Transplantation research最新文献

{"title":"(13)C glucose labelling studies using 2D NMR are a useful tool for determining ex vivo whole organ metabolism during hypothermic machine perfusion of kidneys.","authors":"Jay Nath,&nbsp;Tom Smith,&nbsp;Alex Hollis,&nbsp;Sam Ebbs,&nbsp;Sefa W Canbilen,&nbsp;Daniel A Tennant,&nbsp;Andrew R Ready,&nbsp;Christian Ludwig","doi":"10.1186/s13737-016-0037-0","DOIUrl":"https://doi.org/10.1186/s13737-016-0037-0","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study is to determine the feasibility of using nuclear magnetic resonance (NMR) tracer studies ((13)C-enriched glucose) to detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of porcine kidneys during hypothermic machine perfusion (HMP).</p><p><strong>Methods: </strong>Porcine kidneys (n = 6) were subjected to 24 h of HMP using the Organ Recovery Systems LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable isotope (13)C ([U-(13)C] glucose), was incorporated into KPS-1-like perfusion fluid at a concentration of 10 mM. Analysis of perfusate was performed using both 1D (1)H and 2D (1)H,(13)C heteronuclear single quantum coherence (HSQC) NMR spectroscopy. The metabolic activity was then studied by quantifying the proportion of key metabolites containing (13)C in both perfusate and tissue samples.</p><p><strong>Results: </strong>There was significant enrichment of (13)C in a number of central metabolites present in both the perfusate and tissue extracts and was most pronounced for lactate and alanine. The total amount of enriched lactate (per sample) in perfusion fluid increased during HMP (31.1 ± 12.2 nmol at 6 h vs 93.4 ± 25.6 nmol at 24 h p < 0.01). The total amount of enriched alanine increased in a similar fashion (1.73 ± 0.89 nmol at 6 h vs 6.80 ± 2.56 nmol at 24 h p < 0.05). In addition, small amounts of enriched acetate and glutamic acid were evident in some samples.</p><p><strong>Conclusions: </strong>This study conclusively demonstrates that de novo metabolism occurs during HMP and highlights active metabolic pathways in this hypothermic, hypoxic environment. Whilst the majority of the (13)C-enriched glucose is metabolised into glycolytic endpoint metabolites such as lactate, the presence of non-glycolytic pathway derivatives suggests that metabolism during HMP is more complex than previously thought. Isotopic labelled ex vivo organ perfusion studies using 2D NMR are feasible and informative.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2016-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-016-0037-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34737518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matched-pair analysis: identification of factors with independent influence on the development of PTLD after kidney or liver transplantation.","authors":"Lisa Rausch, Christian Koenecke, Hans-Friedrich Koch, Alexander Kaltenborn, Nikos Emmanouilidis, Lars Pape, Frank Lehner, Viktor Arelin, Ulrich Baumann, Harald Schrem","doi":"10.1186/s13737-016-0036-1","DOIUrl":"10.1186/s13737-016-0036-1","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant lymphoproliferative disorder (PTLD) adversely affects patients' long-term outcome.</p><p><strong>Methods: </strong>The paired t test and McNemar's test were applied in a retrospective 1:1 matched-pair analysis including 36 patients with PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching criteria were age, gender, indication, type of transplantation, and duration of follow-up. All investigated PTLD specimen were histologically positive for EBV. Risk-adjusted multivariable regression analysis was used to identify independence of risk factors for PTLD detected in matched-pair analysis. The resultant prognostic model was assessed with ROC-curve analysis.</p><p><strong>Results: </strong>Patients suffering with PTLD had shorter mean survival (p = 0.004), more episodes of CMV infections or reactivations (p = 0.042), and fewer recipient HLA A2 haplotypes (p = 0.007), a tacrolimus-based immunosuppressive regimen (p = 0.052) and higher dosages of tacrolimus at hospital discharge (Tac dosage) (p = 0.052). Significant independent risk factors for PTLD were recipient HLA A2 (OR = 0.07, 95 % CI = 0.01-0.55, p = 0.011), higher Tac dosages (OR = 1.29, 95 % CI = 1.01-1.64, p = 0.040), and higher numbers of graft rejection episodes (OR = 0.38, 95 % CI = 0.17-0.87, p = 0.023). The following prognostic model for the prediction of PTLD demonstrated good model fit and a large area under the ROC curve (0.823): PTLD probability in % = Exp(y)/(1 + Exp(y)) with y = 0.671 - 1.096 × HLA A2-positive recipient + 0.151 × Tac dosage - 0.805 × number of graft rejection episodes.</p><p><strong>Conclusions: </strong>This study suggests prognostic relevance for recipient HLA A2, CMV, and EBV infections or reactivations and strong initial tacrolimus-based immunosuppression. Patients with risk factors may benefit from intensified screening for PTLD.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2016-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34338133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From motivation to acceptability: a survey of public attitudes towards organ donation in Denmark.","authors":"Francisca Nordfalk, Maria Olejaz, Anja M B Jensen, Lea Larsen Skovgaard, Klaus Hoeyer","doi":"10.1186/s13737-016-0035-2","DOIUrl":"10.1186/s13737-016-0035-2","url":null,"abstract":"<p><strong>Background: </strong>Over the past three decades, public attitudes to organ donation have been a subject of numerous studies focusing on donor motivation. Here, we present a fresh approach. We suggest focusing on public acceptability instead of motivation. The point is to understand public attitudes well enough to avoid risking public support for organ transplantation. We conducted the study in Denmark because there have been significant developments in public attitudes to organ donation in this country. In the 1990s, Denmark was a country with very low public support for organ donation and Denmark was the last country in Europe to introduce brain death as a legal criterion of death, whereas today Eurobarometer surveys rate Denmark as one of the European countries with the highest support for deceased organ donation from brain dead donors.</p><p><strong>Methods: </strong>We conducted a telephone survey in Denmark (N = 1195). A questionnaire was developed on the basis of preceding qualitative studies and pilot testing and included reuse of one item from earlier surveys to facilitate historical comparison. The analysis of the data was carried out using IBM SPSS Statistics 22 and focused on descriptive statistics.</p><p><strong>Results: </strong>A clear majority of 91.9 % are positive or very positive towards organ donation; 85.8 % like the idea of their body being used after their death, 85.0 % is willing to donate their own organs, 82.1 % to donate their tissue and only 2.3 % find that too much has been done to promote organ donation. There is limited support for monetary incentives for organ donation (5.8 %) and presumed consent (30.4 %), while a majority (63.9 %) supports making it mandatory to register a personal decision. Religious self-identification has limited impact on attitudes.</p><p><strong>Conclusions: </strong>We can identify a shift over the past three decades from marked opposition to organ transplantation to strong support as well as a pattern in the contemporary public attitudes, which can help explain what is central to public acceptability: self-determination. Policies fostering choice are met with a majority of positive attitudes, while presumed consent and monetary incentives are met with more negative attitudes. Our approach calls for comparative studies in other countries to generate a better overall understanding of the conditions of acceptability, which need to be in place to ensure the long-term social robustness of organ donation and thereby safeguard this important medical technology.</p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2016-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34516729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocol for a prospective randomized controlled trial of recipient remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial)","authors":"F. Robertson, Rupnayan Goswami, G. Wright, B. Fuller, B. Davidson","doi":"10.1186/s13737-016-0033-4","DOIUrl":"https://doi.org/10.1186/s13737-016-0033-4","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-016-0033-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65794579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some considerations on the current debate about typing resolution in solid organ transplantation","authors":"P. Vogiatzi","doi":"10.1186/s13737-016-0032-5","DOIUrl":"https://doi.org/10.1186/s13737-016-0032-5","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"157 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-016-0032-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65794564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients","authors":"Alina S. R Zaltzman, L. Glick, J. Zaltzman, M. Nash, Michael Huang, G. Prasad","doi":"10.1186/s13737-016-0031-6","DOIUrl":"https://doi.org/10.1186/s13737-016-0031-6","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-016-0031-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65794553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulating effects of the anti-viral agent Silibinin in liver transplant patients with HCV recurrence","authors":"A. Castellaneta, Antonio Massaro, M. Rendina, F. D'errico, S. Carparelli, S. Rizzi, A. Thomson, A. Di Leo","doi":"10.1186/s13737-016-0030-7","DOIUrl":"https://doi.org/10.1186/s13737-016-0030-7","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-016-0030-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65795036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical considerations for the use of mTOR inhibitors.","authors":"Fritz Diekmann,&nbsp;Josep M Campistol","doi":"10.1186/s13737-015-0029-5","DOIUrl":"https://doi.org/10.1186/s13737-015-0029-5","url":null,"abstract":"<p><p>Immunosuppressive therapy after kidney transplantation is based on calcineurin inhibitors (CNI). In most cases CNI therapy is combined with mycophenolate and steroids. In spite of good short-term results this therapy is associated with long-term toxicities, graft loss and patient death. Therefore, alternative immunosuppressive strategies are needed that combine excellent efficacy with low incidences of long-term adverse outcomes. This review focuses on the strategies based on mTOR- inhibitors in combination with minimized exposure to CNI. </p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"4 Suppl 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2015-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-015-0029-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34570092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the 13th international transplantation symposia: mTOR-inhibition: what have we learned and how so we best apply the learning.","authors":"Alan G Jardine","doi":"10.1186/s13737-015-0027-7","DOIUrl":"https://doi.org/10.1186/s13737-015-0027-7","url":null,"abstract":"","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"4 Suppl 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2015-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-015-0027-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34570091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reviewing 15 years of experience with sirolimus.","authors":"Helio Tedesco Silva,&nbsp;Claudia Rosso Felipe,&nbsp;Jose Osmar Medina Pestana","doi":"10.1186/s13737-015-0028-6","DOIUrl":"10.1186/s13737-015-0028-6","url":null,"abstract":"<p><p>Here, we review 15 years of clinical use of sirolimus in our transplant center, in context with the developing immunosuppressive strategies use worldwide. The majority of studies were conducted in de novo kidney transplant recipients, using sirolimus (SRL) in combination with calcineurin inhibitors (CNIs). We also explored steroid (ST) or CNI-sparing therapies, including CNI minimization, elimination, or conversion strategies in combination with mycophenolate (MMF/MPS). Pooled long-term outcomes were comparable with those obtained with CNI and antimetabolite combination. Surprisingly, there are still several areas that need further investigation to improve the risk/benefit profile of SRL in kidney transplantation, including pharmacokinetic/pharmacodynamic drug-to-drug interaction with cyclosporine (CsA) or tacrolimus (TAC), mechanisms of SRL-associated adverse reactions and combinations with other drugs such as belatacept and once-daily TAC, possibly leading to improved long-term adherence. These studies, along with others investigating the benefits of SRL associated lower viral infections and malignancies, are essential as we do not expect the introduction of new immunosuppressive drugs in the near future. </p>","PeriodicalId":89864,"journal":{"name":"Transplantation research","volume":"4 Suppl 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2015-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s13737-015-0028-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34572173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}