Radon Solubility in Different Tissues after Short Term Exposure.

Radon, a naturally occurring radioactive noble gas, contributes significantly to lung cancer when incorporated from our natural environment. However, despite having unknown underlying mechanisms, radon is also used for therapeutic purposes to treat inflammatory diseases such as rheumatoid arthritis. Data on the distribution and accumulation of radon in different tissues represent an important factor in dose determination for risk estimation, the explanation of potential therapeutic effects and the calculation of doses to different tissues using biokinetic dosimetry models. In this paper, radon's solubility in bones, muscle tissue, adipose tissue, bone marrow, blood, a dissolved gelatin and oleic acid were determined. In analogy to current radon use in therapies, samples were exposed to radon gas for 1 h using two exposure protocols combined with established γ-spectroscopic measurements. Solubility data varied over two orders of magnitude, with the lowest values from the dissolved gelatin and muscle tissue; radon's solubility in flat bones, blood and adipose tissue was one order of magnitude higher. The highest values for radon solubility were measured in bone marrow and oleic acid. The data for long bones as well as bone marrow varied significantly. The radon solubility in the blood suggested a radon distribution within the body that occurred via blood flow, reaching organs and tissues that were not in direct contact with radon gas during therapy. Tissues with similar compositions were expected to reveal similar radon solubilities; however, yellow bone marrow and adipose tissue showed differences in solubility even though their chemical composition is nearly the same-indicating that interactions on the microscopic scale between radon and the solvent might be important. We found high solubility in bone marrow-where sensitive hematopoietic cells are located-and in adipose tissue, where the biological impact needs to be further elucidated.

Survey among FELASA members about rehoming of animals used for scientific and educational purposes.

Rehoming is an important fate, which should be considered for animals used for scientific and educational purposes, and which is highlighted in the European Directive 2010/63 EU. In 2018, the Federation of European Laboratory Animal Science Associations (FELASA) convened a working group to review current literature and identify existing practices with the aim of issuing general recommendations on the rehoming of research animals. In order to understand the number and species of animals being rehomed and which species and information to include in the recommendations, the working group launched a survey that was distributed among FELASA members, yielding 97 valid records for analysis. Most respondents of the survey considered the rehoming of cats, dogs, mice, rats, rabbits, pigs and minipigs. The most important issues reported by the respondents were related to availability/suitability of animals, availability of adopters and legal issues. Based on the data and information collected in this survey, the working group decided on the format and content of the future recommendations: a first section containing a general protocol for rehoming, addressing the issues raised by the respondents, and a second section containing species-specific information and advice about cats, dogs, small prey mammals, equines, primates, camelids and minipigs.

FELASA recommendations for the rehoming of animals used for scientific and educational purposes.

Directive 2010/63/EU of the European Parliament and the Council of 22 September 2010 states that at the end of a procedure, the most appropriate decision on the future of an animal previously used or intended for use in scientific procedures should be taken on the basis of animal welfare and potential risks to the environment. Member States may allow animals to be rehomed provided the health of the animal allows it, there is no danger to public health, animal health or the environment and if appropriate measures have been taken to safeguard the wellbeing of the animal. In countries where rehoming is permitted, it is the responsibility of the Animal Welfare Body to advise on a rehoming scheme which must include appropriate socialization in order to help facilitate successful rehoming, avoid unnecessary distress to the animals and guarantee public safety. This paper reviews the EU legislation, existing guidance, current literature and best practice to define rehoming, sets out general considerations for rehoming laboratory animals including socialization and provides practical advice on the steps required in a rehoming scheme. For those species most frequently rehomed, more detailed species-specific sections are included.

Metabolic syndrome and extensive adipose tissue inflammation in morbidly obese Göttingen minipigs.

OBJECTIVE: The worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM). METHODS: Young adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established. RESULTS: DIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM. CONCLUSIONS: The Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity.