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Thiopurine

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https://www.readbyqxmd.com/read/29035443/genetic-variants-of-pre-micrornas-a-499g-rs3746444-and-t-196a2c-rs11614913-with-ulcerative-colitis-uc-and-investigated-with-thiopurine-s-methyltransferase-tpmt-activity
#1
Farideh Ghobadi, Asad Vaisi-Raygani, Fariborz Bahrehmand, Maryam Tanhapour, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed
BACKGROUND: Abnormal expression and different splicing of miRNAs are involved in several human inflammatory disorders. It has been suggested that gene variants of miRNAs may be associated with increased risk of ulcerative colitis (UC). We aimed to evaluate the association of two SNPs (miRNA-A-499G(rs3746444) and miRNA-T196a2C(rs11614913)) with the risk of UC and monitor their effect on thiopurine-S-methyltransferase (TPMT) activity in Kurdish population of Iran. METHODS: This case-control study was performed on 210 UC patients and 212 healthy individuals...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29023888/editorial-do-thiopurines-and-biologics-decrease-the-risk-of-colectomy-authors-reply
#2
EDITORIAL
C Eriksson, Y Cao, S Rundquist, Y Zhulina, I Henriksson, S Montgomery, J Halfvarson
No abstract text is available yet for this article.
November 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29023884/editorial-do-thiopurines-and-biologics-decrease-the-risk-of-colectomy
#3
EDITORIAL
K H Allin, T Jess
No abstract text is available yet for this article.
November 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29019856/cost-utility-analysis-thiopurines-plus-endoscopy-guided-biological-step-up-therapy-is-the-optimal-management-of-postoperative-crohn-s-disease
#4
Roberto Candia, David Naimark, Beate Sander, Geoffrey C Nguyen
BACKGROUND: Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence. METHODS: A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection...
October 9, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28986660/risk-factors-for-rescue-therapy-in-crohn-s-patients-maintained-on-infliximab-after-withdrawal-of-the-immunomodulator-a-long-term-follow-up
#5
Monika Fischer, Sarah C Campbell, Cynthia S J Calley, Debra J Helper, Michael V Chiorean, Hala M Fadda
BACKGROUND: Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn's disease (CD) patients and the optimal length of dual therapy are still debated. AIMS: To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. METHODS: Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009...
October 6, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28981590/a-systematic-review-and-meta-analysis-of-6-thioguanine-nucleotide-levels-and-clinical-remission-in-inflammatory-bowel-disease
#6
Maria Manuela Estevinho, Joana Afonso, Isadora Rosa, Paula Lago, Eunice Trindade, Luís Correia, Cláudia Camila Dias, Fernando Magro
Background and Aims: Thiopurines are widely used in the management of inflammatory bowel diseases. However, their minimum effective dose and dose-response relationship remain undefined, and evidence about their use in clinical practice is mostly heterogeneous. This systematic review and meta-analysis aimed: i] to assess the clinical value of 6-thioguanine nucleotide thresholds; and ii] to compare mean 6-thioguanine nucleotide concentrations between patients in clinical remission vs. those with active disease...
June 30, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28976243/colonic-thioguanine-pro-drug-investigation-of-microbiome-and-novel-host-metabolism
#7
Timothy Florin, Ramya Movva, Jakob Begun, John Duley, Iulia Oancea, Páraic Ó Cuív
Thiopurines are analogues of endogenous purines. They are pro-drugs which require the purine salvage pathway to convert them to the active drug nucleotides (TGN). These drugs are used to maintain clinical remission in patients with inflammatory bowel diseases. In our recent Gut paper, we showed that thioguanine worked quickly to improve colitis in the absence in the host animal of the key guanine salvage enzyme, hypoxanthine-guanine-phosphoribosyltransferase (HPRT). Current evidence favours the proposition that active drug delivery to the host lacking HPRT requires translocation of TGN-loaded bacteria across the inflamed mucosal barrier, and most likely delivery by phagocytosis...
