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Masayoshi Okumi, Yasuyuki Sato, Kohei Unagami, Toshihito Hirai, Hideki Ishida, Kazunari Tanabe
BACKGROUND: The reasons for improved outcomes associated with preemptive kidney transplantation (PKT) are incompletely understood, and post-transplant complications have been scarcely investigated. METHODS: We evaluated the outcomes of PKT in both unmatched (n = 1060) and propensity score matched cohorts (n = 186) of adults who underwent living kidney transplant between 2000 and 2014. Outcomes were estimated glomerular filtration rate (eGFR), biopsy-proven rejection, cytomegalovirus (CMV) infection, post-transplant diabetes mellitus (PTDM), cardiovascular disease (CVD), graft failure (non-censored for death), and malignancy...
October 19, 2016: Clinical and Experimental Nephrology
Hiroki Adachi, Kanae Nakayama, Norifumi Hayashi, Yuki Matsui, Keiji Fujimoto, Hideki Yamaya, Hisao Tonami, Hitoshi Yokoyama
BACKGROUND: A few studies have investigated the role of adiponectin fraction for cardiovascular disease (CVD) in RTx recipients. SUBJECTS AND METHODS: We studied 57 adult subjects (39 males, 18 females; 10 cadaveric donors) with at least three years of allograft survival (median 251 months). We examined clinical backgrounds such as treated drugs, blood pressure (BP, mmHg), body mass index (BMI), and blood chemistry including cholesterol (total, LDL-C, HDL-C), glucose, glycated hemoglobin (HbA1c), and serum high and low-molecular-weight (HMW/LMW) ADPN fractions with regard to the associations of the visceral and subcutaneous fat areas on CT scan...
2016: PloS One
Maria P Martinez Cantarin, Scott W Keith, Zhao Lin, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo Ramirez, Costas D Lallas, Ashesh Shah, Scott A Waldman, Bonita Falkner
BACKGROUND/OBJECTIVE: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. METHODS: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis...
August 2016: Cardiorenal Medicine
Isabell Jahn, Martin Busch, Undine Ott, Gunter Wolf, Wilgard Battefeld
BACKGROUND: Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion. METHODS: 55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study...
September 2016: Deutsche Medizinische Wochenschrift
E Ilker Ozay, Gabriela Gonzalez-Perez, Joe A Torres, Jyothi Vijayaraghavan, Rebecca Lawlor, Heather L Sherman, Daniel T Garrigan, Amy S Burnside, Barbara A Osborne, Gregory N Tew, Lisa M Minter
Targeting cellular proteins with antibodies, to better understand cellular signaling pathways in the context of disease modulation, is a fast-growing area of investigation. Humanized antibodies are increasingly gaining attention for their therapeutic potential, but the collection of cellular targets is limited to those secreted from cells or expressed on the cell surface. This approach leaves a wealth of intracellular proteins unexplored as putative targets for antibody binding. Protein kinase Cθ (PKCθ) is essential to T cell activation, proliferation, and differentiation, and its phosphorylation at specific residues is required for its activity...
October 18, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Eugene Han, Myoung Soo Kim, Yu Seun Kim, Eun Seok Kang
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor)...
October 2016: Metabolism: Clinical and Experimental
Leah M Caffrey, Brittany M deRonde, Lisa M Minter, Gregory N Tew
A fundamental understanding of how polymer structure impacts internalization and delivery of biologically relevant cargoes, particularly small interfering ribonucleic acid (siRNA), is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit, and another based on a diester scaffold that contains two guanidinium moieties per repeat unit...
October 10, 2016: Biomacromolecules
Jin Sug Kim, Seul Ki Kim, Ji Yoon Park, Yang Gyun Kim, Joo Young Moon, Sang Ho Lee, Chun Gyoo Ihm, Tae Won Lee, Su Kang Kim, Joo-Ho Chung, Sun Woo Kang, Tae Hee Kim, Yeong Hoon Kim, Kyung Hwan Jeong
BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population...
2016: Nephron
Mohammad Ehsanul Karim, Paul Gustafson, John Petkau, Helen Tremlett
In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time...
August 15, 2016: American Journal of Epidemiology
Roger D Plaut, Karen M Scanlon, Michael Taylor, Ken Teter, Nicholas H Carbonetti
The active subunit (S1) of pertussis toxin (PT), a major virulence factor of Bordetella pertussis, ADP-ribosylates Gi proteins in the mammalian cell cytosol to inhibit GPCR signaling. The intracellular pathway of PT includes endocytosis and retrograde transport to the trans-Golgi network (TGN) and endoplasmic reticulum (ER). Subsequent translocation of S1 to the cytosol is presumably preceded by dissociation from the holotoxin. In vitro, such dissociation is stimulated by interaction of PT with ATP. To investigate the role of this interaction in cellular events, we engineered a form of PT (PTDM) with changes to two amino acids involved in the interaction with ATP...
August 2016: Pathogens and Disease
Ivar Anders Eide, Thea Anine Strøm Halden, Anders Hartmann, Dag Olav Dahle, Anders Åsberg, Trond Jenssen
BACKGROUND: Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss. METHODS: In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis...
June 29, 2016: Transplantation
Thomas Dienemann, Naohiko Fujii, Yimei Li, Shivali Govani, Nikitha Kosaraju, Roy D Bloom, Harold I Feldman
A decade ago, observations suggested that post-transplant diabetes mellitus (PTDM) was linked to allograft loss and shorter patient survival. Increasing awareness, improvements in care, and changes in the immunosuppressive regimen may have modified this association. Single-center analysis of 1990 (age>18; transplantation date 1996-2012) primary kidney recipients (KTR). Patients with <12 months follow-up were excluded. Diabetes was diagnosed according to ADA criteria and characterized as follows: No diabetes, PTDM in the first post-transplant year not treated with glucose-lowering medications (GLM) at 12 months, PTDM in the first post-transplant year treated with GLM at 12 months, and pretransplant diabetes...
September 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
H S Jeong, J Lee, B J Lim, H J Kwon, Y S Kim, B S Kim, K H Huh, S I Kim, M S Kim, H J Jeong
BACKGROUND: The prevalence of post-transplantation immunoglobulin A nephropathy (PTIgAN) and diabetes mellitus (PTDM) increases with time after transplantation, and recognition and management of these conditions is becoming more important in renal allograft recipients as graft survival increases. METHODS: We explored the influence of concurrent PTDM on renal allograft histology and function in 111 cases with PTIgAN diagnosed from 2000 to 2010 at our institution...
April 2016: Transplantation Proceedings
Michael Lis, Franziska Dorner, Gregory N Tew, Karen Lienkamp
Many biophysical studies of protein transduction domains (PTDs) and their synthetic mimics (PTDMs) focus on the interaction between the polycationic PTD(M) and anionic phospholipid surfaces. Most, but not all, of these studies suggest that these cation-anion interactions are vital for membrane activity. In this study, the effect of anionic lipid content on PTDM performance was examined for three ring-opening metathesis (ROMP)-based PTDMs with varying hydrophobicity. Using a series of dye-loaded vesicles with gradually increasing anionic lipid content, we saw that increased anionic lipid content inhibited dye release caused by these PTDMs...
June 14, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
Brittany M deRonde, Nicholas D Posey, Ronja Otter, Leah M Caffrey, Lisa M Minter, Gregory N Tew
Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siRNA internalization...
June 13, 2016: Biomacromolecules
W James Chon, Amishi Desai, Coady Wing, Divya Arwindekar, Ignatius Y S Tang, Michelle A Josephson, Sanjeev Akkina
BACKGROUND: Rapid steroid withdrawal (RSW) is used increasingly in kidney transplantation but long-term outcomes in African-American (AA) recipients are not well known. We compared 1 and 5 year transplant outcomes in a large cohort of AA patients who were maintained on continued steroid therapy (CST) to those who underwent RSW. METHODS: Post-transplant courses of A as receiving kidney allografts from 2003-2011 at two urban transplant centers in Chicago were followed...
2016: International Journal of Clinical Medicine
Javeria Peracha, Jay Nath, Andrew Ready, Sanna Tahir, Krishan Parekh, James Hodson, Charles J Ferro, Richard Borrows, Adnan Sharif
South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians. Case-control matching was therefore undertaken to remove this bias, resulting in 102 recipient pairs. Median follow-up was 50 months (range 4-127 months)...
June 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
S Fuji, A Rovó, K Ohashi, M Griffith, H Einsele, M Kapp, M Mohty, N S Majhail, B G Engelhardt, A Tichelli, B N Savani
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT...
August 2016: Bone Marrow Transplantation
Imran Ali Khan, Kiran Kumar Vattam, Parveen Jahan, Qurratulain Hasan, Pragna Rao
Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) are non-synonymous forms of diabetes. Glucokinase (GCK) plays a key role in glucose metabolism. The relationship between the GCK promoter and specific types of diabetes, such as PTDM and T2DM, in the Asian Indian population is unknown. We examined the occurrence of a specific GCK promoter variant (-258G/A) in patients with T2DM and PTDM. The case-control study enrolled 640 Asian Indian subjects, including controls (n = 250) and T2DM (n = 250), PTDM (n = 42), and non-post-transplant diabetes mellitus (non-PTDM) (n = 98) patients...
February 2016: Intractable & Rare Diseases Research
Thea A S Halden, Erlend J Egeland, Anders Åsberg, Anders Hartmann, Karsten Midtvedt, Hassan Z Khiabani, Jens J Holst, Filip K Knop, Mads Hornum, Bo Feldt-Rasmussen, Trond Jenssen
OBJECTIVE: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODS: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0...
April 2016: Diabetes Care
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