RESUMEN
Pluripotent stem cell-derived kidney organoids hold great promise as a potential auxiliary transplant tissue for individuals with end-stage renal disease and as a platform for studying kidney diseases and drug discovery. To establish accurate models, it is crucial to thoroughly characterize the morphological features and maturation stages of the cellular components within these organoids. Nephrons, the functional units of the kidney, possess distinct morphological structures that directly correlate with their specific functions. High spatial resolution imaging emerges as a powerful technique for capturing ultrastructural details that may go unnoticed with other methods such as immunofluorescent imaging and scRNA sequencing. In our study, we have applied software capable of seamlessly stitching virtual slides generated from electron microscopy, resulting in high-definition overviews of tissue slides. With this technology, we can comprehensively characterize the development and maturation of kidney organoids when transplanted under the renal capsule of mice. These organoids exhibit advanced ultrastructural developments upon transplantation, including the formation of the filtration barrier in the renal corpuscle, the presence of microvilli in the proximal tubule, and various types of cell sub-segmentation in the connecting tubule similarly to those seen in the adult kidney. Such ultrastructural characterization provides invaluable insights into the structural development and functional morphology of nephron segments within kidney organoids and how to advance them by interventions such as a transplantation. Research Highlights High-resolution imaging is crucial to determine morphological maturation of hiPSC-derived kidney organoids. Upon transplantation, refined ultrastructural development of nephron segments was observed, such as the development of the glomerular filtration barrier.
Asunto(s)
Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Animales , Ratones , Diferenciación Celular , Nefronas/metabolismo , Riñón/ultraestructuraRESUMEN
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease transmitted from dromedary camels to people, which can result in outbreaks with human-to-human transmission. Because it is a subclinical infection in camels, epidemiological measures other than prevalence are challenging to assess. This study estimated the force of infection (FOI) of MERS-CoV in camel populations from age-stratified serological data. A cross-sectional study of MERS-CoV was conducted in Kenya from July 2016 to July 2017. Seroprevalence was stratified into four age groups: <1, 1-2, 2-3 and >3 years old. Age-independent and age-dependent linear and quadratic generalised linear models were used to estimate FOI in pastoral and ranching camel herds. Models were compared based on computed AIC values. Among pastoral herds, the age-dependent quadratic FOI was the best fit model, while the age-independent FOI was the best fit for the ranching herd data. FOI provides an indirect estimate of infection risk, which is especially valuable where direct estimates of incidence and other measures of infection are challenging to obtain. The FOIs estimated in this study provide important insight about MERS-CoV dynamics in the reservoir species, and contribute to our understanding of the zoonotic risks of this important public health threat.
Asunto(s)
Infecciones Asintomáticas/epidemiología , Camelus , Infecciones por Coronavirus/veterinaria , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Animales , Infecciones por Coronavirus/epidemiología , Estudios Transversales , Kenia/epidemiología , PrevalenciaRESUMEN
The liver can be an indicator of the health of an individual or of a group, which can be especially important to identify agents that can cause disease in multiple species. To better characterize hepatic lesions in stranded harbor porpoises (Phocoena phocoena), we analyzed the livers from 39 porpoises that stranded along the Dutch coast between December 2008 and December 2012. The animals were selected because they had either gross or histologic liver lesions with minimal autolysis and no evidence of trematode (Campula oblonga) infection. The most common finding was a chronic hepatitis (22/39, 56.4%) that was often associated with significant disease reported in another organ system (18/22, 81.8%), of which 14 had chronic systemic disease. One case of chronic hepatitis was so severe as to mimic lymphoma, which could only be differentiated with immunohistochemistry. The other common lesions were lipidosis (11/39, 28.2%) and acute hepatitis (6/39, 15.4%), often in combination with mild chronic changes. Overall, although there were no consistent trends in etiology for the hepatic lesions, lipidosis was associated with starvation (8/11, 72.7%) and acute disease, and acute hepatitis was associated with bacterial infections and sepsis (6/6, 100%).
Asunto(s)
Hepatitis Animal/patología , Lipidosis/veterinaria , Hepatopatías/veterinaria , Phocoena , Animales , Femenino , Inmunohistoquímica/veterinaria , Lipidosis/patología , Hígado , Hepatopatías/patología , Masculino , Estudios RetrospectivosRESUMEN
This case report describes orchitis in a stranded adult sexually mature free-living harbour porpoise (Phocoena phocoena). Orchitis, with or without epididymitis, is a rare finding in harbour porpoises and has been reported to be associated with infection with Brucella species or fungi. This porpoise was examined as part of an ongoing investigation into causes of death in harbour porpoises stranded on the Dutch coast. At necropsy, the animal was in very poor body condition and the most significant pathological change encountered was unilateral chronic granulomatous orchitis. Histologically, the seminiferous tubules were multifocally severely distended by large numbers of macrophages and fewer neutrophils that often showed central necrosis, with intra- and extracellular rod-shaped bacteria that stained negatively with Gram stain. No acid-fast bacteria, fungal elements, or spirochetes were detected when the lesions were stained with Ziehl-Neelsen, Fite-Faraco, Warthin-Starry, and Periodic acid-Schiff stains. Culture of samples taken from the testis revealed a pure culture of a bacterium of the Alcaligenaceae family. Further analysis by biochemistry, fatty acid profiling, and 16S rRNA gene sequencing techniques identified the bacterium as a Castellaniella species. The association of this bacterium with the observed lesions remains uncertain.
Asunto(s)
Alcaligenaceae/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/veterinaria , Granuloma/veterinaria , Orquitis/veterinaria , Phocoena , Animales , Resultado Fatal , Infecciones por Bacterias Gramnegativas/diagnóstico , Granuloma/diagnóstico , Granuloma/microbiología , Masculino , Orquitis/diagnóstico , Orquitis/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
Extraskeletal osteosarcomas are rare malignant mesenchymal neoplasms that are able to directly produce osteoid, without requiring a cartilage template. The extraskeletal localization indicates that these neoplasms are not associated with pre-existing skeletal elements or periosteum. We describe the gross and histological findings of a 4-year-old male Rottweiler that presented with an extraskeletal chondroblastic osteosarcoma (also known as osteosarcoma of the chondroblastic subtype) originating from the liver and extending into the lumen of the caudal vena cava, passing through the right atrium and terminating in the right ventricle of the heart immediately below the pulmonary valve. In the liver, predominantly fusiform cells grew in loosely packed streams and whorls. In the vena cava, the neoplasm was multilobular with polygonal neoplastic cells scattered within lacunae in a chondroid matrix. In the cardiac lumen, neoplastic cells produced osteoid that showed multifocal mineralization. Immunohistochemical staining showed no cytokeratin and variable S-100 protein and vimentin immunoreactivity. To the best of our knowledge, this is the first report of a chondroblastic osteosarcoma arising in the liver and showing such extensive and unusual extension into the vasculature.
Asunto(s)
Condrosarcoma/veterinaria , Enfermedades de los Perros/patología , Neoplasias Hepáticas/veterinaria , Osteosarcoma/veterinaria , Animales , Condrosarcoma/patología , Perros , Resultado Fatal , Hígado/irrigación sanguínea , Neoplasias Hepáticas/patología , Masculino , Osteosarcoma/patología , Vena Cava Superior/anomalías , Vena Cava Superior/patologíaRESUMEN
BACKGROUND: We investigated the combination of selective serotonin reuptake inhibitors (SSRIs) with the beta-adrenoceptor/serotonin 1A (5-HT(1A)) antagonist pindolol, based on the concept that 5-HT(1A) receptor blockade would eliminate the need for desensitization of presynaptic 5-HT(1A) receptors and therefore hasten the onset of action and improve the efficacy of SSRIs. However, since pindolol plasma levels after 2.5 mg three times a day are about 60 nmol/L, and the K(i) for the 5-HT(1A) receptor is 30 nmol/L, it is questionable whether pindolol levels in the brain would be sufficient to antagonize 5-HT(1A) receptors. Using microdialysis in the guinea pig, we correlated brain and plasma levels of pindolol with its capability of augmenting paroxetine-induced increases in brain 5-HT levels. In addition, central beta-receptor antagonism of pindolol was studied by investigating blockade of beta-agonist-induced increases in brain cyclic adenosine monophosphate (cAMP) formation. METHODS: Using microdialysis and jugular vein catheterization, we studied the ability of systemically administered pindolol to antagonize central 5-HT(1A) and beta-adrenoceptors, while simultaneously monitoring pindolol plasma and brain concentrations. RESULTS: Augmentation of paroxetine-induced increases in extracellular 5-HT levels in the ventral hippocampus was only observed at steady state plasma levels exceeding 7000 nmol/L (concurrent brain levels 600 nmol/L). In contrast, antagonism of beta-agonist-induced increases of brain cAMP levels was already observed at pindolol plasma levels of 70 nmol/L (concurrent brain levels < 3 nmol/L). CONCLUSIONS: At plasma levels that are observed in patients after 2.5 mg three times a day ( approximately 60 nmol/L), pindolol produces only a partial blockade of presynaptic 5-HT(1A) autoreceptors and does not augment the SSRI-induced 5-HT increase in the guinea pig brain. It is therefore very unlikely that the favorable effects of combining pindolol with SSRIs, as reported in a number of clinical studies, are due to 5-HT(1A) antagonism. Since pindolol completely blocks central beta-adrenoreceptors at clinically relevant plasma levels, it is possible that beta-adrenoceptor antagonism is involved in mediating pindolol's beneficial effects.