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The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro- and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion (tMCAo). We found that des-acylated ghrelin (1 mg/kg) improved neurological and functional performance, reduced infarct and swelling, and decreased apoptosis. In addition, it reduced blood-brain barrier (BBB) disruption in vivo and attenuated the hyper-permeability of mouse cerebral microvascular endothelial cells after oxygen glucose deprivation and reoxygenation (OGD + RO). By contrast, acylated ghrelin (1 mg/kg or 5 mg/kg) had no significant effect on these endpoints of stroke outcome. Next we found that des-acylated ghrelin's vasoprotective actions were associated with increased expression of tight junction proteins (occludin and claudin-5), and decreased cell death. Moreover, it attenuated superoxide production, Nox activity and expression of 3-nitrotyrosine. Collectively, these results demonstrate that post-stroke treatment with des-acylated ghrelin, but not acylated ghrelin, protects against ischaemia/reperfusion-induced brain injury and swelling, and BBB disruption, by reducing oxidative and/or nitrosative damage.Copyright © 2016 The Author(s).

Contains fulltext : 167714.pdf (publisher's version ) (Closed access), Ghrelin exists in two forms in circulation, acyl ghrelin and des-acyl ghrelin, both of which have distinct and fundamental roles in a variety of physiological functions. Despite this fact, a large proportion of papers simply measure and refer to plasma ghrelin without specifying the acylation status. It is therefore critical to assess and state the acylation status of plasma ghrelin in all studies. In this study we tested the effect of des-acyl ghrelin administration on the hypothalamic-pituitary-adrenal axis and on anxiety-like behavior of mice lacking endogenous ghrelin and in ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no endogenous acyl ghrelin and high endogenous des-acyl ghrelin. Our results show des-acyl ghrelin produces an anxiogenic effect under nonstressed conditions, but this switches to an anxiolytic effect under stress. Des-acyl ghrelin influences plasma corticosterone under both nonstressed and stressed conditions, although c-fos activation in the paraventricular nucleus of the hypothalamus is not different. By contrast, GOAT KO are anxious under both nonstressed and stressed conditions, although this is not due to corticosterone release from the adrenals but rather from impaired feedback actions in the paraventricular nucleus of the hypothalamus, as assessed by c-fos activation. These results reveal des-acyl ghrelin treatment and GOAT deletion have differential effects on the hypothalamic-pituitary-adrenal axis and anxiety-like behavior, suggesting that anxiety-like behavior in GOAT KO mice is not due to high plasma des-acyl ghrelin.

Contains fulltext : 155371.pdf (publisher's version ) (Closed access), Ghrelin is a stomach hormone normally associated with feeding behavior and energy homeostasis. Recent studies highlight that ghrelin targets the brain to regulate a diverse number of functions, including learning, memory, motivation, stress responses, anxiety, and mood. In this review, we discuss recent animal and human studies showing that ghrelin regulates the hypothalamic-pituitary-adrenal axis and affects anxiety and mood disorders, such as depression and fear. We address the neural sites of action through which ghrelin regulates the hypothalamic-pituitary-adrenal axis and associated stress-induced behaviors, including the centrally projecting Edinger-Westphal nucleus, the hippocampus, amygdala, locus coeruleus, and the ventral tegmental area. Stressors modulate many behaviors associated with motivation, fear, anxiety, depression, and appetite; therefore, we assess the potential role for ghrelin as a stress feedback signal that regulates these associated behaviors. Finally, we briefly discuss important areas for future research that will help us move closer to potential ghrelin-based therapies to treat stress responses and related disorders.

A passive acoustic emission monitoring system is described which has been tested on two M10000 IsaMills. The analyser detects acoustic emission stress waves generated by grinding media impacts with the mill liner, and locally propagating stress waves can be detected on the exterior lining surface using mounted broadband accelerometers. A six-month field trial showed large variations in acoustic emission power signature with process conditions. Analysis of the enveloped acoustic emission power output showed a strong correlation with mill process conditions, in particular grinding media relative loading, feed pulp density, feed volumetric flow rate and feed type. Accelerometers placed along the length of the mill body provided information on the relative deportment of the grinding media. The enveloped acoustic emission power detected by the mill body, discharge pipe and bearing housing sensors all captured information which was strongly correlated with mill operating parameters and process state., A passive acoustic emission monitoring system is described which has been tested on two M10000 IsaMills. The analyser detects acoustic emission stress waves generated by grinding media impacts with the mill liner, and locally propagating stress waves can be detected on the exterior lining surface using mounted broadband accelerometers. A six-month field trial showed large variations in acoustic emission power signature with process conditions. Analysis of the enveloped acoustic emission power output showed a strong correlation with mill process conditions, in particular grinding media relative loading, feed pulp density, feed volumetric flow rate and feed type. Accelerometers placed along the length of the mill body provided information on the relative deportment of the grinding media. The enveloped acoustic emission power detected by the mill body, discharge pipe and bearing housing sensors all captured information which was strongly correlated with mill operating parameters and process state.

A continuous mill monitoring system has been developed for use on primary grinding mills to give on-line measurements of the mill charge. Outputs can potentially be used to give early warnings of abnormal events and features such as changes in the overall charge level, the distribution between rock and balls in the mill, and the impact of the charge on the mill liners and lifters. Two industrial scale trials showed that the system is rugged enough to operate on an industrial primary grinding mill for a year or more between routine servicing. While initially developed for use on AG/SAG mills, the monitor can also be used on other primary grinding mill types., 7 refs., A continuous mill monitoring system has been developed for use on primary grinding mills to give on-line measurements of the mill charge. Outputs can potentially be used to give early warnings of abnormal events and features such as changes in the overall charge level, the distribution between rock and balls in the mill, and the impact of the charge on the mill liners and lifters. Two industrial scale trials showed that the system is rugged enough to operate on an industrial primary grinding mill for a year or more between routine servicing. While initially developed for use on AG/SAG mills, the monitor can also be used on other primary grinding mill types.