IACUC Research Articles

Iron Chelators Augment Large Osteochondral Allograft Osseointegration in a Preclinical Canine Model.

Osteochondral allograft transplantation (OCAT) can be a successful joint restoration treatment option for large post-traumatic articular defects but is still associated with significant revision and failure rates. Despite recent advances that have improved OCAT success, insufficient osteochondral allograft (OCA) osseointegration remains a major cause of failure. Deferoxamine (DFO) is an effective angiogenic and osteo-anabolic iron chelator that consistently promotes bone neovascularization and regeneration. This study was designed to investigate local delivery of DFO for augmenting OCA osseointegration using a preclinical canine model for OCAT in the knee and hip as commonly affected joints. On Institutional Animal Care and Use Committee (IACUC) approval, 12 purpose-bred dogs underwent OCAT of the femoral head or femoral condyles with DFO or DFO-free (controls) microspheres in recipient sites. OCA revascularization, cellular repopulation, and integration were evaluated based on functional, diagnostic imaging, microcomputed tomography, histology, and immunohistochemistry outcome measures. Local delivery of DFO into OCAT recipient sites was associated with maintained or improved joint function, superior radiographic appearance, significantly greater trabecular thickness, higher bone volume, and new bone ingrowth compared with DFO-free controls. OCA osseointegration is dependent on cellular repopulation and neovascularization, resulting in new bone ingrowth through creeping substitution, and insufficient osseointegration with resorption and subsidence of the OCA remains a major cause of failure after transplantation. The results of this study suggest that local delivery of DFO using a controlled microsphere release system may reduce resorption and improve revascularization and cellular repopulation to increase new bone ingrowth, potentially expediting OCA osseointegration after transplantation.

Comparative Electroencephalographic Profile of a New Anesthetic and Anticonvulsant That Is Selective for the GABAAR Slow Receptor Subtype.

Anesthetics like propofol increase electroencephalography (EEG) power in delta frequencies (0.1-4 Hz), with a decrease of power in bandwidths >30 Hz. Propofol is nonselective for gamma amino butyric acid type A receptor subtypes (GABAAR) as it enhances all 3 GABAAR subtypes (slow, fast, and tonic). Our newly developed anesthetic class selectively targets GABAAR-slow synapses to depress brain responsiveness. We hypothesized that a selective GABAAR-slow agonist, KSEB 01-S2, would produce a different EEG signature compared to the broad-spectrum GABAAR agonist (propofol), and tested this using rat EEG recordings. Male rats were studied after Institutional Animal Care and Use Committees (IACUC) approval from the US Army Medical Research Institute of Chemical Defense and the University of Michigan. Rats were anesthetized using isoflurane (3%-5% induction, 1%-3% maintenance) with oxygen at 0.5 to 1.0 L/min. Stainless steel screws were placed in the skull and used to record subcranial cortical EEG signals. After recovery, either propofol or KSEB 01-S2 was administered and effects on EEG signals were analyzed. As previously reported, propofol produced increased power in delta frequencies (0.1-4 Hz) compared to predrug recordings and produced a decrease in EEG power >30 Hz but no significant changes were seen within ±20 seconds of losing the righting reflex. By contrast, KSEB 01-S2 produced a significant increase in theta frequency percent power (median 14.7%, 16.2/13.8, 75/25 confidence interval; to 34.7%, 35/31.8; P < .015) and a significant decrease in low gamma frequency percent power (16.9%, 18.6/15.8; to 5.45%, 5.5/5.39; P < .015) for all rats at ± 20 seconds of loss of consciousness (LOC). Both anesthetics produced a flattening of chaotic attractor plots from nonlinear dynamic analyses, like that produced by volatile and dissociative anesthetics at LOC. KSEB 01-S2 produced a markedly different EEG pattern, with a selective increase observed in the theta frequency range. KSEB 01-S2 also differs markedly in its activity at the GABAAR-slow receptor subtype, suggesting a possible mechanistic link between receptor subtype specificity and EEG frequency band signatures. Increased theta together with depressed gamma frequencies is interesting because GABAAR slow synapses have previously been suggested to underlie theta frequency oscillations, while fast synapses control gamma activity. These reciprocal effects support a previous model for theta and nested gamma oscillations based on inhibitory connections between GABAAR fast and slow interneurons. Although each anesthetic produced a unique EEG response, propofol and KSEB 01-S2 both increased slow wave activity and flattened chaotic attractor plots at the point of LOC.

