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https://www.readbyqxmd.com/read/29327413/itpa-activity-in-children-treated-by-azathioprine-relationship-to-the-occurrence-of-adverse-drug-reactions-and-inflammatory-response
#1
Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin, Alain Lachaux, Roselyne Boulieu
Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological disease such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reaction (ADRs) and drug response is observed. This study investigated 1) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, 2) the relationship between ITPA activity and the inflammatory activity observed in children with IBD...
January 11, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29324279/inhibition-of-udp-glucose-dehydrogenase-by-6-thiopurine-and-its-oxidative-metabolites-possible-mechanism-for-its-interaction-within-the-bilirubin-excretion-pathway-and-6tp-associated-liver-toxicity
#2
Chamitha J Weeramange, Cassie M Binns, Chixiang Chen, Ryan J Rafferty
6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various diseases ranging from Crohn's disease and other inflammatory diseases to acute lymphocytic leukemia and non-Hodgkin's leukemia. While 6TP has beneficial therapeutic uses, severe toxicities are also reported with its use, such as jaundice and liver toxicity. While numerous investigations into the mode in which toxicity originates has been undertaken. None have investigated the effects of inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl transferase (UGT1A1), which is responsible for the conjugation of bilirubin with UDPGA for excretion...
December 30, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29321348/influence-of-thiopurine-methyltransferase-gene-polymorphism-on-egyptian-children-with-acute-lymphoblastic-leukaemia
#3
Azza A G Tantawy, Fatma S E Ebeid, Amira A M Adly, Eman El-Ghoroury, Mai Mostafa
Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine therapeutic efficacy and toxicity. The aim of this study was to determine the influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol, and who also experiencedmyleosuppresion toxicity and required interruption and/ormodification of thiopurine chemotherapy were recruited over a year period...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29315147/nonmelanoma-skin-cancer-risk-in-patients-with-inflammatory-bowel-disease-undergoing-thiopurine-therapy-a-systematic-review-of-the-literature
#4
Joshua W Hagen, Melissa A Pugliano-Mauro
BACKGROUND: Azathioprine and 6-mercaptopurine (thiopurines) are common adjunct treatments for inflammatory bowel disease (IBD). Although thiopurine therapy in organ transplant recipients is known to increase nonmelanoma skin cancers (NMSCs), dermatologic literature yields less data regarding NMSC risk of thiopurine use in IBD. OBJECTIVE: The aim of this study was to systematically review current literature on NMSC risk in patients with IBD using thiopurine therapy...
January 8, 2018: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/29309905/overall-and-comparative-risk-of-herpes-zoster-with-pharmacotherapy-for-inflammatory-bowel-diseases-a-nationwide-cohort-study
#5
Nabeel Khan, Dhruvan Patel, Chinmay Trivedi, Yash Shah, Gary Lichtenstein, James Lewis, Yu-Xiao Yang
BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. METHODS: We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD...
January 5, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29298871/role-of-thiopurines-as-disease-modifying-agents-in-crohn-s-disease
#6
Jonathan Blackwell, Sonia Saxena, Richard C Pollok
No abstract text is available yet for this article.
January 3, 2018: Gut
https://www.readbyqxmd.com/read/29283382/thiopurine-drugs-repositioned-as-tyrosinase-inhibitors
#7
Joonhyeok Choi, You-Mie Lee, Jun-Goo Jee
Drug repositioning is the application of the existing drugs to new uses and has the potential to reduce the time and cost required for the typical drug discovery process. In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule inhibitors of tyrosinase for therapeutic and cosmetic purposes...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29280181/modeling-time-varying-exposure-using-inverse-probability-of-treatment-weights
#8
Nathalie Grafféo, Aurélien Latouche, Ronald B Geskus, Sylvie Chevret
For estimating the causal effect of treatment exposure on the occurrence of adverse events, inverse probability weights (IPW) can be used in marginal structural models to correct for time-dependent confounding. The R package ipw allows IPW estimation by modeling the relationship between the exposure and confounders via several regression models, among which is the Cox model. For right-censored data and time-dependent exposures such as treatment switches, the ipw package allows a single switch, assuming that patients are treated once and for all...
December 27, 2017: Biometrical Journal. Biometrische Zeitschrift
https://www.readbyqxmd.com/read/29259384/impact-of-inflammatory-bowel-disease-activity-and-thiopurine-therapy-on-birth-weight-a-meta-analysis
#9
Begoña Gonzalez-Suarez, Shreyashee Sengupta, Alan C Moss
AIM: To investigate the effect of disease activity or thiopurine use on low birth weight and small for gestational age in women with inflammatory bowel disease (IBD). METHODS: Selection criteria included all relevant articles on the effect of disease activity or thiopurine use on the risk of low birth weight (LBW) or small for gestational age (SGA) among pregnant women with IBD. Sixty-nine abstracts were identified, 35 papers were full text reviewed and, only 14 of them met inclusion criteria...
