Masahiko Onoda

Lysyl oxidase resolves inflammation by reducing monocyte chemoattractant protein-1 in abdominal aortic aneurysm

Lysyl oxidase (LOX) is an enzyme critical for the stability of extracellular matrix and also known to have diverse biological functions. Little is known, however, about the role of LOX in regulating inflammation. Here we demonstrate that LOX suppresses secretion of monocyte chemoattractant protein-1 (MCP-1) in cultured vascular smooth muscle cells. Furthermore, enhancement of LOX activity reduces MCP-1 in a mouse model of abdominal aortic aneurysm (AAA), thereby preventing macrophage infiltration and AAA progression. These findings suggest that LOX has a novel function in resolving inflammation by reducing MCP-1 in AAA.

Inhibitory Effect of Statins on Inflammation-Related Pathways in Human Abdominal Aortic Aneurysm Tissue

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression.

Infected Aneurysms of Bilateral Deep Femoral Arteries due to Campylobacter fetus Subspecies fetus

Infected aneurysms due to Campylobacter fetus subspecies fetus have rarely been reported. Here, we describe the first case of infected aneurysm of bilateral deep femoral arteries due to C. fetus fetus. We successfully treated this case by administration of antibiotics effective for C. fetus fetus and bilateral obturator bypass with complete resection of the infected aneurysms. The aneurysmal wall culture disclosed the presence of C. fetus fetus in a microaerobic atmosphere after the operation. A distinctive culture condition was necessary to detect C. fetus fetus. In the case of infected aneurysms, we should be aware of the possibility of infection with C. fetus fetus, and an appropriate culture for this organism may be needed.

Bleeding from a diverticulum of the appendix (with video)

volume of oxygen gas that they generatedhelpful information in understanding the rationale for their use to dislodge impacted stool. Thus, when 1 volume of 10-volume H2O2 is decomposed, it produces 10 volumes of oxygen; a 3% solution is equivalent to 10-volume concentration. For laboratory use, 30% solutions are most common, and commercial grades from 70% to 98% are also available, but potentially quite hazardous. H2O2 can cause mucosal damage when it contacts the surface of the GI tract, and the so-called snow-white sign is produced when the H2O2 penetrates the epithelium, contacts catalase, and the resultant microbubbles of oxygen force blood out of the intramural vasculature with ischemic and free radical–induced injury. In larger volume, H2O2 has caused colonic gangrene and rupture, gas embolization, and fulminant colitis. I do not know the effect on Helicobacter pylori of ingested H2O2, but because there are so many available and relatively safer anti–H pylori agents, I would keep H2O2 out of arm’s reach except perhaps to rinse wounds and maybe take advantage of its oxidative properties to render colorless any blood that we might have gotten on garments at work or elsewhere. Lawrence J. Brandt, MD Associate Editor for Focal Points