Resistance to recombinant human erythropoietin therapy in haemodialysis patients: Focus on inflammatory cytokines, leukocyte activation, iron status and erythrocyte damage

Anaemia is a common complication in haemodialysis patients. This condition is associated to a decreased bone marrow production of erythrocytes, mainly due to the inability of the failing kidneys to secrete erythropoietin (EPO). The introduction of recombinant human EPO (rhEPO) therapy led to a significant reduction in anaemia and improved patients’ quality of life. However, there is a marked variability in the sensitivity to rhEPO, with up to 10-fold variability in dose requirements to achieve correction of anaemia. Approximately 5-10% of the patients show a marked resistance to rhEPO therapy. rhEPO resistance is associated to an increased morbidity and mortality of haemodialysis patients. In this paper a revision of the mechanisms underlying resistance to rhEPO therapy will be performed, with particular emphasis on inflammatory cytokines, leukocyte activation, iron status, and erythrocyte damage

Coexistence of congenital red cell pyruvate kinase and band 3 deficiency

The authors report the case of a 9-year-old Caucasian girl, born in northern Portugal, with chronic nonspherocytic haemolytic anaemia and without family history of anaemia. The aethiological study of this anaemia revealed pyruvate kinase deficiency (PKD), because of two previously described mutations (426Arg fi Trp and 510Arg fi Gln). Since the blood smear revealed features not fully compatible with PKD diagnosis, additional tests were performed for the propositus and her parents, namely red blood cell membrane protein analysis. A decrease in proteins band 3 (15%) and 4.2 (18%) was found in the propositus. Her father presented only a decrease in band 3 (11%). Coexistence of PKD and erythrocyte membrane proteins deficiency in the same patient is very uncommon. Our findings suggest that a careful blood smear observation may lead to the identification of a combined deficiency in erythrocyte membrane proteins and enzymopathies

Erythropoietin levels in the different clinical forms of hereditary spherocytosis

Erythropoietin (EPO), the main growth factor responsible for the regulation of red blood cell production, may be overproduced when blood loss or haemolysis occurs. Patients with mild hereditary spherocytosis (HS) are able to maintain normal haemoglobin concentration, whereas typical and severe HS patients develop an anaemic state. Splenectomy usually reverses anaemia. We aimed to clarify the role of EPO in the response to enhanced spherocyte destruction, and to look for a linkage with the broad clinical spectra of HS. EPO levels, reticulocyte count and production index (RPI), other parameters used to classify HS and the protein deficiencies underlying HS were evaluated in previously diagnosed unsplenectomised (n ¼ 24) and splenectomised (n ¼ 10) patients presenting mild, typical or severe HS. A significant increase in EPO was observed in all unsplenectomised HS patients. In the mild form, a significant correlation of EPO with reticulocyte count and RPI was observed; however, this correlation disappeared in typical HS patients. Splenectomised HS patients presented a correction in EPO levels in all forms of HS, although the reticulocyte count and RPI sustained slightly higher values. Our data show HS as a disease linked to an overproduction of EPO, according to the severity of the disease; however, a disturbance in erythropoiesis seems to occur in typical HS. Moreover, splenectomy leads to a correction in the EPO levels

Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood

Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation

Cardiovascular risk factors in Portuguese obese children and adolescents: impact of small reductions in body mass index imposed by lifestyle modifications

Objectives: Evaluate cardiovascular risk factors in Portuguese obese children and adolescents and the long-term effects of lifestyle modifications on such risk factors. Design: Transversal cohort study and longitudinal study. Setting: University Hospital S. João and Children's Hospital Maria Pia, Porto. Patients/Participants: 148 obese children and adolescents [81 females (54.7%); mean age of 11.0 years]and 33 controls (sex and age matched) participated in a cross-sectional study. Sixty obese patients agreed to participate in an one year longitudinal study after medical and nutritionist appointments to improve lifestyle modification; a substantial body mass index (BMI) reduction was defined by a decrease in BMI z-score (BMI z-sc) of 0.3 or more over the studied period. Main Outcome measures: Lipid profile (triglycerides, cholesterol, HDLc, LDLc, lipoprotein (a), apolipoproteins A and B) and circulating levels of C-reactive protein (CRP), adiponectin, glucose, and insulin. Results: Compared with the lean children, obese patients demonstrated statistically significantly higher insulin resistance index [Homeostasis model assessment (HOMA)], and triglycerides, LDLc, apolipoprotein (apo) B, insulin and CRP concentrations, whereas their HDLc and apo A levels were significantly lower (cross-sectional study). In the longitudinal study (n=60), a substantial BMI reduction occurred in 17 (28.3%) obese patients which led to a significant reduction in triglycerides, cholesterol, LDLc, apo B, glucose and insulin levels and in HOMA. The ΔBMI values over the studied period correlated inversely and significantly with BMI (P<0.001) and HOMA (P=0.026) values observed at baseline. In multiple linear regression analysis, BMI at baseline remained associated to changes in BMI over the studied period (standardised Beta: -0.271, P=0.05). Conclusion: Our data demonstrates that small reductions in BMI-zc, imposed by lifestyle modifications in obese children and adolescents, improve the cardiovascular risk profile of such patients. Furthermore, patients with higher BMI and/or insulin resistance seem to experience a greater relative reduction in their BMI after lifestyle improvements.info:eu-repo/semantics/publishedVersio

