Work for Food – A Solution to Restricting Food Intake in Group Housed Rats?

Rodents spend a great proportion of their time searching for food. The foraging drive in rats is so strong  that the animals readily work for food even when food is freely available. Commonly used ad libitum feeding  is associated with a reduced life span, increased incidence of tumours and risk of liver and kidney diseases.  It is also considered to be the most poorly controlled variable in rodent bioassays. The aim of this  study was to assess whether rats will gnaw wood in order to obtain food hidden in wooden walls, whether  this activity has a beneficial effect on controlling weight gain, and whether a typical diurnal activity rhythm  is maintained. A total of 18 BN/RijHsd and 18 F344/NHsd male rats were housed in either open or individually  ventilated cages (IVC), three rats in each cage. 10 of 36 were fitted with a telemetric transponder.  Four groups were used: two groups (diet board and plain board) with a maze made of two crossed aspen  boards, the third having a rectangular aspen tube. One maze was of plainboard, but the other included  drilled holes snugly loaded with food pellets, the “diet board”, such that the rats had to gnaw wood to reach  the food. The other two groups – and the controls – were fed ad libitum. The study used a crossover design  and the added item was changed every two weeks. Rats, added items, and amount of food left at the end of  the two week period were weighed. The statistical assessment showed that in terms of weight gain there  was a significant interaction both in IVC- (p = 0.005) and in open cages (p < 0.001) between the strains  and the group. In the F344 rats the diet board was more effective in controlling weight, but when combining  the strains, all comparisons with diet board were significant (p < 0.05). Use of strain and added item  as main effects, and age as covariate, showed that in the IVC-system there was a significant (p < 0.001)  interaction between the strain and the group, this effect being rather clear in the F344 rats in terms of  amount of food disappearing. In the open cage system, both strain and group were significant (p < 0.001)  factors; all three comparisons with diet board were significant (p < 0.001) in the amount of food disappearing.  In conclusion, the work-for-food approach appears to be a promising way of avoiding obesity  without causing untoward effects on diurnal activity in rats. Hence, the approach may have considerable  refinement and reduction potential.

Exposure in the Shoebox: Comparison of Physical Environment of IVCs and Open Rat Cages

New caging and innovative items for more structured environment within the cage have been introduced.  Many of these innovations cannot be seen as 'pure' or individual procedures, but rather they represent a  mixed exposure with a multitude of operant factors, some possibly having an impact on animals and  research. One kind of new caging system is the individually ventilated cage (IVC), where each cage  receives its own non-contaminated airflow, primarily designed for health status maintenance and occupational  safety. Even though those cages may be the same as those used in open cage systems, the physical  environment inside the cage may not identical. Comparison between cage types is difficult without characterization  of the physical environment, because the change may involve alterations in several parameters  in the environment. The aim of this study is to characterize and compare common physical parameters in  the ordinary situation, where IVC-racks are kept in the same room with open cages. The cage type used  was a polysulfone solid bottom cage. The parameters measured in this study were: illumination, temperature,  relative humidity (RH) and acoustic level in both IVCs and open top cages. No animals were in the  cages during light intensity, but there was bedding in the cage during acoustic measurements and both bedding  as well as a half-full food hopper during the illumination measurements. The temperature and (RH)  measurements were carried out with three male rats in each cage. There were differences between IVCs  and open top cages in all measured parameters. The light intensity was lower in IVCs, most likely due to  more compact cage placement in the rack and the additional plastic cover lid of the cage. Both maximum  and minimum temperatures were 1-4 oC higher in IVCs; which suggests that their ventilation is incapable  of taking away heat, produced inside the cage. Similarly, the relative humidity was higher in the IVCs. The  sound level adjusted to rat's hearing with R-weighting was higher in IVCs when compared to open cages.  Furthermore, the sound level was highest in the corners next to the ventilation valves. In conclusion, there  may be differences between open cages with IVCs involving several physical parameters of cage environment  and this may confound comparisons between results obtained in these cage systems.

