Endothelial cells, endoplasmic reticulum stress and oxysterols

Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress

Fingerprinting the hydration products of hydraulic binders using snapshots from time-resolved in situ multinuclear mas nmr spectroscopy

The very early hydration behavior of a hydraulic binder phase, ye'elimite, Ca4Al6O12SO4, in the absence and in the presence of calcium sulfate, has been investigated. A time-resolved in situ multinuclear magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopic suite involving 1H and 27Al MAS as well as two-dimensional 27Al multiple quantum MAS (MQMAS) experiments has been employed to detect the transient species and to govern the sequence of hydration reactions and the subsequent formation of the hydration products. The results of the study show that the rates of formation of ye'elimite hydration products vary substantially according to the absence or the presence of calcium sulfate. Hydrated calcium sulfoaluminate phases such as ettringite and monosulfate as well as aluminum hydroxide gel have been detected during the various stages of hydration. The direct observation of various transient species during the hydration stages of calcium aluminates and calcium sulfoaluminates illustrates the potential of a newly designed time-resolved in situ 1H MAS NMR experimental approach for fingerprinting phases and offers significant advantages over other established techniques in detecting transient species

Final report on PCRV thermal cylinder axial tendon failures

The post-test examination of the failed tendons from the PCRV thermal cylinder experiment has been concluded. Failures in the wires are attributed to stress-corrosion cracking. The cause of tendon failures has not been unequivocably established, but they may have been due to nitrates in the duct. The wires employed in the manufacture of the tendons will crack in less than 72 hr in a 0.2 M solution of ammonium nitrate at 70$sup 0$C. The quality of the wires is poor, and surface cracks were detected. These could have acted as concentrating sites for both stress and the deleterious contaminants. It is believed that the factors that led to the failures in the thermal cylinder experiment were unique. An improper formulation of the epoxy resin did not provide the tendon anchor plate seal that was desired; indeed, the improper formulation is responsible for the high level of nitrogen in the ducts of the failed tendons. (auth

Detection of Leishmania spp. in Chronic Dermatitis: Retrospective Study in Exposed Horse Populations

Leishmania infantum is a protozoan causing human zoonotic visceral leishmaniasis (ZVL) and visceral–cutaneous canine leishmaniosis (CanL) in the Mediterranean Basin. L. infantum is able to infect a large number of wild and domestic species, including cats, dogs, and horses. Since the 1990s, clinical cases of equine leishmaniasis (EL), typically characterized by cutaneous forms, have been increasingly diagnosed worldwide. The aim of the present study was to evaluate the presence of clinical forms of EL in CanL-endemic areas in Italy, where exposure of equine populations was ascertained from recent serological surveys. For this purpose, formalin-fixed and paraffin-embedded skin biopsies of 47 horses presenting chronic dermatitis compatible with EL were retrospectively selected for the study and subjected to conventional and q-PCR. A singular positivity for L. infantum was found; BLAST analysis of sequence amplicons revealed a 99–100% homology with L. infantum sequences. The histological examination revealed a nodular lymphoplasmacytic and histiocytic infil-trate; immunohistochemistry showed rare macrophages containing numerous positive amastigotes. The present retrospective study reports, for the first time, a case of a cutaneous lesion by L. infantum occurring in an Italian horse. Pathological and healthy skin samples should be investigated on a larger scale to provide information on the potential clinical impact of EL in the practice, and to define the role of horses in epidemiological ZVL and CanL scenarios

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

Objectives: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Design: Cross-sectional, multicenter, clinical study. Participants: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. Measurements: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Results: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. Conclusions: The authors’ study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms

Evidence for immunomodulation and apoptotic processes induced by cationic polystyrene nanoparticles in the hemocytes of the marine bivalve Mytilus

none8sìPolymeric nanoparticles can reach the marine environment from different sources as weathering of plastic debris and nanowaste. Nevertheless, few data are available on their fate and impact on marine biota. Polystyrene nanoparticles (PS NPs) can be considered as a model for studying the effects of nanoplastics in marine organisms: recent data on amino-modified PS NPs (PS-NH2) toxicity in sea urchin embryos underlined that marine invertebrates can be biological targets of nanoplastics. Cationic PS NPs have been shown to be toxic to mammalian cells, where they can induce apoptotic processes; however, no information is available on their effects and mechanisms of action in the cells of marine organisms. In this work, the effects of 50 nm PS-NH2 were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. Hemocytes were exposed to different concentrations (1, 5, 50 μg/ml) of PS-NH2 suspension in ASW. Clear signs of cytoxicity were evident only at the highest concentrations (50 μg/ml). On the other hand, a dose dependent decrease in phagocytic activity and increase in lysozyme activity were observed. PS-NH2 NPs also stimulated increase in extracellular ROS (reactive oxygen species) and NO (nitric oxide) production, with maximal effects at lower concentrations. Moreover, at the highest concentration tested, PS-NH2 NPs induced apoptotic process, as evaluated by Flow cytometry (Annexin V binding and mitochondrial parameters). The results demonstrate that in marine invertebrates the immune function can represent a significant target for PS-NPs. Moreover, in Mytilus hemocytes, PS-NH2 NPs can act through mechanisms similar to those observed in mammalian cells. Further research is necessary on specific mechanisms of toxicity and cellular uptake of nanoplastics in order to assess their impact on marine biota.openCanesi, L; Ciacci, Caterina; Bergami, E; Monopoli, M. P; Dawson, K. A; Papa, Stefano; Canonico, Barbara; Corsi, I.Canesi, L; Ciacci, Caterina; Bergami, E; Monopoli, M. P; Dawson, K. A; Papa, Stefano; Canonico, Barbara; Corsi, I