Warfarin Related Kidney Damage: A Confusing Case of Thrombophlebitis Masquerading as Infection.

Anticoagulant-related nephropathy (ARN) is a rare, newly recognized cause of acute kidney injury and significant but underdiagnosed complication of anticoagulation therapy. ARN occurs in patients taking oral anticoagulant therapy most often warfarin or a novel oral anticoagulant (NOAC). It is a potentially devastating disorder with serious renal consequences and increased all-cause mortality. Anticoagulant-related nephropathy presents as an acute kidney injury (AKI) in the setting of a supratherapeutic INR with profuse glomerular hemorrhage seen as renal tubules filled with red cells and red cell casts on renal biopsy. Being that millions of Americans are on warfarin, a thorough understanding and awareness of the clinical presentation, diagnosis, and therapeutic interventions are crucial to protecting the renal function, lowering all-cause mortality and optimizing treatment. Our goal is to provide education on a newly recognized form of AKI and significant but underdiagnosed complication of anticoagulation therapy.

Post-translational and transcriptional regulation of glycolipid glycosyltransferase genes in apoptotic breast carcinoma cells: VII. Studied by DNA-microarray after treatment with L-PPMP.

Functions of glycosphingolipids on the eukaryotic cell membranes during the onset of oncogenic processes and cell death are not well understood. Inhibitors of glycosphingolipid biosynthesis were recently found to trigger apoptosis in many carcinoma including breast cancer SKBR-3, MCF-7, and MDA-468 cells through either intrinsic or extrinsic apoptotic pathways as we previously reported. These anti-cancer inhibitors could increase ceramide concentration by blocking functions of glycolipid glycosyltransferases (GLTs). In this study, using a novel fluorescent dye (ASK-0) revealed the damage of cell organelle membranes by an inhibitor of glucosylceramide biosynthesis (L-PPMP). A highly drug- and cell-dependent regulation of MAPKs was also found by cis-platin and L-PPMP when inducing apoptosis in SKBR-3, MCF-7, and MDA-468 cells. A dose and time-dependent regulation of GLTs were investigated by enzymatic assay and DNA microarray analyses. These GLTs are involved in biosynthesis of Le(X) and sialosyl-Le(X) (neolactosyl-ceramide series) such as GalT-4 (UDP-Gal: LcOse3cer beta-galactosyltransferase, GalT-5 (UDP-Gal: nLcOse4Cer alpha1, 3galactosyltransferase, FucT-3 (GDP-Fucose: LM1 alpha1, 4fucosyltransferase). A similar effect was observed with the GLTs involved in the biosyntheses of Gg-series gangliosides, such as SAT-4 (CMP-NeuAc: GgOse4Cer alpha2, 3sialyltransferase, and SAT-2 (CMP-NeuAc: GM3 alpha2, 8sialyltransferase). The glycol-related gene DNA-microarrays also suggested the transcriptional regulation of several GLTs involved in the biosynthesis of neolactosylceramide containing cell-surface antigens in these apoptotic breast carcinoma cells. In the early apoptotic stages (2 to 6 h after L-PPMP treatment) in addition to GlcT-1 gene, several genes (betaGalTs and betaGlcNAcTs) in the SA-Le(a) pathway were stimulated.