Acute Fulminant Colitis Caused by Idiopathic Mesenteric Inflammatory Veno-Occlusive Disease

Mesenteric inflammatory veno-occlusive disease (MIVOD) is an uncommon but important cause of bowel inflammation. MIVOD is characterised by lymphocytic inflammation and non-thrombotic occlusion of the mesenteric venules and veins. We present the case of a young man who presented with acute fulminant colitis, requiring colectomy. The differential diagnosis, pathogenesis and treatment are discussed. This case illustrates the rapid progression from ‘well’ to ‘colectomy’ that can occur with MIVOD. MIVOD should be considered in the differential diagnosis of colitis that does not respond to conventional medical treatment

Cationic polyamines inhibit anthrax lethal factor protease

BACKGROUND: Anthrax is a human disease that results from infection by the bacteria, Bacillus anthracis and has recently been used as a bioterrorist agent. Historically, this disease was associated with Bacillus spore exposure from wool or animal carcasses. While current vaccine approaches (targeted against the protective antigen) are effective for prophylaxis, multiple doses must be injected. Common antibiotics that block the germination process are effective but must be administered early in the infection cycle. In addition, new therapeutics are needed to specifically target the proteolytic activity of lethal factor (LF) associated with this bacterial infection. RESULTS: Using a fluorescence-based assay to identify and characterize inhibitors of anthrax lethal factor protease activity, we identified several chemically-distinct classes of inhibitory molecules including polyamines, aminoglycosides and cationic peptides. In these studies, spermine was demonstrated for the first time to inhibit anthrax LF with a K(i )value of 0.9 ± 0.09 μM (mean ± SEM; n = 3). Additional linear polyamines were also active as LF inhibitors with lower potencies. CONCLUSION: Based upon the studies reported herein, we chose linear polyamines related to spermine as potential lead optimization candidates and additional testing in cell-based models where cell penetration could be studied. During our screening process, we reproducibly demonstrated that the potencies of certain compounds, including neomycin but not neamine or spermine, were different depending upon the presence or absence of nucleic acids. Differential sensitivity to the presence/absence of nucleic acids may be an additional point to consider when comparing various classes of active compounds for lead optimization