On the carbohydrate metabolic response to an experimental infection with Brachyspira hyodysenteriae (swine dysentery) in pigs

The carbohydrate metabolic response to experimentally induced swine dysentery was studied in crossbreed pigs. Twelve pigs, with a mean weight of ~20 kg, were orally inoculated with Brachyspira hyodysenteriae strain B204. After an incubation period of 6-20 days, five animals developed swine dysentery with haemorrhagic diarrhoea and two animals developed non-haemorrhagic diarrhoea. Five animals remained healthy throughout the study. Blood samples from the animals with clinical signs of disease were collected before inoculation, several times during the course of the dysentery and finally after recovery. Blood samples from animals that remained healthy were obtained before inoculation and at slaughter four weeks later. Glucose, lactate and cortisol concentrations did not differ between sampling occasions in the healthy animals. In the sick animals, higher concentrations were observed when haemorrhagic diarrhoea occurred (mean peak value ± SD: glucose 7.6 ± 0.7 mmol/L; lactate 4.5 ± 1.7 mmol/L; cortisol 278 ± 86 nmol/L) compared to before inoculation (mean value ± SD: glucose 5.1 ± 1.2 mmol/L; lactate 1.3 ± 0.5 mmol/L; cortisol 24 ± 11 nmol/L). At slaughter, tissue samples from m. biceps femoris, m. longissimus dorsi, myocardium and liver were collected from 10 pigs and glycogen analysis was performed. Glycogen concentrations did not differ between the healthy pigs and those that developed swine dysentery: concentrations were highest in the liver and lowest in the heart. In conclusion, experimental infection with B. hyodysenteriae results in alteration of the carbohydrate metabolism, which is characterised by a transient increase in blood glucose and lactate concentrations during the initial phase of the haemorrhagic period of the disease

A battery-less implantable glucose sensor based on electrical impedance spectroscopy

The ability to perform accurate continuous glucose monitoring without blood sampling has revolutionised the management of diabetes. Newer methods that can allow measurements during longer periods are necessary to substantially improve patients' quality of life. This paper presents an alternative method for glucose monitoring which is based on electrical impedance spectroscopy. A battery-less implantable bioimpedance spectroscope was designed, built, and used in an in vivo study on pigs. After a recovery period of 14 days post surgery, a total of 236 subcutaneous bioimpedance measurements obtained from intravenous glucose tolerance tests, with glucose concentration ranges between 77.4 and 523.8 mg/dL, were analyzed. The results show that glucose concentrations estimated by subcutaneous bioimpedance measurements correlate very well to the blood glucose reference values. The pigs were clinically healthy throughout the study, and the postmortem examinations revealed no signs of adverse effects related to the sensor. The implantation of the sensor requires minor surgery. The implant, being externally powered, could in principle last indefinitely. These encouraging results demonstrate the potential of the bioimpedance method to be used in future continuous glucose monitoring systems

Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting

In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 × 10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores,which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation

Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography

Introduction Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans.Research design and methods GLP-1R distribution and occupancy were measured in pancreas and gastrointestinal tract by ex vivo autoradiography using the GLP-1R-specific radioligand Lu-177-exendin-4 in two groups of pigs, control or bottle-fed an oral glucose load. Positron emission tomography (PET) data from pigs injected with Ga-68-exendin-4 in a previous study were used to retrieve data on biodistribution of GLP-1R in the gastrointestinal tract.Results High homogenous uptake of Lu-177-exendin-4 was found in pancreas, and even higher uptake in areas of duodenum. Low uptake of Lu-177-exendin-4 was found in stomach, jejunum, ileum and colon. During OGTT, there was no increase in plasma GLP-1 concentrations and occupancy of GLP-1Rs was low. The ex vivo autoradiography results were highly consistent with to the biodistribution of Ga-68-exendin-4 in pigs scanned by PET.Conclusion We identified areas with similarities as well as important differences regarding GLP-1R distribution and occupancy in pigs compared with humans. First, there was strong ligand binding in the exocrine pancreas in islets. Second, GLP-1 secretion during OGTT is minimal and GLP-1 might not be an important incretin in pigs under physiological conditions. These findings offer new insights on the relevance of porcine diabetes models

Training Pigs for Oral Glucose Tolerance Test-Six Years' Experience of a Refined Model

Simple Summary Animal models for human diseases are used in situations where studies cannot be carried out on humans. While animal models in biomedical research play a pivotal part in the development of new and safe treatments for humans, it is important that the animals are used in the best way and that possible refinements are considered. Pigs are often used to model humans since the two species share many anatomical and physiological characteristics. This publication describes refinements in the training technique of pigs prior to an oral glucose tolerance test, a test commonly used in diabetes research where the individual drinks a certain amount of glucose followed by blood sampling. Sharing these results with the research community will help other researchers to successfully train pigs in such studies. Animal models of human diseases are important in biomedical research. When using animals for scientific purposes, the 3Rs (replace, reduce, refine) should be considered. Refinement of animal models is essential to ensure best use of animals, which is important for ethical reasons and to retrieve reliable research data. The present publication describes improvements to an oral glucose tolerance test (OGTT) model for pigs published in 2016. Historical data from 42 pigs were used to describe improvements in the training technique over six years. Pigs of various breeds and ages can be trained to bottle-feed glucose dissolved in water to undergo OGTT. This publication describes different tips and techniques to apply for successful training and will help researchers to minimize exclusions of pigs due to unsuccessful training. The improvements are an important contribution to the 3Rs

