Scandinavian Journal of Laboratory Animal Sciences <p>Published by the Scandinavian Society for Laboratory Animal Science, Sweden</p><p>Online ISSN <strong>2002-0112</strong></p> en-US Scandinavian Journal of Laboratory Animal Sciences 2002-0112 #1 Insulin dosing affects plasma levels of biochemical parameters in a time-dependent manner in Sprague-Dawley rats <p>Changes in levels of various biochemical blood parameters are used as indicators of metabolic effects or potential toxicity when performing non-clinical safety studies of new drug candidates in rats. Additionally, since biochemical blood parameters are often affected during safety testing of new insulin analogues the effect of insulin dosing on these parameters was investigated. Non-diabetic rats were dosed with either vehicle or insulin once daily for 28 days. On Day 28, biochemical blood parameters as well as insulin exposure were measured, at two hour intervals during a 24 h period, to investigate time-dependent as well as time-independent changes. Insulin dosing lowered plasma glucose level for 4 h, corresponding to the peak plasma insulin level. Chronic insulin dosing increased food consumption and bodyweights. Additionally, plasma urea as well as CK and LDH levels increased. Hyperphagia was most likely driven by hypoglycaemia thereby also increasing body weight through insulin-stimulated fatty acid uptake into adipose tissue. Increased urea, CK and LDH levels, suggests that the return to normoglycaemia was driven mainly by increased hepatic gluconeogenesis, as reflected by increased ureagenesis and skeletal muscle proteolysis (increased CK and LDH). A better understanding of insulin-induced changes to biochemical blood parameters may aid the interpretation of changes in these parameters in non-clinical safety studies with new drugs</p> Vivi Flou Hjorth Jensen Stine Bartelt Anne-Marie Mølck Lene Andersen Søren Andersen Ingrid Brück Bøgh ##submission.copyrightStatement## 2018-01-03 2018-01-03 44 1 14 #2 PET radioligand injection for pig neuroimaging <p>Pigs are useful models in neuroimaging studies with positron emission tomography (PET). Radiolabeled ligands are injected intravenously at the start of the scan and in pigs the most easily accessible route of administration is the ear vein. However, in brain studies the short distance between the brain and ear vein can be problematic as both are localized inside the field of view and, as a consequence, tracer residues in the catheter may influence the outcome of the scan. Here, we discuss options to avoid this problem. The femoral vein can be used in studies where repeated arterial blood sampling is needed because surgical incision has to be performed to allow access to the artery. When a non-invasive technique is preferred, the ear vein is a good alternative although it is recommended to dilute the tracer sufficiently in saline (20-50 mL) prior to injection. In addition, the tracer can be injected through an extension tube (filled with saline before injection), which is removed together with the syringe immediately after tracer injection. This avoids placing the syringe with tracer inside the PET gantry while injecting. By applying these simple techniques, it is our experience that it is possible to obtain high-quality images without exposing pigs to invasive procedures.</p> Aage KO Alstrup Ole L Munk Anne M Landau Thea P Lillethorup ##submission.copyrightStatement## 2018-03-06 2018-03-06 44 1 5 #3 Effects of exogenous sex hormones on mouse estrous cycle, vaginal microbiota and immune cells <p>Sex hormones are often administered to mice in vaginal microbial studies in order to synchronize estrous. Our objective was to evaluate the effect of estradiol-hemisuccinate (EH) or medroxyprogesterone-acetate (MPA) administration on estrous cycle, vaginal microbiota, and immune cell populations of various organs in a murine model. Two-month-old female BALB/c mice were intramuscularly injected with EH (day -2) or MPA (day -5) to induce estrous (E) or diestrous (DE), respectively. On sampling days (Sd) 0, 2, 6 and 8, vaginal washings (v.w.), vagina, blood, spleen and bone marrow (BM) samples were taken. Most of the animals remained in E or DE states until Sd 6 after EH or MPA administration, respectively. The number of cultivable vaginal bacteria was not modified by hormonal treatments; higher quantities were detected in mice in E. Only EH administration modified serum sex hormone levels, increasing serum estradiol on Sd 0. In v.w., myeloid population was dominant while lymphoid populations were not detected. Only MPA administration induced a reduction in myeloid cells on Sd 0. Hormonal treatments did not affect myeloid populations in BM but caused a slight decrease in T and B cells. In spleen, hormonal administration did not affect B or T population size while an increase in mature B cells and a decrease in immature B cells were observed in MPA-treated mice compared with EH-treated mice. Thus, although both hormonal treatments induced slight changes in some of the parameters evaluated compared to control animals, adequately standardized and consistent experimental protocols were established for further studies.</p> Priscilla Romina De Gregorio, Susana Salva María Silvina Juárez Tomás María Elena Fátima Nader-Macías ##submission.copyrightStatement## 2018-04-24 2018-04-24 44 1 14 #4 Determination of iohexol in canine plasma – strong correlation between enzyme-linked immunosorbent assay, high-performance liquid chromatography, and neutron activation analysis <p>Iohexol is a non-radioactive, iodinated, water-soluble radiographic contrast medium that is widely used in detection imaging for both clinical and scientific purposes. It has also been used as a marker for glomerular filtration rate (GFR) and intestinal permeability (IP) in both humans and animals, such as dogs, rats and cats. Currently, iohexol is determined mainly by high-performance liquid chromatography (HPLC) methods which limit its use in veterinary clinical practice. The aim of this study was to validate an enzyme-linked immunosorbent assay (ELISA) and its accuracy for the measurement of iohexol in canine plasma by comparison with HPLC and neutron activation analysis (NAA). Blank and iohexol-containing blood samples (n=100) from Beagle dogs were collected from the jugular vein in lithium heparin tubes before and after intravenous application of 3.0 g iohexol/dog via the cephalic vein.</p> <p>The results of this study show that the correlation coefficients when comparing ELISA vs. HPLC (r=0.99), ELISA vs. NAA (r=0.99) and HPLC vs. NAA (r=0.98) are all excellent. In conclusion, the measurement of iohexol from canine plasma using ELISA is as reproducible and reliable as using HPLC or NAA. However, using ELISA for measuring iohexol may be more practical, economical and useful for clinical practice and research than using HPLC or NAA.</p> V Ortín-Piqueras T Spillmann M Pöytäkangas D.E. Vaccaro R Frías ##submission.copyrightStatement## 2018-06-05 2018-06-05 44 1 7