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The article shares efforts in antimicrobial use (AMU) data collection by the National Animal Health Monitoring System, administered by the U.S. Department of Agriculture (USDA) and discusses some of the challenges and opportunities in these arenas. The effort calls veterinarians and partners to action in supporting and participating in the collection of AMU data. Also mentioned are examples of treatment outcome data collection in food animal systems and challenges with AMU data collection.

AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT1B) receptor, was explored as a potential treatment for depression. To support clinical trials, repeat dose toxicity studies in rats and dogs were conducted. Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86 days. Extensive pathologic changes were seen in all animals in retina epithelium (inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung, kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues. Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and pathology study showed that the concentration of AZD3783 in the brain was approximately 4 times higher than in the plasma after 4 weeks of dosing, however, they were similar in all regions examined, and did not correlate with areas with pathologic findings. Our findings with AZD3783 in dogs have not been reported previously with other CNS compounds that effect through serotonergic pharmacology. [ABSTRACT FROM AUTHOR]

The development and progression of cancer is controlled by gene expression, often regulated through chromatin packaging. Heterochromatin protein 1Hsα (HP1Hsα), one of three human HP1 family members, participates in heterochromatin formation and gene regulation. HP1Hsα possesses an amino-terminal chromodomain, which binds methylated lysine 9 of histone H3 (meK9 H3), and a carboxyl-terminal chromoshadow domain (CSD) that is required for dimerization and interaction with partner proteins. HP1Hsα is down-regulated in invasive metastatic breast cancer cells compared with poorly invasive nonmetastatic breast cancer cells. Expression of EGFP-HP1Hsα in highly invasive MDA-MB-231 cells causes a reduction in in vitro invasion, without affecting cell growth. Conversely, knock-down of HP1Hsα levels in the poorly invasive breast cancer cell line MCF-7 increased invasion, without affecting cell growth. To determine whether functions of the CSD were required for the regulation of invasion, mutant forms of HP1Hsα were expressed in MDA-MB-231 cells. A W174A mutation that disrupts interactions between HP1Hsα and PXVXL-containing partner proteins reduced invasion similar to that of the wild type protein. In contrast, an 1165E mutation that disrupts dimerization of HP1Hsα did not decrease invasion. No gross changes in localization and abundance of HP1Hsβ, HP1Hsγ, and meK9 H3 were observed upon expression of wild type and mutant forms of HP1Hsα in MDA-MB-231 cells. Taken together, these data demonstrate that modulation of HP1Hsα alters the invasive potential of breast cancer cells through mechanisms requiring HP1 dimerization, but not interactions with PXVXL-containing proteins. [ABSTRACT FROM AUTHOR]