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1. Erratum: Correction: Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence (eLife (2020) 9 PII: e80871)

Author

Alessio N., Squillaro T., Di Bernardo G., Galano G., De Rosa R., Melone M. A. B., Peluso G., Galderisi U., Alessio, N., Squillaro, T., Di Bernardo, G., Galano, G., De Rosa, R., Melone, M. A. B., Peluso, G., and Galderisi, U.

Subjects
medicine, stem cells, regenerative medicine, human, mouse
Abstract

Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.

Published
2022

2. Ngs in hereditary ataxia: When rare becomes frequent

Author

Galatolo, D., De Michele, G., Silvestri, Gabriella, Leuzzi, V., Casali, C., Musumeci, O., Antenora, A., Astrea, G., Barghigiani, M., Battini, R., Battisti, C., Caputi, C., Cioffi, E., Dotti, M. T., Fico, T., Fiorillo, C., Galosi, S., Lieto, M., Malandrini, A., Melone, M. A. B., Mignarri, A., Natale, G., Pegoraro, E., Petrucci, A., Ricca, I., Riso, V., Rossi, Salvatore, Rubegni, A., Scarlatti, A., Tinelli, F., Trovato, R., Tedeschi, G., Tessa, A., Filla, A., Santorelli, F. M., Silvestri G. (ORCID:0000-0002-1950-1468), Rossi S., Galatolo, D., De Michele, G., Silvestri, Gabriella, Leuzzi, V., Casali, C., Musumeci, O., Antenora, A., Astrea, G., Barghigiani, M., Battini, R., Battisti, C., Caputi, C., Cioffi, E., Dotti, M. T., Fico, T., Fiorillo, C., Galosi, S., Lieto, M., Malandrini, A., Melone, M. A. B., Mignarri, A., Natale, G., Pegoraro, E., Petrucci, A., Ricca, I., Riso, V., Rossi, Salvatore, Rubegni, A., Scarlatti, A., Tinelli, F., Trovato, R., Tedeschi, G., Tessa, A., Filla, A., Santorelli, F. M., Silvestri G. (ORCID:0000-0002-1950-1468), and Rossi S.

Abstract

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia‐dominated phenotypes. Massive gene analysis in next‐generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP‐based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.

Published
2021

3. POLR3A variants in hereditary spastic paraparesis and ataxia: clinical, genetic, and neuroradiological findings in a cohort of Italian patients

Author

Di Donato, I., Gallo, A., Ricca, I., Fini, N., Silvestri, Gabriella, Gurrieri, Fiorella, Cirillo, M., Cerase, A., Natale, G., Matrone, F., Riso, V., Melone, M. A. B., Tessa, A., De Michele, G., Federico, A., Filla, A., Dotti, M. T., Santorelli, F. M., Silvestri G. (ORCID:0000-0002-1950-1468), Gurrieri F. (ORCID:0000-0002-6775-5972), Di Donato, I., Gallo, A., Ricca, I., Fini, N., Silvestri, Gabriella, Gurrieri, Fiorella, Cirillo, M., Cerase, A., Natale, G., Matrone, F., Riso, V., Melone, M. A. B., Tessa, A., De Michele, G., Federico, A., Filla, A., Dotti, M. T., Santorelli, F. M., Silvestri G. (ORCID:0000-0002-1950-1468), and Gurrieri F. (ORCID:0000-0002-6775-5972)

Abstract

Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to milder and later-onset gait disorders with central hypomyelination, with or without additional non-neurological signs. Recently, a milder phenotype consisting of late-onset spastic ataxia without hypomyelinating leukodystrophy has been suggested to be specific to the intronic c.1909 + 22G > A mutation in POLR3A. Here, we present 10 patients from 8 unrelated families with POLR3A-related late-onset spastic ataxia, all harboring the c.1909 + 22G > A variant. Most of them showed an ataxic-spastic picture, two a “pure” cerebellar phenotype, and one a “pure” spastic presentation. The non-neurological findings typically associated with POLR3A mutations were absent in all the patients. The main findings on brain MRI were bilateral hyperintensity along the superior cerebellar peduncles on FLAIR sequences, observed in most of the patients, and cerebellar and/or spinal cord atrophy, found in half of the patients. Only one patient exhibited central hypomyelination. The POLR3A mutations present in this cohort were the c.1909 + 22G > A splice site variant found in compound heterozygosity with six additional variants (three missense, two nonsense, one splice) and, in one patient, with a novel large deletion involving exons 14–18. Interestingly, this patient had the most “complex” presentation among those observed in our cohort; it included some neurological and non-neurological features, such as seizures, neurosensory deafness, and lipomas, that have not previously been reported in association with late-onset POLR3A-related disorders, and therefore further expand the phenotype.

Published
2021

4. Neuroacanthocytosis Syndromes in an Italian Cohort: Clinical Spectrum, High Genetic Variability and Muscle Involvement

Author

Vaisfeld, A., Bruno, G., Petracca, M., Bentivoglio, A. R., Servidei, S., Vita, M. G., Bove, F., Straccia, G., Dato, C., Di Iorio, G., Sampaolo, S., Peluso, S., De Rosa, A., De Michele, G., Barghigiani, M., Galatolo, D., Tessa, A., Santorelli, F., Chiurazzi, P., Melone, M. A. B., Vaisfeld A., Petracca M., Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Servidei S. (ORCID:0000-0001-8478-2799), Vita M. G., Bove F., Chiurazzi P. (ORCID:0000-0001-5104-1521), Vaisfeld, A., Bruno, G., Petracca, M., Bentivoglio, A. R., Servidei, S., Vita, M. G., Bove, F., Straccia, G., Dato, C., Di Iorio, G., Sampaolo, S., Peluso, S., De Rosa, A., De Michele, G., Barghigiani, M., Galatolo, D., Tessa, A., Santorelli, F., Chiurazzi, P., Melone, M. A. B., Vaisfeld A., Petracca M., Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Servidei S. (ORCID:0000-0001-8478-2799), Vita M. G., Bove F., and Chiurazzi P. (ORCID:0000-0001-5104-1521)

Abstract

Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis, progressive degeneration of the basal ganglia and neuromuscular features with characteristic persistent hyperCKemia. The main NA syndromes include autosomal recessive chorea-acanthocytosis (ChAc) and X-linked McLeod syndrome (MLS). A series of Italian patients selected through a multicenter study for these specific neurological phenotypes underwent DNA sequencing of the VPS13A and XK genes to search for causative mutations. Where it has been possible, muscle biopsies were obtained and thoroughly investigated with histochemical assays. A total of nine patients from five different families were diagnosed with ChAC and had mostly biallelic changes in the VPS13A gene (three nonsense, two frameshift, three splicing), while three patients from a single X-linked family were diagnosed with McLeod syndrome and had a deletion in the XK gene. Despite a very low incidence (only one thousand cases of ChAc and a few hundred MLS cases reported worldwide), none of the 8 VPS13A variants identified in our patients is shared by two families, suggesting the high genetic variability of ChAc in the Italian population. In our series, in line with epidemiological data, McLeod syndrome occurs less frequently than ChAc, although it can be easily suspected because of its X-linked mode of inheritance. Finally, histochemical studies strongly suggest that muscle pathology is not simply secondary to the axonal neuropathy, frequently seen in these patients, but primary myopathic alterations can be detected in both NA syndromes.

Published
2021

8. Autosomal‐dominant myopia associated to a novel <italic>P4HA2</italic> missense variant and defective collagen hydroxylation.

Author

Gianfrancesco, F., Napolitano, F., Esposito, T., Lombardi, L., Farina, O., Di Iorio, G., Sampaolo, S., Melone, M. A. B., Di Iorio, V., Testa, F., Simonelli, F., Tirozzi, A., and Reccia, M. G.

Subjects
HYDROXYLATION, COLLAGEN, GENOTYPES, PHENOTYPES, MYOPIA
Abstract

We recently described a complex multisystem syndrome in which mild‐moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole‐exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4‐hydroxylase,alpha‐polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4‐hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype‐phenotype correlations. [ABSTRACT FROM AUTHOR]

Published
2018
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10. Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

Author

Santoro, C., Giugliano, T., Melone, M. A. B., Cirillo, M., Schettino, C., Bernardo, P., Cirillo, G., Perrotta, S., and Piluso, G.

Subjects
SPINAL nerve diseases, NEUROFIBROMATOSIS 1, NOONAN syndrome, NEUROFIBROMA, NEUROPATHY
Abstract

Neurofibromatosis type 1 ( NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p. Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. [ABSTRACT FROM AUTHOR]

Published
2018
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15. RB and RB2/p130 genes demonstrate both specific and overlapping functions during the early steps of in vitro neural differentiation of marrow stromal stem cells.

Author

Jori, F. P., Melone, M. A. B, Napolitano, M. A., Cipollaro, M., Cascino, A., Giordano, A., and Galderisi, U.

Subjects
*CELL death, *STEM cells, *CELL proliferation, *IMMUNOCYTOCHEMISTRY, *CELLULAR therapy, *NEURONS
Abstract

Marrow stromal stem cells (MSCs) are stem-like cells that are currently being tested for their potential use in cell therapy for a number of human diseases. MSCs can differentiate into both mesenchymal and nonmesenchymal lineages. In fact, in addition to bone, cartilage and fat, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes. RB and RB2/p130 genes are involved in the differentiation of several systems. For this reason, we evaluated the role of RB and RB2/p130 in the differentiation and apoptosis of MSCs under experimental conditions that allow for MSC differentiation toward the neuron-like phenotype. To this end, we ectopically expressed either RB or RB2/p130 and monitored proliferation, differentiation and apoptosis in rat primary MSC cultures induced to differentiate toward the neuron-like phenotype. Both RB and RB2/P130 decreased cell proliferation rate. In pRb-overexpressing cells, the arrest of cell growth was also observed in the presence of the HDAC-inhibitor TSA, suggesting that its antiproliferative activity does not rely upon the HDAC pathway, while the addition of TSA to pRb2/p130-overexpressing cells relieved growth inhibition. TUNEL reactions and studies on the expression of genes belonging to the Bcl-2 family showed that while RB protected differentiating MSCs from apoptosis, RB2/p130 induced an increase of apoptosis compared to controls. The effects of both RB and RB2/p130 on programmed cell death appeared to be HDAC- independent. Molecular analysis of neural differentiation markers and immunocytochemistry revealed that RB2/p130 contributes mainly to the induction of generic neural properties and RB triggers cholinergic differentiation. Moreover, the differentiation potentials of RB2/p130 and RB appear to rely, at least in part, on the activity of HDACs.Cell Death and Differentiation (2005) 12, 65-77. doi:10.1038/sj.cdd.4401499 Published online 1 October 2004 [ABSTRACT FROM AUTHOR]

Published
2005
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20. Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization, In Vitro and In Vivo Studies

Author

Claudia Riccardi, Federica D’Aria, Filomena Anna Digilio, Maria Rosaria Carillo, Jussara Amato, Dominga Fasano, Laura De Rosa, Simona Paladino, Mariarosa Anna Beatrice Melone, Daniela Montesarchio, Concetta Giancola, Riccardi, C., D'Aria, F., Digilio, F. A., Carillo, M. R., Amato, J., Fasano, D., De Rosa, L., Paladino, S., Melone, M. A. B., Montesarchio, D., Giancola, C., Riccardi, Claudia, D'Aria, Federica, Digilio, Filomena Anna, Carillo, Maria Rosaria, Amato, Jussara, Fasano, Dominga, De Rosa, Laura, Paladino, Simona, Melone, Mariarosa Anna Beatrice, Montesarchio, Daniela, and Giancola, Concetta

Subjects
Huntingtin Protein, G-quadruplex, physico-chemical characterization, Animal, Organic Chemistry, Nuclear Proteins, aptamer, aptamers, Huntington’s disease, Drosophila melanogaster model, Nerve Tissue Proteins, General Medicine, Catalysis, Computer Science Applications, Inorganic Chemistry, Disease Models, Animal, Drosophila melanogaster, Huntington Disease, Nerve Tissue Protein, Animals, Physical and Theoretical Chemistry, cellular models, Drosophila melanogaster model, Molecular Biology, Spectroscopy, Nuclear Protein
Abstract

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.

Published
2022

21. The senescence-associated secretory phenotype (SASP) from mesenchymal stromal cells impairs growth of immortalized prostate cells but has no effect on metastatic prostatic cancer cells

Author

Gianfranco Peluso, Mariarosa Ab Melone, Tiziana Squillaro, Umberto Galderisi, Giovanni Di Bernardo, Domenico Aprile, Mauro Finicelli, Nicola Alessio, Alessio, N., Aprile, D., Squillaro, T., Di Bernardo, G., Finicelli, M., Melone, M. A. B., Peluso, G., Galderisi, U., Alessio, Nicola, Aprile, Domenico, Squillaro, Tiziana, Di Bernardo, Giovanni, Finicelli, Mauro, Melone, Mariarosa Ab, Peluso, Gianfranco, and Galderisi, Umberto

Subjects
Male, Senescence, Aging, senescence, Cell cycle checkpoint, In Vitro Techniques, Biology, Proinflammatory cytokine, Cell Line, Tumor, medicine, Humans, Neoplasm Metastasis, Cellular Senescence, Cell Line, Transformed, Cell Proliferation, Mesenchymal stem cell, mesenchymal stem cells, In Vitro Technique, fungi, Prostate, Prostatic Neoplasms, Cancer, Cell Biology, medicine.disease, Neoplasm Metastasi, secretome, Apoptosis, Cancer cell, Cancer research, Immortalised cell line, Research Paper, Human
Abstract

Senescent cells secrete inflammatory cytokines, proteases, and other factors, which are indicated as senescence-associated secretory phenotype (SASP). There are contrasting studies on the role of the SASP in cancer. Studies suggested that cancer cells may misuse the senescent secretome for their growth. Other investigations evidenced that the SASP may induce cancer growth arrest, senescence, or apoptosis. These conflicting data can be reconciled considering that cancer cells can coax senescent cells to secrete factors for their survival, thus abrogating the SASP’s anti-cancer effect. Cancer stage may also have an impact on the capacity of the SASP to block tumor proliferation and promote senescence. Indeed, senescence is associated with a permanent cell cycle arrest, which needs functional cell cycle checkpoints. We evaluated the SASP effect on the in vitro biological properties of PNT2 and PC3 cells, which are immortalized prostate cells and metastatic prostatic cancer cells, respectively. We evidenced that SASPs, coming either from mesenchymal stromal cells treated with H202 or with low X-ray doses, induced senescence of immortalized cells but not of cancer cells. Hence, the SASP released by acute senescent cells should be considered as an effective weapon against pre-tumorigenesis events rather than an anti-cancer mechanism acting on malignant cells.

Published
2019
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22. Quantitative Evaluation of Upright Posture by x-Ray and 3D Stereophotogrammetry with a New Marker Set Protocol in Late Onset Pompe Disease

Author

Simone Sampaolo, Allegra Fullin, Mariarosa A. B. Melone, Giacomo Lus, Filomena Napolitano, Luca Del Viscovo, Paolo De Blasiis, Chiara Terracciano, Mario Sansone, De Blasiis, P., Fullin, A., Sansone, M., Del Viscovo, L., Napolitano, F., Terracciano, C., Lus, G., Melone, M. A. B., and Sampaolo, S.

Subjects
3D Stereophotogrammetry, Adult, Male, Weakness, Population, Posture, Reproducibility of Result, Scoliosis, Lumbar, x-Ray, medicine, standing alignment, Humans, education, Late Onset Pompe Disease, Aged, Orthodontics, education.field_of_study, Pelvic girdle, business.industry, Glycogen Storage Disease Type II, Reproducibility of Results, Middle Aged, medicine.disease, Lordosi, Trunk, Sagittal plane, Radiography, medicine.anatomical_structure, Neurology, Case-Control Studies, Photogrammetry, Standing Position, Lordosis, marker set protocol, Female, Neurology (clinical), Ankle, medicine.symptom, business, Case-Control Studie, Human
Abstract

Background: Late Onset Pompe Disease (LOPD) is a rare myopathy characterized by prevailing weakness of trunk and pelvic girdle muscles that causes motor disabilities. Spinal deformities have been reported unclearly on clinical examination. No study quantitatively assessed upright posture defining specific alterations of LOPD various phenotype. Objective: Identify postural abnormalities in a homogeneous group of LOPD patients using 3D Stereophotogrammetry (St) and x-Ray (xR). Methods: Seven LOPD siblings were recruited. They were assessed by clinical scales and, in upright posture, using xR and 3D-St with a new marker set protocol. Fourteen healthy individuals, age and sex-matched, were used as controls for St-parameters; normative xR-values were found in literature. Results: LOPD patients showed a significant weakness of trunk and tibialis anterior muscles. Statistical analysis of St-parameters showed a larger ankle, knee, elbow, dorsal, S2-C7, heel-S2-C7, heel-S2-nasion angles and a lower sagittal vertical axis (SVA) than controls. xR-analysis highlighted an absence of scoliosis and a lower occipito-cervical, C2-C7 cervical and Cobb dorsal angles, and a trend to lower lumbar lordosis and SVA compared to normal values. Significant correlation was found in dorsal and lumbar angles calculated using xR-markers placed on spiny apophysis, xR-centre of vertebral bodies, Cobb-method and St-markers. Conclusion: This is the first quantitative study of postural abnormalities in LOPD patients using 3D-St and xR, highlighting sagittal standing alignment changes, difficult to assess to direct exam.Our new St-protocol showed a high reliability compared to xR. Further studies on larger population of LOPD might confirm the usefulness of these instrumental methods for monitoring disease course.

Published
2021

23. 'One Health' Approach for Health Innovation and Active Aging in Campania (Italy)

Author

Cristina Ponsiglione, Giovanni Tramontano, Giovanni Annuzzi, Maddalena Illario, Rosa Zampetti, Anna Marro, Jean Bousquet, Giannamaria Vallefuoco, Regina Roller-Wirnsberger, Guido Iaccarino, Gaetano Cafiero, Alberto Lombardi, Aurelio Crudeli, Giancarlo Bracale, Maria Triassi, Mariarosa A. B. Melone, Mario Losasso, Donatella Tramontano, Umberto Bracale, Maurizio Taglialatela, Maria Luisa Chiusano, Luigi Riccio, Vincenzo De Luca, Carmine Vecchione, Ugo Trama, Francesco Cacciatore, Pietro Buono, De Luca, V., Tramontano, G., Riccio, L., Trama, U., Buono, P., Losasso, M., Bracale, U. M., Annuzzi, G., Zampetti, R., Cacciatore, F., Vallefuoco, G., Lombardi, A., Marro, A., Melone, M. A. B., Ponsiglione, C., Chiusano, M. L., Bracale, G., Cafiero, G., Crudeli, A., Vecchione, C., Taglialatela, M., Tramontano, D., Iaccarino, G., Triassi, M., Roller-Wirnsberger, R., Bousquet, J., Illario, M., De Luca, Vincenzo, Tramontano, Giovanni, Riccio, Luigi, Trama, Ugo, Buono, Pietro, Losasso, Mario, Marcello Bracale, Umberto, Annuzzi, Giovanni, Zampetti, Rosa, Cacciatore, Francesco, Vallefuoco, Giannamaria, Lombardi, Alberto, Marro, Anna, Melone, Mariarosa Anna Beatrice, Ponsiglione, Cristina, Luisa Chiusano, Maria, Bracale, Giancarlo, Cafiero, Gaetano, Crudeli, Aurelio, Vecchione, Carmine, Taglialatela, Maurizio, Tramontano, Donatella, Iaccarino, Guido, Triassi, Maria, Roller-Wirnsberger, Regina, and Bousquet and Maddalena Illario, Jean

Subjects
Aging, Economic growth, Population, digital health, Review, information and communication technologies, silver economy, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), active and healthy aging, Health care, health innovation, Humans, 030212 general & internal medicine, education, Ecosystem, health care economics and organizations, Health policy, Aged, education.field_of_study, information and communication technologie, business.industry, future health and health care, Public Health, Environmental and Occupational Health, health policy, Digital health, One Health, Italy, 030228 respiratory system, General partnership, Sustainability, Quality of Life, Public Health, Business, Public aspects of medicine, RA1-1270, Human
Abstract

This article describes how innovations are exploited in Campania (Italy) to improve health outcomes, quality of life, and sustainability of social and healthcare services. Campania's strategy for digitalization of health and care and for healthy aging is based on a person-centered, life-course, “One Health” approach, where demographic change is considered capable of stimulating a growth dynamic linked to the opportunities of combining the “Silver Economy” with local assets and the specific health needs of the population. The end-users (citizens, patients, and professionals) contribute to the co-creation of products and services, being involved in the identification of unmet needs and test-bed activity. The Campania Reference Site of the European Innovation Partnership on Active and Healthy Aging is a flexible regional ecosystem to address the challenge of an aging population with a life-course approach. The good practices, developed in the context of research and innovation projects and innovative procurements by local stakeholders and collaborations with international networks, have been allowing the transfer of innovative solutions, knowledge, and skills to the stakeholders of such a multi-sectoral ecosystem for health.

Published
2021
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24. Nanoparticle-guided brain drug delivery: Expanding the therapeutic approach to neurodegenerative diseases

Author

Filomena Napolitano, Mariarosa A. B. Melone, Claudia Riccardi, Simone Sampaolo, Daniela Montesarchio, Riccardi, C., Napolitano, F., Montesarchio, D., Sampaolo, S., Melone, M. A. B., Riccardi, Claudia, Napolitano, Filomena, Montesarchio, Daniela, Sampaolo, S, and Melone, Mariarosa Anna Beatrice

Subjects
Disease onset, media_common.quotation_subject, nanoformulations, Drug delivery system, Pharmaceutical Science, Disease, Review, Blood–brain barrier, Neurodegenerative disease, Nose-to-brain delivery, Therapeutic approach, drug delivery systems, Pharmacy and materia medica, medicine, neurodegenerative diseases, Internalization, media_common, Brain targeting, Heterogeneous group, business.industry, RS1-441, medicine.anatomical_structure, Nanoformulation, Drug delivery, Targeted delivery, business, Neuroscience
Abstract

Neurodegenerative diseases (NDs) represent a heterogeneous group of aging-related disorders featured by progressive impairment of motor and/or cognitive functions, often accompanied by psychiatric disorders. NDs are denoted as ‘protein misfolding’ diseases or proteinopathies, and are classified according to their known genetic mechanisms and/or the main protein involved in disease onset and progression. Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are included under this nosographic umbrella, sharing histopathologically salient features, including deposition of insoluble proteins, activation of glial cells, loss of neuronal cells and synaptic connectivity. To date, there are no effective cures or disease-modifying therapies for these NDs. Several compounds have not shown efficacy in clinical trials, since they generally fail to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells that greatly limits the brain internalization of endogenous substances. By engineering materials of a size usually within 1–100 nm, nanotechnology offers an alternative approach for promising and innovative therapeutic solutions in NDs. Nanoparticles can cross the BBB and release active molecules at target sites in the brain, minimizing side effects. This review focuses on the state-of-the-art of nanoengineered delivery systems for brain targeting in the treatment of AD, PD and HD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2021

25. Short and long term effects of Nabiximols on balance and walking assessed by 3D-gait analysis in people with Multiple Sclerosis and spasticity

Author

Paolo De Blasiis, Giacomo Lus, Mario Sansone, Elisabetta Signoriello, Allegra Fullin, Maria Francesca Siani, Simone Sampaolo, Mariarosa A. B. Melone, De Blasiis, Paolo, Siani, Maria Francesca, Fullin, Allegra, Sansone, Mario, Melone, Mariarosa Anna Beatrice, Sampaolo, Simone, Signoriello, Elisabetta, Lus, Giacomo, De Blasiis, P., Siani, M. F., Fullin, A., Sansone, M., Melone, M. A. B., Sampaolo, S., Signoriello, E., and Lus, G.

Subjects
medicine.medical_specialty, Multiple Sclerosis, Nabiximols, Walking, Nabiximol, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, gait analysi, Drug Combination, Multiple Sclerosi, medicine, Numeric Rating Scale, Humans, Cannabidiol, 030212 general & internal medicine, Spasticity, Dronabinol, Balance (ability), business.industry, Multiple sclerosis, spasticity, balance, General Medicine, medicine.disease, Sativex, Safety profile, Drug Combinations, Neurology, Tolerability, Muscle Spasticity, Gait analysis, Neurology (clinical), medicine.symptom, business, Gait Analysis, 030217 neurology & neurosurgery, medicine.drug, Human
Abstract

Background Spasticity in people with Multiple Sclerosis (pwMS) is one of the most disabling symptoms on walking ability and balance. Among the systemic antispastic drugs, Nabiximols showed a good tolerability, safety profile and relevant efficacy. A few studies assessed long-term effects of this drug through clinical scales and instrumental tools, but no study investigated short-term effects. The aim of our study is to quantitatively evaluate the immediate effects of Nabiximols on walking and balance and their maintenance after 4 weeks in pwMS and spasticity. Methods pwMS were enrolled and randomized in 2 treatment groups: Sativex (SG) and control (CG) group. All patients were assessed at T0 (before the first Sativex puff), T1(after 45 minutes) and T2 (after 4 weeks of treatment) using clinical scales and 3d-Gait Analysis . Then, the patients treated with Sativex, were divided into 5 subgroups according to Numeric Rating Scale for spasticity (NRSs) and Berg Balance Score (BBS) response: NRSs responder[1] and non-[2]; BBS responders[3] and non-[4]; NRSs-BBS responders[5]. Results 32 pwMS (22 SG, 10 CG) were recruited. Significant improvements were found between T0 and T1 in SG compared to CG in a few clinical and kinematic parameters. Larger significant differences were found for NRSs and BBS responders’ groups versus CG. Eventually, no significant differences were found comparing the results between T1 and T2, suggesting the persistence of the improvements emerged at T1. Conclusion These results quantitatively demonstrated a short time effect of Nabiximols on balance and walking of pwMS, which is mantained after 4 weeks. Patients identified as responder by combination of NRSs and BBS showed the best efficacy. These findings may suggest how to early select the real responders in order to improve the adherence and cost-effectiveness of the therapy.

Published
2021

26. Vacuolated PAS‐positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy

Author

Giuseppina Franzese, Giovanni Panella, Luca Lombardi, Simone Sampaolo, Silvia Boffo, Olimpia Farina, Giancarlo la Marca, Francesco Tuccillo, Angelo Pascarella, Chiara Terracciano, Teresa Esposito, Sergio Bernardini, Filomena Napolitano, Giuseppe Di Iorio, Antonio Giordano, Mariarosa A. B. Melone, Pascarella, A., Terracciano, C., Farina, O., Lombardi, L., Esposito, T., Napolitano, F., Franzese, G., Panella, G., Tuccillo, F., la Marca, G., Bernardini, S., Boffo, S., Giordano, A., Melone, M. A. B., Di Iorio, G., and Sampaolo, S.

Subjects
Male, 0301 basic medicine, Pathology, Physiology, Clinical Biochemistry, Vacuole, Compound heterozygosity, medicine.disease_cause, screening method for glycogenosis, chemistry.chemical_compound, 0302 clinical medicine, Lymphocytes, Child, Mutation, Glycogen, Glycogen Storage Disease Type II, Settore BIO/12, Pompe disease, glycogen storage myopathies, Middle Aged, GSD II diagnostic algorithm, PAS-positive lymphocytic granules, Cell Biology, Female, medicine.symptom, PAS-positive lymphocytic granule, Adult, medicine.medical_specialty, Adolescent, Offspring, Young Adult, 03 medical and health sciences, Glycogen storage myopathie, Autophagy, medicine, Humans, Muscle, Skeletal, Aged, business.industry, Muscle weakness, alpha-Glucosidases, 030104 developmental biology, chemistry, Vacuoles, Lysosomes, business, 030217 neurology & neurosurgery, Immunostaining
Abstract

Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-?-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects. Number of lymphocytes containing PAS-positive vacuoles was evaluated on blood films from 72 consecutive adult patients with hyperckemia and/or muscle weakness, 13 genetically confirmed late-onset-Pompe-disease (LOPD) and 13 of their offspring. GAA activity, measured on dried blood spot (DBS) in all patients inversely correlated with number of PAS-positive lymphocytes. More than 4 PAS-positive lymphocytes were found in 11 out of the 72 patients (6 new diagnosis of LOPD, 3 different glycogen storage myopathies, 1 glucose-6-phosphate dehydrogenase deficiency, 1 caveolinopathy), in all 13 LOPD patients and in the 13 LOPD offspring. These latter resulted to have all a single GAA mutation but low GAA levels. Immunostaining with the autophagy markers LC3 and p62 confirmed the autophagic nature of lymphocytes vacuoles. ROC curve assessment of PAS-positive lymphocytes disclosed 100% of sensitivity and 94% of specificity in recognizing both compound heterozygous and heterozygous GAA carriers. The other myopathies with more than 4 PAS-positive lymphocytes appeared to be all related to impaired autophagy, which seems to be responsible of PAS-positive vacuolated lymphocytes formation. Quantification of PAS-positive lymphocytes in blood films is useful to identify autophagic vacuolar myopathies and should be routinely used as first level test for Pompe disease.

Published
2018
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27. 'Borderline' idiopathic CD4+ T-cell lymphocytopenia presenting with atypical progressive multifocal leukoencephalopathy

Author

Andrea Elefante, Gianfranco Puoti, Antonella Costagliola, Mariarosa A. B. Melone, Cinzia Coppola, Giorgia Bruno, Giacomo Lus, Clemente Dato, Dato, C., Elefante, A., Coppola, C., Melone, M. A. B., Lus, G., Costagliola, A., Bruno, G., and Puoti, G.

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Immunology, +, 03 medical and health sciences, 0302 clinical medicine, Progressive multifocal leukoencephalopathy, medicine, Immunology and Allergy, T cell lymphocytopenia, PML, Cd4 t cell, John Cunningham vviru, business.industry, Idiopathic CD4, medicine.disease, ICL, JCV, 030104 developmental biology, Neurology, Neurology (clinical), Lymphocytopenia, business, 030217 neurology & neurosurgery
Abstract

Idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder characterized by low counts of CD4+ cells (

Published
2020

28. Successful long-term therapy with flecainide in a family with paramyotonia congenita

Author

Filomena Napolitano, Paolo De Blasiis, Vincenzo Todisco, Giuseppe Di Iorio, Simone Sampaolo, Olimpia Farina, Teresa Esposito, Luca Lombardi, Sergio Bernardini, Francesco Tuccillo, Mariarosa A. B. Melone, Gianluca Ciccone, Chiara Terracciano, Terracciano, C., Farina, O., Esposito, T., Lombardi, L., Napolitano, F., de Blasiis, P., Ciccone, G., Todisco, V., Tuccillo, F., Bernardini, S., di Iorio, G., Melone, M. A. B., Sampaolo, S., Terracciano, Chiara, Farina, Olimpia, Teresa, Esposito, Lombardi, Luca, Filomena, Napolitano, de Blasiis, Paolo, Ciccone, Gianluca, Todisco, Vincenzo, Tuccillo, Francesco, Bernardini, Sergio, DI IORIO, Giuseppe, Melone, Mariarosa Anna Beatrice, and Sampaolo, Simone

Subjects
0301 basic medicine, medicine.medical_specialty, Weakness, channel, Electromyography, 03 medical and health sciences, 0302 clinical medicine, Sodium channel blocker, Internal medicine, Mexiletine, medicine, Flecainide, medicine.diagnostic_test, business.industry, Sodium channel, Settore BIO/12, medicine.disease, Myotonia, Psychiatry and Mental health, 030104 developmental biology, myotonia, emg, quality of life, Paramyotonia congenita, Cardiology, Surgery, Neurology (clinical), Paramyotonia congenita (PC), sodium channel gene (SCN4A), flecainide, medicine.symptom, pharmacology, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Paramyotonia congenita (PC) is a neuromuscular disorder caused by point mutations of the sodium channel gene SCN4A that leads to gating defects in the sodium channel of the muscle membranes, thus resulting in a persistent sodium influx into the sarcoplasma. Classic PC phenotype is characterised by episodes of cold-induced stiffness, prominently in the facial and upper limb muscles, exacerbated by a sustained muscular activity (paramyotonia) and followed by a variable degree of weakness. Electromyography (EMG) at rest discloses myotonic bursts and reduced Compound Muscle Action Potential (CMAP) amplitudes, while short-term forearm exercise and cooling tests induce further decrease resulting in electrical silence in some patients. Muscle paralysis, after paramyotonic attacks, may last from a few dozen minutes to 24–48 hours, thus reducing considerable quality of life and autonomy in daily activities. Among voltage-gating sodium channel blockers, mexiletine is considered the drug of choice in PC and other sodium channel myopathies.1 However, mexiletine efficacy has been investigated only in a few heterogeneous small PC series during a month-lasting follow-up. In experimental studies, flecainide, a class IC antiarrhythmic drug, appeared to be more effective than mexiletine to counteract SCN4A dysfunction.2 However, we lack long-term follow-up studies on flecainide efficiency in patients with PC with homogeneous pheno/genotype. The aim of this study was to assess the responsiveness to flecainide in a large family with classic PC phenotype by electrophysiological and quality of life evaluations. The Italian PC family pedigree includes 60 …

Published
2018
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29. Migraine as possible red flag of PFO presence in suspected demyelinating disease

Author

Giacomo Lus, Gianfranco Puoti, G. Maresca, Mario Cirillo, G. Signoriello, Alberto Negro, A. Rapacciuolo, E. Koci, Mariarosa A. B. Melone, Elisabetta Signoriello, Signoriello, E., Cirillo, M., Puoti, G., Signoriello, G., SPINA NEGRO, Annamaria, Kocid, E., Melone, M. A. B., Rapacciuolo, A., Maresca, G., Lus, G., Negro, A., and Koci, E.

Subjects
Adult, Male, Migraine without Aura, medicine.medical_specialty, Demyelinating disease, Aura, Migraine with Aura, Foramen Ovale, Patent, 030204 cardiovascular system & hematology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, PFO, medicine, Humans, Migraine, Retrospective Studies, medicine.diagnostic_test, Lumbar puncture, business.industry, Oligoclonal Bands, Brain, Heart, Magnetic resonance imaging, medicine.disease, Hyperintensity, Spinal Cord, Neurology, Patent foramen ovale, Female, Neurology (clinical), Radiology, Differential diagnosis, business, 030217 neurology & neurosurgery, Demyelinating Diseases, Follow-Up Studies
Abstract

Objectives To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura. Materials 31 migraine patients, 28 females and 3 males, with MRI evidence of white matter lesions suggestive of demyelinating disease according to the Barkhof Criteria. All patients underwent further diagnostics including lumbar puncture, autoimmunity panel and cardiological evaluation to detect the presence of PFO. The mean duration of follow-up was 3.46 years and MIPAV software was used to analyze MRI imaging. Results 14 of the 31 patients (45%) had PFO. A significant association was found between PFO and migraine with visual aura (p

Published
2018

30. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

Author

Peluso, I., Conte, I., Testa, F., Dharmalingam, G., Pizzo, M., Collin, R.W.J., Meola, N., Barbato, S., Mutarelli, M., Ziviello, C., Barbarulo, A.M., Nigro, V., Melone, M.A., Simonelli, F., Banfi, S., Baere, E. de, Koenekoop, R.K., Leroy, B.P., Cremers, F.P., Kohl, S., Hamel, C., Ayuso, C., Wissinger, B., Inglehearn, C.F., Toomes, C., Hollander, A.I. den, Peluso, I., Conte, I., Testa, F., Dharmalingam, G., Pizzo, M., Collin, R. W. J., Meola, Nicola, Barbato, S., Mutarelli, M., Ziviello, C., Barbarulo, A. M., Nigro, V., Melone, M. A. B., Simonelli, F., Banfi, S., Peluso, I, Conte, I, Testa, F, Dharmalingam, G, Pizzo, M, Collin, Rwj, Meola, N, Barbato, S, Mutarelli, M, Ziviello, C, Barbarulo, Am, Nigro, V, Melone, M, Simonelli, F, and Banfi, S

Subjects
Genetics and epigenetic pathways of disease [NCMLS 6], Oryzias, PROTEIN, lcsh:Medicine, CHILDREN, ADAMTS Protein, DISEASE, MOLECULAR-GENETICS, ADAMTS Proteins, 0302 clinical medicine, Medicine and Health Sciences, Missense mutation, Knobloch syndrome, Genetics(clinical), Pharmacology (medical), Exome, Age of Onset, Genetics (clinical), Exome sequencing, Genetics, Medicine(all), 0303 health sciences, Inherited retinal dystrophies, General Medicine, ADAMTS18, Disease gene identification, 3. Good health, Human, EXPRESSION, ADAM Protein, Molecular Sequence Data, LEBER CONGENITAL AMAUROSIS, Genes, Recessive, Biology, ITALIAN PATIENTS, Polymorphism, Single Nucleotide, 03 medical and health sciences, Homozygosity mapping, Retinal Dystrophies, RETINITIS-PIGMENTOSA, KNOBLOCH SYNDROME, Retinitis pigmentosa, medicine, Animals, Humans, Amino Acid Sequence, Inherited retinal dystrophie, Medaka fish, 030304 developmental biology, Oryzia, Sequence Homology, Amino Acid, MUTATIONS, Genetic heterogeneity, Animal, Research, lcsh:R, Retinal Dystrophie, medicine.disease, ADAM Proteins, Mutation, Eye disorder, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], 030217 neurology & neurosurgery
Abstract

BACKGROUND: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. METHODS: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction. RESULTS: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. CONCLUSION: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases. Background: Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes.Methods: An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes) model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS) dysfunction.Results: This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function.Conclusion: This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

Published
2013

31. Reasons driving treatment modification in Parkinson's disease: Results from the cross-sectional phase of the REASON study

Author

Tinazzi, M, Abbruzzese, G, Antonini, A, Ceravolo, R, Fabbrini, G, Lessi, P, Barone, P, REASON Study Group:Abruzzese, G, Lido, V, Melone, M, Schettino, C, Califano, F, Ceravolo, M, Capecci, M, Andrenelli, E, Iemolo, F, Spadaro, D, Carnemolla, A, Pontieri, F, Pellicano, C, Benincasa, D, Pietracupa, S, Latorre, A, Tedeschi, G, Tessitore, A, Giordano, A, Bonuccelli, U, Frosini, D, Vanelli, F, Comi, G, Volonté, M, Spagnolo, F, Scaglioni, A, Abrignani, G, Avanzino, L, Tamburini, T, Facchini, S, Biundo, R, Altavista, M, Roberti, C, Asteggiano, G, L'Episcopo, M, Saracco, E, Avarello, T, Bono, G, Riboldazzi, G, Leva, S, Del, S, Carabelli, M, E, Traverso, E, Michelucci, R, Nassetti, S, Pasini, E, Padovani, A, Cottini, E, Bigni, B, Ruggieri, S, Modugno, N, Fischetti, M, Stefani, A, Pierantozzi, M, Bassi, M, Ottaviani, S, Ajena, D, Trianni, G, My, F, Caggiula, M, Valenti, G, Grioli, S, La Farina, I, Zambito Marsala, S, Marchini, C, Gioulis, M, Picillo, M, Moccia, M, Denaro, A, Sebastianelli, L, Onofrj, M, Thomas, A, Marini, C, De Santis, F, Spagnoli, V, L'Erario, R, Passadore, P, Belgrado, E, Mucchiut, M, Priori, A, Cogiamanian, F, Marchet, A, Tinazzi, M, Abbruzzese, G, Antonini, A, Ceravolo, R, Fabbrini, G, Lessi, P, Barone, P, Lido, V, Melone, M, Schettino, C, Califano, F, Ceravolo, Mg, Capecci, M, Andrenelli, E, Iemolo, F, Spadaro, D, Carnemolla, A, Pontieri, F, Pellicano, C, Benincasa, D, Pietracupa, S, Latorre, A, Tedeschi, G, Tessitore, A, Giordano, A, Bonuccelli, U, Frosini, D, Vanelli, F, Comi, G, Volonté, M, Spagnolo, F, Scaglioni, A, Abrignani, G, Avanzino, L, Tamburini, T, Facchini, S, Biundo, R, Altavista, M, Roberti, C, Asteggiano, G, L'Episcopo, M, Saracco, E, Avarello, T, Bono, G, Riboldazzi, G, Leva, S, Del, Sette, M, Carabelli, E, Traverso, E, Michelucci, R, Nassetti, S, Pasini, E, Padovani, A, Cottini, E, Bigni, B, Ruggieri, S, Modugno, N, Fischetti, M, Stefani, A, Pierantozzi, M, Bassi, M, Ottaviani, S, Ajena, D, Trianni, G, My, F, Caggiula, M, Valenti, G, Grioli, S, La, Farina, I, Zambito, Marsala, S, Marchini, C, Gioulis, M, Picillo, M, Moccia, M, Denaro, A, Sebastianelli, L, Onofrj, M, Thomas, A, Marini, C, De, Santi, F, Spagnoli, V, L'Erario, R, Passadore, P, Belgrado, E, Mucchiut, M, Priori, A, Cogiamanian, F, Marchet, A., Tinazzi, M., Abbruzzese, G., Antonini, A., Ceravolo, R., Fabbrini, G., Lessi, P., Barone, P., Melone, M. A. B., Schettino, C., Califano, F., Ceravolo, M. G., Capecci, M., Andrenelli, E., Iemolo, F., Spadaro, D., Carnemolla, A., Pontieri, F. E., Pellicano, C., Benincasa, D., Pietracupa, S., Latorre, A., Tedeschi, G., Tessitore, A., Giordano, A., Bonuccelli, U., Frosini, D., Vanelli, F., Comi, G., Volonte, M. A., Spagnolo, F., Scaglioni, A., Abrignani, G., Avanzino, L., Tamburini, T., Facchini, S., Biundo, R., Altavista, M. C., Roberti, C., Asteggiano, G., L'Episcopo, M. R., Saracco, E., Avarello, T., Bono, G., Riboldazzi, G., Leva, S., Del Sette, M., Carabelli, E., Traverso, E., Michelucci, R., Nassetti, S., Pasini, E., Padovani, A., Cottini, E., Bigni, B., Ruggieri, S., Modugno, N., Fischetti, M., Stefani, A., Pierantozzi, M., Stampanoni Bassi, M., Ottaviani, S., Ajena, D., Trianni, G., My, F., Caggiula, M., Valenti, G., Grioli, S., La Farina, I., Zambito Marsala, S., Marchini, C., Gioulis, M., Picillo, M., Moccia, M., Denaro, A., Sebastianelli, L., Onofrj, M., Thomas, A., Marini, C., De Santis, F., Spagnoli, V., L'Erario, R., Passadore, P., Belgrado, E., Mucchiut, M., Priori, A., Cogiamanian, F., Lessi, and Comi, Giancarlo

Subjects
Male, Pediatrics, Parkinson's disease, anti-Parkinson drugs, motor symptoms, non-motor symptoms, Practice Patterns, Socioeconomic Factor, Motor symptoms, Severity of Illness Index, Antiparkinson Agents, Cohort Studies, Motor symptom, Practice Patterns, Physicians', Stage (cooking), Anti-Parkinson drug, Anti-Parkinson drugs, Non-motor symptoms, Aged, Female, Humans, Middle Aged, Parkinson Disease, Patient Satisfaction, Socioeconomic Factors, Geriatrics and Gerontology, Neurology (clinical), Neurology, musculoskeletal, neural, and ocular physiology, Antiparkinson Agent, cardiovascular system, Settore MED/26 - Neurologia, Treatment modification, Human, medicine.medical_specialty, Non-motor symptom, Disease severity, medicine, In patient, Physicians', business.industry, Advanced stage, medicine.disease, nervous system diseases, Physical therapy, Treatment decision making, Cohort Studie, business
Abstract

OBJECTIVES: To assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy. METHODS: Subjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment. RESULTS: 775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1-2 (early PD) and 49% with HY stage 2.5-4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms. CONCLUSIONS: Neurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.

Published
2013

32. Nano-delivery systems for encapsulation of dietary polyphenols: An experimental approach for neurodegenerative diseases and brain tumors.

Author

Squillaro T, Cimini A, Peluso G, Giordano A, and Melone MAB

Subjects
Animals, Antioxidants administration & dosage, Antioxidants chemistry, Antioxidants metabolism, Brain Neoplasms metabolism, Clinical Trials as Topic methods, Humans, Nanoparticles chemistry, Nanoparticles metabolism, Neurodegenerative Diseases metabolism, Neuroprotective Agents administration & dosage, Neuroprotective Agents chemistry, Neuroprotective Agents metabolism, Phytochemicals chemistry, Phytochemicals metabolism, Polyphenols chemistry, Polyphenols metabolism, Brain Neoplasms prevention & control, Drug Delivery Systems methods, Nanoparticles administration & dosage, Neurodegenerative Diseases prevention & control, Phytochemicals administration & dosage, Polyphenols administration & dosage
Abstract

Neurodegenerative diseases (NDs) and brain tumors are severe, disabling, and incurable disorders that represent a critical problem regarding human suffering and the economic burden on the healthcare system. Because of the lack of effective therapies to treat NDs and brain tumors, the challenge for physicians is to discover new drugs to improve their patients' quality of life. In addition to risk factors such as genetics and environmental influences, increased cellular oxidative stress has been reported as one of the potential common etiologies in both disorders. Given their antioxidant and anti-inflammatory potential, dietary polyphenols are considered to be one of the most bioactive natural agents in chronic disease prevention and treatment. Despite the protective activity of polyphenols, their inefficient delivery systems and poor bioavailability strongly limit their use in medicine and functional food. A potential solution lies in polymeric nanoparticle-based polyphenol delivery systems that are able to enhance their absorption across the gastrointestinal tract, improve their bioavailability, and transport them to target organs. In the present manuscript, we provide an overview of the primary polyphenols used for ND and brain tumor prevention and treatment by focusing on recent findings, the principal factors limiting their application in clinical practice, and a promising delivery strategy to improve their bioavailability., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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33. Migraine as possible red flag of PFO presence in suspected demyelinating disease.

Author

Signoriello E, Cirillo M, Puoti G, Signoriello G, Negro A, Koci E, Melone MAB, Rapacciuolo A, Maresca G, and Lus G

Subjects
Adult, Brain diagnostic imaging, Demyelinating Diseases complications, Diagnosis, Differential, Female, Follow-Up Studies, Foramen Ovale, Patent complications, Heart diagnostic imaging, Humans, Male, Migraine with Aura complications, Migraine without Aura complications, Migraine without Aura diagnosis, Oligoclonal Bands cerebrospinal fluid, Retrospective Studies, Spinal Cord diagnostic imaging, Demyelinating Diseases diagnosis, Foramen Ovale, Patent diagnosis, Migraine with Aura diagnosis
Abstract

Objectives: To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura., Materials: 31 migraine patients, 28 females and 3 males, with MRI evidence of white matter lesions suggestive of demyelinating disease according to the Barkhof Criteria. All patients underwent further diagnostics including lumbar puncture, autoimmunity panel and cardiological evaluation to detect the presence of PFO. The mean duration of follow-up was 3.46 years and MIPAV software was used to analyze MRI imaging., Results: 14 of the 31 patients (45%) had PFO. A significant association was found between PFO and migraine with visual aura (p < 0.001). No difference in lesion number, volume or area between patients with and without PFO was found, but the distribution was mainly occipital (p < 0.001) in patients with PFO. The follow-up showed a stationary lesion load in all PFO patients; no infratentorial or spinal cord lesion and no enhancement or corpus callosum lesion was ever detected. At the end of follow-up four patients developed multiple sclerosis: younger age at first MRI and oligoclonal bands were associated risk factors., Conclusions: Migraine is often one of the main symptoms leading to MRI, and in many cases white matter lesions of unspecific significance are discovered, thus placing demyelinating diseases in the differential diagnosis. Our study underlines the potential pathogenetic role of PFO in generating white matter lesions in migraine patients (45%), particularly those with visual aura and occipital lesions. For this reason, we affirm that PFO represents a cardinal point in the differential diagnosis of suspected demyelinating disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
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34. Efficient cultivation of neural stem cells with controlled delivery of FGF-2.

Author

Galderisi U, Peluso G, Di Bernardo G, Calarco A, D'Apolito M, Petillo O, Cipollaro M, Fusco FR, and Melone MA

Subjects
Animals, Cell Differentiation drug effects, Cell Proliferation drug effects, Cells, Cultured, Electrolytes chemistry, Heparitin Sulfate chemistry, Hydrogel, Polyethylene Glycol Dimethacrylate chemistry, Kinetics, Mice, Neural Stem Cells cytology, Polymers chemistry, Cell Culture Techniques methods, Fibroblast Growth Factor 2 pharmacology, Neural Stem Cells drug effects
Abstract

Neural stem cells (NSCs) raised the hope for cell-based therapies in human neurodevelopmental and neurodegenerative diseases. Current research strategies aim to isolate, enrich, and propagate homogeneous populations of neural stem cells. Unfortunately, several concerns with NSC cultures currently may limit their therapeutic promise. Exhaustion of growth factors and/or their uncontrolled release with burst and fall in their concentration may greatly affect the in vitro behavior of NSCs. In this context, we investigate whether a device containing heparan sulfate (HS), which is a co-factor in growth factor-mediated cell proliferation and differentiation, could potentiate and prolong the delivery of fibroblast growth factor-2 (FGF-2) and thus improve in vitro NSC cultivation. We demonstrated that NSCs cultivated in media with a controlled release of FGF-2 from a polyelectrolyte polymer showed a higher proliferation rate, and reduced apoptosis and senescence. In these experimental conditions NSCs preserve their stemness properties for a longer period of time compared with controls. Also of interest is that cell fate properties are conserved as well. The controlled release of FGF-2 reduced the level of oxidative stress and this is associated with a lower level of damaged DNA. This result may explain the reduced level of senescence and apoptosis in NSCs cultivated in the presence of hydrogel-releasing FGF-2., (Copyright © 2012. Published by Elsevier B.V.)

Published
2013
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35. Neurofibromatosis type 1 and optic pathway glioma. A long-term follow-up.

Author

Lama G, Esposito Salsano M, Grassia C, Calabrese E, Grassia MG, Bismuto R, Melone MA, Russo S, and Scuotto A

Subjects
Adolescent, Adult, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Intracranial Hypertension epidemiology, Magnetic Resonance Imaging, Male, Neurofibromatosis 1 pathology, Optic Chiasm pathology, Optic Nerve Glioma pathology, Prevalence, Remission, Spontaneous, Retrospective Studies, Severity of Illness Index, Time Factors, Neurofibromatosis 1 epidemiology, Optic Nerve Glioma epidemiology, Visual Pathways pathology
Abstract

Aim: Optic pathway gliomas (OPG) are the predominant intracranial tumours associated with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the prevalence and the outcome of OPG in 200 NF1 patients (122 males and 78 females, aged 1-25 years) followed up to 16 years (mean of 6 years)., Methods: All children were evaluated by a detailed physical, neurological and ophthalmological examination. Fifteen out of 200 (7.5%) of these patients (7 males, 8 females) were identified with evidence of optic pathway tumours., Results: Nine children had symptoms such as endocranial hypertension, seizures, headache; 4 patients only showed anomalies at ophthalmological examination; 2 patients had no symptoms or signs. All children had evidence of optic pathway tumour on magnetic resonance imaging. Three had a prechiasmal tumour, 2 had a chiasmal tumour, 1 had prechiasmal/chiasmal tumour, 2 had a prechiasmal/chiasmal and postchiasmal tumour, 2 had a chiasmal and postchiasmal tumour, 4 had a massive involvement of the optic system, 1 child exhibited a bilateral involvement of the optic nerves with additional impairment of the chiasm. Four patients had partial and/or subtotal spontaneous regression., Conclusions: Because optic pathway tumours arise in children younger than 6 years of age, all NF1 children should undergo yearly ophtalmologic examination and growth assessment to monitor signs of precocious puberty.

Published
2007

36. EGF-responsive rat neural stem cells: molecular follow-up of neuron and astrocyte differentiation in vitro.

Author

Jori FP, Galderisi U, Piegari E, Cipollaro M, Cascino A, Peluso G, Cotrufo R, Giordano A, and Melone MA

Subjects
Animals, Animals, Newborn, Apoptosis drug effects, Apoptosis physiology, Astrocytes cytology, Astrocytes drug effects, Astrocytes metabolism, Blood Proteins drug effects, Blood Proteins genetics, Blood Proteins metabolism, Cell Cycle Proteins drug effects, Cell Cycle Proteins metabolism, Cell Differentiation physiology, Cell Lineage physiology, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, Glial Fibrillary Acidic Protein drug effects, Glial Fibrillary Acidic Protein genetics, Glial Fibrillary Acidic Protein metabolism, Immunohistochemistry, Intermediate Filament Proteins drug effects, Intermediate Filament Proteins genetics, Intermediate Filament Proteins metabolism, Nestin, Neurons cytology, Neurons drug effects, Neurons metabolism, Proto-Oncogene Proteins c-bcl-2 drug effects, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, RNA, Messenger drug effects, RNA, Messenger metabolism, Rats, Retinoblastoma Protein drug effects, Retinoblastoma Protein genetics, Retinoblastoma Protein metabolism, Retinoblastoma-Like Protein p130, Stem Cells cytology, Stem Cells drug effects, Tumor Suppressor Protein p53 drug effects, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins drug effects, Tumor Suppressor Proteins metabolism, Cell Culture Techniques methods, Cell Differentiation drug effects, Cell Lineage drug effects, Cell Separation methods, Epidermal Growth Factor pharmacology, Nerve Tissue Proteins, Proteins, Stem Cell Transplantation methods, Stem Cells metabolism
Abstract

Neural stem cells (NSCs) could be very useful for the "cell therapy" treatment of neurological disorders. For this reason basic studies aiming to well characterize the biology of NSCs are of great interest. We carried out a molecular and immunocytochemical analysis of EGF-responsive NSCs obtained from rat pups. After the initial growth of NSCs as floating neurospheres in EGF-containing medium, cells were plated on poly-L-ornithine-coated dishes either in the presence or absence of EGF. We followed cell differentiation and apoptosis for 21 days in vitro and analyzed the expression levels of some genes having a major role in these processes, such as pRB, pRB2/p130, p27, and p53. We observed that EGF impairs neuronal differentiation. Furthermore, in the absence of mitogens, apoptosis, which appeared to proceed through the "p53 network," was significantly lower than in the presence of EGF. The cyclin kinase inhibitor p27, while important for cell cycle exit, seemed dispensable for cell survival and differentiation., (Copyright 2003 Wiley-Liss, Inc.)

Published
2003
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