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)

Sulfonylated L-valine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl halides with the title amino acid, followed by treatment with benzyl chloride, and conversion of the COOH moiety to the CONHOH group. Other derivatives were obtained by reaction of N-benzyl-L-valine with arylisocyanates, arylsulfonylisocyanates or benzoylisothiocyanate, followed by the similar conversion of the COOH into the CONHOH moiety, with hydroxylamine in the presence of carbodiimides. The obtained compounds were assayed as inhibitors of the Clostridium histolyticum collagenase, ChC (EC 3.4.24.3), a zinc enzyme which degrades triple helical collagen. The hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series of synthesized derivatives, substitution patterns leading to best ChC inhibitors were those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl; 3- and 4-protected-aminophenylsulfonyl-; 3- and 4-carboxyphenylsulfonyl-; 3-trifluoromethylphenylsulfonyl; or 1- and 2-naphthyl among others. Similarly to the matrix metalloproteinase hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate hydrophobic moieties at the P(2') and P(3') subsites, in order to achieve tight binding to the enzyme. Such compounds might lead to drugs useful in the treatment corneal bacterial keratitis.
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PMID:Protease inhibitors. Part 7. Inhibition of Clostridium histolyticum collagenase with sulfonylated derivatives of L-valine hydroxamate. 1069 84

Reaction of alkyl/arylsulfonyl halides with glycine afforded a series of derivatives which were first N-benzylated by treatment with benzyl chloride, and then converted to the corresponding hydroxamic acids with hydroxylamine in the presence of carbodiimide derivatives. Other derivatives were obtained by reaction of N-benzyl-glycine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate, followed by conversion of their COOH group into the CONHOH moiety, as mentioned above. The 90 new compounds reported here were assayed as inhibitors of the Clostridium histolyticum collagenase (EC 3.4.24.3), a zinc enzyme which degrades triple helical regions of native collagen. The prepared hydroxamate derivatives were generally 100-500 times more active than the corresponding carboxylates. In the series of synthesized hydroxamates, substitution patterns leading to the best inhibitors were those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties, such as pentafluorophenylsulfonyl, 3- and 4-carboxyphenylsulfonyl-, 3-trifluoromethyl-phenylsulfonyl or 1- and 2-naphthyl among others. Thus, it seems that similarly to the matrix metalloproteinase (MMP) hydroxamate inhibitors, Clostridium histolyticum collagenase inhibitors should incorporate hydrophobic moieties at the P(1') and P(2') sites, whereas the alpha-carbon substituent may be a small and compact moiety (such as H, for the Gly derivatives reported here). Such compounds might lead to the design of collagenase inhibitor-based drugs useful as anti-cancer, anti-arthritis or anti-bacterial agents for the treatment of corneal keratitis.
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PMID:Protease inhibitors - part 5. Alkyl/arylsulfonyl- and arylsulfonylureido-/arylureido- glycine hydroxamate inhibitors of Clostridium histolyticum collagenase. 1078 56

A collagen-binding strain of Staphylococcus aureus produced suppurative inflammation in a rabbit model of soft contact lens-associated bacterial keratitis more often than its collagen-binding-negative isogenic mutant. Reintroduction of the cna gene on a multicopy plasmid into the mutant helped it regain its corneal adherence and infectivity. The topical application of a collagen-binding peptide before bacterial challenge decreased S. aureus adherence to deepithelialized corneas. These data suggest that the collagen-binding adhesin is involved in the pathogenesis of S. aureus infection of the cornea.
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PMID:The collagen-binding adhesin is a virulence factor in Staphylococcus aureus keratitis. 1081 47

