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Biomedical subjects

Axel Kornerup Hansen

Publications and source records attributed to Axel Kornerup Hansen.

17 recordsLinked to original sources
PubMed2006

The impact of different blood sampling methods on laboratory rats under different types of anaesthesia.

Rats with implanted telemetry transponders were blood sampled by jugular puncture, periorbital puncture or tail vein puncture, or sampled by jugular puncture in carbon dioxide (CO2), isoflurane or without anaesthesia in a crossover design. Heart rate, blood pressure and body temperature were registered for three days after sampling. Initially blood pressure increased, but shortly after sampling it decreased, which led to increased heart rate. Sampling induced rapid fluctuations in body temperature, and an increase in body temperature. Generally, rats recovered from sampling within 2-3 h, except for rats sampled from the tail vein, which showed fluctuations in body temperature in excess of 30 h after sampling. Increases in heart rate and blood pressure within the first hours after sampling indicated that periorbital puncture was the method that had the largest acute impact on the rats and that it might take an extra hour to recover from it. CO2 anaesthesia seemed unable to prevent the increase in blood pressure and the fluctuations in body temperature induced by blood sampling, and up to 10 h after sampling, the rats were still affected by CO2 anaesthesia. Rats anaesthetized with isoflurane showed lower increases in blood pressure after, and fewer fluctuations in body temperature during sampling, and the post-anaesthetic effects of isoflurane, if any, seemed to disappear immediately after sampling. It is, therefore, concluded that blood sampling in rats by jugular puncture seems to be the method from which rats most rapidly recover when compared with periorbital puncture and tail vein puncture, and that for anaesthesia, isoflurane is recommended in preference to CO2.

Anesthesia, Inhalation↗
PubMed2005

Behavioral response to novelty correlates with dopamine receptor availability in striatum of Göttingen minipigs.

Behavioral response to novelty in rats has been linked both to dopamine transmission in the ventral striatum, and to propensity to self-administer psychostimulant drugs. In order to probe the relationship between behavioral response to novelty and dopamine systems we have developed a behavioral model for correlation with positron emission tomography (PET) of dopamine transmission in brain of Göttingen minipigs. In the present study, we measured exploration of a novel object by recording the number of contacts, and duration of contact with a novel object, in groups of six male and six female adult minipigs. We hypothesized that these novelty scores would correlate with the amphetamine-evoked dopamine release in ventral striatum, measured 2 weeks later in a PET study of the availability of binding sites for the dopamine D2/3 antagonist [11C]raclopride. There were significant correlations between duration of contact with a novel object and the amphetamine-evoked reductions in binding potential (DeltapB) in the left ventral striatum of the 12 animals; Comparison of results by gender revealed that the correlation was driven mainly by the male group, and was not present in the female group. We interpret these results to show that propensity to explore an unfamiliar object is relatively elevated in pigs with low basal occupancy of dopamine D2/3 receptors by endogenous dopamine, and with high amphetamine-induced occupancy of released dopamine in the male pigs.

Adaptation, Psychological↗
PubMed2005

Mapping the amphetamine-evoked dopamine release in the brain of the Göttingen minipig.

The availability of dopamine D(2/3) binding sites in brain of six male and six female Göttingen minipigs was measured in a baseline condition and after challenge with amphetamine sulfate (1mg/kg, i.v.) in PET studies with [(11)C]raclopride. Maps of the binding potential (pB; B(max)/K(d)) of [(11)C]raclopride were spatially normalized and co-registered to a common stereotaxic coordinate system for pig brain. The pB maps were then analyzed by volume of interest and voxel-wise comparisons of gender and condition. The mean baseline pB tended to be 10-20% higher in striatum of the female group, but this gender difference was not significant. Variance of the mean baseline pB was higher in the males (44%) than in females (30%), but there was no correlation between pB and individual plasma cortisol or testosterone concentrations. Using statistical parametric mapping, we detected a focus in the right posterior putamen where the magnitude of the amphetamine-evoked decrease in pB was greater in the male than in the female group. Thus, the spatial pattern of reactivity of dopamine D(2/3) receptor availability to amphetamine challenge is not identical in male and female pigs. Within the entire population, the decline in pB evoked by amphetamine (Delta pB) was greater in the ventral striatum (-28%) than in the caudate nucleus (-17%), consistent with earlier reports in monkeys and humans. The magnitude of Delta pB correlated highly with the baseline pB values in all divisions of the striatum. Based upon the principles of competitive binding, the slope of this empirical relationship, f(i), is equal to the fraction of [(11)C]raclopride binding sites sensitive to endogenous dopamine; the magnitude of this fraction ranged from 0.29 in the caudate to 0.36 in the ventral striatum.