Physiological and Clinical Responses in Pigs in Relation to Plasma Concentrations during Anesthesia with Dexmedetomidine, Tiletamine, Zolazepam, and Butorphanol

Simple Summary Reliable protocols are needed for short-term anesthesia in pigs. The study's aim is to identify an anesthetic procedure that, without the use of sophisticated equipment, ensures an acceptable depth and length of anesthesia, a regular spontaneous breathing pattern, and a stable hemodynamic condition for the animal. A total of 12 pigs were given a single intramuscular injection of dexmedetomidine, tiletamine, zolazepam, and butorphanol. To investigate the possibility of prolonging the anesthesia, six of the pigs also received an intravenous dose of the drug combination after one hour. Physiological and clinical responses and drug plasma concentrations were examined. The main results suggest that intramuscular administration of the drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia. An intravenous administration of one-third of the original dosage prolonged the anesthesia for another 30 min. Since the pigs were able to breathe spontaneously, none of them were intubated. The study also provides new information about each drug's plasma concentrations and the impact of the drug combination in pigs. This technique can be used to perform nonsurgical operations or transports when short-term anesthesia is required. Reliable protocols for short-term anesthetics are essential to safeguard animal welfare during medical investigations. The aim of the study was to assess the adequacy and reliability of an anesthetic protocol and to evaluate physiological and clinical responses, in relation to the drug plasma concentrations, for pigs undergoing short-term anesthesia. A second aim was to see whether an intravenous dosage could prolong the anesthesia. The anesthesia was induced by an intramuscular injection of dexmedetomidine, tiletamine zolazepam, and butorphanol in 12 pigs. In six of the pigs, a repeated injection intravenously of one-third of the initial dose was given after one hour. The physiological and clinical effects from induction to recovery were examined. Plasma concentrations of the drugs were analyzed and pharmacokinetic parameters were calculated. Each drug's absorption and time to maximal concentration were rapid. All pigs were able to maintain spontaneous respiration. The route of administration did not alter the half-life of the drug. The results suggest that intramuscular administration of the four-drug combination provides up to two hours of anesthesia with stable physiological parameters and an acceptable level of analgesia while maintaining spontaneous respiration. A repeated intravenous injection may be used to extend the time of anesthesia by 30 min

The influence of the <it>PRKAG3 </it>mutation on glycogen, enzyme activities and fibre types in different skeletal muscles of exercise trained pigs

Abstract Background AMP-activated protein kinase (AMPK) plays an important role in the regulation of glucose and lipid metabolism in skeletal muscle. Many pigs of Hampshire origin have a naturally occurring dominant mutation in the AMPK γ3 subunit. Pigs carrying this PRKAG3 (R225Q) mutation have, compared to non-carriers, higher muscle glycogen levels and increased oxidative capacity in m. longissimus dorsi, containing mainly type II glycolytic fibres. These metabolic changes resemble those seen when muscles adapt to an increased physical activity level. The aim was to stimulate AMPK by exercise training and study the influence of the PRKAG3 mutation on metabolic and fibre characteristics not only in m. longissimus dorsi, but also in other muscles with different functions. Methods Eight pigs, with the PRKAG3 mutation, and eight pigs without the mutation were exercise trained on a treadmill. One week after the training period muscle samples were obtained after euthanisation from m. biceps femoris, m. longissimus dorsi, m. masseter and m. semitendinosus. Glycogen content was analysed in all these muscles. Enzyme activities were analysed on m. biceps femoris, m. longissimus dorsi, and m. semitendinosus to evaluate the capacity for phosphorylation of glucose and the oxidative and glycolytic capacity. Fibre types were identified with the myosin ATPase method and in m. biceps femoris and m. longissimus dorsi, immunohistochemical methods were also used. Results The carriers of the PRKAG3 mutation had compared to the non-carriers higher muscle glycogen content, increased capacity for phosphorylation of glucose, increased oxidative and decreased glycolytic capacity in m. longissimus dorsi and increased phosphorylase activity in m. biceps femoris and m. longissimus dorsi. No differences between genotypes were seen when fibre type composition was evaluated with the myosin ATPase method. Immunohistochemical methods showed that the carriers compared to the non-carriers had a higher percentage of type II fibres stained with the antibody identifying type IIA and IIX fibres in m. longissimus dorsi and a lower percentage of type IIB fibres in both m. biceps femoris and m. longissimus dorsi. In these muscles the relative area of type IIB fibres was lower in carriers than in non-carriers. Conclusions In exercise-trained pigs, the PRKAG3 mutation influences muscle characteristics and promotes an oxidative phenotype to a varying degree among muscles with different functions.</p