RESUMEN
Recent disease events have heightened awareness for the need for collaboration between the nation's public health and veterinary infectious disease communities to improve preparedness for current and future biological threats. To address this need, the U.S. Department of Agriculture's National Bio- and Agro-Defense Facility (USDA NBAF) has partnered with Texas A&M University through its Global Health Research Complex (TAMGHRC) to establish the Research Alliance for Veterinary Science and Biodefense BSL-3 Network (RAV3N). As a collaborative network of U.S. university and federal BSL-3Ag/BSL-3/BSL-4 laboratory research facilities, the objective of RAV3N is to establish strategic and coordinated approaches for harnessing collective large-animal biocontainment infrastructure and research capacity to improve bio-surveillance, diagnostics, and countermeasure development against high-consequence pathogens of veterinary and zoonotic importance. Here, we describe the origin and development of RAV3N, detail phase I activities, and summarize the proceedings of its first membership meeting held in August 2022.
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Laboratorios , Salud Pública , AnimalesRESUMEN
Osteoarthritis (OA) is a prevalent and economically costly source of lameness in the athletic horse. Previous studies investigating OA pathology have focused on localized trauma to the articular cartilage of a joint, largely ignoring the systemic immune status of the animal. In this study, yearling Quarter Horses were used to evaluate systemic cytokine gene expression and circulating leukocytes following a localized intra-articular inflammatory insult of the endotoxin, lipopolysaccharide (LPS). Treatments for the 35-d experiment included an intra-articular injection of 0.25 ng (n = 7) or 0.50 ng (n = 6) of LPS obtained from Escherichia coli O55:B5 or sterile lactated Ringer's solution (n = 6; control) into the radial carpal joint. Blood and synovial fluid samples were collected at preinjection hour 0 and 2, 6, 12, and 24 h postinjection. Synovial fluid was obtained for a companion study. Total RNA was isolated from plasma leukocytes and real-time PCR was used to determine relative gene expression of the cytokines interleukin (IL)-1beta (ß), IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Total leukocyte subpopulations and differentials were performed using a cell counter. Data were analyzed using the PROC MIXED procedure of SAS. Gene expression of all cytokines were unaffected by intra-articular treatment. However, IL-1ß increased above baseline beginning at hour 6 and remained elevated to 24 h (P = 0.04). In contrast, IL-6 decreased from hours 6 to 12 and then increased to 24 h (P = 0.02). Levels of TNF-α increased at 6 and 12 h (P = 0.01) postinjection. Only IL-8 exceeded a 2-fold change in expression (P = 0.01), peaking at 12 h and indicating greater responsiveness to arthrocentesis when compared with other cytokines. No treatment effects on the leukocyte population were observed; however, total circulating leukocytes increased over time (P = 0.04), peaking at 6 h postinjection. Similarly, an increase over time was observed in monocytes (P = 0.02) and in platelets (P = 0.01) at 24 h postinjection. The results indicate that regardless of treatment, a mild immune response was elicited, which may be due to repeated arthrocentesis. Future experiments should consider the effects of arthrocentesis and potential systemic inflammatory response, even in control animals, when administering intra-articular LPS to young horses.
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Endotoxinas/administración & dosificación , Enfermedades de los Caballos/inmunología , Lipopolisacáridos/administración & dosificación , Animales , Artrocentesis/veterinaria , Cartílago Articular/metabolismo , Citocinas/genética , Femenino , Enfermedades de los Caballos/inducido químicamente , Caballos , Inyecciones Intraarticulares/veterinaria , Leucocitos/efectos de los fármacos , Masculino , Distribución Aleatoria , Líquido Sinovial/efectos de los fármacosRESUMEN
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota.