Ion channel targeting within neuronal and muscle membranes is an important determinant of electrical excitability. Recent evidence suggests that there exists within the membrane specialized microdomains commonly referred to as lipid rafts. These domains are enriched in cholesterol and sphingolipids and concentrate a number of signal transduction proteins such as nitricoxide synthase, ligand-gated receptors, and multiple protein kinases. Here, we demonstrate that the voltagegated K ؉ channel Kv2.1, but not Kv4.2, targets to lipid rafts in both heterologous expression systems and rat brain. The Kv2.1 association with lipid rafts does not appear to involve caveolin. Depletion of cellular cholesterol alters the buoyancy of the Kv2.1 associated rafts and shifts the midpoint of Kv2.1 inactivation by nearly 40 mV without affecting peak current density or channel activation. The differential targeting of Kv channels to lipid rafts represents a novel mechanism both for the subcellular sorting of K ؉ channels to regions of the membrane rich in signaling complexes and for modulating channel properties via alterations in lipid content.The subcellular localization of ion channels is necessary for proper electrical signaling. In cardiac and skeletal myocytes, ion channels show a differential surface distribution (1, 2). Within the brain, voltage-gated K ϩ (Kv) channels often show not only polarized sorting to either axons or dendrites, but also isoform-specific localization within dendrites alone. Thus, there exists specific sorting mechanisms for restricting lateral distribution within a given membrane domain (3). One physiological consequence for such specific localization is that it places various signal transduction molecules near their ion channel substrates (4). Several families of intracellular proteins, PDZs and AKAPs, have been shown to cluster both ion channels and modulatory signaling enzymes. Indeed, great emphasis has been placed on the role of PDZ proteins such as PSD-95 in the targeting and localization of ion channels and neurotransmitter receptors (5). In contrast, the role of membrane lipids in differential targeting and integration of ion channels within the plane of the plasma membrane has not been addressed.Recent advances in the study of cell membrane structure have led to the emerging idea that microdomains exist within the fluid bilayer of the plasma membrane. These dynamic structures, termed lipid rafts, are rich in tightly packed sphingolipids and cholesterol (6). The rafts, which are present in both excitable and non-excitable cells, localize a number of membrane proteins, including multiple signal transduction molecules, while excluding others (7). Different types of rafts are likely to exist based on the presence of specific marker proteins and ultrastructure data (8). Caveolae represent one well studied subpopulation of lipid raft having an invaginated morphology and containing the scaffolding protein, caveolin, which interacts directly with several intracellular proteins (7, 9 -12). Here, we de...

The purpose of this report is to offer a consensus opinion of ACVIM oncology diplomates and technicians on the safe use of cytotoxic chemotherapeutics in veterinary practice. The focus is on minimizing harm to the personnel exposed to the drugs: veterinary practitioners, veterinary technicians, veterinary staff, and pet owners. The safety of the patient receiving these drugs is also of paramount importance, but is not addressed in this statement. Much of the information presented is based on national recommendations by Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, United States Pharmacopeia, and other published regulations. These directives reflect an abundance of caution to minimize exposure to medical personnel, but large‐scale studies about the consequences of long‐term occupational exposure are not available in veterinary medicine. Challenges in the delivery of optimal treatment safely and economically to veterinary patients in general practice without access to a veterinary oncologist or other specialist, because of costs or proximity, remain.

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Background: Nanoparticles for over forty years have been the subject of a large number of physical and bioscience research. In the last decade use of these particles in medicine has gone from theoretical to clinical trials. Passive targeting of metal-based nanoparticles takes advantage of inherent abnormalities in tumor vasculature allowing accumulation in solid tumors through a process known as the ‘‘enhanced permeability and retention’’ (EPR) effect. In animal tumor implant models, combination of gold and silicone nanoparticle (GSN) and exposure of tumors to laser light (at 808nm) generated enough heat to cause tumor cell death. Mast cell tumors (MCT) are the most common skin tumor in dogs, with an estimate of MCT being roughly 20% of canine skin tumors. The goal of this pilot study is to evaluate nanoparticle and laser tumor thermal ablation on low grade canine MCT model.Results: 38 dogs with 44 mast cell tumors were enrolled in this prospective pilot study. All control tumors and those biopsied prior to laser therapy were found to be low grade MCT by histopathology (two grade method). After random number generation 8 dogs were assigned to control group and 30 dogs were assigned to treatment group. Treatment group had 36 total tumors and control group had 8 tumors present at time of enrollment. Treatment dogs had a 100% response rate, with 94% achieving clinical remission (34 tumors). Recurrence rate was 17% in those tumors achieving clinical remission. Mean progression free time (PFT) for the treatment group was 552 days and mean PFT for the control group was 1095 days.Conclusion: In conclusion results of this study suggest that photothermal ablation using gold-silicone nanoparticles and exposure to near infrared light (808 nm) provides an effective local therapy of low-grade mast cell tumors. Median progression free time and survival was not reached in our treatment group. Suggesting that long term tumor control is possible with PTA that potentially equals surgery when margins are narrow (<0.3cm) or incomplete. PTA appears to have better and more durable MCT responses than either radiation therapy and electrochemotherapy when used as sole therapies.