Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder with uncertain aetiology and ill-defined pathophysiology. Activated microglial cells in the substantia nigra (SN) are found in all animal models of Parkinson's disease and patients with the illness. Microglia may, however, have detrimental and protective functions in this disease. In this study, we tested the hypothesis that a sub-toxic dose of an inflammogen (lipopolysaccharide) can shift microglia to a pro-inflammatory state and exacerbate disease progression in an animal model of Parkinson's disease. Central lipopolysaccharide injection in a degenerating SN exacerbated neurodegeneration, accelerated and increased motor signs and shifted microglial activation towards a pro-inflammatory phenotype with increased interleukin-1beta (IL-1beta) secretion. Glucocorticoid treatment and specific IL-1 inhibition reversed these effects. Importantly, chronic systemic expression of IL-1 also exacerbated neurodegeneration and microglial activation in the SN. In vitro, IL-1 directly exacerbated 6-OHDA-triggered dopaminergic toxicity. In vivo, we found that nitric oxide was a downstream molecule of IL-1 action and partially responsible for the exacerbation of neurodegeneration observed. Thus, IL-1 exerts its exacerbating effect on degenerating dopaminergic neurons by direct and indirect mechanisms. This work demonstrates an unequivocal association between IL-1 overproduction and increased disease progression, pointing to inflammation as a risk factor for Parkinson's disease and suggesting that inflammation should be efficiently handled in patients to slow disease progression.

Heme oxygenase-1 is expressed in carotid atherosclerotic plaques infected by Helicobacter pylori and is more prevalent in asymptomatic subjects.

BACKGROUND AND PURPOSE: It is not well established what are the features, if any, that distinguish symptomatic from asymptomatic carotid atherosclerotic plaques. Inducible heme oxygenase-1 (HO-1) is a component of cellular defense mechanisms against oxidative stress. We aimed to assess the presence of Helicobacter pylori (H pylori) and the expression of HO-1 in carotid atherosclerotic plaques of patients with and without prior neurologic symptoms attributable to the operated artery. METHODS: We examined 25 symptomatic and 23 asymptomatic carotid atherosclerotic plaques removed during endarterectomy and 7 normal carotid arteries obtained at autopsy. We investigated the presence of H pylori DNA in the vessel wall and performed immunohistochemical detection of HO-1. RESULTS: H pylori DNA was present in 28 plaques and HO-1 was expressed in 30 plaques. HO-1 was found in 27 H pylori-positive specimens but in only 3 H pylori-negative specimens (P<0.001). All 7 normal carotid arteries were negative for both H pylori and HO-1. Although 82% of asymptomatic specimens were positive for H pylori and 87% for HO-1, only 36% of symptomatic specimens were positive for both H pylori and HO-1 (P<0.01). CONCLUSIONS: This study suggests a strong association between H pylori infection and expression of HO-1 in carotid atherosclerotic plaques. There was a substantial prevalence of these features in specimens obtained from asymptomatic subjects.

Long-term effects of prenatal stress on dopamine and glutamate receptors in adult rat brain.

Prenatal stress greatly influences the ability of an individual to manage stressful events in adulthood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA1 region and core region of nucleus accumbens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders.

Análisis in vitro de la disponibilidad del hierro en el arroz fortificado / In vitro assessment of iron availability on fortified rice

Con el objetivo de determinar la disponibilidad in vitro del hierro en el arroz blanco fortificado con este mineral y el efecto inhibitorio del ácido fítico presente en el salvado en cantidades semejantes a las que se puede encontrar en el arroz integral, se analizaron muestras de arroz comercial blanco fortificado con hierro electrolítico (ABF) y arroz simil integral fortificado. Este se logró mediante mezclas de ABF más salvado de arroz en concentraciones de 4,76 por ciento y 9,09 por ciento en las muestras ABF2 Y ABF3 respectivamente. Antes y después de ser sometidas a una hidrólisis con fitasa se determinó: Hierro total por espectrofotometría de absorción atómica, disponibilidad del hierro por el método in vitro de Kapsokefalou y Miller modificado por Valencia y col., fibra dietaria y ácido fítico según AOAC. Los resultados mostraron que el agregado de salvado deprimió la disponibilidad del hierro, 9,65 por ciento; 4,04 por ciento; y 1,82 por ciento para ABF, ABF2, y ABF3 respectivamente. Estos resultados pueden atribuirse en su mayor parte al contenido en ácido fítico, ya que después de su hidrólisis se obtuvieron valores máximos no significativamente diferentes de 28,20 por ciento; 27,95 por ciento y 25,30 por ciento para las mismas muestras. El contenido de fibra de las muestras disminuyó con el tratamiento con fitasa en las muestras ABF2 y ABF3, respectivamente. Sin embargo de acuerdo al análisis de regresión múltiple realizado, la fibra no influiría en los resultados mientras que el ácido fítico sería el responsable principal de la inhibición de la disponibilidad del hierro. Se concluye que en el arroz integral a pesar de su mayor contenido en hierro con respecto al arroz blanco, requeriría un nivel de fortificación más elevado que éste debido a su mayor contenido de ácido fítico

Taller de anticuerpos antinucleares (ANA): una experiencia latinoamericana / Workshop on antinuclear antibodies (ANA): a latin american experience

En el Taller de Trabajo de Anticuerpos Anti-Nucleares realizado en el marco del Primer Workshop y Conferencia Latinoamericana de Autoinmunidad (1997), se analizaron 27 sueros de pacientes con distintas enfermedades reumáticas sistémicas: lupus eritematosos sistémico (n=15), artritis reumatoide (n=4), síndrome de Sjögren (n=3), enfermedad mixta del tejido conjuntivo (n=1), síndrome indiferenciado del tejido conjuntivo (n=1), polimiositis/dermatomiositis (n=2) y escleroderma (n=1) y 3 sueros de individuos normales para el estudio de ANA por inmunofluorescencia indirecta (IFI), y anticuerpos anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl70 y anti-Jol utilizando las técnicas de Doble Difusión Radial (DDR), Enzimoinmuno Análisis (ELISA) y Western blot (WB) de origen comercial. En el estudio de ANAs por IFI se observaron 4 patrones: nuclear: moteado fino, metafase negativa (n=9); nuclear: moteado grueso, metafase negativa (n=4); nuclear: homogéneo, metafase positiva homogénea (n=10); nucleolar y nucleoplásmico, metafase positiva homogénea (n=1). En 6 sueros, incluyendo los 3 controles normales, los ANA por IFI dieron resultados negativos. Comparando los patrones observados por IFI con las especificidades obtenidas por las téncnicas de DDR, ELISA y WB, surge que los mismos fueron orientativos hacia la especificidad de los distinto anticuerpos presentes, no pudiendo descartar la presencia de ninguno de los otros anticuerpos estudiados. Por último, se compararon los resultados obtenidos por los métodos de DDR, ELISA y WB observándose que la proporción de resultados positivos para el Ac. anti-Sm por WB difiere significativamente (p<0.05) con respecto a la DDR y a uno de los equipos de ELISA utilizados