RESUMO
BACKGROUND: A 9-year-old boy was admitted to the emergency department because of repetitive vomiting and loss of appetite for 4 days. There was peristalsis present and laboratory tests were normal.
RESUMO
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, which arises from a yet elusive concurrence between genetic and environmental factors. The protein α-synuclein (αSyn), the principle toxic effector in PD, has been shown to interfere with neuronal Ca(2+) fluxes, arguing for an involvement of deregulated Ca(2+) homeostasis in this neuronal demise. Here, we identify the Golgi-resident Ca(2+)/Mn(2+) ATPase PMR1 (plasma membrane-related Ca(2+)-ATPase 1) as a phylogenetically conserved mediator of αSyn-driven changes in Ca(2+) homeostasis and cytotoxicity. Expression of αSyn in yeast resulted in elevated cytosolic Ca(2+) levels and increased cell death, both of which could be inhibited by deletion of PMR1. Accordingly, absence of PMR1 prevented αSyn-induced loss of dopaminergic neurons in nematodes and flies. In addition, αSyn failed to compromise locomotion and survival of flies when PMR1 was absent. In conclusion, the αSyn-driven rise of cytosolic Ca(2+) levels is pivotal for its cytotoxicity and requires PMR1.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Cálcio/metabolismo , Modelos Biológicos , Proteínas de Saccharomyces cerevisiae/metabolismo , alfa-Sinucleína/metabolismo , Acetilcisteína/farmacologia , Animais , Apoptose , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , ATPases Transportadoras de Cálcio/deficiência , ATPases Transportadoras de Cálcio/genética , Humanos , Manganês/metabolismo , Chaperonas Moleculares , Estresse Oxidativo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , alfa-Sinucleína/genética , alfa-Sinucleína/toxicidadeRESUMO
The rarity of Spigelian hernias and the frequent subtle clinical findings can cause an important delay in diagnosis, especially in obese patients. Furthermore it has a high risk of incarceration. When this occurs, a fast recognition and adequate treatment are necessary. Treatment can be primary suture or mesh repair. More recently, the laparoscopic approach has become more popular. We present two cases of incarcerated Spigelian hernia and we give a review of the literature, with specific attention for the anatomical features and pathogenesis.
