Early chronic fasudil treatment rescues hippocampal alterations in the Ts65Dn model for down syndrome.

Down syndrome (DS) is the most common genetic disorder associated with intellectual disability. To study this syndrome, several mouse models have been developed. Among the most common is the Ts65Dn model, which mimics most of the alterations observed in DS. Ts65Dn mice, as humans with DS, show defects in the structure, density, and distribution of dendritic spines in the cerebral cortex and hippocampus. Fasudil is a potent inhibitor of the RhoA kinase pathway, which is involved in the formation and stabilization of dendritic spines. Our study analysed the effect of early chronic fasudil treatment on the alterations observed in the hippocampus of the Ts65Dn model. We observed that treating Ts65Dn mice with fasudil induced an increase in neural plasticity in the hippocampus: there was an increment in the expression of PSA-NCAM and BDNF, in the dendritic branching and spine density of granule neurons, as well as in cell proliferation and neurogenesis in the subgranular zone. Finally, the treatment reduced the unbalance between excitation and inhibition present in this model. Overall, early chronic treatment with fasudil increases cell plasticity and eliminates differences with euploid animals.

A targeted polypeptide-based nanoconjugate as a nanotherapeutic for alcohol-induced neuroinflammation.

Alcohol abuse induces the expression of inflammatory mediators by activating the immune receptors to trigger neuroinflammation and brain damage; however, therapies that reduce neuroimmune system activation may protect against alcohol's damaging effects. Curcuminoids possess anti-inflammatory properties but suffer from low bioavailability; therefore, we designed a new receptor-targeted biodegradable star-shaped crosslinked polypeptide polymer that bears propargylamine moieties and bisdemethoxycurcumin (StClPr-BDMC-ANG) as an enhanced anti-inflammatory therapeutic that penetrates the blood-brain-barrier and ameliorates alcohol-induced neuroinflammation. StClPr-BDMC-ANG administration maintains the viability of primary glia and inhibits the ethanol-induced upregulation of crucial inflammatory mediators in the prefrontal and medial cortex in a mouse model of chronic ethanol consumption. StClPr-BDMC-ANG treatment also suppresses the ethanol-mediated downregulation of microRNAs known to negatively modulate neuroinflammation in the brain cortex (miRs 146a-5p and let-7b-5p). In summary, our results demonstrate the attenuation of alcohol-induced neuroinflammation by an optimized and targeted polypeptide-based nanoconjugate of a curcuminoid.

Morphological alterations in the hippocampus of the Ts65Dn mouse model for Down Syndrome correlate with structural plasticity markers.

Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons. Structural plasticity has been analysed using immunohistochemistry for plasticity molecules followed by densitometric analysis (Brain Derived Neurotrophic Factor (BDNF), Polysialylated form of the Neural Cell Adhesion Molecule (PSA-NCAM) and the Growth Associated Protein 43 (GAP43)). We observed an impairment in the dendritic arborisation of granule cells, but not in the pyramidal neurons in the Ts65Dn mice. When we analysed the expression of molecules related to structural plasticity in trisomic mouse hippocampus, we observed a reduction in the expression of BDNF and PSA-NCAM, and an increment in the expression of GAP43. These alterations were restricted to the regions related to dentate granule cells suggesting an interrelation. Therefore the impairment in dendritic arborisation and molecular plasticity is not a general feature of all Down syndrome principal neurons. Pharmacological manipulations of the levels of plasticity molecules could provide a way to restore granule cell morphology and function.

Perfil microbiológico de los pacientes con diagnóstico de neumonía asociada a ventilación mecánica en el servicio de medicina 4, hospital general del Instituto Salvadoreño del Seguro Social, año 2015 / Microbiological profile of patients diagnosed with pneumonia associated with mechanical ventilation in the medical service 4, general hospital of the "Instituto Salvadoreño del Seguro Social", year 2015

El presente trabajo recoge los datos de aislamiento microbiológico en las secreciones bronquiales recolectadas tanto por aspirado bronquial, entendido como aspiración de secreciones mediante una sonda de aspiración con vacío a través de tubo orotraqueal; como por fibrobroncoscopía, utilizando el fibrobroncoscopio flexible mediante toma de lavado bronquioalveolar, en aquellos pacientes con diagnóstico de neumonía asociada a ventilación mecánica, que estando ingresados en el servicio de Medicina 4 del Hospital General del Instituto Salvadoreño del Seguro Social (ISSS), desarrollaron insuficiencia respiratoria por causa no infecciosa y se colocaron en ventilación mecánica, con la posterior complicación infecciosa, que sucedieron durante el período del año 2015. Se contó con una identificación de las principales características clínicas y demográficas de los pacientes y la situación epidemiológica de pacientes que asistieron a este servicio, además de caracterizar el aislamiento bacteriológico de dichas patologías, pudiendo identificar los patógenos y la expresión fenotípica de resistencia antibiótica de las bacterias que afectan a la población de derechohabientes del instituto. Así, tener información de la flora predominante del servicio durante el período de investigación, lograr adecuar proyectos de seguimiento, y poder respaldar medidas de prevención y pautas terapéuticas en base a la evidencia encontrada en el servicio de hospitalización