ANCA with specificity for proteinase 3 (PR3), a neutrophil primary granule enzyme, are of diagnostic value in Wegener's granulomatosis (WG) and certain other forms of systemic vasculitis. There is evidence to suggest that they play a pathogenic role in disease, and that the interaction of ANCA with PR3 is likely to be important. We showed, using a resonant mirror biosensor, that C-ANCA from different patients recognized the same or closely related epitopes on PR3. Studies using linear peptides in the SPOT system confirmed the highly restricted nature of this interaction and identified five linear epitopes. Fluid-phase inhibition studies, using a different set of peptides, validated the sequences involved. Using a computer-generated model of the structure of PR3, four of five epitopes were shown to be intimately linked with the catalytic site. The restricted number of epitopes, and their location at the catalytic site, has important implications for the role of C-ANCA in the pathogenesis of vasculitis.

Diagnostic imaging of the eye can be performed using ultrasonography, MRI or CT. This study describes the CT dimensions, volumes and radiodensities of presumed normal feline intraocular structures. Nineteen adult patients were included in this retrospective study. Fourteen males and five females were included, with domestic short hair (DSH) being the predominant breed. Length, volume and radiodensity values for the lens, anterior chamber, vitreous chamber and optic nerve were calculated as well as measurements of the optic nerve width. There was no significant correlation found on linear regression analysis comparing patient’s body weight with the various ocular measurements. Measurements of the lens, globe and optic nerve had significant differences (P<0.05) noted between the sexes, with males having increased values. These results may be skewed due to the large majority of male patients in the study. There was a weak correlation found between age and right eye (OD) optic nerve width, with an increase in the optic nerve width noted with increasing age. The findings of this study are a first step in establishing CT reference values for feline intraocular structure measurements.

Exercise has multiple beneficial effects including improving peripheral insulin sensitivity, improving central function such as memory, and restoring a dysregulated blood-brain barrier (BBB). Central nervous system (CNS) insulin resistance is a common feature of cognitive impairment, including Alzheimer's disease. Delivery of insulin to the brain can improve memory. Endogenous insulin must cross the BBB to directly act within the CNS and this transport system can be affected by various physiological states and serum factors. Therefore, the current study sought to investigate whether exercise could enhance insulin BBB transport as a mechanism for the underlying benefits of exercise on cognition. We investigated radioactive insulin BBB pharmacokinetics following an acute bout of exercise in young, male and female CD-1 mice. Additionally, we investigated changes in serum levels of substrates that are known to affect insulin BBB transport. Lastly, we measured the basal level of a downstream protein involved in insulin receptor signaling in various brain regions as well as muscle. We found insulin BBB transport in males was greater following exercise, and in males and females to both enhance the level of insulin vascular binding and alter CNS insulin receptor signaling, independent of changes in serum factors known to alter insulin BBB transport.

Activated factor VIIa (FVIIa), von Willebrand factor antigen (vWF:Ag), D-dimer and thrombin-antithrombin III complex (TAT) were measured to monitor coagulation status in patients with juvenile chronic arthritis (JCA). Subjects included 14 patients with systemic JCA, 16 with pauciarticular JCA and 16 with polyarticular JCA without disseminated intravascular coagulopathy, thrombosis or liver dysfunction. All types of JCA showed an increase of FVIIa, D-dimer and TAT, indicating enhanced activation of coagulation. In systemic JCA only there was also characteristically an elevation of vWF:Ag. We conclude that all types of JCA constitute a state of subclinical hypercoagulopathy caused by tissue damage and that additionally systemic JCA involves a prothrombotic state associated with or precipitated by vasculitis.