The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

Using the World Wide Web to develop key professional skills in veterinary undergraduates

This paper outlines the pedagogical and practical reasons for developing two interactive online pathology modules for use by third-year undergraduates in veterinary medicine at the University of Glasgow: namely, to further students' understanding of general and systems pathology, as well as their acquisition of key professional skills, and to provide access to a core-elective system of education and to subsequent employment and lifelong learning

Platelet Function and Coronary Microvascular Dysfunction

The ability of platelets to activate and aggregate to form blood clots in response to endothelial injury is well established. They are therefore critical contributors to ischaemia in atherothrombosis [1]. However, their role in cardiovascular disease is not limited to end-stage thrombosis in large vessels [2]. Abundant experimental evidence has established that activated platelets are also important mediators of microvascular thrombosis and promote the inflammatory response during ischaemia-reperfusion (IR) injury [3–5]. While platelets do not physically interact with the healthy endothelium, they can bind to the wall of hypoxic microvessels and release a plethora of inflammatory mediators that further enhance the activation of the endothelial monolayer and the recruitment of circulating leukocytes (monocytes, neutrophils, T-cells) [2]. In addition, deposition of platelets to the dysfunctional endothelium can lead to vasoconstriction which accelerates microvascular occlusion, thereby impairing tissue perfusion [3]. In this chapter, we discuss the role of platelets in promoting microvascular dysfunction and inflammation during IR injury. Focus is placed on the cross-talk between platelets and other cell types (endothelial cells [ECs] and leukocytes) via platelet adhesion receptors and platelet-derived proinflammatory mediators. We also consider new paradoxical functionalities of platelets promoting cardiac recovery after myocardial infarction (MI)