Diminuição da expressão dos genes APP e CP em doentes de Alzheimer sugere alteração da exportação de ferro celular nesta demência

Recentemente tem-se assistido a um acumular de evidência sugerindo a implicação de uma desregulação do metabolismo do ferro (Fe) na fisiopatologia da doença de Alzheimer (DA). Neste trabalho, pretendemos esclarecer melhor os mecanismos moleculares subjacentes à homeostasia deste metal na DA, particularmente ao nível do efluxo celular. Assim, mediu-se em células mononucleares do sangue periférico de 73 doentes com DA e 74 controlos a expressão de genes diretamente envolvidos na regulação e exportação celular de Fe, utilizando a técnica de PCR quantitativo. Os resultados mostraram uma diminuição significativa na expressão dos genes aconitase (ACO1; P=0,007); ceruloplasmina (CP; P<0,001) e proteína precursora de beta amilóide (APP; P=0,006) em doentes com DA comparativamente com os voluntários saudáveis. Estas observações apontam para uma diminuição significativa da expressão dos genes associados com a exportação de Fe celular mediada pela ferroportina na DA. Assim, o presente estudo reforça resultados anteriores que mostram alterações no metabolismo do Fe e podem estar na origem da retenção intracelular deste metal e aumento de stress oxidativo caraterísticos desta patologia.

Sobre el sujeto-víctima: configuraciones de una ciudadanía limitada

Una de las virtudes que se le han atribuido a la justicia transicional en los países donde se ha implementado es su capacidad de fortalecer las instituciones y contribuir con el afianzamiento de la democracia. Una de las maneras de potenciar tanto la democracia como el restablecimiento de las víctimas ha sido propiciar su participación dentro de los procesos de justicia transicional y otras políticas públicas cuya finalidad es propender por las garantías de sus derechos. No obstante, la participación democrática de las personas está mediada por la calidad que se les otorga a los sujetos que participan. El objeto de este texto es proponer la necesidad de tener un debate acerca de las implicaciones que trae la forma en que se concibe a las “víctimas” en su participación dentro de procesos de reparación. Este documento concluye poniendo en consideración algunos puntos que podrían hacer parte del debate sobre la conceptualización de víctima y su participación.

Prevalência de úlceras de pressão em dois hospitais portugueses: Impacto da Escala de Braden associada a um protocolo de prevenção

As úlceras de pressão constituem um importante problema de saúde pública comum a diversos cenários de cuidados, em todo o mundo, e também em Portugal, nomeadamente para a população mais idosa. O presente estudo teve como objectivos determinar o impacto da escala de Braden associada a um protocolo de prevenção de úlceras de pressão na prevalência destas lesões, assim como, monitorizar o problema das úlceras de pressão em dois hospitais portugueses, em que o Hospital A utiliza estes instrumento e o Hospital 8 não usa esses instrumentos. Foi utilizado o Instrumento de Prevalência de Úlceras de Pressão validado para Portugal na recolha dos dados. Os dados foram obtidos através da observação directa dos doentes. Foram realizadas duas avaliações com um intervalo de três meses em cada hospital. Os resultados encontrados revelaram que as úlceras de pressão constituem um problema de saúde para os dois hospitais observados. No entanto, o Hospital A apresenta menor taxa de prevalência de úlceras de pressão, menor número de úlceras de pressão mais graves, menor possibilidade de um doente adquirir uma úlcera de pressão e maior utilização de medidas preventivas. Os valores encontrados foram estatisticamente significativos para p <0,05. Confirma-se que a utilização da escala de Braden associada a um protocolo de prevenção de úlceras de pressão é uma medida eficaz na redução do número de úlceras de pressão. Para uma maior eficácia deste instrumento será importante a sua utilização como ferramenta de controlo da adequação das medidas preventivas. ABSTRACT; Pressure ulcers are an important public health problem common to several scenarios of care in the world, and also in Portugal, particularly for the elderly. This study aims to determine the impact of the Braden scale associated with a protocol for prevention of pressure ulcers in prevalence of these lesions, as well as monitor the problem of pressure ulcers in two Portuguesa hospitais, the Hospital A uses these instrument and Hospital B doesn’t. It was used the instrument of Prevalence of pressure ulcers validated for Portugal in the data collection. Data were collected through direct observation of patients. There were two assessments with an interval of three months in each hospital. The results showed that the pressure ulcers are a health problem for both hospitals observed. However, the Hospital A provides a lower prevalence rate of pressure ulcers, lower number of pressure ulcers more serious, less possibility of a patient acquiring a pressure ulcer and increased use of preventive measures. The values were statistically significant for p<0.05. lt is confirmed that the use of the Braden scale associated with a protocol for prevention of pressure ulcers is an effective measure in reducing the number of pressure ulcers. For greater efficiency will be important to use it as a tool for monitoring the adequacy of preventive measures.

Extraction and purification of immunoglobulin G with aqueous biphasic systems

The immune system is able to produce antibodies, which have the capacity to recognize and to bind to foreign molecules or pathogenic organisms. Currently, there are a diversity of diseases that can be treated with antibodies, like immunoglobulins G (IgG). Thereby, the development of cost-efficient processes for their extraction and purification is an area of main interest in biotechnology. Aqueous biphasic systems (ABS) have been investigated for this purpose, once they allow the reduction of costs and the number of steps involved in the process, when compared with conventional methods. Nevertheless, typical ABS have not showed to be selective, resulting in low purification factors and yields. In this context, the addition of ionic liquids (ILs) as adjuvants can be a viable and potential alternative to tailor the selectivity of these systems. In this work, ABS composed of polyethylene glycol (PEG) of different molecular weight, and a biodegradable salt (potassium citrate) using ILs as adjuvants (5 wt%), were studied for the extraction and purification of IgG from a rabbit source. Initially, it was tested the extraction time, the effect on the molecular weight of PEG in a buffer solution of K3C6H5O7/C6H8O7 at pH≈7, and the effect of pH (59) on the yield (YIgG) and extraction efficiency (EEIgG%) of IgG. The best results regarding EEIgG% were achieved with a centrifugation step at 1000 rpm, during 10 min, in order to promote the separation of phases followed by 120 min of equilibrium. This procedure was then applied to the remaining experiments. The results obtained in the study of PEGs with different molecular weights, revealed a high affinity of IgG for the PEG-rich phase, and particularly for PEGs of lower molecular weight (EEIgG% of 96 % with PEG 400). On the other hand, the variation of pH in the buffer solution did not show a significant effect on the EEIgG%. Finally, it was evaluated the influence of the addition of different ILs (5% wt) on the IgG extraction in ABS composed of PEG 400 at pH≈7. In these studies, it was possible to obtain EEIgG% of 100% with the ILs composed of the anions [TOS]-, [CH3CO2]-and Cl-, although the obtained YIgG% were lower than 40%. On the other hand, the ILs composed of the anions Br-, as well as of the cation [C10mim]+, although not leading to EEIgG% of 100%, provide an increase in the YIgG%. ABS composed of PEG, a biodegradable organic salt and ILs as adjuvants, revealed to be an alternative and promising method to purify IgG. However, additional studies are still required in order to reduce the loss of IgG.

Unusual presentation of Gilbert disease with high levels of unconjugated bilirubin: report of two cases

Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events, bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dl in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.

Next-generation sequencing of hereditary hemochromatosis-related genes: novel likely pathogenic variants found in the Portuguese population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1GNC)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5′-UTR of HAMP gene(c.-25GNA). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Um enfermeiro presidente da República. Você sabia?

Descreve a vida de Samora Machel, um enfermeiro moçambicano, que liderou guerrilhas até obter a independência e criar a República de Moçambique. Narrar sua história de vida e seu papel na saúde de seu país, tem por objetivo mostrar que a política pode ser um meio para que outros enfermeiros, em outros países, possam também seguir por esse caminho para o beneficio de toda uma população e através do exercício da liderança, também contribuir para melhorar a saúde e as condições de vida das comunidades. Além de lutar contra o racismo, a discriminação, o analfabetismo, a pobreza e a seca durante mais de dez anos em seu governo, Samora Machel teve que lutar internamente contra forças políticas oponentes. De qualquer modo, ele se tornou um exemplo em seu país onde é reverenciado e venerado como herói nacional.

Diferencias culturales en deberes y derechos entre los docentes de Infantil-Primaria y Secundaria

El trabajo analiza las diferencias culturales entre el profesorado de Infantil-Primaria y Secundaria a la luz de sus deberes y derechos. Han participado 394 docentes de toda España de educación Infantil, Primaria y Secundaria, elegidos al azar, contestando a un cuestionario enviado por correo postal a los centros seleccionados aleatoriamente. Se utiliza como instrumento el cuestionario “Deberes y derechos del profesorado en la comunidad educativa” y se confirma la hipótesis: existen diferencias culturales docentes significativas que nos permiten establecer distintas subculturas.

Propriedades antioxidante, anti-hemostástica e antiproliferativa de galactanas sulfatadas da alga vermelha hypnea musciformis (wulfen) j. V. Lamouroux

Marine algae are one of the major sources of biologic compounds. In extracellular matrix of these organisms there are sulfated polysaccharides that functions as structural components and provides protection against dehydration. The fraction 1.0 (F1.0) rich in sulfated galactans obtained from red seaweed Hypnea musciformis was physicochemical characterized and evaluated for pharmacologic activity through antioxidant activity, cytotoxic action on erythrocytes, anticoagulant, stimulatory action under antithrombotic heparan sulfate synthesis and their effects on cell proliferation and cycle cell progression. The main components of F1.0 were carbohydrates (49.70 ± 0.10%) and sulfate (44.59 ± 0.015%), presenting phenolic compounds (4.79 ± 0.016%) and low protein contamination (0.92 ± 0.001%). Fraction 1.0 showed polidisperse profile and signs in infrared analysis in 1262, 1074 and 930, 900 and 850 attributed to sulfate esters S=O bond, presence of a 3,6- anidrogalactose C-O bond, non-sulfated β-D-galactose and a C-O-SO4 bond in galactose C4, respectively. The fraction rich in sulfated galactans exhibited strong antioxidant action under lipid peroxidation assay with IC50 of 0.003 mg/mL. Besides the inhibition of hemolysis induced by H2O2 in erythrocytes treated with F1.0, this fraction did not promote significant cytotoxity under erythrocytes membranes. F1.0 exhibited low anticoagulant activity causing moderate direct inhibition of enzimatic activity of thrombin. This fraction promoted stimulation around of 4.6 times on this synthesis of heparan sulfate (HS) by rabbit aortic endothelial cells (RAEC) in culture when was compared with non treated cells. The fraction of this algae displayed antiproliferative action under RAEC cells causing incresing on cell number on S fase, blocking the cycle cell progression. Thus F1.0 presented cytostatic and no cytotoxic action under this cell lineage. These results suggest that F1.0 from H. musciformis have antioxidant potential which is a great effect for a compound used as food and in food industry which could be an alternative to food industry to prevent quality decay of lipid containing food due to lipid peroxidation. These polysaccharides prevent the lipid peroxidation once the fraction in study exhibited strong inhibitory action of this process. Furthermore that F1.0 present strong antithrombotic action promoting the stimulation of antithrombotic HS synthesis by endothelial cells, being important for thrombosis preventing, by its inhibitory action under reactive oxygen species (ROS) in some in vitro methods, being involved in promotion of hypercoagulability state.