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[PMID]:29395085
[Au] Autor:Wan L; Powell-Palm MJ; Lee C; Gupta A; Weegman BP; Clemens MG; Rubinsky B
[Ad] Endereço:Department of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China; Department of Mechanical Engineering and Department of Bioengineering, University of California, Berkeley, Berkeley, CA, 9472
[Ti] Título:Preservation of rat hearts in subfreezing temperature isochoric conditions to - 8 °C and 78 MPa.
[So] Source:Biochem Biophys Res Commun;496(3):852-857, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Isochoric (constant volume) preservation at subfreezing temperatures is being investigated as a novel method for preserving cells and organs. This study is a first initial effort to evaluate the efficacy of this method for heart preservation, and to provide a preliminary outline of appropriate preservation parameters. To establish a baseline for further studies, rat hearts were preserved in a University of Wisconsin (UW) intracellular solution for one hour under isochoric conditions at: 0 °C (atmospheric pressure - 0.1 MPa), - 4 °C (41 MPa), - 6 °C (60 MPa) and - 8 °C (78 MPa). The viability of the heart was evaluated using Langendorff perfusion and histological examination. The physiological performance of hearts preserved at - 4 °C (41 MPa) was comparable to that of a heart preserved on ice at atmospheric pressure, with no statistically significant difference in histological injury score. However, hearts preserved at -4 °C displayed substantially reduced interstitial edema compared to hearts preserved by conventional hypothermic preservation in UW on ice at atmospheric pressure, suggesting significant protection from increased vascular permeability following preservation. Hearts preserved at - 6 °C (60 MPa) suffered injury from cellular swelling and extensive edema, and at - 8 °C (78 MPa) hearts experienced significant morphological disruption. To the best of our knowledge, this is the first publication showing that a mammalian organ can survive low subfreezing temperatures without the use of a cryoprotective additive. Lowering the preservation temperature reduces metabolism and improves preservation quality, and these results suggest that improvements in preservation are possible at subzero temperatures with low to moderate pressures observed at -4 °C. Notably, tissue damage was observed at lower temperatures (-6 °C or below) accompanying further elevation of pressure associated with isochoric preservation that may prove detrimental. Therefore, subfreezing temperature isochoric preservation protocols should optimize, a combination of temperature and pressure that will minimize the negative effects of elevated pressure while retaining the beneficial effect of lower temperatures and reduced metabolism.
[Mh] Termos MeSH primário: Criopreservação/métodos
Coração/fisiologia
Miocárdio/química
Miocárdio/patologia
Soluções para Preservação de Órgãos/química
Preservação de Órgãos/métodos
[Mh] Termos MeSH secundário: Animais
Masculino
Pressão
Ratos
Ratos Sprague-Dawley
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Organ Preservation Solutions)
[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:180204
[St] Status:MEDLINE


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[PMID]:28452921
[Au] Autor:Noda K; Tane S; Haam SJ; D'Cunha J; Hayanga AJ; Luketich JD; Shigemura N
[Ad] Endereço:Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
[Ti] Título:Targeting Circulating Leukocytes and Pyroptosis During Ex Vivo Lung Perfusion Improves Lung Preservation.
[So] Source:Transplantation;101(12):2841-2849, 2017 12.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation. METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were transplanted, and posttransplant outcomes were compared. RESULTS: Lung function was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in the perfusate did not increase after the lungs were removed from the EVLP circuit, indicating that the cells trapped by the LF were not secreting IL-6. The trapped cells were analyzed with flow cytometry to detect apoptosis and pyroptosis; 26% were pyroptotic (Caspase-1-positive). After transplantation, there was better graft function and less inflammatory response if a LF was used or a caspase-1 inhibitor was administered during EVLP. CONCLUSIONS: Our data demonstrated that circulating leukocytes derived from donor lungs, and not circulating proinflammatory cytokines substantially impaired the quality of lung grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing these cells with a LF and/or inhibiting pyroptosis of the cells can be a new therapeutic approach leading to long-term success after lung transplantation.
[Mh] Termos MeSH primário: Leucócitos/citologia
Transplante de Pulmão/métodos
Pulmão/patologia
Pulmão/fisiologia
Preservação de Órgãos/métodos
Piroptose
[Mh] Termos MeSH secundário: Animais
Ponte Cardiopulmonar
Caspase 1/metabolismo
Citocinas/metabolismo
Seres Humanos
Inflamação
Interleucina-6/metabolismo
Leucócitos/metabolismo
Masculino
Microcirculação
Perfusão
Ratos
Ratos Endogâmicos Lew
Testes de Função Respiratória
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-6); EC 3.4.22.36 (Caspase 1)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001798


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[PMID]:27777501
[Au] Autor:Hawley D; Aluri H; Armaos H; Kim G; Kublin C; Zoukhri D
[Ad] Endereço:Department of Comprehensive Care, Tufts University School of Dental Medicine, Boston, MA.
[Ti] Título:Human postmortem lacrimal and submandibular glands stored in RNA are suitable for molecular, biochemical, and cell biological studies.
[So] Source:Mol Vis;22:1221-1228, 2016.
[Is] ISSN:1090-0535
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Gene expression and protein analysis studies require high-quality human tissue which is a challenge and difficult to obtain through live human biopsies. Human postmortem lacrimal gland (LG) and submandibular gland (SMG) tissues have the potential to provide an invaluable source for studying the mechanisms involved in LG and SMG dysfunction. Therefore, we aimed to test the suitability of post-mortem LG and SMG for molecular, biochemical, and cell biological studies. METHODS: LG and SMG tissue from healthy donors was collected and immediately placed in RNA solution and then shipped overnight at 4 °C. After receipt, each gland was divided into three pieces for RNA, protein, and histological analysis, respectively. Total RNA isolated from each LG and SMG was analyzed for RNA integrity using an Agilent Bioanalyzer and reverse transcription-PCR (RT-PCR). For histology, tissues were embedded in paraffin and stained with hematoxylin and eosin. For protein analysis, lysates were prepared and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. RESULTS: When the LG and SMG samples were preserved in RNA , the RNA integrity number (RIN) values from the LG and SMG were >7.0 from all three donors, while the RNAs from tissue not preserved in RNA were of poorer quality. The gene and/or protein expression of E-cadherin, aquaporin 5, alpha-smooth muscle actin (α-SMA), ß-actin, and GAPDH was preserved in all samples. In addition, histological analyses showed normal tubuloacinar structures of all glands with serous and mucous producing acini within lobules interspersed with adipose fat. CONCLUSIONS: In this study, we determined that RNA, protein, and histological sections obtained from postmortem human LG and SMG tissue preserved in RNA were of high quality. This would provide a viable source of human LG and SMG tissue suitable for studies of diseases that affect these glands, such as Sjögren's syndrome.
[Mh] Termos MeSH primário: Criopreservação
Proteínas do Olho/isolamento & purificação
Aparelho Lacrimal/química
Soluções para Preservação de Órgãos
Preservação de Órgãos
RNA/isolamento & purificação
Glândula Submandibular/química
[Mh] Termos MeSH secundário: Actinas/metabolismo
Idoso de 80 Anos ou mais
Aquaporina 5/metabolismo
Autopsia
Western Blotting
Caderinas/metabolismo
Eletroforese em Gel de Poliacrilamida
Proteínas do Olho/metabolismo
Feminino
Gliceraldeído 3-Fosfato Desidrogenase (NADP+)/metabolismo
Seres Humanos
Aparelho Lacrimal/metabolismo
Meia-Idade
RNA/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Glândula Submandibular/metabolismo
Doadores de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (AQP5 protein, human); 0 (Actins); 0 (Aquaporin 5); 0 (CDH1 protein, human); 0 (Cadherins); 0 (Eye Proteins); 0 (Organ Preservation Solutions); 63231-63-0 (RNA); EC 1.2.1.9 (Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+))
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:29240608
[Au] Autor:Hsin MK; Zamel R; Cypel M; Wishart D; Han B; Keshavjee S; Liu M
[Ad] Endereço:*Toronto Lung Transplant Program, Departments of Surgery, Medicine and Physiology, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada†Latner Thoracic Surgical Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada‡The Metabolomics Innovation Center, University of Alberta, Edmonton, Alberta, Canada.
[Ti] Título:Metabolic Profile of Ex Vivo Lung Perfusate Yields Biomarkers for Lung Transplant Outcomes.
[So] Source:Ann Surg;267(1):196-197, 2018 Jan.
[Is] ISSN:1528-1140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To identify potential biomarkers during ex vivo lung perfusion (EVLP) using metabolomics approach. SUMMARY BACKGROUND DATA: EVLP increases the number of usable donor lungs for lung transplantation (LTx) by physiologic assessment of explanted marginal lungs. The underlying paradigm of EVLP is the normothermic perfusion of cadaveric lungs previously flushed and stored in hypothermic preservation fluid, which allows the resumption of active cellular metabolism and respiratory function. Metabolomics of EVLP perfusate may identify metabolic profiles of donor lungs associated with early LTx outcomes. METHODS: EVLP perfusate taken at 1and 4 hperfusion were collected from 50 clinical EVLP cases, and submitted to untargeted metabolic profiling with mass spectrometry. The findings were correlated with early LTx outcomes. RESULTS: Following EVLP, 7 cases were declined for LTx. In the remaining transplanted cases, 9 cases developed primary graft dysfunction (PGD) 3. For the metabolic profile at EVLP-1h, a logistic regression model based on palmitoyl-sphingomyelin, 5-aminovalerate, and decanoylcarnitine yielded a receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.987 in differentiating PGD 3 from Non-PGD 3 outcomes. For the metabolic profile at EVLP-4h, a logistic regression model based on N2-methylguanosine, 5-aminovalerate, oleamide, and decanoylcarnitine yielded a ROC curve with AUC 0.985 in differentiating PGD 3 from non-PGD 3 outcomes. CONCLUSIONS: Metabolomics of EVLP perfusate revealed a small panel of metabolites highly correlated with early LTx outcomes, and may be potential biomarkers that can improve selection of marginal lungs on EVLP. Further validation studies are needed to confirm these findings.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Transplante de Pulmão
Pulmão/metabolismo
Metabolômica/métodos
Soluções para Preservação de Órgãos/metabolismo
Preservação de Órgãos/métodos
Disfunção Primária do Enxerto/prevenção & controle
[Mh] Termos MeSH secundário: Seguimentos
Seres Humanos
Pulmão/cirurgia
Disfunção Primária do Enxerto/metabolismo
Estudos Retrospectivos
Doadores de Tecidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Organ Preservation Solutions)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE
[do] DOI:10.1097/SLA.0000000000002016


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[PMID]:29176869
[Au] Autor:Vogel T; Brockmann JG; Pigott D; Neil DAH; Muthusamy ASR; Coussios CC; Friend PJ
[Ad] Endereço:Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
[Ti] Título:Successful transplantation of porcine liver grafts following 48-hour normothermic preservation.
[So] Source:PLoS One;12(11):e0188494, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current cold storage organ preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation of liver allografts. Long-term organ preservation using normothermic perfusion might not only allow organ viability assessment before transplantation, but also provide the means for further organ modifications under physiologic conditions. Previous research has shown that porcine livers can be transplanted successfully after normothermic preservation of 20 hours. In the present study we investigate whether similar methodology is capable of further extending the safe limit to 48 hours. In this study, livers from White Landrace pigs were preserved by normothermic, oxygenated sanguineous perfusion. After a 48-hour period of preservation, livers were transplanted into recipient pigs and followed for 5 days. Outcome parameters measured included markers of synthetic and metabolic liver function as well as hepatocellular injury and blood gas analysis during perfusion and follow-up. Histological assessment of morphological liver integrity was performed. All livers showed sustained bile production and metabolic activity throughout the preservation period. Low levels of hepatocellular damage were found. Following transplantation all liver grafts revealed excellent graft function and death-censored graft survival was 100%. Porcine livers were transplanted successfully following 48 hours normothermic machine preservation.
[Mh] Termos MeSH primário: Transplante de Fígado/métodos
Preservação de Órgãos/métodos
[Mh] Termos MeSH secundário: Animais
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188494


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[PMID]:28457409
[Au] Autor:Chedid MF; Bosi HR; Chedid AD; Alvares-da-Silva MR; Leipnitz I; Grezzana-Filho TJM; Reis MJ; Filho GM; Ghissi AJ; Neto PR; de Araujo A; Arruda S; Lopes AB; Michalczuk MT; Backes AN; Kruel CDP; Kruel CRP
[Ad] Endereço:Liver Transplant Program, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: marciochedid@hotmail.com.
[Ti] Título:One Hundred Consecutive Liver Transplants Using Institutes Georges Lopez-1 Preservation Solution: Outcomes and Prognostic Factors.
