Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022575 (keratoconjunctivitis sicca)
772 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiosyncratic toxicity to potentiated sulfonamides occurs in both humans and dogs, with considerable clinical similarities. The syndrome in dogs can consist of fever, arthropathy, blood dyscrasias (neutropenia, thrombocytopenia, or hemolytic anemia), hepatopathy consisting of cholestasis or necrosis, skin eruptions, uveitis, or keratoconjunctivitis sicca. Other manifestations seen less commonly include protein-losing nephropathy, meningitis, pancreatitis, pneumonitis, or facial nerve palsy. The pathogenesis of these reactions is not completely understood, but may be due to a T-cell-mediated response to proteins haptenated by oxidative sulfonamide metabolites. Our laboratory is working on tests to characterize dogs with possible idiosyncratic sulfonamide reactions, to include ELISA for anti-drug antibodies, immunoblotting for antibodies directed against liver proteins, flow cytometry for drug-dependent anti-platelet antibodies, and in vitro cytotoxicity assays. The management of idiosyncratic sulfonamide toxicity involves client education to identify clinical signs early and allow rapid drug discontinuation, supportive care to include possibly ascorbate and glutathione precursors, and avoidance of subsequent re-exposure. It is important to realize that only antimicrobial sulfonamides, such as sulfamethoxazole, sulfadiazine, and sulfadimethoxine, share this clinical syndrome. There is no evidence for cross-reactivity with drugs that have different underlying structures but share a sulfonamide moiety, such as acetazolamide, furosemide, glipizide, or hydrochlorthiazide.
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PMID:Idiosyncratic toxicity associated with potentiated sulfonamides in the dog. 1518 98

Though they are rare in nature, anthropogenic 1,3,5-triazines have been used in herbicides as chemically stable scaffolds. Here, we show that small 1,3,5-triazines selectively target ascorbate peroxidases (APXs) in Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), rice (Oryza sativa), maize (Zea mays), liverwort (Marchantia polymorpha), and other plant species. The alkyne-tagged 2-chloro-4-methyl-1,3,5-triazine probe KSC-3 selectively binds APX enzymes, both in crude extracts and in living cells. KSC-3 blocks APX activity, thereby reducing photosynthetic activity under moderate light stress, even in apx1 mutant plants. This suggests that APX enzymes in addition to APX1 protect the photosystem against reactive oxygen species. Profiling APX1 with KCS-3 revealed that the catabolic products of atrazine (a 1,3,5-triazine herbicide), which are common soil pollutants, also target APX1. Thus, KSC-3 is a powerful chemical probe to study APX enzymes in the plant kingdom.
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PMID:Triazine Probes Target Ascorbate Peroxidases in Plants. 3113 23