Clinical and Pathological Findings in Women with Fabry Disease

Introduction. Fabry disease is a rare metabolic disorder caused by the genetic deficiency of the lysosomal hydrolase alpha-galactosidase A, located on chromosome X. Females with the defective gene are more than carriers and can develop a wide range of symptoms. Nevertheless, disease symptoms generally occur later and are less severe in women than in men. The enzyme deficiency manifests as a glycosphingolipidosis with progressive accumulation of glycosphingolipids and deposit of inclusion bodies in lysosomes giving a myelinlike appearance. Patients and Methods. Records of renal biopsies performed on adults from 1st January 2008 to 31st August 2011, were retrospectively examined at the Renal Pathology Laboratory. We retrieved biopsies diagnosed with Fabry disease and reviewed clinical and laboratory data and pathology findings. Results. Four female patients with a mean age of 49.3±4.5 (44-55) years were identified. The mean proteinuria was 0.75±0.3 g/24h (0.4-1.2) and estimated glomerular filtration rate (CKD EPI equation) was 71±15.7 ml/min/1.73m2 (48-83). Three patients experienced extra-renal organ involvement (cerebrovascular, cardiac, dermatologic, ophthalmologic and thyroid) with distinct severity degrees. Leukocyte α-GAL A activity was below normal range in the four cases but plasma and urinary enzymatic activity was normal. Light microscopy showed predominant vacuolisation of the podocyte cytoplasm and darkly staining granular inclusions on paraffin and plastic-embedded semi-thin sections. Electron microscopy showed in three patients the characteristic myelin-like inclusions in the podocyte cytoplasm and also focal podocyte foot process effacement. In one case the inclusions were also present in parietal glomerular cells, endothelial cells of peritubular capillary and arterioles. Conclusion. Clinical signs and symptoms are varied and can be severe among heterozygous females with Fabry disease. Intracellular accumulation of glycosphingolipids is a characteristic histologic finding of Fabry nephropathy. Since this disease is a potentially treatable condition, its early identification is imperative. We should consider it in the differential diagnosis of any patient presenting with proteinuria and/or chronic kidney disease, especially if there is a family history of kidney disease

Estudo de caso: Gestão do risco operacional ligado às reclamações dos clientes na indústria hoteleira

Cada vez é mais difícil fidelizar os clientes, o desafio para os hotéis continua a ser a diminuição do número de reclamações e a melhoria da satisfação dos hóspedes. A indústria hoteleira já implementou processos para ter uma regularidade na qualidade do serviço. Contudo, no dia a dia os clientes continuam a reclamar quando existe uma falha no serviço. É aqui que entra o conceito do risco operacional, um conceito mais conhecido no setor da banca e pouco estudado na literatura para a indústria do Turismo e da Hotelaria. O relatório de estágio inclui um estudo de caso, criado de maneira a simular as estadias de um casal que vem com regularidade ao Hotel cinco estrelas Penha Longa Ritz-Carlton. Cada reclamação foi resolvida da melhor maneira para satisfazer novamente os hóspedes e o custo associado foi simulado com o objetivo de medir o impacto do risco operacional na rendibilidade. Em conclusão, o risco operacional tem de ser medido com cuidado, mesmo que não seja suposto gerir perdas financeiras significativas, o seu custo tem um impacto na rendibilidade. Existem várias formas de gerir o risco operacional, antecipando processos bem definidos no papel até à gestão das reclamações.As it becomes more complicated to build up customer loyalty, the challenge for hotels continues to be the reduction of customer complaints and the improvement of customer satisfaction. The Hotel industry already implemented processes to assure a regularity in the service quality. However, customers are still complaining on a daily basis when they are victim of a service failure. The operational risk is a concept known in the bank sector and few studies exist for tourism and Hotel industry. The internship report includes a case study, created in a way to simulate various stays of a couple that comes regularly in the five stars Hotel Penha Longa Ritz-Carlton. Each complaint was solved in the best way to satisfy the client and the cost was simulated in order to measure the impact of operational risk on profitability. To conclude, operational risk has to be considered carefully, even if it is not supposed to generate important loss, the cost has impact on profitability. It exists various ways to manage the operational risk, from the anticipation with well-defined processes until the complaints management

