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 double-stranded RNA interferon inducer polyinosinic-polycytidylic acid (In-Cn) was used to treat acute dendritic keratitis in man in a double-blind manner with IDU. The success rate for this agent was similar to IDU and was found efficacious in cases not responsive to IDU. Prophylaxis with In-Cn did not prevent recurrences of epithelial herpes, but such recurrences were responsive to IDU or In-Cn.
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PMID:Therapeutic use of inducers of interferon on Herpes simplex keratitis in humans. 110 35

Dendritic herpetic keratitis developed in a 49-year-old patient during topical acyclovir treatment. A positive herpes simplex culture was obtained. After acyclovir was replaced by trifluorothymidine and interferon, the dendritic lesion disappeared and herpes simplex culture became negative. Six months later a carcinoma of the larynx was diagnosed. The acyclovir-resistant herpetic keratitis may be associated with the carcinoma because resistant herpes simplex virus strains are predominantly described in patients suffering from immune deficiency.
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PMID:Recurrent herpetic keratitis during topical acyclovir application. 133 15

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

An intertypic recombinant isolated from rabbit kidney cells following co-transfection of HSV-1(17) and HSV-2(186) DNA failed to induce overt ocular pathology when inoculated onto the murine sacrificed cornea at concentrations as high as 10(7) PFU per eye. In contrast, both parents induced corneal disease at a 1000-fold lower dose. The reason(s) for the failure of the intertypic recombinant, designated RO25X, to induce corneal pathology was investigated. It was found that the recombinant was 100-fold more sensitive to the inhibitory effects of interferon (IFN) alpha/beta than the parent strains in corneal button growth studies in vitro. R025X readily grew in cultured mouse corneal fibroblasts at a low multiplicity of infection. However, the peak titer was approximately 8-fold lower than that of strain 17. Addition of rabbit anti-IFN alpha/beta to the culture medium resulted in a 4 to 5-fold increase in infectious titer compared to its growth in the absence of antiserum. Most significantly, when mice were pre-treated in vivo with anti-IFN alpha/beta 24 hours prior to virus corneal infection, 67% of the recipients developed moderate to severe stromal keratitis, whereas none of the controls developed corneal pathology. Blepharitis was also significantly increased in incidence and severity in the antiserum treated hosts. We conclude that the inability of R025X to induce ocular disease was due, at least in part, to the inhibitory effects of interferon produced in response to infection.
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PMID:Evidence endogenous interferon production contributed to the lack of ocular virulence of an HSV intertypic recombinant. 165 Jun 72

Susceptibility to Herpes simplex virus type 1 (HSV-1) stromal keratitis (HSK) in the mouse has previously been linked to the Igh-1 locus. The role of natural killer cells (NK) in resistance to viral infections is controversial. The authors studied the influence of the Igh-1 locus on in vitro murine NK activity against HSV-1 infected cell lines. The HSV-1 infected targets were lysed better than uninfected cells by murine splenic lymphocytes. Strain had no influence on virus-augmented cell lysis. Spleen cells from naive HSK-susceptible CAL-20 (Igh-1d) and BALB/c (Igh-1a) mice lysed YAC-1 targets better than HSK-resistant C.B-17 (Igh-1b) mice. The reverse was seen 24 hours after in vivo infection intraperitoneally with HSV-1. In contrast, CAL-20 splenocytes lysed PU5-1R targets better than BALB/c and C.B-17 splenocytes 24 hours after intraperitoneal (IP) infection. No significant differences were detected in interferon (IFN) levels after IP challenge with HSV-1 among the Igh-1 congenics. The data show that differences in NK activity were determined by both the Igh-1 genotype and the uninfected target cell. Susceptibility to HSK in these Igh-1-disparate congenics thus cannot be explained simply by differences in NK activity against HSV-1-infected targets.
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PMID:Natural killer cellular cytotoxicity against herpes simplex virus-infected cells in Igh-1-disparate mice. 170 Jul 71

150 patients with adenovirus type 8 infection where treated at random, in a prospective study. Based upon a quantifiable conjunctivitis severity score we tried to find out where there are differences in treatment. The best results were seen using polyvinylpyrrolidone-iodine (Betaisodona) although it could not prevent totally subepithelial corneal infiltrates. The combination of exogenous interferon alpha with polyvinylpyrrolidone-iodo-drops or trifluorothymidine-drops was less successful. We could not show any prophylactic effect of interferon on uninflamed fellow eyes. Treatment with vasoconstrictor did not show any therapeutic or prophylactic potency. This group of patients must be seen as a control group and the results of effective therapy should significantly differ from the results in this group. Topical corticosteroids should be reserved for severe symptomatic cases and those with iritis and pseudomembranous conjunctivitis. Giving topical corticosteroids in combination with antibiotics we did not find any influence on the incidence of subepithelial keratitis or the number of corneal infiltrates. The mean duration of acute keratoconjunctivitis using this therapy was longer than the mean duration in the control group with vasoconstrictor.
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PMID:[Epidemic keratoconjunctivitis: treatment results during an epidemic]. 170 7

The peripheral blood T-lymphocyte subsets in 52 patients with herpes simplex keratitis (HSK) were assessed with monoclonal antibodies. There was marked decrease in WuT3+ and WuT4+, and increase in WuT8+ with consequent diminution of WuT4+/WuT8+ ratio in stromal HSK, while in superficial HSK the above cell counts differed insignificantly from those of the normal controls. These findings suggested that there was immunoregulatory aberration in cases of stromal HSK. After clinical cure by antiviral agents and herpes simplex vaccine or interferon, these immunologic indexes showed no corresponding amelioration, indicating that the recurrence of HSK was probably related to the immunofunction of the host.
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PMID:[Clinical significance of peripheral blood T-lymphocyte subsets to herpes simplex keratitis]. 184 34

BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determine the reason for the difference in virulence between the two HSV strains. Both HSV-1 strains replicated to similar titers in excised corneal "buttons." However, after in vivo infection of the cornea, the growth of strain 35 was evident only during the first 24 h postinfection, whereas the replication of strain RE persisted for at least 4 days. In vitro tests revealed that HSV-1(35) was greater than 10 times more sensitive to alpha/beta interferon (IFN-alpha/beta) than HSV-1(RE). Both strains induced comparable serum levels of IFN after intraperitoneal inoculation. The kinetics of HSV-1(35) clearance from the eye was markedly altered by treatment with rabbit anti-IFN-alpha/beta. Virus titers exceeding 10(4) PFU per eye could be demonstrated 4 to 5 days postinfection in mice given a single inoculation of antiserum 1 h after infection. Furthermore, anti-IFN treatment in 3-week-old mice infected with HSV-1(35) led to the development of clinically apparent corneal disease which subsequently progressed to stromal keratitis in the majority of recipients. These results indicate that the striking difference in the capacity of HSV-1(35) and HSV-1(RE) to induce corneal disease was related to the inherently greater sensitivity of strain 35 to IFN-alpha/beta produced by the host in response to infection.
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PMID:Ocular avirulence of a herpes simplex virus type 1 strain is associated with heightened sensitivity to alpha/beta interferon. 215 80

It has been shown that the use of interferon (IFN) alone has little or no therapeutic effect in the treatment of herpetic keratitis. However, IFN used in combination with anti-herpetic agents has high therapeutic efficacy. This interaction between IFN and anti-herpetic agents has not been elucidated clearly. In this study, the interaction between human fibroblast interferon (HuIFN-beta) and anti-herpetic agents, 5-iodo-2'-deoxyuridine (IDU), aciclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), was studied in vitro using VERO cells. After the formation of a monolayer of VERO cells, HuIFN-beta of various concentrations was added to the maintenance medium. After 24 hours incubation, the medium was removed and herpes simplex virus (HSV) type 1 was inoculated on the VERO cells. Then, anti-herpetic agents were added to the medium in various concentrations. After 48 hours incubation, plaques were counted and the reduction rate in numbers of plaque was calculated. It was found that the combination of HuIFN-beta with IDU, ACV or DHPG worked synergistically in the inhibition of HSV replication.
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PMID:Effects on herpes simplex virus type 1 of combined use of interferon-beta and anti-herpetic agents in vitro. 216 62

The efficacy of different therapies and vaccine preparations was assessed for treating or preventing herpetic ocular keratitis induced by experimental inoculation in rabbits with two HSV-1 variants that display different pathogenetic potential. Early administration of acyclovir (ACV) promoted fast healing and prevented neurologic involvements: alpha-interferon (alpha-IFN) was less efficient than ACV; combined therapy with both drugs increased the antiviral effects. In an attempt to prevent the disease, rabbits were vaccinated with a slightly pathogenic HSV-1 variant or with a secreted form of an engineered HSV-1 glycoprotein gB (gB-1s) and were subsequently challenged with a highly pathogenic HSV-1 variant. Immunization of rabbits with gB-1s was much more efficient than immunization with live virus in reducing the severity of herpetic keratitis and in preventing CNS disease.
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PMID:Experimental keratitis in rabbits by human HSV-1 variants: prevention and treatment. 217 79


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