ABSTRACT
BACKGROUND: The objective of this study was to thoroughly examine the in vivo angiogenesis activity of human recombinant tumor necrosis factor alpha (rhTNF). METHODS: rhTNF (0.5 ng to 1.0 microgram) was incorporated into the slow release polymers Hydron or HYPAN and implanted into the rabbit cornea. Release of biologically active rhTNF from the polymers was determined with the L929 cytotoxicity assay. RESULTS: All concentrations tested failed to elicit capillary formation beyond that observed for controls. Less than 2% of the rhTNF was released from the Hydron over 7 days. HYPAN released five times the amount of rhTNF in vitro, but even at doses of 500 ng (104.3 ng suggested release) no angiogenesis was stimulated. CONCLUSIONS: Under the circumstances tested, rhTNF is not angiogenic in vivo.
Subject(s)
Cornea/blood supply , Neovascularization, Physiologic/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Acrylic Resins , Animals , Cornea/cytology , Cornea/drug effects , Drug Carriers , Female , Prostheses and Implants , Rabbits , Recombinant Proteins , Statistics, NonparametricABSTRACT
The objective of this study was to explore any age-related morphological changes in the vasa vasorum of the rat femoral artery. Vascular corrosion casts were prepared from 2, 12 and 24-month-old rats. Examination of the casts with the scanning electron microscope revealed dramatic differences in the appearance of the vessels of young and aged rats. The vasa vasorum of 2-month-old rats consisted of a dense network of capillaries. These vessels were dramatically reduced in number by 12 months, and even fewer capillaries were present at 24 months. This reduction in capillary density is consistent with the observed age-related decreases in oxygen tension and may explain why the aged are more prone to atherosclerosis.
Subject(s)
Aging/pathology , Femoral Artery/ultrastructure , Vasa Vasorum/ultrastructure , Aging/physiology , Animals , Corrosion Casting , Male , Microscopy, Electron, Scanning , Rats , Rats, Sprague-Dawley , Vasa Vasorum/growth & developmentABSTRACT
The object of this study was to examine the initiation and pattern of corneal angiogenesis stimulated by transforming growth factor beta (TGF-B) using scanning electron microscopy (SEM) of vascular corrosion casts and transmission electron microscopy (TEM). Fifty nanograms of TGF-B was combined with the slow release polymer Hydron and implanted in the rabbit cornea as an assay for angiogenic activity. Two and 7 days after implantation, the corneas were removed for TEM. At the same time intervals the limbal vasculature was filled with Mercox, an acrylic monomer. After the Mercox hardened, the tissue was digested with alternating immersions in 40% KOH and distilled water. The resulting casts were air-dried, sputter coated with gold and viewed with the scanning electron microscope. TEM revealed that 2 days after implantation, TGF-B elicited an influx of a vast number of inflammatory cells, which at two days were predominantly neutrophils. By 7 days the inflammation had subsided and typical capillaries were seen between the collagenous laminae of the normally avascular corneal stroma. SEM of vascular corrosion casts showed evidence of margination/diapedesis of leukocytes from the limbal venules 2 days post-implantation. In addition, the casts from the 7 day time point showed that new vessels arose solely from limbal venules.
