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)

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.
 ...
PMID:Effect of 9-(2-hydroxyethoxymethyl)guanine on herpesvirus-induced keratitis and iritis in rabbits. 21 1

Herpes simplex virus (HSV) latency in sensory ganglion neurons is well documented, but the existence of extraneuronal corneal latency is less well defined. To investigate the possibility of extraneuronal latency during ocular HSV infection, corneal specimens from 18 patients with quiescent herpes simplex keratitis (HSK) were obtained at the time of keratoplasty. Polymerase chain reaction (PCR) amplification followed by southern blot hybridization with a radiolabeled oligonucleotide probe was done to detect the presence of HSV-1 genome in these human corneal samples. Two pairs of oligonucleotides from the region of the HSV thymidine kinase (TK) gene and the latency-associated transcript (LAT) gene were used as primers in the PCR amplification. The DNA sequences from either the TK or the LAT gene were identified in 15 of 18 HSK corneas (83%). These results demonstrate that the HSV genome was retained, at least in part, in human corneas during quiescent HSV infection, giving further support to the concept of corneal extraneuronal latency.
 ...
PMID:Detection of herpes simplex virus thymidine kinase and latency-associated transcript gene sequences in human herpetic corneas by polymerase chain reaction amplification. 185 32

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).
 ...
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

The development of new antiviral agents has gained increasing momentum. It has kept pace with the identification of specific sites ("targets") in the virus replicative cycle at which potential antiviral drug can interact. The current armamentarium of available antiviral drugs consists of amantadine and rimantadine (against influenza A), ribavirin (against respiratory syncytial virus infection), idoxuridine and trifluridine (against herpetic keratitis), vidarabine and acyclovir (against herpes simplex virus infections), ganciclovir (against cytomegalovirus infections) and Retrovir (against AIDS). Various new compounds have been found which selectively inhibit those viruses [i.e. adenovirus, varicella-zoster virus, thymidine kinase-deficient (TK-) herpes simplex virus strains, and rhinoviruses] that are insensitive or poorly sensitive to the presently available antivirals. Several new compounds have also proven active against human immunodeficiency virus, the causative agent of AIDS; and, as a spin-off of the search for anti-AIDS drugs, new agents may also be expected that are effective against other retrovirus infections as well as hepadnavirus (i.e. hepatitis B virus) infections.
 ...
PMID:New acquisitions in the chemotherapy of viral infections. 216 18

Acyclovir (aciclovir) is a nucleoside antiviral drug with antiviral activity in vitro against members of the herpes group of DNA viruses. As an established treatment of herpes simplex infection, intravenous, oral and to a lesser extent topical formulations of acyclovir provide significant therapeutic benefit in genital herpes simplex and recurrent orofacial herpes simplex. The effect of acyclovir therapy is maximised by early initiation of treatment, especially in non-primary infection which tends to have a less protracted course than the primary episode. Long term prophylactic oral acyclovir, in patients with frequent episodes of genital herpes simplex, totally suppresses recurrences in the majority of subjects; as with other infections responding to acyclovir, viral latency is not eradicated and pretreatment frequencies of recurrence return after discontinuation of treatment. Caution should accompany the prophylactic use of acyclovir in the general population, due to the theoretical risk of the emergence of viral strains resistant to acyclovir and other agents whose mechanism of action is dependent on viral thymidine kinase. Intravenous acyclovir is the treatment of choice in biopsy-proven herpes simplex encephalitis in adults, and has also been successful in the treatment of disseminated herpes simplex in pregnancy and herpes neonatorium. Intravenous and oral acyclovir protect against dissemination and progression of varicella zoster virus infection, but do not protect against post-herpetic neuralgia. In immunocompromised patients, intravenous, oral and topical acyclovir shorten the clinical course of herpes simplex infections while prophylaxis with oral or intravenous dosage forms suppresses reactivation of infection during the period of drug administration. Ophthalmic application of 3% acyclovir ointment rapidly heals herpetic dendritic corneal ulcers and superficial herpetic keratitis. Thus, despite an inability to eradicate latent virus, acyclovir administered in therapeutic or prophylactic fashion is now the standard antiviral therapy in several manifestations of herpes simplex virus infection, and indeed represents a major advance in this regard. With the exception of varicella zoster virus infections, early optimism concerning the use of the drug in diseases due to other herpes viruses has generally not been supported in clinical investigations.
 ...
PMID:Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. 265 90

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).
 ...
PMID:Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts. 295 58

Primary inoculation of mice and rabbits with an avirulent HSV-1 thymidine kinase negative (TK-) mutant reduced keratitis, mortality, and superinfection of the trigeminal ganglion (TG) as measured by cocultivation and iontophoresis-induced ocular shedding following ocular challenge with HSV-1 McKrae and W strains. However species differences were demonstrated; with complete protection in rabbits, and incomplete protection in mice. In mice, BUDR/autoradiography and restriction enzyme analysis identified both HSV-1 McKrae and W strains as having superinfected the TG, established latency and reactivated. Also, the avirulent TK negative inoculating strain was altered to a virulent TK positive strain through possible in vivo selection, mutation &/or host-modification, and possible in vivo recombination with the virulent challenge strains. We conclude that lower species differences require that potential HSV-1 vaccines be tested in non-human primates prior to clinical trials, and that a DNA-free subunit herpes vaccine represents a safer alternative to a live virus vaccine.
 ...
PMID:HSV-1 thymidine kinase negative vaccine: pathogenicity, protection, and perils. 303 Jun 39

A new compound has been found, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA), that has potent and selective activity against a broad spectrum of DNA viruses, including herpes simplex virus (types 1 and 2); varicella zoster virus; thymidine kinase-deficient (TK-) mutants of herpes simplex and varicella zoster virus; human cytomegalovirus; phocid, simian, suid, bovid and equid herpesviruses; African swine fever virus; vaccinia virus; and human adenoviruses. It is also active against retroviruses. We also report that, in mice and rabbits in vivo, the compound is effective against both local and systemic infections with herpes simplex virus type 1, including herpetic keratitis caused by a TK- mutant which is resistant to the classical anti-herpes drugs.
 ...
PMID:A novel selective broad-spectrum anti-DNA virus agent. 376 96

The relationship between thymidine kinase (TK) activity and virulence was studied in the mouse using three HSV-1 strains: (1) NIH TK+ (100% activity), (2) NIH TK+/- (25% TK activity), and (3) NIH TK- (0% TK activity). Following corneal inoculation, keratitis, virus titers (eye, trigeminal ganglia brain), survival, and latency were determined for each strain. The most virulent strain, NIH TK+ (30% survival) produced the worst keratitis, highest CNS titers, and established latency in 78% of surviving mice. NIH TK+/- demonstrated dose-dependent intermediate virulence (57-90% survival) and established latency in 80% of mice. NIH TK-, the most avirulent strain (93-100% survival) produced eye virus titers equal to the other strains but did not appear to invade the CNS or establish latency. These results indicate that TK gene activity is essential for HSV-1 murine neurovirulence (ie, efficient CNS invasion, replication and establishment of latency), but not for ocular replication.
 ...
PMID:HSV-1 thymidine kinase promotes virulence and latency in the mouse. 630 29

Acyclovir is a potent and selective antiviral agent. Unfortunately, drug-resistant (acyclovir-resistant) mutants have already been reported in herpes simplex virus type 1 (HSV-1) orofacial infections. We have developed a laboratory acyclovir-resistant HSV-1 mutant. The natural course of acyclovir-resistant HSV-1 keratitis was found to be less virulent than that observed in wild type HSV-1 keratitis, but the rate of ganglionic latency was as high as that induced by the parental strain. In vitro studies and in vivo observation of rabbit corneas infected with acyclovir-resistant HSV-1 both demonstrated a significant sensitivity to vidarabine and bromovinyldeoxyuridine ([E]-5-[2-bromovinyl]-2'-deoxyuridine). The thymidine kinase activity of the acyclovir-resistant mutant was 69% of that of the wild type HSV-1.
 ...
PMID:Herpes simplex acyclovir-resistant mutant in experimental keratouveitis. 631 52


1 2 3 Next >>