@article {10783, title = {Gadolinium tissue deposition in the periodontal ligament of mice with reduced renal function exposed to Gd-based contrast agents.}, journal = {Toxicol Lett}, volume = {301}, year = {2019}, month = {2019 Feb}, pages = {157-167}, abstract = {

Gadolinium deposition in tissue is linked to nephrogenic systemic fibrosis (NSF): a rare disorder occurring in patients with severe chronic kidney disease and associated with administration of Gd-based contrast agents (GBCAs) for Magnetic Resonance Imaging (MRI). It is suggested that the GBCAs prolonged permanence in blood in these patients may result in a Gd precipitation in peripheral or central organs, where it initiates a fibrotic process. In this study we investigated new sites of retention/precipitation of Gd in a mouse model of renal disease (5/6 nephrectomy) receiving two doses (closely after each other) of a linear GBCA. Two commercial GBCAs (Omniscan{\textregistered} and Magnevist{\textregistered}) were administered at doses slightly higher than those used in clinical practice (0.7 mmol/kg body weight, each). The animals were sacrificed one month after the last administration and the explanted organs (kidney, liver, femur, dorsal skin, teeth) were analysed by X-ray fluorescence (XRF) at two synchrotron facilities. The XRF analysis with a millimetre-sized beam at the SYRMEP beamline (Elettra, Italy) produced no detectable levels of Gd in the examined tissues, with the notable exception of the incisors of the nephrectomised mice. The XRF analyses at sub-micron resolution performed at ID21 (ESRF, France) allowed to clearly localize Gd in the periodontal ligaments of teeth both from Omniscan{\textregistered} and Magnevist{\textregistered} treated nephrectomised mice. The latter results were further confirmed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The study prompts that prolonged permanence of GBCAs in blood may result in Gd retention in this particular muscular tissue, opening possibilities for diagnostic applications at this level when investigating Gd-related toxicities.

}, keywords = {Animals, Contrast Media, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Gadolinium, Gadolinium DTPA, Magnetic Resonance Imaging, Mice, Nephrogenic Fibrosing Dermopathy, Periodontal Ligament, Renal Insufficiency, Tissue Distribution}, issn = {1879-3169}, doi = {10.1016/j.toxlet.2018.11.014}, author = {Delfino, Riccarda and Biasotto, Matteo and Candido, Riccardo and Altissimo, Matteo and Stebel, Marco and Salom{\`e}, Murielle and van Elteren, Johannes T and Vogel Miku{\v s}, Katarina and Zennaro, Cristina and {\v S}ala, Martin and Addobbati, Riccardo and Tromba, Giuliana and Pascolo, Lorella} } @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 {3476, title = {Influence of urine volume on the assessment of intestinal permeability in affected children by multiple sugar probes.}, journal = {Clin Chem Lab Med}, volume = {52}, year = {2014}, month = {2014 Feb}, pages = {227-35}, abstract = {

BACKGROUND: In this study we have looked at the reliability of a multi-sugar test in a pediatric patient population and its accuracy at small urine volumes to evaluate intestinal permeability.

METHODS: Out of 117 subjects enrolled, 31 were healthy and 86 were sick. A solution containing lactulose, rhamnose, sucrose, and sucralose was administered to subjects who were on fasting; the urine excreted during 5 h was collected and measured. Samples were analyzed by gas chromatography-tandem mass spectrometry and results were expressed as percentage of sugar recoveries and lactulose/rhamnose (L/R) ratio.

RESULTS: The analyses showed a clear effect of low urinary volumes (<=240 mL) particularly affecting rhamnose excretion in healthy subjects and sucrose and sucralose recovery in diseased children. Despite the low rhamnose recovery, as lactulose is not similarly affected, the diagnostic reliability of L/R ratio is well preserved at low diuresis conditions. However, this ratio can be useful to discriminate acute conditions vs. clinical remissions only at high urine volumes. Data also suggest potential diagnostic applicability of sucrose and sucralose in children at high urine volumes.

CONCLUSIONS: In conclusion, the multi-sugar test has a good predictivity in pediatric subjects but results must be carefully interpreted in the face of reduced diuresis.

}, keywords = {Carbohydrates, Child, Preschool, Diuresis, Female, Gas Chromatography-Mass Spectrometry, Gastrointestinal Diseases, Humans, Infant, Intestines, Lactulose, Male, Permeability, Rhamnose, Sucrose}, issn = {1437-4331}, doi = {10.1515/cclm-2013-0626}, author = {Addobbati, Riccardo and Pascolo, Lorella and Di Toro, Nicola and Sebastiani, Giulia B and Martellossi, Stefano and Not, Tarcisio} } @article {1981, title = {Presence of CTAK/CCL27, MCP-3/CCL7 and LIF in human colostrum and breast milk.}, journal = {Cytokine}, volume = {61}, year = {2013}, month = {2013 Jan}, pages = {26-8}, abstract = {

Human colostrum and breast milk are known to contain high levels of cytokines and chemokines, which are thought to contribute to the development of the newborn. The aim of this study was to investigate the difference in the presence and levels of 21 soluble cytokines and chemokines in paired samples of human colostrum (day 2 after delivery) and breast milk (day 4-5 after delivery) by using the multiplex technology. Of the 21 cytokine investigated in 10 pairs of samples, only β-NGF was absent in both colostrum and milk, while INF-α2, SCF and TNF-β were present in colostrum but not in human milk. As a general rule, colostrum contained higher concentrations of cytokines and chemokines with respect to breast milk. The majority of cytokines, detected in colostrum alone or in colostrum and human milk (IL-1α, IL-2Rα, IL-3, IL-16, IL-18, GRO-α, HGF, IFN-α2, M-CSF, MIF, MIG, TNF-β, SDF-1α, TRAIL) have been described in previous studies, while for the first time we describe the presence of additional cytokines either in colostrum alone (SCF) or in both colostrum and breast milk (CTAK/CCL27, MCP-3/CCL7, LIF). Our data confirm and expand previous studies showing that some cytokines/chemokines, which might contribute to the development of the gastro-intestinal and nervous systems, are overexpressed in human colostrum and breast milk, and might contribute to the development of these systems.

}, keywords = {Adult, Chemokine CCL27, Chemokine CCL7, Chemokines, Colostrum, Cytokines, Female, Humans, Infant, Newborn, Leukemia Inhibitory Factor, Milk, Human}, issn = {1096-0023}, doi = {10.1016/j.cyto.2012.09.001}, author = {Radillo, Oriano and Norcio, Alessia and Addobbati, Riccardo and Zauli, Giorgio} } @article {1766, title = {Nutlin-3 differentially modulates miRNA34a and miRNA181 versus miR26a and miR155 in p53 proficient and p53 deficient B chronic lymphocytic leukemia (B-CLL) samples.}, journal = {Invest New Drugs}, volume = {30}, year = {2012}, month = {2012 Aug}, pages = {1761-5}, keywords = {Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Humans, Imidazoles, Leukemia, Lymphocytic, Chronic, B-Cell, MicroRNAs, Piperazines, Proto-Oncogene Proteins c-mdm2, Tumor Suppressor Protein p53}, issn = {1573-0646}, doi = {10.1007/s10637-011-9695-4}, author = {di Iasio, Maria Grazia and Addobbati, Riccardo and Radillo, Oriano and Voltan, Rebecca} } @article {1933, title = {Personalized therapies in pediatric inflammatory and autoimmune diseases.}, journal = {Curr Pharm Des}, volume = {18}, year = {2012}, month = {2012}, pages = {5766-75}, abstract = {

Pediatric inflammatory and autoimmune diseases are a wide array of systemic or organ-specific conditions, characterized by an exaggerated immune reactivity, which generally occurs in immunogenetically predisposed children. Among the most important ones, in terms of their diffusion and morbidity in the population worldwide, pediatric inflammatory bowel disease (IBD) and juvenile rheumatoid arthritis (JRA) have to be considered. The aim of personalized therapy is to give to each patient the most appropriate drug and dose regimen, in order to maximize treatment response and reduce the risk of adverse events. In general, several therapeutic options exist for pediatric inflammatory and autoimmune conditions, therefore the perspective of pharmacological tools that allow identification of patients with increased risk of treatment issues related to a particular medication, in terms of lack of efficacy or increased probability of adverse events, is particularly desirable and promising. The present review will be focused on the personalized therapy approaches already available or in development for pediatric patients with IBD or JRA, comprising pharmacokinetic, pharmacodynamic and pharmacogenetic assays.

}, keywords = {Arthritis, Rheumatoid, Autoimmune Diseases, Child, Genetic Predisposition to Disease, Humans, Immunogenetic Phenomena, Individualized Medicine, Inflammation, Inflammatory Bowel Diseases, Pharmacogenetics}, issn = {1873-4286}, author = {Stocco, Gabriele and De Iudicibus, Sara and Franca, Raffaella and Addobbati, Riccardo and Decorti, Giuliana} }