La salud pública en el marco de la administración periférica: el Instituto Provincial de Higiene de Alicante (1924-1936)

Se describe el desarrollo del Instituto Provincial de Higiene de Alicante. En una primera parte se pasa revista al marco normativo nacional que dio lugar a la constitución y a las sucesivas reorganizaciones de los Institutos Provinciales de Higiene. En la segunda parte, utilizando materiales de archivo, reconstruimos la vida del Instituto Provincial de Higiene, desde sus antecedentes como Brigada Sanitaria Provincial hasta el inicio de la Guerra Civil, estudiando las fases en las que dependió de la Diputación Provincial, y, posteriormente con la República, de la Mancomunidad de Municipios.

Genética. Examen de problemas de junio (Curso 2011-2012)

Examen de problemas de la asignatura de Genética.

Los libros de texto de química destinados a estudiantes de medicina y cirugía en España (1788-1845)

Este trabajo forma parte de en un proyecto de investigación sobre la farmacología en la sociedad española del siglo XIX, en particular, acerca del papel de las prácticas y los conocimientos químicos en la transición de la materia médica a la farmacología experimental. Dentro de ese esquema general, el objeto de este artículo es el estudio de los libros de texto destinados a los estudiantes de medicina y de cirugía durante los años finales del siglo XVIII y la primera mitad del siglo XIX. Se trata de establecer las coordenadas institucionales generales dentro de las cuales fueron escritas, publicadas y leídas estas obras. El estudio arranca en 1788, fecha alrededor de la cual aparecieron numerosos libros de texto de química, entre los que figuran varias traducciones francesas y el «Curso de química» de Pedro Gutiérrez Bueno. Tras señalar la importancia de las obras de Antoine Fourcroy, se estudia la polémica acerca de las aplicaciones de la química en medicina a través de un texto de Juan Manuel de Aréjula. A continuación, se describen las principales instituciones de enseñanza de la medicina y la cirugía en las que se impartieron clases de química, con especial atención a los programas y a los libros que se publicaron para estas clases. El artículo finaliza en 1845, fecha de la reforma de planes de estudios de José Pidal.

Pedro Gutiérrez Bueno (1745-1822), los libros de texto y los nuevos públicos de la química en el último tercio del siglo XVIII

El presente trabajo se enmarca en un proyecto de investigación acerca del papel de las prácticas y los conocimientos químicos en la transición de la materia médica a la farmacología experimental. Dentro de ese esquema general, el objeto de este artículo es el estudio de los libros de texto destinados a los estudiantes de medicina y de cirugía durante los años finales del siglo XVIII y la primera mitad del siglo XIX. En un estudio anterior, publicado en esta revista nos ocupamos de establecer las coordenadas institucionales generales dentro de las cuales fueron escritas, publicadas y leídas estas obras. Este trabajo es una continuación del anterior y está dedicado al análisis del «Curso de química» de Pedro Gutiérrez Bueno. A través de esta obra, se intenta ofrecer nuevos datos sobre los nuevos públicos de la química a finales del siglo XVIII y su influencia en la estructura y contenidos de los nuevos libros de texto.

Overexpression of guanylate cyclase activating protein 2 in rod photoreceptors in vivo leads to morphological changes at the synaptic ribbon

Guanylate cyclase activating proteins are EF-hand containing proteins that confer calcium sensitivity to retinal guanylate cyclase at the outer segment discs of photoreceptor cells. By making the rate of cGMP synthesis dependent on the free intracellular calcium levels set by illumination, GCAPs play a fundamental role in the recovery of the light response and light adaptation. The main isoforms GCAP1 and GCAP2 also localize to the synaptic terminal, where their function is not known. Based on the reported interaction of GCAP2 with Ribeye, the major component of synaptic ribbons, it was proposed that GCAP2 could mediate the synaptic ribbon dynamic changes that happen in response to light. We here present a thorough ultrastructural analysis of rod synaptic terminals in loss-of-function (GCAP1/GCAP2 double knockout) and gain-of-function (transgenic overexpression) mouse models of GCAP2. Rod synaptic ribbons in GCAPs−/− mice did not differ from wildtype ribbons when mice were raised in constant darkness, indicating that GCAPs are not required for ribbon early assembly or maturation. Transgenic overexpression of GCAP2 in rods led to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies. Restoration of GCAP2 expression in the GCAPs−/− background (GCAP2 expression in the absence of endogenous GCAP1) had the striking result of shortening ribbon length to a much higher degree than overexpression of GCAP2 in the wildtype background, as well as reducing the thickness of the outer plexiform layer without affecting the number of rod photoreceptor cells. These results indicate that preservation of the GCAP1 to GCAP2 relative levels is relevant for maintaining the integrity of the synaptic terminal. Our demonstration of GCAP2 immunolocalization at synaptic ribbons at the ultrastructural level would support a role of GCAPs at mediating the effect of light on morphological remodeling changes of synaptic ribbons.

