Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Salud Global/educación , Educación en Salud , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Oftalmología/estadística & datos numéricos , Neumonía Viral/epidemiología , COVID-19 , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Urgencias Médicas/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Cuarentena , SARS-CoV-2 , España/epidemiologíaRESUMEN
CASE REPORT: An 84 year-old woman was referred for evaluation of a painless swelling with small purulent discharge in her left upper canaliculus, and an associated epiphora of one-month duration. The patient was diagnosed with acute primary canaliculitis. She was treated with topical and oral antibiotics, as well as topical corticoids for three months, with little response. Surgical treatment with left upper canaliculotomy and curettage was then performed, and Gemella haemolysans was identified from the curetted material. The patient had no recurrence of the disease two months after the surgery. DISCUSSION: This is the first time that Gemella haemolysans is described as unique agent causing primary canaliculitis.
Asunto(s)
Canaliculitis/microbiología , Gemella/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Anciano de 80 o más Años , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Canaliculitis/tratamiento farmacológico , Canaliculitis/cirugía , Terapia Combinada , Legrado , Dexametasona/uso terapéutico , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/cirugía , Humanos , Ofloxacino/uso terapéutico , Tobramicina/uso terapéuticoRESUMEN
Eight colostrum-deprived calves were inoculated intranasally with a non-cytopathic strain of bovine viral diarrhoea virus (BVDV) genotype-1 and killed in batches of two at 3, 6, 9 and 14 days post-inoculation (dpi). Two non-inoculated animals with similar background served as controls. All infected calves developed mild pyrexia and transient leucopenia due primarily to lymphopenia. Viraemia was correlated with body temperature and inversely related to leucocyte count. Ileal Peyer's patches developed mild follicular lymphoid depletion from 3dpi. This change was accompanied by cellular fragmentation and pyknosis, characteristic of apoptosis, which was most prominent from 6dpi. Lymphocyte apoptosis was confirmed by ultrastructural examination. Stellate cells and macrophages located in the lymphoid follicles were identified as infected by virus from 3dpi and the number of these infected cells increased until 9dpi. Fewer lymphocytes expressed BVDV antigen. Macrophages had morphological features consistent with activation of secretory and phagocytic function from 3dpi. These findings suggest that BVDV is only directly responsible for the destruction of a small number of lymphocytes. Although lymphocyte infection coincided with the onset of apoptosis, the intensity of infection was disproportionate to the marked depletion of gut-associated lymphoid tissue, particularly during the early stages of this process. Characterization of the indirect pathogenic mechanisms involved in the lymphoid depletion associated with BVDV infection will require additional study.
Asunto(s)
Diarrea Mucosa Bovina Viral/inmunología , Diarrea Mucosa Bovina Viral/patología , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Íleon/inmunología , Íleon/patología , Animales , Diarrea Mucosa Bovina Viral/virología , Bovinos , Calostro/inmunología , Femenino , Íleon/ultraestructura , Masculino , Ganglios Linfáticos Agregados/inmunología , Ganglios Linfáticos Agregados/patología , Ganglios Linfáticos Agregados/ultraestructura , Embarazo , VacunaciónRESUMEN
The cross-reactivity of antibodies against human tumour necrosis factor (TNF)alpha, interleukin (IL)-1alpha, IL-1beta and porcine IL-6, and the distribution of immunolabelled cells were evaluated on paraffin wax-embedded tissues from five healthy calves. The tissues were fixed in 10% buffered formalin or Bouin's solution and processed for structural studies and immunohistochemical studies by the avidin-biotin-peroxidase technique. Bouin's solution proved to be the more suitable fixative and Tween 20 the most effective antigen unmasking technique for increasing detectable antigenicity. Constitutive expression of TNFalpha, IL-1alpha, IL-1beta and IL-6 by different cell populations, mainly macrophage-like cells, was detected. Lymphoid organs displayed a higher presence of immunolabelled cells than did lung, liver or kidney. TNFalpha and IL-1alpha appeared as the predominant cytokines, especially in the gut-associated lymphoid tissue of the ileum and in the regional mesenteric lymph nodes. The results will facilitate investigation of the role of these cytokine-producing cells in inflammatory disease processes in calves.
Asunto(s)
Anticuerpos Monoclonales , Bovinos , Citocinas/biosíntesis , Inmunohistoquímica/veterinaria , Adhesión en Parafina/veterinaria , Animales , Reacciones Cruzadas , Femenino , Humanos , MasculinoRESUMEN
The aim of this study was to report on the lesions occurring in the central nervous system (CNS) during experimental classical swine fever (CSF) to clarify the spatial and chronologic distribution of the lesions and virus antigen in the CNS. To learn more about the pathogenetic mechanisms of the lesions during CSF in the CNS and to investigate the role of the virus in these mechanisms, cellular infiltrates and infected cells have been characterized. Twenty-eight pigs were inoculated with the virulent CSF virus isolate Alfort 187 and slaughtered from 2 to 15 postinoculation days; 4 animals of similar background served as a control group. Immunohistochemistry, electron microscopy, and the transferase-mediated deoxyuridine triphosphate nick-end labeling method were used to detect viral antigens and apoptosis. The results showed the presence of nonpurulent meningoencephalitis, occasional microhemorrhages, and apoptosis of the lymphocytes forming the perivascular and interstitital infiltrate in swine with CSF. Macrophages appeared to display little involvement in CNS lesions. The infected cells observed at the early stage of disease were lymphocytes and microglial cells in the rostral portion of the telencephalon, with infection of these cells in other areas in the next stages. The relationship between these lesions and the presence of viral antigen varied according to the type of lesion: hemorrhages were not associated with the presence of antigen in endothelial cells, but infiltrate-cell apoptosis was temporally and spacially associated to viral infection. However, the link between viral infection and the presence of cell infiltrate was far from clear.
Asunto(s)
Enfermedades del Sistema Nervioso Central/veterinaria , Sistema Nervioso Central/patología , Virus de la Fiebre Porcina Clásica/crecimiento & desarrollo , Peste Porcina Clásica/patología , Animales , Antígenos Virales/análisis , Apoptosis/fisiología , Encéfalo/patología , Encéfalo/ultraestructura , Encéfalo/virología , Sistema Nervioso Central/virología , Enfermedades del Sistema Nervioso Central/patología , Enfermedades del Sistema Nervioso Central/virología , Peste Porcina Clásica/virología , Femenino , Histocitoquímica/veterinaria , Etiquetado Corte-Fin in Situ , Masculino , Microscopía Electrónica de Transmisión/veterinaria , PorcinosRESUMEN
Pigs inoculated with the Alfort 187 isolate of classical swine fever (CSF) virus were used to study the immunological mechanisms associated with the humoral immune response in the disease. Quantitative and qualitative changes in the B-cell population (lambda light chain [C-lambda]-positive, immunoglobulins [Ig]-M-positive, and IgG-positive were demonstrated in the spleen, thymus and ileocaecal lymph node. Blood and serum samples were used to examine changes in leucocytes, albumin/globulin ratios and specific antibodies against CSF virus titration. Despite the lymphoid depletion shown by infected animals, an increase in B cells and potentially immunoglobulin-producing C-lambda+ plasma cells was observed in the lymphoid organs from the onset of disease. The increase in C-lambda+ B cells was matched by a parallel increase in IgM+ cells, which attained peak values from 7 days post-inoculation (dpi), while IgG+ cells increased from 11 dpi onwards. The enhanced biosynthetic capacity of these cells may have been linked to the initiation of a humoral response to CSF virus, and to the progressive decline in the albumin/globulin ratios of inoculated animals. Activation, proliferation and differentiation of B cells coincided with the presence of viral antigen, and with an intense phagocytic and biosynthetic activity of monocytes-macrophages and T lymphocytes. The previously reported increase of cytokine (TNFalpha, IL-1alpha and IL-6) production by monocytes-macrophages, and the release of IL-2, IL-4 and IFNgamma by T lymphocytes, may play a role in the initiation of the humoral immune response in CSF. These changes may have influenced the late appearance of virus-specific antibodies in the study, as well as the progressive increase of immunoglobulins.
