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)

Although oxygen toxicity of tissues can be decreased by a variety of antioxidants and some enzymes, such as SOD and catalase, their protective effect on tissue injury in various diseases are fairly small predominantly because of their unfavorable in vivo behavior. To minimize oxidative stress in various diseases, such as ischemic myocardial injury, circulatory disturbance and corneal inflammation, we synthesized three types of SOD derivatives by gene and protein engineering technique. One type of SOD (SM-SOD covalently linked with hydrophobic anions) circulates bound to albumin with a half life of 6 h and accumulates in tissues whose local pH is decreased. The other type of SOD (AC-SOD covalently linked with long chain fatty acids via the epsilon-amino group of lysyl residues) anchors onto membrane/lipid bilayers of various cells. The last type of SOD (HB-SOD synthesized by constructing a fusion gene coding human CuZn-type SOD and a C-terminal heparin-binding domain) binds to heparin-like proteoglycans on vascular endothelial cell surface. Intravenous administration of either SM-SOD or HB-SOD markedly inhibited postischemic reflow arrhythmias in the rat. When the left anterior descending artery was occluded permanently, about 65% of animals died within 30 min predominantly due to irreversible ventricular fibrillation; the motality of animals decreased to 15% by administering SM-SOD either before or after occlusion. Topically administered AC-SOD bound to the corneal epithelial cell surface and polymorphonuclear leukocytes and efficiently dismutated superoxide radicals at their cell surface. Thus, endotoxin-induced keratitis was inhibited markedly by topical instillation of AC-SOD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Targeting SOD by gene and protein engineering and inhibition of free radical injury. 207 Oct 43

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

Tears are absorbed by a tuft of cotton and subjected to stix test for leucocyte-esterase (L), nitrite (N), haemoglobin (H), and albumin (A). Testing of 84 cases of infectious conjunctivitis and 282 normals revealed nosographic sensitivity to L in 89% and a specificity of 98%. By including N (only 26% positive with infectious conjunctivitis) and H the sensitivity rose to 98% while the specificity fell to 95%. A was generally raised in cases of infectious conjunctivitis. An additional number of 607 stix tests were carried out on a clinical series. The reaction was controlled before, during, and after cataract extraction. Conjunctivitis patients were observed for possible infection, the result of antibiotic treatment was studied, and contact lens wearers were controlled for infection. Predominantly stix-positive reaction was noticed in keratitis, allergic conjunctivitis, and ocular prosthesis socket. Predominantly negative reaction was seen in chronic simple conjunctivitis, sicca, scleritis, and iritis, the latter despite pronounced ciliary hyperaemia. Contralateral reflexly induced L and H were rendered probable. H-positive reaction predominated immediately after removal of suture. The tear stix test is easy to carry out, reasonably precise, and valuable in the clinical work.
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PMID:Tear stix tests for leucocyte-esterase, nitrite, haemoglobin, and albumin in normals and in a clinical series. 265 63

The adherence of Pseudomonas aeruginosa to extended-wear soft contact lenses (EWSCLs) may be an important initial step in the pathogenesis of EWSCL-associated infectious keratitis. P. aeruginosa tend to adhere more to worn EWSCLs than unworn EWSCLs (P less than 0.05). Normal tear components such as aqueous solutions of albumin, lysozyme, and lactoferrin all significantly enhance adherence of P. aeruginosa to unworn EWSCLs often by as much as 300%. The presence of a 1% solution of sialic acid in the bathing medium significantly reduces the adherence of P. aeruginosa to both unworn and worn lenses. Inhibition of bacterial adherence could also be achieved with the addition of mucin (which contains terminal sialic acid residues in its major sugar chains). Therefore, selective adherence by P. aeruginosa to a specific sugar (sialic acid) may be important in the initial attachment of the bacterium to soft contact lenses.
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PMID:The adherence of Pseudomonas aeruginosa to soft contact lenses. 312 75

The adherence of microorganisms to contact lenses may be an important initial step in the pathogenesis of contact lens-associated infectious keratitis. Using a strain of Candida albicans whose interaction with various polymers has been well characterized we systematically investigated the adherence of this pathogen to hard hydrophobic and soft hydrophilic extended-wear contact lenses. Yeasts adhere to the hydrophobic lenses in direct proportion to the wetting angle of the lens whereas yeasts adhere to the hydrophilic lenses in direct proportion to the water content of the lens. Tear proteins such as albumin, lactoferrin, and lysozyme in addition to fibronectin enhance yeast adherence to both types of lenses (P less than 0.01). Concanavalin A reduces adherence of yeasts to both lens types (P less than 0.01). Among tear components however, only mucin (0.5%) consistently reduced yeast adherence to both lens types. Hydrophilic extended wear lenses worn for at least 28 days by normal patients consistently had greater adherence of yeasts than unworn lenses of the same type, often as much as ten-fold or greater yeasts/mm2 of lens surface area (P less than 0.05). These investigations indicate that tear components both in solution and adsorbed to the lens surface enhance microorganism adherence to contact lenses.
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PMID:Blocking Candida adherence to contact lenses. 353 31

We treated 45 patients with virologically verified dendritic keratitis with a combination of interferon and acyclovir 3% or with placebo and acyclovir 3% in a double-masked study. One drop of human leukocyte interferon (30 X 10(6) IU/ml) or albumin-placebo was administered daily. Acyclovir ointment was applied five times daily. The mean healing time of the corneal ulcers in 24 patients treated with interferon and acyclovir was 3.9 days and the mean healing time in 21 patients treated with placebo and acyclovir was seven days. The difference was significant (P less than .001).
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PMID:Combination therapy for dendritic keratitis with human leukocyte interferon and acyclovir. 618 16

