In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles.

Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1-DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.

Progressive Lameness of a Greater One-Horned Rhinoceros (Rhinoceros unicornis) Associated with a Retroperitoneal Abscess and Thrombus Caused by Streptococcus dysgalactiae Subspecies equisimilis.

In rhinoceroses, lameness is an occasionally seen symptom primarily caused by lesions affecting the feet and interdigital space. A 3-year-old male Greater one-horned rhinoceros developed a progressive, severe movement disorder of the right hind limb with subsequent death. The pathological analysis diagnosed a severe, retroperitoneal abscess and chronic thrombosis of the right iliac artery. Streptococci detected in the abscess were further identified as Streptococcus dysgalactiae subspecies equisimilis by culture and molecular techniques. The identical isolate was also identified in a vaginal swab of the dam. The list of differential diagnoses for lameness in rhinoceroses must be expanded by processes affecting other than the extremities per se.