Biomedical subjects
JT Powell
Publications and source records attributed to JT Powell.
Vascular surgical society of great britain and ireland: non-steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm
BACKGROUND: Prostaglandin E2 (PGE2) and inflammatory cytokine levels are raised in the wall of abdominal aortic aneurysms (AAAs) and inflammatory processes appear to contribute to aneurysm expansion. The effect of PGE2 on aortic smooth muscle cells (SMCs) and the influence of indomethacin on AAA growth and production of inflammatory mediators were investigated. METHODS: Proliferation and apoptosis of aortic SMCs cultured with PGE2 were assessed by 5-bromo-2'-deoxyuridine uptake and oligonucleosome enzyme-linked immunosorbent assay. Full-thickness AAA explant cultures were used to measure the secretion of PGE2, interleukin (IL) 1beta and IL-6 in the presence and absence of indomethacin. In a case-control study, the effect of non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, on AAA growth was examined. RESULTS: PGE2 suppressed proliferation (IC50 6 ng ml-1) and increased apoptosis of aneurysm SMCs. Indomethacin diminished secretion of PGE2, IL-1beta and IL-6 by AAA explants (see Table below). The median AAA growth rate of 19 patients taking NSAIDs was 1.8 (range 0-11.2) mm per year compared with 3.2 (0.4-10.9) mm per year in 59 patients (matched for age, sex, smoking and initial AAA diameter) not taking these drugs (P = 0.004). CONCLUSION: PGE2 is produced in the AAA wall in concentrations that are detrimental to SMCs. Indomethacin reduces PGE2, IL-1beta and IL-6 synthesis in aneurysm tissue and NSAIDs appear to reduce AAA growth. These drugs warrant further consideration for the treatment of AAA.
Vascular surgical society of great britain and ireland: uptake of tetracycline in aortic aneurysms: influence on inflammation and proteolysis
BACKGROUND: Derivatives of tetracycline (TC), through their inhibition of matrix metalloproteinases (MMPs), have been suggested as potential medical therapy to limit growth of abdominal aortic aneurysms (AAAs), but penetration of the aortic wall in vivo has not been demonstrated. The uptake and concentration of TC in aneurysm wall, and its effect on MMP and cytokine production, were investigated. METHODS: Patients undergoing elective AAA repair (n = 5) were given a single bolus of intravenous TC 500 mg on induction of anaesthesia. The TC concentrations achieved in serum, aneurysm wall and mural thrombus were determined using a microbiological assay. In separate patients, not given TC, AAA biopsy explants were established and the effect of TC (0, 10 and 100 &mgr;g ml-1) on hydroxyproline, MMP-9 and cytokine (MCP-1 and interleukin (IL) 6) secretion were investigated using colorimetric assays and immunoassays. RESULTS: At the time of aortic cross-clamping median TC concentration was 9 (range 5-12) &mgr;g ml-1 in serum, 2.7 (1.3-9. 6) &mgr;g g-1 in AAA wall and nil in mural thrombus (see Table ). CONCLUSION: TC rapidly penetrates AAA wall in vivo and inhibits MMP-9 and MCP-1 release by AAA explants. This suggests that TCs have the potential to limit aneurysm growth.