Diclofenac is a nonsteroidal anti-inflammatory drug frequently found in the aquatic environment. Previous studies have reported histological changes in the liver, kidney, and gills of fish at concentrations similar to those measured in treated sewage effluents (approximately 1 µg/L). Analyses or predictions of blood plasma levels in fish allow a direct comparison with human therapeutic plasma levels and may therefore be used to indicate a risk for pharmacological effects in fish. To relate internal exposure to a pharmacological interaction, we investigated global hepatic gene expression together with bioconcentration in blood plasma and liver of rainbow trout (Oncorhynchus mykiss) exposed to waterborne diclofenac. At the highest exposure concentration (81.5 µg/L), the fish plasma concentration reached approximately 88% of the human therapeutic levels (C(max) ) after two weeks. Using an oligonucleotide microarray followed by quantitative PCR, we found extensive effects on hepatic gene expression at this concentration, and some genes were found to be regulated down to the lowest exposure concentration tested (1.6 µg/L), corresponding to a plasma concentration approximately 1.5% of the human C(max) . Thus, at concentrations detected in European surface waters, diclofenac can affect the expression of multiple genes in exposed fish. Functional analysis of differentially expressed genes revealed effects on biological processes such as inflammation and the immune response, in agreement with the mode of action of diclofenac in mammals. In contrast to some previously reported results, the bioconcentration factor was found to be stable (4.02 ± 0.75 for blood plasma and 2.54 ± 0.36 for liver) regardless of the water concentration.

No abstract

No abstract

No abstract

BackgroundGlaucoma is an optic neuropathy associated with visual field loss. There are different types of glaucoma, among them exfoliative glaucoma. Glaucoma can present as unilateral or bilateral. The present study aimed to show the association between gene expression and exfoliation in unilateral glaucoma cases.MethodsIncluded patients were suffering from exfoliative glaucoma in one eye, meanwhile the other eye was healthy and used as a control. Lens capsule and conjunctival biopsies were taken from both eyes. Gene expression was analyzed.ResultsBoth groups were completely different at baseline regarding intraocular pressure, visual acuity before the operation, visual field damage, optic nerve damage, etc. As for gene expression, the only significant difference was found in CYP1B1 from lens capsules. None of the other genes studied showed differential expression in either lens capsules or conjunctival biopsies.ConclusionNo difference in gene expression was found between eyes with and without exfoliative glaucoma. Exfoliative glaucoma seems to be a bilateral disease, though the phenotype is not always clinically present.