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)

Herpes simplex viruses (HSV) types 1 and 2 encode their own ribonucleotide reductases (RNRs) (EC 1.17.4.1) to convert ribonucleoside diphosphates into the corresponding deoxyribonucleotides. Like other iron-dependent RNRs, the viral enzyme is formed by the reversible association of two distinct homodimeric subunits. The carboxy terminus of the RNR small subunit (R2) is critical for subunit association and synthetic peptides containing these amino-acid sequences selectively inhibit the viral enzyme by preventing subunit association. Increasing evidence indicates that the HSV RNR is important for virulence and reactivation from latency. Previously, we reported on the design of HSV RNR inhibitors with enhanced inhibitory potency in vitro. We now report on BILD 1263, which to our knowledge is the first HSV RNR subunit-association inhibitor with antiviral activity in vivo. This compound suppresses the replication of HSV-1, HSV-2 and acyclovir-resistant HSV strains in cell culture, and also strongly potentiates the antiviral activity of acyclovir. Most importantly, its anti-herpetic activity is shown in a murine ocular model of HSV-1-induced keratitis, providing an example of potent nonsubstrate-based antiviral agents that prevent protein-protein interactions. The unique antiviral properties of BILD 1263 may lead to the design of new strategies to treat herpesvirus infections in humans.
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PMID:A potent peptidomimetic inhibitor of HSV ribonucleotide reductase with antiviral activity in vivo. 799 Sep 63

Invasive bacterial eye infections in the neonate range from perforating keratitis to endophthalmitis. Endophthalmitis secondary to Pseudomonas aeruginosa has gained clinical and therapeutic importance since mortality rates are high and prognosis concerning preservation of vision is poor, especially in premature infants. We presented two cases with meningitis, septicemia and P. aeruginosa endophthalmitis. If premature infants develop a sepsis-like picture with cloudy cornea and purulent conjunctivitis, we have to consider the possibility of endophthalmitis and do a full ophthalmologic evaluation. Treatment should be started early and consists of systemic antibiotic therapy, as in septicemia. As P. aeruginosa spreads easily, prompt isolation and strict handwashing are indicated.
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
PMID:Pseudomonas aeruginosa endophthalmitis in prematurity: report of two cases. 915 72

Seven herpes simplex type-1 (HSV-1) isolates from herpes simplex keratitis (HSK) cases clinically resistant to acyclovir (ACV) were analyzed for the mechanism of ACV resistance in them. The purpose of the study was to focus the attention of ophthalmologists on the frequency of occurrence of ACV resistance in HSK and to characterize such a phenomenon. We employed in-vitro plaque reduction assay, thymidine kinase assay, polymerase chain reaction, single-strand confirmation polymorphism analysis and sequencing to detect any mutation(s) in thymidine kinase gene in this analytical study. Four of the seven HSV-1 isolates proved ACV resistant by plaque reduction assay and three of them showed reduced thymidine kinase activity. Altered mobility pattern indicative of mutation within 335 base pair PCR product bracketing the suggested homopolymer mutational hotspot (7 Guanosine) was detected in 2 of these 3 isolates. DNA sequencing showed a deletion at nucleotide position 336 from the tk gene transcription start in both the isolates. This mutation has generated the first TGA stop codon 27 nucleotides downstream in the tk open reading frame. Our study also suggests the need of clinical/molecular surveillance of ACV resistance in HSV types in a given geographic location for better management of HSV infections.
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PMID:Acyclovir resistance in herpes simplex virus isolates from keratitis cases: an analysis from a developing country. 1083 67