Fifty-nine patients with superficial herpetic keratitis were treated with 3% acyclovir ointment five times a day in combination with alpha-interferon (30 million IU/mL) or albumin-placebo once a day in a stratified double-masked clinical trial. All patients had minimal wiping of the superficial lesion to isolate virus. The healing time of the corneal ulcers was substantially lower with the combination of acyclovir and interferon than with the combination of acyclovir and placebo. Only minor toxic effects were observed. The combination of acyclovir and interferon appears to be the best presently known treatment for dendritic keratitis.
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PMID:Combination therapy for dendritic keratitis with acyclovir and alpha-interferon. 636 Jan 10

A severe keratitis can be produced after the direct injection of bacterial endotoxin, or lipopolysaccharide (LPS), in rabbits. Corneal inflammation can progress to scarring and vascularization within a 2 to 3 week period. Pretreatment with systemic adrenal corticosteroids (triamcinolone) prevents this response. Limbal cellular and vascular events were studied during the first 20 hr after injection of LPS in treated and nontreated rabbits. Perivascular limbal inflammatory cells were counted and limbal vascular permeability was assessed by extravasation of 131I-albumin and 125I-fibrinogen in the cornea. Corticosteroids decreased but did not prevent the early protein extravasation and profoundly altered the inflammatory cell population around blood vessels at the limbus. Mononuclear cells, particularly mononuclear phagocytes, were sharply reduced. It is proposed that these cell types play an important role in the perpetuation and amplification of the inflammatory response in this reaction.
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PMID:Mononuclear cells in the corneal response to endotoxin. 703 77

A rapid (5- to 10-min), sensitive (detection limit 0.6 IU/L), and moderately specific fluorometric plasmin assay for small volume tear fluid samples was developed. Addition of albumin (up to 0.1% final concentration) to the assay buffer improved the sensitivity of the test so that plasmin activity in healthy controls could be detected. pH in the reaction buffer was 8.0, Michaelis-Menten constant for the substrate, H-D-Val-Leu-Lys.7-amido-4-methyl-coumarin (AMC), was 0.28 mM, and final substrate concentration in the reaction buffer was 1 mM. Intra- and interassay imprecisions were 1.6 and 4.4%, respectively at a plasmin level of 10 IU/L. Tear fluid flow was significantly higher in the patients than in the healthy controls, and this dilatory effect must be considered when using plasmin determination for diagnostic purposes. This effect was counteracted by correcting the plasmin activity values by tear fluid flow. Plasmin flux is plasmin activity (microIU) secreted in units of time (min). This parameter showed highly significant differences between the patients and controls. All patients with microbial keratitis, corrosive trauma, ocular trauma, herpetic infection, and other diseases showed highly significant elevation of plasmin flux compared with controls. The highest plasmin flux values (several hundredfold that of controls) were recorded in patients with severe corneal ulcers. Few patient samples showed some involvement of other proteases, which were not inhibited by aprotinin.
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PMID:A rapid fluorometric assay for tear fluid plasmin activity. 815 87

Acanthamoeba castellanii is a free-living protozoan that causes keratitis in humans and has been associated with pneumonia and granulomatous amebic encephalitis in dogs, sheep, and other species. Adherence of the Acanthamoeba to epithelial cells is critical to the pathogenesis of this disease. In this study, several mouse monoclonal antibodies (MAb) generated to whole Acanthamoeba trophozoites identified surface membrane epitopes by ELISA and IFA. Nine antibodies inhibited adherence of [(35)S]-methionine-labeled Acanthamoeba trophozoites to hamster corneal epithelial cells by 27-90%. Sodium periodate treatment, but not proteinase K digestion, of whole Acanthamoeba destroyed epitopes recognized by adherence-inhibiting antibodies such as MAb 7H6, suggesting that the adherence epitopes are carbohydrates. Other antibodies, MAb 2A8 for example, recognized surface membrane peptide epitopes that were proteinase K sensitive and sodium periodate resistant. Purified MAb 2A8 was used in an antigen-capture ELISA with peroxidase-labeled MAb 7H6 and demonstrated that the carbohydrate adhesion molecule was linked to the peptide recognized by MAb 2A8. Both MAbs 7H6 and 2A8 recognized a >207-kDa band on a Western blot of eluant from a MAb 2A8 immunoaffinity column, confirming that MAb 7H6 and MAb 2A8 recognize different epitopes on the same adherence molecule. MAbs 7H6 and 2A8 also identified the adhesion molecule in soluble Acanthamoeba membrane preparations and MAb 2A8 immunoaffinity column eluant by ELISA and Western blot. Neither of these antibodies were inhibited from binding to whole trophozoites nor membrane extracts by mannose or mannan in competitive binding assays. When our Acanthamoeba membrane preparations were electrophoresed and immunoblotted with alpha-d-mannosylated-biotin albumin, no bands were recognized in the >207 kDa range by our adherence-associated antibodies. These results suggest that the Acanthamoeba adhesin is not identical to the mannose binding protein of Acanthamoeba but rather is a distinct surface membrane glycoprotein.
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PMID:Acanthamoeba castellanii: characterization of an adhesin molecule. 1040 57


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