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Thiopurine

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https://www.readbyqxmd.com/read/28818801/development-and-validation-of-a-reliable-method-for-thiopurine-methyltransferase-tpmt-enzyme-activity-in-human-whole-blood-by-lc-ms-ms-an-application-for-phenotypic-and-genotypic-correlations
#1
Supaporn Wiwattanakul, Santirhat Prommas, Nuttawut Jenjirattithigarn, Siwalee Santon, Apichaya Puangpetch, Samart Pakakasama, Usanarat Anurathapan, Chonlaphat Sukasem
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of thiopurine methyltransferase (TPMT) activity in human whole blood lysate, based on conversion of 6-mercaptopurine (6-MP) by TPMT to 6-methylmercaptopurine (6-MMP) using S-adenosyl-l-methionine (SAM) as the methyl donor. This method was improved from the previous laborious method for washing of red cell lysate preparation to develop whole blood EDTA lysate. In addition, the TPMT incubation was optimized and the chromatography was performed in a short runtime of 7min on a C18-column by detection via triple quadrupole mass spectrometry...
August 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28811125/pharmacokinetics-and-pharmacodynamics-of-thiopurines-in-an-in-vitro-model-of-human-hepatocytes-insights-from-an-innovative-mass-spectrometry-assay
#2
Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti
AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by Trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival...
August 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28805309/safety-of-herpes-zoster-vaccination-among-inflammatory-bowel-disease-patients-being-treated-with-anti-tnf-medications
#3
N Khan, Y Shah, C Trivedi, J D Lewis
BACKGROUND: The risk of herpes zoster (HZ) is elevated in inflammatory bowel disease (IBD) patients treated with anti-TNF medications. While it is optimal to give herpes zoster vaccine prior to initiation of therapy clinical circumstances may not always allow this. AIM: To determine the safety of giving herpes zoster vaccine while patients are on anti-TNF therapy. METHODS: We conducted a retrospective cohort study involving IBD patients who were followed in the Veterans Affairs (VA) healthcare system between 2001 and 2016...
August 14, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28804920/thiopurines-prevented-surgical-recurrence-in-patients-with-crohn-s-disease-after-intestinal-resection-strategy-based-on-risk-stratification
#4
Jing Guo, Bai-Li Chen, Zhi-Hui Chen, Xia-Peng Luo, Yun Qiu, Sheng-Hong Zhang, Rui Feng, Yao He, Zhi-Rong Zeng, Xin-Ming Song, Shomron Ben-Horin, Ren Mao, Min-Hu Chen
BACKGROUND: Thiopurines (TPs) are effective in reducing risk of clinical and endoscopic recurrence in postoperative patients with Crohn's disease (CD). However, whether TPs could prevent surgical recurrence (SR) remains unknown. AIM: To explore whether TPs could prevent SR and identify risk factors associated with SR in postoperative CD patients. METHODS: This was a retrospective cohort study of 246 postoperative patients with CD. Cox proportional hazard model was used to identify risk factors for SR...
August 14, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28803932/the-thiopurine-nucleoside-analogue-6-methylmercaptopurine-riboside-6mmpr-effectively-blocks-zika-virus-replication
#5
Otavio Valério de Carvalho, Daniele Mendes Félix, Leila Rodrigues de Mendonça, Catarina Maria Cataldi Sabino de Araújo, Rafael Freitas de Oliveira Franca, Marli Tenório Cordeiro, Abelardo Silva Júnior, Lindomar José Pena
Since the emergence of Zika virus (ZIKV) in Brazil in 2015, 48 countries and territories in the Americas have confirmed autochthonous cases of the disease caused by the virus. The ZIKV-associated neurological manifestations and congenital defects make the development of safe and effective antivirals against ZIKV of utmost importance. Here, we evaluated the antiviral activity of 6-methylmercaptopurine riboside (6MMPr), a thiopurine nucleoside analog derived from the prodrug azathioprine (AZA), against the epidemic ZIKV strain circulating in Brazil...
August 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28791279/pneumocystis-jirovecii-pneumonia-in-pediatric-inflammatory-bowel-disease-a-case-report-and-literature-review
#6
Sally J Lawrence, Manish Sadarangani, Kevan Jacobson
Immunosuppressive therapy is a known risk factor for opportunistic infections. We report the first case of severe Pneumocystis jirovecii infection requiring intensive care in a pediatric patient with inflammatory bowel disease (IBD). The literature was reviewed and there were 92 reported cases of Pneumocystis pneumonia (PCP) in patients with IBD. Most sources were case reports and there was likely reporting bias toward patients receiving immunomodulators, anti-tumor necrosis factor (anti-TNF) therapy, and those who died...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28774547/american-gastroenterological-association-technical-review-on-the-role-of-therapeutic-drug-monitoring-in-the-management-of-inflammatory-bowel-diseases
#7
Niels Vande Casteele, Hans Herfarth, Jeffry Katz, Yngve Falck-Ytter, Siddharth Singh
Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease...
July 31, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28753181/real-life-anti-tumour-necrosis-factor-experience-in-500-paediatric-united-kingdom-inflammatory-bowel-disease-patients
#8
Victoria M Merrick, Kajal Mortier, Linda J Williams, Rafeeq Muhammed, Marcus Kh Auth, Mamoun Elawad, John Me Fell, R Mark Beattie, Sabarinathan Loganathan, Franco Torrente, Mary-Anne Morris, Charles Charlton, Nick M Croft, Astor Rodrigues, Mark Furman, Babu Vadamalayan, Huw Jenkins, Veena Zamvar, Sally G Mitton, Sonny Chong, Mike Cosgrove, Anthony Akobeng, David C Wilson, Richard K Russell
OBJECTIVES: To measure the effectiveness, safety and use of anti-Tumour necrosis Factor (TNF) therapy in paediatric inflammatory bowel disease (PIBD) in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment (PGA) +/or the Paediatric Crohn's Disease Activity Index (PCDAI). RESULTS: 37 centres participated (23 of 25 specialist PIBD sites)...
July 27, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28749985/fatigue-in-out-patients-with-inflammatory-bowel-disease-prevalence-and-predictive-factors
#9
Albert Villoria, Víctor García, Angelina Dosal, Laura Moreno, Antònia Montserrat, Ariadna Figuerola, Diana Horta, Xavier Calvet, María José Ramírez-Lázaro
BACKGROUND AND AIM: Fatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue. METHODS: Consecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores...
2017: PloS One
https://www.readbyqxmd.com/read/28740837/histological-remission-of-autoimmune-hepatitis-after-the-addition-of-allopurinol-and-azathioprine-dose-reduction
#10
Ana Luiza Vilar Guedes, Adriana Ribas Andrade, Vinicius Santos Nunes, Fabiana Roberto Lima, Evandro Sobroza de Mello, Suzane Kioko Ono, Débora Raquel Benedita Terrabuio, Eduardo Luiz Rachid Cançado
The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite...
April 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/28731668/-azathioprine-induced-pancytopenia-case-series
#11
Cristina Martínez Faci, Ignacio Ros Arnal, José M Martínez de Zabarte Fernández, Jordi Sorribes Estorch, Mónica López Campos, Carmen Rodríguez-Vigil Iturrate
Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts...
August 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28723860/higher-thioguanine-nucleotide-metabolite-levels-are-associated-with-better-long-term-outcomes-in-patients-with-inflammatory-bowel-diseases
#12
Andres J Yarur, Bilal Gondal, Ayal Hirsch, Britt Christensen, Russell D Cohen, David T Rubin
GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28681659/the-relationship-of-genetics-nursing-practice-and-informatics-tools-in-6-mercaptopurine-dosing-in-pediatric-oncology-formula-see-text
#13
Wendy J Haylett
An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care...
September 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28679280/assessing-medication-adherence-in-inflammatory-bowel-diseases-a-comparison-between-a-self-administered-scale-and-a-pharmacy-refill-index
#14
María Luisa de Castro, Luciano Sanromán, Alicia Martín, Montserrat Figueira, Noemi Martínez, Vicent Hernández, Victor Del Campo, Juan R Pineda, Jesús Martínez-Cadilla, Santos Pereira, José Ignacio Rodríguez Prada
BACKGROUND: Medication non-adherence in inflammatory bowel disease (IBD) has a negative impact on disease outcome. Different tools have been proposed to assess non-adherence. We aimed to compare a self-administered scale and a pharmacy refill index as a reliable measure of medication adherence and to determine what factors are related to adherence. METHODS: Consecutive non-active IBD outpatients were asked to fill in the self-reported Morisky Medication Adherence Scale (MMAS-8) and the Beliefs about Medication Questionnaire (BMQ)...
July 6, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28678626/optimising-use-of-thiopurines-in-inflammatory-bowel-disease
#15
Robin J Dart, Peter M Irving
Thiopurines are central to inflammatory bowel disease (IBD) therapeutics, either as monotherapy or in combination with newer biologic therapies, however it is only recently that focus has increased on improving effectiveness and tolerability through optimisation. Areas covered: We review the role of thiopurines in IBD and the importance of the timing of initiation of therapy. Drug metabolism and pharmacogenetics have increasingly played a role in determining dosing and dose optimisation and we review the rationale for this in both thiopurine monotherapy and in combination with biologic agents...
September 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28670229/nudt15-fto-and-runx1-genetic-variants-and-thiopurine-intolerance-among-japanese-patients-with-inflammatory-bowel-diseases
#16
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect...
July 2017: Intestinal Research
https://www.readbyqxmd.com/read/28659275/novel-variants-in-nudt15-and-thiopurine-intolerance-in-children-with-acute-lymphoblastic-leukemia-from-diverse-ancestry
#17
Takaya Moriyama, Yung-Li Yang, Rina Nishii, Hany Ariffin, Chengcheng Liu, Ting-Nien Lin, Wenjian Yang, Dong-Tsamn Lin, Chih-Hsiang Yu, Shirley Kham, Ching-Hon Pui, William E Evans, Sima Jeha, Mary V Relling, Allen Eng-Juh Yeoh, Jun J Yang
Prolonged exposure to thiopurines (e.g., mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL) but is also associated with frequent dose-limiting hematopoietic toxicities, partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (e.g., TPMT). Recently, our group and others identified germline genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asians and Hispanics. Herein we described three novel NUDT15 coding variants (p...
June 28, 2017: Blood
https://www.readbyqxmd.com/read/28651549/6-methylmercaptopurine-riboside-a-thiopurine-nucleoside-with-antiviral-activity-against-canine-distemper-virus-in-vitro
#18
Otávio Valério de Carvalho, Daniele Mendes Félix, Claudia de Camargo Tozato, Juliana Lopes Rangel Fietto, Márcia Rogéria de Almeida, Gustavo Costa Bressan, Lindomar José Pena, Abelardo Silva-Júnior
BACKGROUND: Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper...
June 26, 2017: Virology Journal
https://www.readbyqxmd.com/read/28650902/itpa-activity-in-adults-and-children-treated-with-or-without-azathioprine-relationship-between-tpmt-activity-thiopurine-metabolites-and-co-medications
#19
Boulieu Roselyne, Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin
BACKGROUND: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data is available on its role on thiopurine metabolites. ITPA' ability to modify the thiopurine metabolite levels currently used to optimize azathioprine (AZA) therapy in relation to TPMT activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites...
June 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28644183/more-dose-dependent-side-effects-with-mercaptopurine-over-azathioprine-in-ibd-treatment-due-to-relatively-higher-dosing
#20
Mark M T J Broekman, Marieke J H Coenen, Corine J van Marrewijk, Geert J A Wanten, Dennis R Wong, Andre L M Verbeek, Olaf H Klungel, Piet M Hooymans, Henk-Jan Guchelaar, Hans Scheffer, Luc J J Derijks, Dirk J de Jong
BACKGROUND: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy. METHODS: Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care...
June 20, 2017: Inflammatory Bowel Diseases
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