Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhabdomyolysis is a clinical condition that causes renal failure up to 40%. Rhabdomyolysis may be traumatic or nontraumatic. Colistin (polymyxin E) is an effective antibiotic. Nephrotoxicity is a frequently encountered side effect. The nephrotoxic effect of colistin is thought to be associated with increased membrane permeability, cell swelling and lysis, and the development of acute tubular necrosis. Here, we report a case of nontraumatic rhabdomyolysis associated with the use of colistin. There is only one report of rhabdomyolysis secondary to colistin in the literature, and there is no report of a case developing severe tetraparesis, as in our case.
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PMID:Rhabdomyolysis and severe muscle weakness secondary to colistin therapy. 2258 77

Colistin (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 55% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a dose of 16 mg/kg/day in 2 divided intraperitoneal doses and killed after either 3 or 15 days of colistin. After 15 days, mice exposed to colistin had elevated blood urea nitrogen (BUN), creatinine, and pathologic evidence of acute tubular necrosis and apoptosis. After 3 days, mice had neither BUN elevation nor substantial pathologic injury; however, urinary neutrophil gelatinase-associated lipocalin was elevated (P = 0.017). An Illumina gene expression array was performed on kidney RNA harvested 72 h after first colistin dose to identify differentially expressed genes early in drug treatment. Array data revealed 21 differentially expressed genes (false discovery rate < 0.1) between control and colistin-exposed mice, including LGALS3 and CCNB1. The gene signature was significantly enriched for genes involved in cell cycle proliferation. RT-PCR, immunoblot, and immunostaining validated the relevance of key genes and proteins. This murine model offers insights into the potential mechanism of colistin-mediated nephrotoxicity. Further studies will determine whether the identified genes play a causative or protective role in colistin-induced nephrotoxicity.
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PMID:Cell cycle arrest in a model of colistin nephrotoxicity. 2392 29