Calbindin D28k Expression and the Absence of Apoptosis in the Cerebellum of Solatium bonariense L-lntoxicated Bovines

Solanum bonariense intoxication is characterized by cerebellar neuronal vacuolation, degeneration, and necrosis. Cerebellar Purkinje cells seem especially susceptible, but more research is needed to determine the pathogenesis of neuronal necrosis and the mechanism of Purkinje cell susceptibility. Calbindin D28k (CbD28k) is highly expressed in Purkinje cells and has been used as a marker for normal and degenerative Purkinje cells. The goal of this study was to describe S bonariense-induced disease by ascertaining Purkinje cell-specific degenerative changes using CbD28k expression and to correlate this with apoptosis in Purkinje cells, as determined using TUNEL (transferase-mediated dUTP-biotin nick end-labeling) and ultrastructural changes. In all cases, an increase in both dose and duration of S bonariense intoxication resulted in a decrease in the number of Purkinje cells. CbD28k immunohistochemistry was an excellent marker for Purkinje cells because immunoreactivity did not change in normal or degenerative tissues. This finding suggests that excessive calcium excitatory stimulation does not induce rapid neuronal degeneration and death. As found in previous studies, TUNEL tests and electron microscopy suggest that Purkinje cell degeneration and death are not occurring via an apoptotic process. These findings suggest that S bonariense poisoning induces progressive Purkinje cell death that is not mediated by excitotoxicity or apoptotic activation.Facultad de Ciencias Veterinaria

Calbindin D28k Expression and the Absence of Apoptosis in the Cerebellum of Solatium bonariense L-lntoxicated Bovines

Solanum bonariense intoxication is characterized by cerebellar neuronal vacuolation, degeneration, and necrosis. Cerebellar Purkinje cells seem especially susceptible, but more research is needed to determine the pathogenesis of neuronal necrosis and the mechanism of Purkinje cell susceptibility. Calbindin D28k (CbD28k) is highly expressed in Purkinje cells and has been used as a marker for normal and degenerative Purkinje cells. The goal of this study was to describe S bonariense-induced disease by ascertaining Purkinje cell-specific degenerative changes using CbD28k expression and to correlate this with apoptosis in Purkinje cells, as determined using TUNEL (transferase-mediated dUTP-biotin nick end-labeling) and ultrastructural changes. In all cases, an increase in both dose and duration of S bonariense intoxication resulted in a decrease in the number of Purkinje cells. CbD28k immunohistochemistry was an excellent marker for Purkinje cells because immunoreactivity did not change in normal or degenerative tissues. This finding suggests that excessive calcium excitatory stimulation does not induce rapid neuronal degeneration and death. As found in previous studies, TUNEL tests and electron microscopy suggest that Purkinje cell degeneration and death are not occurring via an apoptotic process. These findings suggest that S bonariense poisoning induces progressive Purkinje cell death that is not mediated by excitotoxicity or apoptotic activation.Facultad de Ciencias Veterinaria

Immunohistochemical analysis of cytoskeleton and ubiquitin in cerebellum of poisoned cattle by Solanum bonariense

El Solanum bonariense L., es un arbusto perenne, autóctono en Uruguay, Argentina y sur de Brasil. Al ser ingerido por los bovinos en pastoreo, les ocasiona una degeneración cortical cerebelosa, afectando específicamente a las células de Purkinje. Estas presentan el pericario extensamente vacuolado con desplazamiento del núcleo, con progresiva muerte neuronal. En los axones de estas neuronas se observa presencia de esferoides axonales en la sustancia blanca cerebelosa, que finalmente son sustituidos por microcavitaciones en la sustancia blanca. El objetivo del presente trabajo fue describir el patrón de inmunoreactividad contra diferentes elementos del citoesqueleto y la ubiquitina conjugada a proteínas marcadas para degradarse dentro de las células de Purkinje de cerebelos de bovinos intoxicados natural o experimentalmente por ingestión de Solanum bonariense L.Facultad de Ciencias Veterinaria

Calbindin d 28k expression in the cerebellum of normal and solanum bonariense L. Intoxicated bovines

La ingestión natural o experimental de Solanum bonariense L. ocasiona una degeneración cortical cerebelosa en bovinos. Esta lesión se debe a la degeneración específica de las células de Purkinje, postulándose que la misma se debe a alteraciones metabólicas específicas, demostradas previamente por estudios ultraestructurales e inmunohistoquímicos. La Calbindina-28kD (Cb28k) ha sido considerada como un marcador específico de células de Purkinje. La alteración de esta inmunoreacción se vincula al desarrollo de diferentes enfermedades neurodegenerativas en humanos. El objetivo del presente trabajo fue analizar la expresión de Cb28k en cerebelos de bovinos normales y en los intoxicados con Solanum bonariense L.Facultad de Ciencias Veterinaria

Calbindin D28k Expression and the Absence of Apoptosis in the Cerebellum of Solatium bonariense L-lntoxicated Bovines

