RESUMEN
La luxación de codo asociada a fractura ipsilateral del radio distal y lesión de la arteria braquial constituye una patología traumática infrecuente. Las 2 referencias de esta asociación de lesiones aparecieron en 2015, aunque en ambas, los autores no advirtieron que constituían los 2 primeros casos publicados en la literatura médica; incluso en el título de sus artículos, no se hizo mención de la fractura del extremo distal del radio, pero sí en sus textos. El objeto de este trabajo es dar a conocer 3 casos con esta nueva entidad patológica traumática, explicar su posible mecanismo patogénico, el tratamiento utilizado y los resultados obtenidos (AU)
Elbow dislocation associated with ipsilateral fracture of the distal radius and a brachial artery injury is an uncommon traumatic entity. The two references of this injury combination appeared in 2015, although both authors did not realise that they were the first two cases published in the medical literature. Although mentioned in the text of the articles, no mention was made of the fracture of the distal radius in the titles. The purpose of this paper is to present three cases with this new traumatic pathological entity, explaining its pathogenetic mechanism, the treatment used, and the results obtained (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Anciano , Codo/lesiones , Codo/cirugía , Codo , Arteria Braquial/lesiones , Arteria Braquial , Fracturas del Radio/cirugía , Fracturas del Radio , Fijación Interna de Fracturas , Isquemia/complicacionesRESUMEN
Elbow dislocation associated with ipsilateral fracture of the distal radius and a brachial artery injury is an uncommon traumatic entity. The two references of this injury combination appeared in 2015, although both authors did not realise that they were the first two cases published in the medical literature. Although mentioned in the text of the articles, no mention was made of the fracture of the distal radius in the titles. The purpose of this paper is to present three cases with this new traumatic pathological entity, explaining its pathogenetic mechanism, the treatment used, and the results obtained.
Asunto(s)
Arteria Braquial/lesiones , Lesiones de Codo , Luxaciones Articulares/diagnóstico , Traumatismo Múltiple/diagnóstico , Fracturas del Radio/diagnóstico , Lesiones del Sistema Vascular/diagnóstico , Adulto , Anciano , Femenino , Humanos , Luxaciones Articulares/etiología , Masculino , Traumatismo Múltiple/etiología , Fracturas del Radio/etiología , Lesiones del Sistema Vascular/etiologíaRESUMEN
INTRODUCTION: Treatment of acute high-grade acromioclavicular joint (ACJ) injuries with metal hardware alters the biomechanics of the ACJ, implying a second surgery for hardware removal. The period during which the plate is present involves functional limitations, pain and a risk factor for the development of hardware-related-injuries. Arthroscopy-assisted procedures compared to open-metal hardware techniques offer: less morbidity, the possibility to treat associated lesions and no need for a second operation. The aim was to compare the Quality of life (QoL) of patients with acute high-grade ACJ injuries (Rockwood grade III-V), managed arthroscopically with a non-rigid coracoclavicular (CC) fixation versus the QoL of patients managed with a hook plate, 24 months or more after their shoulder injury. PATIENTS AND METHODS: A retrospective revision of high-grade ACJ injuries managed in three institutions was performed. Patients treated by means of an arthroscopy-assisted CC fixation or by means of a hook plate were included. The inclusion period was between 2008 and 2012. The QoL was evaluated at the last follow-up visit by means of the SF36, the visual analog scale (VAS), the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, the Constant score and the global satisfaction (scale from 0 to 10). The presence of scapular dyskinesis and remaining vertical instability were evaluated. Comparison between groups was performed. RESULTS: Thirty-one patients were included: 20 arthroscopy-group (ARTH group: 3 Rockwood III, 3 IV and 14 V) and 11 hook plate-group (HOOK group: 5 Rockwood III and 6 V). The mean age was 36 [25-52] year-old for the ARTH group and 41 [19-55] for the HOOK group (P=0.185). The mean results of the questionnaires were: (1) physical SF36 score (ARTH group 58.24±2.16 and HOOK group 53.70±4.33, P<0.001); (2) mental SF36 score (ARTH group 56.15±2.21 and HOOK group 53.06±6.10, P=0.049); (3) VAS (ARTH group 0.40±0.50 and HOOK group 1.45±1.51, P=0.007); (4) DASH (ARTH group 2.98±2.03 and HOOK group 4.79±5.60, P=0.200); (5) Constant score (ARTH group 95.30±2.45 and HOOK group 91.36±6.84, P=0.026); (6) global satisfaction (ARTH group 8.85±0.93 and HOOK group 8.00±1.18, P=0.035). There was evidence of scapular dyskinesis in 15% (3/20) of the patients of the ARTH group and in 18% (2/11) of the patients of the HOOK group (P=1.000). Remaining vertical ACJ instability was observed in 40% (8/20) of the patients of the ARTH group and in 36.36% (4/11) of the patients of the HOOK group (P=1.000). CONCLUSION: Patients with acute high-grade ACJ injuries managed arthroscopically with a non-rigid CC fixation seem to have a better QoL than patients managed with a hook plate. LEVEL OF EVIDENCE: Level IV therapeutic; retrospective comparative study.
