In Vivo Comparative Study on Acute and Sub-acute Biological Effects Induced by Ultrafine Particles of Different Anthropogenic Sources in BALB/c Mice

Exposure to ultrafine particles (UFPs) leads to adverse effects on health caused by an unbalanced ratio between UFPs deposition and clearance efficacy. Since air pollution toxicity is first direct to cardiorespiratory system, we compared the acute and sub-acute effects of diesel exhaust particles (DEP) and biomass burning-derived particles (BB) on bronchoalveolar Lavage Fluid (BALf), lung and heart parenchyma. Markers of cytotoxicity, oxidative stress and inflammation were analysed in male BALB/c mice submitted to single and repeated intra-tracheal instillations of 50 g UFPs. This in-vivo study showed the activation of inflammatory response (COX-2 and MPO) after exposure to UFPs, both in respiratory and cardiovascular systems. Exposure to DEP results also in pro- and anti-oxidant (HO-1, iNOS, Cyp1b1, Hsp70) protein levels increase, although, stress persist only in cardiac tissue under repeated instillations. Statistical correlations suggest that stress marker variation was probably due to soluble components and/or mediators translocation of from first deposition site. This mechanism, appears more important after repeated instillations, since inflammation and oxidative stress endure only in heart. In summary, chemical composition of UFPs influenced the activation of different responses mediated by their components or pro-inflammatory and pro-oxidative molecules, indicating DEP as the most damaging pollutant in the comparison

Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles.

The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood-brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed

Scavo con TBM-EPB di ammassi rocciosi contenenti metano

La nota presenta, in maniera sintetica, i problemi che si sono affrontati e risolti durante la realizzazione con TBM-EPB (Tunnel Boring Machine-Earth Pressure Balance) della Galleria Sparvo in un ammasso roccioso con accertata presenza di metano. L’opera è la prima della Variante Autostradale di Valico (VAV) ad essere stata realizzata con tecnica di scavo meccanizzato. L’adozione dello scavo meccanizzato con TBM, prima della Sparvo, non aveva trovato applicazione nel progetto VAV in quanto non era disponibile una soluzione tecnica compatibile con la potenziale presenza di metano nelle formazioni da scavare e d’altra parte non erano disponibili indicazioni normative sui principi realizzativi di una TBM idonea ad operare in un contesto grisutoso. Pertanto la Galleria Sparvo rappresenta un importante caso di studio, poiché la TBM-EPB progettata ad hoc è un prototipo di grande diametro in grado di operare con assoluta sicurezza in formazioni grisutose. La nota si sofferma sull’analisi e sull’interpretazione delle misure di monitoraggio metano e presenta analisi di correlazione tra le formazioni attraversate e le portate di metano emesse dall’ammasso roccioso durante l’avanzamento della fresa

Changes in the mechanical properties of the respiratory system during the development of interstitial lung edema

Abstract Background Pulmonary edema induces changes in airway and lung tissues mechanical properties that can be measured by low-frequency forced oscillation technique (FOT). It is preceded by interstitial edema which is characterized by the accumulation of extravascular fluid in the interstitial space of the air-blood barrier. Our aim was to investigate the impact of the early stages of the development of interstitial edema on the mechanical properties of the respiratory system. Methods We studied 17 paralysed and mechanically ventilated closed-chest rats (325–375 g). Total input respiratory system impedance (Zrs) was derived from tracheal flow and pressure signals by applying forced oscillations with frequency components from 0.16 to 18.44 Hz distributed in two forcing signals. In 8 animals interstitial lung edema was induced by intravenous infusion of saline solution (0.75 ml/kg/min) for 4 hours; 9 control animals were studied with the same protocol but without infusion. Zrs was measured at the beginning and every 15 min until the end of the experiment. Results In the treated group the lung wet-to-dry weight ratio increased from 4.3 ± 0.72 to 5.23 ± 0.59, with no histological signs of alveolar flooding. Resistance (Rrs) increased in both groups over time, but to a greater extent in the treated group. Reactance (Xrs) did not change in the control group, while it decreased significantly at all frequencies but one in the treated. Significant changes in Rrs and Xrs were observed starting after ~135 min from the beginning of the infusion. By applying a constant phase model to partition airways and tissue mechanical properties, we observed a mild increase in airways resistance in both groups. A greater and significant increase in tissue damping (from 603.5 ± 100.3 to 714.5 ± 81.9 cmH2O/L) and elastance (from 4160.2 ± 462.6 to 5018.2 ± 622.5 cmH2O/L) was found only in the treated group. Conclusion These results suggest that interstitial edema has a small but significant impact on the mechanical features of lung tissues and that these changes begin at very early stages, before the beginning of accumulation of extravascular fluid into the alveoli.</p

Morphological organization of somatosensory cortex in Otxl(-/-) mice

Knock-out Otx1 mice show brain hypoplasia, spontaneous epileptic seizures and abnormalities of the dorsal region of the neocortex. We investigated structural alterations in excitatory and inhibitory circuits in somatosensory cortex of Otx1 12/ 12 mice by immunocytochemistry using light, confocal and electron microscopy. Immunostaining for non-phosphorylated neurofilament SMI311 and subunit 1 of the NMDA receptor \u2013 used as markers of pyramidal neurons \u2013 showed reduced layer V pyramidal cells and ectopic pyramidal cells in layers II and III of the mutant cortex. Immunostaining for calcium-binding proteins calbindin, calretinin and parvalbumin \u2013 markers of non-overlapping types of GABAergic interneurons \u2013 showed no differences between wild-type and knock-out cortex for calbindin and calretinin neurons, while parvalbumin neurons were only patchily distributed in Otx1 12/ 12 cortex. The pattern of positivity of the GABAergic marker glutamic acid decarboxylase in Otx1 12/ 12 cortex was also altered and similar to that of parvalbumin. GABA transporter 1 immunoreactivity was greater in Otx1 12/ 12 than wild-type; quantitation of structures immunoreactive for this transporter in layer V showed that they were increased overall in Otx1 12/ 12 but the density of inhibitory terminals on pyramidal neurons in the same layer labeled with this transporter was similar to that in wild-type mice. No differences in the distribution or intensity of the glial markers GABA transporter 3 or glial fibrillary acidic protein were found. The defects found in the cortical GABAergic system of the Otx1 12/ 12 mouse can plausibly explain the cortical hyperexcitability that produces seizures in these animals

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