Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rabbit corneal pocket assay is one of the most frequently used systems for the study of angiogenesis. This model particularly is useful to identify stimulators of new blood vessel formation. More recently, however, interest in inhibitors of angiogenesis has grown, and several antiangiogenic agents have been identified. Investigations of angiogenesis inhibitors require a reliable model for the stimulation of neovascularization. One method was modified to produce corneal neovascularization by implanting into the rabbit cornea a sustained-release polymer containing endotoxin (Escherichia coli lipopolysaccharide). The implant was prepared by mixing weighed quantities of endotoxin with ethylene vinyl acetate copolymer (Elvax) and forming 1-mm3 pellets containing 1%, 7.5%, 15%, 20%, 30%, and 40% (w/w) of endotoxin. Pure Elvax pellets were implanted as controls. Intrastromal corneal pockets were created in 92 eyes of male, albino New Zealand rabbits (n = 80), and sterilized endotoxin-copolymer implants were introduced. The growth rate of new vessels was measured by slit-lamp biomicroscopy. Endotoxin loads of 15% (n = 40) produced a strong neovascularization response with minimal stromal edema, with a mean growth rate of 0.21 +/- 0.12 mm/day. Loads of 1%, 7.5%, and 20% yielded 0.1 +/- 0.03 mm/day, 0.27 +/- 0.05 mm/day, 0.30 +/- 0.06 mm/day, respectively (n = 8, each group). Higher loads (30% and 40%; n = 8, each group) produced intense neovascularization, accompanied by severe corneal edema that obscured accurate measurement of the vessels. Corneal pockets that did not contain polymer implants were avascular. When endotoxin-Elvax pellets were removed, the new vessels regressed within 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained-release endotoxin. A model for inducing corneal neovascularization. 191 94

The 56-kilodalton (56K) protease isolated from a culture filtrate of Serratia marcescens caused vascular permeability enhancement followed by edema formation when injected into guinea pig peripheral corneas and subconjunctival space or skin. The character and the mechanism of permeability enhancement were analyzed in vivo. The enhancement was maximum at 5 to 10 min. The permeability reaction increased exponentially by the amount of enzyme used. The enhancement of permeability induced by the 56K protease was not affected by treatment with an antihistamine but was greatly augmented by simultaneous injection of a kinin potentiator, Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro-OH (SQ 20,881). Furthermore, the permeability activity of the protease, but not the amidolytic activity, was inhibited by soybean trypsin inhibitor, a well-known inhibitor of plasma kallikrein, as well as by corn trypsin inhibitor, the best inhibitor of activated Hageman factor. Results of these in vivo studies indicate that the permeability-enhancing reaction induced by the 56K protease is caused by activation of the Hageman factor-dependent pathway in the tissue. The permeability-increasing activity of the 56K protease was parallel with the enzyme activity. Serratial lipopolysaccharide did not produce a permeability enhancement reaction within 30 min when injected into guinea pig skin. These results are consistent with the results of recent in vitro experiments in which activation of the purified Hageman factor but not of prekallikrein by the 56K protease was elucidated (Matsumoto et al., J. Biochem. (Tokyo) 96:739-749, 1984). Thus, the molecular mechanism described above appears to be operative in the pathogenesis of corneal edema and chemosis, which is induced by S. marcescens, in addition to the direct tissue destruction by the protease.
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PMID:A serratial protease causes vascular permeability reaction by activation of the Hageman factor-dependent pathway in guinea pigs. 286 69

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.
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PMID:Steroid-eluting contact lenses for corneal and intraocular inflammation. 3281 40