Psicofarmacología y drogodependencias. Una respuesta docente en estudiantes de medicina

Se ha diseñado una asignatura optativa y de libre elección, para estudiantes de la Facultad de Medicina, de la Universitat de Lleida. El actual curso académico ha sido el cuarto que se viene realizando dicha asignatura. Por ella ha pasado cerca de 320 alumnos. Se trata de cubrir un vacío habitual en los planes de estudio para futuros médicos, ofreciendo tanto información específica sobre teoría del tema drogas, como experiencias prácticas referidas a modalidades de tratamiento, aspectos preventivos, recursos asistenciales, intervenciones mínimas, etc. La valoración de los alumnos de la experiencia ha sido excelente. Se insiste especialmente en transmitir el modelo bio- psico-social del fenómeno drogas, tanto en su vertiente originaria de la adicción, como en su aspecto terapéutico, por lo que implica el trabajo interdisciplinar entre profesionales.

Los orígenes del lazareto pabellonario. La arquitectura cuarentenaria en el cambio del setecientos al ochocientos

El modelo de lazareto pabellonario se configuró a partir de las bases científicas establecidas durante el proceso de reforma hospitalaria acaecido en Francia en el último tercio del setecientos. La adopción de soluciones que dieran forma a la nueva tipología cuarentenaria no vino dada precisamente por el ejemplo prestado por los nuevos tipos de hospital resultantes de este debate sino por el de otras instalaciones de cuarentena y, en general, de encierro, ya existentes. En este artículo se analizarán todos los factores que influyeron en la configuración de este modelo de lazaretos.

Investigaciones sobre la detección, difusión natural y control del enrollamiento clorótico del albaricoquero

Se ha aplicado la técnica de la tinción con el fluorocromo DAPI (4'-6- diamidino- 2-fenilindol) a la detección de organismos del tipo micoplasma («mycoplasma-like organisms» o MLOs) y al seguimiento, a lo largo de un año, de la distribución de MLOs en albaricoqueros enfermos de enrollamiento clorótico («apricot chloroiic leaf roll» o ACLR). Los resultados obtenidos confirman la poca fiabilidad de esta técnica para la detección precoz de micoplasmosis en árboles frutales, a causa de la baja concentración e irregular distribución de MLOs dentro de los árboles enfermos. Én cambio, la tinción con DAPI es útil para la observación a lo largo del año de la distribución de MLOs en diferentes partes de los árboles infectados por ACLR. A lo largo del invierno y la primavera, los MLOs fueron detectados solamente en las raíces y en los ramos formados el año anterior. La presencia de MLOs en los nuevos brotes no pudo ser detectada hasta el principio del verano. En trabajos previos se observaron grandes variaciones en la difusión natural del ACLR, incluso entre áreas próximas de la misma provincia de Valencia. Las investigaciones efectuadas ahora sobre las poblaciones de cicadélidos han mostrado que tanto el número de especies como el de individuos capturados son superiores en un área con una importante difusión natural del ACLR que en otra zona donde la difusión de la enfermedad es prácticamente nula. Las diferencias entre los cicadélidos capturados en estas dos áreas han proporcionado indicaciones acerca de las especies que tienen más probabilidades de ser vectores del ACLR. Se ha estudiado también, durante tres años, la influencia de tratamientos insecticidas y herbicidas sobre la difusión natural del ACLR en una plantación de albaricoqueros. En la mitad de la plantación que se dejó sin tratar, el número de cicadélidos capturados, así como el de nuevos árboles con síntomas de ACLR fue mayor que en la parte de la plantación que había sido tratada.

Zim17/Tim15 links mitochondrial iron–sulfur cluster biosynthesis to nuclear genome stability

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron–sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron–sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron–sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.

Glutaredoxins Grx3 and Grx4 regulate nuclear localisation of Aft1 and the oxidative stress response in Saccharomyces cerevisiae

Grx3 and Grx4, two monothiol glutaredoxins of Saccharomyces cerevisiae, regulate Aft1 nuclear localisation. We provide evidence of a negative regulation of Aft1 activity by Grx3 and Grx4. The Grx domain of both proteins played an important role in Aft1 translocation to the cytoplasm. This function was not, however, dependent on the availability of iron. Here we demonstrate that Grx3, Grx4 and Aft1 interact each other both in vivo and in vitro, which suggests the existence of a functional protein complex. Interestingly, each interaction occurred independently on the third member of the complex. The absence of both Grx3 and Grx4 induced a clear enrichment of G1 cells in asynchronous cultures, a slow growth phenotype, the accumulation of intracellular iron and a constitutive activation of the genes regulated by Aft1. The grx3grx4 double mutant was highly sensitive to the oxidising agents hydrogen peroxide and t-butylhydroperoxide but not to diamide. The phenotypes of the double mutant grx3grx4 characterised in this study were mainly mediated by the Aft1 function, suggesting that grx3grx4 could be a suitable cellular model for studying endogenous oxidative stress induced by deregulation of the iron homeostasis. However, our results also suggest that Grx3 and Grx4 might play additional roles in the oxidative stress response through proteins other than Aft1.

Hepatocyte nuclear factor-4 alpha regulates the human apolipoprotein AV gene: Identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway

The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4 (HNF-4 ) as a novel regulator of human apoAV gene. Inhibition of HNF-4 expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4 directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4 consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor- coactivator-1 was capable of stimulating the HNF-4 -dependent transactivation of apoAV promoter. Furthermore, analyses in human hepatic cells demonstrated that AMP-activated protein kinase (AMPK) and the MAPK signaling pathway regulate human apoAV expression and suggested that this regulation may be mediated, at least in part, by changes in HNF-4 . Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4 gene revealed a species-distinct regulation of apoAV by HNF-4 , which resembles that of a subset of HNF-4 target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4 and underscore the role of HNF-4 in regulating triglyceride metabolism.

Neutron skin thickness in the droplet model with surface width dependence: Indications of softness of the nuclear symmetry energy

We analyze the neutron skin thickness in finite nuclei with the droplet model and effective nuclear interactions. The ratio of the bulk symmetry energy J to the so-called surface stiffness coefficient Q has in the droplet model a prominent role in driving the size of neutron skins. We present a correlation between the density derivative of the nuclear symmetry energy at saturation and the J/Q ratio. We emphasize the role of the surface widths of the neutron and proton density profiles in the calculation of the neutron skin thickness when one uses realistic mean-field effective interactions. Next, taking as experimental baseline the neutron skin sizes measured in 26 antiprotonic atoms along the mass table, we explore constraints arising from neutron skins on the value of the J/Q ratio. The results favor a relatively soft symmetry energy at subsaturation densities. Our predictions are compared with the recent constraints derived from other experimental observables. Though the various extractions predict different ranges of values, one finds a narrow window L∼45-75 MeV for the coefficient L that characterizes the density derivative of the symmetry energy that is compatible with all the different empirical indications.

Nuclear DNA content variation in life history phases of the Bonnemaisoniaceae (Rhodophyta)

Nuclear DNA content in gametophytes and sporophytes or the prostrate phases of the following species of Bonnemaisoniaceae (Asparagopsis armata, Asparagopsis taxiformis, Bonnemaisonia asparagoides, Bonnemaisonia clavata and Bonnemaisonia hamifera) were estimated by image analysis and static microspectrophotometry using the DNA-localizing fluorochrome DAPI (4′, 6-diamidino-2-phenylindole, dilactate) and the chicken erythrocytes standard. These estimates expand on the Kew database of DNA nuclear content. DNA content values for 1C nuclei in the gametophytes (spermatia and vegetative cells) range from 0.5 pg to 0.8 pg, and for 2C nuclei in the sporophytes or the prostrate phases range from 1.15-1.7 pg. Although only the 2C and 4C values were observed in the sporophyte or the prostrate phase, in the vegetative cells of the gametophyte the values oscillated from 1C to 4C, showing the possible start of endopolyploidy. The results confirm the alternation of nuclear phases in these Bonnemaisoniaceae species, in those that have tetrasporogenesis, as well as those that have somatic meiosis. The availability of a consensus phylogenetic tree for Bonnemaisoniaceae has opened the way to determine evolutionary trends in DNA contents. Both the estimated genome sizes and the published chromosome numbers for Bonnemaisoniaceae suggest a narrow range of values consistent with the conservation of an ancestral genome.

Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability.

Secondary structure-forming DNA sequences such as CAG repeats interfere with replication and repair, provoking fork stalling, chromosome fragility, and recombination. In budding yeast, we found that expanded CAG repeats are more likely than unexpanded repeats to localize to the nuclear periphery. This positioning is transient, occurs in late S phase, requires replication, and is associated with decreased subnuclear mobility of the locus. In contrast to persistent double-stranded breaks, expanded CAG repeats at the nuclear envelope associate with pores but not with the inner nuclear membrane protein Mps3. Relocation requires Nup84 and the Slx5/8 SUMO-dependent ubiquitin ligase but not Rad51, Mec1, or Tel1. Importantly, the presence of the Nup84 pore subcomplex and Slx5/8 suppresses CAG repeat fragility and instability. Repeat instability in nup84, slx5, or slx8 mutant cells arises through aberrant homologous recombination and is distinct from instability arising from the loss of ligase 4-dependent end-joining. Genetic and physical analysis of Rad52 sumoylation and binding at the CAG tract suggests that Slx5/8 targets sumoylated Rad52 for degradation at the pore to facilitate recovery from acute replication stress by promoting replication fork restart. We thereby confirmed that the relocation of damage to nuclear pores plays an important role in a naturally occurring repair process.

Nuclear surface properties in relativistic effective field theory

We perform Hartree calculations of symmetric and asymmetric semi-infinite nuclear matter in the framework of relativistic models based on effective hadronic field theories as recently proposed in the literature. In addition to the conventional cubic and quartic scalar self-interactions, the extended models incorporate a quartic vector self-interaction, scalar-vector non-linearities and tensor couplings of the vector mesons. We investigate the implications of these terms on nuclear surface properties such as the surface energy coefficient, surface thickness, surface stiffness coefficient, neutron skin thickness and the spin-orbit force.

Dificultad en la comunicación del riesgo de padecer cáncer hereditario.

Diferentes estudios han demostrado que, en ocasiones, los pacientes tienen dificultades a la hora de entender lo que el médico quiere comunicarles. El presente artículo intenta reflexionar sobre cuáles son los determinantes que pueden influir en el proceso de comunicación del riesgo en pacientes que tienen antecedentes familiares de cáncer y acuden a las Unidades de Consejo Genético en busca de asesoramiento. Existen estudios que señalan que los pacientes con antecedentes familiares de cáncer se preocupan por padecer dicha enfermedad. Sólo algunos de ellos han explorado cómo los pacientes entienden y perciben el concepto de riesgo y los posibles sesgos asociados a él. Como primeras aproximaciones, creemos que es necesario utilizar un lenguaje sencillo, claro y fácil de entender por parte de los pacientes, huyendo del lenguaje epidemiológico o médico. Del mismo modo es importante diseñar programas de formación psicoeducativos y material de soporte adecuado, así como el correcto manejo del counselling como herramienta principal de trabajo por parte de los profesionales y fomentar futuras investigaciones en este área determinada.

Nuclear receptor peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer

We review the functions of peroxisome proliferator activated receptor (PPAR) beta/delta in skin wound healing and cancer. In particular, we highlight the roles of PPAR beta/delta in inhibiting keratinocyte apoptosis at wound edges via activation of the PI3K/PKB alpha/Akt1 pathway and its role during re-epithelialization in regulating keratinocyte adhesion and migration. In fibroblasts, PPAR beta/delta controls IL-1 signalling and thereby contributes to the homeostatic control of keratinocyte proliferation. We discuss its therapeutic potential for treating diabetic wounds and inflammatory skin diseases such as psoriasis and acne vulgaris. PPAR beta/delta is classified as a tumour growth modifier; it is activated by chronic low-grade inflammation, which promotes the production of lipids that, in turn, enhance PPAR beta/delta transcription activity. Our earlier,work unveiled a cascade of events triggered by PPAR beta/delta that involve the oncogene Src, which promotes ultraviolet-induced skin cancer in mice via enhanced EGFR/Erk1/2 signalling and the expression of epithelial-to-mesenchymal transition (EMT) markers. Interestingly, PPAR beta/delta expression is correlated with the expression of SRC and EMT markers in human skin squamous cell carcinoma. Furthermore, there is a positive interaction between PPAR beta/delta, SRC, and TGF beta 1 at the transcriptional level in various human epithelial cancers. Taken together, these observations suggest the need for evaluating PPAR beta/delta modulators that attenuate or increase its activity, depending on the therapeutic target.

Hepatocyte nuclear factor 4alpha transactivates the mitochondrial alanine aminotransferase gene in the kidney of Sparus aurata

Alanine aminotransferase (ALT) plays an important role in amino acid metabolism and gluconeogenesis. The preference of carnivorous fish for protein amino acids instead of carbohydrates as a source of energy lead us to study the transcriptional regulation of the mitochondrial ALT (mALT) gene and to characterize the enzyme kinetics and modulation of mALT expression in the kidney of gilthead sea bream (Sparus aurata) under different nutritional and hormonal conditions. 5′-Deletion analysis of mALT promoter in transiently transfected HEK293 cells, site-directed mutagenesis and electrophoretic mobility shift assays allowed us to identify HNF4α as a new factor involved in the transcriptional regulation of mALT expression. Quantitative RT-PCR assays showed that starvation and the administration of streptozotocin (STZ) decreased HNF4α levels in the kidney of S. aurata, leading to the downregulation of mALT transcription. Analysis of the tissue distribution showed that kidney, liver, and intestine were the tissues with higher mALT and HNF4α expression. Kinetic analysis indicates that mALT enzyme is more efficient in catalyzing the conversion of L-alanine to pyruvate than the reverse reaction. From these results, we conclude that HNF4α transactivates the mALT promoter and that the low levels of mALT expression found in the kidney of starved and STZ-treated fish result from a decreased expression of HNF4α. Our findings suggest that the mALT isoenzyme plays a major role in oxidazing dietary amino acids, and points to ALT as a target for a biotechnological action to spare protein and optimize the use of dietary nutrients for fish culture.

Nuclear Symmetry Energy Probed by Neutron Skin Thickness of Nuclei

We describe a relation between the symmetry energy coefficients csym(ρ) of nuclear matter and asym(A) of finite nuclei that accommodates other correlations of nuclear properties with the low-density behavior of csym(ρ). Here, we take advantage of this relation to explore the prospects for constraining csym(ρ) of systematic measurements of neutron skin sizes across the mass table, using as example present data from antiprotonic atoms. The found constraints from neutron skins are in harmony with the recent determinations from reactions and giant resonances.