Effects of perinatal asphyxia on rat striatal cytoskeleton.

Perinatal asphyxia (PA) is a medical condition associated with a high short-term morbimortality and different long-term neurological diseases. In previous works, we have shown that neuronal and synaptic changes in rat striatum lead to ubi-protein accumulation in post-synaptic density (PSD) after six months of sub-severe PA. However, very little is known about the synaptic and related structural modifications induced by PA in young rats. In the present work, we studied neuronal cytoskeleton modifications in striatum induced by subsevere PA in 30-day-old rats. We observed a significant decrease in the number of neurons, in particular calbindin immunoreactive neurons after PA. In addition, it was also observed that actin cytoskeleton was highly modified in the PSD as well as an increment of F-actin staining by Phalloidin-alexa(488) in the striatum of PA rats. Using correlative fluorescence-electron microscopy photooxidation, we confirmed and extended confocal observations. F-actin staining augmentation was mostly related with an increment in the number of mushroom-shaped spines. Consistent with microscopic data, Western blot analysis revealed a ß-actin increment in PSD in PA rats. On the other hand, MAP-2 immunostaining was decreased after PA, being NF-200 expression unmodified. Although neuronal death was observed, signs of generalized neurodegeneration were absent. Taken together these results showed early post-synaptic F-actin cytoskeleton changes induced by PA with slightly modifications in the other components of the neuronal cytoskeleton, suggesting that F-actin accumulation in the dendritic spines could be involved in the neuronal loss induced by PA.

Thioredoxin 1 Plays a Protective Role in Retinas Exposed to Perinatal Hypoxia-Ischemia.

Thioredoxin family proteins are key modulators of cellular redox regulation and have been linked to several physiological functions, including the cellular response to hypoxia-ischemia. During perinatal hypoxia-ischemia (PHI), the central nervous system is subjected to a fast decrease in O2 and nutrients with a subsequent reoxygenation that ultimately leads to the production of reactive species impairing physiological redox signaling. Particularly, the retina is one of the most affected tissues, due to its high oxygen consumption and exposure to light. One of the main consequences of PHI is retinopathy of prematurity, comprising changes in retinal neural and vascular development, with further compensatory mechanisms that can ultimately lead to retinal detachment and blindness. In this study, we have analyzed long-term changes that occur in the retina using two well established in vivo rat PHI models (perinatal asphyxia and carotid ligation model), as well as the ARPE-19 cell line that was exposed to hypoxia and reoxygenation. We observed significant changes in the protein levels of the cytosolic oxidoreductase thioredoxin 1 (Trx1) in both animal models and a cell model. Knock-down of Trx1 in ARPE-19 cells affected cell morphology, proliferation and the levels of specific differentiation markers. Administration of recombinant Trx1 decreased astrogliosis and improved delayed neurodevelopment in animals exposed to PHI. Taken together, our results suggest therapeutical implications for Trx1 in retinal damage induced by hypoxia-ischemia during birth.

Single-electron transport in a three-ion magnetic molecule modulated by a transverse field.

We study single-electron transport in a three-ion molecule with strong uniaxial anisotropy and in the presence of a transverse magnetic field. Two magnetic ions are connected to each other through a third, nonmagnetic ion. The magnetic ions are coupled to ideal metallic leads and a back gate voltage is applied to the molecule, forming a field-effect transistor. The microscopic Hamiltonian describing this system includes inter-ion hopping, on-site repulsions and magnetic anisotropies. For a range of values of the parameters of the Hamiltonian, we obtain an energy spectrum similar to that of single-molecule magnets in the giant spin approximation where the two states with maximum spin projection along the uniaxial anisotropy axis are well separated from other states. In addition, upon applying an external in-plane magnetic field, the energy gap between the ground and first excited states of the molecule oscillates, going to zero at certain special values of the field, analogous to the diabolical points resulting from Berry phase interference in the giant spin model. Thus, our microscopic model provides the same phenomenological behavior expected from the giant spin model of a single-molecule magnet but with direct access to the internal structure of the molecule, thus making it more appropriate for realistic electronic transport studies. To illustrate this point, the nonlinear electronic transport in the sequential tunneling regime is evaluated for values of the field near these degeneracy points. We show that the existence of these points has a clear signature in the I-V characteristics of the molecule, most notably the modulation of excitation lines in the differential conductance.

[Comparison between echocardiographic and hemodynamic indices in the evaluation of mitral stenosis]. / Comparación entre los índices ecocardiográficos y hemodinámicos en la valoración de la estenosis mitral.

The echocardiographic data (the amplitude of the mitral echogram, the velocity of the E to F slope and the dimension of the left atrium) of 12 patients with mitral stenosis were compared with hemodynamic data obtained during a cardiac catheterization (the mitral valve area and the peak left ventricular filling rate, expressed in millimeters/second [dv/dtD] and normalized by the end-diastolic volume [dv/dtD/VTD seg-1]). None of the echocardiographic variables showed a good correlation with the hemodynamic indices. It is concluded that echocardiography is a useful total in the diagnosis of mitral stenosis, but at the same time there is not a single echocardiographic sign which by itself evaluate correctly the severity of mitral stenosis.