ABSTRACT Antibiotics are the principal cause of drug-associated nephropathy. They are responsible for acute interstitial nephropathy (AIN) or acute tubulo-interstitial nephropathy (ATIN) due to two different pathophysiologic mechanisms: a drug-induced immunologic process and direct action due to drug accumulation. 1) Ain of immunologic origin. These are rare and are induced either by beta-lactamines or by rifampicin. Among the beta-lactamines, methicillin is the most often responsible, while penicillin and ampicillin are less often, and only rarely are carbenicillin, oxacillin, nafcillin, cephalothin and cephalexin. Macroscopic hematuria occurring 10 to 15 days after initiation of treatment usually reveals the renal involvement. It is associated with or preceded by fever, skin eruption and blood eosinophilia. Renal insufficiency (RI) is not severe and rarely requires hemodialysis (HD). The course is usually favorable. Rifampicin-induced AIN is observed in two circumstances, either during intermittent treatment or when previous treatment is resumed. Macroscopic hematuria is rare and RI often severe. Anti-rifampicin anti-bodies are usually found. 2) ATIN due to direct toxicity. Several classes of antibiotics may be responsible: cephalosporins, polymyxins or cyclins, but it is usually observed with aminoglycosides (AG). The incidence of renal involvement due to the latter group is estimated to be 4 to 10%. Nephrotoxicity is initially reflected by polyuria, tubular proteinuria and increased enzymuria, followed by cylindruria and reduced glomerular filtration. HD is rarely required. The proximal tubule is predominantly affected; pathological findings are disappearance of the brush border and tubular necrosis. Electronic microscopy shows lysosomal alterations with numerous myelinic bodies. Tubular regeneration occurs within 15 to 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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ABSTRACT: Background. Drug-induced hepatotoxicity (DIH) is quite common, and there are several recommendations for its treatment based upon its etiology. DIH may range from mild and subclinical to fulminant liver failure and death. Even though there is extensive list of drugs causing DIH, antibiotics, as a class of drugs, are the most common cause of DIH. Here, we present a fatal case of nafcillin-induced hepatotoxicity confirmed by liver biopsy, with total bilirubin peaking to 21.8 mg/dl and subsequent further extensive evaluation for hepatic injury turning out to be negative.Case Reports in Medicine 01/2012; 2012:953714.
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ABSTRACT: A polymyxin-B/bovine-serum-albumin/gold complex was used as a probe to detect the binding sites of polymyxin B on thin sections of cochlea embedded in Spurr's resin. The binding sites were found to be mainly located on the stereocilia, the cuticular plate of hair cells, the head plate of Deiters' cells, the tonofilaments in pillar cells and Deiters' cells, fibrous structures in the spiral limbus, the tectorial membrane and the basilar membrane and neural elements such as nerve endings, fibers, and the myelin sheath. The mitochondria, plasma membrane, and chromatin of the nuclei of the cells observed also exhibited binding. Our results suggest that phospholipids, glycoconjugates, cytoskeletal proteins and nucleic acids are responsible for this binding activity.Histochemistry 02/1986; 86(2):191-4.
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ABSTRACT: Understanding the cellular mechanism(s) by which the oto- and nephrotoxic aminoglycoside antibiotics penetrate cells, and the precise intracellular distribution of these molecules, will enable identification of aminoglycoside-sensitive targets, and potential uptake blockers. Clones of two kidney cell lines, OK and MDCK, were treated with the aminoglycoside gentamicin linked to the fluorophore Texas Red (GTTR). As in earlier reports, endosomal accumulation was observed in live cells, or cells fixed with formaldehyde only. However, delipidation of fixed cells revealed GTTR fluorescence in cytoplasmic and nuclear compartments. Immunolabeling of both GTTR and unconjugated gentamicin corresponded to the cytoplasmic distribution of GTTR fluorescence. Intra-nuclear GTTR binding co-localized with labeled RNA in the nucleoli and trans-nuclear tubules. Cytoplasmic and nuclear distribution of GTTR was quenched by phosphatidylinositol-bisphosphate (PIP2), a known ligand for gentamicin. Cytoplasmic and nuclear GTTR binding increased over time (at 37 degrees C, or on ice to inhibit endocytosis), and was serially competed off by increasing concentrations of unconjugated gentamicin, i.e., GTTR binding is saturable. In contrast, little or no reduction of endocytotic GTTR uptake was observed when cells were co-incubated with up to 4 mg/mL unconjugated gentamicin. Thus, cytoplasmic and nuclear GTTR uptake is time-dependent, weakly temperature-dependent and saturable, suggesting that it occurs via an endosome-independent mechanism, implicating ion channels, transporters or pores in the plasma membrane as bioregulatory routes for gentamicin entry into cells.Hearing Research 07/2005; 204(1-2):156-69. · 2.54 Impact Factor