October 4, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28974897/temporal-trends-in-the-misdiagnosis-rates-between-crohn-s-disease-and-intestinal-tuberculosis
#8
Hyungil Seo, Seohyun Lee, Hoonsub So, Donghoi Kim, Seon-Ok Kim, Jae Seung Soh, Jung Ho Bae, Sun-Ho Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Kyung-Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Byong Duk Ye
AIM: To investigate the temporal trends in the misdiagnosis rate between Crohn's disease (CD) and intestinal tuberculosis (ITB) in South Korea. METHODS: We retrospectively reviewed the medical records of patients managed for CD or ITB at Asan Medical Center, a tertiary referral hospital, Seoul, Korea between 1996 and 2014. The temporal trends in the misdiagnosis rates between the two diseases were analyzed. The demographic and clinical characteristics were compared between CD patients who were initially misdiagnosed as ITB (final CD group) and vice versa (final ITB group)...
September 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28966507/thiopurine-s-methyltransferase-polymorphisms-in-korean-dermatologic-patients
#9
Minseok Lee, Jimyung Seo, Dongsik Bang, Do Young Kim
BACKGROUND: Thiopurine S-methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurines including azathioprine (AZA), 6-mercaptopurine, and 6-thioguanine. TPMT genotyping is widely used for screening of AZA-related toxicity during routine clinical practice in Korea. However, the data of TPMT genotypes and its AZA-related toxicity have not been studied in the field of dermatology. OBJECTIVE: The aim of this study was to evaluate the genetic basis of TPMT polymorphism in Korean dermatologic patients and subsequently to investigate the relationship between mutant TPMT and adverse responses to AZA treatment...
October 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28963908/emerging-role-of-nudt15-polymorphisms-in-6-mercaptopurine-metabolism-and-dose-related-toxicity-in-acute-lymphoblastic-leukaemia
#10
REVIEW
Minu Singh, Prateek Bhatia, Sanjeev Khera, Amita Trehan
Despite more than 80% long term survival in ALL, morbidity due to drug related myelotoxicity remains high. Germline variants of thiopurine metabolizing enzymes (TPMT and ITPA) have been described which are associated with increased drug toxicity during maintenance phase, but their prevalence in different ethnic groups is variable to account for relatively high myelotoxicity incidence. NUDT15 variant (rs116855232) has been recently identified as a novel polymorphism related with thiopurine-induced leucopenia in inflammatory bowel disease and ALL...
September 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28961920/benzimidazoles-promote-anti-tnf-mediated-induction-of-regulatory-macrophages-and-enhance-therapeutic-efficacy-in-a-murine-model
#11
Manon E Wildenberg, Alon D Levin, Alessandro Ceroni, Zhen Guo, Pim J Koelink, Theodorus B M Hakvoort, Liset Westera, Felicia M Bloemendaal, Johannan F Brandse, Alison Simmons, Geert R D'Haens, Daniel Ebner, Gijs R van den Brink
Background and aims: Regulatory macrophages play a critical role in tissue repair and we have previously shown that anti-TNF antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the combination of anti-TNF and thiopurines, consistent with the enhanced efficacy of this combination therapy described in clinical trials. As thiopurines are unfortunately associated with significant side effects, we here aimed to identify alternatives for combination therapy with anti-TNF, using the macrophage induction model as a screening tool...
August 16, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28961694/a-severe-neonatal-lymphopenia-associated-with-administration-of-azathioprine-to-the-mother-in-a-context-of-crohn-s-disease
#12
C Thomas, C Monteil-Ganiere, S Mirallié, C Hémont, C Dert, A Léger, C Joyau, D Caldari, M Audrain
Azathioprine is commonly used in Crohn's Diseases. It has been administered to many pregnant women over many years without significant side effects. However, pancytopenia and Severe Combined Immune Deficiency-like disease have been reported in infants whose mothers received azathioprine throughout pregnancy. Moreover, myelotoxicity has been described in patients treated with azathioprine and having a low or absent thiopurine S-methyl transferase (TPMT) activity.Here, we describe the case of a new-born girl found highly lymphopenic (<300 CD3+ T cells) after a positive new-born screening for Severe Combined Immuno Deficiency...