Asunto(s)
Articulación Acromioclavicular/lesiones , Artroscopía/métodos , Placas Óseas , Luxaciones Articulares/cirugía , Calidad de Vida , Articulación Acromioclavicular/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Valorar los resultados de la técnica quirúrgica asistida por artroscopía indicada para el tratamiento de la inestabilidad acromioclavicular crónica (IAC), basada en la fijación coracoclavicular (CC) no-rígida más reconstrucción CC anatómica con aloinjerto tendinoso. Se incluyó a los pacientes con IAC intervenidos entre 2008 y 2012. Las valoraciones clínicas se realizaron mediante el SF36, la EVA y el DASH, aplicados en la visita previa (VPI) a la intervención y en la última visita de seguimiento (UVS). El Constant score y la Escala de Satisfacción General (0-10) se aplicaron en la última visita de seguimiento. Se valoró el desarrollo de subluxaciones secundarias. Se incluyeron 10 pacientes. Edad media 41 años [rango 33-55]. Seguimiento medio 25.50 meses [rango 24-30].En todos los pacientes el tratamiento quirúrgico se indicó cuando el tratamiento conservador fracasó. Cuestionarios aplicados en la VPI y en la UVS: 1. SF36 físico: VPI 29.60 ± 3.41 y UVS 59.58 ± 1.98 (p = 0.000); 2. SF36 mental: VPI 46.57 ± 3.80 y UVS 56.62 ± 1.89 (p = 0.000); 3. EVA: VPI 5.17 ± 2.40 y UVS 1.67 ± 2.07 (p = 0.022); y 4. DASH: VPI 63.33 ± 23.56 y UVS 2.61 ± 1.79 (p = 0.000). El Constant score y la satisfacción general de la UVS fueron 95.56 ± 3.28 y 9.22 ± 0.67 respectivamente. No hubo subluxaciones secundarias. El tratamiento de la IAC mediante un dispositivo de suspensión CC y una reconstrucción anatómica de los ligamentos CC asistida por artroscopía, puede ofrecer una mejoría significativa de la calidad de vida de los pacientes y representa una estrategia que al contemplar una fijación CC mecánica primaria, puede minimizar las posibilidades de fracaso y desarrollo de subluxaciones secundarias.
