Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022568 (keratitis)
5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients with active herpes simplex dendritic keratitis, in whom topical idoxuridine was unsuccessful in controlling their disease, were treated with topical adenine arabinoside (ara-A), a purine analogue effective against many DNA viruses. This drug was an effective antiviral agent in these patients. No signs of ocular or adnexal toxicity were noted.
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PMID:Adenine arabinoside in idoxuridine unresponsive and intolerant herpetic keratitis. 12 13

In the rabbit 5% phosphonoacetic acid ointment suppressed herpetic keratitis as well as 0-5% idoxuridine ointment. After 5 days of treatment quantitative virus titres showed that phosphonoacetic acid was superior to idoxuridine in the inhibition of herpes virus replication. Phosphonoacetic acid was found to be nontoxic to the eye in both clinical and histopathological studies. Recent reports suggest that the mechanism of action of phosphonoacetic acid appears to be the blocking of the virus DNA polymerase, which is essential for the synthesis of herpes virus DNA.
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PMID:Effect of phosphonoacetic acid in the treatment of experimental herpes simplex keratitis. 19 32

Amphotericin B methyl ester (AME), a semisynthetic derivative of amphotericin B, was studied in the rabbit cornea for its potential role in prevention and therapy of HSV, vaccinia virus, and vesicular stomatitis virus. It was effective in the prevention of lesion formation by these three viruses and dose-related antiviral effects were shown. Of these viruses HSV was the most sensitive to AME. The antiviral effect of AME was additive with those of IDU and ribavirin. However, it was not effective in treating established lesions due to HSV and vaccinia virus. Since its mode of action is to bind to the sterol sites of the viral envelope, it is suggested that AME should also be effective against other enveloped DNA and RNA viruses. A new method of therapy for epithelial herpetic keratitis in humans using a combination of AME with MWD is proposed.
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PMID:Potential role of amphotericin B methyl ester in the prevention and therapy of herpetic keratitis. 20 16

Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits.
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PMID:Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits. 21 1

The authors report two cases of severe herpetic keratitis and briefly discuss the possible mechanism of acquired idoxuridine resistance of herpes simplex virus. They believe that acquired resistance to IDU may be due to the treatment itself because of activity site of the inhibitor, i.e. the viral DNA.
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PMID:[Acquired idoxuridine resistance of herpes simplex virus. Clinical data (author's transl)]. 22 Jul 19

Three days after herpes simplex virus inoculation, an increased amount of DNA and RNA was observed in the superficial epithelium cells of rabbit cornea. Histochemical staining demonstrated the development of acid mucopolysaccharides and the destruction of reticulin. In the early stages, on rare occasions, giant polykaryocytes with multiple micronuclei were seen. From 1 week after infection, more and more cells became rounded and shrunken. Cytoplasm of these cells might contain DNA diffusely interspersed with RNA. This DNA is probably viral in nature. The nuclei of these cells varied in shape, size, and staining intensity. Nuclear fragments were often observed in the cytoplasm. Stainings for acid mucopolysaccharides were strongly positive in the rounded cells. These cells fused to form syncytia Variable-sized pseudopodialike processes containing DNA and RNA extend from some of the rounded and liquefied cells toward other cells. In the later stages, development of ghost cells was seen. Histochemical methods demonstrated the deposition of acid mucopolysaccharides on their cell membranes. Necrosis was more often present in the late stages. Nuclear debris and deformed cells were encountered in such areas. On the healing of the keratitis, 3 months after inoculation, the cell cytology and staining reactions reverted to normal.
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PMID:Histopathology and histochemistry of the superficial corneal epithelium in experimental herpes simplex keratitis. 31

Several 5-alkyl derivatives of 1-beta-d-arabinofuranosyluracil (araU) were tested for antiherpesviral activity and inhibitory action on cell growth in human embryonic lung fibroblasts. 1-beta-d-Arabinofuranosylcytosine, 9-beta-d-arabinofuranosyladenine, and 5-iododeoxyuridine (IUdR) were included as reference materials. Among the 5-alkyl derivatives of araU, arabinosylthymine was the most active, followed by 5-ethyl- and 5-propyl-araU. 5-Ethyl-araU was as active as IUdR and more active than 9-beta-d-arabinofuranosyladenine against herpes simplex virus (HSV) type 1 and did not inhibit cell growth at a concentration as high as 1,000 mug/ml. 5-Butyl- and 5-methoxymethyl-araU, as well as araU, exhibited relatively low activity. The araU derivatives tested were as active against HSV WT-34, an isolate from a patient with keratitis, as against HSV type 1. Against an IUdR-resistant isolate, HSV WT-20, arabinosylthymine was less inhibitory than IUdR. Deoxyribonucleic acid synthesis in HSV type 1-infected cells was markedly inhibited by arabinosylthymine, IUdR, and 5-ethyl-araU, whereas cellular deoxyribonucleic acid synthesis in uninfected cells was significantly inhibited by IUdR but not by arabinosylthymine or 5-ethyl-araU.
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PMID:In vitro antiherpesviral activity of 5-alkyl derivatives of 1-beta-D-arabinofuranosyluracil. 48 26

New antiviral compounds are being tested constantly and may be of considerable value with increasing availability. More than 200 analogues of purines and pyrimidines have been found to inhibit DNA and RNA viruses. Adenine arabinoside is most effective against disseminated herpes simplex virus and disseminated herpes zoster. Idoxuridine is useful in treatment of herpetic keratitis. Interferon still is in the experimental stage, and, because of its short half-life and high cost, it probably will not be released in the near future. Amantadine appears to be useful in prevention of A2 influenza, but its value against swine flu has not been established. Methisazone is effective in prevention of smallpox and in the treatment of complications of vaccinia.
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PMID:Viral chemotherapy. 58 11

Certain D-arabinosyl nucleosides, notably D-arabinosyl cytosine (araC) and D-arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell or virus-induced DNA polymerases, competing with dCTP and dATP, respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the arnaucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g. against herpes virus in herpetic keratitis.
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PMID:The lethality of aranucleotides. 82 87

In vitro studies by workers in basic fields of biology have shown that halogenated DNA-base analogs are capable of sensitizing the DNA of various infectious agents in such a way that exposure to fluorescent light results in lethal damage to the DNA. In the present studies we treated experimental herpetic keratitis in rabbits with fluorescent light after using topical iododeoxyuridine (IDU) as a photosensitizing agent. So far as it clinical course was concerned, there was no significant difference between the disease treated with both IDU and light, and the disease treated with IDU alone. This was true in both the standard experimental disease and in the disease made more severe by prelimiary subconjunctival injection of corticosteroid.
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PMID:Therapy of experimental herpetic keratitis with IDU and fluorescent light: A negative study. 112 52


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