September 2, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28950720/biomarkers-of-adverse-drug-reactions
#13
Daniel F Carr, Munir Pirmohamed
Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28945288/thiopurine-induced-mitotic-catastrophe-in-rad51d-deficient-mammalian-cells
#14
Michael D Wyatt, Nicole M Reilly, Shikha Patel, Preeti Rajesh, Gary P Schools, Phillip G Smiraldo, Douglas L Pittman
Thiopurines are part of a clinical regimen used for the treatment of autoimmune disorders and childhood acute lymphoblastic leukemia. However, despite these successes, there are also unintended consequences such as therapy-induced cancer in long-term survivors. Therefore, a better understanding of cellular responses to thiopurines will lead to improved and personalized treatment strategies. RAD51D is an important component of homologous recombination (HR), and our previous work established that mammalian cells defective for RAD51D are more sensitive to the thiopurine 6-thioguanine (6TG) and have dramatically increased numbers of multinucleated cells and chromosome instability...
September 25, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28914560/thiopurine-metabolite-levels-in-patients-with-atopic-dermatitis-and-or-chronic-hand-foot-eczema-treated-with-azathioprine
#15
F M Garritsen, J van der Schaft, C A F Bruijnzeel-Koomen, R H van Schaik, M de Graaf, M P H van den Broek, M S de Bruin-Weller
BACKGROUND: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. OBJECTIVE: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema...
September 26, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28914446/risk-factors-for-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype
#16
M M T J Broekman, M J H Coenen, G J Wanten, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, D R Wong, D J de Jong
BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial...
September 15, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28903549/nudt15-variants-cause-hematopoietic-toxicity-with-low-6-tgn-levels-in-children-with-acute-lymphoblastic-leukemia
#17
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Purpose: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). Materials and Methods: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant)...
September 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28903094/effectiveness-of-mesalazine-thiopurines-and-tumour-necrosis-factor-antagonists-in-preventing-post-operative-crohn-s-disease-recurrence-in-a-real-life-setting
#18
Mariangela Allocca, Rosario Landi, Stefanos Bonovas, Gionata Fiorino, Alfredo Papa, Antonino Spinelli, Federica Furfaro, Laurent Peyrin-Biroulet, Alessandro Armuzzi, Silvio Danese
BACKGROUND: Most Crohn's disease (CD) patients develop endoscopic recurrence within one year of intestinal resection. The best treatment method to prevent post-operative CD recurrence remains uncertain. METHODS: A total of 155 CD patients from 2 referral centres, who were undergoing intestinal resection with ileo-colonic anastomosis (January 2004-January 2015), were included. All subjects received preventive therapy with tumour necrosis factor antagonists (anti-TNFs), thiopurinesor mesalazine...
September 14, 2017: Digestion
https://www.readbyqxmd.com/read/28901267/therapeutic-drug-monitoring-in-pediatric-ibd-current-application-and-future-perspectives
#19
Sara Lega, Matteo Bramuzzo, Marla Dubinsky
As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28884254/elderly-onset-and-adult-onset-ulcerative-colitis-are-more-similar-than-previously-reported-in-a-nationwide-cohort
#20
Vinayak Kumar, Yash Shah, Dhruvan Patel, Nabeel Khan
BACKGROUND: Elderly-onset ulcerative colitis (EO-UC) is recognized as a distinct subpopulation of UC. To our knowledge, there have been no nationwide studies of EO-UC populations in the USA. AIMS: We aim to characterize differences in presentation at diagnosis and clinical course between EO-UC and adult-onset UC (AO-UC) patients in a national cohort. METHODS: Complete medical records of patients newly diagnosed with UC from October 2001 to October 2011 in the Veterans Affairs health system were obtained...
October 2017: Digestive Diseases and Sciences
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