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Thiopurine

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https://www.readbyqxmd.com/read/28410340/inflammatory-bowel-disease-is-similar-in-patients-with-older-onset-and-younger-onset
#1
Bharati Kochar, Millie D Long, Joseph Galanko, Laura E Raffals, Ashwin Ananthakrishnan, Robert S Sandler
BACKGROUND: As the American population is aging, the number of older people with inflammatory bowel disease is increasing. We used clinical data from the Sinai-Helmsley Alliance for Research Excellence (SHARE), a prospective cohort, to examine disease and treatment differences in older adults. METHODS: We performed a cross-sectional study assessing demographics and disease behavior by age at diagnosis with univariate, bivariate, and multivariate analyses. "Older-onset" patients were diagnosed after age 60, "younger-onset" patients were diagnosed before age 60 but are older than 60 years, and the remainder were "young...
April 13, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28406961/pharmacogenetic-variants-in-tpmt-alter-cellular-responses-to-cisplatin-in-inner-ear-cell-lines
#2
Amit P Bhavsar, Erandika P Gunaretnam, Yuling Li, Jafar S Hasbullah, Bruce C Carleton, Colin J D Ross
Cisplatin is a highly-effective and widely-used chemotherapeutic agent that causes ototoxicity in many patients. Pharmacogenomic studies of key genes controlling drug biotransformation identified variants in thiopurine methyltransferase (TPMT) as predictors of cisplatin-induced ototoxicity, although the mechanistic basis of this interaction has not been reported. Expression constructs of TPMT*3A, *3B and *3C variants were generated and monitored in cultured cells. Cellular TPMT*3A levels were detected at >20-fold lower amounts than the wild type confirming the unstable nature of this variant...
2017: PloS One
https://www.readbyqxmd.com/read/28406092/safety-of-azathioprine-and-6-mercaptopurine-in-patients-with-inflammatory-bowel-disease-na%C3%A3-ve-to-thiopurine-treatment%C3%A2
#3
Ram Alaish, David Lundgren, Ole B Suhr, Mårten Werner, Pontus Karling
OBJECTIVES: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naïve to thiopurine treatment. STUDY: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naïve to thiopurines (82 patients treated with AZA and 31 patients with MP)...
April 13, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28404197/mercaptopurine-versus-placebo-to-prevent-recurrence-of-crohn-s-disease-after-surgical-resection-toppic-a-multicentre-double-blind-randomised-controlled-trial
#4
Craig Mowat, Ian Arnott, Aiden Cahill, Malcolm Smith, Tariq Ahmad, Sreedhar Subramanian, Simon Travis, John Morris, John Hamlin, Anjan Dhar, Chuka Nwokolo, Cathryn Edwards, Tom Creed, Stuart Bloom, Mohamed Yousif, Linzi Thomas, Simon Campbell, Stephen J Lewis, Shaji Sebastian, Sandip Sen, Simon Lal, Chris Hawkey, Charles Murray, Fraser Cummings, Jason Goh, James O Lindsay, Naila Arebi, Lindsay Potts, Aileen J McKinley, John M Thomson, John A Todd, Mhairi Collie, Malcolm G Dunlop, Ashley Mowat, Daniel R Gaya, Jack Winter, Graham D Naismith, Holly Ennis, Catriona Keerie, Steff Lewis, Robin J Prescott, Nicholas A Kennedy, Jack Satsangi
BACKGROUND: Up to 60% of patients with Crohn's disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. METHODS: We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohn's disease and had undergone intestinal resection...
December 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28404188/postoperative-thiopurines-in-smokers-with-crohn-s-disease
#5
Jacques Cosnes
No abstract text is available yet for this article.
December 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28394806/immunogenicity-of-pertussis-booster-vaccination-in-children-and-adolescents-with-inflammatory-bowel-disease-a-controlled-study
#6
Aleksandra Banaszkiewicz, Agnieszka Gawronska, Beata Klincewicz, Anna Kofla-Dłubacz, Urszula Grzybowska-Chlebowczyk, Ewa Toporowska-Kowalska, Ilona Malecka, Joanna Stryczynska-Kazubska, Wojciech Feleszko, Izabella Lazowska-Przeorek, Katarzyna Karolewska-Bochenek, Jarosław Walkowiak, Janusz Slusarczyk, Andrzej Radzikowski, Urszula Demkow, Piotr Albrecht
BACKGROUND: There are limited data on antibody response to vaccination in patients with inflammatory bowel disease (IBD). In this study, we aimed to assess the immunogenicity of a booster dose of pertussis vaccine in pediatric patients with IBD and to compare their response with healthy controls. METHODS: We performed a multicenter, prospective, and controlled trial. Eligible for inclusion were children and adolescents (11-18 year olds), with no history of pertussis booster immunization after the age of 6 years or history of pertussis...
May 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#7
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 6, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28374975/enrichment-of-genetic-variants-in-the-glucocorticoid-receptor-signalling-pathway-in-autoimmune-hepatitis-with-failure-of-standard-treatment
#8
Peter Lykke Eriksen, Martin Kreutzfeldt, Henning Grønbaek, Kasper Thorsen, Søren Vang, Niels Jessen, Hendrik Vilstrup
The standard treatment for autoimmune hepatitis (AIH) is predniso(lo)ne for remission induction, tapered and followed by azathioprine, which effectively controls the disease in the majority of patients. However, some patients prove to be unresponsive or non-tolerant and require alternative immunosuppressive regimens for disease control. We aimed to investigate whether these AIH patients who experience failure of standard treatment have a genomic basis for their problem in the form of pharmacogenetic variants...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28350354/proteomic-profiling-comparing-the-effects-of-different-heat-treatments-on-camel-camelus-dromedarius-milk-whey-proteins
#9
COMPARATIVE STUDY
Hicham Benabdelkamel, Afshan Masood, Ibrahim O Alanazi, Dunia A Alzahrani, Deema K Alrabiah, Sami A AlYahya, Assim A Alfadda
Camel milk is consumed in the Middle East because of its high nutritional value. Traditional heating methods and the duration of heating affect the protein content and nutritional quality of the milk. We examined the denaturation of whey proteins in camel milk by assessing the effects of temperature on the whey protein profile at room temperature (RT), moderate heating at 63 °C, and at 98 °C, for 1 h. The qualitative and quantitative variations in the whey proteins before and after heat treatments were determined using quantitative 2D-difference in gel electrophoresis (DIGE)-mass spectrometry...
March 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28349233/low-dose-cannabidiol-is-safe-but-not-effective-in-the-treatment-for-crohn-s-disease-a-randomized-controlled-trial
#10
Timna Naftali, Refael Mechulam, Amir Marii, Gila Gabay, Asaf Stein, Miriam Bronshtain, Ido Laish, Fabiana Benjaminov, Fred M Konikoff
BACKGROUND: Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases. AIM: To assess the effects of cannabidiol on Crohn's disease in a randomized placebo-controlled trial. PATIENTS AND METHODS: Twenty patients aged 18-75 years with a Crohn's disease activity index (CDAI) >200 were randomized to receive oral (10 mg) CBD or placebo twice daily...
March 27, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28348471/role-of-allopurinol-in-optimizing-thiopurine-therapy-in-patients-with-autoimmune-hepatitis-a-review
#11
REVIEW
Shivani Deswal, Anshu Srivastava
Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes...
March 2017: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/28346068/institutional-profile-university-of-florida-health-personalized-medicine-program
#12
Larisa H Cavallari, Kristin W Weitzel, Amanda R Elsey, Xinyue Liu, Scott A Mosley, Donald M Smith, Benjamin J Staley, Almut G Winterstein, Carol A Mathews, Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo, Petr Starostik, Michael J Clare-Salzler, David R Nelson, Julie A Johnson
The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with CYP2C19 genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded CYP2C19 genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs: TPMT-thiopurines, IFNL3 (IL28B)-PEG IFN-α-based regimens, CYP2D6-opioids, CYP2D6/CYP2C19-antidepressants and CYP2C19-proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28342949/use-of-thiopurines-during-conception-and-pregnancy-not-associated-with-adverse-pregancy-outcomes-or-health-of-infants-at-1-year-in-a-prospective-study
#13
Shannon L Kanis, Alison de Lima-Karagiannis, Nanne K H de Boer, C Janneke van der Woude
BACKGROUND & AIMS: Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, making it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children. METHODS: We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016...
March 22, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28333190/early-thiopurine-treatment-is-probably-beneficial-but-time-from-diagnosis-must-be-evaluated
#14
Cristina Concellón, Sara Gómez-Enjuto, Luis Fernández-Salazar
No abstract text is available yet for this article.
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28333183/machine-learning-algorithms-for-objective-remission-and-clinical-outcomes-with-thiopurines
#15
Akbar K Waljee, Kay Sauder, Anand Patel, Sandeep Segar, Boang Liu, Yiwei Zhang, Ji Zhu, Ryan W Stidham, Ulysses Balis, Peter D R Higgins
Background and Aims: Big data analytics leverage patterns in data to harvest valuable information, but are rarely implemented in clinical care. Optimising thiopurine therapy for inflammatory bowel disease [IBD] has proved difficult. Current methods using 6-thioguanine nucleotide [6-TGN] metabolites have failed in randomized controlled trials [RCTs], and have not been used to predict objective remission [OR]. Our aims were to: 1) develop machine learning algorithms [MLA] using laboratory values and age to identify patients in objective remission on thiopurines; and 2) determine whether achieving algorithm-predicted objective remission resulted in fewer clinical events per year...
March 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28317081/pharmacogenetic-predictors-of-treatment-related-toxicity-among-children-with-acute-lymphoblastic-leukemia
#16
REVIEW
Rochelle R Maxwell, Peter D Cole
PURPOSE OF REVIEW: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). RECENT FINDINGS: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28296824/multicentric-case-control-study-on-azathioprine-dose-and-pharmacokinetics-in-early-onset-pediatric-inflammatory-bowel-disease
#17
Gabriele Stocco, Stefano Martelossi, Serena Arrigo, Arrigo Barabino, Marina Aloi, Massimo Martinelli, Erasmo Miele, Daniela Knafelz, Claudio Romano, Samuele Naviglio, Diego Favretto, Eva Cuzzoni, Raffaella Franca, Giuliana Decorti, Alessandro Ventura
BACKGROUND: Early-onset inflammatory bowel disease (IBD) is generally aggressive, with a high probability of complications and need of surgery. Despite the introduction of highly effective biological drugs, treatment with azathioprine continues to be important even for early-onset IBD; however, in these patients azathioprine response seems to be reduced. This study evaluated azathioprine doses, metabolite concentrations, and their associations with patients' age in children with IBD treated at 6 tertiary pediatric referral centers...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28295989/pharmacokinetics-of-two-6-mercaptopurine-liquid-formulations-in-children-with-acute-lymphoblastic-leukemia
#18
Jaszianne A Tolbert, Shasha Bai, Susan M Abdel-Rahman, Keith J August, Scott J Weir, Gregory L Kearns, Kathleen A Neville
BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28278299/combination-treatment-with-6-mercaptopurine-and-allopurinol-in-hepg2-and-hek293-cells-effects-on-gene-expression-levels-and-thiopurine-metabolism
#19
Sofie Haglund, Svante Vikingsson, Sven Almer, Jan Söderman
Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28277331/nudt15-genotype-distributions-in-the-korean-population
#20
Hyoung-Tae Kim, Rihwa Choi, Hong-Hee Won, Yon Ho Choe, Ben Kang, Kiwuk Lee, Hong Hoe Koo, Keon Hee Yoo, Young-Ho Kim, Soo-Youn Lee
Thiopurines have a narrow therapeutic range because of frequent toxicity (i.e. marrow suppression), which is only partly explained by TPMT genetic polymorphisms, especially within Asian populations. Recent studies have identified NUDT15 variation as another important factor affecting thiopurine metabolism. In this study, a total of four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal) were genotyped in 920 Korean individuals using direct sequencing of NUDT15 for the first time in a Korean population...
May 2017: Pharmacogenetics and Genomics
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