Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 70
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Neurol Sci ; 36(5): 751-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25528460

RESUMO

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers.


Assuntos
Redes Comunitárias , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/epidemiologia , Disseminação de Informação , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Feminino , Humanos , Itália , Masculino , Prevalência
2.
Nat Genet ; 2(4): 330-4, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1303289

RESUMO

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.


Assuntos
Doença de Alzheimer/genética , Cromossomos Humanos Par 14 , Idoso , Alelos , Precursor de Proteína beta-Amiloide/genética , Sequência de Bases , Mapeamento Cromossômico , DNA/genética , Feminino , Marcadores Genéticos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2270-2273, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018460

RESUMO

Iron plays important roles in healthy brain but altered homeostasis and concentration have been correlated to aging and neurodegenerative diseases. Iron enters the central nervous system by crossing the brain barrier systems: the Blood- Brain Barrier separating blood and brain and the Blood-Cerebrospinal Fluid Barrier (BCSFB) between blood and CSF, which is in contact with the brain by far less selective barriers. Herein, we develop a two-compartmental model for the BCSFB, based on first-order ordinary differential equations, performing numerical simulations and sensitivity analysis. Furthermore, as input parameters of the model, experimental data from patients affected by Alzheimer's disease, frontotemporal dementia, mild cognitive impairment and matched neurological controls were used, with the aim of investigating the differences between physiological and pathological conditions in the regulation of iron passage between blood and CSF which can be possibly targeted by therapy.


Assuntos
Doenças Neurodegenerativas , Barreira Hematoencefálica , Encéfalo , Humanos , Ferro , Modelos Teóricos
4.
Cephalalgia ; 29(6): 687-90, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19220302

RESUMO

Status migrainosus is a condition characterized by a migraine attack causing disability, with or without aura, lasting for > 72 h. The pathophysiological mechanisms underlying this complication of migraine remain a matter of debate. We describe a migraine without aura patient who presented two episodes of status migrainosus associated with recurrent and reversible brain magnetic resonance imaging abnormalities. These abnormalities, confirmed also by positron emission tomography, suggest that status migrainosus can be associated with a condition of vasogenic cerebral oedema.


Assuntos
Encéfalo/patologia , Transtornos de Enxaqueca/patologia , Adolescente , Analgésicos/uso terapêutico , Criança , Eletroencefalografia , Epilepsia/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Convulsões/complicações
5.
Cephalalgia ; 29(8): 818-25, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17714520

RESUMO

There are conflicting data concerning the association between migraine and C677T polymorphism of the MTHFR gene. The C677T polymorphism reduces enzymatic capability by 50% and causes hyperhomocysteinaemia. We performed a meta-analysis of all published studies investigating the association between the MTHFR gene and migraine. Pooled odds ratios (OR) were estimated using random (RE) and fixed effects (FE) models. Among the overall 2961 migraineurs there was no significant difference compared with controls. Only in migraine with aura was the TT genotype associated with a higher risk of disease compared with the CC genotype [FE OR 1.30, 95% confidence interval (CI) 1.06, 1.58; RE OR 1.66, 95% CI 1.06, 2.59]. In the same subgroup a significant difference was observed in the comparison between TT and CT + CC genotypes (FE OR 1.32, 95% CI 1.10, 1.59; RE OR 1.63, 95% CI 1.10, 2.43). This study provides evidence for an association of the MTHFR gene only in migraine with aura.


Assuntos
Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único/genética , Humanos , Incidência , Medição de Risco , Gestão de Riscos
6.
Eur J Neurol ; 16(7): 870-3, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19473369

RESUMO

BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is considered as a proteinopathy; therefore, it is conceivable that genes encoding for factors involved in protein misfolding and/or degradation could play a role in its pathogenesis. METHODS: An association study of defective in cullin neddylation 1 (DCN-1)-domain containing 1 (DCUN1D1), which is involved in protein degradation, was carried out in a population of 220 patients with FTLD as compared with 229 age-matched controls. RESULTS: A statistically significant increased frequency of the GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) was observed in patients compared with controls (6.9 vs. 1.7%, P = 0.011, adjusted OR: 4.39, 95% CI: 1.40-13.78). Stratifying according to the clinical syndrome, significant differences were observed between the behavioral variant of frontotemporal dementia and controls (GG frequency: 6.3 vs. 1.7%, P = 0.02, OR:4.0, 95%, CI = 1.24-12.92), as well as between patients with progressive aphasia compared with controls (15.4 vs. 1.7%, P = 0.014, OR = 11.30, 95%, CI = 1.63-78.45), but not in patients with SD versus controls (8.3 vs. 1.7%, P = 0.18, OR = 5.24, 95% C.I. = 0.45-60.63). No significant differences in allelic and genotypic frequencies of the DCUN1D1 rs4859147 SNP were found. CONCLUSIONS: The GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold.


Assuntos
Demência/etiologia , Demência/genética , Predisposição Genética para Doença , Proteínas Oncogênicas/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Análise Mutacional de DNA/métodos , Éxons/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas , Proteínas Proto-Oncogênicas , Fatores de Risco
7.
Eur J Neurol ; 16(1): 37-42, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19087148

RESUMO

BACKGROUND AND AIMS: Neuronal nitric oxide synthase (NOS)1 C276T polymorphism was shown to increase the risk for frontotemporal lobar degeneration (FTLD). In the brain, both NOS1 and NOS3 (endothelial isoform) have been detected. The distribution of NOS3 G894T (Glu298Asp) and T-786C single nucleotide polymorphisms (SNPs) was analyzed in a population of 222 patients with FTLD compared with 218 age-matched controls to determine whether they could influence the susceptibility to develop the disease. RESULTS: A statistically significant increased frequency of the NOS3 G894T SNP was observed in patients as compared with controls (40.0 vs. 31.4%, P = 0.011, OR: 1.65, CI: 1.13-2.42). Conversely, the distribution of the T-786C SNP was similar in patients and controls. No differences were observed stratifying according to gender. DISCUSSION: The NOS3 G894T polymorphism likely acts as risk factor for sporadic FTLD, but studies in larger populations are needed to confirm these preliminary findings.


Assuntos
Degeneração Lobar Frontotemporal/enzimologia , Degeneração Lobar Frontotemporal/genética , Predisposição Genética para Doença/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Degeneração Lobar Frontotemporal/epidemiologia , Predisposição Genética para Doença/epidemiologia , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/deficiência , Gravidez , Fatores de Risco
8.
J Headache Pain ; 10(2): 111-4, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19209385

RESUMO

Aquaporin4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. The purpose of our work was to evaluate the association of polymorphisms in the AQP4 gene with the risk and the clinical features of migraine. A total of 293 migraineurs and 249 controls were involved in the study. They were genotyped for four single nucleotide polymorphisms (SNPs) of AQP4 gene. No significant difference in the distribution of AQP4 genotypic and allelic frequencies between cases and controls was found. In addition, haplotype analysis did not show any significant difference. Comparison of the clinical features of the disease according to different AQP4 genotypes showed no significant difference. Our data do not support the hypothesis that the AQP4 gene could represent a genetic susceptibility factor for migraine.


Assuntos
Aquaporina 4/genética , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
9.
Exp Gerontol ; 118: 106-116, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30658120

RESUMO

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.


Assuntos
Analgesia/métodos , Transtornos Neurocognitivos/fisiopatologia , Idoso , Doença de Alzheimer/fisiopatologia , Função Executiva/fisiologia , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Percepção da Dor , Efeito Placebo , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia
10.
Neuron ; 13(3): 727-36, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7917302

RESUMO

Mutations in the Cu, Zn superoxide dismutase (SOD1) gene have been reported in some pedigrees with Familial Amyotrophic Lateral Sclerosis (FALS). We have investigated the functional and structural effects of a Gly-->Ser mutation at codon 41 of SOD1 in a pedigree with FALS and the topography of SOD1 expression in the mammalian CNS. These analyses show that the 41Gly-->Ser mutation causes a 27% reduction in Cu, Zn SOD activity. SOD1 is transcribed at high levels in rat motoneurons and four other types of neurons homologous to upper motoneurons that degenerate in human ALS. However, SOD1 is transcribed at lower levels in other types of neurons, such as cerebellar Purkinje cells, which are not usually involved significantly in human ALS. On the other hand, immunocytochemical studies indicate that most types of rat neurons contain similar levels of Cu, Zn SOD immunoreactive protein. Nevertheless, these results suggest that the essential feature causing this subtype of ALS is either a reduction in Cu, Zn SOD activity in cell types that presumably critically require Cu, Zn SOD for protection against oxidative damage or the fact that the mutation in SOD1 associated with FALS results in a novel gain of function that is particularly deleterious to those cell types expressing SOD1 at high levels.


Assuntos
Esclerose Lateral Amiotrófica/enzimologia , Mutação , Superóxido Dismutase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Imuno-Histoquímica , Hibridização In Situ , Masculino , Biologia Molecular , Sondas Moleculares/genética , Dados de Sequência Molecular , Ratos , Ratos Sprague-Dawley
11.
J Neurol Neurosurg Psychiatry ; 79(4): 471-3, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18344399

RESUMO

OBJECTIVE: Several lines of evidence indicate a role for inflammatory processes in the development of cerebral aneurysms. Recently, polymorphisms in the promoter region of the interleukin 6 (IL6) gene were shown to be associated with intracranial aneurysmal disease. The purpose of this study was to verify the association of two functionally active polymorphisms (-174 G>C and -572 G>C) in the promoter region of the IL6 gene with the risk and clinical features of aneurysmal subarachnoid haemorrhage (SAH) in an Italian population. METHODS: A total of 179 consecutive aneurysmal SAH patients and 156 healthy controls were involved in the study. Cases and controls were genotyped for the -174 G

Assuntos
Genética Populacional , Interleucina-6/genética , Aneurisma Intracraniano/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Hemorragia Subaracnóidea/genética , Adulto , Idoso , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Cephalalgia ; 28(7): 714-22, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18479471

RESUMO

The study set out to investigate the role of corticotrophin-releasing factor (CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache (MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled. Control CSF specimens were obtained from 20 age-matched subjects who underwent lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests excluded central nervous system or systemic diseases. Orexin-A and CRF were determined by radioimmunoassay methods. Significantly higher levels of orexin-A and CRF were found in the CSF of MOH and to a lesser extent in patients with CM compared with control subjects (orexin-A: P < 0.001 and P < 0.02; CRF: P < 0.002 and P < 0.0003). A significant positive correlation was also found between CSF orexin-A values and those of CRF (R = 0.71; P < 0.0008), monthly drug intake group (R = 0.39; P < 0.03) and scores of a self-completion 10-item instrument to measure dependence upon a variety of substances, the Leeds Dependence Questionnaire (LDQ) in the MOH group (R = 0.68; P < 0.0003). The significantly higher orexin-A levels found in CM and MOH can be interpreted as a compensatory response to chronic head pain or, alternatively, as an expression of hypothalamic response to stress due to chronic pain. A potential role for orexin-A in driving drug seeking in MOH patients through activation of stress pathways in the brain can also be hypothesized.


Assuntos
Hormônio Liberador da Corticotropina/líquido cefalorraquidiano , Transtornos da Cefaleia Secundários/fisiopatologia , Transtornos da Cefaleia/fisiopatologia , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Transtornos de Enxaqueca/fisiopatologia , Neuropeptídeos/líquido cefalorraquidiano , Adulto , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Quimioterapia Combinada , Feminino , Transtornos da Cefaleia/diagnóstico , Transtornos da Cefaleia Secundários/diagnóstico , Humanos , Hipotálamo/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Orexinas , Radioimunoensaio , Valores de Referência , Punção Espinal , Estresse Fisiológico/fisiopatologia
13.
Neurobiol Aging ; 25(10): 1293-8, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15465625

RESUMO

Inflammatory processes are involved in the pathogenesis of Alzheimer's disease (AD). Several studies have addressed the effects of interleukin-1 (IL-1) genes polymorphisms on the risk of developing AD. The results are not in full agreement on whether these polymorphisms are associated with the disease. To clarify this issue, we performed a meta-analysis of all the association studies between IL-1 genes and AD. Due to the relatively small number of published articles, the meta-analysis was restricted to the association of the IL-1alpha -889 C/T gene polymorphism and AD. Under a random effects model, the risk for the disease was significantly higher in subjects with the T/T genotype in comparison with both C/T (OR: 1.51; 95% C.I.: 1.15-1.99) and C/C (OR: 1.49; 95% C.I.: 1.09-2.03) subjects. There was modest heterogeneity for these effect estimates. Analysis of subgroups showed a significant association in patients with early-onset AD but not in late-onset AD. Our data support a significant but modest association between the T/T genotype of the IL-1alpha gene and AD.


Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Interleucina-1/genética , Medição de Risco/métodos , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Fatores de Risco
14.
Arch Neurol ; 45(9): 973-6, 1988 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2458094

RESUMO

Intravenous administration of methylphenidate hydrochloride, a central stimulant, was unexpectedly found to exert a potent analgesic effect on primary sensory symptoms in a group of patients with Parkinson's disease. This effect, which has now been studied in a short-term, double-blind, placebo-controlled experiment, subsequently disappeared if patients were pretreated with a beta-blocker or with a serotonin antagonist. Cerebrospinal fluid monoamine metabolites were determined in some of these patients, and the 5-hydroxyindoleacetic acid level was found to be significantly lower than in parkinsonian patients without pain and in normal volunteers. Given the mechanism of action of methylphenidate on the central nervous system, the adrenergic and serotoninergic mediation of its analgesic effect, and the demonstration of impaired central serotonin metabolism in the patient group, it is concluded that not only central dopaminergic deficiency but also altered noradrenergic and serotoninergic transmission in the spinal cord are quite likely to play a role in the pathophysiology of pain in Parkinson's disease.


Assuntos
Analgésicos/uso terapêutico , Metilfenidato/uso terapêutico , Cuidados Paliativos , Doença de Parkinson/tratamento farmacológico , Sensação , Idoso , Aminas Biogênicas/líquido cefalorraquidiano , Fenômenos Biomecânicos , Humanos , Masculino , Metilfenidato/antagonistas & inibidores , Metisergida/farmacologia , Pessoa de Meia-Idade , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/fisiopatologia , Pré-Medicação , Propranolol/farmacologia
15.
Arch Neurol ; 45(11): 1224-7, 1988 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2847695

RESUMO

We measured alpha-melanocyte-stimulating hormonelike immunoreactivity in cerebrospinal fluid of 12 healthy control subjects and nine patients with Parkinson's disease, four of whom had never been treated. Mean cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentration was two-fold greater in parkinsonian patients (44.1 +/- 9.3 [SD] pg/mL) as compared with control subjects (21.8 +/- 10.0 pg/mL). No significant correlation was found between cerebrospinal fluid alpha-melanocyte-stimulating hormonelike immunoreactivity concentrations and patient age, disease severity, or duration of disease. These results suggest a functional relation between dopaminergic and melanotropinergic systems in the human brain.


Assuntos
Doença de Parkinson/líquido cefalorraquidiano , alfa-MSH/líquido cefalorraquidiano , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Neurology ; 33(11): 1453-9, 1983 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6685238

RESUMO

When muscle fibers are stimulated in the distal portion of the human biceps brachii, far enough from the end-plate region, a discrete single fiber activity can be picked up proximally by means of a selective recording electrode. The distally evoked potentials show a linear relationship between latency and distance and can be recorded also in curarized patients. The risk of stimulating the intramuscular nerve endings is remote and, when it occasionally happens, the indirectly evoked muscle activity can be distinguished from the direct one. As direct muscle stimulation is feasible and safe, propagation velocity along single fibers can be determined in situ over a long distance. The results obtained in 50 normal subjects are presented.


Assuntos
Contração Muscular , Condução Nervosa , Adolescente , Adulto , Idoso , Braço , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Junção Neuromuscular/fisiologia
17.
Neurology ; 38(8): 1281-4, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2840605

RESUMO

We measured CSF alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-LI) in 35 patients with dementia of the Alzheimer type (DAT) and in 27 healthy control subjects. Mean alpha-MSH-LI concentration was significantly decreased in DAT patients as compared with age-matched controls. However, when the DAT patients were analyzed according to age at onset of dementia or presence of extrapyramidal signs, alpha-MSH-LI concentrations remained significantly lower than in controls only in DAT patients with late onset of dementia (greater than 65 years of age). No correlation was found between alpha-MSH levels and degree of mental impairment. A significant negative correlation was found between CSF concentrations of alpha-MSH and homovanillic acid in the group of all DAT patients (p less than 0.001). These results suggest that hypothalamic neurons which produce pro-opiomelanocortin-related peptides may be involved in Alzheimer's disease.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , alfa-MSH/líquido cefalorraquidiano , Adulto , Idoso , Química Encefálica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Neurology ; 44(2): 347-9, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8309590

RESUMO

We have discovered a new Italian pedigree with autosomal-dominant ALS. The pedigree, at present, comprises 75 members distributed in five generations. ALS was diagnosed in eight patients. The mean +/- SD age of onset of the disease was 46.8 +/- 13.5 years, with a range of 29 to 63 years. The mean +/- SD duration of the disease was 11.6 +/- 1.7 months. Molecular genetic studies showed a missense mutation (Gly-->Ser, codon 41) in exon 2 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21 in the available affected member and in 45% of the at-risk subjects of the pedigree. This study confirms the presence of SOD1 point mutations in families with autosomal-dominant ALS and suggests that additional genetic or environmental factors may be involved in the full expression of the disease.


Assuntos
Esclerose Lateral Amiotrófica/enzimologia , Esclerose Lateral Amiotrófica/genética , Cromossomos Humanos Par 21 , Mutação Puntual , Superóxido Dismutase/genética , Adulto , Sequência de Bases , DNA/sangue , Primers do DNA , Família , Feminino , Glicina , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Serina
19.
Neurology ; 43(11): 2275-9, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8232942

RESUMO

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Cromossomos Humanos Par 14 , Genes fos/genética , Regiões Promotoras Genéticas/genética , Adulto , Ligação Genética , Humanos , Pessoa de Meia-Idade , Linhagem , Polimorfismo Genético , Mapeamento por Restrição
20.
Pain ; 80(1-2): 377-82, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10204751

RESUMO

We tested both pain thresholds and pain tolerance in patients with Alzheimer's disease (AD) by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case arm ischemia was studied. By comparing AD patients with normal subjects of the same age, we found no differences in stimulus detection and pain thresholds, whereas a clearcut increase in pain tolerance was present in AD patients. The severity of AD was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram (EEG). There was a straightforward correlation between MMSE scores and pain tolerance such that the more severe the cognitive impairment the higher the tolerance to pain. In addition, analysis of the EEG power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia. These findings show that, whereas the sensory-discriminative component of pain is maintained in AD patients, pain tolerance is altered and depends on cognitive and affective factors. Thus, pain tolerance is tightly related to the severity of the disease according to the rule, 'the more severe the MMSE and EEG changes, the higher the tolerance to pain'.


Assuntos
Doença de Alzheimer/psicologia , Limiar da Dor , Idoso , Doença de Alzheimer/fisiopatologia , Cognição , Estimulação Elétrica , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Escalas de Graduação Psiquiátrica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA