Use of intraoperative impression smear cytology to guide successful treatment of a large renal cyst in a dog: a case report

A 13-yr-old Shih tzu was referred for surgical management of right-sided cranial abdominal mass, which corresponded to large, cavitated renal mass on ultrasonography, and was suspected to represent neoplasia. Intraoperative impression smear cytology (ISC) of the renal mass wall was consistent with benign renal cyst (RC), without evidence of neoplasia or infection. Deroofing and omentalisation were performed and histopathology was consistent with benign RC. Chronic kidney disease was diagnosed 4 mon postoperatively, however, the dog was asymptomatic, without cyst reoccurrence. Intraoperative ISC is an expedient and inexpensive diagnostic technique that can guide most appropriate treatment in dogs with large RCs.

Application of cell-based assay systems for the early screening of human drug hepatotoxicity in the discovery phase of drug development

While drug toxicity [especially hepatotoxicity] is the most frequent reason cited for withdrawal of an approved drug, no simple solution exists to adequately predict such adverse events. Simple cytotoxicity assays in HepG2 cells are relatively insensitive to human hepatotoxic drugs in a retrospective analysis of marketed pharmaceuticals. In comparison, a panel of pre-lethal mechanistic cellular assays hold the promise to deliver a more sensitive approach to detect endpoint-specific drug toxicities. The panel of assays covered by this review includes steatosis, cholestasis, phospholipidosis, reactive intermediates, mitochondria membrane function, oxidative stress, and drug interactions. In addition, the use of metabolically competent cells or the introduction of major human hepatocytes in these in-vitro studies allow a more complete picture of potential drug side effect. Since inter-individual therapeutic index [TI] may differ from patient to patient, the rational use of one or more of these cellular assay and targeted in-vivo exposure data may allow pharmaceutical scientists to select drug candidates with a higher TI potential in the drug discovery phase

Involvment of metabolic reactive intermediate G [IV] in chromium [VI] cytotoxic effects.

Addition of Cr VI [dichromate] to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species [ROS] formation, lipid peroxidation, decreased mitochondrial membrane potential and lysosomal membrane rupture before hepatocyte lysis occurred. Cytotoxicity was prevented by ROS scavengers, antioxidants, and glutamine [ATP generator]. Hepatocyte dichlorofluorescin oxidation to dichlorofluorescein [DCF] to determine ROS formation was inhibited by mannitol [a hydroxyl radical scavenger] or butylated hydroxyanisole and butylated hydroxytoluene [antioxidants]. The Cr VI reductive mechanism required for toxicity is not known. Cytochrome P450 inhibitors, Particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase also prevented cytotoxicity. This suggests that P450 reductase and/or reduced cytochrome P450 contributes to Cr VI reduction to Cr IV. Glutathione depleted hepatocytes were resistant to Cr [VI] toxicity and much less dichlorofluorescin oxidation occurred. Reduction of dichromate by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Mn II [a Cr IV reductant]. Cr VI induced cytotoxicity and ROS formation was also inhibited by Mn II, which suggests that, Cr IV and Cr IV GSH mediate "ROS" formation in isolated hepatocytes. In conclusion Cr VI cytotoxicity is associated with mitochondrial/lysosomal toxicity by the metabolic reactive intermediate Cr IV and "ROS"