Protection of Rabbits Against Colonization and Morbidity Associated With Toxigenic by Immunization With Inactivated Heat-labile Toxin.

Background/aim: Pasteurella multocida is a significant cause of morbidity and mortality in rabbits, as well as other species. Some isolates elaborate a heat-labile toxin (PMT) that has been shown to be an important virulence factor. Though previous studies have demonstrated protective immunity can be conferred via immunization of rabbits with heat-inactivated PMT (IPMT), we investigated the ability of immunization to impact colonization of P.

Overview and Approaches for Handling of Animal Models of Leishmaniasis.

Leishmaniasis, a disease of global relevance, results from infection with the protozoan parasite, , which is transmitted to susceptible hosts through the bite of sand flies. Multiple forms of leishmaniasis may occur, including cutaneous, mucocutaneous, and visceral. Research with animal models remains an important approach to help define basic pathophysi- ologic processes associated with infection and disease.

Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors.

Seasonal Variation of Laboratory Animals as a Consideration for Research Reproducibility.

Laboratory rodents are generally maintained under standardized conditions in order to control the effects of extrinsic factors on research. However, despite attempts to standardize conditions, variability can nonetheless confound efforts directed toward research reproducibility. Here we explore some of the existing literature on the potential impact of seasonal variability as an extrinsic factor that can potentially impact research results.

Evaluation of Cage Mate-induced Postsurgical Trauma in Mice.

Although mice are social animals, individual housing is sometimes requested after surgery. We questioned whether pair-housing mice after surgery resulted in greater trauma to the surgical site as compared with single housing. We further evaluated the effect of individual housing after surgery on the wellbeing of mice that had previously been pair-housed.

Use of Conditioned Extracellular Matrix as a Tissue-engineered Tumor Matrisome for Prostate Cancer and Melanoma Immunotherapy.

Background/aim: Decellularized extracellular matrix (ECM) acts as a depot for biochemical factors when conditioned by the growth of cells that are subsequently removed, and in the case of tumors, this ECM depot is known as the matrisome. This study was undertaken to determine whether a tissue-engineered matrisome could be used as an antigenic depot to stimulate protective immunity against tumor regrowth and metastasis following surgical reduction of the tumor.

Materials And Methods: Using two transplanted tumor cell models, the PAIII rat model of prostate cancer and the B16F1 mouse model of melanoma, mice were administered either media (control), a suspension of inactivated tumor cells, extracellular matrix (SIS), or a matrisome engineered through growth and removal of tumor cells on SIS that was then implanted either directly onto the resected tumor bed or at an anatomical site distant to the tumor bed.

Field Safety Experience With an Autologous Cancer Vaccine in 41 Horses: A Retrospective Study (2019-2021).

Autologous cancer vaccines (ACV) are an emerging option for adjuvant cancer treatment in veterinary medicine. With this form of active immunotherapy, the patient's tumor cells are processed ex vivo and returned to the patient with the goal of stimulating an immune response to unique, patient-specific antigens. The case accession database at Torigen was queried to identify horses that underwent biopsy or surgical resection of their primary tumor and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine.

Feeding treats containing cannabidiol (CBD) did not alter canine immune response to immunization with a novel antigen.

Due to the potential risk for cannabidiol (CBD) to negatively impact the immune system, the objective of the current study was to evaluate the effect of CBD on the canine immune response to immunization with a novel antigen, keyhole limpet hemocyanin (KLH). Thirty-two dogs (22.4 ± 6.

Field safety experience with an autologous cancer vaccine in tumor-bearing cats: a retrospective study of 117 cases (2015-2020).

Objectives: The aim of this study was to determine the frequency and severity of adverse events (AEs) reported from use of an adjuvanted whole-cell autologous cancer vaccine in cats with solid tumors under field conditions.

Methods: The case accession database at Torigen Pharmaceuticals was searched to identify client-owned cats that underwent biopsy or surgical resection of their primary tumor, had histologic confirmation of neoplasia and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. Records were reviewed for any reported AEs.

Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study.

