25 results on '"Vladimiro Pietrini"'
Search Results
2. Pesticide exposure assessed through agricultural crop proximity and risk of amyotrophic lateral sclerosis
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Marco Vinceti, Tommaso Filippini, Federica Violi, Kenneth J. Rothman, Sofia Costanzini, Carlotta Malagoli, Lauren A. Wise, Anna Odone, Carlo Signorelli, Laura Iacuzio, Elisa Arcolin, Jessica Mandrioli, Nicola Fini, Francesco Patti, Salvatore Lo Fermo, Vladimiro Pietrini, Sergio Teggi, Grazia Ghermandi, Renato Scillieri, Caterina Ledda, Cristina Mauceri, Salvatore Sciacca, Maria Fiore, and Margherita Ferrante
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Amyotrophic lateral sclerosis ,Pesticides ,Case-control study ,Epidemiology ,Risk ,Industrial medicine. Industrial hygiene ,RC963-969 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Epidemiologic studies have raised the possibility that some pesticide compounds induce the neurodegenerative disease amyotrophic lateral sclerosis (ALS), though the available evidence is not entirely consistent. Methods We conducted a population-based case-control study in two Italian populations to assess the extent to which residence in the vicinity of agricultural crops associated with the application of neurotoxic pesticides is a risk factor for ALS, using crop acreage in proximity to the residence as an index of exposure. Results Based on 703 cases and 2737 controls, we computed an ALS odds ratio of 0.92 (95% confidence interval 0.78-1.09) for those in proximity to agricultural land. Results were not substantially different when using alternative exposure categories or when analyzing specific crop types, with the exception of a higher risk related to exposure to citrus orchards and olive groves in Southern Italy, though based on few exposed subjects (N = 89 and 8, respectively). There was little evidence of any dose-response relation between crop proximity and ALS risk, and using long-term residence instead of current residence did not substantially change our estimates. Conclusions Though our index of exposure is indirect and subject to considerable misclassification, our results offer little support for the hypothesis that neurotoxic pesticide exposure increases ALS risk.
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- 2017
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3. A Rare Case of Systemic AL Amyloidosis with Muscle Involvement: A Misleading Diagnosis
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Fabrizio Accardi, Valentina Papa, Anna Rita Capozzi, Gian Luca Capello, Laura Verga, Cristina Mancini, Eugenia Martella, Roberta Costa, Laura Notarfranchi, Benedetta Dalla Palma, Franco Aversa, Vladimiro Pietrini, Giovanna Cenacchi, and Nicola Giuliani
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Muscle involvement in AL amyloidosis is a rare condition, and the diagnosis of amyloid myopathy is often delayed and underdiagnosed. Amyloid myopathy may be the initial manifestation and may precede the diagnosis of systemic AL amyloidosis. Here, we report the case of a 73-year-old man who was referred to our center for a monoclonal gammopathy of undetermined significance (MGUS) diagnosed since 1999. He reported a progressive weakness of proximal muscles of the legs with onset six months previously. Muscle biopsy showed mild histopathology featuring alterations of nonspecific type with a mixed myopathic and neurogenic involvement, and the diagnostic turning point was the demonstration of characteristic green birefringence under cross-polarized light following Congo red staining of perimysial vessels. Transmission electron microscopy (TEM) confirmed amyloid fibrils around perimysial vessels associated with collagen fibrils. A stepwise approach to diagnosis and staging of this disorder is critical and involves confirmation of amyloid deposition, identification of the fibril type, assessment of underlying amyloidogenic disorder, and evaluation of the extent and severity of amyloidotic organ involvement.
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- 2018
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4. Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study
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Francesca Bonvicini, Norina Marcello, Jessica Mandrioli, Vladimiro Pietrini, and Marco Vinceti
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sclerosi laterale amiotrofica ,pesticidi ,epidemiologia ,studi caso-controllo ,Public aspects of medicine ,RA1-1270 - Abstract
A few epidemiologic studies have suggested an association of agricultural work and pesticides exposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis (ALS), though conflicting results have also been provided. We investigated through a populationbased case-control study the possible relation between overall occupational exposure to pesticides and ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire, we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the 1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. More cases than controls were found to have been exposed to pesticides for at least six months (31.7% vs 13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regression model, we found an excess ALS risk associated with exposure to pesticides, with a relative risk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statistical analysis of potential confounders. Despite the limited statistical stability of the risk estimates, these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS, suggesting the need to further investigate this issue.
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- 2010
5. Living near waterbodies as a proxy of cyanobacteria exposure and risk of amyotrophic lateral sclerosis: a population based case-control study
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Jessica Mandrioli, Carlo Signorelli, Mario Zappia, Sofia Costanzini, Cristaldi Antonio, Gea Oliveri Conti, Maria Fiore, Valerio Mantione, Alessandra Nicoletti, Roberto Parisio, Tommaso Filippini, Armando Platania, Pietro Zuccarello, Marco Vinceti, Vladimiro Pietrini, Sergio Teggi, Anna Odone, and Margherita Ferrante
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Risk ,medicine.medical_specialty ,Epidemiology ,Cyanotoxins ,Population ,Disease ,010501 environmental sciences ,Cyanobacteria ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Environmental health ,Medicine ,Humans ,030212 general & internal medicine ,Amyotrophic lateral sclerosis ,education ,0105 earth and related environmental sciences ,General Environmental Science ,education.field_of_study ,business.industry ,Amyotrophic Lateral Sclerosis ,Case-control study ,Neurodegenerative Diseases ,Odds ratio ,Cyanotoxin ,medicine.disease ,Italy ,Case-Control Studies ,Residence ,business ,Amyotrophic lateral sclerosis, Cyanotoxins, Case-control study, Epidemiology, Risk - Abstract
Epidemiological studies highlighted the possibility that exposure to cyanotoxins leads to the development of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).We devised a population-based case-control study in two Italian populations. We used residential proximity of the residence to water bodies as a measure of possible exposure to cyanotoxins.Based on 703 newly-diagnosed ALS cases and 2737 controls, we calculated an ALS odds ratio (OR) of 1.41 (95% CI: 0.72-2.74) for current residence in the vicinity of water bodies, and a slightly lower estimate for historical residence (OR: 1.31; 95% CI: 0.57-2.99). Subjects65 years and people living in the Northern Italy province of Modena had higher ORs, especially when historical residence was considered.Overall, despite some risk of bias due to exposure misclassification and unmeasured confounding, our results appear to support the hypothesis that cyanotoxin exposure may increase ALS risk.