[So] Source:Transplant Proc;49(4):848-851, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There are only 4 prior studies reporting on outcomes of liver transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation solution. Detection of negative predictors of LT using IGL-1 may help finding strategies to protect selected recipients at higher risk of graft failure and death. METHODS: Review of all consecutive adult patients who underwent a first whole-graft LT using IGL-1 at authors' institution from 2013 to 2016. Primary end point was graft failure within the first 90 postoperative days (PODs). Graft losses due to any cause (including all deaths with a functioning graft) were recorded as graft failures. RESULTS: Of all 100 patients included in this study, 37 were women; median age was 58 years (range 18-71). There were 12 graft losses during the first 90 PODs (including 3 cases of primary nonfunction of the liver allograft), and 10 of the 12 graft losses occurred on first 30 PODs. All 12 patients who experienced graft loss (including 1 patient who underwent liver retransplantation) died within the first 90 PODs. Of the total 100 patients, 14 experienced biliary complications. Univariate analysis revealed prolonged warm ischemic time (WIT) as the only predictor of 90-day graft failure (odds ratio = 23.5, confidence interval = 1.29-430.18, P = .03). The cutoff by receiver operating characteristic curve for WIT was 38 minutes (area under the curve = 0.70). Positive predictive value for WIT >38 minutes was 94.3%. CONCLUSIONS: LT using IGL-1 can be performed safely. Similar to prior reports on LT using other preservation solutions, prolonged WIT was associated with adverse outcomes.
[Mh] Termos MeSH primário: Transplante de Fígado/métodos
Soluções para Preservação de Órgãos
Preservação de Órgãos/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Doença Hepática Terminal/cirurgia
Feminino
Sobrevivência de Enxerto
Seres Humanos
Masculino
Meia-Idade
Período Pós-Operatório
Prognóstico
Reoperação
Estudos Retrospectivos
Fatores de Tempo
Isquemia Quente
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organ Preservation Solutions)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28457385
[Au] Autor:Baroncelli F; Alberione MC; Cacciotti V; Artusio D; Vergano M; Livigni S
[Ad] Endereço:Scuola di Specializzazione in Anestesia, Rianimazione e Terapia Intensiva, Università degli Studi di Torino, Torino, Italy.
[Ti] Título:Blood Lactate Concentrations Before and After Withdrawal of Life-Sustaining Treatments in Controlled Donation After Circulatory Death: A Case Report From Italy.
[So] Source:Transplant Proc;49(4):740-742, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A 20-minute hands-off period with isoelectric electrocardiography (ECG) monitoring is currently required for the declaration of cardiac death in Italy, thus prolonging the warm ischemia time (WIT) during donation after circulatory death (DCD). Normothermic regional perfusion (NRP) can be a valid tool to optimize organ perfusion as a bridge to donation. A 62-year-old woman with catastrophic brain injury due to massive intracranial hemorrage, not fulfilling brain death criteria, underwent controlled DCD after withdrawal of life-sustaining therapies (WLST). NRP was established after a functional WIT of 43 minutes. Despite concerns regarding a prolonged WIT imposed by the national legislation on declaration of cardiac death, NRP was successful in restoring an adequate perfusion to liver and kidneys, as evidenced by a sustained reduction in blood lactate concentration. Liver and kidneys were successfully transplanted after ex vivo machine perfusion.
[Mh] Termos MeSH primário: Morte Encefálica/diagnóstico
Ácido Láctico/sangue
Preservação de Órgãos/métodos
Coleta de Tecidos e Órgãos/métodos
Isquemia Quente
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Itália
Meia-Idade
Perfusão
Doadores de Tecidos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
33X04XA5AT (Lactic Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28457381
[Au] Autor:Pezzati D; Ghinolfi D; Balzano E; De Simone P; Coletti L; Roffi N; Rreka E; Meacci L; Campani D; Mazzoni A; Paolicchi A; Caponi L; Marchetti P; Marselli L; Filipponi F
[Ad] Endereço:Hepatobiliary Surgery and Liver Transplantation Unit, University of Pisa Medical School Hospital, Pisa, Italy.
[Ti] Título:Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case Report.
[So] Source:Transplant Proc;49(4):726-728, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used.
[Mh] Termos MeSH primário: Transplante de Fígado/métodos
Doadores de Tecidos/provisão & distribuição
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Seres Humanos
Preservação de Órgãos/métodos
Obtenção de Tecidos e Órgãos/métodos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28457391
[Au] Autor:Zaouali MA; Panisello A; Lopez A; Folch E; Castro-Benítez C; Adam R; Roselló-Catafau J
[Ad] Endereço:Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC-IDIBAPS, Barcelona, Spain; Research Unit of Biology and Molecular Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, Tunisia; High Inst
[Ti] Título:Cross-Talk Between Sirtuin 1 and High-Mobility Box 1 in Steatotic Liver Graft Preservation.
[So] Source:Transplant Proc;49(4):765-769, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide +-dependent histone deacetylase that regulates various pathways involved in ischemia-reperfusion injury (IRI). Moreover, high-mobility group box 1 protein (HMGB1) has also been involved in inflammatory processes during IRI. However, the roles of both SIRT1 and HMGB1 in liver preservation is poorly understood. In this communication, we evaluated the potential relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts preserved in Institute Georges Lopez solution (IGL-1) preservation solution enriched or not enriched with trimetazidine (TMZ). METHODS: Steatotic and non-steatotic livers were preserved in IGL-1 preservation solution (24 hours, 4°C), enriched or not enriched with TMZ (10 µmol/L), and then submitted to ex vivo reperfusion (2 hours; 37°C). Liver injury (AST/ALT) and function (bile output, vascular resistance) were evaluated. SIRT1, HMGB1, autophagy parameters (beclin-1, LC3B), PPAR-γ, and heat-shock protein (HO-1, HSP70) expression were determined by means of Western blot. Also, we assessed oxidative stress, mitochondrial damage (glutamate dehydrogenase), and TNF-α levels. RESULTS: Elevated SIRT1 and enhanced autophagy were found after reperfusion in steatotic livers preserved in IGL-1+TMZ when compared with IGL-1. However, these changes were not seen in the case of non-steatotic livers. Also, HO-1 increases in the IGL-1 + TMZ group were evident only in the case of steatotic livers, whereas HSP70 and PPAR-γ protein expression were enhanced only in non-steatotic livers. All reported changes were consistent with decreased liver injury diminution, ameliorated hepatic function, and decreased TNF-α and HMGB levels. In addition, the oxidative stress and mitochondrial damage were efficiently prevented by the IGL-1 + TMZ use. CONCLUSIONS: SIRT1 is associated with HMGB1 decreases and increased autophagy in steatotic livers, contributing to increased tolerance to cold IRI.
[Mh] Termos MeSH primário: Fígado Gorduroso/metabolismo
Proteína HMGB1/fisiologia
Preservação de Órgãos/métodos
Sirtuína 1/fisiologia
Transplantes/metabolismo
[Mh] Termos MeSH secundário: Animais
Fígado Gorduroso/cirurgia
Proteínas de Choque Térmico/metabolismo
Fígado/fisiopatologia
Transplante de Fígado
Mitocôndrias Hepáticas/metabolismo
Soluções para Preservação de Órgãos
Estresse Oxidativo
Ratos
Ratos Zucker
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGB1 Protein); 0 (Heat-Shock Proteins); 0 (IGL-1 solution); 0 (Organ Preservation Solutions); 0 (Tumor Necrosis Factor-alpha); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171218
[Lr] Data última revisão:
171218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28457390
[Au] Autor:Reigada CHP; de Ataide EC; Mattosinho TDAP; Costa LBE; Escanhoela CA; Boin IFSF
[Ad] Endereço:Unit of Liver Transplantation, State University of Campinas, Brazil.
[Ti] Título:Association Safety of Liver Preservation Solutions at the State University of Campinas From 2010 to 2014.
[So] Source:Transplant Proc;49(4):761-764, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The probable reason for mixing solutions during the harvesting procedure is due to the presence of multiple transplant teams that have their own solution usage tradition. Despite numerous studies comparing the efficacy of different preservation solutions, there is no study addressing the associating solution and if there is any impact on liver graft and patient survival. The aim was to evaluate the effect of the association of preservation solutions during the harvesting procedure on liver transplantation outcomes, especially in relation to the degree of preservation injury in the postreperfusion period and patient survival. We analyzed 206 transplants that were distributed as follows: when there was association (89/206 = 43.2%) and when there was no association (117/206 = 56.8%). There was a statistically significant difference in relation to the degree of preservation injury correlated to cold ischemia time (P = .009, odds ratio 1.992; 95% confidence interval 1.185-3.347). Severe harvesting (grades III and IV) was 71.8% when the solution was not associated (P = .008). There was no difference regarding patient survival either. We found that the association of liver preservation solutions has no impact on patient survival, so it can be done safely. The best survival rate was associated with minimal harvesting.
[Mh] Termos MeSH primário: Sobrevivência de Enxerto/efeitos dos fármacos
Transplante de Fígado/mortalidade
Soluções para Preservação de Órgãos/efeitos adversos
Preservação de Órgãos/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Isquemia Fria
Feminino
Seres Humanos
Fígado/efeitos dos fármacos
Estudos Longitudinais
Masculino
Meia-Idade
Estudos Retrospectivos
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organ Preservation Solutions)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171218
[Lr] Data última revisão:
171218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE



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