Retinal Temperature Determination Based on Photopic Porcine Electroretinogram

Objective: Subthreshold retinal laser therapy (SLT) is a treatment modality where the temperature of the retinal pigment epithelium (RPE) is briefly elevated to trigger the therapeutic benefits of sublethal heat shock. However, the temperature elevation induced by a laser exposure varies between patients due to individual differences in RPE pigmentation and choroidal perfusion. This study describes an electroretinography (ERG)-based method for controlling the temperature elevation during SLT. Methods: The temperature dependence of the photopic ERG response kinetics were investigated both ex vivo with isolated pig retinas and in vivo with anesthetized pigs by altering the temperature of the subject and recording ERG in different temperatures. A model was created for ERG-based temperature estimation and the feasibility of the model for controlling SLT was assessed through computational simulations. Results: The kinetics of the photopic in vivo flash ERG signaling accelerated between 3.6 and 4.7%/degrees C, depending on the strength of the stimulus. The temperature dependence was 5.0%/degrees C in the entire investigated range of 33 to 44 degrees C in ex vivo ERG. The simulations showed that the method is suitable for determining the steady-state temperature elevation in SLT treatments with a sufficiently long laser exposure and large spot size, e.g., during > 30 s laser exposures with > 3 mm stimulus spot diameter. Conclusions: The described ERG-based temperature estimation model could be used to control SLT treatments such as transpupillary thermotherapy. Significance: The introduced ERG-based method for controlling SLT could improve the repeatability, safety, and efficacy of the treatment of various retinal disorders.Peer reviewe

Refinement and Reduction Value of Aspen Furniture and Restricted Feeding of Rats in Conventional Cages

This study evaluated the impact of aspen furniture on cardiovascular parameters, locomotor activity (LA) and faecal welfare indicators in rats. A total of 12 BN and 12 F344 male rats were group housed (n=3) in conventional cages. In this crossover study, responses of all rats to the following cage furniture items were investigated: two types of simple maze, a rectangular tube and a control with no cage furniture. In one of the two maze groups, the rats had to gnaw through wood in order to obtain food. The mean values of the LA in all groups and differences in mean arterial pressure (MAP) and heart rate of the rats housed in the various furniture item groups were compared to the values of the rats housed in control cages with no furniture, on days two, six, ten and 14 in each period (both light and dark phases). The F344 rats were generally more active than the BN rats during the dark phase, but not during the light phase. Based on the MAP results, the tube appeared to be a poor choice for F344 rats, while for BN rats all furniture items seemed beneficial, with both board types apparently superior to the tube. In general, F344 rats had higher faecal corticosterone levels than BN rats with the reverse being true for secretory IgA values. In conclusion, LA and cardiovascular parameters seemed appropriate ways to evaluate the impact of cage furniture on physiological parameters, and covered structures such as tubes do not seem to provide any enrichment value in these two rat strains

Atrial fibrillation and stroke – Coexistence and attitude to preventive therapy on the basis of Szczecin and Szczecin region patients

Atrial fibrillation (AF) is an independent factor increasing the risk of an ischemic stroke (IS) fivefold. The objective of the study was to evaluate the frequency of coexistence of non-valvular AF and IS during the acute stroke and to analyze the attitude of AF patients to treatment. The study included 3712 successive patients presenting either an IS or a transient ischemic attack. The analysis revealed a significant increase in the rate of patients with AF and IS in the years 2010–2013 (31.9%) compared with 2002–2005 (20.2%). A rise in the proportion of AF and IS patients was recorded over the course of consecutive years in group II. The proportion of newly detected AF cases during hospital stay differed significantly between the groups (16.9% vs. 31.9%). Group I and II patients differed essentially with regards to hypertension incidence and female rates. Antiplatelet medications or OACs were taken by a significantly greater number of AF patients in group II. Low number of therapeutic levels of INR was recorded in both groups. IS and AF coexist more frequently than indicated by previous assessments and demographic data from other countries. Increase in the number of IS and AF patients may result from higher detectability of AF and older age of patients affected with stroke, women in particular. Despite a well grounded knowledge about the benefits of OACs use in the prophylaxis of thrombotic-embolic events in AF patients, they are rarely used. A surprisingly low proportion of patients taking OACs reaches a therapeutic INR level

