Lucia Santoro

Publications (13)35.77 Total impact

• Article: Plasmatic kinetics of dermatan sulfate during enzyme replacement therapy with iduronate-2-sulfatase in a mucopolysaccharidosis II Patient.

  Nicola Volpi, Lucia Zampini, Francesca Maccari, Lucia Santoro, Fabio Galeotti, Tiziana Galeazzi, Orazio Gabrielli, Giovanni V Coppa
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  ABSTRACT: Enzyme replacement therapy (ERT) is the worldwide standard of care for a number of mucopolysaccharidosis (MPS) diseases. We report a kinetic study of plasmatic dermatan sulfate (DS) in a 3-year-old subject affected by a severe form of MPS II during the first 10 months of ERT with Idursulfase. A strong increase in the DS plasmatic concentration was measured immediately after the first enzyme infusion, with a maximum after 3 h, followed by a continuous decrease in the 8-15 days following the beginning of treatment. After this, a constant plasmatic content of DS concentration was observed. Overall, during the 10-month treatment period, ERT reduced the plasmatic concentration of DS up to ~80-85 %, but it was unable to totally remove it from the blood. We can suppose that immediately after the first enzyme administrations, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and thereafter only minimal changes are observed. The persistency of the residual amounts of DS with the actually recommended dosage in our Patient may suggest the opportunity to promote further studies with increased enzyme dosages to completely remove the accumulation of lysosomal DS.
  Glycoconjugate Journal 03/2013; · 2.12 Impact Factor
• Article: Human milk glycosaminoglycans: the state of the art and future perspectives.

  Giovanni Valentino Coppa, Orazio Gabrielli, Enrico Bertino, Lucia Zampini, Tiziana Galeazzi, Lucia Padella, Lucia Santoro, Rita Lucia Marchesiello, Fabio Galeotti, Francesca Maccari, Nicola Volpi
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  ABSTRACT: Recently, a complete characterization and detailed evaluation of the glycosaminoglicans of human milk were performed. The total glycosaminoglican content in milk from healthy mothers having delivered term or preterm newborns showed a constant pattern which was essentially composed of two main polysaccharides: chondroitin sulfate (60-70%) and heparin (30-40%). Moreover, considerable variations of glycosaminoglican concentration were found during the first month of lactation, the highest values being present in colostrum compared to mature milk. Metabolism and potential biological functions of human milk glycosaminoglicans are hypothesized and future studies are encouraged.
  Italian Journal of Pediatrics 01/2013; 39(1):2.
• Article: Mild mental retardation and low levels of urinary heparan sulfate in a patient with the attenuated phenotype of Mucopolysaccharidosis type IIIA.

  Giovanni V Coppa, Fabio Galeotti, Lucia Zampini, Tiziana Galeazzi, Lucia Padella, Lucia Santoro, Francesca Maccari, Orazio Gabrielli, Nicola Volpi
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  ABSTRACT: OBJECTIVES: We report the case of a 28-year-old female subject affected by the attenuated phenotype of mucopolysaccharidosis type IIIA characterized by moderate slowly evolving mental retardation in which the urinary content of heparan sulfate was demonstrated as being substantially low compared to that found in patients with the severe phenotype. DESIGN AND METHODS: The specific evaluation of macromolecular heparan sulfate by electrophoresis and the determination of related glucosamine in the urine were performed. RESULTS: In our patient, the urinary macromolecular heparan sulfate content (4.2 μg/mg creatinine) was ~7.5-times higher than in healthy subjects (0.56 μg/mg creatinine ± 0.9 SD) while it was ~28-times lower compared to the severe mucopolysaccharidosis IIIA group (117 μg/mg creatinine ± 44.8 SD). Furthermore, the urinary glucosamine (86.4 μg/mg creatinine) was ~2.4-times greater than in healthy subjects (36.0 μg/mg creatinine ± 18.2 SD) but ~2.4-times lower than in severe subjects (208.1 μg/mg creatinine ± 55.0 SD). CONCLUSIONS: The above data could reflect the reduced heparan sulfate storage in her tissues and organs, and in particular in the brain, consequently explaining her moderate mental retardation. Furthermore, the clinical presentation of patients with an attenuated form of MPS III confirms the need for a specific evaluation of urinary GAGs in all young and adult subjects showing a not well-defined or not particularly severe mental retardation, along with an early MPS diagnosis. Such investigation should also be associated with a more specific characterization of heparan sulfate.
  Clinical biochemistry 12/2012; · 2.02 Impact Factor
• Article: On-line high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry profiling of human milk oligosaccharides derivatized with 2-aminoacridone.

  Fabio Galeotti, Giovanni V Coppa, Lucia Zampini, Francesca Maccari, Tiziana Galeazzi, Lucia Padella, Lucia Santoro, Orazio Gabrielli, Nicola Volpi
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  ABSTRACT: A high-resolution normal-phase high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry separation and structural characterization of the main oligosaccharides along with lactose from human milk samples is described. A total of 22 commercially available oligosaccharides were fluorotagged with 2-aminoacridone and separated on an amide column and identified on the basis of their retention times and mass spectra. Derivatized species having mass lower than approximately 800 to 900 exhibited mainly [M-H](-1) anions, oligomers with mass up to approximately 1000 to 1100 were represented by both [M-H](-1) and [M-2H](-2) anions, and oligomers greater than approximately 1200 to 1300 were characterized by a charge state of -3. Furthermore, the retention times were directly related to the glycans' molecular mass. Human milk samples from the four groups of donors (Se±/Le±) were analyzed for their composition and amount of free oligosaccharides after rapid and simple prepurification and derivatization steps also in the presence of lactose in high content. This analytical approach enabled us to perform the determination of species not detected by traditional techniques, such as sialic acid, as well as of species present in low content easily mistaken with other peaks. Finally, labeled human milk oligosaccharides were analyzed without any interference from excess fluorophore or interference from proteins, peptides, salts, and other impurities normally present in this complex biological fluid.
  Analytical Biochemistry 08/2012; 430(1):97-104. · 3.00 Impact Factor
• Article: Plasmatic and Urinary Glycosaminoglycans Characterization in Mucopolysaccharidosis II Patient Treated with Enzyme-Replacement Therapy with Idursulfase.

  Giovanni V Coppa, Dania Buzzega, Lucia Zampini, Francesca Maccari, Lucia Santoro, Fabio Galeotti, Tiziana Galeazzi, Orazio Gabrielli, Nicola Volpi
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  ABSTRACT: We report the structural characterization of plasmatic and urinary GAGs in a patient affected by MPS II (Hunter syndrome) before and during the first 10 months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% ΔDi4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% ΔDi4s with minor percentages of monosulfated and disulfated disaccharides, in particular ΔDi2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich ΔDi4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% ΔDi4s, ~11% ΔDi6s and ~4% ΔDi0s with the persistence of ΔDi2,4dis (~4%). About 40% of IdoA-formed ΔDi4s were also calculated, thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about 2 weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following 9 months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures.
  JIMD reports. 01/2012; 4:79-90.
• Article: Preterm milk oligosaccharides during the first month of lactation.

  Orazio Gabrielli, Lucia Zampini, Tiziana Galeazzi, Lucia Padella, Lucia Santoro, Chiara Peila, Francesca Giuliani, Enrico Bertino, Claudio Fabris, Giovanni V Coppa
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  ABSTRACT: Oligosaccharides represent one of the main components of human milk, and they have been assigned important biological functions for newborns. Qualitatively and quantitatively, their presence in milk is strictly related to the expression of the mother's Se and/or Le genes, on the basis of which 4 different milk groups have been described. The aim of the study was to provide new data on the oligosaccharide composition of preterm milk in relation to the 4 groups. High-pH anion-exchange chromatography was used to quantify levels of 23 oligosaccharides and lactose in 252 milk samples collected from 63 mothers during the first month of lactation and to identify the 4 milk groups. Substantial differences in oligosaccharide contents were found within the groups and were strictly related to the presence or absence of specific fucosyl-oligosaccharides. The highest concentration was found in group 1 (>20 g/L), the lowest level was found in group 4 (∼10 g/L), and intermediate values were observed in groups 2 and 3. No statistically significant differences in lactose concentrations were observed among the groups. Our data confirm lower lactose concentrations in preterm milk, compared with term milk, and they provide the first detailed characterization of oligosaccharides in preterm milk, demonstrating important differences in oligosaccharide contents in the 4 groups. These differences might exert an influence on several biological functions that are particularly important for preterm infants and currently are attributed to milk oligosaccharides.
  PEDIATRICS 12/2011; 128(6):e1520-31. · 4.47 Impact Factor
• Article: Agarose-gel electrophoresis for the diagnosis of mucopolysaccharidoses.

  Giovanni V Coppa, Dania Buzzega, Lucia Zampini, Francesca Maccari, Tiziana Galeazzi, Lucia Padella, Lucia Santoro, Orazio Gabrielli, Nicola Volpi
  Clinical Chemistry and Laboratory Medicine 11/2011; 50(3):589-92. · 2.15 Impact Factor
• Article: Oligosaccharides in 4 different milk groups, Bifidobacteria, and Ruminococcus obeum.

  Giovanni V Coppa, Orazio Gabrielli, Lucia Zampini, Tiziana Galeazzi, Anna Ficcadenti, Lucia Padella, Lucia Santoro, Sara Soldi, Antonio Carlucci, Enrico Bertino, Lorenzo Morelli
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  ABSTRACT: The aim of this study was to identify a link between the total amount of breast milk oligosaccharides and faecal microbiota composition of newborns at the end of the first month of life, with special attention paid to bifidobacteria, and establish the role, if any, of the different oligosaccharides in determining the gut microbiota composition. Milk oligosaccharide groups were identified by high-performance anion exchange chromatography analysis. DPCRNA from newborns' faecal samples at 30 days of life was isolated and processed by polymerase chain reaction analyses that allow the identification of 6 species of bifidobacteria (adolescentis, bifidum, breve, catenulatum, longum, infantis) and Ruminococcus spp; denaturing gradient gel electrophoresis analysis was also performed. No substantial differences in bifidobacteria species composition within milk groups 1, 2, and 3 were observed; however, infants fed with group 4 milk show a microbiota characterised by a greater frequency of Bifidobacteria adolescentis and the absence of Bifidobacteria catenulatum. For the first time, a high percentage of the Ruminococcus genus in infants fed with all milk groups was found. Our data show that milk groups 1, 2, and 3, containing an amount of oligosaccharides ranging within 10 to 15 g/L, share a substantially identical composition of the intestinal microbiota in breast-fed infants, despite quali-quantitative difference in oligosaccharides content. Newborns taking milk with only 5 g/L of oligosaccharides (group 4) harbour a different intestinal microbiota.
  Journal of pediatric gastroenterology and nutrition 07/2011; 53(1):80-7. · 2.18 Impact Factor
• Article: Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation.

  Luca Tiano, Lucia Padella, Lucia Santoro, Paola Carnevali, Federica Principi, Francesca Brugè, Orazio Gabrielli, Gian Paolo Littarru
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  ABSTRACT: Oxidative stress is known to play a relevant role in Down syndrome (DS) and its effects are documented from embryonic life. Oxidative DNA damage has been shown to be significantly elevated in Down syndrome patients, and this has been indicated as an early event promoting neurodegeneration and Alzheimer type dementia. The aim of this study was to investigate the efficacy of coenzyme Q(10) (CoQ(10)) in delaying the effect of oxidative damage in these patients. In our previous study we demonstrated a mild protective effect of CoQ(10) on DNA, although the treatment was unable to modify the overall extent of oxidative damage at the patient level. Possible limitations of the previous study were: time of treatment (6 months) or spectrum of DNA lesions detected. In order to overcome these limitations we planned a continuation of the trial aimed at evaluating the effects of CoQ(10) following a prolonged treatment. Our results highlight an age-specific reduction in the percentage of cells showing the highest amount of oxidized bases, indicating a potential role of CoQ(10) in modulating DNA repair mechanisms.
  Neurobiology of aging 05/2011; 33(3):626.e1-8. · 5.94 Impact Factor
• Article: High-throughput determination of urinary hexosamines for diagnosis of mucopolysaccharidoses by capillary electrophoresis and high-performance liquid chromatography.

  Giovanni V Coppa, Fabio Galeotti, Lucia Zampini, Francesca Maccari, Tiziana Galeazzi, Lucia Padelia, Lucia Santoro, Orazio Gabrielli, Nicola Volpi
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  ABSTRACT: Mucopolysaccharidoses (MPS) diagnosis is often delayed and irreversible organ damage can occur, making possible therapies less effective. This highlights the importance of early and accurate diagnosis. A high-throughput procedure for the simultaneous determination of glucosamine and galactosamine produced from urinary galactosaminoglycans and glucosaminoglycans by capillary electrophoresis (CE) and HPLC has been performed and validated in subjects affected by various MPS including their mild and severe forms, Hurler and Hurler-Scheie, Hunter, Sanfilippo, Morquio, and Maroteaux-Lamy. Contrary to other analytical approaches, the present single analytical procedure, which is able to measure total abnormal amounts of urinary GAGs, high molecular mass, and related fragments, as well as specific hexosamines belonging to a group of GAGs, would be useful for possible application in their early diagnosis. After a rapid urine pretreatment, free hexosamines are generated by acidic hydrolysis, derivatized with 2-aminobenzoic acid and separated by CE/UV in ∼10min and reverse-phase (RP)-HPLC in fluorescence in ∼21min. The total content of hexosamines was found to be indicative of abnormal urinary excretion of GAGs in patients compared to the controls, and the galactosamine/glucosamine ratio was observed to be related to specific MPS syndromes in regard to both their mild and severe forms. As a consequence, important correlations between analytical response and clinical diagnosis and the severity of the disorders were observed. Furthermore, we can assume that the severity of the syndrome may be ascribed to the quantity of total GAGs, as high-molecular-mass polymers and fragments, accumulated in cells and directly excreted in the urine. Finally, due to the high-throughput nature of this approach and to the equipment commonly available in laboratories, this method is suitable for newborn screening in preventive public health programs for early detection of MPS disorders, diagnosis, and their treatment.
  Analytical Biochemistry 04/2011; 411(1):32-42. · 3.00 Impact Factor
• Article: Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy.

  Renzo Manara, Elena Priante, Marco Grimaldi, Lucia Santoro, Luca Astarita, Rita Barone, Daniela Concolino, Maja Di Rocco, Maria Alice Donati, Simona Fecarotta, [......], Irene Giovannini, Franco Lilliu, Rodica Mardari, Gabriele Polonara, Elena Procopio, Angelica Rampazzo, Andrea Rossi, Graziolina Sanna, Rossella Parini, Maurizio Scarpa
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  ABSTRACT: BACKGROUD: Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce. To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT). Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1-16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales. Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes. The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.
  Journal of Inherited Metabolic Disease 04/2011; 34(3):763-80. · 3.58 Impact Factor
• Article: Mental retardation, facial anomalies, brachydactyly, cerebral angiomas, femoral nucleus necrosis: a new entity or Hall-Riggs syndrome?

  Anna Ficcadenti, Lucia Santoro, Valeria Petroni, Cecilia Carini, Orazio Gabrielli
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  ABSTRACT: We report on a 4-year-old boy with mental retardation, facial and skeletal anomalies, cerebral angiomas, femoral nucleus necrosis, mild biochemical abnormalities. This complex of features resembles the Hall-Riggs syndrome but could represent a novel syndrome.
  American Journal of Medical Genetics Part A 05/2009; 149A(5):1001-5. · 2.39 Impact Factor
• Article: Assessment of DNA damage in Down Syndrome patients by means of a new, optimised single cell gel electrophoresis technique.

  Luca Tiano, Gian Paolo Littarru, Federica Principi, Marco Orlandi, Lucia Santoro, Paola Carnevali, Orazio Gabrielli
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  ABSTRACT: Single cell gel electrophoresis (SCGE), also known as comet assay is a widely used method to detect DNA damage. Its use is nonetheless subjected to some pitfalls, due to differences in experimental set-up, to operator-dependent variability and to quantification of the comets, which is usually accomplished by visual scoring or by image-analysis software. Biological variability in the extent of DNA damage must be taken into account particularly regarding in vivo studies. In the present paper we propose an improved methodology where major features are: a) cryopreservation of lymphocytes collected at different time points and simultaneous analysis in a single run; b) use of an internal control on each slide; c) development of a custom-made software with semi - automated image analysis in order to overcome operator dependent variability. Cryopreservation was accomplished by storing lymphocytes in liquid nitrogen in a solution commonly used for preserving vital cells to be reinfused. We found that this procedure did not alter DNA after 2 and 4 months of storage. The use of quality control from a batch of aliquoted lymphocytes from a healthy donor on each slide, enabled to highlight possible experimental anomalies as well as verify inter-experimental variability. Moreover, by using a newly developed software able to automatically recognise comets we minimised operator-dependent variability in the scoring process. This improved methodology is proposed for longitudinal in vivo studies and in the present work its application made it possible to assess a significant increase of DNA in pediatric Down Syndrome patients compared to healthy controls of the same age.
  BioFactors 02/2005; 25(1-4):187-95. · 4.93 Impact Factor