RESUMEN
OBJECTIVE: To determine survival rate and athletic ability after nonsurgical or surgical treatment of cleft palate in horses. DESIGN: Retrospective case series. ANIMALS: 55 horses with cleft palate. PROCEDURES: 13 of the 55 horses died or were euthanized without treatment and were not included in all analyses. Medical records were reviewed for signalment, history, method of diagnosis, soft or hard palate involvement, type of surgical procedure performed, postoperative complications, and survival to hospital discharge. Information on athletic ability was acquired from race records and follow-up conversations with owners, trainers, or referring veterinarians. RESULTS: The predominant reason for initial evaluation was milk or feed in the nostrils (60%). The diagnosis was confirmed by means of videoendoscopy of the upper portion of the airway in all cases. Most cases involved the soft palate only (92.7%). Twenty-six of the 55 (47.3%) horses underwent surgical repair, and 12 of these had dehiscence at the caudal edge of the soft palate. Among potential racehorses, 14 of 33 had surgery. Of these, 12 of 14 survived to discharge and 2 horses raced. Among potential racehorses, 10 of 33 were discharged without surgery and 2 of these raced. Among nonracehorses, 12 of 22 underwent surgery and 11 survived to discharge. All horses that were discharged and for which follow-up information was available survived to 2 years of age or older without ill thrift despite dehiscence at the caudal edge of the soft palate and continued mild nasal discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Horses with cleft palate had a higher survival rate than previously reported.
Asunto(s)
Fisura del Paladar/veterinaria , Enfermedades de los Caballos/terapia , Animales , Fisura del Paladar/terapia , Femenino , Caballos , Masculino , Complicaciones Posoperatorias/veterinaria , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/veterinaria , Carrera , Deportes , Dehiscencia de la Herida Operatoria/veterinaria , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To evaluate early cellular influences of bone morphogenetic protein (BMP)12 and BMP2 on equine superficial digital flexor tenocytes (SDFTNs) and equine bone marrow-derived mesenchymal stem cells (BMDMSCs). ANIMALS: 9 adult clinically normal horses. PROCEDURES: BMDMSCs and SDFTNs were cultured in monolayer, either untreated or transduced with adenovirus encoding green fluorescent protein, adenovirus encoding BMP12, or adenovirus encoding BMP2. Cytomorphologic, cytochemical, immunocytochemical, and reverse transcriptase-quantitative PCR (RT-qPCR) analyses were performed on days 3 and 6. Genetic profiling for effects of BMP12 was evaluated by use of an equine gene expression microarray on day 6. RESULTS: BMDMSCs and SDFTNs had high BMP12 gene expression and remained viable and healthy for at least 6 days. Type l collagen immunocytochemical staining for SDFTNs and tenocyte-like morphology for SDFTNs and BMDMSCs were greatest in BMP12 cells. Cartilage oligomeric matrix protein, as determined via RT-qPCR assay, and chondroitin sulfate, as determined via gene expression microarray analysis, were upregulated relative to control groups in SDFTN-BMP12 cells. The BMDMSCs and SDFTNs became mineralized with BMP2, but not BMP12. Superficial digital flexor tenocytes responded to BMP12 with upregulation of genes relevant to tendon healing and without mineralization as seen with BMP2. CONCLUSIONS AND CLINICAL RELEVANCE: Targeted equine SDFTNs may respond to BMP12 with improved tenocyte morphology and without mineralization, as seen with BMP2. Bone marrow-derived mesenchymal stem cells may be able to serve as a cell delivery method for BMP12.
Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Tendones/citología , Animales , Médula Ósea , Proteína Morfogenética Ósea 2/genética , Proteínas Morfogenéticas Óseas/genética , Diferenciación Celular , Células Cultivadas , Regulación de la Expresión Génica , Técnicas de Transferencia de Gen , Caballos , Análisis por Matrices de ProteínasRESUMEN
Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-gamma transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1alpha and MIP-1beta mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP-1beta-driven macrophage immunopathology.
Asunto(s)
Encefalitis Viral/inmunología , Encefalitis Viral/fisiopatología , Glicoproteínas de Membrana/metabolismo , Virus de la Hepatitis Murina/patogenicidad , Proteínas del Envoltorio Viral/metabolismo , Animales , Encéfalo/citología , Encéfalo/inmunología , Encéfalo/virología , Linfocitos T CD8-positivos/inmunología , Quimiocina CCL3 , Quimiocina CCL4 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Encefalitis Viral/virología , Citometría de Flujo , Proteínas Inflamatorias de Macrófagos/metabolismo , Macrófagos/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Virus de la Hepatitis Murina/genética , Glicoproteína de la Espiga del Coronavirus , VirulenciaRESUMEN
Viral encephalitis is a global health concern. The ability of a virus to modulate the immune response can have a pivotal effect on the course of disease and the fate of the infected host. In this study, we sought to understand the immunological basis for the fatal encephalitis following infection with the murine coronavirus, mouse hepatitis virus (MHV)-JHM, in contrast with the more attenuated MHV-A59. Distinct glial cell cytokine and chemokine response patterns were observed within 3 days after infection, became progressively more polarized during the course of infection and with the infiltration of leukocytes. In the brain, MHV-JHM infection induced strong accumulation of IFNbeta mRNA relative to IFNgamma mRNA. This trend was reversed in MHV-A59 infection and was accompanied by increased CD8 T cell infiltration into brain compared to MHV-JHM infection. Increased apoptosis appeared to contribute to the diminished presence of CD8 T cells in MHV-JHM-infected brain with the consequence of a lower potential for IFNgamma production and antiviral activity. MHV-JHM infection also induced sustained mRNA accumulation of the innate immune response products interleukin (IL)-6 and IL-1. Furthermore, high levels of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2 mRNA were observed at the onset of MHV-JHM infection and correlated with a marked elevation in the number of macrophages in the brain on day 7 compared to MHV-A59 infection. These observations indicate that differences in the severity of viral encephalitis may reflect the differential ability of viruses to stimulate innate immune responses within the CNS and subsequently the character of infiltrating leukocyte populations.