Patricia Hedenqvist

Glioblastomas (GB) are the most common and deadly primary malignant brain tumors due to their infiltrative growth and resistance to conventional therapies. GB cell plasticity and differentiation into drug‐resistant mesenchymal‐like (MES) states protect tumors from conventional treatments. This study introduces a novel precision medicine approach employing heparin‐based nanoparticles (HP‐NPs) engineered to cross the blood‐brain barrier and target MES‐like glioma stem cells (GSCs). Encapsulating doxorubicin (DOX) in HP‐NPs reduces drug‐mediated complement and coagulation cascades, enhancing hemocompatibility in human whole blood. In vitro, HP‐NPs demonstrate efficient uptake by patient‐derived GSCs. Preclinical evaluations in patient avatars indicate plain HP‐NPs outperform DOX‐loaded HP‐NPs in reducing GB progression. Transcriptomic studies show HP‐NPs downregulate heparin‐binding epidermal growth factor (HBEGF), shifting MES GSCs into less plastic astroglial‐like cells, impairing tumorigenesis. HP‐NPs are well‐tolerated and safe at therapeutic doses in healthy rats, offering a promising new paradigm in anticancer therapy to overcome GB recurrence and improve therapeutic outcomes.

Study Design.: Experimental porcine anterior cervical discectomy and fusion (ACDF) model: a proof-of-concept study. Objective.: The effect of monetite synthetic bone graft (SBG) containing calcium pyrophosphate and β-tricalcium phosphate on cervical spinal fusion in a noninstrumented two-level large animal model. Summary of Background Data.: ACDF is the gold standard surgical technique for the treatment of degenerative cervical spinal diseases. However, pseudarthrosis associated with increased patient morbidity occurs in ∼2.6% of the surgeries. SBG may enhance bony fusion and subsequently decrease the risk of pseudarthrosis. Recent studies on monetite-based SBGs for use in large cranial defects in humans have shown promising bone healing results, necessitating further investigation of their use in cervical spinal fusion. Materials and Methods.: Four adult female Danish Göttingen minipigs received partial cervical anterior discectomy and intervertebral defects at an upper and lower level. One defect was filled with SBG, and the other was left empty. Bony fusion was evaluated using computed tomography (CT) at three-month intervals for 12 months. Fifteen months postsurgery, the animals were euthanized for further ex vivo qualitative histopathologic and micro-CT evaluations. Fusion rates were compared using the Fisher exact test at each time point. Results.: Increased interbody bony fusion rates were observed at SBG levels (4/4) compared with control levels (0/4) evaluated by CT at 6 and 9 months postsurgery (P=0.029). Fusion was observed at all SBG levels 12 months postsurgery and at only one control level. Histopathologic evaluation confirmed high-quality interbody bony fusion at all SBG levels and fusion by spondylosis at one control level. Conclusion.: This proof-of-concept study provides preliminary evidence of a novel, calcium pyrophosphate-containing, and β-tricalcium phosphate-containing monetite SBG that promotes bony fusion compared with a negative control in a clinically relevant porcine model of ACDF.

Laboratory animal medicine (LAM) is a corner stone of animal-based research and has been a veterinary specialty for over 60 y. Today 5 Colleges of LAM (American, European, Japanese, Korean, and Indian) that certify specialists (Diplomates) in LAM are members of the International Association of Colleges of LAM (IACLAM). Goals of IACLAM are to support the development of new Colleges of LAM, to harmonize expectations for the knowledge and skills of newly certified LAM Diplomate, and to harmonize the standards (best practices) for training and examination of candidates among the member Colleges. IACLAM recently conducted an in-depth review and comparison of oversight, training, credentialing, and examination standards in the 5 Colleges as part of an initiative to create a framework for harmonization and consistency for these activities across the 5 Colleges. The process has led to an agreement on recommendations for knowledge and skill requirements for a newly certified Diplomate, as described by each College in a detailed role delineation document (RDD). The RDD is based on task analyses of the work responsibilities of laboratory animal veterinary Diplomates. This agreement is an important step toward the goal of global harmonization of LAM Diplomate training. Further efforts are planned for areas such as training, research, publication, and examination. This paper describes the role and content of the RDD and lists the differences and similarities among the RDDs of 5 Colleges of LAM.

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.

An amendment to this paper has been published and can be accessed via the original article.

Background: Buprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01–0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS. Results: The area under the time concentration curve (AUC_0-t) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008). Conclusions: The lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability.