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https://www.readbyqxmd.com/read/28429555/management-of-mineral-and-bone-disorders-in-renal-transplant-recipients
#1
Matthew J Damasiewicz, Peter R Ebeling
The management of post-transplantation bone disease is a complex problem that remains under-appreciated in clinical practice. In these patients, pre-existing metabolic bone disorder is further impacted by the use of immunosuppressive medications (glucocorticoids and calcineurin-inhibitors), variable post-transplantation renal allograft function and post-transplantation diabetes mellitus. The treatment of post-transplantation bone loss should begin pre-transplantation. All patients active on transplant waiting lists should be screened for bone disease...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28418012/cyp3a4-is-a-crosslink-between-vitamin-d-and-calcineurin-inhibitors-in-solid-organ-transplant-recipients-implications-for-bone-health
#2
REVIEW
A Prytuła, K Cransberg, A Raes
The use of calcineurin inhibitors (CNIs) and vitamin D deficiency may contribute to the pathogenesis of post-transplant bone disease. CNIs and 1,25-dihydroxyvitamin D₃ (1,25(OH)2D3) are substrates of the drug-metabolizing enzyme CYP3A4. This review summarizes the indications for the use of activated vitamin D analogs in post-transplant care and the current knowledge on the impact of CNIs on bone. We searched for clinical evidence of the interaction between CNIs and 1,25(OH)2D3. We also provide an overview of the literature on the interplay between vitamin D metabolism and CYP3A4 in experimental and clinical settings and discuss its possible implications for solid organ transplant recipients...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28413871/comparison-of-the-gene-expression-profiles-of-human-hematopoietic-stem-cells-between-humans-and-a-humanized-xenograft-model
#3
Hideyuki Matsuzawa, Hiromichi Matsushita, Takashi Yahata, Masayuki Tanaka, Kiyoshi Ando
The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ(null)(NOG) mice transplanted with human CD34(+)/CD38(-)/Lin(-/low) hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34(+)/CD38(-)/Lin(-/low) cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34(+)/CD38(-)/Lin(-/low) HSCs between CB and BM, and that 17 of them--which were mostly related to cellular survival, RNA metabolism and lymphoid development--were shared with the xenograft model...
April 20, 2017: Tokai Journal of Experimental and Clinical Medicine
https://www.readbyqxmd.com/read/28389253/role-of-genetic-polymorphism-of-aldh2-in-hematopoietic-stem-cell-transplantation
#4
Tomotaka Ugai, Yoshinobu Kanda, Yasuo Morishima, Keitaro Matsuo
Aldehyde dehydrogenase 2 (ALDH2) is involved in critically important biological processes, such as the metabolism of aldehydes and aldehyde-induced genotoxicity in hematopoietic stem cells. Given its role in these biological processes, we hypothesized that a functional ALDH2 polymorphism could affect transplant outcome after hematopoietic stem cell transplantation. Here, we analyzed the Japanese national registry data for 409 patients who underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor...
April 4, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28382618/effects-of-single-agent-bortezomib-as-post-transplant-consolidation-therapy-on-multiple-myeloma-related-bone-disease-a-randomized-phase-ii-study
#5
Orhan Sezer, Meral Beksac, Roman Hajek, Gülsan Sucak, Seckin Cagirgan, Werner Linkesch, Olga Meltem Akay, Zafer Gülbas, Hareth Nahi, Torben Plesner, John A Snowden, Ayşen Timurağaoğlu, Tobias Dechow, Alois Lang, Tülin Tuğlular, Johannes Drach, Gabriele Armbrecht, Anna Potamianou, Catherine Couturier, Robert A Olie, Caroline Feys, Nathalie Allietta, Evangelos Terpos
This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m(2) intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation)...
April 6, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28368259/role-of-18-f-fdg-pet-ct-in-the-diagnosis-and-management-of-multiple-myeloma-and-other-plasma-cell-disorders-a-consensus-statement-by-the-international-myeloma-working-group
#6
REVIEW
Michele Cavo, Evangelos Terpos, Cristina Nanni, Philippe Moreau, Suzanne Lentzsch, Sonja Zweegman, Jens Hillengass, Monika Engelhardt, Saad Z Usmani, David H Vesole, Jesus San-Miguel, Shaji K Kumar, Paul G Richardson, Joseph R Mikhael, Fernando Leal da Costa, Meletios-Athanassios Dimopoulos, Chiara Zingaretti, Niels Abildgaard, Hartmut Goldschmidt, Robert Z Orlowski, Wee Joo Chng, Hermann Einsele, Sagar Lonial, Bart Barlogie, Kenneth C Anderson, S Vincent Rajkumar, Brian G M Durie, Elena Zamagni
The International Myeloma Working Group consensus aimed to provide recommendations for the optimal use of (18)fluorodeoxyglucose ((18)F-FDG) PET/CT in patients with multiple myeloma and other plasma cell disorders, including smouldering multiple myeloma and solitary plasmacytoma. (18)F-FDG PET/CT can be considered a valuable tool for the work-up of patients with both newly diagnosed and relapsed or refractory multiple myeloma because it assesses bone damage with relatively high sensitivity and specificity, and detects extramedullary sites of proliferating clonal plasma cells while providing important prognostic information...
April 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28355970/clinical-impact-and-management-of-fluconazole-discontinuation-on-sirolimus-levels-in-bone-marrow-transplant-patients
#7
Edith Nwaroh, Jennifer Jupp, Esther Jadusingh, Gregory Guilcher
Sirolimus, an immunosuppressant, is indicated post-allogeneic stem cell transplant to reduce the risk of graft-versus-host-disease. Sirolimus is metabolized by cytochrome P450 3A4 and is a substrate of the P-glycoprotein (P-gp) drug efflux pump. Interactions with known inhibitors of the CYP3A4 enzyme and P-glycoprotein, such as fluconazole, are anticipated. Co-administration of fluconazole leads to an increase in sirolimus blood concentrations due to an inhibition of metabolism. The discontinuation of fluconazole will likely result in a decline in sirolimus blood concentrations, leaving patients at risk of graft-versus-host-disease...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28337956/acute-renal-graft-versus-host-disease-in-a-murine-model-of-allogeneic-bone-marrow-transplantation
#8
Peter M Schmid, Abdellatif Bouazzaoui, Karin Schmid, Christoph Birner, Christian Schach, Lars S Maier, Ernst Holler, Dierk H Endemann
Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols...
March 23, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28320485/mesenchymal-stem-cells-increase-expression-of-heme-oxygenase-1-leading-to-anti-inflammatory-activity-in-treatment-of-acute-liver-failure
#9
Zhi-Heng Zhang, Wei Zhu, Hao-Zhen Ren, Xin Zhao, Shuai Wang, Hu-Cheng Ma, Xiao-Lei Shi
BACKGROUND: Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28302033/effects-of-hyperlipidemia-and-cardiovascular-diseases-on-proliferation-differentiation-and-homing-of-mesenchymal-stem-cells
#10
Xin Ye, Chengfei Zhang
Various clinical studies have revealed that cardiovascular diseases (CVD) are associated with bone loss diseases such as osteoporosis and periodontitis, especially in older population. As one of the best-established risk factors of CVD, hyperlipidemia is also reported to interfere with the metabolism, function and regeneration of mineralized tissues. Derived from postnatal tissue reservoirs, mesenchymal stem cells (MSCs) are considered promising cell sources for mesenchymal and non-mesenchymal tissue regeneration based on their capacities for self-renewal and multi-lineage differentiation as well as potent immunosuppressive effects, secretion of cytokines and regulation of vascularization...
March 16, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28281103/current-evidence-on-vitamin-d-deficiency-and-kidney-transplant-what-s-new
#11
REVIEW
Gerardo Sarno, Riccardo Nappi, Barbara Altieri, Giacomo Tirabassi, Emanuele Muscogiuri, Gianmaria Salvio, Stavroula A Paschou, Aristide Ferrara, Enrico Russo, Daniela Vicedomini, Cerbone Vincenzo, Andromachi Vryonidou, Silvia Della Casa, Giancarlo Balercia, Francesco Orio, Paride De Rosa
Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve...
March 9, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28252220/metabolic-oscillations-in-co-cultures-of-hepatocytes-and-mesenchymal-stem-cells-effects-of-seeding-arrangement-and-culture-mixing
#12
Dalia Abdelrahim Alzebdeh, Howard William Matthew
In vitro assembly of functional liver tissue is a prerequisite for the transplantation of tissue-engineered livers. There is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability. Recent reports have demonstrated that bone marrow mesenchymal stem cells (BM-MSCs) can provide a number of cues promoting hepatocyte growth and development...
March 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28246290/co-transplantation-of-mesenchymal-stem-cells-with-neonatal-porcine-islets-improve-graft-function-in-diabetic-mice
#13
Julie A Hayward, Cara E Ellis, Karen Seeberger, Timothy Lee, Bassem Salama, Aillette Mulet-Sierra, Purushothaman Kuppan, Adetola Adesida, Gregory S Korbutt
Mesenchymal stem cells (MSCs) possess immuno-regulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow derived MSCs have on neonatal porcine islets (NPIs) in vitro and determine islet engraftment and metabolic outcomes when co-transplanted in a mouse model. NPIs co-cultured with MSCs had greater cellular insulin content and increased glucose stimulate insulin secretion. NPIs were co-transplanted with or without MSCs in diabetic B6...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28192253/hematopoietic-stem-cell-transplantation-using-preimplantation-genetic-diagnosis-and-human-leukocyte-antigen-typing-for-human-leukocyte-antigen-matched-sibling-donor-a-turkish-multicenter-study
#14
Emin Kurekci, Alphan Küpesiz, Sema Anak, Gülyüz Öztürk, Orhan Gürsel, Serap Aksoylar, Talia Ileri, Barış Kuşkonmaz, İbrahim Eker, Mualla Cetin, Gülsün Tezcan Karasu, Zühre Kaya, Tunç Fışgın, Mehmet Ertem, Savaş Kansoy, Mehmet Akif Yeşilipek
Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008...
February 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28182733/pyruvate-dehydrogenase-kinase-1-is-essential-for-transplantable-mouse-bone-marrow-hematopoietic-stem-cell-and-progenitor-function
#15
Camilla Halvarsson, Pernilla Eliasson, Jan-Ingvar Jönsson
BACKGROUND: Accumulating evidence suggests that hypoxic areas in the bone marrow are crucial for maintenance of hematopoietic stem cells (HSCs) by supporting a quiescent state of cell cycle and regulating the transplantation capacity of long-term (LT)-HSCs. In addition, HSCs seem to express a metabolic profile of energy production away from mitochondrial oxidative phosphorylation in favor of glycolysis. At oxygen deprivation, hypoxia inducible factor 1α (HIF-1α) is known to induce glycolytic enzymes as well as suppressing mitochondrial energy production by inducing pyruvate dehydrogenase kinase 1 (Pdk1) in most cell types...
2017: PloS One
https://www.readbyqxmd.com/read/28176272/effects-of-combined-raav-mediated-tgf-%C3%AE-and-sox9-gene-transfer-and-overexpression-on-the-metabolic-and-chondrogenic-activities-in-human-bone-marrow-aspirates
#16
Ke Tao, Ana Rey-Rico, Janina Frisch, Jagadeesh Kumar Venkatesan, Gertrud Schmitt, Henning Madry, Jianhao Lin, Magali Cucchiarini
BACKGROUND: Transplantation of genetically modified bone marrow concentrates is an attractive approach to conveniently activate the chondrogenic differentiation processes as a means to improve the intrinsic repair capacities of damaged articular cartilage. METHODS: Human bone marrow aspirates were co-transduced with recombinant adeno-associated virus (rAAV) vectors to overexpress the pleiotropic transformation growth factor beta (TGF-β) and the cartilage-specific transcription factor sox9 as a means to enhance the chondroreparative processes in conditions of specific lineage differentiation...
December 2017: Journal of Experimental Orthopaedics
https://www.readbyqxmd.com/read/28174669/cell-therapy-for-liver-disease-using-bioimaging-rats
#17
REVIEW
Junko Haga, Shin Enosawa, Eiji Kobayashi
Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28170175/genetic-modification-of-human-peripheral-blood-aspirates-using-recombinant-adeno-associated-viral-vectors-for-articular-cartilage-repair-with-a-focus-on-chondrogenic-transforming-growth-factor-%C3%AE-gene-delivery
#18
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])...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28161839/osteoprotegerin-and-uremic-osteoporosis-in-chronic-hemodialysis-patients
#19
Diana Moldovan, Crina Rusu, Alina Potra, Ioan Moldovan, Ioan Mihai Patiu, Mirela Gherman-Caprioara, Ina Maria Kacso
INTRODUCTION: Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the relationship between OPG and bone mineral density (BMD) is important, but remains unclear yet. The study objective was to assess the OPG role related to uremic osteoporosis in HD patients. METHODS: This cross-sectional study has been realized on a cohort of 63 chronic HD patients. INCLUSION CRITERIA: elderly prevalent HD patients with an age over 55 years old...
February 4, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28148490/characterisation-of-osteophytes-as-an-autologous-bone-graft-source-an-experimental-study-in-vivo-and-in-vitro
#20
K Ishihara, K Okazaki, T Akiyama, Y Akasaki, Y Nakashima
OBJECTIVES: Osteophytes are products of active endochondral and intramembranous ossification, and therefore could theoretically provide significant efficacy as bone grafts. In this study, we compared the bone mineralisation effectiveness of osteophytes and cancellous bone, including their effects on secretion of growth factors and anabolic effects on osteoblasts. METHODS: Osteophytes and cancellous bone obtained from human patients were transplanted onto the calvaria of severe combined immunodeficient mice, with Calcein administered intra-peritoneally for fluorescent labelling of bone mineralisation...
February 2017: Bone & Joint Research
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