—A method by which to overcome the clinical symptoms of atherosclerosis is the insertion of a graft to bypass an artery blocked or impeded by plaque. However, there may be insufficient autologous mammary artery for multiple or repeat bypass, saphenous vein may have varicose degenerative alterations that can lead to aneurysm in high-pressure sites, and small-caliber synthetic grafts are prone to thrombus induction and occlusion. Therefore, the aim of the present study was to develop an artificial blood conduit of any required length and diameter from the cells of the host for autologous transplantation. Silastic tubing, of variable length and diameter, was inserted into the peritoneal cavity of rats or rabbits. By 2 weeks, it had become covered by several layers of myofibroblasts, collagen matrix, and a single layer of mesothelium. The Silastic tubing was removed from the harvested implants, and the tube of living tissue was everted such that it now resembled a blood vessel with an inner lining of nonthrombotic mesothelial cells (the “intima”), with a “media” of smooth muscle–like cells (myofibroblasts), collagen, and elastin, and with an outer collagenous “adventitia.” The tube of tissue (10 to 20 mm long) was successfully grafted by end-to-end anastomoses into the severed carotid artery or abdominal aorta of the same animal in which they were grown. The transplant remained patent for at least 4 months and developed structures resembling elastic lamellae. The myofibroblasts gained a higher volume fraction of myofilaments and became responsive to contractile agonists, similar to the vessel into which they had been grafted. It is suggested that these nonthrombogenic tubes of living tissue, grown in the peritoneal cavity of the host, may be developed as autologous coronary artery bypass grafts or as arteriovenous access fistulae for hemodialysis patients.
This study utilized both in vivo and in vitro techniques to investigate whether cells of bone marrow origin can differentiate into smooth muscle-like cells (myofibroblasts) with contractile filaments and proteins. Female C57BL/6 mice expressing the Ly5.2 antigen on the surface of their haemopoietic cells had four pieces of silastic tubing (3 × 0.5 mm outer diameter) or boiled blood clot (2–3 mm diameter) placed in their peritoneal cavity. After 3, 5, 7 and 14 days (n = 4/group) the implants were removed and those that had remained free-floating were processed for light microscopy, immunohistochemistry and electron microscopy. In the first 3–5 days, rounded cells adhered to the entire surface of the tubing then flattened. These cells stained with fluoresceinated antibodies to Ly5.2 showing that they were derived from haemopoietic cells. By 14 days the cells had become elongated and multilayered in a collagen matrix, forming a thick tissue capsule around the tubing or boiled clot. They contained contractile filaments and stained with antibodies to α-smooth muscle actin but no longer stained for Ly5.2. A separate set of female C57BL/6 Ly5.2 mice were X-irradiated to destroy bone marrow then immediately transfused with 106 nucleated bone marrow cells taken from the femur and tibia of a congenic strain of male mice expressing the Ly5.1 allele. Eight of the female mice with successful engraftment (80–99%) had silastic tubing implanted in the peritoneal cavity. After 14 days, in situ hybridization with Y chromosome probe confirmed the male donor, and thus bone marrow, origin of the elongated cells that formed the capsule. In vitro studies showed that cells of the murine macrophage cell lines RAW 264.7 and J774 express α-smooth muscle actin after exposure to the cytokine γ-interferon in vitro. These data show that bone marrow-derived cells can differentiate into smooth muscle-like cells and raises the possibility that blood-derived cells may contribute to the development of fibro-proliferative vascular diseases such as atherosclerosis.
The aim of this study was to determine the mechanism by which the aged garlic extract "Kyolic" has a protective effect against atherosclerosis. Plasma cholesterol of rabbits fed a 1% cholesterol-enriched diet for 6 wk was not reduced by supplementation with 800 microL Kyolic/(kg body. d). In spite of this, Kyolic reduced by 64% (P < 0.05) the surface area of the thoracic aorta covered by fatty streaks and significantly reduced aortic arch cholesterol. Kyolic also significantly inhibited by approximately 50% the development of thickened, lipid-filled lesions in preformed neointimas produced by Fogarty 2F balloon catheter injury of the right carotid artery in cholesterol-fed rabbits. In vitro studies found that Kyolic completely prevented vascular smooth muscle phenotypic change from the contractile, high volume fraction of filament (V(v)myo) state, and inhibited proliferation of smooth muscle cells in the synthetic state with a 50% effective dose (ED(50)) of 0.2%. Kyolic also slightly inhibited the accumulation of lipid in cultured macrophages but not smooth muscle, and had no effect on the expression of adhesion molecules on the surface of the endothelium or the adherence of leukocytes. It is concluded that Kyolic exerts antiatherogenic effects through inhibition of smooth muscle phenotypic change and proliferation, and by another (unclarified) effect on lipid accumulation in the artery wall.
Intradural extramedullary tumors can be safely and effectively removed using minimally invasive techniques. The pros and cons of minimally invasive vs open surgery are discussed.
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