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- 2020
6. Magnetic fields exposure from high-voltage power lines and risk of amyotrophic lateral sclerosis in two Italian populations
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Alessia Arena, Grazia Ghermandi, Daniela Sesti, P Zanichelli, Carlo Signorelli, Marco Vinceti, Vladimiro Pietrini, Silvia Violanti, Leeka Kheifets, Sara Fabbi, Federica Violi, Francesco Patti, Mario Zappia, Salvatore Sciacca, Nicola Fini, Margherita Ferrante, Cristina Mauceri, Anna Odone, A Dimartino, Elisa Arcolin, Caterina Ledda, Roberto Fava, S. Caldara, Carlotta Malagoli, Jessica Mandrioli, Tommaso Filippini, Paola Oleari, Maria Fiore, Laura Iacuzio, B Notari, Sergio Teggi, R. Calzolari, Maurizio Poli, Vinceti, Marco, Malagoli, Carlotta, Fabbi, Sara, Kheifets, Leeka, Violi, Federica, Poli, Maurizio, Caldara, Salvatore, Sesti, Daniela, Violanti, Silvia, Zanichelli, Paolo, Notari, Barbara, Fava, Roberto, Arena, Alessia, Calzolari, Roberta, Filippini, Tommaso, Iacuzio, Laura, Arcolin, Elisa, Mandrioli, Jessica, Fini, Nicola, Odone, Anna, Signorelli, Carlo, Patti, Francesco, Zappia, Mario, Pietrini, Vladimiro, Oleari, Paola, Teggi, Sergio, Ghermandi, Grazia, Dimartino, Angela, Ledda, Caterina, Mauceri, Cristina, Sciacca, Salvatore, Fiore, Maria, and Ferrante, Margherita
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Male ,Amyotrophic lateral sclerosis ,case-control study ,electromagnetic fields ,epidemiology ,power lines ,risk ,Neurology ,Neurology (clinical) ,Pathology ,Disease ,0302 clinical medicine ,Electricity ,Risk Factors ,Epidemiology ,Prevalence ,Medicine ,030212 general & internal medicine ,Unmeasured confounding ,Aged, 80 and over ,education.field_of_study ,Middle Aged ,Radiation Exposure ,power line ,Italy ,Female ,High voltage power lines ,medicine.medical_specialty ,Population ,Radiation Dosage ,03 medical and health sciences ,Age Distribution ,electromagnetic field ,Humans ,Sex Distribution ,Radiation Injuries ,education ,Amyotrophic lateral sclerosi ,Aged ,business.industry ,Amyotrophic Lateral Sclerosis ,Case-control study ,Amyotrophic lateral sclerosis, electromagnetic fields, case-control study, epidemiology, risk, power lines ,medicine.disease ,Magnetic Fields ,Etiology ,business ,030217 neurology & neurosurgery ,Demography - Abstract
The aetiology of amyotrophic lateral sclerosis (ALS), a rare and extremely severe neurodegenerative disease, has been associated with magnetic fields exposure. However, evidence for such a relation in the general population is weak, although the previous null results might also be due to exposure misclassification, or a relationship might exist only for selected subgroups. To test such a hypothesis we carried out a population-based case-control study in two Northern and Southern Italy regions, including 703 ALS cases newly diagnosed from 1998 to 2011 and 2737 controls randomly selected from the residents in the study provinces. Overall, we found that a residence near high-voltage power lines, within the corridors yielding a magnetic fields of ≥0.1 μT, was not associated with an excess disease risk, nor did we identify a dose-response relationship after splitting the exposed corridor according to the 0.1, 0.2 and 0.4 μT cut-points of exposure. These results were confirmed taking into account age at onset, period of diagnosis, sex, geographical area, and length of exposure. Overall, despite the residual possibility of unmeasured confounding or small susceptible subgroups not identified in our study, these results appear to confirm that the exposure to magnetic fields from power lines occurring in the general population is not associated with increased ALS risk.
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- 2017
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7. Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma
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A. Di Stefano, Carla Galeone, Nicola Scichilone, Bruno Balbi, Gianluigi Bajocchi, F. Bellanova, Mirco Lusuardi, N. Facciolongo, Vladimiro Pietrini, Francesco Menzella, Roberto Piro, Debora Formisano, P. P. Salsi, L. Agostini, Facciolongo, N., Di Stefano, A., Pietrini, V., Galeone, C., Bellanova, F., Menzella, F., Scichilone, N., Piro, R., Bajocchi, G.L., Balbi, B., Agostini, L., Salsi, P.P., Formisano, D., and Lusuardi, M.
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Male ,Severe asthma ,Bronchial biopsie ,Biopsy ,medicine.medical_treatment ,Vital Capacity ,Gastroenterology ,Bronchial thermoplasty ,0302 clinical medicine ,Bronchoscopy ,Quality of life ,Forced Expiratory Volume ,Submucosa ,030212 general & internal medicine ,medicine.diagnostic_test ,CD68 ,Middle Aged ,Nerve fiber ,Ablation ,Immunohistochemistry ,Residual Volume ,Treatment Outcome ,medicine.anatomical_structure ,Asthma Control Questionnaire ,Female ,Research Article ,Adult ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Bronchi ,Bronchial biopsies ,Nerve fibers ,Respiratory Mucosa ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,Asthma ,lcsh:RC705-779 ,business.industry ,Total Lung Capacity ,lcsh:Diseases of the respiratory system ,medicine.disease ,respiratory tract diseases ,030228 respiratory system ,business - Abstract
Background Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year. Methods Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, exacerbations, hospitalizations, oral corticosteroids use were also collected at the same time points. Results A statistically significant reduction at T1, T2 and T12 of nerve fibers was observed in the submucosa and in ASM compared to T0. Among inflammatory cells, only CD68 showed significant changes at all time points. Improvement of all clinical outcomes was documented and persisted at the end of follow up. Conclusions A reduction of nerve fibers in epithelium and in ASM occurs earlier and persists at one year after BT. We propose that nerve ablation may contribute to mediate the beneficial effects of BT in severe asthma. Trial registration Registered on April 2, 2013 at ClinicalTrials.gov Identifier: NCT01839591.
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- 2018
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8. The effect of bronchial thermoplasty on nerve C-fibers and inflammatory cells in patients with severe asthma
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Federica Bellanova, Carla Galeone, Nicola Facciolongo, Antonino Di Stefano, Vladimiro Pietrini, Francesco Menzella, Bruno Balbi, Luigi Zucchi, Mirco Lusuardi, and Roberto Piro
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medicine.medical_specialty ,Pathology ,Bronchial thermoplasty ,business.industry ,CD68 ,medicine.disease ,Gastroenterology ,Epithelium ,Mononuclear cell infiltration ,medicine.anatomical_structure ,Mechanism of action ,Internal medicine ,Submucosa ,medicine ,medicine.symptom ,business ,CD8 ,Asthma - Abstract
Bronchial thermoplasty (BT) is a novel intervention for asthma but the mechanism of action is not yet well understood. The aim of our study is to analyze the impact of BT on the inflammatory state and the nerve C-fibers in the bronchial mucosa. We obtained bronchial biopsies from 12 subjects (age mean 47 year; 6Male and 6 Female) with severe refractory asthma recruited from the Pneumology A.S.M Hospital-IRCCS Reggio Emilia Italyfrom march 2013 to july 2014. The severity of asthma was classified according to the GINA criteria. Biopsies were performed before (T0) ,after 1 (T1) and 2 (T2) months following the BT treatment. A significant reduction at T1 and T2 times of total scored nerve C-fibers was observed in the submucosa (Wilcoxon test p=0.007 and p=0.003, respectively) and in the smooth muscle (p=0.005 and p=0.003, respectively) compared to T0. Nerve C-fibers in the epithelium and bronchial glands was only occasionally observed. Total inflammatory cells CD45+, CD8+ cells and eosinophils were not changed in T1 and T2 compared to T0. The CD4+ cells and macrophages CD68+ was significantly higher in T1 (p=0.018 and p=0.041, respectively) and T2 (p=0.020 and p=0.041, respectively)compared to T0. A transitory increase of neutrophils was observed at T1 (p=0.049) returning at basic values at T2 (p=0.507) compared to T0. In the two months after treatment, the BT causes a significant reduction of nerve C-Fibers, a transitory increase of neutrophils and a more persistent increase of mononuclear cell infiltration of the bronchial mucosa.
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- 2015
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9. Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study of long term treatment in Tg2576 mice
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Maria Francesca Baroc, Marco Gusciglio, Alessandro Giuliani, Simone Ottonello, Sandra Sivilia, Laura Calzà, Mercedes Fernandez, Luca Ferraro, Luciana Giardino, Vito Antonio Baldassarro, Arturo Roberto Viscomi, Vladimiro Pietrini, Gino Villetti, Chiara Mangano, Bruno P. Imbimbo, Luca Lorenzini, Sandra Sivilia, Luca Lorenzini, Alessandro Giuliani, Marco Gusciglio, Mercedes Fernandez, Vito Antonio Baldassarro, Chiara Mangano, Luca Ferraro, Vladimiro Pietrini, Maria Francesca Baroc, Arturo R Viscomi, Simone Ottonello, Gino Villetti, Bruno P Imbimbo, Laura Calzà, and Luciana Giardino
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Cyclopropanes ,Alzheimer’ s disease ,Cell-cycle events ,CHF5074 ,Dendrite pathology ,Tg2576 mice ,Plaque, Amyloid ,Disease ,Amyloid beta-Protein Precursor ,Mice ,General Neuroscience ,Neurodegeneration ,NEURODEGENERATION ,Brain ,Female ,Microglia ,Alzheimer's disease ,cognitive evaluation ,Alzheimer’s disease ,Research Article ,Antipsychotic Agents ,Genetically modified mouse ,Silver Staining ,gamma secretase inhibitor ,Transgene ,Mice, Transgenic ,Cyclin A ,Biology ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,In vivo ,Extracellular ,medicine ,Animals ,Humans ,Analysis of Variance ,Amyloid beta-Peptides ,Dose-Response Relationship, Drug ,Recognition, Psychology ,medicine.disease ,Peptide Fragments ,In vitro ,Mice, Inbred C57BL ,Disease Models, Animal ,Flurbiprofen ,Phosphopyruvate Hydratase ,Mutation ,Exploratory Behavior ,Neuroscience - Abstract
Background Alzheimer disease is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The pathological hallmarks includes extracellular amyloid plaques and intraneuronal neurofibrillary tangles, but the primary cause is only partially understood. Thus, there is growing interest in developing agents that might target multiple mechanisms leading to neuronal degeneration. CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to behave as a γ-secretase modulator in vitro and to inhibit plaque deposition and to reverse memory deficit in vivo in transgenic mouse models of Alzheimer’s disease (AD). In the present study, the effects of a long-term (13-month) treatment with CHF5074 on indicators of brain functionality and neurodegeneration in transgenic AD mice (Tg2576) have been assessed and compared with those induced by a prototypical γ-secretase inhibitor (DAPT). Results To this end, plaque-free, 6-month-old Tg2576 mice and wild-type littermates were fed with a diet containing CHF5074 (125 and 375 ppm/day), DAPT (375 ppm/day) or vehicle for 13 months. The measured indicators included object recognition memory, amyloid burden, brain oligomeric and plasma Aβ levels, intraneuronal Aβ, dendritic spine density/morphology, neuronal cyclin A positivity and activated microglia. Tg2576 mice fed with standard diet displayed an impairment of recognition memory. This deficit was completely reverted by the higher dose of CHF5074, while no effects were observed in DAPT-treated mice. Similarly, amyloid plaque burden, microglia activation and aberrant cell cycle events were significantly affected by CHF5074, but not DAPT, treatment. Both CHF5074 and DAPT reduced intraneuronal Aβ content, also increasing Aβ40 and Aβ42 plasma levels. Conclusions This comparative analysis revealed a profoundly diverse range of clinically relevant effects differentiating the multifunctional anti-inflammatory derivative CHF5074 from the γ-secretase inhibitor DAPT and highlighted unique mechanisms and potential targets that may be crucial for neuroprotection in mouse models of AD.
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- 2013
10. Miller Fisher syndrome with positivity of anti-GAD antibodies
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Vladimiro Pietrini, Francesca Andreetta, and Giovanni Pavesi
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Gait Ataxia ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Ataxia ,Facial Paralysis ,Glutamate decarboxylase ,Polymerase Chain Reaction ,Speech Disorders ,Cerebrospinal fluid ,Blood serum ,Humans ,Medicine ,Miller-Fisher syndrome ,Aged ,Autoantibodies ,Neurologic Examination ,Miller Fisher Syndrome ,biology ,Glutamate Decarboxylase ,business.industry ,Brain ,Fisher Syndrome ,General Medicine ,Middle Aged ,Magnetic Resonance Imaging ,Electric Stimulation ,Anti gad antibodies ,Immunology ,biology.protein ,Surgery ,Neurology (clinical) ,Antibody ,medicine.symptom ,business - Abstract
Miller Fisher syndrome (MFS) is a variant of Guillain Barre yndrome (GBS) characterized by ophthalmoplegia, ataxia and areexia [1]. IgG antibodies against GQ1b are present inmore than 90% f acute MFS patients [2,3]. We report a case with typical clinical nd electrophysiological features of MFS with no anti-GQ1b antiodies in the blood serum and cerebrospinal fluid (CSF), but with ositivity of antibodies against glutamic acid decarboxylase (GAD) oth in serum and CSF.
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- 2013
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11. Doxycycline in Creutzfeldt-Jakob disease: A phase 2, randomized, double-blind, placebo-controlled trial
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Jean-Philippe, Brandel, Marcon, Gabriella, Mathieu, Coudert, Mauro, Tettamanti, Arlette, Welaratne, Georgio, Giacone, Shohreh, Azimi, Vladimiro, Pietrini, Jean-Roch, Fabreguettes, Daniele, Imperiale, Christophe, Aucan, Ugo, Lucca, Alain, Mallet, Mario, Salmona, Inga, Zerr, Veronica, Redaelli, Gianluigi, Forloni, Stephane, Haik, and Fabrizio, Tagliavini
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- 2013
12. P3‐016: Chronic administration of CHF5074, a novel γ‐secretase modulator, prevents brain neurodegeneration in aged Alzheimer's disease transgenic mice
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Luciana Giardino, Luca Lorenzini, Gino Villetti, Mercedes Fernandez, Bruno P. Imbimbo, Maria Francesca Baroc, Sandra Sivilia, Alessandro Giuliani, Marco Gusciglio, Vladimiro Pietrini, and Laura Calzà
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Genetically modified mouse ,Epidemiology ,business.industry ,Health Policy ,Neurodegeneration ,γ secretase modulator ,Disease ,Pharmacology ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2011
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13. CHF5074, a Novel gamma-Secretase Modulator, Restores Hippocampal Neurogenesis Potential and Reverses Contextual Memory Deficit in a Transgenic Mouse Model of Alzheimer’s Disease
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Vladimiro Pietrini, Elda Del Giudice, Bruno P. Imbimbo, Marco Gusciglio, Antonello D'Arrigo, G Villetti, Alberta Leon, Luciana Giardino, Alessandro Giuliani, Sandra Sivilia, Laura Calzà, Imbimbo, B., Giardino, Luciana, Sivilia, Sandra, Giuliani, Alessandro, Gusciglio, M., Pietrini, V., Del Giudice, E., D'Arrigo, A., Leon, A., Villetti, G., and Calza', Laura
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Cyclopropanes ,Conditioning, Classical ,Statistics as Topic ,Hippocampus ,Hippocampal formation ,Amyloid beta-Protein Precursor ,Mice ,Cortex (anatomy) ,Cerebral Cortex ,General Neuroscience ,Neurogenesis ,Age Factors ,General Medicine ,Psychiatry and Mental health ,Clinical Psychology ,medicine.anatomical_structure ,ALZHEIMER'S DISEASE ,Microglia ,Genetically modified mouse ,medicine.medical_specialty ,Synaptophysin ,Mice, Transgenic ,Biology ,NEUROGENESIS ,tg2576 ,Alzheimer Disease ,Internal medicine ,Neuroplasticity ,Glial Fibrillary Acidic Protein ,mental disorders ,medicine ,Presenilin-1 ,Animals ,Humans ,gamma secretase modulator ,Analysis of Variance ,Memory Disorders ,Amyloid beta-Peptides ,Dentate gyrus ,Disease Models, Animal ,Endocrinology ,Flurbiprofen ,Gene Expression Regulation ,nervous system ,Mutation ,biology.protein ,Geriatrics and Gerontology ,Neuroscience - Abstract
The effects of compounds interfering with gamma-secretase, the enzymatic complex responsible of the formation of the amyloid-beta (Abeta) peptide from amyloid-beta protein precursor (AbetaPP), on plaque deposition in transgenic mouse models of Alzheimer's disease are known but scanty data are available on the effects of these drugs on brain plasticity. We evaluated the effects of long-term treatment with CHF5074, a new gamma-secretase modulator, on hippocampal neurogenesis, cortical synaptophysin levels, and contextual memory in transgenic mice carrying the double Swedish mutation of AbetaPP (Tg2576). Six-month old Tg2576 mice were treated with CHF5074 (375 ppm in the diet) up to 15 months of age. Age-matched control transgenic and wild-type mice received standard diet. Compared to wild-type animals, transgenic controls showed a significant decrease in the number of doublecortin-positive neuroblasts in dentate gyrus, synaptophysin intensity in the cortex, freezing to context in the contextual fear conditioning test. Compared to transgenic controls, CHF5074 treatment of Tg2576 mice resulted in a significant attenuation of the neurogenesis impairment in hippocampus (p=0.036), normalization of synaptophysin levels in cortex (p< 0.001), attenuation of plaque burden in the cortex (p=0.033), increases astroglial reaction around plaques (p=0.001), and attenuation of activated microglia (p=0.040). These effects were associated to a complete reversal of contextual memory deficit (p=0.006). Contextual memory significantly correlated with synaptophysin immunoreactivity in the cortex (r=0.548, p=0.0038).
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- 2010
14. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity
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Antonello D'Arrigo, Fabrizio Facchinetti, Bruno P. Imbimbo, Lutgarde Serneels, Elda Del Giudice, Maurizio Dalle Carbonare, Maria Francesca Baroc, Davide Colavito, Roberta Volta, Alberta Leon, Bart De Strooper, Gino Villetti, and Vladimiro Pietrini
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Genetically modified mouse ,Cyclopropanes ,Male ,medicine.medical_specialty ,Aging ,Mice, Transgenic ,Cell Line ,Amyloid beta-Protein Precursor ,Mice ,Alzheimer Disease ,Internal medicine ,medicine ,Amyloid precursor protein ,Animals ,Humans ,Tissue Distribution ,Gamma secretase ,Pharmacology ,Gastrointestinal tract ,Amyloid beta-Peptides ,biology ,Molecular Structure ,Anti-Inflammatory Agents, Non-Steroidal ,Brain ,medicine.disease ,In vitro ,Peptide Fragments ,Disease Models, Animal ,Endocrinology ,Flurbiprofen ,Toxicity ,biology.protein ,Molecular Medicine ,Female ,Alzheimer's disease ,Amyloid Precursor Protein Secretases ,Amyloid precursor protein secretase - Abstract
Some nonsteroidal anti-inflammatory drugs has been shown to allosterically modulate the activity of gamma-secretase, the enzymatic complex responsible for the formation of beta-amyloid (Abeta). 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074) is a new gamma-secretase modulator, devoid of anticyclooxygenase (COX) and Notch-interfering activities in vitro. We evaluated the effects of chronic CHF5074 treatment on brain Abeta pathology in Tg2576 transgenic mice. Twenty-eight animals of 9.5 to 10.5 months of age received CHF5074-medicated diet (375 ppm) or standard diet for 17 weeks. Compared with controls, CHF5074 treatment significantly reduced the area occupied by plaques and the number of plaques in cortex (-52.2 +/- 5.6%, p = 0.0003 and -48.9 +/- 6.6%, p = 0.0004, respectively) and hippocampus (-76.7 +/- 6.4%, p = 0.004 and -66.2 +/- 10.3%, p = 0.037, respectively). Biochemical analysis confirmed the histopathological measures, with CHF5074-treated animals showing reduced total brain Abeta40 (-49.2 +/- 9.2%, p = 0.017) and Abeta42 (-43.5 +/- 9.7%, p = 0.027) levels. In a human neuroglioma cell line expressing Swedish mutated form of amyloid precursor protein (H4swe), CHF5074 reduced Abeta42 and Abeta40 secretion, with an IC50 of 3.6 and 18.4 microM, respectively, values consistent with those measured in the brain of the CHF5074-treated Tg2576 mice (6.4 +/- 0.4 microM). At 5 microM, no effects were observed on Notch intracellular cleavage in human embryonic kidney 293swe cells. CHF5074 was well tolerated by Tg2576 mice. No abnormal findings were observed upon histopathological examination of the gastrointestinal tract, indicating the absence of COX-related toxicity. Semiquantitative histochemical evaluation of goblet cells in the ileum of vehicle- and CHF5074-treated animals yielded similar results, suggesting no effects on Notch pathway. CHF5074 is therefore a promising therapeutic agent for Alzheimer's disease.
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- 2007
15. Conformation-sensitive antibodies against alzheimer amyloid-beta by immunization with a thioredoxin-constrained B-cell epitope peptide
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Steven J. Del Signore, Karen M. Smith, Nadia Moretto, Robert J. Ferrante, Angelo Bolchi, Gino Villetti, Luciano Polonelli, Vladimiro Pietrini, Simone Ottonello, Bruno Pietro Imbimbo, and Claudio Rivetti
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Male ,Models, Molecular ,Peptide ,Mice, Transgenic ,Biochemistry ,Epitope ,Antibodies ,Mice ,Thioredoxins ,Antigen ,Alzheimer Disease ,medicine ,Animals ,Humans ,Molecular Biology ,B cell ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Amyloid beta-Peptides ,biology ,P3 peptide ,Brain ,Cell Biology ,Molecular biology ,Peptide Fragments ,Recombinant Proteins ,Protein Structure, Tertiary ,medicine.anatomical_structure ,chemistry ,biology.protein ,Epitopes, B-Lymphocyte ,Antibody ,Thioredoxin ,Conformational epitope - Abstract
Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy.
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- 2007
16. Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region
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S. Cozzolino, Vincenzo Tegazzin, Lucia Galli, Alfredo Orrico, Vladimiro Pietrini, and Vincenzo Sorrentino
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Male ,Proband ,Patients ,Physiology ,Molecular Sequence Data ,Biology ,Exon ,Risk Factors ,Genotype ,medicine ,Humans ,Amino Acid Sequence ,Myopathy, Central Core ,Molecular Biology ,Minicore myopathy ,Genetics ,RYR1 ,Malignant hyperthermia ,Ryanodine Receptor Calcium Release Channel ,Cell Biology ,musculoskeletal system ,medicine.disease ,Phenotype ,Pedigree ,Italy ,Mutation ,Female ,Malignant Hyperthermia ,Central core disease - Abstract
Mutations in the ryanodine receptor type 1 (RYR1) gene are associated with Malignant Hyperthermia (MH) and Central Core Disease (CCD). We report here on the molecular analysis of the RYR1 gene in Italian families referred as potential cases of MH or in patients with CCD or multicore/minicore myopathy. Of a total of 20 individuals with mutations in the RYR1 gene, 14 were part of a group of 47 MH susceptible (MHS) patients, 4 of 34 individuals diagnosed as MH equivocal (MHE), and 2 were patients diagnosed with minicore myopathy and CCD, respectively. Mutations were found to segregate with the MHS or MHE phenotype within the families of the probands. A discordance between phenotype and genotype was observed in a family where a mutation detected in an MHS proband was also found in the father who had been diagnosed MH normal (MHN) at the IVCT. In addition to known mutations, seven novel mutations were found, five of which occurred in exons encoding the C-terminal region of RYR1. These results indicate that the C-terminal region of RYR1 represents an additional hot spot for mutations in patients with MH, similar to what has been reported for patients with CCD.
- Published
- 2002
17. NEUROPATHOLOGICALLY CONFIRMED SPORADIC CREUTZFELDT-JAKOB DISEASE
- Author
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H. Diringer, Pilz P, R. Kleinert, Kurt A. Jellinger, J. A. Hainfellner, Vladimiro Pietrini, Hans Maier, Herbert Budka, Gianriccardo Trabattoni, Marin Guentchev, and Filippo Gullotta
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Cellular and Molecular Neuroscience ,Pathology ,medicine.medical_specialty ,Neurology ,Incidence (epidemiology) ,medicine ,Distribution (pharmacology) ,Neurology (clinical) ,General Medicine ,Sporadic Creutzfeldt-Jakob disease ,Biology ,Pathology and Forensic Medicine - Published
- 1996
- Full Text
- View/download PDF
18. Migraine and Intercalated Seizures With Occipital EEG Paroxysms: Observations on a Family
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Vladimiro Pietrini, Mario Giovanni Terzano, Francesco Ferro Milone, and Liborio Parrino
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medicine.diagnostic_test ,Migraine Disorders ,Electroencephalography ,medicine.disease ,Pedigree ,Prodrome ,Epilepsy ,Epilepsy, Temporal Lobe ,Neurology ,Migraine ,Cortical spreading depression ,Right posterior ,medicine ,Humans ,Female ,Neurology (clinical) ,Child ,Occipital lobe ,Psychology ,Neuroscience ,Flunarizine ,medicine.drug - Abstract
SYNOPSIS A 12-year-old girl presented three distinct attacks of classic migraine. In all attacks, an occipital seizure with impairment of consciousness was intercalated between the visual prodrome and the headache. A right occipital epileptogenic focus was detected by the EEG. Neurologic examination was normal. CT-scan and laboratory work were unremarkable. Flunarizine treatment controlled both the migraine and seizure components. Periodic migraine episodes with visual phenomena occurred in three other female components of the same family. However, the attacks were never associated with epileptic manifestations. Only the 10-year-old sister, who suffered from common migraine, showed sporadic interictal EEG abnormalities in the right posterior leads. The possible neurophysiologic interplay between classic migraine and epilepsy in intercalated attacks may be explained on the basis of the “spreading depression” mechanism. The intense neuronal excitation preceding the migraine aura might play a “triggering” role on the occipital epileptogenic focus. Similarities and differences between this benign though unusual syndrome and other forms of epilepsy in childhood, are also discussed.
- Published
- 1986
- Full Text
- View/download PDF
19. Acute confusional migraine attacks resolved by sleep: lack of significant abnormalities in post-ictal polysomnograms
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Vladimiro Pietrini, Maria Cristina Spaggiari, Mario Giovanni Terzano, and Liborio Parrino
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Migraine Disorders ,Sleep, REM ,Polysomnography ,Electrocardiography ,Medicine ,Humans ,Ictal ,Confusion ,Acute Confusional Migraine ,medicine.diagnostic_test ,business.industry ,Respiration ,Eeg abnormalities ,Electroencephalography ,General Medicine ,medicine.disease ,Sleep in non-human animals ,Functional integrity ,Electrooculography ,Migraine ,Anesthesia ,Acute Disease ,Neurology (clinical) ,Sleep Stages ,business ,Cognition Disorders ,Sleep - Abstract
We observed acute confusional migraine (ACM) attacks in two adolescents, and in both cases the episodes ended when the patients fell asleep spontaneously. Laboratory and neuroradiologic examinations were unremarkable. The post-ictal polysomnograms displayed a regular quality and duration of the physiologic components of sleep. Random posterior slow waves occurred only during the nocturnal awakenings and REM periods. The observation that sleep may resolve migraine attacks is emphasized. ACM is characterized by peculiar and relatively quickly reversible clinical manifestations and EEG abnormalities. The lack of significant abnormalities in post-ictal polysomnograms corresponds to a functional integrity of the brainstem structures involved in the global organization of sleep and may represent a useful laboratory feature in the diagnosis of ACM.
- Published
- 1986
20. Megalencephaly with formation of Rosenthal fibers in symmetric subependymal gliomatous proliferations: clinicopathologic report
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Vladimiro Pietrini, Tagliavini, F., Tedeschi, F., and Lechi, A.
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Brain Neoplasms ,Ependyma ,Brain ,Humans ,Infant ,Female ,Glioma - Abstract
Clinical and neuropathologic observations are reported concerning a girl with retarded psychomotor development accompanied with a steady increase in the volume of the cranium and brain, tetraparesis, and a serious epileptic syndrome resulting in death at the age of 13 years. The neuropathologic study revealed a marked megalencephaly and the presence of two bilateral and symmetric areas of atypical glial proliferation, corresponding with the optostriatal groove, with endoventricular protrusion: in this region the histologic findings gave evidence of a tapetum of Rosenthal fibers. Discussion is focused on the observed neuropathologic aspects in relation to the various diagnostic hypotheses: Alexander's disease, primary megalencephaly associated with astrocytomas or reactive gliosis, or megalencephaly associated with subependymal hamartomas.
- Published
- 1983
21. Environmental exposure to trace elements and risk of amyotrophic lateral sclerosis: a population-based case-control study
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Patrizia Sola, Luciano Vescovi, Margherita Bergomi, Marco Vinceti, Angela Ferrari, Grazia Nacci, Peter Brätter, Chiara Aramini, Dorothea Alber, Susanna Malagu, D. Guidetti, Vladimiro Pietrini, and Gianfranco Vivoli
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Male ,medicine.medical_specialty ,case-control study ,Population ,chemistry.chemical_element ,Physiology ,trace elements ,Zinc ,Biochemistry ,Amyotrophic Lateral Sclerosis ,medicine ,Humans ,Amyotrophic lateral sclerosis ,education ,General Environmental Science ,Cadmium ,education.field_of_study ,business.industry ,Trace element ,Case-control study ,Environmental exposure ,Environmental Exposure ,medicine.disease ,Surgery ,Trace Elements ,chemistry ,Italy ,Nails ,Case-Control Studies ,Disease Progression ,Regression Analysis ,Female ,business ,Selenium ,Biomarkers - Abstract
We analyzed the association between the environmental exposure to trace elements and the risk of sporadic amyotrophic lateral sclerosis (ALS) in a population-based case-control study in the Emilia-Romagna region in northern Italy. We evaluated exposure to selected trace elements by measuring toenail concentrations of the same by means of inductively coupled plasma optical spectrometry and instrumental neutron activation analysis. The final number enrolled in the study was 22 patients and 40 controls. Disease progression, assessed through a clinical score, was generally unassociated with toenail trace element levels, with the exception of an inverse relation with zinc and selenium content and a direct correlation with copper concentration. In logistic regression analysis, we found no evidence of an association between ALS risk and toenail content of cadmium, lead, copper, zinc, manganese, selenium, chromium, cobalt, iron, and aluminum. This investigation does not suggest a major role in sporadic ALS etiology of environmental exposure to these trace elements, though results for zinc, selenium, and copper should be evaluated with caution due to the potential limitations of toenails as biomarkers of chronic exposure in patients.
