The use of extended-release tacrolimus twice a day might be beneficial for selected kidney transplant recipients: a case report.

The calcineurin inhibitor tacrolimus, which is available as an immediate- or extended-release formulation, is the standard-of-care immunosuppression after kidney transplantation with low rejection rates, especially in the first year after transplantation. However, its highly variable metabolism rate, narrow therapeutic window, and nephrotoxic side effects require close drug monitoring and individual dosing. Here, we describe first the application of extended-release tacrolimus (ER-Tac) twice daily with beneficial effects in a kidney transplant recipient under extensive therapeutic drug monitoring. A 47-year-old female kidney transplant recipient, who was identified as a fast metabolizer for tacrolimus, presented with declining allograft function and low tacrolimus through levels over time and 8 years after a second kidney transplantation despite the administration of high doses of ER-Tac once daily. Therefore, the area under the concentration-time curve (AUC) showed exceedingly high blood levels of ER-Tac. The latest biopsy of the kidney transplant showed arteriolar hyalinosis with pole vessel stenosis as a sign of chronic transplant vasculopathy and transplant glomerulopathy as a sign of chronic humoral rejection. After the exclusion of other options for immunosuppressive therapy due to the patient's high immunological risk, the patient was switched from ER-Tac once daily to ER-Tac twice daily. After switching to ER-Tac twice daily, the AUC for oral tacrolimus decreased and the transplant function improved despite higher tacrolimus trough levels and a lower total dose administered. This case highlights the importance of careful therapeutic drug monitoring with the performance of an AUC in the follow-up management of kidney transplant recipients.

'Do I know you?' Categorizing individuals on the basis of familiarity in kea (Nestor notabilis).

Categorizing individuals on the basis of familiarity is an adaptive way of dealing with the complexity of the social environment. It requires the use of conceptual familiarity and is considered higher order learning. Although, it is common among many species, ecological need might require and facilitate individual differentiation among heterospecifics. This may be true for laboratory populations just as much as for domesticated species and those that live in urban contexts. However, with the exception of a few studies, populations of laboratory animals have generally been given less attention. The study at hand, therefore, addressed the question whether a laboratory population of kea parrots (Nestor notabilis) were able to apply the concept of familiarity to differentiate between human faces in a two-choice discrimination task on the touchscreen. The results illustrated that the laboratory population of kea were indeed able to differentiate between familiar and unfamiliar human faces in a two-choice discrimination task. The results provide novel empirical evidence on abstract categorization capacities in parrots while at the same time providing further evidence of representational insight in kea.

Detection of Local Tissue Reactions after Anti-GnRF Injection in Male Pigs Assessed Using Magnetic Resonance Imaging.

This study aimed at evaluating the local tissue reaction of an anti-GnRF product, which is used for the so called "immunocastration" in male pigs. A total of 34 pigs were injected two times (including a booster injection) with an anti-GnRF product. Injection was performed using the prescribed safety vaccinator. Injection sites were evaluated three times post injection using magnetic resonance imaging. Two examinations were performed after the first injection and one after the booster. The local tissue reaction was evaluated three-dimensionally by semi-automatic analyses, by linear measurements of injection depth and length, and by scoring the kind of tissue affected. Results showed a long-lasting reaction in affected muscle tissue. Therefore, needle length should be discussed, and an evaluation of the injection site after slaughter should be performed include behavioural scorings post injection to evaluate the impact on animal well-being and carcass quality.

"Sex" and body region effects on bone mineralization in male pigs.

Lameness in pigs is one of the major reasons for culling and early losses in pigs. This can be linked to osteoporosis due to pathologic alterations in bone mineral density (BMD) or bone mineral content (BMC) and may also be linked to the sex. Dealing with the ban on piglet castration without anaesthesia in Germany 2021, we have three male "sex" types: entire boars (EB), immunocastrated boars (IB), and surgically castrated boars (SB). The hypothesis of the present study is that BMC or BMD varies between different male sex types. If sex has an effect on bone mineralization (BMC or BMD) and if this affects leg health, it could result in more lameness and problems during fattening in the negatively affected sex type. The present study evaluated bone mineralization (in terms of BMD and BMC) and body composition traits using dual-energy X-ray absorptiometry (DXA) three times during growth at 30, 50, and 90 kg live body weight. Nine body regions were analysed for bone mineral traits and compared for different male sex types and the fattening season. Significant differences were found regarding BMD (and BMC) among EB, IB, and SB for whole-body BMD (BMC). Additionally significant differences were found in the front and lower hind limbs, where SB showed a significantly higher BMD compared to EB, with IB in between. Additionally regional differences were detected among the groups. Further studies are needed to evaluate the effect of these differences in bone mineralization on leg health.

Magnetic resonance imaging to detect local tissue reactions after vaccination in sheep in vivo.

OBJECTIVES: Vaccination is one of the most effective methods to keep up the health status in humans and in livestock. Therefore, farm animals are vaccinated several times during their lifetime. Although vaccines are being checked regarding their local reactogenicity, side effects occur frequently-especially in the case of the application of adjuvanted products. Many reports exist about local reactions in sheep. The present study aimed at testing MRI as a method to document injection site reactions three-dimensionally. DESIGN: Two groups of Merino lambs (n=16 each) were vaccinated subcutaneously into the left neck side. Two different, licensed inactivated vaccines were used. Both groups of lambs were anaesthetised and scanned using MRI at days 1, 3, 8, 15, 22 and 29 after vaccination. SETTING: The study was performed on a commercial-like farm. PARTICIPANTS: Thirty-two Merino lambs entered the experiment, 16 male and 16 female ones (one animal died at day 22 after vaccination). At first examination day they were approximately three months old. PRIMARY AND SECONDARY OUTCOME MEASURES: Volume differences were measured between vaccination and control neck side to evaluate the time pattern of local tissue reactions. RESULTS: Local tissue reactions were visible on the skin surface and also appeared in deeper tissue layers on MRI. These deeper reactions would not have been found without MRI or, alternatively, without sacrificing the animals. Some of these extensive local reactions lasted for more than 29 days. CONCLUSIONS: The in vivo MRI results proved suitable to record local tissue reactions in terms of three-dimensional extent over a longer period of time in large farm animals without the need to sacrifice test animals. A three-dimensional MRI examination of the injection site during regulatory licensing studies offers an objective evaluation that could be used in a benefit-risk assessment of veterinary vaccines. TRIAL REGISTRATION NUMBER: District Government of Upper Bavaria:55.2-1-54-2532-2-13.

Assessment of local reaction to vaccines in live piglets with magnetic resonance imaging compared to histopathology.

The safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction.

Safety testing of veterinary vaccines using magnetic resonance imaging in pigs.

Safety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes amongst others the pathological examination of the injection site in frequent intervals. For this a selected killing of animals in frequent intervals is inevitable. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible inflammatory reactions after vaccination in vivo. Sixty four pigs were subdivided into 4 experimental groups (n=16); two groups consisting of 12 weeks old pigs and 2 of 6 month old pigs at vaccination day. The pigs were vaccinated with four licensed products (each group receiving one vaccine) and examined up to 6 times using MRI during a period of 5 weeks. The MRI images were evaluated semi-automatically comparing the volumes of altered signal intensities at the vaccination side (VS) with the volumes of the signal intensities at the control side (CS). A paired t-Test was used to identify significant differences (p<0.05) between VS and CS. The results show that MRI allows a 3D-quantification of the extent of local reactions in vivo, scanning the same animals at several points of time after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be used as an alternative method to reduce animal numbers for safety testing purposes.