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bone metabolism and transplant

Kyla L Naylor, Amit X Garg, S Joseph Kim, Gregory A Knoll
Fractures are associated with morbidity and mortality. Individuals with chronic kidney disease (CKD) experience bone mineral metabolism changes, which increases fracture risk. Researchers have quantified the epidemiology of fractures in adults with CKD using administrative health databases from Ontario, Canada, held at the Institute for Clinical Evaluative Sciences. Results demonstrated that many individuals with non-transplant CKD sustain fractures, with the risk increasing as kidney function declines. However, fracture risk in kidney transplant recipients was lower than previously described, which suggests recipients may not be a high-risk fracture group...
2016: Healthcare Quarterly
Hong Seok Kim, Sina Tavakoli, Leigh Ann Piefer, Huynh Nga Nguyen, Reto Asmis
Diabetes promotes the S-glutathionylation, inactivation and subsequent degradation of mitogen-activated protein kinase phosphatase 1 (MKP-1) in blood monocytes, and hematopoietic MKP-1-deficiency in atherosclerosis-prone mice accelerates atherosclerotic lesion formation, but the underlying mechanisms were not known. Our aim was to determine the mechanisms through which MKP-1 deficiency in monocytes and macrophages promotes atherogenesis. Transplantation of MKP-1-deficient bone marrow into LDL-R(-/-) (MKP-1LeuKO) mice accelerated high-fat diet (HFD)-induced atherosclerotic lesion formation...
September 27, 2016: Scientific Reports
Abdikarim Abdullahi, Peter Chen, Mile Stanojcic, Ali-Reza Sadri, Natalie Coburn, Marc G Jeschke
The hypermetabolic stress response after burn contributes to multi-organ failure, sepsis, morbidity, and mortality. The cytokine interleukin 6 (IL-6) has been hypothesized to mediate not only white adipose tissue (WAT) browning in burns, but also other hypermetabolic conditions. In addition to its inflammatory effects, IL-6 also acts as a metabolic mediator that affects metabolic tissues. Therefore, we sought to uncover the origin of circulating IL-6 post burn injury that regulates WAT browning. WAT and sera samples were collected from both adult burn patients admitted to the Ross Tilley Burn Centre at Sunnybrook Hospital and mice subjected to a burn injury...
September 19, 2016: Shock
Yung Fong Tsai, Hsiu Pin Chen, Fu Chao Liu, Shih Hao Liu, Chun Yu Chen, Chih Wen Cheng, Jr Rung Lin
Post-transplant malignancy is a major cause of late mortality for liver transplant recipients (LTRs). This nationwide population-based cohort study investigated the cancer type, incidence, and risk factors associated with post-transplant malignancies in 2938 Taiwanese LTRs who underwent transplantation between 1998 and 2012. Data from the National Health Insurance Research Database were extracted on the basis of the International Classification of Disease, Ninth Revision, Clinical Modification codes. Among these patients, 284 post-transplant malignancies were diagnosed...
September 10, 2016: Oncotarget
Mikael Rydén
In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes...
July 2016: Adipocyte
Benjamin Bakondi, Sergey Girman, Bin Lu, Shaomei Wang
: : We previously demonstrated that subretinal injection (SRI) of isogenic mesenchymal stem cells (MSCs) reduced the severity of retinal degeneration in Royal College of Surgeons rats in a focal manner. In contrast, intravenous MSC infusion (MSC(IV)) produced panoptic retinal rescue. By combining these treatments, we now show that MSC(IV) supplementation potentiates the MSC(SRI)-mediated rescue of photoreceptors and visual function. Electrophysiological recording from superior colliculi revealed 3...
September 9, 2016: Stem Cells Translational Medicine
Ran Orgad, Bar Nathansohn-Levi, Sivan Kagan, Yair Reisner
The recently described generation of a highly defined population of dendritic cells which express perforin and granzyme A (termed "perf-DCs") and their ability to selectively delete cognate CD8+ T cell has raised the possibility that these cells play a role in the maintenance of peripheral tolerance. Using bone marrow transplantation, we generated mice selectively lacking perforin expressing dendritic cells. These mice progressively gain weight and exhibit features resembling metabolic syndrome as well as an enhanced susceptibility to autoimmunity induction...
August 30, 2016: Seminars in Immunopathology
Janina Frisch, Patrick Orth, Jagadeesh Kumar Venkatesan, Ana Rey-Rico, Gertrud Schmitt, Dieter Kohn, Henning Madry, Magali Cucchiarini
: : Transplantation of genetically modified peripheral blood aspirates that carry chondrogenically competent progenitor cells may offer new, convenient tools to treat articular cartilage lesions compared with the more complex and invasive application of bone marrow concentrates or of bone marrow-derived mesenchymal stem cells. Here, we show that recombinant adeno-associated viral (rAAV) vectors are powerful gene vehicles capable of successfully targeting primary human peripheral blood aspirates in a stable and safe manner, allowing for an efficient and long-term transgene expression in such samples (up to 63 days with use of a lacZ reporter gene and for at least 21 days with application of the pleiotropic, chondrogenic factor transforming growth factor-β [TGF-β])...
August 29, 2016: Stem Cells Translational Medicine
Johannes Fabian, Desirée Opitz, Kristina Althoff, Marco Lodrini, Barbara Hero, Ruth Volland, Anneleen Beckers, Katleen de Preter, Anneleen Decock, Nitin Patil, Mohammed Abba, Annette Kopp-Schneider, Kathy Astrahantseff, Jasmin Wünschel, Sebastian Pfeil, Maria Ercu, Annette Künkele, Jamie Hu, Theresa Thole, Leonille Schweizer, Gunhild Mechtersheimer, Daniel Carter, Belamy B Cheung, Odilia Popanda, Andreas V Deimling, Jan Koster, Rogier Versteeg, Manfred Schwab, Glenn M Marshall, Frank Speleman, Ulrike Erb, Margot Zoeller, Heike Allgayer, Thorsten Simon, Matthias Fischer, Andreas E Kulozik, Angelika Eggert, Olaf Witt, Johannes H Schulte, Hedwig E Deubzer
The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor...
August 27, 2016: Oncotarget
Salvatore Fabbiano, Nicolas Suárez-Zamorano, Dorothée Rigo, Christelle Veyrat-Durebex, Ana Stevanovic Dokic, Didier J Colin, Mirko Trajkovski
Caloric restriction (CR) extends lifespan from yeast to mammals, delays onset of age-associated diseases, and improves metabolic health. We show that CR stimulates development of functional beige fat within the subcutaneous and visceral adipose tissue, contributing to decreased white fat and adipocyte size in lean C57BL/6 and BALB/c mice kept at room temperature or at thermoneutrality and in obese leptin-deficient mice. These metabolic changes are mediated by increased eosinophil infiltration, type 2 cytokine signaling, and M2 macrophage polarization in fat of CR animals...
September 13, 2016: Cell Metabolism
Yasuyoshi Ishiwata, Masashi Nagata, Takafumi Arai, Misato Makiishi, Maho Yoshikawa, Hiromitsu Takahashi, Hitoshi Kohsaka, Masato Yasuhara
BACKGROUND: Although azole antifungal agents have been shown to affect the pharmacokinetics of calcineurin inhibitors such as tacrolimus and cyclosporine by inhibiting drug metabolism, there are few clinical reports on drug interactions between miconazole oral gel and calcineurin inhibitors. In the present study, the effects of miconazole oral gel on the blood concentrations of tacrolimus and cyclosporine were investigated. METHODS: In this retrospective study, 18 patients concomitantly administered miconazole oral gel and tacrolimus (9 for dermatomyositis, 3 for myasthenia gravis, 2 for systemic lupus erythematosus, 2 for rheumatoid arthritis, 1 for polymyositis, 1 for prevention of graft-versus-host disease post bone marrow transplantation), and 15 patients concomitantly administered miconazole oral gel and cyclosporine (11 for interstitial pneumonia, 2 for pemphigus, 1 for eosinophilic granulomatosis with polyangiitis, 1 for systemic lupus erythematosus) were evaluated...
August 23, 2016: Therapeutic Drug Monitoring
Zhenhua Dai, Golay D Nie
Previous studies have demonstrated that patients develop de novo cardiovascular risk factors following hematopoietic stem cell transplantation (HSCT)(1). The risk of developing metabolic syndrome in HSCT survivors was increased when compared to normal subjects (2, 3). HSCT survivors were also more likely to develop hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and abdominal obesity than non-HSCT patients or healthy controls (4). This article is protected by copyright. All rights reserved...
August 24, 2016: American Journal of Transplantation
Z DeFilipp, R F Duarte, J A Snowden, N S Majhail, D M Greenfield, J L Miranda, M Arat, K S Baker, L J Burns, C N Duncan, M Gilleece, G A Hale, M Hamadani, B K Hamilton, W J Hogan, J W Hsu, Y Inamoto, R T Kamble, M T Lupo-Stanghellini, A K Malone, P McCarthy, M Mohty, M Norkin, P Paplham, M Ramanathan, J M Richart, N Salooja, H C Schouten, H Schoemans, A Seber, A Steinberg, B M Wirk, W A Wood, M Battiwalla, M E D Flowers, B N Savani, B E Shaw
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality...
August 22, 2016: Bone Marrow Transplantation
Eike Müller, Weijia Wang, Wenlian Qiao, Martin Bornhäuser, Peter W Zandstra, Carsten Werner, Tilo Pompe
Homeostasis of hematopoietic stem cells (HSC) in the mammalian bone marrow stem cell niche is regulated by signals of the local microenvironment. Besides juxtacrine, endocrine and metabolic cues, paracrine and autocrine signals are involved in controlling quiescence, proliferation and differentiation of HSC with strong implications on expansion and differentiation ex vivo as well as in vivo transplantation. Towards this aim, a cell culture analysis on a polymer microcavity carrier platform was combined with a partial least square analysis of a mechanistic model of cell proliferation...
2016: Scientific Reports
Zhimin Chen, Abdul Rashid Qureshi, Jonaz Ripsweden, Lars Wennberg, Olof Heimburger, Bengt Lindholm, Peter Barany, Mathias Haarhaus, Torkel B Brismar, Peter Stenvinkel
OBJECTIVE: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major complication of end-stage renal disease (ESRD). Reduced bone mineral density (BMD) is associated with vascular calcification. Here we investigated associations between vertebral bone density (VBD) and coronary artery calcification (CAC), quantified by cardiac computed tomography (CT), and BMD quantified by dual-energy X-ray absorptiometry (DXA), and their relations with mortality. METHODS: In 231 ESRD patients (median age 56years, 63% males) comprising incident dialysis patients, prevalent peritoneal dialysis patients and recipients of living donor kidney transplant, VBD (Hounsfield units, HUs) and CAC scores (Agatston units, AUs) were quantified by cardiac CT, and, in 143 of the patients, BMD was measured by DXA of total body...
November 2016: Bone
Pooja Khandelwal, Tsuyoshi Fukuda, Kana Mizuno, Ashley Teusink-Cross, Parinda A Mehta, Rebecca A Marsh, Angela D M Kashuba, Alexander A Vinks, Stella M Davies
Maraviroc is an allosteric small molecule antagonist of chemokine receptor type 5 (CCR5) and has been used in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients to prevent acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract and liver. The goal of this study was to establish feasibility and pharmacokinetic and pharmacodynamic profiles of maraviroc in pediatric HSCT recipients. Children ages 2 to 12 years were enrolled and maraviroc was added to standard GVHD prophylaxis, which included a calcineurin inhibitor and either steroids or mycophenolate mofetil...
October 2016: Biology of Blood and Marrow Transplantation
E Ważna-Jabłońska, Z Gałązka, M Durlik
INTRODUCTION: Hypercalcemia caused by persistent hyperparathyroidism after successful kidney transplantation (KT) is a common problem and may negatively affect graft function, bone metabolism and the cardiovascular system. Cinacalcet is a novel, available tool to control hypercalcemia after KT. The aim of the study was to examine the efficacy of cinacalcet in lowering calcium in KT recipients with persistent hypercalcemia owing to hyperparathyroidism. METHODS: In this retrospective observational study, we analyzed 30 patients with persistent hypercalcemia >10...
June 2016: Transplantation Proceedings
Halley Wasserman, Chijioke Ikomi, Einar T Hafberg, Alexander G Miethke, Kevin E Bove, Philippe F Backeljauw
Cholestatic liver disease has long been associated with childhood rickets, secondary to impaired absorption of fat-soluble vitamin D. Elevated serum levels of fibroblast growth factor 23 (FGF23), secondary to genetic defects or tumor-induced osteomalacia, causes hypophosphatemic rickets in childhood. We present 2 infants with end-stage liver disease due to biliary atresia (BA) who developed hypophosphatemia with renal phosphate wasting. Serum FGF23 levels were elevated more than 8 times the upper limit of normal, and the older infant showed radiographic evidence of rickets...
August 2016: Pediatrics
Cornelis J H Pronk, Dominik Turkiewicz, Kristina Vult von Steyern, Mats Ehinger, Josefina Dykes, Jacek Toporski
In osteopetrosis, osteoclast dysfunction can lead to deafness, blindness, bone marrow failure and death. Hematopoietic cell transplantation (HCT) is currently the only curative treatment, but outcome remains disappointing. Although a rapid progression towards HCT is detrimental to prevent further progress of disease manifestations, 70 percent of cases lack an HLA-matched sibling and require alternative stem cell sources. We present two cases of osteopetrosis that successfully received an HCT with haploidentical TcRαβ-depleted cells from one of the parents...
July 22, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Adele Soltani, Hassan Argani, Hooman Rahimipour, Fateme Soleimani, Foroug Rahimi, Faranak Kazerouni
OBJECTIVES: The mortality rate of chronic kidney disease (CKD) patients that have undergone renal replacement therapy is very high due to cardiovascular diseases (CVD). Some studies have indicated that cyclosporine A, a drug used to prevent transplant rejection, is associated with bone loss following transplantation. Furthermore, it has an oxidative effect on circulating lipids. Its prooxidant effect on cell membranes causes calcium release. This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and some variables in the prediction of CVD risk in Renal Transplantation (RT) patients that were compared with the control group...
June 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
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