Systemic inflammatory response syndrome (SIRS) is a highly mortal inflammatory disease, associated with systemic inflammation and organ dysfunction. SIRS can have a sterile cause or can be initiated by an infection, called sepsis. The prevalence is high, and available treatments are ineffective and mainly supportive. Consequently, there is an urgent need for new treatments. The brain is one of the first organs affected during SIRS, and sepsis and the consequent neurological complications, such as encephalopathy, are correlated with decreased survival. The choroid plexus (CP) that forms the blood-CSF barrier (BCSFB) is thought to act as a brain "immune sensor" involved in the communication between the peripheral immune system and the CNS. Nevertheless, the involvement of BCSFB integrity in systemic inflammatory diseases is seldom investigated. We report that matrix metalloprotease-8 (MMP8) depletion or inhibition protects mice from death and hypothermia in sepsis and renal ischemia/reperfusion. This effect could be attributed to MMP8-dependent leakage of the BCSFB, caused by collagen cleavage in the extracellular matrix of CP cells, which leads to a dramatic change in cellular morphology. Disruption of the BCSFB results in increased CSF cytokine levels, brain inflammation, and downregulation of the brain glucocorticoid receptor. This receptor is necessary for dampening the inflammatory response. Consequently, MMP8 ϩ/ϩ mice, in contrast to MMP8 Ϫ/Ϫ mice, show no anti-inflammatory response and this results in high mortality. In conclusion, we identify MMP8 as an essential mediator in SIRS and, hence, a potential drug target. We also propose that the mechanism of action of MMP8 involves disruption of the BCSFB integrity.
Monovarietal virgin olive oils (VOOs) are very effective to study relationships among sensory attributes, the compounds responsible for flavour, and factors affecting them. The stimulation of the human sensory receptors by volatile and non-volatile compounds present in monovarietal virgin olive oils gives rise to the sensory attributes that describe their peculiar delicate and fragrant flavours. The formation of these compounds is briefly illustrated and the influence of the agronomic and technological factors that affect their concentrations in the oil is examined. The relationships between compounds responsible for the olive oil flavour and sensory attributes are discussed. Several approaches for the varietal differentiation of monovarietal virgin olive oils are also overviewed.
Olive fruits at the green, cherry and black stages were used to investigate the structural and microstructural changes in tissues during ripening. Scanning electron microscopy (SEM) tissue fracture of green olives resulted in cell wall breakage of epicarp and mesocarp cells. Tissue fracture resulted in fewer broken cells in cherry than in green olives and even less in black olive tissues. Cell separation occurred in the middle lamella region in some of the cells of the cherry fruit and in most of the black olive cells. Solubilization and loss of pectic polysaccharides, mainly the arabinan moiety, and glucuronoxylans occurred in the green to cherry stages. The pulp cell wall constituent polysaccharides, pectic polysaccharides, cellulose, glucuronoxylans and xyloglucans, were degraded and/or solubilized at the cherry to black ripening stages. The resultant depolymerization of the pectic polymers, especially those of the middle lamella region, was consistent with the progressive cell separation at the different ripening stages by SEM. This showed that partial solubilization of pectic, hemicellulosic and cellulosic polysaccharides within the cell wall matrix weakened the cell wall structures, preventing the breaking of cells when the tissues were fractured.
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