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1.
Eur J Neurol ; 18(3): 471-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20722713

RESUMO

BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson's disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). METHODS: We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age-matched subjects. RESULTS: Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. CONCLUSION: These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages.


Assuntos
Encéfalo/patologia , Doença de Parkinson/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
2.
Eur J Neurol ; 17(5): 661-5, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20050890

RESUMO

BACKGROUND: Patients with Parkinson's disease (PD) and chronically treated with L-DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after discontinuation of 1-month folate supplementation given to normalize plasma tHcy levels. METHODS: Plasma tHcy, cobalamin and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years) stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day. RESULTS: After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2-month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper-tHcy. CONCLUSIONS: One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD.


Assuntos
Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/tratamento farmacológico , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Idoso , Estudos Transversais , Dopaminérgicos/efeitos adversos , Dopaminérgicos/uso terapêutico , Feminino , Predisposição Genética para Doença/genética , Homocisteína/biossíntese , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/fisiopatologia , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/genética , Estudos Prospectivos , Prevenção Secundária , Resultado do Tratamento , Vitamina B 12/sangue
3.
Neuromolecular Med ; 9(3): 249-54, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17914182

RESUMO

High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.


Assuntos
Antiparkinsonianos/uso terapêutico , Homocisteína/sangue , Hiper-Homocisteinemia/enzimologia , Levodopa/uso terapêutico , Metilenotetra-Hidrofolato Redutase (NADPH2)/fisiologia , Doença de Parkinson/tratamento farmacológico , Polimorfismo Genético , Idoso , Feminino , Ácido Fólico/sangue , Humanos , Hiper-Homocisteinemia/genética , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Vitamina B 12/sangue
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