22. Precocious loss of physiological sleep in a case of Creutzfeldt Jakob disease: A serial polygraphic study
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Terzano, M. G., Parrino, L., Vladimiro Pietrini, Mancia, D., Spaggiari, M. C., Rossi, G., and Tagliavini, F.
23. Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene
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Vladimiro Pietrini, Puoti, G., Limido, L., Rossi, G., Di Fede, G., Giaccone, G., Mangieri, M., Tedeschi, F., Bondavalli, A., Mancia, D., Bugiani, O., Tagliavini, F., Pietrini, V, Puoti, Gianfranco, Limido, L, Rossi, G, DI FEDE, G, Giaccone, G, Mangieri, M, Tedeschi, F, Bondavalli, A, Mancia, D, Bugiani, O, and Tagliavini, F.
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Brain Chemistry ,Male ,Amyloid ,Heterozygote ,Tyrosine 3-Monooxygenase ,Prions ,Homozygote ,Immunoblotting ,Brain ,Electroencephalography ,tau Proteins ,Middle Aged ,Immunohistochemistry ,Polymerase Chain Reaction ,Creutzfeldt-Jakob Syndrome ,Prion Proteins ,14-3-3 Proteins ,Endopeptidases ,Mutation ,Humans ,Neurology (clinical) ,Protein Precursors - Abstract
—The authors investigated two unrelated patients with Creutzfeldt-Jakob disease (CJD) with clinical features of sporadic CJD (sCJD) carrying one extra octapeptide repeat in the prion protein (PrP) gene (PRNP). A synaptic type PrP distribution throughout the cerebral gray matter and plaque-like PrP deposits in the subcortical gray structures were detected immunocytochemically. The different patterns of PrP deposition were associated with distinct types of proteaseresistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.
24. Erythrocyte zinc, copper, and copper/zinc superoxide dismutase and risk of sporadic amyotrophic lateral sclerosis: A population-based case-control study
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Grazia Nacci, Katia Fortini, Domenico Mancia, Marco Vinceti, Angela Ferrari, Patrizia Sola, Vladimiro Pietrini, Gianfranco Vivoli, Enrico Rocchi, D. Guidetti, and Margherita Bergomi
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Male ,Risk ,medicine.medical_specialty ,amyotrophic lateral sclerosis ,Erythrocytes ,case-control study ,Population ,SOD1 ,Statistics as Topic ,erythrocyte zinc ,copper ,copper/zinc superoxide dismutase ,epidemiology ,chemistry.chemical_element ,Zinc ,Community Health Planning ,Superoxide dismutase ,Internal medicine ,medicine ,Humans ,Amyotrophic lateral sclerosis ,education ,education.field_of_study ,biology ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Case-control study ,medicine.disease ,Copper ,Confidence interval ,Endocrinology ,chemistry ,Case-Control Studies ,biology.protein ,Female ,Neurology (clinical) - Abstract
We investigated through a population-based case-control study the hypothesis that disturbances in the chemistry of copper and zinc and in activity of the antioxidant enzyme copper/zinc superoxide-dismutase (SOD1) are involved in the etiopathogenesis of sporadic amyotrophic lateral sclerosis (ALS). We recruited 20 patients with sporadic ALS and 22 population controls from three northern Italian provinces, and we analyzed zinc and copper content and SOD1 activity in erythrocytes. These variables were unrelated to disease progression as evaluated through a disability score; zinc concentrations inversely correlated with copper in referents but not in patients. SOD1 activity was lower and erythrocyte zinc and copper levels were slightly higher in patients than in referents. Comparing the second to the bottom tertile of erythrocyte SOD1 activity, relative risk of ALS was 0.4 (95% confidence interval 0.1-2.0); the risk further decreased to 0.1 (95% confidence interval 0-0.9) for comparison of highest to lowest tertile (P for trend 0.027). Copper and zinc levels were not associated with disease risk. Our findings indicate that a lower SOD1 activity is associated with ALS, but we cannot be sure whether this association is a marker of causal action or is secondary to a confounder, or to disease onset itself.
25. Neuropathy in Tangier disease: A clinicopathologic study and a review of the literature
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Vladimiro Pietrini, Nicola Rizzuto, C. Vergani, F. Ferro Milone, and F. Zen
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Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Temperature sensation ,Facial diplegia ,Pathology ,medicine.medical_specialty ,Biopsy ,Nerve Fibers ,Tangier disease ,Humans ,Medicine ,Peripheral Nerves ,Wasting ,Tangier Disease ,Hand muscles ,medicine.diagnostic_test ,business.industry ,Superficial peroneal nerve ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,Hypolipoproteinemias ,medicine.disease ,Microscopy, Electron ,Neurology ,Nerve Degeneration ,Schwann Cells ,Neurology (clinical) ,medicine.symptom ,Peroneus brevis ,business - Abstract
A new case of Tangier disease is described. It is the 33rd case in world literature and only the 2nd in Italy. A 52-year-old man showed a widely spread neuropathy with facial diplegia, bilateral wasting of hand muscles and dissociated loss of pain and temperature sensation sparing the distal parts of the lower limbs. Clinical and laboratory data were typical of Tangier disease. A histological and ultrastructural study of the patient's superficial peroneal nerve and brevis peroneus muscle was carried out. A revision of the clinical and neuropathological aspects of the neuropathy of Tangier disease allowed our case to be included within a particular neurological description. Four patients with similar clinical characteristics had been noted previously. Clinical, morphological and biochemical data suggest the hypothesis that there are two different neuropathic forms of Tangier disease.
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