Organochlorine compounds, particularly polychlorinated biphenyls (PCBs), alter serum thyroid hormone levels in humans. Hydroxylated organochlorines have relatively high affinities for the serum transport protein transthyretin, but the ability of these compounds to interact with the human thyroid receptor is unknown. Using a baculovirus expression system in insect cells (Sf9 cells), we produced recombinant human thyroid receptor ss (hTRss). In competitive binding experiments, the recombinant receptor had the expected relative affinity for thyroid hormones and their analogs. In competitive inhibition experiments with PCBs, hydroxylated PCBs (OH-PCBs), DDT and its metabolites, and several organochlorine herbicides, only the OH-PCBs competed for binding. The affinity of hTRss for OH-PCBs was 10,000-fold lower (Ki = 20-50 microM) than its affinity for thyroid hormone (3,3',5-triiodothyronine, T3; Ki = 10 nM). Because their relative affinity for the receptor was low, we tested the ability of OH-PCBs to interact with the serum transport proteins--transthyretin and thyroid-binding globulin (TBG). With the exception of one compound, the OH-PCBs had the same affinity (Ki = 10-80 nM) for transthyretin as thyroid hormone (thyroxine; T4). Only two of the OH-PCBs bound TBG (Ki = 3-7 microM), but with a 100-fold lower affinity than T4. Hydroxylated PCBs have relatively low affinities for the human thyroid receptor in vitro, but they have a thyroid hormonelike affinity for the serum transport protein transthyretin. Based on these results, OH-PCBs in vivo are more likely to compete for binding to serum transport proteins than for binding to the thyroid receptor.ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7

The objective of this observational, descriptive, retrospective study was to report CT characteristics associated with fractures following stereotactic radiosurgery in canine patients with appendicular osteosarcoma. Medical records (1999 and 2012) of dogs that had a diagnosis of appendicular osteosarcoma and undergone stereotactic radiosurgery were reviewed. Dogs were included in the study if they had undergone stereotactic radiosurgery for an aggressive bone lesion with follow-up information regarding fracture status, toxicity, and date and cause of death. Computed tomography details, staging, chemotherapy, toxicity, fracture status and survival data were recorded. Overall median survival time (MST) and fracture rates of treated dogs were calculated. CT characteristics were evaluated for association with time to fracture. Forty-six dogs met inclusion criteria. The median overall survival time was 9.7 months (95% CI: 6.9-14.3 months). The fracture-free rates at 3, 6, and 9 months were 73%, 44%, and 38% (95% CI: 60-86%, 29-60%, and 22-54%), respectively. The region of bone affected was significantly associated with time to fracture. The median time to fracture was 4.2 months in dogs with subchondral bone involvement and 16.3 months in dogs without subchondral bone involvement (P-value = 0.027, log-rank test). Acute and late skin effects were present in 58% and 16% of patients, respectively. Findings demonstrated a need for improved patient selection for this procedure, which can be aided by CT-based prognostic factors to predict the likelihood of fracture.

The University of Florida LOPP protocol may be an acceptable alternative to the mechlorethamine, vincristine, procarbazine, and prednisone protocol as a rescue protocol for dogs with lymphoma.

Stereotactic radiosurgery (SRS) is a relatively new therapeutic option in veterinary oncology. The role of this modality has not been extensively evaluated for the use in canine nasal tumors. The objective of this retrospective, observational study was to describe the clinical outcome and prognostic factors associated with survival times in a sample of canine patients treated with SRS for sinonasal tumors. Fifty-seven dogs with sinonasal tumors met inclusion criteria. Histologic diagnoses included sarcoma (SA) (n = 9), carcinoma (CA) (n = 40), osteosarcoma (OSA) (n = 7), and round cell (n = 1). Four of 57 cases were treated twice with SRS. For these, the median and mean doses delivered were 30Gy and 33Gy, respectively (range 18.75Gy-56Gy). Late effects occurred in 23 cases and ranged from grades I-III. The median overall survival time was 8.5 months. The median overall survival times in dogs with tumor type of CA, SA, and OSA were 10.4, 10.7, and 3.1 months, respectively. Dogs with the tumor type of OSA had shorter overall survival time than that in dogs with tumor type of CA and SA. Findings from this retrospective study indicated that SRS may be beneficial for canine patients with sinonasal tumors, however a controlled clinical trial would be needed to confirm this. Prospective studies are also needed to better define the role of SRS as palliative or curative, and to further investigate the risk of clinically significant toxicity.

Nitrogen fixation is a symbiotic process initiated by chemical signals from legumes that are recognized by soil bacteria. Here we show that some endocrine-disrupting chemicals (EDCs), so called because of their effect on hormone-signalling pathways in animal cells, also interfere with the symbiotic signalling that leads to nitrogen fixation. Our results raise the possibility that these phytochemically activated pathways may have features in common with hormonal signalling in vertebrates, thereby extending the biological and ecological impact of EDCs.