Asunto(s)
Linfocitos B/inmunología , Virus de la Fiebre Porcina Clásica/patogenicidad , Peste Porcina Clásica/inmunología , Animales , Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Linfocitos B/metabolismo , Linfocitos B/virología , Peste Porcina Clásica/sangre , Peste Porcina Clásica/virología , Virus de la Fiebre Porcina Clásica/genética , Virus de la Fiebre Porcina Clásica/aislamiento & purificación , Femenino , Inmunohistoquímica/veterinaria , Tejido Linfoide/inmunología , Tejido Linfoide/patología , Masculino , Sus scrofaRESUMEN
We observed the changes in the central nervous system (CNS) of transgenic mice expressing bovine prion protein (Bo-PrP) as a contribution to our knowledge of the pathogenesis of bovine spongiform encephalopathy (BSE). The main result was the detection of hyperphosphorylated tau. This protein was detected for the first time, using immunohistochemical techniques, in the neurons and glial cells of mice experimentally infected with BSE. The results highlighted the involvement of tau protein in the pathogenesis of BSE and the close link between hyperphosphorylated tau deposits and prion protein. Ultrastructural examination revealed a novel arrangement of intraneuronal tau deposits not hitherto reported.
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Encéfalo/metabolismo , Encefalopatía Espongiforme Bovina/metabolismo , Priones/metabolismo , Proteínas tau/metabolismo , Animales , Encéfalo/patología , Encéfalo/ultraestructura , Bovinos , Encefalopatía Espongiforme Bovina/etiología , Encefalopatía Espongiforme Bovina/patología , Femenino , Inmunohistoquímica/veterinaria , Ratones , Ratones Endogámicos CBA , Ratones Transgénicos , Microscopía Electrónica de Transmisión/veterinaria , Fosforilación , Priones/genéticaRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) is well recognized for its role in mediating innate immune responses. However, the mechanisms of TNF-alpha that influence the adaptive immune response to virus infections are not well understood. In this study, we have investigated the role of TNF-alpha in activating the cellular and humoral responses to systemic viral challenge with recombinant replication-defective adenovirus (rAd). Evaluation of T cell function in TNF-alpha-deficient (TNFKO) mice revealed impaired virus-specific proliferation of T cells derived from the draining lymph nodes of the liver. Analysis of dendritic cells (DC) isolated from local draining lymph nodes after systemic challenge showed that DC from TNFKO mice were relatively immature compared with those from strain-matched wild-type mice. In vitro, TNF-alpha was required to mature DC efficiently during virus-mediated stimulation. Adoptive transfer of primed, mature DC into TNFKO mice restored T cell responses and reconstituted anti-adenovirus antibody responses. Thus, TNF-alpha plays a significant role in the maturation of DC after adenovirus challenge both in vitro and in vivo, highlighting the importance of this innate cytokine in activating adaptive immunity to viral challenge.
Asunto(s)
Infecciones por Adenoviridae/inmunología , Células Dendríticas/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adaptación Fisiológica/inmunología , Adenovirus Humanos/inmunología , Traslado Adoptivo , Animales , Linfocitos B/inmunología , Células de la Médula Ósea/inmunología , Diferenciación Celular , Virus Defectuosos/inmunología , Células Dendríticas/citología , Inmunidad Activa , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Large numbers of new neurons are born continuously in the adult subventricular zone (SVZ). The molecular niche of SVZ stem cells is poorly understood. Here, we show that the bone morphogenetic protein (BMP) antagonist Noggin is expressed by ependymal cells adjacent to the SVZ. SVZ cells were found to express BMPs as well as their cognate receptors. BMPs potently inhibited neurogenesis both in vitro and in vivo. BMP signaling cell-autonomously blocked the production of neurons by SVZ precursors by directing glial differentiation. Purified mouse Noggin protein promoted neurogenesis in vitro and inhibited glial cell differentiation. Ectopic Noggin promoted neuronal differentiation of SVZ cells grafted to the striatum. We thus propose that ependymal Noggin production creates a neurogenic environment in the adjacent SVZ by blocking endogenous BMP signaling.
Asunto(s)
Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Neuronas/metabolismo , Proteínas/metabolismo , Receptores de Factores de Crecimiento , Transducción de Señal/fisiología , Animales , Receptores de Proteínas Morfogenéticas Óseas , Proteínas Morfogenéticas Óseas/biosíntesis , Proteínas Morfogenéticas Óseas/farmacología , Trasplante de Tejido Encefálico , Proteínas Portadoras , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cuerpo Estriado/citología , Cuerpo Estriado/metabolismo , Epéndimo/citología , Epéndimo/metabolismo , Trasplante de Tejido Fetal , Expresión Génica , Humanos , Ratones , Ratones Mutantes , Ratones Transgénicos , Microinyecciones , Neuronas/citología , Neuronas/trasplante , Proteínas/farmacología , Receptores de Superficie Celular/biosíntesis , Transducción de Señal/efectos de los fármacosRESUMEN
The cellular and humoral immune responses to adenovirus (Ad) remain a major barrier to Ad-mediated gene therapy. We recently reported that mice deficient in tumor necrosis factor alpha (TNF-alpha) or Fas (APO-1, CD95) have prolonged expression of an Ad transgene expressing a foreign protein in the liver. To determine whether blockade of TNF-alpha or Fas would have the same effect in normal mice, we created transgenes that expressed soluble murine CD8 or CD8 fused to the extracellular regions of TNF receptor 1 (TNFR) or Fas and inserted into the left-end region of first-generation (E1/E3-) Ad vectors. Consistent with the results observed in TNF-deficient mice, expression of the TNFR-CD8 fusion protein was prolonged in vivo compared to that of control proteins. Not only did expression of TNFR-CD8 persist in the liver and the lung, but when coadministered with another first-generation vector, the protein provided "transprotection" for the companion vector and transgene. In addition, TNFR-CD8 attenuated the humoral immune response to the Ad. Together, these findings demonstrate that blockade of TNF-alpha is likely to be useful in extending the expression of an Ad-encoded transgene in a gene therapy application.
Asunto(s)
Adenoviridae/genética , Hígado/metabolismo , Pulmón/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Transgenes , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Anticuerpos Antivirales/biosíntesis , Antígenos CD/fisiología , Antígenos CD8/fisiología , Ensayo de Inmunoadsorción Enzimática , Terapia Genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones SCID , Receptores del Factor de Necrosis Tumoral/fisiología , Receptores Tipo I de Factores de Necrosis Tumoral , Receptor fas/fisiologíaRESUMEN
Adenovirus (Ad) gene transfer vectors are rapidly cleared from infected hepatocytes in mice. To determine which effector mechanisms are responsible for elimination of the Ad vectors, we infected mice that were genetically compromised in immune effector pathways [perforin, Fas, or tumor necrosis factor alpha (TNF-alpha)] with the Ad vector, Ad5-chloramphenicol acetyl transferase (CAT). Mice were sacrificed at 7-60 days postinfection, and the levels of CAT expression in the liver determined by a quantitative enzymatic assay. When the livers of infected mice were harvested 28 days postinfection, the levels of CAT expression revealed that the effectors most important for the elimination of the Ad vector were TNF-alpha > Fas > perforin. TNF-alpha did not have a curative effect on infected hepatocytes, as the administration of TNF-alpha to infected severe combined immunodeficient mice or to infected cultures in vitro had no specific effect on virus persistence. However, TNF-alpha-deficient mice demonstrated a striking reduction in the leukocytic infiltration early on in the infection, suggesting that TNF-alpha deficiency resulted in impaired recruitment of inflammatory cells to the site of inflammation. In addition, the TNF-deficient mice had a significantly reduced humoral immune response to virus infection. These results demonstrate a dominant role of TNF-alpha in elimination of Ad gene transfer vectors. This result is particularly important because viral proteins that disable TNF-alpha function have been removed from most Ad vectors, rendering them highly susceptible to TNF-alpha-mediated elimination.