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)

The phosphonylmethoxyalkyl derivatives HPMPA [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], HPMPC [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] and PMEA [9-(2-phosphonylmethoxyethyl)adenine] were evaluated as 0.2% eyedrops for their efficacy in the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in the rabbit model. BVDU 0.2% eyedrops were used as the reference treatment. HPMPA, HPMPC, PMEA and BVDU eyedrops showed a rapid and highly significant healing effect (P less than 0.005) on keratitis caused by TK+ HSV-1 (McIntyre strain) when compared with placebo eyedrops, whereas BVDU treatment did not affect the course of TK- HSV-1 (VMW-1837) keratitis. HPMPA and HPMPC treatment again caused a highly significant healing (P less than 0.005, compared with placebo eyedrops). Although PMEA eyedrops were less effective than HPMPA or HPMPC eyedrops, the effect of PMEA eyedrops was significantly (P less than 0.05) different from the effect of either BVDU or placebo eyedrops.
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PMID:Effects of phosphonylmethoxyalkyl-purine and -pyrimidine derivatives on TK+ and TK- HSV-1 keratitis in rabbits. 166 31

The phosphonylmethoxyalkyl derivative, (S)-1-(3-hydroxy-2-phosphonyl methoxypropyl)cytosine (HPMPC), was evaluated for its efficacy in the topical treatment of experimental keratitis caused by thymidine kinase-positive (TK+) or thymidine kinase-deficient (TK-) herpes simplex virus type 1 (HSV-1) strains. The HPMPC 0.2% eyedrops were as effective as the reference compound, (E)-5-(2-bromovinyl)-2'-deoxyuridine, (BVDU) 0.2% eyedrops in stimulating the healing of epithelial disease caused by the HSV-1 TK+ strain. Both drugs achieved a significant (P less than 0.005) healing effect compared with placebo eyedrops. No significant differences were noted in the efficacy of HPMPC 0.2% eyedrops when instilled one, three, or nine times a day. In the treatment of keratitis caused by the HSV-1 TK- strain, 0.2% BVDU eyedrops were similar to placebo; 0.2% HPMPC eyedrops again had a brisk and significant healing effect (P less than 0.005).
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PMID:(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine in the therapy of thymidine kinase-positive and -deficient herpes simplex virus experimental keratitis. 185 33

Various 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) and 2-phosphonylmethoxyethyl (PME) derivatives of purine [adenine (A), guanine (G), 2,6-diaminopurine (DAP), 2-monoaminopurine (MAP), hypoxanthine (HX)] and pyrimidine [cytosine (C), uracil (U), thymine (T)] have been evaluated for their antiviral properties. PMEDAP, (S)-HPMPA [and the cyclic phosphonate thereof, (S)-cHPMPA)], (S)-HPMPC, PMEG, PMEA, HPMPG and HPMPDAP proved to be effective inhibitors of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). (S)-HPMPA and (S)-cHPMPA were the most effective inhibitors of varicella-zoster virus (VZV), and (S)-HPMPC was the most effective inhibitor of cytomegalovirus (CMV). Against adenovirus (types 2, 3 and 4) and vaccinia virus again (S)-HPMPA and (S)-cHPMPA showed the greatest inhibitory activity. As a rule, the PME derivates were much less inhibitory to VZV, CMV, vaccinia and adenovirus than the HPMP derivatives. However, PMEA, PMEDAP and PMEMAP showed marked and selective activity against the human immunodeficiency virus (HIV). (S)-HPMPA was selected for further evaluation in animal model infections. It proved efficacious in the topical treatment of HSV-1 keratitis in rabbits and cutaneous HSV-1 infection in hairless mice, and in the systemic treatment of both HSV-1 and vaccinia virus infections in mice.
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PMID:Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. 345 98

Previously, we demonstrated that HPMPC, a new, broad-spectrum antiviral agent, inhibited adenovirus type 5 in the New Zealand (NZ) rabbit ocular model (Cornea 1992; 11:529-33). Historically, no antiviral agent has been demonstrated to be effective against both herpes simplex virus type 1 (HSV-1) and adenovirus eye infections in an experimental animal model. In this study, we compared topical 0.2% HPMPC to 1% trifluridine and vehicle control in the NZ rabbit HSV-1 keratitis model. Using a double-masked, two-eye design, NZ rabbits were inoculated in both eyes with HSV-1 W strain (10(5) pfu/eye), and dendritic keratitis and HSV-1 ocular titers were measured serially. Compared with the control group, both topical 0.2% HPMPC and 1% trifluridine significantly reduced healing time of HSV-1 dendritic keratitis, lowered HSV-1 ocular titers on days 3 through 11, and shortened duration of HSV-1 shedding in the tear film. For all outcome parameters measured, topical 0.2% HPMPC was as effective as 1% trifluridine. A new concept of a broad-spectrum topical antiviral agent was shown to be effective against HSV-1 in an NZ rabbit keratitis model, and further development toward clinical application appears desirable.
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PMID:HPMPC, a broad-spectrum topical antiviral agent, inhibits herpes simplex virus type 1 replication and promotes healing of dendritic keratitis in the New Zealand rabbit ocular model. 784 11