A 71-year-old man with intestinal pseudo-obstruction was found to have a diffusely thickened adynamic small bowel with AA-amyloid in submucosal vessels and muscularis propria, foreign body giant cell reaction to amyloid, and necrotizing angiitis. The mucosa was unremarkable. Immunostains demonstrated numerous CD68+ monocyte/macrophages and CD8+ T cells associated with the amyloid deposits. The patient had no evidence of systemic vasculitis and no underlying cause for AA-amyloidosis was identified. Necrotizing angiitis coexistent with amyloid angiopathy has been reported in brain and temporal arteries, but not in the gastrointestinal tract and not with AA-amyloid. The inflammatory cell infiltrates in this case are consistent with a foreign-body and/or cell-mediated immunologic reaction to AA-amyloid, although a role for these cells in amyloid formation cannot be excluded.
A patient who was referred to the eye department for routine ocular assessment prior to commencement of antituberculous therapy was found to have periphlebitis in both eyes despite being visually asymptomatic. Fluorescein angiography confirms the presence of vasculitis without any retinal oedema or areas of non-perfusion, which may sometimes accompany the condition. Within 2 months of systemic treatment, the ocular signs regressed without any permanent effect on vision. This case highlights a rare ocular complication associated with systemic tuberculosis which fortunately did not result in loss of vision due to prompt treatment.
Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail -/- mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.