@article {3592, title = {5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis.}, journal = {Rheumatol Int}, volume = {35}, year = {2015}, month = {2015 Apr}, pages = {619-27}, abstract = {

For children with juvenile idiopathic arthritis (JIA) who fail to respond to methotrexate, the delay in identifying the optimal treatment at an early stage of disease can lead to long-term joint damage. Recent studies indicate that relevant variants to predict methotrexate response in JIA are those in 5-aminoimidazole-4-carboxamide ribonucleotide-transformylase (ATIC), inosine-triphosphate-pyrophosphatase (ITPA) and solute-liquid-carrier-19A1 genes. The purpose of the study was, therefore, to explore the role of these candidate genetic factors on methotrexate response in an Italian cohort of children with JIA. Clinical response to methotrexate was evaluated as clinical remission stable for a 6-month period, as ACRPed score and as change in Juvenile Arthritis Disease score. The most relevant SNPs for each gene considered were assayed on patients{\textquoteright} DNA. ITPA activity was measured in patients{\textquoteright} erythrocytes. Sixty-nine patients with JIA were analyzed: 52.2 \% responded to therapy (ACRPed70 score), while 37.7 \% reached clinical remission stable for 6 months. ATIC rs2372536 GG genotype was associated with improved clinical remission (adjusted p value = 0.0090). For ITPA, rs1127354 A variant was associated with reduced clinical remission: (adjusted p value = 0.028); this association was present even for patients with wild-type ITPA and low ITPA activity. These preliminary results indicate that genotyping of ATIC rs2372536 and ITPA rs1127354 variants or measuring ITPA activity could be useful to predict methotrexate response in children with JIA after validation by further prospective studies on a larger patient cohort.

}, issn = {1437-160X}, doi = {10.1007/s00296-014-3131-y}, author = {Pastore, Serena and Stocco, Gabriele and Moressa, Valentina and Zandon{\`a}, Luigi and Favretto, Diego and Malus{\`a}, Noelia and Decorti, Giuliana and Lepore, Loredana and Ventura, Alessandro} } @article {7762, title = {Genetic determinants for methotrexate response in juvenile idiopathic arthritis.}, journal = {Front Pharmacol}, volume = {6}, year = {2015}, month = {2015}, pages = {52}, abstract = {

Juvenile idiopathic arthritis (JIAs) is the most common chronic rheumatic disease of childhood and is an important cause of disability. The folic acid analog methotrexate is the first choice disease-modifying anti-rheumatic drug in this disease, however, 35-45\% of patients fail to respond. Molecular elements, such as variants in genes of pharmacological relevance, influencing response to methotrexate in JIA, would be important to individualize treatment strategies. Several studies have evaluated the effects of candidate genetic variants in the complex pathway of genes involved in methotrexate pharmacodynamics and pharmacokinetics, however, results are still contrasting and no definitive genetic marker of methotrexate response useful for the clinician to tailor therapy of children with JIA has been identified. Recently, genome-wide approaches have been applied, identifying new potential biological processes involved in methotrexate response in JIA such as TGF-beta signaling and calcium channels. If these genomic results are properly validated and integrated with innovative analyses comprising deep sequencing, epigenetics, and pharmacokinetics, they will greatly contribute to personalize therapy with methotrexate in children with JIA.

}, issn = {1663-9812}, doi = {10.3389/fphar.2015.00052}, author = {Pastore, Serena and Stocco, Gabriele and Favretto, Diego and De Iudicibus, Sara and Taddio, Andrea and d{\textquoteright}Adamo, Pio and Malus{\`a}, Noelia and Addobbati, Riccardo and Decorti, Giuliana and Lepore, Loredana and Ventura, Alessandro} } @article {1653, title = {Fasting increases tobramycin oral absorption in mice.}, journal = {Antimicrob Agents Chemother}, volume = {54}, year = {2010}, month = {2010 Apr}, pages = {1644-6}, abstract = {

The pharmacokinetics of the aminoglycoside tobramycin was evaluated after oral administration to fed or fasting (15 h) mice. As expected, under normal feeding conditions, oral absorption was negligible; however, fasting induced a dramatic increase in tobramycin bioavailability. The dual-sugar test with lactulose and l-rhamnose confirmed increased small bowel permeability via the paracellular route in fasting animals. When experiments aimed at increasing the oral bioavailability of hydrophilic compounds are performed, timing of fasting should be extremely accurate.

}, keywords = {Administration, Oral, Animals, Anti-Bacterial Agents, Biological Availability, Fasting, Injections, Intramuscular, Injections, Intravenous, Intestinal Absorption, Lactulose, Male, Mice, Mice, Inbred BALB C, Rhamnose, Tobramycin}, issn = {1098-6596}, doi = {10.1128/AAC.01172-09}, author = {De Leo, Luigina and Di Toro, Nicola and Decorti, Giuliana and Malus{\`a}, Noelia and Ventura, Alessandro and Not, Tarcisio} } @article {1706, title = {Usefulness of the measurement of azathioprine metabolites in the assessment of non-adherence.}, journal = {J Crohns Colitis}, volume = {4}, year = {2010}, month = {2010 Nov}, pages = {599-602}, abstract = {

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.

}, keywords = {6-Mercaptopurine, Adolescent, Azathioprine, Child, Child, Preschool, Female, Guanine Nucleotides, Hepatitis, Autoimmune, Humans, Immunosuppressive Agents, Inflammatory Bowel Diseases, Male, Medication Adherence, Thionucleotides, Young Adult}, issn = {1876-4479}, doi = {10.1016/j.crohns.2010.04.003}, author = {Stocco, Gabriele and Londero, Margherita and Campanozzi, Angelo and Martelossi, Stefano and Marino, Sara and Malus{\`a}, Noelia and Bartoli, Fiora and Decorti, Giuliana and Ventura, Alessandro} }