Amphetamine↗
PubMed2004

Pre-pulse inhibition of the acoustic startle eye-blink in the Göttingen minipig.

Pre-pulse inhibition (PPI) of the startle response is a measure of sensorimotor gating which has been frequently shown to be deficient in schizophrenic patients. In humans it is typically measured as the attenuation of the startle eye-blink reflex EMG when a startle eliciting noise is preceded by a weak white noise pre-pulse (PP), the interval between the PP and the startle noise stimulus (SNS) determining the degree of inhibition. Aiming at developing a new animal model of schizophrenia, we have investigated the acoustic startle eye-blink and PPI in 10 Göttingen minipigs. The stimuli and the block design of the stimulation were similar to paradigms used in human research. Initially the startle habituation across trials and blocks, secondarily the PPI at PP to SNS intervals of 30, 60, 120, 220, 520, 1020 and 2020 ms was investigated. One pig out of ten did not have a startle response, and three other pigs did not have a startle response of a sufficient magnitude to demonstrate the PPI seen in the other six pigs at the expected PP intervals of 60, 120, and 220 ms. Maximal inhibition was seen at the 220 ms interval (mean PPI 58.6%, range -18.4 to 94.6%, N = 9). Most of the results in the pigs are in accordance with findings in studies of the human startle eye-blink EMG and this initial study promotes further studies and the use of the PPI measure in the validation of minipig models of psychiatric disorders.

Acoustic Stimulation↗
PubMed2004

Problems related to an intraoral approach for experimental surgery on minipigs.

The purpose of the present study was to compare block and particulated bone grafts for jaw augmentation in combination with immediate implant placement. Bone defects measuring 10 mm x 10 mm x 30 mm were prepared on each side of the mandible of eight minipigs. After a healing period of 3 months, the defects in four animals were augmented with iliac crest grafts as a block or particulated graft, combined with immediate implant insertion. Clinical inspection was performed after 14 days. Complete exposure of grafts and implants was discovered. The surgical procedures were altered in the fifth animal. Inspection was made after 4 days showing no alterations. However, after another 7 days, grafts and implants were exposed. Consequently, the study was discontinued and all eight animals were killed. It is concluded that an intraoral approach is not applicable for this type of experimental surgery in minipigs. This paper describes some of the presumed reasons for the failure of the study.

Alveolar Ridge Augmentation↗
PubMed2003

Minipig negative slow wave demonstrates target/nontarget differences in P300 paradigm.

The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six Göttingen minipigs. Before training, we observed no difference between target and nontarget NSW. After training, target NSW amplitude was increased 50% compared to nontarget. A P350 was recognized, but the finding of a lack of target/nontarget difference is not conclusive.

Acoustic Stimulation↗
PubMed2003

Feeding minipigs fish oil for four weeks lowers postprandial triacylglycerolemia.

We wanted to establish a minipig model for the study of postprandial lipemia and plasma lipid clearance after fish oil consumption. Seven minipigs were fed a fish oil-enriched nonpurified diet and a control diet for 4 wk in a randomized cross-over study. After each intervention period, each pig was challenged with a gastric fat load (2 g fat/kg body) and an intravenous fat bolus (0.1 g/kg body) on separate days. Frequent blood samples were collected for 6 h after the gastric fat load and for 40 min after the intravenous bolus. The fish oil-enriched diet was associated with lower triacylglycerol, glycerol and nonesterified fatty acid concentrations in the hours after the gastric fat load than the control diet (P < 0.05). In contrast, the triacylglycerol disappearance rate after the intravenous fat bolus was not affected by fish oil (P = 0.19). In conclusion, dietary fish oil supplementation attenuates postprandial lipemia in minipigs similarly to what occurs in humans. Minipigs could serve as a useful model for future studies of this phenomenon. We observed no significant effect of fish oil supplementation on plasma triacylglycerol clearance and thus were unable to identify the mechanism explaining the attenuated lipemia in minipigs.

Animals↗
PubMed2003

The resistance of delayed xenograft rejection to alpha(1,3)-galactosyltransferase gene inactivation and CD4 depletion in a mouse-to-rat model.

