scholarly journals Implication of Mitochondrial Cytoprotection in Human Islet Isolation and Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Yong Wang ◽  
Joshua E. Mendoza-Elias ◽  
Meirigeng Qi ◽  
Tricia A. Harvat ◽  
Sang Joon Ahn ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Islet Transplantation ◽  
Mitochondrial Function ◽  
Graft Function ◽  
Complex Nature ◽  
Islet Isolation ◽  
Success Rates ◽  
Mitochondrial Integrity ◽  
Multistep Process ◽  
Underlying Mechanisms

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short- and long-term insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention has been placed on preserving mitochondrial function as increasing evidences suggest that impaired mitochondrial integrity can adversely affect clinical outcomes. Some recent studies have demonstrated that it is possible to achieve islet cytoprotection by maintaining mitochondrial function and subsequently to improve islet transplantation outcomes. However, the benefits of mitoprotection in many cases are controversial and the underlying mechanisms are unclear. This article summarizes the recent progress associated with mitochondrial cytoprotection in each step of the islet isolation and transplantation process, as well as islet potency and viability assays based on the measurement of mitochondrial integrity. In addition, we briefly discuss immunosuppression side effects on islet graft function and how transplant site selection affects islet engraftment and clinical outcomes.

scholarly journals Reduced glycemic variability and flexible graft function after islet transplantation: A case report

2020 ◽  
Vol 11 (6) ◽  
pp. 1677-1680 ◽  
Author(s):  
Toshihiro Nakamura ◽  
Junji Fujikura ◽  
Takayuki Anazawa ◽  
Ryo Ito ◽  
Masahito Ogura ◽  
...  
Keyword(s):  
Case Report ◽  
Islet Transplantation ◽  
Graft Function ◽  
Glycemic Variability

Efficacy of Human Islet Isolation From the Tail Section of the Pancreas for the Possibility of Living Donor Islet Transplantation

2004 ◽  
Vol 78 (6) ◽  
pp. 839-843 ◽  
Author(s):  
Shinichi Matsumoto ◽  
Koichi Tanaka ◽  
D Michael Strong ◽  
Jo Anna Reems
Keyword(s):  
Islet Transplantation ◽  
Living Donor ◽  
Human Islet ◽  
Islet Isolation

scholarly journals The purine pathway in liver tissue biopsies from donors for transplantation is associated to immediate graft function and survival

2019 ◽  
Author(s):  
Jin Xu ◽  
Mohammad Hassan-Ally ◽  
Ana María Casas-Ferreira ◽  
Tommi Suvitaival ◽  
Yun Ma ◽  
...  
Keyword(s):  
Liver Function ◽  
Clinical Data ◽  
Liver Tissue ◽  
Graft Function ◽  
List Type ◽  
Purine Metabolites ◽  
Data Driven Approach ◽  
Liver Biopsies ◽  
Purine Pathway ◽  
Underlying Mechanisms

AbstractBackground & AimsThe current shortage of livers for transplantation has increased the use of organs sourced from donation after circulatory death (DCD). These organs are prone to higher incidence of graft failure, but the underlying mechanisms are largely unknown. Here we aimed to find biomarkers of liver function before transplantation to better inform clinical evaluation.MethodsMatched pre- and post-transplant liver biopsies from DCD (n=24) and donation after brain death (DBD, n=70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. First, a discrimination analysis DCD vs DBD was used to parse metabolites associated to DCD. Then a data-driven approach was used to predict Immediate Graft Function (IGF). The metabolites were tested in models to predict survival.ResultsFive metabolites in the purine pathway were selected and investigated. The ratios of: adenine monophosphate (AMP), adenine, adenosine and hypoxanthine to urate, differed between DBD and DCD biopsies at pre-transplantation stage (q<0.05). The ratios of AMP and adenine to urate also differed in biopsies from recipients undergoing IGF (q<0.05). Using random forest a panel composed by alanine aminotransferase (ALT) and AMP, adenine, hypoxanthine ratio to urate predicted IGF with AUC 0.84 (95% CI [0.71, 0.97]). In comparison AUC 0.71 (95%CI [0.52, 0.90]) was achieved by clinical measures. Survival analysis revealed that the metabolite classifier could stratify 6-year survival outcomes (p = 0.0073) while clinical data and donor class could not.ConclusionsAt liver pre-transplantation stage, a panel composed of purine metabolites and ALT in tissue could improve prediction of IGF and survival.Lay summaryNew liver function biomarkers could help clinicians assess livers before transplantation. Purines are small molecules that are found in healthy livers, and in this work we found that their levels changed critically in livers from cardiac death donors. Measuring them before transplantation improved the prediction of the liver’s immediate graft function.Graphic abstractHighlightsThe ratios of purine metabolites to urate differ between DCD and DBD in liver tissue at pre-transplantation.The ratios of purine metabolites to urate and ALT pre-transplantation can improve prediction of IGF after transplantation.Purine metabolites ratios to urate stratified 6-year survival outcome better than clinical data and donor class.

Liver focal fatty changes at ultrasound after islet transplantation: an early sign of altered graft function?

2010 ◽  
Vol 27 (8) ◽  
pp. 960-964 ◽  
Author(s):  
M. Venturini ◽  
E. Angeli ◽  
P. Maffi ◽  
C. Losio ◽  
P. Pozzi ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Graft Function ◽  
Early Sign

scholarly journals Quantifying Donor Effects on Transplant Outcomes Using Kidney Pairs from Deceased Donors

2019 ◽  
Vol 14 (12) ◽  
pp. 1781-1787
Author(s):  
Kathleen F. Kerr ◽  
Eric R. Morenz ◽  
Heather Thiessen-Philbrook ◽  
Steven G. Coca ◽  
F. Perry Wilson ◽  
...  
Keyword(s):  
Relative Risk ◽  
Clinical Outcomes ◽  
Graft Failure ◽  
Absolute Risk ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Kidney Donor ◽  
Excess Absolute Risk ◽  
Deceased Donors ◽  
Concordance Measures

Background and objectivesIn kidney transplantation, the relative contribution of donor versus other factors on clinical outcomes is unknown. We sought to quantify overall donor effects on transplant outcomes for kidney donations from deceased donors.Design, setting, participants, & measurementsFor paired donations from deceased donors resulting in transplants to different recipients, the magnitude of donor effects can be quantified by examining the excess of concordant outcomes within kidney pairs beyond chance concordance. Using data from the Organ Procurement and Transplantation Network between the years 2013 and 2017, we examined concordance measures for delayed graft function, death-censored 1-year graft failure, and death-censored 3-year graft failure. The concordance measures were excess relative risk, excess absolute risk, and the fixation index (where zero is no concordance and one is perfect concordance). We further examined concordance in strata of kidneys with similar values of the Kidney Donor Profile Index, a common metric of organ quality.ResultsIf the transplant of the kidney mate resulted in delayed graft function, risk for delayed graft function was 19% higher (95% confidence interval [95% CI], 18% to 20%), or 1.76-fold higher (95% CI, 1.73- to 1.80-fold), than baseline. If a kidney graft failed within 1 year, then the kidney mate’s risk of failure was 6% higher (95% CI, 4% to 9%), or 2.85-fold higher (95% CI, 2.25- to 3.48-fold), than baseline. For 3-year graft failure, the excess absolute risk was 7% (95% CI, 4% to 10%) but excess relative risk was smaller, 1.91-fold (95% CI, 1.56- to 2.28-fold). Fixation indices were 0.25 for delayed graft function (95% CI, 0.24 to 0.27), 0.07 for 1-year graft failure (95% CI, 0.04 to 0.09), and 0.07 for 3-year graft failure (95% CI, 0.04 to 0.10). Results were similar in strata of kidneys with a similar Kidney Donor Profile Index.ConclusionsOverall results indicated that the donor constitution has small or moderate effect on post-transplant clinical outcomes.

scholarly journals Protection against Doxorubicin-Induced Cardiac Dysfunction Is Not Maintained Following Prolonged Autophagy Inhibition

2020 ◽  
Vol 21 (21) ◽  
pp. 8105
Author(s):  
Ryan N. Montalvo ◽  
Vivian Doerr ◽  
Oh Sung Kwon ◽  
Erin E. Talbert ◽  
Jeung-Ki Yoo ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Redox Balance ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Sprague Dawley ◽  
Autophagosome Formation ◽  
Underlying Mechanisms ◽  
Autophagy Inhibition

Doxorubicin (DOX) is a highly effective chemotherapeutic agent used in the treatment of various cancer types. Nevertheless, it is well known that DOX promotes the development of severe cardiovascular complications. Therefore, investigation into the underlying mechanisms that drive DOX-induced cardiotoxicity is necessary to develop therapeutic countermeasures. In this regard, autophagy is a complex catabolic process that is increased in the heart following DOX exposure. However, conflicting evidence exists regarding the role of autophagy dysregulation in the etiology of DOX-induced cardiac dysfunction. This study aimed to clarify the contribution of autophagy to DOX-induced cardiotoxicity by specifically inhibiting autophagosome formation using a dominant negative autophagy gene 5 (ATG5) adeno-associated virus construct (rAAV-dnATG5). Acute (2-day) and delayed (9-day) effects of DOX (20 mg/kg intraperitoneal injection (i.p.)) on the hearts of female Sprague–Dawley rats were assessed. Our data confirm established detrimental effects of DOX on left ventricular function, redox balance and mitochondrial function. Interestingly, targeted inhibition of autophagy in the heart via rAAV-dnATG5 in DOX-treated rats ameliorated the increase in mitochondrial reactive oxygen species emission and the attenuation of cardiac and mitochondrial function, but only at the acute timepoint. Deviation in the effects of autophagy inhibition at the 2- and 9-day timepoints appeared related to differences in ATG5–ATG12 conjugation, as this marker of autophagosome formation was significantly elevated 2 days following DOX exposure but returned to baseline at day 9. DOX exposure may transiently upregulate autophagy signaling in the rat heart; thus, long-term inhibition of autophagy may result in pathological consequences.

scholarly journals Influence of Insertion Torque on Clinical and Biological Outcomes before and after Loading of Mandibular Implant-Retained Overdentures in Atrophic Edentulous Mandibles

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Fernanda Faot ◽  
Amália Machado Bielemann ◽  
Alessandra Julie Schuster ◽  
Raissa Micaella Marcello-Machado ◽  
Altair Antoninha Del Bel Cury ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Dental Implants ◽  
Survival Rates ◽  
Rank Correlation ◽  
Primary Stability ◽  
Insertion Torque ◽  
Success Rates ◽  
Implant Stability ◽  
Before And After ◽  
Edentulous Patients

Aim. To evaluate the influence of primary insertion torque (IT) values of narrow dental implants on the peri-implant health, implant stability, immunoinflammatory responses, bone loss, and success and survival rates. Methods. Thirty-one edentulous patients received two narrow implants (2.9x10mm, Facility NeoPoros) to retain mandibular overdentures. The implants were categorized in four groups according to their IT: (G1) IT > 10 Ncm; (G2) IT ≥ 10Ncm and ≤ 30 Ncm; (G3) IT >30Ncm and < 45Ncm; (G4) IT ≥ 45Ncm, and all implants were loaded after 3 months of healing. The following clinical outcomes were evaluated 1, 3, 6, and 12 months after implant insertion: (i) peri-implant tissue health (PH), gingival index (GI), plaque index (PI), calculus presence (CP), probing depth (PD), and bleeding on probing (BOP); (ii) implant stability quotient (ISQ) by resonance frequency analysis; and (iii) IL-1β and TNF-α concentration in the peri-implant crevicular fluid. The marginal bone level (MBL) and changes (MBC) were evaluated. The Chi2 test, Kruskal-Wallis test, mixed-effects regression analysis, and the Kendall rank correlation coefficient were used for statistical analysis (α = 5%). Results. G1 presented the highest PD at all evaluated periods. G2 presented higher PI at month 6 and 12. G4 showed increased GI at month 3 and 12 and more CP at month 1 (p=.003). G2 and G4 had higher ISQ values over the study period, while those from G1 and G3 presented lower ISQ values. The IL-1β concentration increased until month 12 and was independent of IT and bone type; G4 had a higher IL-1β concentration in month 3 than the other groups (p=.015). The TNF-α release was negatively correlated with IT, and TNF-α release was highest in G1 at month 12. The MBL immediately after surgery and the MBC at month 12 were similar between the groups, and G4 presented a positive MBC at month 12. The survival and success rates were 75% for G1, 81.3% for G2, 64.3% for G3, and 95% for G4. Conclusion. The IT did not influence the clinical outcomes and the peri-implant immunoinflammatory responses and was weakly correlated with the narrow dental implants primary stability. The observed success rates suggest that the ideal IT for atrophic fully edentulous patients may deviate from the standardized IT of 32 Ncm.

scholarly journals Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

2014 ◽  
Vol 34 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Yao-Peng Hsieh ◽  
Chia-Chu Chang ◽  
Yao-Ko Wen ◽  
Ping-Fang Chiu ◽  
Yu Yang
Keyword(s):  
Peritoneal Dialysis ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Drop Out ◽  
Kaplan Meier ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact ◽  
Technique Failure

ObjectivePeritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes.MethodsOur retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality.ResultsThe peritonitis rate was 0.196 episodes per patient–year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis ( p < 0.001). Kaplan–Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free ( p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD ( p = 0.03).ConclusionsThe peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified.

scholarly journals Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

2015 ◽  
Vol 59 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Jakeline Rheinheimer ◽  
Andrea C. Bauer ◽  
Sandra P. Silveiro ◽  
Aline A. F. Estivalet ◽  
Ana P. Bouças ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Islet Isolation ◽  
Pancreatic Islet Transplantation ◽  
Human Pancreatic Islet ◽  
Pancreatic Islet Isolation
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