Background: Canine hemangiosarcoma (HSA) is an aggressive cancer arising from multipotential bone marrow-derived stem cells. Anthracycline chemotherapy drugs have been the mainstay adjuvant chemotherapy following surgery with only modest improvement in survival and an attendant risk for adverse events. Immunotherapy, using a whole cell autologous cancer vaccine adjuvanted with MIM-SIS, may improve outcomes for dogs with HSA with a lower risk for adverse events compared with chemotherapy.

Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them.

Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation.

Structure-Activity Relationship for the Oxadiazole Class of Antibacterials.

A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant (MRSA) infection. Oxadiazole shows potent antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection.

Predictive modeling for cancer drug discovery using canine models.

Introduction: Rodent models of cancer lack many features associated with the disease in humans. Because dogs closely share an environment with humans, as well as comparable pathophysiology of cancer, they represent a powerful model with which to study novel approaches to cancer treatment.

Areas Covered: The authors summarize the weaknesses of rodent models of cancer and the ongoing need for better animal models with which to study potential therapeutic approaches.

Hyperbaric oxygen therapy accelerates wound healing in diabetic mice by decreasing active matrix metalloproteinase-9.

Diabetic foot ulcers are characterized by hypoxia. For many patients, hyperbaric oxygen (HBO) therapy is the last recourse for saving the limb from amputation, for which the molecular basis is not understood. We previously identified the active form of matrix metalloproteinase-9 (MMP-9) as responsible for diabetic foot ulcer's recalcitrance to healing.

Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer.

Castration Resistant Prostate Cancer (CRPC) is thought to be driven by a collaborative mechanism between TNFα/NFκB and TGFβ signaling, leading to inflammation, Epithelial-to-Mesenchymal-Transition (EMT), and metastasis. Initially, TGFβ is a tumor suppressor, but in advanced metastatic disease it switches to being a tumor promoter. TGFBR2 may play a critical role in this collaboration, as its expression is driven by NFκB and it is the primary receptor for TGFβ.

Zwitterionic amino acid-based Poly(ester urea)s suppress adhesion formation in a rat intra-abdominal cecal abrasion model.

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties.

Pain as a Clinical Factor and Experimental Variable in Research Rodents.

It is broadly accepted that, as part of the humane care and use of animals in research, the pain experienced by animals should be minimized to the extent possible, consistent with the goals of the research. In some cases, pain may be the subject under study, whereas in other cases, the use of some types of analgesics may interfere with the experimental objectives of the work. This issue of provides reviews related to the recognition and treatment of pain, the interaction of pain and pain relief on experimental outcomes, and ethical perspectives on the need to reduce pain in research rodents, whenever possible.

Safety Evaluation of Autologous Tissue Vaccine Cancer Immunotherapy in a Canine Model.

Background/aim: Previous work in rodent models showed that an autologous tissue vaccine is both a safe and effective approach for treating cancer; however, as a translational step, safety must first be evaluated in a more clinically-relevant model.

Materials And Methods: An autologous immunotherapy produced from resected tumors, was evaluated in a clinically-relevant canine model to assess safety. Ninety-three dogs with spontaneously occurring tumors received vaccination with inactivated autologous tumor tissue combined with an adjuvant of particulate porcine small intestinal submucosa extracellular matrix (SIS-ECM).

Validation of Matrix Metalloproteinase-9 (MMP-9) as a Novel Target for Treatment of Diabetic Foot Ulcers in Humans and Discovery of a Potent and Selective Small-Molecule MMP-9 Inhibitor That Accelerates Healing.

Diabetic foot ulcers (DFUs) are a significant health problem. A single existing FDA-approved drug for this ailment, becaplermin, is not standard-of-care. We previously demonstrated that upregulation of active matrix metalloproteinase (MMP)-9 is the reason that the diabetic wound in mice is recalcitrant to healing and that MMP-8 participates in wound repair.

In Search of Selectivity in Inhibition of ADAM10.

The metalloproteinase ADAM10 has been reported as an important target for drug discovery in several human diseases. In this vein, (6,7)--hydroxy-5-methyl-6-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazine-1-carbonyl)-5-azaspiro[2.5]octane-7-carboxamide (compound ) has been reported as a selective ADAM10 inhibitor.

Expression of active matrix metalloproteinase-9 as a likely contributor to the clinical failure of aclerastide in treatment of diabetic foot ulcers.

Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds.