RESUMEN
INTRODUCTION: The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinson's disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment. AIMS: To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function. PATIENTS AND METHODS: 58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation. RESULTS: Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients). CONCLUSIONS: Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evident in patients with cognitive impairment.
Asunto(s)
Trastornos del Conocimiento , Homocisteína/sangre , Levodopa/efectos adversos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/sangre , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Femenino , Ácido Fólico/sangre , Humanos , Levodopa/sangre , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/tratamiento farmacológico , Vitamina B 12/sangreRESUMEN
Introducción. La relación entre homocisteína (Hc) y enfermedades vasculares se conoce desde hace más de 30 años. En los últimos años se ha relacionado también con deterioro cognitivo y motor. En la enfermedad de Parkinson (EP), el tratamiento crónico con levodopa puede inducir un incremento en los niveles de Hc, implicando un riesgo añadido para el deterioro cognitivo. Objetivos. Confirmar la elevación de los niveles de Hc en pacientes con EP tratados con levodopa, su relación con los niveles de vitamina B12 y folato, y si podía existir una relación entre dichas variables y la función cognitiva. Pacientes y métodos. Se incluyeron 58 pacientes diagnosticados de EP (45 en tratamiento con levodopa), se determinaron los niveles basales de Hc, vitamina B12 y folato, y se realizó una evaluación neuropsicológica en 45 de los pacientes. Resultados. El nivel de Hc estaba significativamente más elevado en los pacientes en tratamiento con levodopa, sin relación con la dosis ni el tiempo en tratamiento. Existía una correlación negativa entre los valores de Hc y vitamina B12 y folato en los hombres, que no se observó en las mujeres. Tomar entacapona no redujo los niveles de Hc. El nivel de Hc estaba significativamente más elevado en los pacientes con deterioro cognitivo (9 de los 45 evaluados).Conclusiones. Nuestro estudio confirma la elevación de los niveles de Hc en pacientes con EP en tratamiento con levodopa, y de forma más evidente en los pacientes con deterioro cognitivo (AU)
Introduction. The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinsons disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment. Aims. To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function. Patients and methods. 58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation. Results. Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients). Conclusions. Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evidentin patients with cognitive impairment (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Parkinson/fisiopatología , Trastornos del Conocimiento/fisiopatología , Homocisteína/efectos adversos , Homocisteína/análisis , Levodopa/efectos adversos , Vitamina B 12/sangre , Ácido Fólico/sangre , Pruebas NeuropsicológicasAsunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Inmunoglobulina G/efectos adversos , Esclerosis Múltiple/inducido químicamente , Adulto , Artritis Psoriásica/tratamiento farmacológico , Etanercept , Femenino , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética/métodos , Hemisuccinato de Metilprednisolona/uso terapéutico , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Prednisolona/uso terapéutico , Receptores del Factor de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeoRESUMEN
The cause of Parkinson's disease remains unknown although some evidence suggests that an inflammatory reaction, mediated by cytokines such as TNF-alpha and IL-1beta, is related with dopaminergic degeneration in the brain. In the present work we measured the plasma levels of TNF-alpha and IL-1beta in parkinsonian monkeys one year after MPTP administration. TNF-alpha levels were seen to have increased in parkinsonian monkeys reflecting the clinical symptoms observed, while IL-1beta levels remained unchanged. These results suggest that TNF-alpha plays a role in sustaining of dopaminergic degeneration in chronic parkinsonism.
Asunto(s)
Interleucina-1/sangre , Trastornos Parkinsonianos/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Dopamina/fisiología , Macaca fascicularis , Masculino , Degeneración Nerviosa/sangre , Degeneración Nerviosa/inmunología , Neurotoxinas/farmacología , Trastornos Parkinsonianos/sangreRESUMEN
Inflammatory changes have been found in Parkinson's disease, in humans intoxicated with the parkinsonian toxin MPTP, and in animal models of the disease. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or if they have a protective role against neurodegeneration. In this study, we analyzed the glial reaction in the substantia nigra pars compacta (SNpc) and the striatum of monkeys rendered parkinsosian by chronic MPTP injections. At postmortem examination 1 year after the last MPTP injection, the density of astroglial cells and activated microglial cells in the SNpc, but not in the striatum, of MPTP-intoxicated animals was significantly higher than in the two control animals. These data suggest that neurodegeneration was still active despite the absence of the agent triggering cell death and that the glial reaction is associated with long-term neurodegeneration.
Asunto(s)
Gliosis/patología , Microglía/efectos de los fármacos , Trastornos Parkinsonianos/patología , Sustancia Negra/patología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Astrocitos/citología , Astrocitos/efectos de los fármacos , Biomarcadores , Calbindinas , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/patología , Cuerpo Estriado/fisiopatología , Modelos Animales de Enfermedad , Dopamina/metabolismo , Encefalitis/inducido químicamente , Encefalitis/patología , Encefalitis/fisiopatología , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/inducido químicamente , Gliosis/fisiopatología , Antígenos HLA-DR/metabolismo , Inmunohistoquímica , Macaca fascicularis , Microglía/patología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/fisiopatología , Proteína G de Unión al Calcio S100/metabolismo , Sustancia Negra/efectos de los fármacos , Sustancia Negra/fisiopatología , Tiempo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
In 1988 McGeer and colleagues (Neurology 38, 1285-91) observed an activation of the microglia in substantia nigra pars compacta (SNpc) and striatum of brains from patients with Parkinson's disease. In the years that followed several studies performed in the cerebrospinal fluid and during post-mortem analysis in parkinsonian patients revealed increased levels of cytokines, suggesting the activation of a proinflammatory response. Moreover, Langston and his group described the presence of active microglia in the SNpc of three patients who had been exposed to MPTP several years before death. These results suggested that the inflammatory response may increase negative feed-back into the damaged area of the cerebral parenchyma, inducing an imbalance that could perpetuate and/or accelerate neuronal death over a period of years. Similar results have been obtained in parkinsonian monkeys, rats and mice. For these reasons, several groups have treated parkinsonian animals with different anti-inflammatory drugs and obtained promising results. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or whether they play a protective role in neurodegeneration. These changes are putatively related to neuronal loss and suggest that anti-inflammatory treatment for parkinsonian patients could have beneficial effects in the progression of the disease by slowing down the process of neuronal loss.