Using cage ladders as a handling device reduces aversion and anxiety in laboratory mice, similar to tunnel handling

Summary Handling laboratory animals for husbandry and other procedures can be an important source of anxiety and stress, compromising animal welfare as well as the reliability of research that is sensitive to background stressors. Studies have revealed that picking up laboratory mice by the tail induces aversion, anxiety, physiological stress and depression-like behaviour, but such negative responses can be reduced substantially by using a handling tunnel that mice enter readily with minimal familiarisation. It has not been tested whether anxiety and aversion can be reduced similarly by using other objects to lift up mice from their home cage. Here we compared the willingness of C57BL/6NRj mice to interact voluntarily with their handler after being picked up either on a plastic ladder present in the home cage, or inside a familiar tunnel, or lifted by the base of the tail and then returned to the home cage. We also tested anxiety in open field and elevated plus maze tests once animals were familiarised with their assigned handling method. While mice picked up briefly by the tail were unwilling to interact with the hand that picked them up, mice picked up by ladder or tunnel readily approached, climbed on or entered these devices, with no significant difference in time spent with ladder or tunnel. Anxiety in an unfamiliar open field was reduced to a similar extent in ladder and tunnel handled mice compared with those picked up by the tail. Mice handled by tunnel also showed reduced anxiety in an elevated plus maze compared to those handled by tail, while ladder handling resulted in an intermediate response. Our study shows that, like tunnels, using home cage ladders to pick up mice reduces anxiety and avoids the aversion that is induced by picking up mice by their tails. We discuss the potential practicality of using ladders and tunnels to handle mice in different contexts

Low-Temperature Mobility of Surface Electrons and Ripplon-Phonon Interaction in Liquid Helium

The low-temperature dc mobility of the two-dimensional electron system localized above the surface of superfluid helium is determined by the slowest stage of the longitudinal momentum transfer to the bulk liquid, namely, by the interaction of surface and volume excitations of liquid helium, which rapidly decreases with temperature. Thus, the temperature dependence of the low-frequency mobility is \mu_{dc} = 8.4x10^{-11}n_e T^{-20/3} cm^4 K^{20/3}/(V s), where n_e is the surface electron density. The relation T^{20/3}E_\perp^{-3} << 2x10^{-7} between the pressing electric field (in kV/cm) and temperature (in K) and the value \omega < 10^8 T^5 K^{-5}s^{-1} of the driving-field frequency have been obtained, at which the above effect can be observed. In particular, E_\perp = 1 kV/cm corresponds to T < 70 mK and \omega/2\pi < 30 Hz.Comment: 4 pages, 1 figur

Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites

Background: Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug-and/or metabolite-specific antibodies in selective DF hypersensitivity. Methodology/Principal Findings: DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14%) displayed drug/metabolite-specific IgG. Conclusions/Significance: We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded