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 effect of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir, DHPG) eye drops and the anti-inflammatory effect of cyclosporine (CYA) eye drops on experimental herpetic stromal keratitis in rabbits with herpes simplex virus (HSV) were studied. Ten rabbits were presensitized by subcutaneous injection of HSV, type 1, on days 14 and 7 before intrastromal inoculation of the same virus. These rabbits were divided into 2 groups and treatment was started 48 hours after virus inoculation. The eye drops used were 0.1% DHPG, 0.1% CYA or the vehicles of these eye drops. Eye drops were given 5 times a day and eyes were scored every day for 3 weeks after inoculation. The right eyes of Group 1 were treated with 0.1% DHPG and 0.1% CYA eye drops, and the left eyes with 0.1% DHPG and the vehicle of CYA eye drops. The right eyes of Group 2 were treated with 0.1% CYA and the vehicle of DHPG eye drops, and the left eyes with the vehicles of CYA and DHPG eye drops. The combination of DHPG and CYA was the most effective in decreasing the severity of herpetic stromal keratitis. Treatment with DHPG alone was also effective, but CYA alone was less effective.
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PMID:Effects of 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG) eye drops and cyclosporine eye drops in the treatment of herpetic stromal keratitis in rabbits. 165 Jun 68

Addition of interferon (IFN) to nucleoside analog therapy for herpetic keratitis has been shown to significantly increase the efficacy of therapy compared to nucleoside alone. We have analysed several nucleoside analogs and recombinant IFN-alpha 2 to determine which combinations have increased anti-herpes simplex virus type 1 (HSV) activity. Synergistic anti-HSV activity between IFN-alpha 2 and the acyclic guanosine analogs, acyclovir (ACV) and ganciclovir (DHPG), was demonstrated in cytopathic effect reduction assay in human corneal cell cultures as well as in Vero cells. In this assay system IFN-alpha 2 alone had little detectable antiviral activity at titers of greater than or equal to 2,000 IU/ml, however, treatment of cells with about 100 IU/ml of IFN-alpha 2 for 24 hrs prior to infection decreased the ED50 of ACV approximately 2- to 3-fold and of DHPG approximately 5- to 6-fold in Vero cells. Combinations of IFN-alpha 2 with bromovinyldeoxyuridine (BVdU) in Vero cells or human corneal stromal cells did not increase the antiviral activity of BVdU. Combinations of IFN-alpha 2 with trifluorothymidine (TFT) also did not increase the effective antiviral activity of this nucleoside and resulted in decreased uptake of TFT from the medium. These studies document that combinations of acyclic nucleoside analogs, ACV and DHPG, with IFN-alpha 2 resulted in synergistic anti-HSV activities in both Vero and human corneal stromal cells, while the pyrimidine analogs, TFT and BVdU, were not synergistic with IFN-alpha 2. IFN-alpha 2 treatment of cells induced modifications of nucleoside (e.g., thymidine and TFT), but not nucleobase (e.g., ACV) uptake. These studies suggest that selective inhibition of nucleoside versus nucleobase uptake may contribute to the mechanism of IFN/nucleobase synergy in the inhibition of HSV replication.
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PMID:Combined anti-herpes virus activity of nucleoside analogs and interferon. 165 Jun 69

Fifty-one corneal buttons obtained by penetrating keratoplasty from patients with a preoperative clinical diagnosis of nonulcerative herpetic keratitis and/or disciform stromal scarring (44) as well as ulcerative necrotizing stromal keratitis (7) were processed for herpes simplex virus (HSV) antigens using an immunoperoxidase technique and for HSV DNA by the polymerase chain reaction (PCR). HSV antigens were detected significantly more often (p less than 0.025) in specimens with avascular nonulcerative keratitis than in those with vascularization. In contrast to HSV antigens, HSV DNA was identified at equal proportions in avascular and vascularized lesions. Both HSV antigens and HSV DNA were detected in all specimens from patients with ulcerative necrotizing stromal keratitis. The implications of these findings with regard to possible mechanisms underlying herpetic keratitis in man are discussed.
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PMID:HSV antigens and HSV DNA in avascular and vascularized lesions of human herpes simplex keratitis. 165 Jun 74