Solanum bonariense intoxication is characterized by cerebellar neuronal vacuolation, degeneration, and necrosis. Cerebellar Purkinje cells seem especially susceptible, but more research is needed to determine the pathogenesis of neuronal necrosis and the mechanism of Purkinje cell susceptibility. Calbindin D28k (CbD28k) is highly expressed in Purkinje cells and has been used as a marker for normal and degenerative Purkinje cells. The goal of this study was to describe S bonariense-induced disease by ascertaining Purkinje cell-specific degenerative changes using CbD28k expression and to correlate this with apoptosis in Purkinje cells, as determined using TUNEL (transferase-mediated dUTP-biotin nick end-labeling) and ultrastructural changes. In all cases, an increase in both dose and duration of S bonariense intoxication resulted in a decrease in the number of Purkinje cells. CbD28k immunohistochemistry was an excellent marker for Purkinje cells because immunoreactivity did not change in normal or degenerative tissues. This finding suggests that excessive calcium excitatory stimulation does not induce rapid neuronal degeneration and death. As found in previous studies, TUNEL tests and electron microscopy suggest that Purkinje cell degeneration and death are not occurring via an apoptotic process. These findings suggest that S bonariense poisoning induces progressive Purkinje cell death that is not mediated by excitotoxicity or apoptotic activation.Facultad de Ciencias Veterinaria

Predicting hospital stay, mortality and readmission in people admitted for hypoglycaemia: prognostic models derivation and validation

Aims/hypothesis: Hospital admissions for hypoglycaemia represent a significant burden on individuals with diabetes and have a substantial economic impact on healthcare systems. To date, no prognostic models have been developed to predict outcomes following admission for hypoglycaemia. We aimed to develop and validate prediction models to estimate risk of inpatient death, 24 h discharge and one month readmission in people admitted to hospital for hypoglycaemia. Methods: We used the Hospital Episode Statistics database, which includes data on all hospital admission to National Health Service hospital trusts in England, to extract admissions for hypoglycaemia between 2010 and 2014. We developed, internally and temporally validated, and compared two prognostic risk models for each outcome. The first model included age, sex, ethnicity, region, social deprivation and Charlson score (‘base’ model). In the second model, we added to the ‘base’ model the 20 most common medical conditions and applied a stepwise backward selection of variables (‘disease’ model). We used C-index and calibration plots to assess model performance and developed a calculator to estimate probabilities of outcomes according to individual characteristics. Results: In derivation samples, 296 out of 11,136 admissions resulted in inpatient death, 1789/33,825 in one month readmission and 8396/33,803 in 24 h discharge. Corresponding values for validation samples were: 296/10,976, 1207/22,112 and 5363/22,107. The two models had similar discrimination. In derivation samples, C-indices for the base and disease models, respectively, were: 0.77 (95% CI 0.75, 0.80) and 0.78 (0.75, 0.80) for death, 0.57 (0.56, 0.59) and 0.57 (0.56, 0.58) for one month readmission, and 0.68 (0.67, 0.69) and 0.69 (0.68, 0.69) for 24 h discharge. Corresponding values in validation samples were: 0.74 (0.71, 0.76) and 0.74 (0.72, 0.77), 0.55 (0.54, 0.57) and 0.55 (0.53, 0.56), and 0.66 (0.65, 0.67) and 0.67 (0.66, 0.68). In both derivation and validation samples, calibration plots showed good agreement for the three outcomes. We developed a calculator of probabilities for inpatient death and 24 h discharge given the low performance of one month readmission models. Conclusions/interpretation: This simple and pragmatic tool to predict in-hospital death and 24 h discharge has the potential to reduce mortality and improve discharge in people admitted for hypoglycaemia

Segurança do paciente no uso de medicamentos após a alta hospitalar: estudo exploratório1

No Brasil, são escassos os estudos sobre estratégias para a segurança do paciente no processo de uso de medicamentos após a alta hospitalar, o que dificulta o conhecimento sobre a atuação de hospitais brasileiros nessa área. Neste artigo, buscou-se compreender a dinâmica e os desafios do cuidado fornecido ao paciente pela equipe hospitalar, visando à segurança no processo de uso de medicamentos após a alta hospitalar. Realizou-se pesquisa exploratória por meio de entrevistas com médicos, enfermeiros, farmacêuticos e assistentes sociais do Hospital Universitário da Universidade de São Paulo. Foram pesquisadas as atividades de cuidado com a farmacoterapia durante e após a hospitalização, incluindo o acesso a medicamentos após alta, a existência de articulação do hospital com outros serviços de saúde, e barreiras para desenvolver essas atividades. A principal estratégia adotada é a orientação de alta, realizada de forma estruturada, principalmente para cuidadores de pacientes pediátricos. Em situações específicas, ocorre mobilização da equipe para viabilização do acesso a medicamentos prescritos na alta. Reconciliação medicamentosa está em fase de implantação, e visita domiciliar é realizada apenas para pacientes críticos com problemas de locomoção. As principais barreiras identificadas foram insuficiência de recursos humanos e falta de tecnologias de informação. Conclui-se que são desenvolvidas algumas estratégias, porém com limitações e sem articulação adequada com outros serviços de saúde para a continuidade do cuidado. Isto sugere a necessidade de concentração de esforços para transpor as barreiras identificadas, contribuindo para a segurança do paciente na interface entre hospital, atenção básica e domicílio