14 results on '"Cosentino, G."'
Search Results
2. A case of carotid cavernous fistula mimicking Graves’ orbitopathy
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Cosentino, G., Comi, S., Maglionico, M. N., and Marinò, M.
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- 2024
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3. Are there gender differences between subthalamic or globus pallidus internus DBS in Parkinson’s disease? Results from a single center
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Belluscio, G., primary, Malaspina, S., additional, Avenali, M., additional, Cosentino, G., additional, Pacchetti, C., additional, Zangaglia, R., additional, and Valentino, F., additional
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- 2024
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4. Near-infrared observations of outflows and young stellar objects in the massive star-forming region AFGL 5180
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Crowe, S., primary, Fedriani, R., additional, Tan, J. C., additional, Whittle, M., additional, Zhang, Y., additional, Caratti o Garatti, A., additional, Farias, J. P., additional, Gautam, A., additional, Telkamp, Z., additional, Rothberg, B., additional, Grudić, M., additional, Andersen, M., additional, Cosentino, G., additional, Garcia-Lopez, R., additional, Rosero, V., additional, Tanaka, K., additional, Pinna, E., additional, Rossi, F., additional, Miller, D., additional, Agapito, G., additional, Plantet, C., additional, Ghose, E., additional, Christou, J., additional, Power, J., additional, Puglisi, A., additional, Briguglio, R., additional, Brusa, G., additional, Taylor, G., additional, Zhang, X., additional, Mazzoni, T., additional, Bonaglia, M., additional, Esposito, S., additional, and Veillet, C., additional
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- 2024
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5. Exploring Structural Requirements for Sigma-1 Receptor Linear Ligands: Experimental and Computational Approaches.
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Lombardo L, Mirabile S, Gitto R, Cosentino G, Alcaro S, Dichiara M, Marrazzo A, Amata E, Ortuso F, and De Luca L
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- Ligands, Humans, Piperazines chemistry, Piperazines metabolism, Protein Binding, Binding Sites, Protein Conformation, Receptors, sigma metabolism, Receptors, sigma chemistry, Sigma-1 Receptor, Molecular Dynamics Simulation
- Abstract
Sigma-1 receptor (S1R) is involved in a large array of biological functions due to its ability to interact with various proteins and ion channels. Crystal structures of human S1R revealed the trimeric organization for which each protomer comprises the ligand binding pocket. This study applied a multistep computational procedure to develop a pharmacophore model obtained from molecular dynamics simulations of available cocrystal structures of well-known S1R ligands. Apart from the well-established positive ionizable and hydrophobic features, the obtained model included an additional specific hydrophobic feature and different excluded volumes, thus increasing the selectivity of the model as well as a more detailed determination of the distance between two essential features. The obtained pharmacophore model passed the validation test by receiver operating characteristic (ROC) curve analysis of active and inactive S1R ligands. Finally, the pharmacophoric performance was experimentally investigated through the synthesis and binding assay of new 4-phenylpiperazine-based compounds. The most active new ligand 2-(3-methyl-1-piperidyl)-1-(4-phenylpiperazin-1-yl)ethanone ( 3 ) showed an S1R affinity close to the reference compound haloperidol ( K
i values of 4.8 and 2.6 nM, respectively). The proposed pharmacophore model can represent a useful tool to design and discover new potent S1R ligands.- Published
- 2024
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6. Diagnostic accuracy of voluntary and stimulated neuromuscular jitter studies in ocular myasthenia gravis.
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Cosentino G, Prunetti P, Tammam G, Zaffina C, Gastaldi M, Tassorelli C, Alfonsi E, and Todisco M
- Abstract
Introduction/aims: There is a lack of studies comparing the accuracy of neuromuscular jitter analysis during voluntary activation (v-jitter study) versus axonal stimulation (s-jitter study). The study aimed to compare these two techniques in the same population of patients with suspected ocular myasthenia gravis (OMG)., Methods: Fourteen control subjects (mean age: 55.5 ± 15.2 years) and 34 patients with suspected OMG (mean age: 59 ± 13.9 years) were prospectively evaluated. Twenty spike pairs and 30 individual spikes were analyzed during v-jitter and s-jitter study, respectively. Two different criteria for abnormal individual jitter values were evaluated: ≥ or > than 10% values exceeding the upper normal limit., Results: OMG was diagnosed in 19 patients based on clinical and laboratory findings, without considering jitter measurements. In most patients, v-jitter and s-jitter analyses provided comparable results. The maximum sensitivity (89%) was achieved with s-jitter study using the ≥10% criterion, while the maximum specificity (93%) was found with v-jitter study using the >10% criterion., Discussion: Both v-jitter and s-jitter studies showed good to very good accuracy for the diagnosis of OMG, in the absence of any statistically significant difference. Therefore, the patient's cooperation level and examiner's experience should guide the choice of performing v-jitter or s-jitter analysis in patients with suspected OMG., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)
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- 2024
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7. Design, Synthesis, and Cytotoxic Assessment of New Haloperidol Analogues as Potential Anticancer Compounds Targeting Sigma Receptors.