Competências não técnicas do enfermeiro instrumentista

Relatório de Estágio apresentado para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Enfermagem PerioperatóriaO presente relatório de estágio enquadra-se no 1º Curso de Mestrado em Enfermagem Perioperatória, da Escola Superior de Saúde do Instituto Politécnico de Setúbal. Foi redigido segundo a metodologia de projeto, focando-se na integração de conhecimentos e competências adquiridas durante o curso, no domínio da enfermagem perioperatória. Tem como objetivos estabelecidos: (1) reflexão crítica acerca das atividades realizadas em contexto de estágio; (2) desenvolvimento de um projeto acerca das competências não técnicas do enfermeiro instrumentista; (3) reflexão crítica acerca do desenvolvimento de competências de mestre em enfermagem perioperatória. De forma a responder aos objetivos propostos organizou-se a estrutura deste relatório por três capítulos distintos: Capítulo I – onde consta o enquadramento concetual, considerando a teoria do autocuidado de Dorothea Elizabeth Orem; e enquadramento teórico, acerca do conceito de competência em enfermagem perioperatória. Capítulo II – corresponde ao enquadramento metodológico, onde é fundamentado o método seguido para a construção do projeto, exposto o tipo de estudo conduzido, o trabalho de campo desenvolvido, bem como os processos de colheita e tratamento de dados, considerando sempre as questões éticas do processo de investigação. Capítulo III – é realizada a reflexão sobre o estágio realizado, assim como a aquisição do perfil de competências de mestre em enfermagem perioperatória. A realização deste relatório de estágio permitiu a aquisição de conhecimentos no domínio da enfermagem perioperatória. Com os contributos da investigação elaborada, foi possível a compreensão e aplicação destes saberes para a resolução de problemas, em ambiente clinico multidisciplinar, consciente das implicações científicas, éticas, deontológicas e jurídicas.This internship report is part of the 1st Master in Perioperative Nursing, taken in Escola Superior de Saúde do Instituto Politécnico de Setúbal. It has been drafted according to project methodology, focusing on the integration of knowledge and skills acquired during the course in the field of perioperative nursing. Its stated objetives are: (1) critical analysis of the activities undertaken in the stage context; (2) project development for scrub nurses non-technical skills; (3) critical assessment on the development master competencies in perioperative nursing. In order to meet the proposed objetives, this report is organized by three chapters: Chapter I – with the conceptual framework, considering the self-care theory of Dorothea Elizabeth Orem; and theoretical framework of competence in perioperative nursing. Chapter II - corresponds to the methodological framework, which is based the method followed for the construction of the project, stated the type of study conducted, the field work and the procedures for collection and processing of data, always considering ethical issues in research process. Chapter III - is held to assess the internship stage, as well as the acquisition of master skills profile in perioperative nursing. The completion of this internship report allowed the acquisition of knowledge in the field of perioperative nursing. With the contributions of elaborate investigation, it was possible the understanding and application of this knowledge to solve problems in a multidisciplinary clinical environment, aware of the scientific, ethical, ethical and legal implications

Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells: Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity

Uncoupling proteins (UCPs) uncouple oxidative phosphorylation from ATP synthesis by dissipating proton gradient across mitochondrial inner membrane. The physiological role of neuronal specific UCP5 is unknown. We explored the effects of reduced UCP5 expression on mitochondrial membrane potential (MMP), oxidative stress, ATP levels, and cell viability, under normal and MPP +-induced cytotoxic conditions, in human catecholaminergic SH-SY5Y cells. UCP5 expression was reduced by 56% by siRNA, compared to scrambled-siRNA controls. UCP5 knockdown induced apoptosis but did not affect basal levels of ATP, oxidative stress and MMP in the cells under normal conditions. However, UCP5 knockdown increased MPP+-induced cytotoxicity by 15% and oxidative stress levels by 40%, and partially restored MPP+-induced mitochondrial depolarization by 57%. UCP2 and UCP4 expression were unaffected by UCP5 knockdown. Exacerbation of cytotoxicity, oxidative stress and modification of MMP with reduced UCP5 expression in the face of MPP+ toxicity suggest that UCP5 might be physiologically important in the pathology of oxidative stress-induced neurodegeneration. © 2006 Wiley-Liss, Inc.link_to_subscribed_fulltex

Uncoupling proteins: Targets of endocrine disruptors?

The roles of uncoupling proteins (UCPs) are discussed. Particular attention has been paid to the roles of UCP2 to UCP5 as agents mediating thermogenesis, and to the concept of limited or "mild" uncoupling as a means of reducing oxidative stress. The role of the endocrine system, thyroid hormones and catecholamines, in regulating expression of UCPs is also discussed. © 2005 Elsevier Ireland Ltd. All rights reserved.link_to_subscribed_fulltex

Anti-aquaporin-4 antibodies in idiopathic inflammatory 9 demyelinating disorders

Introduction: Idiopathic inflammatory demyelinating disorders (IIDD) affect the central nervous system. In classical multiple sclerosis (CMS), brain, optic nerves (optic neuritis [ON]) and spinal cord (acute transverse myelitis [ATM]) are affected. In neuromyelitis optica (NMO), optic nerves and spinal cord are predominantly affected. NMO-IgG, an antibody targeting aquaporin-4 (AQP4) water channel, is a marker for NMO. We studied the frequency and clinical relevance of anti-AQP4 antibodies seropositivity in IIDD patients. Methods: NMO-IgG was detected by indirect immunofluorescence using primate cerebellum. Results: NMO-IgG was detected in 6 of 10 NMO patients (60%), 6 of 10 idiopathic relapsing transverse myelitis (IRTM) patients (60%), 2 of 9 idiopathic relapsing optic neuritis patients (22%), 1 of 11 patients (9%) having single ON attack, 1 of 30 CMS patients (3%), and none of patients having single ATM attack or controls. Comparing NMO-IgG–seropositive (n=12) with NMO-IgG–seronegative (n=8) patients having NMO or IRTM, NMO-IgG seropositivity was associated with a higher relapse rate in the first 2 years, 1.5 and 0.6 attacks/year for seropositive and seronegative groups respectively (P=0.006), and non-significant trend towards more severe ON and myelitis with poorer clinical outcome. Conclusion: Anti-AQP4 antibodies facilitate diagnosis of NMO spectrum disorders and anti-AQP4 antibodies seropositivity is associated with higher relapse rate in the first 2 years

Ascorbic acid inhibits ROS production, NF-κB activation and prevents ethanol-induced growth retardation and microencephaly

In this study, we established an embryo model to study the effects of ethanol on fetal development. When embryos of Xenopus laevis (the African clawed frog) were exposed to ethanol, the resultant tadpoles had significantly reduced brain sizes (microencephaly) and retarded growth rates. These effects, similar to those observed in human fetal alcohol syndrome (FAS), were dose- and time-dependent. We further showed that the antioxidant ascorbic acid (vitamin C) could inhibit the ethanol-induced reactive oxygen species (ROS) production and NF-κB activation and protect the ethanol-treated embryos against microencephaly and growth retardation. These results suggest the involvement of NF-κB and oxidative stress in ethanol-mediated developmental defects, and the potential use of ascorbic acid as a new and effective protective agent for FAS. © 2004 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

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Transcriptional regulation of UCP4 by NF-kappa B and its role in mediating protection against MPP+ toxicity

Mitochondrial uncoupling protein-4 (UCP4) enhances neuronal cell survival in MPP+-induced toxicity by suppressing oxidative stress and preserving intracellular ATP and mitochondrial membrane potential. UCP4 expression is increased by MPP+, but its regulation is unknown. Using serial human UCP4 promoter-luciferase reporter gene constructs, we identified and characterized several cis-acting elements that can regulate UCP4 expression. Core promoter activity exists within 100bp upstream of the transcription initiation site (TIS=+1). Both CAAT box (-33/-27) and Sp1 (-62/-49) elements are crucial and act synergistically in its transcription. We identified a NF-κB putative binding site at -507/-495. Mutation of this site significantly decreased UCP4 promoter activity. Activation of NF-κB by TNFα or cycloheximide increased, whereas its inhibition by 4-hydroxy-2-nonenal or transfection of pIκBαM suppressed, UCP4 promoter activity. NF-κB inhibition significantly suppressed the MPP+-induced increase in UCP4 expression. MPP+ increased specific binding of NF-κB protein complexes to this site in electrophoretic mobility shift assay. Both UCP4 knockdown and NF-κB inhibition exacerbated MPP+-induced cell death. We present the first direct evidence that UCP4 is regulated by NF-κB, mediated via a functional NF-κB site in its promoter region, and that UCP4 has a significant role in NF-κB prosurvival signaling, mediating its protection against MPP+ toxicity. © 2010 Elsevier Inc.link_to_subscribed_fulltex