No abstract

Calcinosis circumscripta is an uncommon syndrome of ectopic idiopathic, dystrophic, metastatic or iatrogenic mineralization characterized by deposition of calcium salts in soft tissues. This paper is a retrospective study of 77 canine cases. The age of dogs in the study varied from 4 months to 15 years and 55% were <1 year old, 74% <2 years old and 88% <4 years old. Several pure and mixed, typically large breed dogs were affected so that 28.6, 13 and 9% were German Shepherd, Rottweiler and Labrador Retriever respectively. The size of lesions varied from 2 mm to 13 cm in diameter but most lesions were between 0.5 cm and 3 cm in diameter. Lesions were solitary in 82% of the affected dogs, and occurred most commonly on the hind feet (50%) and tongue (23%). With multiple lesions there was no apparent body symmetry. Microscopically, most lesions were well-defined single or multiple variably sized aggregates of amorphous to granular, lightly to darkly basophilic material with or without peripheral granulomatous reaction and surrounded by varying amounts of fibrous connective tissue. Additionally, three small nodular masses in the wall of the jejunum of a dog were diagnosed as calcinosis circumscripta. This is the first reported case of idiopathic intestinal calcinosis circumscripta in the dog.

In vitro evidence of the involvement of the endoplasmic reticulum (ER) during drug-induced renal toxicity is accumulating. ER stress and ER-mediated cell death markers have been reported after exposure of renal cells to model toxicants and nephrotoxic drugs in various in vitro models, but in vivo experiments with clinically relevant nephrotoxic compounds are lacking. In order to determine the relevance of the in vitro findings, markers of ER stress (XBP1 messenger RNA processing and protein expression; GRP78 and GRP94 upregulation) and ER-mediated cell death (caspase-12 and calpain activation) were examined in kidney tissue of rats exposed to nephrotoxic doses of cisplatin (CIS), gentamicin (GEN), and p-aminophenol (PAP), a nephrotoxic metabolite of acetaminophen. XBP1 signaling was observed with all three drugs and was associated with increased expression of GRP94 and GRP78 in GEN- and PAP-treated animals, but surprisingly not after CIS exposure. m-Calpain expression was increased after 7 days of CIS treatment, whereas it was decreased in PAP-treated rats. Caspase-12 cleavage products were increased after CIS, GEN, and PAP administration. The results of this study demonstrate that three clinically relevant nephrotoxic drugs are all associated with changes in markers of ER stress and ER-mediated cell death in vivo. Further investigation is warranted to determine the role of the ER, the calpain system, and caspase-12 in drug-induced renal cell death.