Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are potent chemokines which attract circulating monocytes and neutrophils respectively to inflamed tissues. JE/MCP-1 gene expression has been previously studied in rabbit aortae after endothelial denudation and the rapid appearance of this transcript was thought to precede emigration of phagocytes. We now report MCP-1 gene expression following de-endothelialization of iliac arteries in the pig, a species which can develop spontaneous atherosclerosis. Using Northern blot analysis, we demonstrated that MCP-1 mRNA was rapidly induced in pig arteries at 2 h and continued to increase to reach a maximum at 8 h before returning to low levels at 16-24 h after injury. The increase seen for MCP-1 mRNA at 8 h was also observed for IL-8 mRNA but was not apparent for growth-related gene expressions, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1). Since smooth muscle cells, endothelial cells, and phagocytes are all capable of expressing MCP-1, we examined pig arteries for immunostaining using a monoclonal antibody to human MCP-1 (5D3-F7). At 8 h after injury, the predominant cell type staining positive for MCP-1 was the monocyte/macrophage. Staining was also observed in occasional scattered neutrophils, but MCP-1 protein could not be detected in smooth muscle cells or on extracellular matrix within the sensitivity constraints posed by our methodology. Our results are consistent with invading monocyte/macrophages having a major input into the production of this chemokine in the arterial wall following injury. The fact that MCP-1 expression accompanied monocyte/macrophage presence in damaged artery, rather than preceding it, is suggestive that continued MCP-1 expression is required for functions other than chemoattraction.
Although a high dose of vitamin D3 is known to cause arterial calcification and degeneration, its effect on intimal hyperplasia has never been studied. The aim of this study was to examine the influence of a moderate supplement of vitamin D3 on intimal hyperplasia in the balloon-injured rat carotid artery. Forty-four rats had balloon injury to the carotid artery; 22 were given oral vitamin D3 supplementation (0.25 microgram kg-1 day-1). Animals were killed at 4 weeks and the carotid arteries were perfusion fixed and assessed morphometrically by means of computerized image analysis of transverse sections. Mean (s.e.m.) intimal area was significantly greater in the vitamin D3-treated animals than in controls: 0.92(0.05) versus 0.71(0.07) mm2 (P = 0.02). The area of the media of both injured and uninjured arteries was not influenced by vitamin D3 administration. A small dose of vitamin D3 resulted in significant exacerbation of intimal hyperplasia in this rat carotid artery model and raises the question of the role of dietary vitamin D3 in restenosis following vascular intervention.
KT is the most effective therapeutic option for ESRF. We present our first experiences in a developing country. All children who underwent kidney transplantation since the inception of this program in July 2004 until 30 September 2005 were studied. Their demographic data, operative and peri-operative details, graft and host survival, and drug compliance are described here. Data were collected from patient records and nursing observation records. Eleven children were transplanted during this period (median recipient age 10.75 yr, range: 8-16). The median age of the donors was 41 yr (range: 38-45) and was the mother in eight, father in two and uncle in one. The median (range) follow-up period following transplantation was 12.5 months (7-12). The vascular anastomotic site was aorta and inferior vena cava in nine patients and the cold ischemia time was mean (s.d.) 1.9 h (0.96). All patients received steroids, cyclosporine and MMF for immunosuppression. Hypotension, heart failure and septicemia were common medical complications. Four were treated for acute rejection. Vascular anastomotic leak, burst abdomen, intestinal obstruction, intra-abdominal leak of supra pubic catheter and vesico-ureteric junction obstruction were surgical complications. There were no graft losses or deaths. Despite limited resources good outcomes are possible following renal transplantation in children in developing countries.
The timings of increases in TGF-beta1, u-PA and PAI-1 mRNAs in injured arteries are consistent with contributions to processes prior to proliferation. The observation of a second protracted elevation in TGF-beta1 expression is supportive of an additional role in stimulation of ECM protein synthesis. Functional specialisation exists within the thickened intima of arteries late in repair.
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