According to Which Criteria Should We Determine Whether and When IACUCs Are Sufficient for Protecting the Welfare of Nonhuman Animals Used in Research?

Nonhuman animals used in biomedical research frequently suffer and are harmed as part of their use as experimental models. The Institutional Animal Care and Use Committee (IACUC) of a given institution is meant to ensure that research protocols follow federal guidelines, but research protocols such as those described in this case can generate unnecessary suffering; this problem suggests limitations of IACUCs' capacity to protect nonhuman animals' welfare. This commentary on the case considers how to more fully protect nonhuman animals used in scientific research and identifies barriers to more comprehensive protection of nonhuman animals' welfare.

The partnership between statisticians and the Institutional Animal Care and Use Committee (IACUC)

AbstractIn this tutorial we explore the valuable partnership between statisticians and Institutional Animal Care and Use Committees (IACUCs) in the context of animal research, shedding light on the critical role statisticians play in ensuring the ethical and scientifically rigorous use of animals in research. Pharmaceutical statisticians have increasingly become vital members of these committees, contributing expertise in study design, data analysis, and interpretation, and working more generally to facilitate the integration of good statistical practices into experimental procedures. We review the “3Rs” principles (Replacement, Reduction, and Refinement) which are the foundation for the humane use of animals in scientific research, and how statisticians can partner with IACUC to help ensure robust and reproducible research while adhering to the 3Rs principles. We also highlight emerging areas of interest, such as the use of virtual control groups.

Multispecies comparative prostate anatomy by imaging: Implications for experimental models of prostatic disease.

There is an increasing interest in using preclinical models for development and assessment of medical devices and imaging techniques for prostatic disease care. Still, a comprehensive assessment of the prostate's radiological anatomy in primary preclinical models such as dogs, rabbits, and mice utilizing human anatomy as a reference point remains necessary with no optimal model for each purpose being clearly defined in the literature. Therefore, this study compares the anatomical characteristics of different animal models to the human prostatic gland from the imaging perspective. We imaged five Beagle laboratory dogs, five New Zealand White rabbits, and five mice, all sexually mature males, under Institutional Animal Care and Use Committee (IACUC) approval. Ultrasonography (US) was performed using the Vevo® F2 for mice (57 MHz probe). Rabbits and dogs were imaged using the Siemens® Acuson S3000 (17 MHz probe) and endocavitary (8 MHz) probes, respectively. Magnetic resonance imaging (MRI) was also conducted with a 7T scanner in mice and 3T scanner in rabbits and dogs. Canine transrectal US emerged as the optimal method for US imaging, depicting a morphologically similar gland to humans but lacking echoic zonal differentiation. MRI findings in canines indicated a homogeneously structured gland similar to the human peripheral zone on T2-weighted images (T2W) and apparent diffusion coefficient (ADC). In rabbits, US imaging faced challenges due to the pubic symphysis, whereas MRI effectively visualized all structures with the prostate presenting a similar aspect to the human peripheral gland on T2W and ADC maps. Murine prostate assessment revealed poor visualization of the prostate glands in ultrasound due to its small size, while 7T MRI delineated the distinct prostates and its lobes, with the lateral and dorsal prostate resembling the peripheral zone and the anterior prostate the central zone of the human gland. Dogs stand out as superior models for advanced preclinical studies in prostatic disease research. However, mice present as a good model for early stage studies and rabbits are a cost-effective alternative and serve as valuable tools in specific research domains when canine research is not feasible.

A survey of the impact of COVID-19 on the management of animal experiments and laboratory animal facilities in Korea.

The pandemic has affected the lives of people all over the world. The effects of the pandemic on laboratory animal facilities and their operations through this unusual global event are poorly understood. Here, we have applied a methodological framework of qualitative approach including semi-structured interviews to investigate laboratory animal operations in Korea and how it has shaped the on-going management and laboratory operations of such facilities. A total of fifty-two individuals, including members and administrators of the Institutional Animal Care and Use Committee (IACUC), researchers, and animal facility managers and staff, were surveyed through purposeful sampling. Survey questions explored how the pandemic impacted the IACUC and the functioning of animal facilities, and what steps to take in preparation of a future pandemic-like crisis. Our survey found evidence of an increase in animal experiments in Korea during the pandemic that correlated with increases in research funding during that period, such as for vaccine development. Also, operational challenges due to pandemic-related health issues in personnel were resolved through overtime, rather than by reducing facility operations. Moreover, a refinement of post-approval monitoring (PAM) practices was also discussed by respondents. Taken together, our study offers insights into animal facility operations during the pandemic and outlines recommendations for safeguarding operations in such future scenarios.

Development of Two Korean IACUC Guidance Documents to Foster Implementation of the Three Rs.

In Korea, Institutional Animal Care and Use Committees (IACUCs) have been legally required to apply the Three Rs principles (i.e. replacement, reduction and refinement) and undertake the ethical review of animal study protocols, since 2008. According to Korean law, each IACUC is required to appoint at least one lay member recommended by a non-governmental animal protection organisation, who participates in the ethical review process as part of this role. Despite the importance of the Three Rs and the ethical review process, limited information and practical resources are available for IACUC members in the Korean language, particularly for lay members who are inexperienced in animal experimentation. In January 2020, the Animal and Plant Quarantine Agency announced the funding for a six-month research project to develop guidance to assist IACUC members in carrying out effective and efficient protocol reviews in line with Korean legislative requirements. This funding was awarded for the production of two IACUC guidance documents - 'Guide for Animal Study Protocols' and 'Guide for the IACUC Lay Member' - which were published in December 2020. These guidance documents aim to foster the implementation of the Three Rs and provide practical resources for IACUC members, researchers and other relevant personnel. This paper describes the framework for animal use in Korea and the overall production of these two IACUC Guidance Documents.

Differentiating research from management in welfare review of wildlife activities

AbstractA common understanding and clear process to apply the Animal Welfare Act (AWA) to wildlife‐related activities is crucial to promote animal welfare when conducting wildlife research and for streamlining review by an Institutional Animal Care and Use Committee (IACUC). Current interpretation of the AWA and United States government policies advise that wildlife research activities be reviewed for compliance by an IACUC; however, guidance regarding which wildlife activities are categorized as research and therefore subject to review and oversight is limited. In our opinion and experience, this lack of clarity creates a challenge, particularly for natural resource agencies that conduct a range of wildlife activities, to ensure that research is properly identified for IACUC review and differentiated from management activities that are exempt from review. To fill the gap in current guidance, we propose a decision‐making model that clarifies research and management activities. We apply our model to case studies involving wildlife to highlight nuanced differences between the 2 types of activities. Wildlife agencies conducting potentially regulated activities could use this adaptable model, which has been successfully employed by the National Park Service IACUC, to clarify when the AWA might apply, streamline IACUC reviews, and promote welfare of wildlife.

Librarians and Research Integrity Committees: Finding professional joy and fulfillment in practice and service

This article describes how librarians can benefit from being members of research integrity committees. As two academic librarians, the authors share the ways that they have found professional fulfillment and joy through service on the Institutional Animal Care and Use Committee (IACUC) for vertebrate animal research activities and the Institutional Review Board (IRB) for human subjects research. Their participation on research integrity committees has provided opportunities to build new relationships, demonstrate their expertise, and find meaning in their contributions to research production. Participation on the IACUC has allowed one author to better understand research designs and instrumentation and laboratory techniques. She has built new relationships with research administrators, scientists, and lab managers, and found new opportunities to use her unique search skills. The other author, while serving on the IRB, has extended her professional network and highlighted her expertise as a qualitative researcher. She has built stronger relationships with research administrators and scholars and found new opportunities for advancing responsible data management conversations across campus. Participating in these committees has been professionally empowering and has allowed the authors to contribute to research integrity in important ways.&amp;nbsp;

Jaboticaba (Myrciaria cauliflora) Fruit Extract Suppressed Aberrant Crypt Formation in 1,2-Dimetylhydrazine-Induced Rats.

Early intervention can significantly improve the colorectal cancer survival rate. Foods rich in phenolic compounds, such as jaboticaba (Myrciaria cauliflora), may prevent tumorigenesis. We investigated the effectivity of jaboticaba whole fruit ethanolic extract (FEX) in suppressing aberrant crypt foci (ACF), the earliest lesion of colorectal cancer (CRC), in 1,2-dimethylhydrazine (DMH)-induced rats and the underlying mechanisms related to the gut microbiota composition and short chain fatty acid (SCFA). This study was approved by the Institutional Animal Care and Use Committee (IACUC) of Providence University (Trial Registration Number 20180419A01, registration date: 22 December 2018). The FEX contains gallic acid and an especially high ellagic acid concentration of 54.41 ± 1.80 and 209.79 ± 2.49mg/100g FEX. The highest total ACF number (150.00 ± 43.86) was recorded in the DMH control (D) group. After 56 days of oral FEX treatment, the total ACF number in the low FEX dosage (DL) group was significantly lower compared to the D group (p < 0.05). The large-sized ACF (> 5 foci), which has a higher probability of progressing to later stage, was significantly decreased in the high FEX dosage (DH) group. The 16s rDNA metagenomic sequencing of the cecal material revealed that the CRC biomarker Lachnoclostridium was significantly suppressed in the DH group (p < 0.05), whereas some SCFA-producing taxa and the cecal butyrate concentration were significantly elevated in the DL and DH groups (p < 0.05). This study demonstrated the potential of jaboticaba whole fruit in CRC prevention, especially in the initial stage, by shifting gut microbiota composition and improving cecal butyrate level.

Potential problems and solutions of opioid-based treatment in neonatal opioid withdrawal syndrome (NOWS): a scoping review protocol

IntroductionRates of neonatal opioid withdrawal syndrome (NOWS) have paralleled the rise of opioid use during pregnancy. While short-term phenotypic symptoms of NOWS are well defined, molecular implications and long-term effects...

OCE-205 in rats and non-human primates: Pharmacokinetic and pharmacodynamic analysis

Treatment for complications associated with the hemodynamic consequences of decompensated cirrhosis remains suboptimal. Terlipressin, the latest pharmacological management of hepatorenal syndrome–acute kidney injury (HRS-AKI), targets the vasopressin system but has serious side effects. OCE-205 is a novel peptide designed to target the vasopressin receptor system as a mixed V1a agonist/antagonist, resulting in effective partial agonism without V2 agonism. We examined the in vivo pharmacokinetic/pharmacodynamic properties of OCE-205 in healthy rats and cynomolgus monkeys. OCE-205 was administered by IV or SC bolus injection; arginine vasopressin (AVP) or terlipressin were comparators. After IV OCE-205 administration in rats, mean plasma concentration decreased in a mostly linear manner to 2 mg/mL after 120 min, and for SC administration, slowly decreased to ∼50 ng/mL after 300 min. Compared with pre-test values, arterial blood pressure values significantly increased after all OCE-205 doses tested. For monkeys, the concentration after IV OCE-205 administration was mostly linear to 5 ng/mL after 180 min, and for SC administration, ∼3 ng/mL after 480 min. Subcutaneous OCE-205 administration increased mean arterial pressure (MAP) versus baseline, with ΔMAP in OCE-205–treated animals marked and long-lasting while terlipressin induced an increase from baseline in MAP, with negligible ΔMAP, on average, by 150 min after administration in all groups. AVP, but not OCE-205, significantly increased blood lactate concentrations. OCE-205 was well tolerated in adult male rats and cynomolgus monkeys following single-dose bolus administration. The preclinical results of OCE-205, with its demonstrated V1a selective partial agonist activity and potentially tolerable safety profile, suggest its potential utility for treatment of the cardiovascular complications of cirrhosis. Institutional protocol numberProcedures were approved by the Ferring Research Institute (FRI) Institutional Animal Care and Use Committee (IACUC) on November 27, 2006 under protocol FRI 06-011, and by the Sinclair Research Center IACUC under protocol S11177.

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

A Cleavable Self-Inclusion Conjugate with Enhanced Biocompatibility and Antitumor Bioactivity

THE STUDY ON THE EFFECT OF ARTIFICIAL OSTEOPOROSIS CREATED BY COMBINED OVARIECTOMY AND CALCIUM-RESTRICTED DIETS IN A PORCINE MODEL

This study design is to evaluate the mid-term changes in bone mineral density (BMD) with combined calcium-restricted and ovariectomized miniature porcine models as a large animal model in osteoporosis. The combined old practice hangs on for almost 30 years. Four 6-month-old (T0) female miniature pigs were enrolled in this study. The pigs were fed a normal diet prior to the ovariectomy at the age of 1 year and 3 months (T1) but switched to a diet with restricted calcium content afterwards. Each of the pigs received dual-energy X-ray absorptiometry (DXA) once before ovariectomy, and once every three months (T2, T3, T4) after the ovariectomy to evaluate the changes in BMD. The body weight of all four subject pigs increased significantly during this study ([Formula: see text]). The initial changes in both the BMD levels (T1/T2) were found to be statistically insignificant ([Formula: see text] and [Formula: see text], respectively). However, upon comparison of later BMD changes (T3/T4, T1/T3 and T1/T4), statistically significant elevations were found ([Formula: see text] for all three comparisons). Ovariectomy and calcium-restricted diets are ineffective in achieving an osteoporotic porcine model based on BMD assessments. BMD levels of the subject pigs continued to rise until the point at which body growth had stopped because the ideal pigs for surgical experiments were far from maturity. This finding is not unexpected; after all, the subject pigs are not senile. Without violations of the physiology and Institutional Animal Care and Use Committee (IACUC) regulations, moreover, pigs could be fed by strictly calcium-restricted diets or deprived of soybean component feed. Furthermore, the alternative protocols in osteoporotic porcine model shall perform experiments as soon as possible after ovariectomy. We should take other studies about artificial osteoporotic pigs more into consideration whether it is based on a rational method.

Listeria-Based Vaccines Targeting Interferon-Stimulated Gene 15 (ISG15) for Renal Cell Carcinoma and Colorectal Cancer

<h3>Purpose/Objective(s)</h3> Interferon-stimulated gene 15 (ISG15) is the first identified ubiquitin-like modifier and has been implicated for its central role in innate immunity against intracellular pathogens. Since cancer cells oftentimes have defects in type I IFN signaling pathways, there is a growing body of evidence that demonstrated the role of ISG15 in cancer progression. Here, we investigate to understand if ISG15 could be another novel cancer-associated antigen in renal cell carcinomas (RCC) and colorectal cancer (CRC). Our research objectives include (i) to identify if the elevated expression of ISG15 in RCC and CRC has any prognosis signature, (ii) to explore if ISG15 can be targeted by mean of Listeria-based vaccines, and (iii) to analyze how Listeria-based vaccines targeting ISG15 change the tumor microenvironment of RCC and CRC in syngeneic mouse models. <h3>Materials/Methods</h3> Data on RNA and protein expression of ISG15 and the Kaplan–Meier survival analysis was obtained from Human Protein Atlas, The Cancer Genome Atlas, and from the University of Alabama at Birmingham, Comprehensive Cancer Center (UALCAN). RNA was extracted from tissue or cells and converted to cDNA. The cDNA was then subjected to qPCR analysis with primers specific to ISG15. All mouse experiments were performed in accordance with the regulations of the Institutional Animal Care and Use Committee (IACUC) at the TTUHSC. <h3>Results</h3> We found that the elevated expression of ISG15 in RCC and CRC is significantly associated with an unfavorable prognosis. Similarly, RCC and CRC murine cell lines also expressed a higher level of ISG15 compared to the normal fibroblast cell line. In subcutaneous syngeneic mouse models of RCC and CRC, vaccination with a Listeria-based vaccine targeting ISG15, designated Lm-LLO-ISG15, significantly controls primary tumor burden and extends median survival compared to control groups. In both models, treatment with Lm-LLO-ISG15 inflames the tumor microenvironment, enhances the influx of immune cells, and induces the expression of programmed cell death protein 1 (PD-1). <h3>Conclusion</h3> ISG15 is a novel cancer-associated antigen and a potential target for active immunotherapies such as Listeria-based vaccines. Treatment with Lm-LLO-ISG15 significantly controls tumor burden in both RCC and CRC syngeneic mouse models and sensitizes the tumors with anti-PD-1 therapies.

104. Effects of cannabinoids on spinal fusion in a rat model

<h3>BACKGROUND CONTEXT</h3> The opioid epidemic is a public health crisis causing significant morbidity, mortality and economic costs nationwide. As a result, discovering alternative forms of pain management is becoming imperative. Medical marijuana is an option for a nonopioid analgesic and is under investigation for potential uses in fields such as oncology and chronic pain, but it is yet to be studied in the surgical setting. Specifically, its effects on bone healing are not fully understood, significantly affecting its potential analgesic efficacy for postorthopaedic surgical care. <h3>PURPOSE</h3> The goal of this this study is to determine the effect of cannabis derivatives, D9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on bone healing. The effects of marijuana on spinal arthrodesis specifically have yet to be investigated. We hypothesized that THC and CBD will not decrease bone healing in a rat model for spinal fusion. <h3>STUDY DESIGN/SETTING</h3> A basic science study utilizing a validated experimental model to assess spinal fusion performed on rats. <h3>PATIENT SAMPLE</h3> N/A (Sprague-Dawley rats were used for this basic science study). <h3>OUTCOME MEASURES</h3> Manual palpation was done to assess strength of the L4-L5 arthrodesis on all rats. Twelve rats underwent lumbar three-dimensional micro-computed tomography (μCT) imaging and histological analysis. The remaining half were subjected to quantitative polymerase chain reaction (qPCR) analyses which are currently pending. The μCT bone analysis was comprised of quantifying the ratio of bone volume (BV) to total volume (TV) within each volume of interest (VOI), as well as bone mineral density (BMD) and tissue mineral density (TMD) for the corresponding VOI. During follow-up, one animal from the saline and one from the combination group were lost due to wound dehiscence. Kruskal-Wallis test followed by Dunn's multiple comparisons test was performed using GraphPad Prism. Two-tailed values of p < 0.05 were considered statistically significant. <h3>METHODS</h3> Animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC). Twenty-eight adult Sprague-Dawley rats were used for this study. Utilizing allogenic bone graft (4 donor rats), posterolateral inter-transverse lumbar fusion at the L4-L5 level was performed under surgical microscopy. The animals were divided into four groups of 6, each receiving 0.1ml intraperitoneal injections weekly as follows: placebo (saline), 5 mg/kg THC, 5 mg/kg CBD, and a combination of 5 mg/kg THC and 5 mg/kg CBD (combo). Eight weeks postsurgery, animals were euthanized and fusions were assessed. <h3>RESULTS</h3> The combination treatment group had the highest fusion rates, with 66.7% demonstrating full fusion and 33.3% demonstrating partial fusion. This was followed by the THC group demonstrating 60% of rats with full fusion, 20% with partial fusion, and 20% with no fusion. Fusion rates were lower in the CBD and saline groups. However, the fusion rates were not significantly different between the treatment groups based on our manual palpation scoring. Callus formation was visually more extensive in THC and Combo treatments on μCT 3D reconstruction images. This observation was confirmed though μCT data, in which bone volume fraction (BV/TV) was significantly higher for the CBD and THC treatment groups compared to the saline treatment group (P <0.05). BMD and TMD values were higher for all cannabis treatment groups compared to the saline treatment group, though not statistically significant. <h3>CONCLUSIONS</h3> This study preliminarily demonstrates that CBD and THC have no adverse effect on bone regeneration and rate of spinal fusion in rats. Cannabinoids may possess osteoinductive properties which require further investigation. Future larger animal studies should further investigate the effects of cannabinoid receptor agonists on bone healing and formation, with additional exploration of cannabinoid receptor agonists as a potential alternative approach to postoperative analgesia following spinal fusion and other procedures requiring bone formation. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Guideline for Vascular Access Port Use and Maintenance in Large Animals for Biomedical Research

Purpose Vascular Access Ports (VAPs) consist of an indwelling catheter connected to an implanted port that provides direct access for sample collection or infusion. The use of VAPs in biomedical research reduces trauma on vessels from repeated venipuncture, decreases secondary infections, promotes social housing and animal welfare, and increases the accuracy and efficiency of study procedures. In addition to enabling comprehensive data collection, VAPs increase satisfaction, and well-being by minimizing interference with daily routines and fostering cooperation. The responsible use of VAPs includes approval by the institutional animal care and use committee (IACUC), verification of the surgeon′s skill and experience, and confirmation that research staff are trained on the proper maintenance and access techniques. This document aims to provide surgeons, researchers and research staff, veterinary staff, and IACUCs with guidelines for implanting, maintaining, accessing, and troubleshooting vascular access ports in large animal species. (Rabbit, Canine, Feline, Nonhuman Primate, Porcine).

Improvement plans on the operation of the Institutional Animal Care and Use Committee: focusing on the case of Seoul National University

BackgroundThe Institutional Animal Care and Use Committee (IACUC) became compulsory in 2008 by the Animal Protection Act in Korea. Seoul National University (SNU), which conducts 5% of Korea’s total animal protocol reviews and uses 10% of national laboratory animal usage, has been influential in the review of animal protocols and management of animal facilities. This study was undertaken to suggest the operational improvement of the IACUC. It focused on the case of SNU.ResultsThe methodological framework consists of a qualitative approach. In particular, this study is focused on the grounded theory approach and sixty people were surveyed through purposeful sampling. Through this study, we found that various practical educations are necessary such as: (1) education for researchers on how to write a protocol, (2) standardization of screening criteria for various animal experiments by presenting various cases, (3) training on a detailed understanding of relevant laws and policies. In particular, an integrated management system, making it possible to share information among the related committees, would be essential for smoother operation of the IACUC.ConclusionsIf various levels of education and the integrated management system are established, it will be possible to enhance the excellence of researchers and to better manage the operation of the IACUC.

Influence of Exercise on Inferior Vena Cava Wall Interaction with Inferior Vena Cava Filters: Results of a Pilot In Vivo Porcine Study

Abstract Objectives The aim of this study was to assess the effect of mild exercise on inferior vena cava (IVC) filter interaction with imaging and pathological features with the neighboring vessel wall utilizing a porcine model. Materials and Methods After Institutional Animal Care and Use Committee (IACUC) approval, retrievable Option Elite IVC filters were implanted in six Yorkshire pigs utilizing the right common femoral vein approach under general anesthesia. Group A (n = 4) pigs remained sedentary for 4 weeks. Group B (n = 2) pigs were exercised using a harness and treadmill for 10 minutes/day for 4 days/week. At approximately 4 weeks, IVC venograms were performed and the pigs were sacrificed. After laparotomy, the IVC was ligated above and below the filter, excised and fixed in formalin. Gross and histological examination of the IVC was performed. Gross images of each sample were captured before removal of the filters. One longitudinal, one tangential, and five transverse representative sections were processed for paraffin sectioning and hematoxylin and eosin slides were prepared. A pathologist examined all tissues to assess differences between normal vein, group A and group B pigs. The pathologist provided an overall assessment and representative images. Results All IVC filter implantations were technically successful without adverse effects. There was no incidence of caval thrombosis, filter strut fracture, or filter migration in either group. On gross pathological examination, IVC of the pigs in group B demonstrated more perivascular and mural fibrosis than those pigs in group A. Histopathological findings correlated with gross findings. Conclusions In this pilot study, there were no incidence of IVC filter strut fracture, penetration or IVC occlusion in sedentary or exercised pigs. However, there tended to be more perivascular and mural fibrosis on pathological examination of inferior vena cavas from exercised pigs. Further larger scale studies may employ the porcine model to further understand the role exercise may play on IVC filter and caval wall interaction.

DAP10 integration in CAR-T cells enhances the killing of heterogeneous tumors by harnessing endogenous NKG2D

Although chimeric antigen receptor T (CAR-T) cells have achieved remarkable successes in hematological malignancies, the efficacies of CAR-T cells against solid tumors remains unsatisfactory. Heterogeneous antigen expression is one of the obstacles on its effective elimination of solid cancer cells. DNAX-activating protein 10 (DAP10) interacts with natural killer group 2D (NKG2D), acting as an adaptor that targets various malignant cells for surveillance. Here, we designed a DAP10 chimeric receptor that utilized native NKG2D on T cells to target NKG2D ligand-expressing cancer cells. We then tandemly incorporated it with anti-glypican 3 (GPC3) single-chain variable fragment (scFv) to construct a dual-antigen-targeting system. T cells expressing DAP10 chimeric receptor (DAP10-T cells) displayed with an enhancement on both cytotoxicity and cytokine secretion against solid cancer cell lines, and its tandem connection with anti-GPC3 scFv (CAR GPC3-DAP10-T cells) exhibited a dual-antigen-targeting capacity on eliminating heterogeneous cancer cells in vitro and suppressing the growth of heterogeneous cancer in vivo. Thus, this novel dual-targeting system enabled a high efficacy on killing cancer cells and extended the recognition profile of CAR-T cells toward tumors, which providing a potential strategy on treatment of solid cancer clinically.