In patients taking p-glycoprotein inhibitors, maximum recommended dose is 0.3mg per day. In renal or hepatic impairment, recommendation is to avoid concomitant administration of p-glycoprotein inhibitors and colchicine. Case Summary We present an 82year old patient, with a history of gout, chronic kidney disease and recurrent renal cell buy Copanlisib carcinoma who was admitted with features of colchicine toxicity after taking a cumulative dose of 41.4mg over ten days, and taking sunitinib 50mg daily from day seven of his
high dose colchicine regimen. Symptoms started after commencing his cycle of sunitinib, which he had taken in 14day cycles for many years. He developed severe diarrhea, normal anion gap metabolic acidosis, fever, pneumonia, white cell abnormalities including 30% bands and toxic granulation with Dohle bodies. Red cell abnormalities included anemia, burr cells and acanthocytosis. He also
developed acute cardiovascular collapse with hypotension and acute systolic heart failure. Cardiac catheterization showed previously known coronary artery disease, with no significant progression to explain degree of cardiovascular collapse. What is new and Conclusion P-glycoprotein inhibition by sunitinib has been demonstrated. Interaction with colchicine metabolism precipitated colchicine toxicity in this case. Knowledge of p-glycoprotein and its role in drug interactions and potential drug toxicity may not be widespread among PARP activity clinicians. MK-1775 molecular weight We report the first case of colchicine toxicity
precipitated by interaction with a tyrosine kinase inhibitor.”
“Brassinosteroids (BRs) are plant hormones that are perceived at the cell surface by a membrane-bound receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1). BRI1 interacts with BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1) to initiate a signal transduction pathway in which autophosphorylation and transphosphorylation of BRI1 and BAK1, as well as phosphorylation of multiple downstream substrates, play critical roles. Detailed mechanisms of BR signaling have been examined in Arabidopsis (Arabidopsis thaliana), but the role of BRI1 and BAK1 phosphorylation in crop plants is unknown. As a foundation for understanding the mechanism of BR signaling in tomato (Solanum lycopersicum), we used liquid chromatography-tandem mass spectrometry to identify multiple in vitro phosphorylation sites of the tomato BRI1 and BAK1 cytoplasmic domains. Kinase assays showed that both tomato BRI1 and BAK1 are active in autophosphorylation as well as transphosphorylation of each other and specific peptide substrates with a defined sequence motif. Site-directed mutagenesis revealed that the highly conserved kinase domain activation loop residue threonine-1054 was essential for tomato BRI1 autophosphorylation and peptide substrate phosphorylation in vitro.