Arthroscopic International Cartilage Repair Society Classification System Has Only Moderate Reliability in a Porcine Cartilage Repair Model

Background: The International Cartilage Repair Society (ICRS) score was designed for arthroscopic use to evaluate the quality of cartilage repair. Purpose: To evaluate the reliability of the ICRS scoring system using an animal cartilage repair model. Study Design: Controlled laboratory study. Methods: A chondral defect with an area of 1.5 cm(2) was made in the medial femoral condyle of 18 domestic pigs. Five weeks later, 9 pigs were treated using a novel recombinant human type III collagen/polylactide scaffold, and 9 were left to heal spontaneously. After 4 months, the pigs were sacrificed, then 3 arthroscopic surgeons evaluated the medial femoral condyles via video-recorded simulated arthroscopy using the ICRS scoring system. The surgeons repeated the evaluation twice within a 9-month period using their recorded arthroscopy. Results: The porcine cartilage repair model produced cartilage repair tissue of poor to good quality. The mean ICRS total scores for all observations were 6.6 (SD, 2.6) in arthroscopy, 5.9 (SD, 2.7) in the first reevaluation, and 6.2 (SD, 2.8) in the second reevaluation. The interrater reliability with the intraclass correlation coefficient (ICC) for the ICRS total scores (ICC, 0.46-0.60) and for each individual subscore (ICC, 0.26-0.71) showed poor to moderate reliability. The intrarater reliability with the ICC also showed poor to moderate reliability for ICRS total scores (ICC, 0.52-0.59) and for each individual subscore (ICC, 0.29-0.58). A modified Bland-Altman plot for the initial arthroscopy and for the 2 reevaluations showed an evident disagreement among the observers. Conclusion: In an animal cartilage repair model, the ICRS scoring system seems to have poor to moderate reliability.Peer reviewe

Comparison Between Arthroscopic and Histological International Cartilage Repair Society Scoring Systems in Porcine Cartilage Repair Model : h

Objective The arthroscopic and histological International Cartilage Repair Society (ICRS) scores are designed to evaluate cartilage repair quality. Arthroscopic ICRS score can give a maximum score of 12 and the histological score can give values between 0% and 100% for each of its 14 subscores. This study compares these methods in an animal cartilage repair model. This study hypothesizes that there is a significant correlation between these methods. Design A chondral defect was made in the medial femoral condyle of 18 pigs. Five weeks later, 9 pigs were treated with a novel recombinant human type III collagen/polylactide scaffold and 9 were left untreated to heal spontaneously. After 4 months, the medial condyles were evaluated with a simulated arthroscopy using the ICRS scoring system followed by a histological ICRS scoring. Results This porcine cartilage repair model produced repaired cartilage tissue ranging from good to poor repair tissue quality. The mean arthroscopic ICRS total score was 6.8 (SD = 2.2). Histological ICRS overall assessment subscore was 38.2 (SD = 31.1) and histological ICRS average points were 60.5 (SD = 19.5). Arthroscopic ICRS compared with histological ICRS average points or its overall assessment subscore showed moderate correlation (r = 0.49 and r = 0.50, respectively). The interrater reliability with the intraclass correlation coefficients for arthroscopic ICRS total scores, histological ICRS overall assessment subscore, and ICRS average points showed moderate to excellent reliability. Conclusions Arthroscopic and histological ICRS scoring methods for repaired articular cartilage show a moderate correlation in the animal cartilage repair model.Peer reviewe

Concentrations of vatinoxan and xylazine in plasma, cerebrospinal fluid and brain tissue following intravenous administration in sheep