Critical to the prevention of xenograft loss is the prevention of delayed xenograft rejection (DXR), due to its resistance to conventional immunosuppression. The role of the carbohydrate galactose-alpha1,3-galactose (alpha1,3Gal) has been a matter of great debate and it has been proposed that the reaction between alpha1,3Gal epitopes on donor endothelial cells and recipient anti-alpha1,3Gal antibodies (Abs) may damage the graft during DXR. Recipient anti-alpha1,3Gal Abs are produced by CD4-dependent B cells. To test the above-mentioned hypothesis, hearts from alpha1,3Gal-free mice (GT-Ko mice), generated by alpha1,3-galacto-syltransferase gene disruption, were transplanted to anti-alpha1,3Gal antibody-free Lew/Mol rats. This model consists of an alpha1,3Gal/alpha1,3Gal-antibody-free environment, eliminating a possible influence of this specific system on DXR. A subgroup of recipients were furthermore CD4 depleted in order to inhibit CD4-dependent B-cell antibody production. Rejected hearts were evaluated by light- and immunofluorescence microscopy. Treatment effects on recipient T-cell subsets and cytokine expression were analyzed by flow cytometry, while antibody production was measured by ELISA. All recipients developed DXR with no differences among the groups. DXR was related to thrombosis with IgG and IgM desposition in vessel walls, as well as macrophage and granulocyte accumulation in the myocardium. No complement C3, CD4 cells or NK cells were found. Flow cytometric analysis confirmed peripheral blood CD4 depletion and IFN-gamma suppression in CD4 Ab-treated recipients. Finally, ELISA showed that specific anti-alpha1,3Gal Ab production was absent. However, Ab(s) against an unidentified Galalpha 1 were found among recipients. In our model, DXR is resistant to alpha1,3-galactosyltransferase gene inactivation and CD4 depletion. However, other Galalpha 1 epitopes and antibodies may play a role during DXR. Further studies are needed to elucidate the precise pathways leading to DXR.

Animals↗
PubMed2003

Genetically modified laboratory animals--what welfare problems do they face?

In this article, we respond to public concern expressed about the welfare of genetically modified (GM) nonhuman animals. As a contribution to the debate on this subject, we attempt in this article to determine in what situations the practice of genetic modification in rodents may generate significant welfare problems. After a brief discussion of the principles of animal welfare, we focus on the problem of animal suffering and review some types of gene modifications likely to cause predictable welfare problems. In this article, we also consider suffering that may be involved in the process of generating GM animals. Finally, we discuss the role of GM animals in attempts to reduce, replace, and refine the use of animals in research.

Animal Welfare↗
PubMed2003

The impact of cage ventilation on rats housed in IVC systems.

Today the use of individually ventilated cage systems (IVC systems) is common, especially for housing transgenic rodents. Typically, in each cage a ventilation rate of 40 to 50 air changes per hour is applied, but in some systems even up to 120 air changes per hour is applied. To reach this rate, the air is blown into the cage at a relatively high speed. However, at the animal's level most systems ventilate with an air speed of approximately 0.2 m/s. In the present paper, two studies were conducted, one analysing whether an air speed below 0.2 m/s or just above 0.5 m/s affects the rats, and another study analysing whether air changes of 50, 80 and 120 times per hour affect the rats. In both studies, monitoring of preferences as well as physiological parameters such as heart rate and blood pressure, was used to show the ability of the animals to register the different parameters and to avoid them if possible. Air speeds inside the cage of as high as 0.5 m/s could not be shown to affect the rats, while the number of air changes in each cage should be kept below 80 times per hour to avoid impacts on physiology (heart rate and systolic blood pressure). Also the rats prefer cages with air changes below 80 times per hour if they have the opportunity of choosing, as shown in the preference test.

Air Movements↗
PubMed2003

The impact of low levels of carbon dioxide on rats.

The widespread use of individually ventilated cage (IVC) systems today has made the impact of CO(2) on rodents a highly important matter. Leaving cages from these systems without ventilation increases CO(2) concentrations inside the cages, as CO(2) generated from the animals is no longer removed actively. In modern IVC systems the CO(2) levels may reach 3-5% within a very short time, as the cages are very tightly sealed. The aim of the present study was to investigate the effects of 1%, 3%, and 5% CO(2) by studying the preferences of the animals as well as changes in the heart rate and systolic blood pressure as measured by telemetry. The rats avoided the cages, which contained 3% CO(2). In the telemetric study an anaesthetic effect on the rats were seen at 3% as a drop in the heart rate, and at 5% CO(2) a drop in the systolic blood pressure was also seen. The results from the present study could indicate that CO(2) levels of up to 3% do not affect the animals, or at least only to a minor extent, but that if the animals are exposed to CO(2) levels of higher than 3% they are affected directly as seen by changes in physiological parameters and preferences.

Animal Husbandry↗
PubMed2002

Spontaneous object recognition in the Göttingen minipig.

Göttingen minipigs were tested in an object recognition procedure based on spontaneous exploration. Eight pigs were exposed to two similar objects in a sample trial and after a one-hour delay exposed to two objects, one familiar and one novel, in a test trial. The pigs explored the novel object significantly more than the familiar object in the test trial (p<0.05), thereby showing recognition of the familiar object. Furthermore, habituation of exploration of the familiar object between the sample trial and the test trial was found (p<0.05). The procedure can be useful for testing of spontaneous trial-unique memory in pigs.

Animals↗
PubMed2002

Carbon dioxide concentrations in unventilated IVC cages.

The use of individually ventilated cage (IVC) systems has become more common worldwide. The various systems are becoming more and more sealed in order to protect the animals against infections and the staff against allergens; which, however, may lead to problematic CO2 concentrations, if the cages are left unventilated. In this study it is shown that, depending on how tight the cage is and the number of animals housed in each cage, CO2 inside the cage within 2 h will increase to levels of between 2 and 8%.

Air↗
PubMed2002

Assessment of the postoperative discomfort of intra-auricularly hypophysectomized rats.

Rats subjected to hypophysectomy make up one of the largest groups of experimental animals in Europe, since there is a legal demand for batch testing of industrially produced growth hormones. To describe the clinical performance of rats having undergone hypophysectomy, animals were examined postoperatively by monitoring behaviour, body temperature and food intake. Behavioural changes were observed in rats that had only been anaesthetized, as well as in sham-operated rats, while no behavioural deviations could be shown in hypophysectomized rats. On the first day after surgery all rats had declining body temperature and food intake; and this change was not reversed by treatment with carprofen, buprenorphine or oxytetracycline. The mortality rate in rats treated with buprenorphine was increased, as was the mortality rate in rats hypophysectomized when weighing more than 100 g. As there seemed to be no differences whether methohexital or a combination of fentanyl, fluanison and midazolam was used, the latter anaesthesia is recommended due to its analgesic potential. For post-surgical analgesic treatment, carprofen is recommended rather than buprenorphine. At best, the use of hypophysectomized rats should be replaced in industrial batch testing by an existing in vitro method.

Analgesics, Opioid↗
PubMedDate not supplied

Diabetes preventive gluten-free diet decreases the number of caecal bacteria in non-obese diabetic mice.

BACKGROUND: A gluten-free diet reduces the incidence of diabetes mellitus in non-obese diabetic (NOD) mice, but the mechanism is not known. The aim of this study was to examine the possible influence of the diet on the caecal bacterial flora, which may affect the intestinal physiology and mediate disease prevention. METHODS: Two groups of NOD mice from the age of 3 weeks were fed either a gluten-free diet or a standard diet. Each diabetic mouse, when diagnosed, along with a non-diabetic mouse from the same diet group and two non-diabetic mice from the alternate diet group were euthanized and sampled for classical bacteriological examination. RESULTS: Nine out of 19 (47%) standard-fed mice and 1 out of 19 (5%) gluten-free-fed mice developed diabetes (p < 0.01). Mice on the gluten-free diet had significantly fewer aerobically (p < 0.01) and microaerophilically (p < 0.001) cultivated bacteria in their intestines than standard-fed mice. Non-diabetic mice also had significantly fewer microa erophilic and anaerobic bacteria than diabetic mice (p < 0.05). These differences were primarily due to a difference in the Gram-positive flora. CONCLUSIONS: The gluten-free diet compared to the standard diet both qualitatively and quantitatively substantially altered the composition of the caecal bacterial flora in NOD mice. Although Gram-positive bacteria might influence the beta cells through certain digestive products, it is more likely to assume that any effect on diabetes incidence is immunological.

Animal Feed↗