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 authors report an experimental study on the effect of cAMP on HSV-I keratitis. Rabbit corneas developed typical dendritic keratitis on the 3rd day after inoculation of HSV-I. On the 9th day, the cAMP level in plasma significantly decreased from 174.9 +/- 20.2 to 52.1 +/- 18.2 pmol/ml, while the cGMP level increased. The cAMP level in aqueous humour also decreased, with an increase in cGMP level increased. The cAMP level in aqueous humour also decreased, with an increase in cGMP level. cAMP was used subconjunctivally for treatment of HSV-I keratitis. 48 hours after injection, the cAMP level in aqueous humour markedly rose from 11.1 +/- 2.0 to 35.6 +/- 12.9 pmol/ml and 6 days later to 65.0 +/- 30.9 pmol/ml, with concurrent decrease in cGMP level, and the ratio of cAMP/cGMP increased from 1.6 +/- 0.6 to 15.3 +/- 4.6. In the group of treatment by acyclovir, the level of cAMP in aqueous humour increased by 9.5 times after 3 days of treatment, with no remarkable effect on the cGMP level. These results showed that cAMP was equally effective as ACV in treatment of experimental HSV 1 keratitis. The antiviral action of cAMP was discussed and the pharmacological effect of cAMP approached.
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PMID:[Effect of cyclic nucleotides (cAMP) on experimental HSV-I keratitis]. 255 11

Endogenous proliferation of corneal epithelial cells is regulated by a bidirectional control process characterized by an adrenergic, cAMP-dependent 'off', and a cholinergic, muscarinic cGMP-dependent 'on' response. The adrenergic receptor(s) are located in the plasma membrane (microsomal fraction), whereas the novel feature of the system is a cholinergic receptor specific for acetylcholine (ACH) located in the nuclear membrane. Exogenous substances which raise intracellular cAMP levels such as isoproterenol or PGE1, shut off epithelial mitosis: and, carbamylcholine or ACH raise intranuclear cGMP levels and increase mitosis by specific, regulatory stimulation of RNA-polymerase II activity. We believe that this regulatory system explains the transitory mitotic suppression induced by superficial corneal wounding (interruption of adrenergic fibres, chalone-effect); and the marked, permanent depression of epithelial mitosis associated with decreased intracellular ACH levels which are produced by total corneal denervation, and which results in neurotrophic keratitis.
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PMID:The molecular basis of neurotrophic keratitis. 255 41

Activity of phosphodiesterases disintegrating cAMP and cGMP in the cornea, sclera and ciliary body was investigated in health and in different stages of experimental herpetic keratitis. The problems concerning the role of the cyclase system in the pathogenesis of herpetic keratitis and the possibility of applying some of the drugs to the disease treatment are discussed.
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PMID:[Enzymes of cyclic nucleotide degradation in eye tissues during experimental ocular herpes]. 629 26

Pathogenic and opportunistic free-living amoebae such as Acanthamoeba spp. can cause keratitis (AK), which may ultimately lead to permanent visual impairment or blindness. Acanthamoeba can also cause a rare but usually fatal granulomatous amoebic encephalitis (GAE). Current therapeutic options for AK require a lengthy treatment with nonspecific drugs that often are associated with adverse effects. Recent developments in the field led us to target cAMP pathways, specifically phosphodiesterase. Guided by computational tools we targeted the Acanthamoeba phosphodiesterase, RegA. Computational studies led to the construction and validation of a homology model followed by a virtual screening protocol guided by induced-fit docking and chemical scaffold analysis using our MBC chemical library. Subsequently, 18 virtual screening hits were prioritized for further testing in vitro against A. castellanii, identifying amoebicidal hits containing piperidine and urea imidazole cores. Promising activities were confirmed in the resistant cyst form of the amoeba and in additional clinical Acanthamoeba strains, increasing their therapeutic potential. Mechanism of action studies revealed that these compounds produce apoptosis through ROS-mediated mitochondrial damage. These chemical families show promise for further optimization to produce effective anti-Acanthamoebal drugs.
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PMID:Discovery of Amoebicidal Compounds by Combining Computational and Experimental Approaches. 3322 26