RESUMO
The influence of mouse strain, immune competence and age on the pathogenesis of a field strain of minute virus of mice (MVMm) was examined in BALB/c, C3H, C57BL/6 and SCID mice experimentally infected as neonates, weanlings and adults. Sera, bodily excretions and tissues were harvested at 7, 14, 28 and 56 days after inoculation and evaluated by serology, quantitative PCR and histopathology. Seroconversion to recombinant viral capsid protein 2 was consistently observed in all immunocompetent strains of mice, regardless of the age at which they were inoculated, while seroconversion to the viral nonstructural protein 1 was only consistently detected in neonate inoculates. Viral DNA was detected by quantitative PCR in multiple tissues of immunocompetent mice at each time point after inoculation, with the highest levels being observed in neonate inoculates at 7 days after inoculation. In contrast, viral DNA levels in tissues and bodily excretions increased consistently over time in immunodeficient SCID mice, regardless of the age at which they were inoculated, with mortality being observed in neonatal inoculates between 28 and 56 days after inoculation. Overall, productive infection was observed more frequently in immunocompetent mice inoculated as neonates as compared to those inoculated as weanlings or adults, and immunodeficient SCID mice developed persistent, progressive infection, with mortality being observed in mice inoculated as neonates. Importantly, the clinical syndrome observed in experimentally infected SCID neonatal mice recapitulates the clinical presentation reported for the naturally infected immunodeficient NOD µ-chain knockout mice from which MVMm was initially isolated.
Assuntos
Vírus Miúdo do Camundongo/fisiologia , Infecções por Parvoviridae/veterinária , Doenças dos Roedores/virologia , Fatores Etários , Animais , Feminino , Especificidade de Hospedeiro , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Vírus Miúdo do Camundongo/classificação , Vírus Miúdo do Camundongo/genética , Vírus Miúdo do Camundongo/isolamento & purificação , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Recombinação Genética , Doenças dos Roedores/imunologia , Proteínas Virais/genéticaRESUMO
OBJECTIVE: To determine the ratio of collagen type III to collagen type I in the periurethral tissues of sexually intact and neutered female dogs. ANIMALS: 8 neutered and 34 sexually intact female dogs. PROCEDURES: Tissues were obtained from female dogs euthanized for non-urinary tract-related reasons. Indirect immunofluorescent antibody detection of type I and collagen type III was performed by use of confocal microscopy on 2 periurethral samples from each dog, and the ratios of collagen type III to type I area fraction and total area were determined. RESULTS: No significant differences were detected in the collagen ratios of periurethral tissues between sexually intact and neutered female dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to differences in periurethral collagen content found between pre- and postmenopausal women, such differences may not occur in dogs. This implies that changes in pelvic organ support structures may not play an important role in urinary incontinence in neutered female dogs. Further evaluation is needed to determine the role of age on collagen and pelvic organ support structures in the pathogenesis of canine urinary incontinence.
Assuntos
Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Cães/metabolismo , Uretra/metabolismo , Animais , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Microscopia de Fluorescência/veterinária , Ovariectomia/veterinária , Estatísticas não ParamétricasRESUMO
PURPOSE: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell-mediated killing. EXPERIMENTAL DESIGN: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to (153)Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to T cell-mediated killing. RESULTS: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class I (50%), and intercellular adhesion molecule-1 (40%) in response to (153)Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. CONCLUSIONS: Doses of (153)Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that (153)Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.
Assuntos
Neoplasias da Mama/terapia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/terapia , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Neoplasias da Próstata/terapia , Radioisótopos/farmacologia , Samário/farmacologia , Linfócitos T Citotóxicos/imunologia , Linhagem Celular Tumoral , Separação Celular , Feminino , Humanos , Masculino , Fenótipo , Linfócitos T Citotóxicos/metabolismo , Resultado do TratamentoRESUMO
Fecal shedding and transmission of mouse parvovirus 1 (MPV) to naive sentinels, breeding mates, and progeny were assessed. Neonatal SCID and BALB/c mice inoculated with MPV were evaluated over 24 wk; several mice from each strain were mated once during this period. Fecal MPV loads for each cage were determined weekly by quantitative polymerase chain reaction (PCR) analysis, and all mice were evaluated by quantitative PCR analysis of lymphoid tissues and seroconversion to MPV antigens in immunocompetent mice. Results indicated persistently high fecal shedding of MPV in SCID mice throughout the evaluation period sufficient to allow transmission to sentinels, naive breeding partners, and the progeny of infected male mice and naive partners. Lymphoid tissue viral loads in the progeny of infected female SCID mice were high at weaning but low at 6 wk of age. Infected BALB/c mice shed high levels of MPV in feces for 3 wk postinoculation, with seroconversion only in sentinels exposed during the first 2 wk postinoculation. Thereafter the feces of infected BALB/c mice and the lymphoid tissues of sentinels, naive breeding partners, and progeny intermittently contained extremely low levels of MPV DNA. Although pregnancy and lactation did not increase viral shedding in BALB/c mice, MPV exposure levels were sufficient to induce productive infection in some BALB/c progeny. These data indicate that the adaptive immune response suppresses, but does not eliminate, MPV shedding; this suppression is sufficient to inhibit infection of weanling and adult mice but allows productive infection of some progeny.
Assuntos
Transmissão de Doença Infecciosa/veterinária , Transmissão Vertical de Doenças Infecciosas/veterinária , Camundongos , Vírus Miúdo do Camundongo/genética , Infecções por Parvoviridae/veterinária , Doenças dos Roedores/transmissão , Animais , Fezes/virologia , Feminino , Camundongos Endogâmicos BALB C , Camundongos SCID , Infecções por Parvoviridae/transmissão , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Testes Sorológicos/veterinária , Fatores de Tempo , Eliminação de Partículas ViraisRESUMO
The objective of this retrospective study was to describe the responses to treatment with intravenous lipid emulsion (ILE) and the outcomes for a variety of severe intoxications. This case series includes 10 client-owned animals, 9 dogs and 1 cat, that underwent treatment with ILE for a variety of severe intoxications over a 4-year period. History, physical examination findings, clinical signs, clinicopathological test results, treatment, response to treatment, and outcome were recorded. Eight of the 10 patients survived to discharge. The toxicities included in this case series were baclofen, ivermectin and spinosad plus milbemycin oxime, baclofen and tadalafil, carbamate, methamphetamine, dextroamphetamine sulfate, amlodipine, bromethalin, and organophosphate. The two patients who died were intoxicated with bromethalin and an organophosphate. Six of the 10 patients developed lipemia secondary to ILE administration, and there were no other known adverse effects. Overall, ILE was a safe therapeutic option. This case series provides clinical evidence of successful treatment with ILE as an antidote for previously unpublished toxicities (amlodipine, carbamate, methamphetamine, and dextroamphetamine sulfate), additional evidence of success in treating baclofen and ivermectin toxicosis, as well as unsuccessful treatment of bromethalin and organophosphate toxicities.