The purpose of this paper is to assess the results obtained with the arthroscopy-assisted surgical technique for the treatment of chronic acromioclavicular joint instability (CACJI), based on non-rigid coracoclavicular (CC) fixation and anatomical CC reconstruction with a tendinous allograft. Patients with CACJI who underwent surgery between 2008 and 2012 were included in the study. Clinical assessments included SF36, VAS and DASH, applied at the preoperative visit (POV) and at the last follow-up visit (LFUV). The Constant score and the General Satisfaction Score (0-10) were applied at the last follow-up visit. Occurrence of secondary subluxations was assessed. Ten patients were included; mean age was 41 years (range 33-55). Mean follow-up was 25.50 months (range 24-30). Surgical treatment was indicated in all patients after failure of conservative treatment. Questionnaires applied at the POV and the LFUV showed the following results: 1. SF36: physical, POV = 29.60 ± 3.41 and LFUV = 59.58 ± 1.98 (p = 0.000); 2. SF36 mental, POV = 46.57 ± 3.80 and LFUV = 56.62 ± 1.89 (p = 0.000); 3. VAS: POV = 5.17 ± 2.40 and LFUV: 1.67 ± 2.07 (p = 0.022); and 4. DASH: POV = 63.33 ± 23.56 and LFUV = 2.61 ± 1.79 (p = 0.000). The Constant score and the general satisfaction at the LFUV were 95.56 ± 3.28 and 9.22 ± 0.67, respectively. There were no secondary subluxations. Treatment of CACJI with a CC suspension device and arthroscopically-assisted anatomical reconstruction of CC ligaments may provide a significant quality of life improvement to patients. It is a strategy that, upon considering primary mechanical CC fixation, may minimize the chance of failure and occurrence of secondary subluxations.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Articulación Acromioclavicular/cirugía , Artroscopía/métodos , Inestabilidad de la Articulación/cirugía , Procedimientos de Cirugía Plástica/métodos , Aloinjertos , Articulación Acromioclavicular/patología , Enfermedad Crónica , Estudios de Cohortes , Estudios de Seguimiento , Inestabilidad de la Articulación/patología , Satisfacción del Paciente , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , Tendones/trasplanteRESUMEN
The purpose of this paper is to assess the results obtained with the arthroscopy-assisted surgical technique for the treatment of chronic acromioclavicular joint instability (CACJI), based on non-rigid coracoclavicular (CC) fixation and anatomical CC reconstruction with a tendinous allograft. Patients with CACJI who underwent surgery between 2008 and 2012 were included in the study. Clinical assessments included SF36, VAS and DASH, applied at the preoperative visit (POV) and at the last follow-up visit (LFUV). The Constant score and the General Satisfaction Score (0-10) were applied at the last follow-up visit. Occurrence of secondary subluxations was assessed. Ten patients were included; mean age was 41 years (range 33-55). Mean follow-up was 25.50 months (range 24-30). Surgical treatment was indicated in all patients after failure of conservative treatment. Questionnaires applied at the POV and the LFUV showed the following results: 1. SF36: physical, POV = 29.60 ± 3.41 and LFUV = 59.58 ± 1.98 (p = 0.000); 2. SF36 mental, POV = 46.57 ± 3.80 and LFUV = 56.62 ± 1.89 (p = 0.000); 3. VAS: POV = 5.17 ± 2.40 and LFUV: 1.67 ± 2.07 (p = 0.022); and 4. DASH: POV = 63.33 ± 23.56 and LFUV = 2.61 ± 1.79 (p = 0.000). The Constant score and the general satisfaction at the LFUV were 95.56 ± 3.28 and 9.22 ± 0.67, respectively. There were no secondary subluxations. Treatment of CACJI with a CC suspension device and arthroscopically-assisted anatomical reconstruction of CC ligaments may provide a significant quality of life improvement to patients. It is a strategy that, upon considering primary mechanical CC fixation, may minimize the chance of failure and occurrence of secondary subluxations.
Asunto(s)
Articulación Acromioclavicular/cirugía , Artroscopía/métodos , Inestabilidad de la Articulación/cirugía , Procedimientos de Cirugía Plástica/métodos , Articulación Acromioclavicular/patología , Adulto , Aloinjertos , Enfermedad Crónica , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inestabilidad de la Articulación/patología , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Tendones/trasplante , Resultado del TratamientoRESUMEN