Mycotic keratitis, being frequently refractive to most of the currently available antifungal therapy, continues to pose a therapeutic challenge to the clinician. In keratitis of infectious etiology stromal dissolution may be brought about by a combination of agent and host factors. An understanding of the source and nature of corneal tissue damage is essential for evolving more effective therapeutic modalities in the treatment of fungal keratitis. In the present study, we have characterized the extracellular proteases produced in vitro by corneal fungal pathogens namely the Aspergillus flavus and Fusarium solani when collagen was provided as the sole nitrogen source. In addition, fungal infected rabbit corneas were investigated for proteolytic activities and nature of inflammatory reaction. Gelatin zymography detected protease bands with molecular mass ranging from 100 to 200 kDa in the culture extracts of A. flavus, and a single major band of molecular mass approximately 200 kDa in the culture extracts of F. solani. A basal proteolytic activity of mass 65 kDa was visualized in all uninfected and infected rabbit corneal extracts. Infected corneas in addition revealed the presence of additional proteolytic species of mass 92 and 200 kDa. The enzyme inhibitory profile suggested that fungal cultures in vitro contained predominantly serine protease activity and to a lesser extent metalloprotease activity. However, fungal infected corneal homogenates showed the presence of metalloproteinase activity alone, the enzymatic activities entirely being sensitive to ethylene diamine tetra acetate (EDTA), a metalloprotease inhibitor. Interestingly, the serine proteolytic activity detected in fungal cultures in vitro was not present in the fungal infected corneas in vivo. However, the possible role of fungal serine proteases in the activation of corneal matrix metalloproteinases (MMPs) cannot be ruled out. Based on the criteria of molecular mass, proteolytic activity in the presence of calcium at neutral pH, and sensitivity to inhibition by a metalloprotease inhibitor, the 65 and 92 kDa gelatinases were identified as MMP 2 and MMP 9, respectively. The expression of 92 and 200 kDa gelatinases correlated positively with the amount of polymorphonuclear cells present in the infected tissues. Activated resident corneal cells or inflammatory cells may largely contribute to the increased proteolytic activities in fungal infected corneas resulting in tissue matrix degradation in fungal keratitis.
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PMID:Enzymatic, clinical and histologic evaluation of corneal tissues in experimental fungal keratitis in rabbits. 1127 71

Collagen corneal shields were developed as a corneal bandage lens and are currently indicated for ocular surface protection following surgery and in traumatic and nontraumatic corneal conditions. Collagen shields are manufactured from porcine or bovine collagen and three different collagen shields are currently available with dissolution times of 12, 24, and 72 hours. The theoretical, experimental, and clinical evidence supports a role for collagen corneal shields as a drug delivery device and in the promotion of epithelial and stromal healing. Presoaking the collagen shield in a pharmacological agent with adjunctive topical treatment represents the most efficacious method of utilizing collagen shields for drug delivery. In microbial keratitis collagen shields can enhance drug delivery, promote epithelial and stromal healing, neutralize collagenases, and reduce corneal inflammation. This review will examine the evidence that supports the role of collagen shields in drug delivery and corneal wound healing. Despite a large volume of experimental (animal) work, studies on human subjects, particularly randomized controlled trials, are lacking. The authors are advocating the reassessment of the application and benefits of corneal collagen shields to clinical practice.
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PMID:Collagen corneal shields. 1268 15

Chicken pox is a very common infectious disease in children. Its corneal involvement is less serious than with measles, which may lead to blindness in numerous developing countries. However, with occasional cases occur. A case of a 59-year-old male patient whose left cornea was involved during a chicken pox infection at the age of 7 is reported. More recently, the vision of the right eye was normal at 20/20 and reduced to visual perception in the affected left eye. Corneal sensitivity was maintained in the left eye, which, however exhibited a central epithelial defect. A central round opacity of the left corneal stroma was believed to be the scar resulting from a previous disciform keratitis. The left central cornea was thinned and there was neither an anterior chamber flare nor new corneal vessels. This corneal condition required a corneal allograft, performed quickly because of the potential risk of perforation. Histopathological study of the corneal button showed a central corneal thinning with an increase in epithelial thickness. The corneal stroma was disorganized, with irregular collagen bundles. No inflammatory cells could be observed, however. All the histopathological changes observed were those of a corneal scar.
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PMID:[Followup of chicken pox keratitis. Anatomic-clinical case report]. 1239 39

The effects of glucosamine hydrochloride on the metabolic and repair processes were studied on a model of post-traumatic osteoarthrosis in the articular cartilage and on a model of post-traumatic keratitis in the cornea. The administration of glucosamine hydrochloride stimulated repair and favored inhibition of dystrophic post-traumatic processes in the connective-tissue structures. It is suggested that a probable mechanism of the drug action consists in stimulation of the synthesis of glucosaminoglycanes and collagen.
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PMID:[Experimental study of the effect of glucosamine hydrochloride on metabolic and repair processes in connective tissue structures]. 1259 39

Salzmann's nodular degeneration is a rare, noninflammatory, slowly progressive, degenerative condition. Bluish-white nodules raised above the surface of the cornea characterize it. It has usually developed in corneas with a history of phlyctenulosis, trachoma, vernal keratoconjunctivitis, measles, scarlet fever, and various other viral diseases. However, today the majority of cases have been seen without recognized previous keratitis. It is composed of dense irregularly arranged collagen tissue with hyalinization between epithelium and Bowman's layer or beyond. Manual removal, phototherapeutic keratectomy (PTK) with or without the use of topical mitomycin-C, lamellar or penetrating keratoplasty have been used in the treatment of this disease. Salzmann's nodular degeneration does not seem to consist of one clinical entity. In some cases, elevated and pannus-like tissue can be separated easily from the corneal surface leaving Bowman's layer almost untouched. In these eyes, subsequent PTK may be necessary to smooth the surface. Recurrences are rare in these eyes. In contrast, some eyes (often with major peripheral vascularization) are left with deep defects in Bowman's layer and superficial stroma after difficult mechanical removal of nodules. In these eyes, multiple masking/laser ablation procedures are mandatory to acquire a homogenous surface. In our experience, the required laser ablation depth is significantly greater and the best-corrected visual acuity to be expected is reduced in contrast to the eyes with easy removal of the nodules. In these eyes recurrences seem to occur more frequently after treatment. Of 35 eyes documented to have Salzmann's nodular degeneration during the last 15 years in our department, 22 needed PTK treatment. Visual acuity increased from 0.4 to 0.7 on average. As a routine, laser ablation should be combined with previous conventional removal of nodules and excessive pannus tissue. By doing so, lamellar and penetrating keratoplasty techniques are hardly ever required in those eyes.
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PMID:Salzmann's nodular degeneration of the cornea: a review and case series. 1616 Apr 90

We report the confocal microscopic findings in a case of interlamellar stromal keratopathy induced by elevated intraocular pressure (IOP) after laser in situ keratomileusis (LASIK). In vivo confocal microscopy showed swollen and enlarged cellular structures and the presence of microlacunae separating the stromal collagen lamellae. Inflammatory mononuclear cells and granulocytes typically seen in patients with diffuse lamellar keratitis (DLK) were absent. Stopping the topical steroids with concurrent lowering of the IOP resulted in improvement in the uncorrected and best corrected visual acuities and was associated with resolution of the corneal findings. In vivo confocal microscopy is a useful tool to study interlamellar stromal keratopathy induced by elevated IOP after LASIK in humans and the response to treatment and to differentiate interlamellar stromal keratopathy from DLK.
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PMID:In vivo confocal microscopic findings of interlamellar stromal keratopathy induced by elevated intraocular pressure. 1693 Dec 74

Recently, a number of medications approved for nondermatologic use have proved useful against dermatologic diseases. This article reviews the dermatologic uses and effects of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops. Deferasirox--an oral iron chelator--could be an effective treatment against porphyria cutanea tarda, hemochromatosis, and pathogens such as mucor that thrive in iron rich environments. Bortezomib, a proteasome inhibitor and multiple myeloma treatment, may be effective against nodular amyloid and has been effectively used against squamous cell carcinoma; although trials demonstrate it is ineffective against metastatic melanoma. Bortezomib has many cutaneous side effects including erythematous plaques or nodules, a generalized morbilliform erythema with ulcerations and fever, purpuric eruptions, leukocytoclastic vasculitis, Sweet's syndrome, and folliculitis. Dasatinib is a multi-targeted tyrosine kinase inhibitor active in vitro against most cell lines containing BCR-ABL mutations that confer resistance to imatinib. Dasatinib is likely to be effective against dermatofibroma sarcoma protuberans and cutaneous acute lymphoblastic leukemia, and has caused panniculitis. Cyclosporine 0.05% ocular emulsion (eye drops) are approved to treat dry eyes including dry eyes caused by collagen vascular disease. Cyclosporine eye drops might also have utility in treating eye pathology of ocular rosacea, atopic keratoconjunctivitis, graft versus host disease, herpes keratitis, chronic sarcoidosis of the conjunctiva, conjunctival manifestations of actinic prurigo, keratitis of keratitis-ichthyosis deafness (KID) syndrome, and lichen planus-related kerato-conjunctivitis. This article speculates that cyclosporine eye drops would also be useful for any disease causing ectropion or eclabion of the eye as well as toxic epidermal necrolysis-related eye pathology (in particular corneal scarring).
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PMID:A review of deferasirox, bortezomib, dasatinib, and cyclosporine eye drops: possible uses and known side effects in cutaneous medicine. 1737 1


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