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)

Previous studies to determine the efficacy of new antiviral compounds in treating HSV ocular infections have used rabbit models. However, rabbits are expensive to purchase and maintain, and require the use of substantial amounts of test compounds. We have used the currently licensed antiviral trifluorothymidine in a murine model of HSV-induced ocular infection to demonstrate that the less expensive murine model can be used for the in vivo evaluation of potentially useful antiviral compounds. Treatment with TFT reduced the severity of blepharitis, vascularization of the cornea, stromal keratitis, and the percentage of animals developing symptoms. TFT treatment did not reduce the peak titers of infectious virus in the eyes of the infected animals, but did enhance clearance of virus from the tissues in a dose-dependent manner. Treatment with 1.0% TFT prevented the establishment of reactivatable latent infections. However, treatment with 0.01% or 0.1% TFT did not affect latency. The ED50 values for blepharitis, vascularization, and stromal keratitis ranged between 0.007% and 0.023%. These results are very similar to results obtained in rabbits and establish baseline data for comparing rabbit and murine models. This murine model provides a potentially less expensive alternative for in vivo drug testing.
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PMID:A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing. 156 Jan 5

We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation. Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment. 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated. Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M). A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M. We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside. Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes. Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic. Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%). Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic. Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system. These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies. Our model may be useful in the toxicologic study of future topical ophthalmic agents.
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PMID:An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents. 248 34

Trifluridine (TFT) and a structurally related analogue, 5-fluoro-2'-deoxyuridine (FDU), were investigated for their efficacy in the topical treatment of experimental keratitis caused by thymidine kinase-positive (TK+) and thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. Bromovinyldeoxyuridine (BVDU) was used as a reference compound. Both 0.2% BVDU and 0.2% TFT eyedrops produced a highly significant healing of TK+HSV-1 keratitis as compared to the placebo and 0.2% FDU eyedrops (P much less than 0.005), whereas the latter compound did not differ from placebo eyedrops. In the treatment of TK HSV-1 keratitis, none of the drugs exhibited a beneficial healing effect, although the virus strain used was inhibited in vitro by TFT and FDU at a very low concentration (0.02-0.04 microgram/mL).
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PMID:Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts. 295 58

Clinical resistance of herpetic keratitis to antiviral agents constitutes one of the reasons for failure of treatment after their administration. A retrospective study of 42 cases of superficial herpetic keratitis resistant to IDU, IDU and IDC, and Ara-A demonstrated that in 2 out of 3 cases this resistance appeared in patients previously treated locally with antiviral compounds for anterior ocular lesions. Patients resistant to IDU were then treated with Ara-A, and those not responding to Ara-A, with TFT. Resistance may be observed following this new treatment during the subsequent relapses.
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PMID:[Clinical resistance of herpetic keratitis to antiviral agents (author's transl)]. 626 Aug 50

The modes of action of IDU and TFT were compared in tests employing them both as a monotherapy and in combination with iodine debridement in 60 patients suffering from superficial herpetic keratitis. The combination therapy was used for patients showing only dendritic stains in the corneal epithelium, while the monotherapy was used for patients who had additional lesions in the region of Bowman's membrane. Both with the monotherapies and the combination therapies the average duration of healing was shorter with TFT.
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PMID:[Clinical experience with different methods of treating herpes corneae (author's transl)]. 677 29