The authors characterized a murine model of herpes simplex virus (HSV) reactivation in which recurrent herpetic keratitis was obtained in up to 80% of animals. Five weeks after ganglionic latency was established in National Institutes of Health inbred mice after corneal inoculation, HSV type 1 (HSV-1) was reactivated by irradiating the previously inoculated eye with ultraviolet (UV) light. Comparison of different UV wavelengths showed UVB to be optimal for reactivation, with peak viral recurrence being induced by a total exposure of approximately 250 mJ/cm2. Reactivated infectious virus generally began to appear in trigeminal ganglia 2 days postirradiation and was subsequently detectable in the cornea by both corneal swabbing and immunostaining for viral antigens. Two consecutive outbreaks of viral recurrence at the ocular surface were induced in selected animals by serial exposure to UVB. Advantages of this model over other models of recurrent keratitis are discussed.
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PMID:Characterization of a murine model of recurrent herpes simplex viral keratitis induced by ultraviolet B radiation. 165 9

We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6 delta) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 delta was unable to induce vascularization of the cornea or stromal keratitis following inoculation into the cornea of BALB/c mice, but was able to induce a transient mild blepharitis. The parental strain (HSV-1 KOS) and a revertant of ICP6 delta, ICP6 delta+3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 delta grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6 delta+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 delta is due to poor growth in the host. ICP6 delta also grew less well in primary human corneal fibroblasts, suggesting that RR may be required for virulence in humans. These results indicate that drugs inhibiting the function of RR might be effective in treating ocular HSV infections.
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PMID:The herpes simplex virus ribonucleotide reductase is required for ocular virulence. 165 68

In order to investigate the mechanism of recurrence in herpes simplex keratitis, it is very important to establish an animal model. As a first step, mice were examined with the slit-lamp biomicroscope to determine whether they spontaneously showed recurrent epithelial keratitis after healing of primary herpetic keratitis. Among 90 eyes of 45 inbred C57BL/6 mice, recurrent epithelial keratitis stained with fluorescein was observed in 10 eyes of 9 mice during the observation period up to 50 days after the primary corneal infection with herpes simplex virus (HSV) type I Amakata strain (virulent strain). Recurrent epithelial keratitis was observed in 17 eyes of 15 mice among 116 eyes of 58 ddy mice infected with HSV-I Ska strain (avirulent strain). The epithelial lesions showed punctate or dendritic patterns and continued for one to 7 days. HSV antigen was detected by the fluorescent antibody technique in the cornea of 5 out of 8 eyes which showed recurrent epithelial keratitis using another ddy mice group tested. It was limited in the epithelium of the cornea. These results show that mice herpetic keratitis recurs spontaneously.
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PMID:[Recurrent herpetic keratitis in mice]. 165 37

The degree of susceptibility of various human corneal cells to infection by the Mckrae strain of herpes simplex type 1 at different time-points in vitro was found to be the epithelial cells, the endothelial cells, and the keratocytes in increasing order. This finding was in agreement with the natural resistance of the three types of cells, and explained the mechanism of clinical manifestations of herpes simplex keratitis.
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PMID:[An experimental study on the susceptibility of human corneal cells to infection by herpes simplex virus type 1]. 165 54

Typical herpesvirus keratitis that developed in a 12-year-old boy was initially diagnosed cytologically by the Papanicolaou method demonstrating the 'ground-glass' appearance of the nuclei with multinucleated syncytial cells. Subsequently, the in situ hybridization technique was applied to identify the herpes simplex virus (HSV) DNA in the Papanicolaoudestained cellular samples. Positive hybridization was found with intense staining for the HSV DNA in the nuclei of cells having a 'ground-glass' appearance. In situ hybridization has been shown to be a useful technique for the identification of HSV in corneal scrapes, and similar studies may be carried out in cellular samples from the other body sites.
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PMID:Cytological diagnosis of herpesvirus keratitis by means of in situ hybridization: report of a case. 166 6

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 combined antiviral effects of acyclovir (ACV) and ribavirin (Rbv) on herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV) in cell cultures and on experimental HSV-1 keratitis in rabbits were studied. The antiviral activity in vitro was based on cytopathogenicity inhibition and yield reduction. The combination of the two drugs exhibited synergy as evaluated graphically (isobolograms). Rbv also potentiated the antiviral effect of ACV in vivo, in the experimental HSV-1 keratitis model in rabbits. This was evident from both the severity of corneal lesions and virus shedding in the tear film. The potentiating effect of Rbv on the anti-HSV-1 activity of ACV in vitro was reversed by guanosine.
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PMID:Potentiating effect of ribavirin on the anti-herpes activity of acyclovir. 166 59


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