Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-34355622

RESUMO

Objective: To evaluate how Amyotrophic Lateral Sclerosis (ALS) patients' mortality rates change, based on different levels of forced vital capacity (FVC) and disease duration, providing a scheme of mortality rates of a real population of ALS patients to improve the design of future RCTs. Methods: One random spirometry for each ALS patient was selected during four time intervals from disease onset: (1) ≤12 months; (2) ≤18 months; (3) ≤24 months; (4) ≤36 months. Date of spirometry corresponded to date of trial entry, while time interval onset-spirometry to disease duration at enrollment. Mortality rates from inclusion were computed at different time intervals. Based on progression rates, patients were stratified in slow, intermediate and fast progressors. Survival from recruitment was calculated depending on FVC, disease duration and progression rate. Results: We included 659 patients in group 1, 888 in group 2, 1019 in group 3 and 1102 in group 4. Mortality rates were higher in each group at reducing the FVC cutoff used for recruitment (p < 0.001). Median survival decreased when lowering FVC and disease duration cutoffs (p < 0.001); a higher median disease progression rate of included patients led to lower median survival from recruitment. The proportion of recruited fast progressors raised when shortening disease duration and lowering FVC cutoff. Conclusions: This is a simple model for setting eligibility criteria, based on mortality rates of patients depending on FVC and disease duration, to select the best population for RCTs, tailored to trials' primary endpoints and duration.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33860702

RESUMO

Objective: To assess patients Quality of life (QoL) and the burden of their caregivers during Covid-19 pandemic and specifically the impact of two-month lockdown period. Methods: In April 2020, a total of 60 patients and 59 caregivers were administered by phone scales assessing patients' QoL (McGill QoL Questionnaire), general health status (EQ-5D-5L), and caregiver burden (Zarit Burden Interview). The administration was repeated one month after the end of lockdown measures, with the addition of a qualitative questionnaire (COVID-QoL Questionnaire) exploring family reorganization and personal perception of lock down. Results: QoL and perceived health status did not worsen during lockdown, while caregiver burden increased (p = 0.01). Patient's QoL and caregiver burden were inversely correlated at T1 (ZBI total score mildly correlated with Mc Gill existential subscore, p = 0.02, rho = 0.30 and with Mc Gill total score, p = 0.05, rho = 0.265). No significant correlations were found at T2. According to the COVID-QoL questionnaire, caregivers perceived lower family help compared to patients (p < 0.001). Conclusions: Restricted measures of lockdown period during COVID-19 pandemic did not result in a significant reduction of QoL in our cohort of ALS patients, while caregiver burden significantly increased. ALS motor impairment may have played a role in the unchanged life conditions of patients. Instead, the restriction of family help for primary caregivers could be responsible of their increased burden, reflecting the importance of a wide social support in the management of this clinical condition.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33879000

RESUMO

Objective: To investigate the impact of a novel heterozygous FUS mutation in the acceptor splice site of intron 14 (c.1542 - 1 g > t) on protein expression in Peripheral Blood Mononuclear Cells (PBMC) from a familial ALS patient. Methods: PBMC were isolated for mRNA analysis (cDNA synthesis, sequencing and one-step RT-PCR), Western Immunoblot (WI), and Immunofluorescence (IF). Results: cDNA analysis revealed the skipping of exon 15 and a premature stop codon at c.228. RT-PCR showed reduced FUS mRNA by more than half compared to a healthy control (HC) and an ALS patient without genetic mutations (wtALS). In WI FUS band intensity in the proband was 30-50% compared to HC and wtALS. An antibody expected to detect only the wild-type protein did not reveal any reduction of FUS band intensity compared to the other antibodies. IF showed no difference among HC, wtALS, and the proband. Discussion: The reduction of FUS mRNA and protein in PBMC suggests the absence of the truncated protein, probably due to nonsense-mediated decay, leading to loss of function.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32924624

RESUMO

We describe the telemedicine experience of an Italian ALS tertiary Center during COVID-19 pandemic. A total of 144 visits were scheduled between 6th March and 6th April 2020. These mostly consisted of neurological or psychological visits (139, 96.5%). One hundred thirty-nine (96.5%) visits were performed as telemedicine and mostly via phone call (112, 80.6%). Three (2.1%) visits were considered as urgent and maintained as outpatient care. Additionally, patients were still able to telephone, being put through directly to their neurologists. Many requests of contact were addressed at getting information about the scheduled visits or examinations (45, 43.3%). Globally, patients and caregivers were satisfied with the telemedicine service. However, the majority (85, 65.9%) would prefer a face-to-face visit. In conclusion, telemedicine could be considered a good complement to face-to-face care, even after social restrictions have been eased.


Assuntos
Esclerose Amiotrófica Lateral/terapia , COVID-19 , Neurologia , Preferência do Paciente , Satisfação do Paciente , Psicologia , Telemedicina/métodos , Idoso , Esclerose Amiotrófica Lateral/fisiopatologia , Esclerose Amiotrófica Lateral/psicologia , Gerenciamento Clínico , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , SARS-CoV-2 , Fonoterapia , Centros de Atenção Terciária
5.
BMJ Open ; 10(3): e034049, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209625

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN. G-CSF safety in humans has been demonstrated and many observations suggest that it may affect neural cells. Therefore, we decided to use G-CSF to mobilise BMCs into the peripheral circulation in patients with ALS, planning a clinical trial to evaluate the effect of G-CSF administration in ALS patients compared with placebo. METHODS AND ANALYSIS: STEMALS-II is a phase II multicentre, randomised double-blind, placebo-controlled, parallel group clinical trial on G-CSF (filgrastim) and mannitol in ALS patients. Specifically, we investigate safety, tolerability and efficacy of four repeated courses of intravenous G-CSF and mannitol administered in 76 ALS patients in comparison with placebo (indistinguishable glucose solution 5%). We determine increase of G-CSF levels in serum and cerebrospinal fluid as CD34+ cells and leucocyte count after treatment; reduction in ALS Functional Rating Scale-Revised Score, forced vital capacity, Scale for Testing Muscle Strength Score and quality of life; the adverse events/reactions during the treatment; changes in neuroinflammation biomarkers before and after treatment. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Azienda Ospedaliera Universitaria 'Città della Salute e della Scienza', Torino, Italy. Results will be presented during scientific symposia or published in scientific journals. TRIAL REGISTRATION NUMBER: Eudract 2014-002228-28.


Assuntos
Esclerose Amiotrófica Lateral , Filgrastim/uso terapêutico , Esclerose Amiotrófica Lateral/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Método Duplo-Cego , Humanos , Itália , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Neurol ; 261(11): 2178-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25178511

RESUMO

NADPH-oxidases (NOX) catalyze the formation of reactive oxygen species (ROS), which play a role in the development of neurological diseases, particularly those generated by the phagocytic isoform NOX2. Increased ROS has been observed in the amyotrophic lateral sclerosis (ALS) SOD1 transgenic mouse, and in this preclinical model the inactivation of NOX2 decreases ROS production and extends survival. Our aim was to evaluate NOX2 activity measuring neutrophil oxidative burst in a cohort of 83 ALS patients, and age- and gender-matched healthy controls. Oxidative burst was measured directly in fresh blood using Phagoburst™ assay by flow cytometry. Mean fluorescence intensity (MFI), emitted in response to different stimuli, leads to produce ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity (GeoMean). No difference was found between the MFI values in cases and controls. NOX2 activity was independent from gender and age, and in patients was not related to disease duration, site of onset (bulbar vs. spinal), or ALSFRS-R score. However, patients with a NOX2 activity lower than the median value showed a 1-year increase of survival from onset (p = 0.011). The effect of NOX2 was independent from other known prognostic factors. These findings are in keeping with the observations in the mouse model of ALS, and demonstrate the strong role of NOX2 in modifying progression in ALS patients. A proper modulation of NOX2 activity might hold therapeutic potential for ALS.


Assuntos
Esclerose Amiotrófica Lateral/enzimologia , Esclerose Amiotrófica Lateral/mortalidade , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Idoso , Esclerose Amiotrófica Lateral/diagnóstico , Ativação Enzimática/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 2 , Taxa de Sobrevida/tendências
7.
PLoS One ; 8(2): e56282, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23437108

RESUMO

In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improves nerve regeneration following traumatic injury, possibly through the up-regulation of soluble NRG1 isoforms.


Assuntos
Envelhecimento/patologia , Nervo Mediano/fisiopatologia , Regeneração Nervosa/fisiologia , Receptor ErbB-2/metabolismo , Ferimentos e Lesões/fisiopatologia , Análise de Variância , Animais , Contagem de Células , Força da Mão , Masculino , Nervo Mediano/metabolismo , Nervo Mediano/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Compressão Nervosa , Neuregulina-1/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Células de Schwann/metabolismo , Células de Schwann/patologia , Solubilidade , Transgenes/genética , Ferimentos e Lesões/patologia
8.
Free Radic Biol Med ; 53(9): 1708-17, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22981873

RESUMO

Lipid peroxidation is generally considered as primarily implicated in the pathogenesis of Alzheimer's disease (AD); one of its more reactive end products, 4-hydroxynonenal (HNE), has been shown to cause neuron dysfunction and degeneration. HNE production in the brain is stimulated by the amyloid-ß peptide (Aß), whose excessive accumulation in specific brain areas is a hallmark of AD. Conversely, Aß production is up-regulated by this multifunctional aldehyde. Findings reported here point to the ability of HNE and Aß to interact, with consequent potentiation of Aß's cytotoxicity as determined in vitro using neuron-like cells derived from human dental-pulp progenitor cells. Preincubation of cells with the aldehyde markedly up-regulated Aß uptake and intracellular accumulation, by overexpressing two of the three components of the plasma membrane multireceptor complex CD36/CD47/ß1-integrin: experimental and clinical data indicate that intraneuronal accumulation of Aß is an early event possibly playing a primary role in AD pathogenesis. That HNE-mediated overexpression of CD36 and ß1-integrin, which plays a key role in HNE's potentiating Aß neurotoxicity, in terms of necrosis, was confirmed when this effect was prevented by specific antibodies against the two receptors.


Assuntos
Aldeídos/farmacologia , Peptídeos beta-Amiloides/fisiologia , Polpa Dentária/citologia , Peroxidação de Lipídeos , Neurônios/metabolismo , Adulto , Doença de Alzheimer , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Antígenos de Diferenciação/metabolismo , Apoptose , Antígenos CD36/genética , Antígenos CD36/metabolismo , Antígeno CD47/genética , Antígeno CD47/metabolismo , Diferenciação Celular , Forma do Núcleo Celular/efeitos dos fármacos , Forma Celular , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Integrina beta1/genética , Integrina beta1/metabolismo , L-Lactato Desidrogenase/metabolismo , Lipídeos de Membrana/metabolismo , Necrose , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Cultura Primária de Células , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Regulação para Cima/efeitos dos fármacos
9.
Stem Cells Dev ; 21(18): 3278-88, 2012 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-22582744

RESUMO

The stemness state is characterized by self-renewal and differentiation properties. However, stem cells are not able to preserve these characteristics in long-term culture because of the intrinsic fragility of their phenotype easily undergoing senescence or neoplastic transformation. Furthermore, although isolated from the same original tissue using similar protocols, adult stem cells can display dissimilar phenotypes and important cell clone/species contamination. Finally, the lack of a clear standardization contributes to complicate the comprehension about the stemness condition. In this context, cell lines displaying a particularly stable phenotype must be identified to define one or multiple benchmarks against which other stem cell lines could be reliably assessed. The present paper demonstrates that it is possible to isolate from the rat dental pulp a stem cell line (MUR-1) that does not display neoplastic transformation in long-term culture. MUR-1 cells stably express a broad range of stemness markers and are able to differentiate into adipogenic, osteogenic, chondrogenic, neurogenic, and cardiomyogenic lineages independently of the culture passages. Moreover, serial in vitro passages have not changed their immunophenotype, proliferation capacity, or differentiation potential. The uniqueness of these characteristics candidates MUR-1 as a model to reliably improve the understanding of the mechanisms governing the stem cell fate in the same as well as in other stem cell populations.


Assuntos
Células-Tronco Adultas/citologia , Células-Tronco Adultas/metabolismo , Diferenciação Celular , Polpa Dentária/citologia , Animais , Técnicas de Cultura de Células , Linhagem da Célula , Proliferação de Células , Transformação Celular Neoplásica , Células Cultivadas , Técnicas de Cocultura , Citometria de Fluxo , Masculino , Fenótipo , Ratos , Ratos Wistar
10.
Cancer Chemother Pharmacol ; 69(4): 983-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22139443

RESUMO

PURPOSE: Differentiation-inducing factor-1 (DIF-1) is a morphogen originally identified in the amoebozoan Dictyostelium discoideum. In mammalian cells, it has been shown to activate GSK3ß, which in turn is expected to reduce levels of ß-catenin and cyclin D1, thus mediating DIF-1 antiproliferative properties. Since this could alter the expression and activity of E2F1 transcription factor and consequently those of the prognostic marker/chemotherapy target thymidylate synthase (TS), we evaluated (1) whether DIF-1 could effectively regulate these genes, (2) whether it could interfere with cell viability, and (3) whether DIF-1 activity could enhance the efficacy of the TS inhibitor 5-fluorouracil (5-FU). METHODS: We investigated the effects of DIF-1 in continuous human cell lines derived from two oral tumor histotypes (corresponding to an adenosquamous and a squamous carcinoma) and a gingival epithelium. We evaluated mRNA accumulation by means of quantitative real-time PCR and efficacy of drugs on cell viability by means of MTT assay. RESULTS: DIF-1 inhibited the accumulation of E2F1 mRNA and reduces TS mRNA levels in tumor cell lines, but did not alter mRNA levels in the gingival counterpart. As a result, it inhibited proliferation preferentially of tumor cell in time- and concentration-dependent manner. Moreover, it enhanced cytotoxic effects of 5-FU only in tumor cell, whereas reduced them in the gingival counterpart. CONCLUSIONS: These findings suggest a tumor-specific action of DIF-1 on oral carcinoma cells. Thus, interfering with E2F1 and TS transcription, DIF-1 potentiates TS enzymatic inhibitors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fator de Transcrição E2F1/antagonistas & inibidores , Fluoruracila/farmacologia , Hexanonas/farmacologia , Neoplasias Bucais/tratamento farmacológico , RNA Mensageiro/antagonistas & inibidores , Timidilato Sintase/antagonistas & inibidores , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Fator de Transcrição E2F1/biossíntese , Fator de Transcrição E2F1/genética , Fluoruracila/administração & dosagem , Expressão Gênica , Hexanonas/administração & dosagem , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Timidilato Sintase/biossíntese , Timidilato Sintase/genética
11.
Cancer Prev Res (Phila) ; 4(7): 994-1001, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21733823

RESUMO

Vaccines against oncoantigens halt early neoplastic lesions in several cancer-prone, genetically engineered mouse models, whereas their ability to prevent chemical carcinogenesis has not been explored. This is a significant issue, as exposure to chemical mutagens is responsible for a substantial percentage of cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is transiently overexpressed in Syrian hamsters during the early stages of 7,12-dimethylbenz[α]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA vaccinations against ERBB2 significantly reduce the number, size, and severity of oral lesions in a manner directly proportional to the anti-ERBB2 antibody response. These results support the prospects of vaccines as a fresh strategy in the management of individuals at risk for exposure to defined carcinogenic agents.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/prevenção & controle , Neoplasias Bucais/prevenção & controle , Receptor ErbB-2/genética , Vacinas de DNA/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Western Blotting , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Cricetinae , Técnicas Imunoenzimáticas , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia , Invasividade Neoplásica , Receptor ErbB-2/metabolismo
12.
Oral Oncol ; 46(1): 42-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19932051

RESUMO

Oral squamous cell carcinoma (OSCC) develops slowly and it is usually preceded by identifiable oral preneoplastic lesions (OPLs): chemoprevention could be a promising approach. Resveratrol (RV) is a plant-based agent characterized by a strong in vitro antineoplastic action, but this effect has not been clinically confirmed owing to its metabolic inactivation. In order to circumvent this limitation and to improve RV efficacy, it was locally applied and complexed with a protective and solubilising vehicle (2-hydroxypropyl-beta-cyclodextrin, HPbetaCD). The experimentation was performed in vitro on 7,12-dimethylbenz[a]anthracene-induced hamster OSCC cell line (HCPC I) and in vivo in the related animal model, by comparison of two RV-HPbetaCD formulations (cream and mouthwash) and RV alone. Vehicles and RV-formulations were free from toxicity. Antiproliferative action of RV on HCPC I was concentration- and time-dependent, and was improved in HPbetaCD-formulations. In vivo, RV prevented OPL and OSCC appearance and growth. Here, too, HPbetaCD-formulations (mainly mouthwash) demonstrated the best chemopreventive effects in terms of lesions prevalence, multiplicity, dimension, and histological signs of malignancy. HPLC detection of RV corroborated that its action is concentration-correlated and is improved by its inclusion in HPbetaCDs. In summary, our study demonstrates that RV is effective in the chemoprevention of DMBA-induced oral carcinogenesis and when it is complexed with HPbetaCDs its efficacy is significantly improved.


Assuntos
Anticarcinógenos/administração & dosagem , Carcinoma de Células Escamosas/prevenção & controle , Transformação Celular Neoplásica , Neoplasias Bucais/prevenção & controle , Estilbenos/administração & dosagem , beta-Ciclodextrinas/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina , 9,10-Dimetil-1,2-benzantraceno , Administração Tópica , Animais , Anticarcinógenos/química , Carcinógenos , Carcinoma de Células Escamosas/induzido quimicamente , Linhagem Celular Tumoral , Transformação Celular Neoplásica/induzido quimicamente , Bochecha , Cricetinae , Combinação de Medicamentos , Mesocricetus , Neoplasias Bucais/induzido quimicamente , Veículos Farmacêuticos/administração & dosagem , Veículos Farmacêuticos/química , Resveratrol , Estilbenos/química , beta-Ciclodextrinas/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...