Objetivo. Analizar la movilidad meniscal mediante tomografía axial computarizada (TAC) en prótesis total de rodilla con meniscos móviles de polietileno. Material y método. Quince prótesis con un seguimiento mínimo de 24 meses fueron sometidas a un estudio con TAC funcional para determinar la movilidad meniscal con movimientos de extensión, flexión y rotación axial de la rodilla. Se analizó la cinemática articular y el grado de desplazamiento de los soportes meniscales con el sistema digital de medición GP-9 Sonic Digitizer. Resultados. Observamos desplazamiento de los soportes meniscales en todos los casos analizados. El menisco interno se desplazó un promedio de 4,5 mm (mínimo 1 mm y máximo 9,5 mm) y el menisco externo 5 mm (1,1 mínimo y 11,6 máximo). El grado de movimiento fue mayor en el compartimento externo (p = 0,19) y durante la rotación axial (p = 0,09). Se vieron dos tipos básicos de movimiento; en 12 artroplastias (80 por ciento) el movimiento meniscal se aproximaba al desplazamiento de los meniscos de una rodilla normal; en el resto, se produjo un movimiento anómalo anterior de los meniscos al realizar la flexión de rodilla, sin relación con inestabilidad ligamentosa (p > 0,05) ni repercusión funcional aparente. Conclusiones. El movimiento meniscal se conservó a medio plazo, siendo similar al de una rodilla normal en la mayoría de las artroplastias estudiadas. (AU)
Asunto(s)
Anciano , Femenino , Masculino , Persona de Mediana Edad , Humanos , Tomografía Computarizada por Rayos X , Meniscos Tibiales/fisiología , Meniscos Tibiales/cirugía , Artroplastia de Reemplazo de Rodilla , Polietileno/uso terapéutico , Estudios de Seguimiento , Fenómenos Biomecánicos , Meniscos TibialesRESUMEN
Objetivo: Ante la controversia existente en relación con el reemplazo rotuliano en las prótesis totales de rodilla, se pretende cuantificar la morbilidad que esta sustitución tiene.Diseño experimental: El estudio retrospectivo de los fracasos del componente patelar (reintervenciones debidas exclusivamente a problemas relacionados con la patela) en una serie, donde el reemplazo patelar se llevó a cabo de manera sistemática.Material y método: 335 artroplastias de diversos diseños fueron colocadas por el mismo cirujano o bajo su directa supervisión. El seguimiento medio fue de 7,3 años.Resultados: Hubo 7 fracasos del componente patelar (2,08 por ciento), debido a: 2 subluxaciones, 3 fracturas patelares, una disociación del implante y un caso de fibrosis peripatelar. Los gestos quirúrgicos realizados fueron: realineacion proximal en el caso de las subluxaciones, patelectomía en las fracturas y en el caso de la disociación del implante, y exéresis del tejido fibroso en el caso de la fibrosis peripatelar. El índice de fracasos no mostró relación estadísticamente significativa ni con el modelo protésico (Chi cuadrado; p = 0,15) ni con el diagnóstico de base (Chi cuadrado; p = 0,64).Conclusiones: Considerando la baja incidencia de complicaciones obtenida y las ventajas clínicas y biomecánicas que supone, el reemplazo patelar sistemático en las prótesis totales de rodilla, llevado a cabo con una técnica meticulosa, supone un riesgo perfectamente asumible (AU)
Asunto(s)
Anciano , Femenino , Masculino , Persona de Mediana Edad , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Rótula/cirugía , Luxación de la Rótula/epidemiología , Fibrosis/epidemiología , Falla de Prótesis , Complicaciones Posoperatorias/epidemiologíaRESUMEN
There is growing evidence that apoptotic mechanisms underlie the neurodegeneration leading to Parkinson's disease. 1-Methyl-4-phenylpyridinium ion (MPP(+)), the active metabolite of the parkinsonism-inducing drug MPTP, induced apoptosis in cultures of human SH-SY5Y neuroblastoma cells. Nuclear fragmentation, DNA laddering, and a 20% decrease in viability were seen after a 4-day incubation with 5 microM MPP(+). Cell viability decreased by 40% at 100 microM MPP(+), but the degree of apoptosis was not correlatively increased. The MPP(+)-induced apoptosis was completely prevented by the broad caspase inhibitor zVAD.fmk but not by the caspase-8 inhibitor IETD.fmk. Furthermore, MPP(+) had no effect on the levels of Fas or Fas-L, suggesting lack of activation of the Fas-L/Fas/caspase-8 pathway of apoptosis. There was no evidence of mitochondrial dysfunction at 5 microM MPP(+): No differences were seen in transmembrane potential or in cytochrome c release from controls. At 100 microM MPP(+), the mitochondrial potential decreased, and cytoplasmic cytochrome c and caspase-9 activation increased slightly. At both low and high concentrations of MPP(+), VDVADase and DEVDase activities increased. We conclude that MPP(+) can induce caspase-mediated apoptosis, which is prevented by caspase inhibition, at concentrations lower than those needed to trigger mitochondrial dysfunction and closer to those found in the brains of MPTP-treated animals.
