Comparative Medicine Volume 74: Issue 2

The pig has long been used as a research animal and has now gained importance as a potential source of organs for clinical xenotransplantation. When an organ from a wild-type (i.e., genetically unmodified) pig is transplanted into an immunosuppressed nonhuman primate, a vigorous host immune response causes hyperacute rejection (within minutes or hours). This response has been largely overcome by 1) extensive gene editing of the organ-source pig and 2) the administration to the recipient of novel immunosuppressive therapy based on blockade of the CD40/CD154 T cell costimulation pathway. Gene editing has consisted of 1) deletion of expression of the 3 known carbohydrate xenoantigens against which humans have natural (preformed) antibodies and 2) the introduction of human ‘protective’ genes. The combination of gene editing and novel immunosuppressive therapy has extended life-supporting pig kidney graft survival to greater than 1 y and of pig heart survival to up to 9 mo. This review briefly describes the techniques of gene editing, the potential risks of transfer of porcine endogenous retroviruses with the organ, and the need for breeding and housing of donor pigs under biosecure conditions.

Experimental maxillofacial surgery is commonly performed in pigs; however, locoregional anesthesia of this area has not been described. This study evaluated the feasibility of a novel maxillary nerve block approach. In part I, cadavers were used to determine anatomic landmarks and assess maxillary nerve dye staining by using 0.03 mL kg⁻¹ of a 1:10 mixture of commercial food dye and 0.5% bupivacaine. In part II, 10 additional pig cadavers underwent bilateral ultrasound-guided maxillary nerve blocks by using trans-infraorbital canal needle placement. The maxillary nerve was harvested and scored based on degree of staining (0 and 1, absent or incomplete staining; 2, staining; >1 cm circumferentially). Intracranial and intraconal spread of dye was evaluated. A Kruskal–Wallis test was used to compare infraorbital canal length estimated either externally via landmarks, internally via ultrasound, or actually measured after dissection. In 18 of 20 (90%) injections, successful staining (score = 2) of maxillary nerves was obtained for a nerve length of 2.4 ± 0.3 cm. Two of 20 cases (10%) had inadequate staining (score <2). At dissection of these 2 cases, the needle tip was observed to have collided with an unerupted tooth (third molar). No intracranial or intraconal spread of dye was observed. We detected no statistical differences between the estimated external, estimated internal, or actual dissection methods for measurement of infraorbital canal length (P = 0.3). Ultrasound-guided trans-infraorbital maxillary nerve block in pigs is a feasible technique, warranting further work to evaluate its in vivo efficacy and safety.

Disturbances in gut microbiota are prevalent in inflammatory bowel disease (IBD), which includes ulcerative colitis (UC). However, whether these disturbances contribute to development of the disease or are a result of the disease is unclear. In pairs of human twins discordant for IBD, the healthy twin has a higher risk of developing IBD and a gut microbiota that is more similar to that of IBD patients as compared with healthy individuals. Furthermore, appropriate medical treatment may mitigate these disturbances. To study the correlation between microbiota and IBD, we transferred stool samples from a discordant human twin pair: one twin being healthy and the other receiving treatment for UC. The stool samples were transferred from the disease-discordant twins to germ-free pregnant dams. Colitis was induced in the offspring using dextran sodium sulfate. As compared with offspring born to mice dams inoculated with stool from the healthy cotwin, offspring born to dams inoculated with stool from the UC-afflicted twin had a lower disease activity index, less gut inflammation, and a microbiota characterized by higher α diversity and a more antiinflammatory profile that included the presence and higher abundance of antiinflammatory species such as Akkermansia spp., Bacteroides spp., and Parabacteroides spp. These findings suggest that the microbiota from the healthy twin may have had greater inflammatory properties than did that of the twin undergoing UC treatment.

General

The American Association for Laboratory Animal Science (AALAS) currently publishes two journals containing data-driven, peer-reviewed articles.

The mission of Comparative Medicine (CM) is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

Facts and Statistics

Average submission to final decision time: 30 days
495 pages printed in 2023
42% acceptance rate

JAALAS

Average submission to final decision time: 37 days
570 pages printed in 2023
68%

Schistosoma mansoni Infection in Three Green Monkeys (Chlorocebus sabaeus) Originating from Saint Kitts

Michael A EckhausVMD, DACVP,

Jeremy J BearssDVM, DACVP,

Rachel M FleischmannBS,

Jennifer KetzisPhD,

Tiffany LavinderDVM,

Amy BeierschmittDVM,

Jessica PlunkardMPH, DVM, and

Gregory W SalyardsDVM, MPH, DACLAM

Pigs in Transplantation Research and Their Potential as Sources of Organs in Clinical Xenotransplantation

A Feasibility Study for a Novel Trans-infraorbital Canal Approach to the Maxillary Nerve in Pigs (Sus domesticus)

Assessment of the Inflammatory Effects of Gut Microbiota from Human Twins Discordant for Ulcerative Colitis on Germ-free Mice

Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model

Comparison of Two Different Alfaxalone Concentrations Combined with Midazolam to Anesthetize Cynomolgus Macaques (Macaca fascicularis) for Plethysmography

Investigation of Factors Associated with Subclinical Infections of Giardia duodenalis and Cryptosporidium canis in Kennel-Housed Dogs (Canis lupus familiaris)

Methods for Decreasing Preweaning Mortality in a Fragile Mouse Model of Hypomorphic Collagen VII Deficiency

Carprofen Attenuates Postoperative Mechanical and Thermal Hypersensitivity after Plantar Incision in Immunodeficient NSG Mice

Abnormal Feather Phenotype Associated with a Fatal Stress Response and Unusual Tolerance to Human Contact in the Zebra Finch (Taeniopygia castanotis)

Chlamydia muridarum Associated Pulmonary and Urogenital Disease and Pathology in a Colony of Enzootically Infected Il12rb2 Deficient and Stat1 Knockout Mice

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Schistosoma mansoni Infection in Three Green Monkeys (Chlorocebus sabaeus) Originating from Saint Kitts

Pharmacokinetic Evaluation of Topical Long-Acting Buprenorphine in New Zealand White Rabbits (Oryctolagus cuniculus)

Serum Pharmacokinetics of a Highly Concentrated Buprenorphine Formulation in Older Female Sprague–Dawley Rats (Rattus norvegicus)

Association of Primate Veterinarians Guidelines for Weight Management in Research Nonhuman Primates

Metabolic Cage Analysis of Surgically Catheterized C57BL/6J Mice (Mus musculus) Treated with Carprofen and Sustained-Release Buprenorphine

Science, a Key AALAS Initiative

Science, a Key AALAS Initiative

Aspects of Common Marmoset Basic Biology and Life History Important for Biomedical Research

Study of Low-Temperature (4°C) Transport of Mouse Two-Cell Embryos Enclosed in Oviducts

Clinical Care and Diseases of the Common Marmoset (Callithrix jacchus)