<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Pelin, Marco</style></author><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author><author><style face="normal" font="default" size="100%">Spizzo, Riccardo</style></author><author><style face="normal" font="default" size="100%">Dei Rossi, Sveva</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress.</style></title><secondary-title><style face="normal" font="default" size="100%">Curr Drug Metab</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Curr. Drug Metab.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">17</style></volume><pages><style face="normal" font="default" size="100%">542-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Thiopurine antimetabolites are important agents for the treatment of severe diseases, such as acute lymphoblastic leukemia and inflammatory bowel disease. Their pharmacological actions depend on biotransformation into active thioguanine-nucleotides; intracellular metabolism is mediated by enzymes of the salvage pathway of nucleotide synthesis and relies on polymorphic enzymes involved in thiopurines' catabolism such as thiopurine-S-methyl transferase. Given the enzymes involved in thiopurines' metabolism, it is reasonable to hypothesize that these drugs are able to induce significant oxidative stress conditions, possibly altering their pharmacological activity.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;A systemic search of peer-reviewed scientific literature in bibliographic databases has been carried out. Both clinical and preclinical studies as well as mechanistic studies have been included to shed light on the role of oxidative stress in thiopurines' pharmacological effects.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Sixty-nine papers were included in our review, allowing us to review the contribution of oxidative stress in the pharmacological action of thiopurines. Thiopurines are catabolized in the liver by xanthine oxidase, with potential production of reactive oxidative species and azathioprine is converted into mercaptopurine by a reaction with reduced glutathione, that, in some tissues, may be facilitated by glutathione- S-transferase (GST). A clear role of GSTM1 in modulating azathioprine cytotoxicity, with a close dependency on superoxide anion production, has been recently demonstrated. Interestingly, recent genome-wide association studies have shown that, for both azathioprine in inflammatory bowel disease and mercaptopurine in acute lymphoblastic leukemia, treatment effects on patients' white blood cells are related to variants of a gene, NUDT15, involved in biotransformation of oxidated nucleotides.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Basing on previous evidences published in literature, oxidative stress may contribute to thiopurine effects in significant ways that, however, are still not completely elucidated.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26935390?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Amaddeo, Alessandro</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author><author><style face="normal" font="default" size="100%">Marchetti, Federico</style></author><author><style face="normal" font="default" size="100%">Benettoni, Alessandra</style></author><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Should cardiac involvement be included in the criteria for diagnosis of Churg Strauss syndrome?</style></title><secondary-title><style face="normal" font="default" size="100%">J Pediatr</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Pediatr.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Churg-Strauss Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Apr</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">160</style></volume><pages><style face="normal" font="default" size="100%">707</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22050872?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">De Iudicibus, Sara</style></author><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author><author><style face="normal" font="default" size="100%">Ebner, Egle</style></author><author><style face="normal" font="default" size="100%">Pontillo, Alessandra</style></author><author><style face="normal" font="default" size="100%">Lionetti, Paolo</style></author><author><style face="normal" font="default" size="100%">Barabino, Arrigo</style></author><author><style face="normal" font="default" size="100%">Bartoli, Fiora</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases.</style></title><secondary-title><style face="normal" font="default" size="100%">J Clin Gastroenterol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Clin. Gastroenterol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Follow-Up Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Glucocorticoids</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Multivariate Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Glucocorticoid</style></keyword><keyword><style  face="normal" font="default" size="100%">Regression Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Retrospective Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Sex Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Treatment Outcome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">45</style></volume><pages><style face="normal" font="default" size="100%">e1-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Glucocorticoids (GCs) are used in moderate-to-severe inflammatory bowel diseases (IBD) but their effect is often unpredictable.&lt;/p&gt;&lt;p&gt;&lt;b&gt;AIM: &lt;/b&gt;To determine the influence of 4 polymorphisms in the GC receptor [nuclear receptor subfamily 3, group C, member 1 (NR3C1)], interleukin-1β (IL-1β), and NACHT leucine-rich-repeat protein 1 (NALP1) genes, on the clinical response to steroids in pediatric patients with IBD.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;One hundred fifty-four young IBD patients treated with GCs for at least 30 days and with a minimum follow-up of 1 year were genotyped. The polymorphisms considered are the BclI in the NR3C1 gene, C-511T in IL-1β gene, and Leu155His and rs2670660/C in NALP1 gene. Patients were grouped as responder, dependant, and resistant to GCs. The relation between GC response and the genetic polymorphisms considered was examined using univariate, multivariate, and Classification and Regression Tree (CART) analysis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Univariate analysis showed that BclI polymorphism was more frequent in responders compared with dependant patients (P=0.03) and with the combined dependant and resistant groups (P=0.02). Moreover, the NALP1 Leu155His polymorphism was less frequent in the GC responsive group compared with resistant (P=0.0059) and nonresponder (P=0.02) groups. Multivariate analysis comparing responders and nonresponders confirmed an association between BclI mutated genotype and steroid response (P=0.030), and between NALP1 Leu155His mutant variant and nonresponders (P=0.033). An association between steroid response and male sex was also observed (P=0.034). In addition, Leu155His mutated genotype was associated with steroid resistance (P=0.034). Two CART analyses supported these findings by showing that BclI and Leu155His polymorphisms had the greatest effect on steroid response (permutation P value=0.046). The second CART analysis also identified age of disease onset and male sex as important variables affecting response.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;These results confirm that genetic and demographic factors may affect the response to GCs in young patients with IBD and strengthen the importance of studying high-order interactions for predicting response.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20697295?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Pastore, Serena</style></author><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author><author><style face="normal" font="default" size="100%">Cont, Gabriele</style></author><author><style face="normal" font="default" size="100%">Di Leo, Grazia</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Refractory iron-deficiency anaemia in a child with portal cavernoma.</style></title><secondary-title><style face="normal" font="default" size="100%">Gut</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Gut</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Anemia, Iron-Deficiency</style></keyword><keyword><style  face="normal" font="default" size="100%">Antihypertensive Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Hemangioma, Cavernous</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypertension, Portal</style></keyword><keyword><style  face="normal" font="default" size="100%">Ileal Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Propranolol</style></keyword><keyword><style  face="normal" font="default" size="100%">Vascular Neoplasms</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Mar</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">60</style></volume><pages><style face="normal" font="default" size="100%">317, 377</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21051450?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author><author><style face="normal" font="default" size="100%">Pastore, Serena</style></author><author><style face="normal" font="default" size="100%">Zanazzo, Giulio A</style></author><author><style face="normal" font="default" size="100%">Bruno, Irene</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A child with pain after mild trauma.</style></title><secondary-title><style face="normal" font="default" size="100%">J Pediatr</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J. Pediatr.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Antigens, CD</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, CD31</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, CD34</style></keyword><keyword><style  face="normal" font="default" size="100%">Antigens, Differentiation, Myelomonocytic</style></keyword><keyword><style  face="normal" font="default" size="100%">Biopsy</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Factor VIII</style></keyword><keyword><style  face="normal" font="default" size="100%">Fingers</style></keyword><keyword><style  face="normal" font="default" size="100%">Hand Injuries</style></keyword><keyword><style  face="normal" font="default" size="100%">Hemangioendothelioma</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunohistochemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Injury Severity Score</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Osteolysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Pain</style></keyword><keyword><style  face="normal" font="default" size="100%">Pain Measurement</style></keyword><keyword><style  face="normal" font="default" size="100%">S100 Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Vascular Neoplasms</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">157</style></volume><pages><style face="normal" font="default" size="100%">693</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20553843?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Stocco, Gabriele</style></author><author><style face="normal" font="default" size="100%">Londero, Margherita</style></author><author><style face="normal" font="default" size="100%">Campanozzi, Angelo</style></author><author><style face="normal" font="default" size="100%">Martelossi, Stefano</style></author><author><style face="normal" font="default" size="100%">Marino, Sara</style></author><author><style face="normal" font="default" size="100%">Malusà, Noelia</style></author><author><style face="normal" font="default" size="100%">Bartoli, Fiora</style></author><author><style face="normal" font="default" size="100%">Decorti, Giuliana</style></author><author><style face="normal" font="default" size="100%">Ventura, Alessandro</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Usefulness of the measurement of azathioprine metabolites in the assessment of non-adherence.</style></title><secondary-title><style face="normal" font="default" size="100%">J Crohns Colitis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Crohns Colitis</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">6-Mercaptopurine</style></keyword><keyword><style  face="normal" font="default" size="100%">Adolescent</style></keyword><keyword><style  face="normal" font="default" size="100%">Azathioprine</style></keyword><keyword><style  face="normal" font="default" size="100%">Child</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Guanine Nucleotides</style></keyword><keyword><style  face="normal" font="default" size="100%">Hepatitis, Autoimmune</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunosuppressive Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Medication Adherence</style></keyword><keyword><style  face="normal" font="default" size="100%">Thionucleotides</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">4</style></volume><pages><style face="normal" font="default" size="100%">599-602</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Azathioprine is a thiopurine immunosuppressive antimetabolite used to chronically treat inflammatory bowel disease and autoimmune hepatitis. Azathioprine treatment is a long-term therapy and therefore it is at risk for non-adherence, which is considered an important determinant of treatment inefficacy. Measurement of 6-thioguanine and 6-methylmercaptopurine nucleotides has been recently suggested as a screener for non-adherence detection. We describe four young patients in which non-adherence to azathioprine therapy was detected only through the measurement of drug metabolite concentrations, and the criterion for non-adherence was undetectable metabolite levels. After the identification of non-adherence, patients and their families were approached and the importance of a correct drug administration was thoroughly enlightened and discussed; this allowed obtaining a full remission in all subjects. Our observations support the use of undetectable metabolite levels as indicators of non-adherence to therapy in azathioprine treated patients. The additional level of medical supervision given by this assay allows getting a better adherence to medical treatment, which results in an improvement in the response to therapy; these benefits may justify the costs associated with the assay.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/21122567?dopt=Abstract</style></custom1></record></records></xml>