Asunto(s)
1-Metil-4-fenilpiridinio/farmacología , Apoptosis/efectos de los fármacos , Caspasas/fisiología , Proteínas de Neoplasias/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuroblastoma/patología , 1-Metil-4-fenilpiridinio/administración & dosificación , Clorometilcetonas de Aminoácidos/farmacología , Apoptosis/fisiología , Caspasa 8 , Caspasa 9 , Inhibidores de Caspasas , Ciclosporina/farmacología , Inhibidores de Cisteína Proteinasa/farmacología , Grupo Citocromo c/metabolismo , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Proteína Ligando Fas , Humanos , Glicoproteínas de Membrana/fisiología , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Oligopéptidos/farmacología , Concentración Osmolar , Enfermedad de Parkinson/etiología , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/patología , Receptor fas/fisiologíaRESUMEN
Bone morphogenetic proteins (BMPs) are a family of growth differentiation factors which induce bone formation from mesenchymal cells. These proteins are members of the transforming growth factor-beta super-family. The expression of BMPs in the nervous system as well as in other tissues has been reported. In this study, we show that the presence of BMP-2 resulted in a dose-dependent increase in the number of tyrosine hydroxylase-immunoreactive ventral mesencephalic cells after 7 days in serum-free medium cultures. A maximal response was elicited at 10 ng/mL. BMP-2 also increased the number of primary neurites and branch points as well as the length of the longest neurite in a dose-dependent manner, with a maximal effect at 1 ng/mL. In contrast, BMP-2 did not modify the number or the function of GABAergic neurons. On the other hand, we observed stimulation of proliferation and morphological changes in glial cells (astrocytes become more fibrous shaped) in the presence of a high BMP-2 concentration (100 ng/mL), but not with lower doses, suggesting that the neurotrophic effect in dopaminergic neurons is not mediated by astroglial cells. This is consistent with the fact that the BMP-2 effect on dopaminergic neurons was observed even when the cultures were treated with alpha-aminoadipic acid to exclude the presence of glial cells. In summary, our data indicate that BMP-2 is a potent neurotrophic factor for ventral mesencephalic dopaminergic cells in culture.
Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Dopamina/fisiología , Mesencéfalo/citología , Neuronas/efectos de los fármacos , Factor de Crecimiento Transformador beta/farmacología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/enzimología , Proteína Morfogenética Ósea 2 , Recuento de Células/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Inmunohistoquímica , Mesencéfalo/efectos de los fármacos , Mesencéfalo/enzimología , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Patients with paraneoplastic cerebellar degeneration and Hodgkin's disease develop autoantibodies (Tr-Ab) that immunoreact with the cytoplasm of the Purkinje cells and produce a characteristic punctate pattern in the molecular layer of the cerebellum. In the present study, we analyzed the structures of the adult rat cerebellar cortex identified by Tr-Ab and the expression of the antigen recognized by Tr-Ab in the developing rat brain. By laser confocal microscopy and immunoelectron microscopy, Tr-Ab immunoreactivity was found localized in the cytosol and outer surface of the endoplasmic reticulum of the perikarya of neurons of the molecular layer and the cell body and dendrites of Purkinje cells without a particular concentration in dendritic spines. Tr-Ab reactivity was more widespread in the developing rat brain. Tr-Ab labeling of Purkinje cells was already observed at P0 (day of birth). The staining of the molecular layer followed the development of the dendritic tree. The internal and inner level of the external granule cell layer were labeled with Tr-Ab with a dotted pattern that became almost negative by the 2nd postnatal week. The staining probably corresponded to granule cells as suggested by the positive Tr-Ab labeling of cultures of embryonic granule neurons. The present findings suggest that the antigen recognized by Tr-Ab appears early and is widely expressed in the developing rat brain. In the adult cerebellum, the antigen is localized in the cell body and dendrites of the Purkinje cells but is not concentrated in the dendritic spines.
Asunto(s)
Antígenos/análisis , Autoanticuerpos , Enfermedades Cerebelosas/patología , Enfermedad de Hodgkin/patología , Sistema Nervioso/patología , Enfermedades Neurodegenerativas/patología , Neuronas/inmunología , Síndromes Paraneoplásicos/patología , Animales , Autoanticuerpos/inmunología , Células Cultivadas , Enfermedades Cerebelosas/metabolismo , Cerebelo/metabolismo , Cerebelo/patología , Enfermedad de Hodgkin/metabolismo , Humanos , Inmunohistoquímica , Microscopía Confocal , Microscopía Inmunoelectrónica , Sistema Nervioso/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Síndromes Paraneoplásicos/metabolismo , Células de Purkinje/metabolismo , Células de Purkinje/ultraestructura , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
The neuroprotective effect of tachykinins against excitotoxic death of cholinergic neurons was studied in rat striatal cell cultures. Quinolinic acid (QUIN) and kainic acid (KA) produced a dose dependent decrease in choline acetyltransferase activity, but KA was more potent. Our results show that substance P (SP) totally reversed the toxicity induced by 125 microM QUIN but not by 40 microM KA. This effect was also observed using protease inhibitors or a SP-analog resistant to degradation, [Sar9]-Substance P. The survival of neuron specific enolase- and acetylcholinesterase (AChE)-positive cells after treatment with QUIN alone or in the presence of SP was also examined. We observed that, while a decrease in total cell number produced by QUIN was not prevented by SP treatment, AChE-positive cells were rescued from the toxic damage. To characterize the SP protective effect we used more selective agonists of the three classes of neurokinin (NK) receptors. [Sar9, Met(O2)11]-Substance P (NK1 receptor agonist), [Nle10]-Neurokinin A (NK2 receptor agonist) or [Me-Phe7]-Neurokinin B (NK3 receptor agonist) were all able to block the toxic effect of QUIN on cholinergic activity. These results show that tachykinins provide an important protective support for striatal neurons, suggesting a possible therapeutical benefit in neurodegenerative disorders affecting cholinergic neurons.
Asunto(s)
Fibras Colinérgicas/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Ácido Quinolínico/toxicidad , Taquicininas/farmacología , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
The neostriatum is one of the areas with relatively high levels of glial cell line-derived neurotrophic factor (GDNF) messenger RNA expression in the developing and adult brain. GDNF expression in the neostriatum has been suggested to be involved in promoting the survival of nigral dopaminergic neurons, acting as a target-derived neurotrophic factor. However, GDNF messenger RNA expression in the striatum starts several days before dopaminergic and other afferent neurons reach the striatum, suggesting additional trophic effects of this factor on striatal neurons. In the present report, we have examined whether GDNF is able to prevent the degeneration of striatal calbindin- and parvalbumin-immunoreactive neurons in a lesion model of Huntington's disease. Fischer 344 rat 3T3 fibroblast cell line expressing high levels of GDNF (F3A-GDNF) was used to assess the protective effect of this factor, on striatal neurons, against excitotoxicity. Quinolinate (34 nmol) was injected at two different coordinates, and calbindin, parvalbumin and tyrosine hydroxylase immunoreactivity were examined seven days after lesion. Dopaminergic afferents were spared after quinolinate injection, but the number of calbindin- and parvalbumin-immunoreactive neurons was decreased. Interestingly, implantation of F3A-GDNF cells increased the density of tyrosine hydroxylase staining in the intact and also in the quinolinate-lesioned striatum. Furthermore, GDNF partially protected calbindin- but not parvalbumin-immunoreactive neurons from quinolinate excitotoxicity. Instead, mock-transfected fibroblasts did not affect any of these parameters. Our results show that GDNF specifically protects a subpopulation of striatal calbindin-immunoreactive neurons against quinolinate lesion, suggesting that GDNF administration may have a potential therapeutic application in the prevention and treatment of striatonigral degenerative disorders.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Aminoácidos Excitadores/toxicidad , Neostriado/efectos de los fármacos , Factores de Crecimiento Nervioso/farmacología , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/farmacología , Neuroglía/metabolismo , Neuronas/efectos de los fármacos , Proteína G de Unión al Calcio S100/metabolismo , Células 3T3 , Animales , Calbindinas , Línea Celular , Factor Neurotrófico Derivado de la Línea Celular Glial , Inmunohistoquímica , Ratones , Neostriado/citología , Neostriado/metabolismo , Factores de Crecimiento Nervioso/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , Ácido Quinolínico/toxicidad , Ratas , Ratas Endogámicas F344RESUMEN
Adenosine has been shown to inhibit dopamine release from striatal slices and synaptosomes. Recently, a direct interaction between the adenosine A2 receptor and dopamine D2 receptor has been provided. Activation of striatal adenosine A1 receptors is known to partially inhibit the release of dopamine (DA), but some aspects of this mechanism remain unclear. We have studied the participation of adenosine A1 receptors in the control of DA release 'in vivo' in awake, freely moving rats using microdialysis. To this end, the effects of 2-chloroadenosine (2-CADO), a non-metabolizable adenosine A1 receptor agonist, were studied on basal and stimulated striatal DA release. Basal levels were found to be slightly decreased by a maximal concentration of 2-CADO without any changes in DA metabolites. Haloperidol stimulated DA release was fully counteracted by 2-CADO. However, high K+ (100 mM) or (+)-amphetamine stimulated DA release was not altered by 2-CADO. Altogether, these data suggest that adenosine acting through A1 receptors possibly localized on striatal dopaminergic nerve terminals can block an induced D2 receptor blockade, but not the releasing effects caused by (+)-amphetamine and high K+ concentration. It is postulated that the increase in DA release by haloperidol is mainly due to an increased firing rate of the DA neurons and that A1 receptor activation can block the DA release observed in response to the action potential activation of DA nerve terminals.