December 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29259376/albumin-as-a-prognostic-marker-for-ulcerative-colitis
#10
Nabeel Khan, Dhruvan Patel, Yash Shah, Chinmay Trivedi, Yu-Xiao Yang
AIM: To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS: Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3...
December 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29226420/editorial-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype-the-perils-of-ageing-authors-reply
#11
EDITORIAL
M M T J Broekman, G J Wanten, D J de Jong
No abstract text is available yet for this article.
January 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29226409/editorial-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype-the-perils-of-ageing
#12
EDITORIAL
A J Willington, R B Gearry
No abstract text is available yet for this article.
January 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29220429/combination-therapy-with-adalimumab-and-thiopurines-in-inflammatory-bowel-disease-is-it-a-case-of-nepotism-in-pharmacology
#13
Turki AlAmeel, Mahmoud H Mosli
No abstract text is available yet for this article.
December 6, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29210335/predictive-role-of-nudt15-variants-on-thiopurine-induced-myelotoxicity-in-asian-inflammatory-bowel-disease-patients
#14
Natalia Sutiman, Sylvia Chen, Khoon Lin Ling, Sai Wei Chuah, Wai Fook Leong, Vinayak Nadiger, Madeline Tjai, Chris San Choon Kong, Brian John Schwender, Webber Chan, Hang Hock Shim, Wee Chian Lim, Chiea Chuen Khor, Yin Bun Cheung, Balram Chowbay
BACKGROUND: Genetic variants of TPMT and NUDT15 have been reported to predict the inter-patient variability in response and toxicity profiles of patients receiving thiopurine therapy. However, the clinical utility of TPMT genotyping in guiding thiopurine doses has been questionable, in part due to underlying differences in the prevalence of TPMT variants in both Caucasian and Asian populations. Several NUDT15 variants have been associated with thiopurine-induced leukopenia, particularly in Asian cohorts...
December 6, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29206869/measurements-of-6-thioguanine-nucleotide-levels-with-tpmt-and-nudt15-genotyping-in-patients-with-crohn-s-disease
#15
Ji Hyeon Lee, Tae Jun Kim, Eun Ran Kim, Sung Noh Hong, Dong Kyung Chang, Li-Hwa Choi, Hye In Woo, Soo-Youn Lee, Young-Ho Kim
The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD...
2017: PloS One
https://www.readbyqxmd.com/read/29205426/systematic-review-with-meta-analysis-thiopurines-decrease-the-risk-of-colorectal-neoplasia-in-patients-with-inflammatory-bowel-disease
#16
REVIEW
M J Lu, X Y Qiu, X Q Mao, X T Li, H J Zhang
BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high risk of developing colorectal neoplasia. AIM: To investigate whether thiopurines can decrease the risk of developing colorectal neoplasia in patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We conducted a meta-analysis of 24 observational studies involving 76,999 participants to evaluate the risks of developing colorectal neoplasia in IBD patients receiving thiopurine treatment...
December 4, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29197117/addition-of-allopurinol-for-altering-thiopurine-metabolism-to-optimize-therapy-in-patients-with-inflammatory-bowel-disease
#17
Geoffrey C Wall, Hamid Muktar, Cassandra Effken, Pramod B Mahajan
Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease...
December 1, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29194039/validation-of-a-high-performance-liquid-chromatography-method-for-thiopurine-s-methyltransferase-activity-in-whole-blood-using-6-mercaptopurine-as-substrate
#18
Hannah Rieger, Patrik Schmidt, Elke Schaeffeler, Manabu Abe, Mira Schiffhauer, Matthias Schwab, Nicolas von Ahsen, Gabriela Zurek, Hartmut Kirchherr, Maria Shipkova, Eberhard Wieland
BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor...
December 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29192347/pharmacogenetics-of-thiopurines-for-inflammatory-bowel-disease-in-east-asia-prospects-for-clinical-application-of-nudt15-genotyping
#19
REVIEW
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
The thiopurine drugs 6-mercaptopurine (6-MP) and azathiopurine (AZA) are widely used to treat inflammatory bowel disease. However, the incidence of adverse reactions is high, particularly in Asia, and the mechanisms of toxicity in Asian populations remain unclear. Thiopurine S-methyltransferase (TPMT) is a well-known enzyme that inactivates AZA or 6-MP through methylation and is one of the few pharmacogenetic predictors used in clinical settings in Western countries. Individuals carrying TPMT-deficient genetic variants require reduced drug doses, but this treatment modification is are not applicable to East Asian populations...
November 30, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29191122/association-between-tpmt-3c-and-decreased-thiopurine-s-methyltransferase-activity-in-patients-with-neuromyelitis-optica-spectrum-disorders-in-china
#20
Xiaoqing Gong, Shenghui Mei, Xindi Li, Xingang Li, Heng Zhou, Yonghong Liu, Anna Zhou, Li Yang, Zhigang Zhao, Xinghu Zhang
AIM OF THE STUDY: Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT*3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China...
December 1, 2017: International Journal of Neuroscience
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