Immunohistochemical evidence of synaptic retraction, cytoarchitectural remodeling, and cell death in the inner retina of the rat model of Oygen-Induced Retinopathy (OIR)

Purpose. Postnatal exposure to hyperoxia destroys the plexiform layers of the neonatal rat retina, resulting in significant electroretinographic anomalies. The purpose of this study was to identify the mechanisms at the origin of this loss. Methods. Sprague-Dawley (SD) and Long Evans (LE) rats were exposed to hyperoxia from birth to postnatal day (P) 6 or P14 and from P6 to P14, after which rats were euthanatized at P6, P14, or P60. Results. At P60, synaptophysin staining confirmed the lack of functional synaptic terminals in SD (outer plexiform layer [OPL]) and LE (OPL and inner plexiform layer [IPL]) rats. Uneven staining of ON-bipolar cell terminals with mGluR6 suggests that their loss could play a role in OPL thinning. Protein kinase C(PKC)-α and recoverin (rod and cone ON-bipolar cells, respectively) showed a lack of dendritic terminals in the OPL with disorganized axonal projections in the IPL. Although photoreceptor nuclei appeared intact, a decrease in bassoon staining (synaptic ribbon terminals) suggests limited communication to the inner retina. Findings were significantly more pronounced in LE rats. An increase in TUNEL-positive cells was observed in LE (inner nuclear layer [INL] and outer nuclear layer [ONL]) and SD (INL) rats after P0 to P14 exposure (425.3%, 102.2%, and 146.3% greater than control, respectively [P < 0.05]). Conclusions. Results suggest that cell death and synaptic retraction are at the root of OPL thinning. Increased TUNEL-positive cells in the INL confirm that cells die, at least in part, because of apoptosis. These findings propose a previously undescribed mechanism of cell death and synaptic retraction that are likely at the origin of the functional consequences of hyperoxia.

Tauroursodeoxycholic acid prevents retinal degeneration in transgenic P23H rats

Purpose. To evaluate the preventive effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). Methods. P23H line-3 rats were injected with TUDCA once a week from postnatal day (P)21 to P120, in parallel with vehicle-administered controls. At P120, functional activity of the retina was evaluated by electroretinographic (ERG) recording. The effects of TUDCA on the number, morphology, integrity, and synaptic connectivity of retinal cells were characterized by immunofluorescence confocal microscopy. Results. The amplitude of ERG a- and b-waves was significantly higher in TUDCA-treated animals under both scotopic and photopic conditions than in control animals. In the central area of the retina, TUDCA-treated P23H rats showed threefold more photoreceptors than control animals. The number of TUNEL-positive cells was significantly smaller in TUDCA-treated rats, in which photoreceptor morphology was preserved. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in TUDCA-treated P23H rats. Furthermore, in TUDCA-treated rat retinas, the number of both rod bipolar and horizontal cell bodies, as well as the density of their synaptic terminals in the outer plexiform layer, was greater than in control rats. Conclusions. TUDCA treatment was capable of preserving cone and rod structure and function, together with their contacts with their postsynaptic neurons. The neuroprotective effects of TUDCA make this compound potentially useful for delaying retinal degeneration in RP.

Partial rescue of retinal function in chronically hypoglycemic mice

Purpose. Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of this study was to establish whether long-term administration of high dietary glucose rescues retinal function and circuit connectivity in aged Gcgr−/− mice. Methods. Gcgr−/− mice were administered a carbohydrate-rich diet starting at 12 months of age. After 1 month of treatment, retinal function and structure were evaluated using electroretinographic (ERG) recordings and immunohistochemistry. Results. Treatment with a carbohydrate-rich diet raised blood glucose levels and improved retinal function in Gcgr−/− mice. Blood glucose increased from moderate hypoglycemia to euglycemic levels, whereas ERG b-wave sensitivity improved approximately 10-fold. Because the b-wave reflects the electrical activity of second-order cells, we examined for changes in rod-to-bipolar cell synapses. Gcgr−/− retinas have 20% fewer synaptic pairings than Gcgr+/− retinas. Remarkably, most of the lost synapses were located farthest from the bipolar cell body, near the distal boundary of the outer plexiform layer (OPL), suggesting that apical synapses are most vulnerable to chronic hypoglycemia. Although treatment with the carbohydrate-rich diet restored retinal function, it did not restore these synaptic contacts. Conclusions. Prolonged exposure to diet-induced euglycemia improves retinal function but does not reestablish synaptic contacts lost by chronic hypoglycemia. These results suggest that retinal neurons have a homeostatic mechanism that integrates energetic status over prolonged periods of time and allows them to recover functionality despite synaptic loss.