Asunto(s)
2-Cloroadenosina/farmacología , Cuerpo Estriado/fisiología , Dopamina/metabolismo , Receptores Purinérgicos P1/fisiología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Anfetamina/farmacología , Animales , Haloperidol/farmacología , Masculino , Neuronas/fisiología , Potasio/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
To learn about the mechanisms of excitotoxic cell death in vivo, three different excitatory amino acid receptor agonists (kainic acid, quinolinic acid or quisqualic acid) were injected in the left striatum of adult rats. Brains were examined at 24 and 48 h after injection. Morphological and biochemical studies were performed using conventional stains, histochemistry, in situ labelling of nuclear DNA fragmentation, and agarose gel electrophoresis of extracted DNA. Large numbers of cells with cytoplasmic shrinkage and nuclear condensation or granular degeneration of the chromatin, and fewer cells with apoptotic morphology were distributed at random in the injured areas of the three groups of treated animals but not in rats injected with vehicle alone. A ladder pattern, typical of internucleosomal DNA fragmentation, was observed 24 h after treatment. This was replaced by a smear pattern, consistent with random DNA breakdown, at 48 h. These morphological and biochemical results suggest that prevailing necrosis together with apoptosis occur following intrastriatal injection of different excitotoxins.
Asunto(s)
Apoptosis , Necrosis/inducido químicamente , Neurotoxinas/efectos adversos , Animales , Muerte Celular , Cuerpo Estriado/química , Inmunohistoquímica , Ácido Kaínico/efectos adversos , Masculino , Ácido Quinolínico/efectos adversos , Ratas , Ratas Sprague-DawleyRESUMEN
Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered.
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Bloqueadores de los Canales de Calcio/farmacología , Cuerpo Estriado/efectos de los fármacos , Dopamina/fisiología , Haloperidol/farmacología , Transmisión Sináptica/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Administración Oral , Animales , Calcio/fisiología , Cuerpo Estriado/química , Dopamina/metabolismo , Espacio Extracelular/química , Masculino , Microdiálisis , Ratas , Ratas Sprague-DawleyRESUMEN
The density and distribution of dopamine D1 and D2 receptors visualized by in vitro autoradiography were investigated in adult and senescent BL C57 mice. A significant decrease was observed in regions of the basal ganglia of senescent animals, which was more pronounced for the D1 subtype. Chronic treatment with cinnarizine, an organic Ca2+ channel antagonist, alters both D1 and D2 receptor densities, with a higher sensitivity of the D1 subtype. These results could indicate that the interactions between dopamine receptor subtypes may be necessary for the full expression of behavioral events mediated by the D2 receptors.
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Envejecimiento/metabolismo , Encéfalo/metabolismo , Cinarizina/farmacología , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animales , Autorradiografía , Encéfalo/efectos de los fármacos , Cinarizina/administración & dosificación , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos C57BL , Receptores de Dopamina D1/efectos de los fármacos , Receptores de Dopamina D2/efectos de los fármacosRESUMEN
The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on D1 and D2 dopamine receptors was assayed using in vitro quantitative autoradiography. D1 receptor subtype was labeled using 1 nM of 3H-SCH 23390 and D2 receptor subtype was labeled using 0.4 nM of 3H-spiroperidol. The results are compared to the effect of MPTP on the striatal levels of dopamine and its metabolites, in BL C57 mice. While 2 and 5 doses of MPTP 30 mg/kg/day intraperitoneally reduced the content of striatal dopamine and its metabolites, no modifications were detected in D2 receptor subtype in any cerebral area studied. However, D1 receptors were reduced in the substantia nigra 24 hr after the last of 2 doses, but not later. We suggest a compensatory mechanism of the surviving dopaminergic neurones as well as the participation of spare receptors. This would explain the lack of receptor modification after the lesion obtained as seen by the striatal reduction of dopamine and metabolites content, after MPTP administration.
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Intoxicación por MPTP , Enfermedad de Parkinson Secundaria/fisiopatología , Receptores Dopaminérgicos/efectos de los fármacos , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Autorradiografía , Benzazepinas/farmacología , Encéfalo/metabolismo , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Espiperona/farmacologíaRESUMEN
We have measured the levels of monoamines and their metabolites in rat striata implanted with a dialysis tube, in contralateral nonimplanted striata, and in dialysates obtained from the dialysis tube. The perfusion was done with Ringer solution. The animals were perfused either for a continuous period of 7 h at 1 day after implantation or for periods of 2 h on days 1, 4, and 7 after implantation. In animals perfused for 7 h, levels of monoamine metabolites in dialysates remained stable for the first 4 h of perfusion, but a reduction was observed during the last 3 h. In animals perfused for 2 h on days 1, 4, and 7 after implantation, we observed a progressive reduction in levels of metabolites in dialysates with respect to the first day of perfusion. The levels of dopamine and its metabolites in the striata in which a dialysis cannula had been implanted showed a progressive reduction during the period postimplantation comparable to that observed in dialysates. The levels of 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were elevated 24 h after implantation in the implanted striata with respect to the contralateral nonimplanted striata, but 7 days after implantation, the levels of dopamine were decreased in the implanted striata, and the levels of metabolites were unchanged.
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Aminas Biogénicas/metabolismo , Cuerpo Estriado/metabolismo , Diálisis , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Diálisis/instrumentación , Dopamina/análogos & derivados , Dopamina/metabolismo , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Cinética , Masculino , Prótesis e Implantes , Ratas , Ratas EndogámicasRESUMEN
In order to obtain further insight into the interactions between the purinergic and dopaminergic pathways in the striatum, we studied both metabolisms simultaneously, using a microdialysis technique in 1-methyl-1,4-phenylpyridinium ion (MPP+) unilaterally-denervated conscious rats. In these rats the contralateral side was used as control. The perfusates were collected every 20-25 min using 4 mm dialysis probes, implanted in each striatum, and assayed for dopamine and purine metabolites. After MPP+ administration, all adenosine metabolites - with the exception of uric acid - and dopamine levels were significantly increased in the extracellular medium. However, the time-course change in dopamine level did not correlate with the adenosine and inosine time-courses, suggesting a different mechanism of liberation in response to MPP+ administration.
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Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Purinas/metabolismo , Compuestos de Piridinio/farmacología , 1-Metil-4-fenilpiridinio , Animales , Cuerpo Estriado/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in animal models of dopamine deficiency as an experimental approach to the treatment of levodopa induced fluctuations in Parkinson's disease. Dopamine deficiency was produced in rats by unilateral lesion of the nigrostriatal pathway or by chronic treatment with reserpine. Monkeys were lesioned by intravenous injection of MPTP. The animals were treated with intracerebral infusions of dopamine (with or without associated intraperitoneal administration or intracerebroventricular infusion of pargyline), lisuride and pergolide. The intracerebroventricular infusion of these drugs was performed with osmotic minipumps in rats and with infusaid pumps in the monkeys. The infusion of dopamine or dopamine agonists in rats with unilateral lesions by 6-OH-dopamine produced a persistent rotation contralateral to the lesioned and implanted side. The infusion of dopamine reversed reserpine-induced akinesia only when pargyline was associated. In the range of concentration used, maximum allowed by solubility of compounds, the effects of dopamine were more potent than those of the agonists. In spite of the stability of dopamine "in vitro" when dissolved in antioxidants and at low pH, a pigment, product of autooxidation, was found in the brains of the animals infused with dopamine. The monkeys were implanted with infusaid pumps and infused for up to 3 weeks. The pump was not well tolerated due to its huge size for the animals. One monkey showed reversal of the MPTP-induced akinesia while the other, whose catheter had moved from the correct implantation site, remained unchanged. In both monkeys there was evidence of autooxidation of dopamine. Intracerebral infusion of dopamine agonists may be a possible experimental alternative to the treatment of levodopa induced fluctuations in Parkinson's disease but stable and soluble dopamine agonists and suitable delivery systems are needed.