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Zampieri D, Romano M, Fortuna S, Amata E, Dichiara M, Cosentino G, Marrazzo A, and Mamolo MG
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- Humans, Cell Line, Tumor, Structure-Activity Relationship, Molecular Structure, Cell Survival drug effects, Ligands, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Receptors, sigma metabolism, Receptors, sigma antagonists & inhibitors, Haloperidol pharmacology, Haloperidol analogs & derivatives, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Drug Design
- Abstract
Sigma receptors (SRs), including SR1 and SR2 subtypes, have attracted increasing interest in recent years due to their involvement in a wide range of activities, including the modulation of opioid analgesia, neuroprotection, and potential anticancer activity. In this context, haloperidol (HAL), a commonly used antipsychotic drug, also possesses SR activity and cytotoxic effects. Herein, we describe the identification of novel SR ligands, obtained by a chemical hybridization approach. There wereendowed with pan-affinity for both SR subtypes and evaluated their potential anticancer activity against SH-SY5Y and HUH-7 cancer cell lines. Through a chemical hybridization approach, we identified novel compounds ( 4d , 4e , 4g , and 4j ) with dual affinity for SR1 and SR2 receptors. These compounds were subjected to cytotoxicity testing using a resazurin assay. The results revealed potent cytotoxic effects against both cancer cell lines, with IC
50 values comparable to HAL. Interestingly, the cytotoxic potency of the novel compounds resembled that of the SR1 antagonist HAL rather than the SR2 agonist siramesine (SRM), indicating the potential role of SR1 antagonism in their mechanism of action. The further exploration of their structure-activity relationships and their evaluation in additional cancer cell lines will elucidate their therapeutic potential and may pave the way for the development of novel anticancer agents that target SRs.- Published
- 2024
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8. Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database.
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Doneddu PE, Gentile L, Cocito D, Fazio R, Luigetti M, Briani C, Filosto M, Siciliano G, Benedetti L, Antonini G, Matà S, Marfia GA, Inghilleri M, Manganelli F, Cosentino G, Brighina F, Carpo M, Carta F, Mazzeo A, Peci E, Strano C, Romano A, Campagnolo M, Cotti-Piccinelli S, Viola DV, Germano F, Leonardi L, Sperti M, Mataluni G, Ceccanti M, Spina E, Vegezzi E, Di Stefano V, and Nobile-Orazio E
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- Humans, Peripheral Nerves, Magnetic Resonance Imaging, Immunoglobulin M, Italy, Neural Conduction physiology, Polyneuropathies diagnosis, Motor Neuron Disease diagnosis, Motor Neuron Disease drug therapy
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Background and Purpose: This study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients., Methods: Clinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria., Results: The European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied., Author: When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations., Conclusions: This study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2024
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9. Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.
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De Lorenzo A, Liberatore G, Doneddu PE, Manganelli F, Cocito D, Briani C, Fazio R, Mazzeo A, Schenone A, Di Stefano V, Cosentino G, Marfia GA, Benedetti L, Carpo M, Filosto M, Antonini G, Clerici AM, Luigetti M, Matà S, Rosso T, Lucchetta M, Siciliano G, Lauria Pinter G, Cavaletti G, Inghilleri M, Cantisani T, Notturno F, Ricciardi D, Habetswallner F, Spina E, Peci E, Salvalaggio A, Falzone Y, Strano C, Gentile L, Vegezzi E, Mataluni G, Cotti Piccinelli S, Leonardi L, Romano A, and Nobile-Orazio E
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- Humans, Peripheral Nerves, Neural Conduction physiology, Databases, Factual, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating diagnosis
- Abstract
Background and Purpose: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated., Methods: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP., Results: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did., Conclusions: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
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- 2024
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10. Pediatric Migraine and Visual Cortical Excitability: A Prospective Observational Study with Sound-Induced Flash Illusions.
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Di Marco S, Pilati L, Torrente A, Maccora S, Santangelo A, Cosentino G, Correnti E, Raieli V, Fierro B, and Brighina F
- Abstract
The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine.
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- 2024
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11. Designing drugs optimized for both blood-brain barrier permeation and intra-cerebral partition.
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Dichiara M, Cosentino G, Giordano G, Pasquinucci L, Marrazzo A, Costanzo G, and Amata E
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- Animals, Brain, Biological Transport, Drug Delivery Systems, Blood-Brain Barrier, Artificial Intelligence
- Abstract
Introduction: With the increasing incidence and prevalence of neurological disorders globally, there is a paramount need for new pharmacotherapies. BBB effectively protects the brain but raises a profound challenge to drug permeation, with less than 2% of most drugs reaching the CNS., Areas Covered: This article reviews aspects of the most recent design strategies, providing insights into ideas and concepts in CNS drug discovery. An overview of the products available on the market is given and why clinical trials are continuously failing is discussed., Expert Opinion: Among the available CNS drugs, small molecules account for most successful CNS therapeutics due to their ability to penetrate the BBB through passive or carrier-mediated mechanisms. The development of new CNS drugs is very difficult. To date, there is a lack of effective drugs for alleviating or even reversing the progression of brain diseases. Particularly, the use of artificial intelligence strategies, together with more appropriate animal models, may enable the design of molecules with appropriate permeation, to elicit a biological response from the neurotherapeutic target.
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- 2024
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12. Retinal and Cortical Visual Processing Dysfunction in a Case of Mild Cognitive Impairment with Lewy Bodies: A Case Report.
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Perini G, Cotta Ramusino M, Conca F, Cosentino G, Farina LM, Costa A, and Farina E
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The prodromal stage of Lewy body dementia includes a mild cognitive impairment with visual processing and/or attention-executive deficits. A clinical presentation with progressive visual loss is indeed seldom reported and can be misleading with a posterior cortical atrophy disease. While the neurodegeneration at the occipital cortex can only partially explain the visual disturbances of Lewy body dementia, more recently a retinal dysfunction has been suggested by preliminary optical coherence tomography and autoptic findings. Herein, we present a case of a mild cognitive impairment with Lewy bodies, who presented initially with visual disturbances and signs of both retinal and cortical visual processing dysfunction. A complete neuropsychological, neurophysiological and brain imaging assessment highlighted a prominent ventral visual pathway involvement. This report provides first that the prodromal stage of Lewy body dementia can manifest as a primarily progressive visual loss, second that the involvement of visual pathway, particularly the ventral stream, can be detectable from the retinal to the cortical level., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)
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- 2024
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13. Neurophysiological Alterations of the Visual Pathway in Posterior Cortical Atrophy: Systematic Review and a Case Series.
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Cotta Ramusino M, Scanu L, Gritti L, Imbimbo C, Farina LM, Cosentino G, Perini G, and Costa A
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Background: The clinical features of posterior cortical atrophy (PCA), a rare condition often caused by Alzheimer's disease, have been recently defined, while little is known about its neurophysiological correlates., Objective: To describe neurophysiological alterations of the visual pathway as assessed using visual field test (VF), visual evoked potentials (VEP), and electroretinogram (ERG) in PCA patients., Methods: Studies reporting VF, VEPs, and ERG in PCA patients were selected according PRISMA method. Of the 323 articles that emerged from the literature, 17 included the outcomes of interest. To these data, we added those derived from a patient cohort enrolled at our clinic., Results: The literature review included 140 patients, half of them (50%) presented with homonymous hemianopia or quadrantanopia. VEPs were available in 4 patients (2 normal findings, 1 decreased amplitude, and 1 increased latency) and ERG in 3 patients (substantially normal findings). Our case series included 6 patients, presenting with homonymous lateral hemianopia in 50% and contralateral cortical atrophy. VEPs showed normal amplitude in 66-83% according to the stimulation check, and increased latency in 67% in absence of myelin damage on MRI. Latency was increased in both eyes in 50% and only on one side in the other 50%. Such alterations were observed in patients with more severe and symmetric atrophy. ERG showed normal findings., Conclusions: Neurophysiological investigations of the visual pathway in PCA are almost absent in literature. Alterations involve both amplitude and latency and can be also monocular. A multiple-point involvement of the optical pathway can be hypothesized.
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- 2024
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14. Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum.
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Quartesan I, Vegezzi E, Currò R, Heslegrave A, Pisciotta C, Iruzubieta P, Salvalaggio A, Fernández-Eulate G, Dominik N, Rugginini B, Manini A, Abati E, Facchini S, Manso K, Albajar I, Laban R, Rossor AM, Pichiecchio A, Cosentino G, Saveri P, Salsano E, Andreetta F, Valente EM, Zetterberg H, Giunti P, Stojkovic T, Briani C, López de Munain A, Pareyson D, Reilly MM, Houlden H, Tassorelli C, and Cortese A
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- Humans, Cross-Sectional Studies, Longitudinal Studies, Phenotype, Biomarkers, Intermediate Filaments
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Background: Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date., Objectives: In this multicenter cross-sectional study, we aimed to evaluate neurofilament light (NfL) chain serum levels in a cohort of RFC1 disease patients and to correlate NfL serum concentrations with clinical phenotype and disease severity., Methods: Sixty-one patients with genetically confirmed RFC1 disease and 48 healthy controls (HCs) were enrolled from six neurological centers. Serum NfL concentration was measured using the single molecule array assay technique., Results: Serum NfL concentration was significantly higher in patients with RFC1 disease compared to age- and-sex-matched HCs (P < 0.0001). NfL level showed a moderate correlation with age in both HCs (r = 0.4353, P = 0.0020) and patients (r = 0.4092, P = 0.0011). Mean NfL concentration appeared to be significantly higher in patients with cerebellar involvement compared to patients without cerebellar dysfunction (27.88 vs. 21.84 pg/mL, P = 0.0081). The association between cerebellar involvement and NfL remained significant after controlling for age and sex (β = 0.260, P = 0.034)., Conclusions: Serum NfL levels are significantly higher in patients with RFC1 disease compared to HCs and correlate with cerebellar involvement. Longitudinal studies are warranted to assess its change over time., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2024
- Full Text
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