A new procedure for amyloid ß oligomers preparation enables the unambiguous testing of their effects on cytosolic and mitochondrial Ca(2+) entry and cell death in primary neurons.

Oligomers of the amyloid ß peptide (Aßo) are becoming the most likely neurotoxin in Alzheimer's disease. Controversy remains on the mechanisms involved in neurotoxicity induced by Aßo and the targets involved. We have reported that Aßo promote Ca(2+) entry, mitochondrial Ca(2+) overload and apoptosis in cultured cerebellar neurons. However, recent evidence suggests that some of these effects could be induced by glutamate receptor agonists solved in F12, the media in which Aßo are prepared. Here we have tested the effects of different media on Aßo formation and on cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in rat cerebellar and hippocampal cell cultures. We found that Aßo prepared according to previous protocols but solved in alternative media including saline, MEM and DMEM do not allow oligomer formation and fail to increase [Ca(2+)]cyt. Changes in the oligomerization protocol and supplementation of media with selected salts reported to favor oligomer formation enable Aßo formation. Aßo prepared by the new procedure and containing small molecular weight oligomers increased [Ca(2+)]cyt, promoted mitochondrial Ca(2+) overload and cell death in cerebellar granule cells and hippocampal neurons. These results foster a role for Ca(2+) entry in neurotoxicity induced by Aßo and provide a reliable procedure for investigating the Ca(2+) entry pathway promoted by Aßo.

Farmacología de los ácidos grasos omega-3 / Pharmacology of omega-3 polyinsaturated fatty acids

El consumo de ácidos grasos omega-3, como el ácido eicosapentanoico (EPA) y el ácido docosahexanoico (DHA), derivados de alimentos marinos y de plantas ha demostrado, en estudios epidemiológicos y clínicos, que reduce la incidencia de mortalidad coronaria y la muerte por arritmias. Recientemente, un suplemento que contiene una concentración del 90% de ácidos omega-3 (EPA y DHA) en forma de etil ésteres (Omacor®) ha sido autorizado como tratamiento adjunto a la dieta para reducir la hipertrigliceridemia en pacientes adultos y, también, como tratamiento adjunto a la dieta y a otros tratamientos en la prevención secundaria del infarto de miocardio. En este artículo, en primer lugar, revisamos la estructura química, las acciones farmacológicas y los mecanismos por los cuales los ácidos grasos n-3 y, en particular, el Omacor ®, pueden reducir el riesgo de muerte cardiovascular. A continuación, se analizan las propiedades farmacocinéticas, la seguridad y las recomendaciones de diversos organismos para administrar suplementos de EPA+DHA u Omacor® en los pacientes con enfermedades cardiovasculares (AU)

Epidemiological and clinical trials have shown that the consumption of omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), derived from seafood and plant sources reduces the incidence of fatal coronary artery disease and death due to arrhythmia. Recently, a food supplement containing a 90% concentration of omega-3 fatty acids (i.e., EPA and DHA) in the form of ethyl esters (Omacor®) has been licensed for use as an adjunct to dietary modification for the reduction of hypertriglyceridemia in adults and as an adjuvant to standard medical treatment for the secondary prevention of myocardial infarction. In this article, we review firstly the chemical structure of omega-3 fatty acids, and the pharmacological actions and mechanisms through which they may reduce the risk of cardiovascular disease. Thereafter, we discuss the pharmacokinetics, safety profile, and the recommendations made in several guidelines concerning the use of EPA+DHA supplements or Omacor® in patients with cardiovascular disease (AU)

Multifunctional cells in human pituitary adenomas: implications for paradoxical secretion and tumorigenesis.

Pituitary adenomas are very common in humans. They are of monoclonal origin, very heterogeneous, and produce frequently paradoxical secretion. The normal anterior pituitary (AP) contains some unorthodox multifunctional cells able to store more than one AP hormone (polyhormonal) and/or to express multiple hypothalamic-releasing hormone receptors (multiresponsive). Multifunctional AP cells seem to be involved in plasticity processes such as transdifferentiation or paradoxical secretion. Here, we have characterized the single-cell phenotypes of 15 human pituitary tumors, including prolactinomas, nonfunctioning adenomas, and adenomas from multiple endocrine neoplasia type I (MEN-I) and pituitary Cushing's disease patients. Individual tumor cells were typed according to expression of AP hormones and hypothalamic-releasing hormone receptors by combination of calcium imaging and multiple sequential immunocytochemistry in the same cells. We found a large heterogeneity among the different tumors. In eight of the 15 tumors studied, more than 80% of the cells presented a multifunctional phenotype. This may explain the occurrence of paradoxical secretion. In addition, our results suggest that human pituitary adenomas might derive from multifunctional cells. This is consistent with the existence of a link between pituitary plasticity and tumorigenesis.

Anterior pituitary thyrotropes are multifunctional cells.

Anterior pituitary (AP) contains some unorthodox multifunctional cells that store and secrete two different AP hormones (polyhormonal cells) and/or respond to several hypothalamic-releasing hormones (HRHs; multiresponsive cells). Multifunctional cells may be involved in paradoxical secretion (secretion of a given AP hormone evoked by a noncorresponding HRH) and transdifferentiation (phenotypic switch between different mature cell types without cell division). Here we combine calcium imaging (to assess responses to the four HRHs) and multiple sequential immunoassay of the six AP hormones to perform a single-cell phenotypic study of thyrotropes in normal male and female mice. Surprisingly, most of the thyrotropes were polyhormonal, containing, in addition to thyrotropin (TSH), luteinizing hormone (40-42%) and prolactin (19-21%). Thyrotropes costoring growth hormone and/or ACTH were found only in females (24% of each type). These results suggest that costorage of the different hormones does not happen at random and that gender favors certain hormone combinations. Our results indicate that thyrotropes are a mosaic of cell phenotypes rather than a single cell type. The striking promiscuity of TSH storage should originate considerable mix-up of AP hormone secretions on stimulation of thyrotropes. However, response to thyrotropin-releasing hormone was much weaker in the polyhormonal thyrotropes than in the monohormonal ones. This would limit the appearance of paradoxical secretion under physiological conditions and suggests that timing of hormone and HRH receptor expression during the transdifferentiation process is finely and differentially regulated.

Estudio clínico patológico de las glomerulopatías primarias

Se revisaron las historias clínicas y los diagnósticos anatomopatológicos de 382 biopsias renales realizadas en nuestro centro durante el período de 1995-1998. De ellas se seleccionaron para esta investigación 241 con diagnóstico de glomerulopatías primarias, las cuales se estudiaron por Microscopía óptica, inmunohistoquímica y algunos casos por Microscopía electrónica. Se observó mayor incidencia entre los 21-30 años representado por un 29,87 porciento y la raza blanca fue más afectada con un 53,11 porciento. La variedad de Glomerulopatía más frecuente resultó la glomerulosclerosis segmentaria Focal con 22,82 porciento siguiéndole en orden de frecuencia la glomerulosclerosis proliferativa mesangial con 17,82 porciento y la glomerulonefritis proliferativa endocapilar con 16,18 porciento.la menos frecuente fue la glomerulonefritis esclerosante. (1,65%). Se analizaron aspectos clínicos y de laboratorio constatándose que la proteinuria e Hipertensión arterial se presentaron en el 87,27 porciento y 41,81 porciento respectivamente en la Glomerulosclerosis segmentaria Focal y el Síndrome nefrótico se constató en el 38,18 porciento en esta variedad. En la Glomerulonefritis proliferativa mesangial el aspecto más relevante lo constituyó la proteinuria con 93,02 porciento y en la glomerulonefritis Proliferativa endocapilar proteinuria, hematuria y hipertensión arterial. La proteinuria fue la manifestación más frecuente en todas las variedades de glomerulopatías. Se realizaron estudios de inmunofluorescencia para valorar la positividad de inmunoglobulinas así como complementos que ayudan a corroborar el diagnóstico. Todos los resultados fueron reflejados en tablas y figuras(AU)

The clinical histories and the diagnoses anatomopatológicos of 382 renal biopsies were revised carried out in our center during the period of 1995-1998. Of them they were selected pear this investigation 241 with diagnosis of Primary glomerulopatías, which were studied by optic Microscopy, inmunohistoquímica and some cases by electronic Microscopy. Bigger incidence was observed among the 21-30 years represented by 29,87 percent and the white race was more affected with 53,11 percent. The variety of more frequent Glomerulipatía was the Focal segmental glomerulosclerosis with 22,82 percent following him in order of frequency the glomerulosclerosis proliferativa mesangial with 17,82 percent and the glomerulonefritis proliferativa endocapilar with 16,18 percent less frequent .la it was the glomerulonefritis esclerosante. ( 1,65 percent ). Clinical aspects were analyzed and of laboratory constatándoce that the proteinuria and arterial Hypertension were presented respectively in 87,27 percent and 41,81 percent in the Focal segmental Glomerulosclerosis and the Syndrome nefrótico was verified in 38,18 percent in this variety. In the Glomerulonefritis proliferativa mesangial the most excellent aspect constituted it the proteinuria with 93,02 percent and in the glomerulonefritis Proliferativa endocapilar proteinuria, hematuria and arterial hypertension. The proteinuria was the most frequent manifestation in all the glomerulopatías varieties. They were carried out inmunofluorescencia studies to value the inmunoglobulinas positividad as well as complements that you/they help to corroborate the diagnosis. All the results were reflected in charts and figures(AU)