Objectives To investigate the extent of vatinoxan distribution into sheep brain, and whether vatinoxan influences brain concentrations of xylazine; and to examine the utility of cerebrospinal fluid (CSF) as a surrogate of brain tissue concentrations for vatinoxan and xylazine. Study design Randomised, blinded, experimental study. Animals A total of 14 adult female sheep. Methods Sheep were randomly allocated into two equal groups and premeditated with either intravenous (IV) vatinoxan (750 mu g kg(-1), VX) or saline (SX) administered 10 minutes before IV xylazine (500 mu g kg(-1)). Sedation was subjectively assessed at selected intervals before and after treatments. At 10 minutes after xylazine administration, a venous blood sample was collected and the sheep were immediately euthanised with IV pentobarbital (100 mg kg(-1)). Plasma, CSF and brain tissues were harvested, and concentrations of vatinoxan and xylazine were quantified using liquid chromatography-tandem mass spectrometry. Drug ratios were then calculated and the data were analysed as appropriate. Results The brain-to-plasma and CSF-to-plasma ratios of vatinoxan were 0.06 +/- 0.013 and 0.05 +/- 0.01 (mean +/- standard deviation), respectively. Xylazine brain concentrations were not significantly different (835 +/- 262 versus 1029 +/- 297 ng g(-1) in groups VX and SX, respectively) and were approximately 15-fold higher than those in plasma. The CSF-to-brain ratio of vatinoxan was 0.8 +/- 0.2, whereas xylazine concentrations in the brain were approximately 17-fold greater than those in CSF, with and without vatinoxan. Conclusions and clinical relevance Vatinoxan did not significantly affect sedation with xylazine or the concentrations of xylazine in the brain. CSF is not a good predictor of xylazine concentrations in the brain, whereas vatinoxan concentrations were concordant between the brain and CSF, using the dosages in this study.Peer reviewe

Effects of vatinoxan on xylazine-induced pulmonary alterations in sheep

It was hypothesized that premedication with vatinoxan, a peripheral alpha(2)-adrenoceptor antagonist, would mitigate xylazine-induced pulmonary alterations in sheep. Fourteen adult sheep were allotted into two equal groups and premedicated with either vatinoxan (750 mu g/kg IV) or saline and sedated 10 min later with xylazine (500 mu g/kg IV). Arterial oxygen saturation (SpO(2)) was measured and respiratory rate (RR) counted at intervals. The sheep were euthanized with IV pentobarbital 10 min after xylazine administration. The severity of pulmonary parenchymal alterations was assessed and graded grossly and histologically and correlations of the morphological changes with SpO(2) evaluated. Following xylazine injection, SpO(2) was significantly higher and RR significantly lower with vatinoxan than with saline and the sheep administered vatinoxan exhibited significantly smaller quantities of tracheal foam than those receiving saline. No significant differences in macroscopic oedema scores were detected between treatments. In contrast, the vatinoxan-treated animals exhibited significantly graver microscopic interstitial alveolar oedema and haemorrhage than saline-treated animals. The histological severity scores did not correlate with changes in SpO(2). In conclusion, xylazine induced a marked reduction in SpO(2) which was abolished by the prior administration of vatinoxan. The histologically detected alterations after pentobarbital euthanasia with vatinoxan premedication need to be studied further.Peer reviewe

Phage Treatment Trial to Eradicate LA-MRSA from Healthy Carrier Pigs

The increase of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) causes a threat to human health. LA-MRSA can be transmitted from animals to animal caretakers, which may further spread MRSA to communities and health care facilities. The objective of this work was to study the efficacy of phage treatment in the eradication of LA-MRSA from healthy carrier pigs. A total of 19 MRSA -positive weanling pigs were assigned to a test (n = 10) and a control group (n = 9). A phage cocktail containing three Staphylococcus phages, or a control buffer was administered to the nares and skin of the pigs three times every two days, after which the phage and MRSA levels in nasal and skin swab samples were monitored for a three-week period. The sensitivity of the strains isolated during the follow-up period to the phage cocktail and each phage individually was analyzed and the pig sera were tested for antibodies against the phages used in the cocktail. The phage treatment did not cause any side effects to the pigs. Phages were found in the skin and nasal samples on the days following the phage applications, but there was no reduction in the MRSA levels in the sampled animals. Phage-resistant strains or phage-specific antibodies were not detected during the experiment. The MRSA load in these healthy carrier animals was only 10–100 CFU/swab or nasal sample, which was likely below the replication threshold of phages. The effectiveness of phage treatment to eradicate MRSA from the pigs could thus not be (reliably) determined