Quantification of nucleobases/gold nanoparticles interactions: energetics of the interactions through apparent binding constants determination.

We explore the possibilities of quantifying the interaction of both adenine and thymine with non-functionalized, anionic citrate gold nanoparticles (AuNPs). Following the plasmon absorbance band's red shifts, dependent of the AuNPs aggregation state, apparent binding free energies of the system are obtained for the sum of the two processes (nucleobase interaction plus nanoparticle aggregation). A deconvolution procedure confirms those results. Those apparent binding free energies are, in both cases, in good agreement with previous studies indicating an increased reactivity for adenine. Moreover, density functional theory (DFT) calculations were carried out both to model the structures and to theoretically support and help understand the observed experimental stability of adenine as compared to thymine over gold nanoparticles. Theoretical results indicate the N atom in the amino group of adenine adopts a pyramidal sp3 hybridization character, stabilizing the interaction with Au as compared to thymine.

Polineuropatía tardía secundaria a intoxicación por insecticidas organofosforados / Delayed polyneuropathy induced by organophosphorus insecticides poisoning

Los insecticidas organofosforados presentan como mecanismo tóxico más importante la inhibición directa de la acetilcolinesterasa.También pueden producir efectos tóxicos directos, un síndrome intermedio y con me-nor frecuencia una polineuropatía tardía, que afecta fundamentalmente a nervios periféricos y que puede evolucionar de forma retrógrada y ascendente, afectando al sistema nervioso central. Presentamos el caso de un paciente de 72 años, que dos semanas después de fumigar con insecticidas organofosforados inició un cuadro progresivo de disestesias, déficit de fuerza de predominio en extremidades inferiores y progresivo trastorno de la marcha, que desembocó en una tetraparesia flácida. El electromiograma confirmó una polineuropatía mixta motora y sensitiva, compatible con neuropatía desmielinizante con componente axonopático sensitivo grave. No existe tratamiento farmacológico específico para la polineuropatía tardía.Tras el tratamiento sintomático de las complicaciones en fase aguda, únicamente el tratamiento rehabilitador puede tener utilidad a la hora de minimizar las secuelas funcionales (AU)

The most important poisoning mechanism of organophosphorus insecticides is the direct inhibition of acetylcholinesterase.This may also cause direct toxicity, an intermediate syndrome and less frequently delayed polyneuropathy, which mainly affects peripheral nerves and may progress in an ascending retrograde way, compromising the central nervous system.We present the case of a 72-year old man who at two weeks of fumigating with organophosphorus insecticides developed a progressive picture of paresthesias, dysesthesias, lower limb weakness and gait disorders that resulted in flaccid tetraparesia.The electromyography confirmed the presence of mixed sensorimotor polyneuropathy in the lower limbs consistent with demyelinating neuropathy and severe axonopathy component.There is no specific pharmacological treatment for delayed polyneuropathy and once the symptomatic treatment has been provided in the acute phase, only rehabilitation has proven to be effective in minimizing functional sequelae of these patients (AU)

Continuous expression of corticotropin-releasing factor in the central nucleus of the amygdala emulates the dysregulation of the stress and reproductive axes.

An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequences of chronic stress exposure and cause dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increase emotionality and disrupt reproduction. To test this hypothesis, we used a lentiviral vector to increase CRF-expression site specifically in CeA of female rats. Increased synthesis of CRF in CeA amplified CRF and arginine vasopressin peptide concentration in the paraventricular nucleus of the hypothalamus, and decreased glucocorticoid negative feedback, both markers associated with the pathophysiology of depression. In addition, continuous expression of CRF in CeA also increased the acoustic startle response and depressive-like behavior in the forced swim test. Protein levels of gonadotropin-releasing hormone in the medial preoptic area were significantly reduced by continuous expression of CRF in CeA and this was associated with a lengthening of estrous cycles. Finally, sexual motivation but not sexual receptivity was significantly attenuated by continuous CRF synthesis in ovariectomized estradiol-progesterone-primed females. These data indicate that unrestrained CRF synthesis in CeA produces a dysregulation of the HPA axis, as well as many of the behavioral, physiological and reproductive consequences associated with stress-related disorders.Molecular Psychiatry (2009) 14, 37-50; doi:10.1038/mp.2008.91; published online 12 August 2008.