Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corneal scarring as a consequence of bacterial keratitis is an important cause of visual loss and a major indication for penetrating keratoplasty. Anti-inflammatory agents might be useful in this condition for limiting corneal damage, but benefit from adjunctive anti-inflammatory therapy has never been demonstrated. In this limited pilot study, we compared the effect on clinical outcome of treating Pseudomonas keratitis in guinea pigs with prednisolone (a corticosteroid), flurbiprofen (a cyclo-oxygenase inhibitor), nordihydroguaiaretic acid (a lipoxygenase inhibitor), and a leukotriene antagonist, SKF104353 [R-(R*, S*)]-beta-[(2-carboxyethyl) thio-alpha-hydroxy-2-(8-phenyloctyl) benzenepropanoic acid, zinc salt]. None of the anti-inflammatory agents prevented sterilization of ulcers with antibiotic (ofloxacin) therapy. Therapy with the leukotriene antagonist appeared to reduce infiltrate size more quickly and produce a more rapid reduction in lesion size, but the differences were not statistically significant. Sample size calculations suggest that very large numbers of animals would be required to prove efficacy. The role of anti-inflammatory agents in reducing the stromal destruction caused by bacterial keratitis remains controversial.
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PMID:Anti-inflammatory therapy and outcome in a guinea pig model of Pseudomonas keratitis. 142 67

The role of metabolites of arachidonic acid in experimental Pseudomonas keratitis was studied using inhibitors of arachidonic acid metabolism. Nordihydroguaiaretic acid 1%, which inhibits predominantly the lipoxygenase pathway, and flurbiprofen 0.03%, which inhibits predominantly the cyclo-oxygenase pathway were administered topically to rabbit eyes after intrastromal injection of Pseudomonas aeruginosa. Levels of the cyclo-oxygenase product prostaglandin E2 (PGE2) and the lipoxygenase product leukotriene B4 (LTB4) were measured, and the number of ulcers that had progressed to descemetocele formation by 24 hours was determined. Corneal ulceration was accelerated by flurbiprofen, but nordihydroguaiaretic acid limited the flurbiprofen-induced worsening. The use of flurbiprofen was associated with decreased levels of PGE2 and a relative increase in LTB4, a potent chemoattractant and activator of polymorphonuclear leukocytes. These results suggest that inhibition of the cyclo-oxygenase pathway may be contraindicated in Pseudomonas keratitis; inhibition of lipoxygenase can prevent this worsening of the keratitis.
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PMID:Treatment of experimental Pseudomonas keratitis with cyclo-oxygenase and lipoxygenase inhibitors. 166 77

Intrastromal injection with human serum albumin (HSA) in the rabbit cornea induced edema and a ring-shaped leukocyte infiltrate followed by neovascularization. The effect of topically administered lipoxygenase and cyclooxygenase inhibitors on this inflammatory keratitis was studied. The lipoxygenase inhibitors Bay 08276 and Rev 5901 and the cyclooxygenase inhibitor suprofen were given as 1% eye drops three times daily during the experiment. In eyes treated with lipoxygenase inhibitors leukocyte infiltration, neovascularization and edema formation decreased. In eyes treated with a cyclooxygenase inhibitor the period of neovascularization was slightly shortened and corneal edema decreased. No influence on leukocyte infiltration was seen.
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PMID:Modulation of immunogenic keratitis in rabbits by topical administration of inhibitors of lipoxygenase and cyclooxygenase. 245 19

The paper describes the topical anti-inflammatory activity of 2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride (CBS-113 A), a dual inhibitor of cyclooxygenase/lipoxygenase and a potent free radical scavenger. When applied in eye drops (0.01 to 0.1% according to the model used), the drug inhibited inflammation in experimental conjunctivitis and uveitis induced by various procedures (e.g. paracentesis, endotoxin, S-antigen, albumin, Fe2+). The compound also inhibited leukocyte infiltration and histamine release when administered locally in pleural cavity with carrageenan. CBS-113 A could decrease plasma leakage induced by arachidonic acid or platelet activating factor in skin and airway, respectively. However, it was devoid of any activity when administered by systemic route. The compound appears as a potentially useful anti-inflammatory drug, in particular in ophthalmology and as an alternative to glucocorticoids, since it does not present the side effects of these steroids (e.g. worsening of herpetic keratitis).
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PMID:2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride as a dual inhibitor of cyclooxygenase/lipoxygenase and a free radical scavenger. 2nd communication: anti-inflammatory activity. 251 93

We tested 3 non steroidal anti-inflammatory drugs in experimental herpes keratitis in order to determine possible pro-infectious consequences. The drugs were Indomethacine, Flurbiprofen and a new non steroidal anti-inflammatory, CBS 113 A, mixed inhibitor of cycloxygenase and lipoxygenase. We studied simultaneously the evolution of the keratitis and viral excretion. We considered that an anti-inflammatory agent had a pro-infectious effect if the keratitis was more serious and/or viral excretion longer in comparison with placebo. We have shown, for the 3 drugs, in comparison with dexamethasone activity, absence of a pro-infectious effect. We compared our results on Flurpiprofen with an other study which gave this anti-inflammatory drug pro-infectious capacities; the concentration used was higher. CBS 113 A, inhibiting the metabolism of arachidonic acid via lipoxygenase and cycloxygenase and thus preventing the formation of metabolitis involved in inflammation (prostaglandins, leukotrienes,...), should have a spectrum of activity wider than that of NSAID. Subject to further studies, these 3 nonsteroidal anti-inflammatory could be used in herpetic kerato-uveitis.
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PMID:[Experimental herpes simplex keratitis in rabbits. Evaluation of pro-infectious effects of topical non-steroidal anti-inflammatory agents]. 262 69

The effect of topically administrated indomethacin was studied in rabbits on an experimentally provoked inflammatory keratitis. Intrastromal injection with horse serum induced in the cornea a ring-shaped infiltration with leukocytes and neovascularization. Indomethacin was given as eye drops three times daily during the experiment. In the indomethacin treated eyes leukocyte infiltration was prolonged but not the concomitant neovascularization. The potentiation of the leukocyte response may be due to a facilitation of chemotactic lipoxygenase products.
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PMID:Effect of indomethacin on immunogenic keratitis. 370 9

In experimental immunogenic keratitis, provoked in rabbits by intracorneal injection of 20 microliters of human serum albumin (HSA), various anti-inflammatory agents were studied in their effects on corneal edema, neovascularisation and leukocyte infiltration. Prophylactic treatment with a corticosteroid completely prevented the occurrence of keratitis. Nonsteroidal anti-inflammatory drugs such as a cyclooxygenase inhibitor partly prevented neovascularisation and corneal edema, a lipoxygenase inhibitor, a leukotriene antagonist or platelet-activating factor (PAF)-antagonist BN 52021 partially prevented mainly leukocyte infiltration. Prophylactic topical treatment with the poly-unsaturated fatty acids eicosapentaenoic acid and columbinic acid or a dietary supplement with fish oil showed less symptoms of keratitis in all respects.
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PMID:Antagonists and inhibitors of lipid mediators in experimental inflammation of the cornea. 810 42

Alterations in the normal healing process after corneal injury can produce undesirable outcomes that range from corneal haze to ulceration and perforation. Lipids play important roles in the complex inflammatory processes that occur after corneal wounding. While some lipid mediators, such as the lipoxygenase derivatives of arachidonic acid, 12-hydroxyeicosatetraenoic acid (12[S]-HETE and 15[S]-HETE), act as second messengers to promote cell proliferation and are possibly involved in the synthesis of other molecules that suppress inflammation, others, such as platelet-activating factor (PAF), exert their actions through specific receptors, play key roles during sustained corneal inflammation (as might occur with chemical burns), and contribute to tissue destruction and neovascularization. PAF is also a strong inducer of selective metalloproteinases (MMPs) that degrade the extracellular matrix. The use of a new PAF antagonist has shown great promise for the treatment of diffuse lamellar keratitis (DLK) and alkali-burned corneas.
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PMID:Cellular and molecular events in corneal wound healing: significance of lipid signalling. 1578 Dec 73

Although autacoids primarily derived from the cyclooxygenase-2 and 5-lipoxygenase (LOX) pathways are essential mediators of inflammation, endogenous specialized proresolving mediators (SPMs) act as robust agonists of resolution. SPM biosynthesis is initiated by the conversion of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid primarily via the 12/15-LOX pathway. Although 12/15-LOX activity is prominent in the cornea, the role of SPM pathway activation during infection remains largely unknown and is the focus of the current study. Pseudomonas keratitis was induced in resistant BALB/c and susceptible C57BL/6 (B6) mice. Biosynthetic pathways for proinflammatory autacoids and SPMs were assessed. Divergent lipid mediator profiles demonstrate the importance of 15-LOX pathways in the pathogenesis of ocular infectious disease. Results indicate that an imbalance of LOX enzymatic pathways contributes to susceptibility observed in B6 mice where deficient activation of SPM circuits, as indicated by reduced 15-hydroxy-eicosatetraenoic acid and 17-hydroxydocosahexaenoic acid levels, prevented transition toward resolution and led to chronic inflammation. In sharp contrast, BALB/c mice demonstrated a well-balanced axis of 5-LOX/12-LOX/15-LOX pathways, resulting in sufficient proresolving bioactive metabolite formation and immune homeostasis. Furthermore, a novel immunoregulatory role for 15-LOX was revealed in inflammatory cells (polymorphonuclear leukocytes and macrophages), which influenced phagocytic activity. These data provide evidence that SPM circuits are essential for host defense during bacterial keratitis.-Carion, T. W., Greenwood, M., Ebrahim, A. S., Jerome, A., Suvas, S., Gronert, K., Berger, E. A. Immunoregulatory role of 15-lipoxygenase in the pathogenesis of bacterial keratitis.
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PMID:Immunoregulatory role of 15-lipoxygenase in the pathogenesis of bacterial keratitis. 2991 56