolimus was not detectable in the patient's blood. A favorable treatment effect was obtained by changing tacrolimus to cyclosporine. It is notable that genotypes in patients where tacrolimus was not detected in the blood were wild types: 2677G/G and 3435C/C in MDR1. CONCLUSIONS: The measurement of genetic polymorphisms in metabolizing enzymes of tacrolimus, within one medical facility, is applicable for the selection of immunosuppressants and individual dosing for the treatment of autoimmune disease.
[Mh] Termos MeSH primário: Citocromo P-450 CYP3A/genética
Genótipo
Imunossupressores/sangue
Polimorfismo Genético/genética
Tacrolimo/sangue
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Administração Oftálmica
Adolescente
Adulto
Idoso
Doenças Autoimunes/tratamento farmacológico
Feminino
Seres Humanos
Imunossupressores/metabolismo
Masculino
Meia-Idade
Medicina de Precisão
Tacrolimo/administração & dosagem
Tacrolimo/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Immunosuppressive Agents); EC 1.14.14.1 (Cytochrome P-450 CYP3A); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1272/jnms.84.274


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[PMID]:29254315
[Au] Autor:Akhtar T; Sheikh N; Shan T; Ghazanfar R
[Ad] Endereço:Cell and Molecular Biology Lab, Department of Zoology, University of the Punjab, Q-A Campus, Lahore, Pakistan.
[Ti] Título:Tacrolimus induced nephrotoxicity and pulmonary toxicity in Wistar rats.
[So] Source:J Biol Regul Homeost Agents;31(4):1061-1066, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:Transplantation has evolved into an accepted treatment for end-stage organ failure. The major limitation for solid organ transplantation is organ rejection, which is an adaptive immune response caused by the activation of T-cells. Immunosuppressant drugs are used to overcome this problem. Tacrolimus is a powerful immunosuppressive drug which is used to minimize the risk of organ rejection. The present study was designed to find the toxic effects of tacrolimus on lungs and kidneys. Wistar rats were divided into 4 experimental groups and one control group (n=9). Each rat of the experimental group was orally given the aqueous suspension of tacrolimus powder (3mg/ml) and dissected after 6, 12, 24 and 48 hours of tacrolimus suspension dose. Lungs and kidneys were excised and processed for histopathological and histochemical alterations. Kidney tissues presented signs of toxic potential on tissue architecture such as increased interstitial spaces, necrosis, especially acute tubular necrosis, glomerular shrinkage, dilated blood vessels and enlargement of Bowman’s capsule. Lung sections also confirmed the toxic potential, characterized by bronchiolar wall thickening, alveolar cells necrosis, collapsing of alveolar spaces and interstitial round cell infiltrate. Results of Prussian blue iron staining showed no iron deposition in kidney architecture while in lung sections, iron accumulation was evident. Taken together from these observations we can conclude that tacrolimus may induce toxicity to a certain extent with structural distortion of the kidneys and lungs.
[Mh] Termos MeSH primário: Imunossupressores/toxicidade
Rim/efeitos dos fármacos
Pulmão/efeitos dos fármacos
Tacrolimo/toxicidade
[Mh] Termos MeSH secundário: Animais
Ferrocianetos
Histocitoquímica
Rim/patologia
Rim/ultraestrutura
Pulmão/patologia
Pulmão/ultraestrutura
Microtomia
Ratos
Ratos Wistar
Inclusão do Tecido
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ferrocyanides); 0 (Immunosuppressive Agents); TLE294X33A (ferric ferrocyanide); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


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Registro de Ensaios Clínicos
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[PMID]:27779572
[Au] Autor:Lee D; Keymeulen B; Hilbrands R; Ling Z; Van de Velde U; Jacobs-Tulleneers-Thevissen D; Maleux G; Lapauw B; Crenier L; De Block C; Mathieu C; Pipeleers D; Gillard P
[Ad] Endereço:1 Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium. 2 University Hospital and Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium. 3 Department of Interventional Radiology, University Hospitals Leuven, KUL, Leuven, Belgium. 4 Department of Endocrinology, Gent University Hospital, Gent, Belgium. 5 Department of Endocrinology, Université Libre de Bruxelles-Hôpital Erasme, Bruxelles, Belgium. 6 Department of Diabetology, University Hospital Antwerp-UA, Antwerp, Belgium.
[Ti] Título:Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.
[So] Source:Transplantation;101(9):2218-2227, 2017 09.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. METHODS: Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. RESULTS: Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. CONCLUSIONS: These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.
[Mh] Termos MeSH primário: Soro Antilinfocitário/uso terapêutico
Diabetes Mellitus Tipo 1/cirurgia
Imunossupressores/uso terapêutico
Transplante das Ilhotas Pancreáticas
Ácido Micofenólico/uso terapêutico
Tacrolimo/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Soro Antilinfocitário/efeitos adversos
Biomarcadores/sangue
Glicemia/metabolismo
Peptídeo C/sangue
Diabetes Mellitus Tipo 1/sangue
Quimioterapia Combinada
Feminino
Seres Humanos
Imunossupressores/efeitos adversos
Transplante das Ilhotas Pancreáticas/efeitos adversos
Masculino
Meia-Idade
Ácido Micofenólico/efeitos adversos
Complicações Pós-Operatórias/etiologia
Medição de Risco
Fatores de Risco
Tacrolimo/efeitos adversos
Fatores de Tempo
Transplante Homólogo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antilymphocyte Serum); 0 (Biomarkers); 0 (Blood Glucose); 0 (C-Peptide); 0 (Immunosuppressive Agents); D7RD81HE4W (thymoglobulin); HU9DX48N0T (Mycophenolic Acid); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001543


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[PMID]:28452920
[Au] Autor:Egeland EJ; Robertsen I; Hermann M; Midtvedt K; Størset E; Gustavsen MT; Reisæter AV; Klaasen R; Bergan S; Holdaas H; Hartmann A; Åsberg A
[Ad] Endereço:1 School of Pharmacy, University of Oslo, Oslo, Norway. 2 Western Norway University of Applied Sciences, Norway. 3 Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. 4 Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 5 Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
[Ti] Título:High Tacrolimus Clearance Is a Risk Factor for Acute Rejection in the Early Phase After Renal Transplantation.
[So] Source:Transplantation;101(8):e273-e279, 2017 08.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with high tacrolimus clearance eliminate more drug within a dose interval compared with those with low clearance. Delays in dosing time will result in transient periods of lower concentrations in high versus low clearance patients. Transient subtherapeutic tacrolimus concentrations may induce acute rejection episodes. METHODS: A retrospective study in all renal transplant patients treated with tacrolimus at our center from 2009 to 2013 was conducted. The association between individually estimated tacrolimus clearance (daily tacrolimus dose [mg]/trough concentration [µg/L]) and biopsy-proven acute rejection (BPAR) the first 90 days posttransplantation was investigated. RESULTS: In total, 638 patients treated with oral tacrolimus were included in the analysis. Eighty-five (13.3%) patients experienced BPAR. Patients were stratified into 4 groups per their estimated clearance. The patients in the high clearance group had significantly higher incidence of BPAR (20.6%) with a hazard ratio of 2.39 (95% confidence interval, 1.30-4.40) compared with the low clearance group. Clearance estimate (as a continuous variable) showed a hazard ratio of 2.25 (95% confidence interval, 1.70-2.99) after adjusting for other risk factors. There were no significant differences in neither trough concentrations the first week after transplantation nor time to target trough concentration between patients later experiencing BPAR or not. CONCLUSIONS: High estimated clearance is significantly associated with increased risk of BPAR the first 90 days posttransplantation and may predict an increased risk of rejection in the early phase after renal transplantation.
[Mh] Termos MeSH primário: Rejeição de Enxerto/prevenção & controle
Transplante de Rim/efeitos adversos
Tacrolimo/farmacocinética
[Mh] Termos MeSH secundário: Doença Aguda
Biópsia
Relação Dose-Resposta a Droga
Feminino
Seguimentos
Rejeição de Enxerto/diagnóstico
Rejeição de Enxerto/metabolismo
Seres Humanos
Imunossupressores/administração & dosagem
Imunossupressores/farmacocinética
Incidência
Masculino
Meia-Idade
Noruega/epidemiologia
Estudos Retrospectivos
Fatores de Risco
Tacrolimo/administração & dosagem
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001796


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[PMID]:29314799
[Au] Autor:Vavic N; Rancic N; Cikota-Aleksic B; Magic Z; Cimesa J; Obrencevic K; Radojevic M; Mikov M; Dragojevic-Simic V
[Ti] Título:The distribution of genetic polymorphism of CYP3A5, CYP3A4 and ABCB1 in patients subjected to renal transplantation.
[So] Source:Vojnosanit Pregl;73(7):663-7, 2016 Jul.
[Is] ISSN:0042-8450
[Cp] País de publicação:Serbia
[La] Idioma:eng
[Ab] Resumo:Background/Aim: Polymorphisms of genes which encode transporter P-glycoprotein and most important enzymes for tacrolimus pharmacokinetics can have significant influence reflecting on blood concentrations of this drug. The aim of this study was to examine the distribution of polymorphisms of CYP3A5, CYP3A4 and ABCB1 genes in patients subjected to renal transplantation, for the first time in our transplantation center. Methods: The research was designed as a prospective cross-sectional study which included 211 patients subjected to renal transplantation in the Centre for Solid Organ Transplantation of the university tertiary health care hospital, Military Medical Academy, Belgrade, Serbia. Patients of both genders, 22−69-year-old, Caucasians, subjected to immunosuppressive regimen, including tacrolimus, were recruited for the study. CYP3A5 6986A>G (the *3 or *1, rs776746), CYP3A4 - 392A>G (the *1 or *1B, rs2740574) and ABCB1 3435C>T (rs1045642) genotypes were determined by TaqMan® SNP genotyping assays. Restults: Most of our patients (94.8%) had functional CYP3A4 enzyme, while 87.7% of all the patients had diminished CYP3A5 enzymatic activity. On the other hand, about one third of them, 31.3%, had functional ABCB1 transporter. Conclusion: A total of 84.8% of our patients were found to express both the CYP3А5*3*3 genotype (associated with diminished CYP3А5 enzymatic activity) and CYP3А4*1*1/*1*1B (associated with functional CYP3А4 enzymatic activity), while out of all the patients with diminished CYP3A5 enzymatic activity, 68.7% had diminished activity of ABCB1 transporter. However, further studies are necessary in order to show the influence of these genetic polymorphisms on tacrolimus blood concentrations in patients after renal transplantation.
[Mh] Termos MeSH primário: Citocromo P-450 CYP3A/genética
Imunossupressores/farmacocinética
Transplante de Rim
Polimorfismo Genético
Tacrolimo/farmacocinética
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Adulto
Idoso
Estudos Transversais
Feminino
Seres Humanos
Imunossupressores/sangue
Masculino
Meia-Idade
Estudos Prospectivos
Tacrolimo/sangue
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Immunosuppressive Agents); EC 1.14.14.1 (Cytochrome P-450 CYP3A); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.2298/VSP150505016V


  9 / 14370 MEDLINE  
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[PMID]:28461684
[Au] Autor:Aguiar D; Martínez-Urbistondo D; Baroja-Mazo A; de la Mata M; Rodríguez-Perálvarez M; Rubín A; Puchades L; Serrano T; Montero J; Cuadrado A; Casafont F; Salcedo M; Rincón D; Pons JA; Herrero JI
[Ad] Endereço:Liver Unit, University Clinic of Navarra, Pamplona, Spain.
[Ti] Título:Real-World Multicenter Experience of Immunosuppression Minimization Among 661 Liver Transplant Recipients.
[So] Source:Ann Transplant;22:265-275, 2017 May 02.
[Is] ISSN:2329-0358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Long-term morbidity and mortality in liver transplant recipients is frequently secondary to immunosuppression toxicity. However, data are scarce regarding immunosuppression minimization in clinical practice. MATERIAL AND METHODS In this cross-sectional, multicenter study, we reviewed the indications of immunosuppression minimization (defined as tacrolimus levels below 5 ng/mL or cyclosporine levels below 50 ng/mL) among 661 liver transplant recipients, as well as associated factors and the effect on renal function. RESULTS Fifty-three percent of the patients received minimized immunosuppression. The median time from transplantation to minimization was 32 months. The most frequent indications were renal insufficiency (49%), cardiovascular risk (19%), de novo malignancy (8%), and cardiovascular disease (7%). The factors associated with minimization were older age at transplantation, longer post-transplant follow-up, pre-transplant diabetes mellitus and renal dysfunction, and the hospital where the patients were being followed. The patients who were minimized because of renal insufficiency had a significant improvement in renal function (decrease of the median serum creatinine level, from 1.50 to 1.34 mg/dL; P=0.004). Renal function significantly improved in patients minimized for other indications, too. In the long term, glomerular filtration rate significantly decreased in non-minimized patients and remained stable in minimized patients. CONCLUSIONS Immunosuppression minimization is frequently undertaken in long-term liver transplant recipients, mainly for renal insufficiency. Substantial variability exists regarding the use of IS minimization among centers.
[Mh] Termos MeSH primário: Ciclosporina/administração & dosagem
Imunossupressores/administração & dosagem
Hepatopatias/cirurgia
Transplante de Fígado/métodos
Tacrolimo/administração & dosagem
[Mh] Termos MeSH secundário: Fatores Etários
Doenças Cardiovasculares/induzido quimicamente
Estudos Transversais
Ciclosporina/efeitos adversos
Ciclosporina/uso terapêutico
Feminino
Seres Humanos
Imunossupressores/efeitos adversos
Imunossupressores/uso terapêutico
Masculino
Meia-Idade
Fatores de Risco
Tacrolimo/efeitos adversos
Tacrolimo/uso terapêutico
Transplantados
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 83HN0GTJ6D (Cyclosporine); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  10 / 14370 MEDLINE  
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[PMID]:28461110
[Au] Autor:Zhu J; Zeng Y; Dolff S; Bienholz A; Lindemann M; Brinkhoff A; Schedlowski M; Xu S; Sun M; Guberina H; Kirchhof J; Kribben A; Witzke O; Wilde B
[Ad] Endereço:Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
[Ti] Título:Granzyme B producing B-cells in renal transplant patients.
[So] Source:Clin Immunol;184:48-53, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB B-cells in renal transplant patients (RTX). METHODS: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB B-cells were determined via flow cytometry. RESULTS: RTX Patients showed a diminished fraction of GrB B-cells as compared to HC. CsA treatment of healthy volunteers had no impact on the development of GrB B-cells. RTX patients with a history of allograft rejection showed an increased frequency of GrB B-cells. RTX patients with at least one episode of CMV viremia tended to have lower GrB B-cells as compared to patients without viremic episodes. CONCLUSION: We demonstrate that treatment with CsA does not impair the development of GrB B-cells. GrB B-cells may have a dual role in renal transplantation as regulatory cells to maintain allospecific tolerance and as effector cells enhancing viral control.
[Mh] Termos MeSH primário: Linfócitos B/metabolismo
Granzimas/metabolismo
Transplante de Rim
[Mh] Termos MeSH secundário: Corticosteroides/uso terapêutico
Idoso
Linfócitos B/efeitos dos fármacos
Estudos de Casos e Controles
Ciclosporina/farmacologia
Ciclosporina/uso terapêutico
Feminino
Rejeição de Enxerto/prevenção & controle
Granzimas/efeitos dos fármacos
Seres Humanos
Imunossupressores/farmacologia
Imunossupressores/uso terapêutico
Interleucinas/farmacologia
Masculino
Meia-Idade
Ácido Micofenólico/uso terapêutico
Tacrolimo/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Immunosuppressive Agents); 0 (Interleukins); 0 (interleukin-21); 83HN0GTJ6D (Cyclosporine); EC 3.4.21.- (GZMB protein, human); EC 3.4.21.- (Granzymes); HU9DX48N0T (Mycophenolic Acid); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE



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