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| 1 | Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease:Effect of N-acetyl transferase polymorphisms显示文摘AIM: To evaluate variation of the concentration of thiopurine metabolites after 5-aminosalicylate(5-ASA) interruption and the role of genetic polymorphisms of N-acetyl transferase(NAT) 1 and 2. METHODS: Concentrations of thioguanine nucleotides(TGN) and methymercaptopurine nucleotides(MMPN), metabolites of thiopurines, were measured by high performance liquid chromatography in 12 young patients(3 females and 9 males, median age 16 years) with inflammatory bowel disease(6 Crohn's disease and 6 ulcerative colitis) treated with thiopurines(7 mercaptopurine and 5 azathioprine) and 5-ASA. Blood samples were collected one month before and one month after the interruption of 5-ASA. DNA was extracted and genotyping of NAT1, NAT2, inosine triphosphate pyrophosphatase(ITPA) and thiopurine methyl transferase(TPMT) genes was performed using PCR assays. RESULTS: Median TGN concentration before 5-ASA interruption was 270 pmol/8 x 108 erythrocytes(range: 145-750); after the interruption of the aminosalicylate, a 35% reduction in TGN mean concentrations(absolutemean reduction 109 pmol/8 × 108 erythrocytes) was observed(median 221 pmol/8 × 108 erythrocytes, range: 96-427, P value linear mixed effects model 0.0011). Demographic and clinical covariates were not related to thiopurine metabolites concentrations. All patients were wild-type for the most relevant ITPA and TPMT variants. For NAT1 genotyping, 7 subjects presented an allele combination corresponding to fast enzymatic activity and 5 to slow activity. NAT1 genotypes corresponding to fast enzymatic activity were associated with reduced TGN concentration(P value linear mixed effects model 0.033), putatively because of increased 5-ASA inactivation and consequent reduced inhibition of thiopurine metabolism. The effect of NAT1 status on TGN seems to be persistent even after one month since the interruption of the aminosalicylate. No effect of NAT1 genotypes was shown on MMPN concentrations. NAT2 genotyping revealed that 6 patients presented a genotype corresponding to fast enzymatic activity and 6 to slow activity; NAT2 genotypes were not related to thiopurine metabolites concentration in this study. CONCLUSION: NAT1 genotype affects TGN levels in patients treated with thiopurines and aminosalicylates and could therefore influence the toxicity and efficacy of these drugs; however the number of patients evaluated is limited and this has to be considered a pilot study. | Gabriele Stocco Eva Cuzzoni Sara De Iudicibus Diego Favretto Noelia Malusà Stefano Martelossi Elena Pozzi Paolo Lionetti Alessandro Ventura Giuliana Decorti | 2015 | World Journal of Gastroenterology2015，21，12： | 5 |
| 2 | Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?显示文摘Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease(IBD).In vivo it is active after reaction with reduced glutathione(GSH)and conversion to mercaptopurine.Although this reaction may occur spontaneously,the presence of isoforms M and A of the enzyme glutathione-S-transferase(GST)may increase its speed.Indeed,in pediatric patients with IBD,deletion of GST-M1,which determines reduced enzymatic activity,was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites.In addition to increase the activation of azathioprine to mercaptopurine,GSTs may contribute to azathioprine effects even by modulating GSH consumption,oxidative stress and apoptosis.Therefore,genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.reserved. | Gabriele Stocco Marco Pelin Raffaella Franca Sara De Iudicibus Eva Cuzzoni Diego Favretto Stefano Martelossi Alessandro Ventura Giuliana Decorti | 2014 | World Journal of Gastroenterology2014，20，13： | 2 |
| 3 | Contribution of CT to treatment planning in patients with GIST 显示文摘 | Rimondini A Belgrano M Favretto G | 2007 | Radiol Med2007，112，5： | 1 |
| 4 | Contribution of CT to treatment planning in patients with GIST显示文摘 | Rimondini A Belgrano M Favretto G | 2007 | Radiol Med2007，112，10： | 1 |
| 5 | Determination of ketamine and norketamine in hair by micropulverized extraction and liquid chromatography-high resolution mass spectrometry显示文摘 | FAVRETTO D VOGLIARDI S NALESSO A | 2013 | Forensic Science International2013，226，13： | 1 |
| 6 | Spectrophotometric determination of polyoxyethylene in the presence of cationic surfactants显示文摘 | FAVRETTO L STANCHER B TENIS F | 1983 | International Journal of Environmental Analytical Chemistry1983，14，4： | 1 |
| 7 | 查看详情显示文摘 | L Favretto | | 0，，： | 1 |
| 8 | Selective intrauterine growth restriction in monochorionic twin pregnancies:markers of endothelial damage and metabolomic profile显示文摘 | COSMI E VISENTIN S FAVRETTO D | 2013 | Twin Research and Human Genetics:the Official Journal of the International Society for Twin Studies2013，16，4： | 1 |
| 9 | Associa tion between depression and heart rate variabili ty in patients after cardiac surgerya pilot study显示文摘 | Patron E Messerotti Benvenuti S Favretto G | 2012 | J Psychosom Res2012，73，1： | 1 |
| 10 | Potentials of ion trap collisional spectrometry for liquid chromatography/ electrospray ionization tandem mass spectrometry determination of buprenorphine and nor - buprenorphlne in urine, blood and hair samples显示文摘 | Favretto D Frison G Vogliardi S | 2006 | Rapid communications in mass spectrometry2006，20，8： | 1 |
| 11 | Cord blood metabolomic profiling in intrauterine growth restriction显示文摘 | Favretto D Cosmi E Ragazzi E | | 0，，03： | 1 |
| 12 | Depression and re- duced heart rate variability after cardiac surgery : the mediating role of emotion regulation 显示文摘 | Patron E Messerotti Benvenuti S Favretto G | 2014 | Auton Neurosci2014，180，： | 1 |
| 13 | Contribution-of CT to treatment pianning in patients with GIST显示文摘 | Rimon-dini A Belgrano M Favretto G | 2007 | Radiol Med2007，112，： | 1 |
| 14 | Contribution of CT to treaunent planning in patients with GIST显示文摘 | Rimondini A Belgrano M Favretto G | 2007 | Radiol Med2007，112，： | 1 |
| 15 | Contribution of CT to Treatment Planning in Patients with GIST显示文摘 | Rimondini A Belgrano M Favretto G | 2007 | Radiol Med2007，112，10： | 1 |
| 16 | Electrospray ionization mass spectra and collision induced mass spectra of anti-tumour Catharanthus alkaloids显示文摘 | Favretto D Piovan A Cappelletti E M | 1998 | Rapid communications in Mass Spectrom1998，12，： | 1 |
| 17 | Cord blood metabolomie profiling in intrauterine growth restriction 显示文摘 | Favretto D Cosmi E Ragazzi E | 2012 | Anal Bioanal Chem2012，402，3： | 1 |
| 18 | Microwave accelerated steam distillation of essential oil from lavender: A rapid, clean and environmentally friendly approach 显示文摘 | F Chemat M E Lucchesi J Smadja L Favretto G Colnaghi F Visinoni | 2006 | Analytica Chimica Acta2006，555，1： | 1 |
| 19 | Contribution of CT to treatment planning in patients with GIST 显示文摘 | Rimondini A Belgrano M Favretto G | 2007 | Radiol Med(Torino)2007，112，5： | 1 |
| 20 | Delermina lion of ketamine and norketamine in hair by micropulverized extraction and liquid chromatography-high resolution mass spectrometry 显示文摘 | Favretto D Vogliardi S Stocchero G | 2013 | Forensic Science International2013，，226： | 1 |
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