Linkage of cytosolic peroxiredoxin 2 to erythrocyte membrane imposed by hydrogen peroxide-induced oxidative stress

Human erythrocyte peroxiredoxin 2 (Prx2) is a typical 2-cys cytosolic peroxiredoxin with thiol-dependent hydrogen peroxide scavenger activity. In a previous work, we reported Prx2 erythrocyte membrane linkage in some Hereditary Spherocytosis patients and that it seemed to be related to oxidative stress. The aim of the present work was to determine if Prx2 linkage to erythrocyte membrane could be induced by oxidative stress mediated by H2O2 and to further understand how and why this process occurs. We performed in vitro assays in which catalase or both Hb autoxidation and catalase were inhibited, under H2O2-induced oxidative stress conditions. Erythrocyte membrane linked Prx2 was detected by immunoblotting and quantified by densitometry. As oxidative stress markers, we determined membrane bound hemoglobin and lipid peroxidation, and we found that their values increased with H2O2 concentration. Prx2 linkage to the membrane also rose with increasing H2O2 concentration, and was only observed when the oxidized form of the enzyme was present in the cytosol. Oxidized Hb and Prx2 membrane linkages appear to be independent processes, although, both result from oxidative stress and may be useful as oxidative stress and/or erythrocyte damage/senescence markers

O direito à aposentadoria como uma dimensão da luta pela valorização dos professores: perfil das redes municipais brasileiras a partir da RAIS.

O artigo argumenta que o direito à aposentadoria especial de professores da educação básica pode ser compreendido como uma dimensão da valorização profissional (FERREIRA JR, 2013; GROCHOSKA, 2017; GOUVEIA, 2018). Esta perspectiva amplia dimensões já contempladas na literatura, como as de formação, remuneração, carreira e condições de trabalho (OLIVEIRA, 2010; CAMARGO; JACOMINI, 2011; GROCHOSKA, 2015; DARLING-HAMMOND, 2017). A partir da análise dos dados de perfil dos professores que efetivaram a aposentadoria nos anos de 2008 e 2016 cotejados por idade, tempo de serviço e formação, problematiza-se a ideia de mudanças no direito à aposentadoria especial dado que os professores, sob efeito das últimas reformas da previdência, já sofreram impactos não avaliados devidamente e têm apresentado maior tempo de permanência no sistema e, portanto, maior média de idade. A fonte de informações de perfil é a Relação Anual de Informações Sociais (RAIS), registro administrativo anual de empregos formais do Ministério do Trabalho e Emprego. Apresentam-se também alguns elementos do debate sindical recente sobre o direito à aposentadoria especial no Brasil.Palavras-chave: Políticas Educacionais, Remuneração Docente, Aposentadoria   The retirement right as dimension of teachers’ appreciation figth: profile of brazilian municipal systems from RAISABSTRACTThe article argues that rigth to special retirement for teachers in basic education can be understood how a dimension of profissional appreciattion ((FERREIRA JR, 2013; GROCHOSKA, 2017; GOUVEIA, 2018). This perspective expands dimensions already contemplated in the literature such as trainning, remuneration, career and working conditions (OLIVEIRA, 2010; CAMARGO; JACOMINI, 2011; GROCHOSKA, 2015; DARLING-HAMMOND, 2017). Based on the analysis of the profile data of the teachers who made the retirement in the years 2008 and 2016, based on age, length of service and trainning, the idea of changes in the right to special retirement is problematized since the teachers, pension reforms, have already had an impact that has not been duly assessed and has been shown to be longer in the system and, therefore, a higher average age. The source of profile information is the Annual Social Information Relation (RAIS), the annual administrative record of formal jobs from Ministry of Labor and Employment. It also presents some elements of the recent trade union debate on the right to special retirement in Brazil.Keywords: Education Policies. Teachers’ remuneration. Retirement. El derecho a la jubilación como una dimensión de la lucha por la valorización de los profesores: perfil de las redes municipales brasileñas a partir de la RAIS. RESUMENEl artículo argumenta que el derecho a la jubilación especial de profesores de la educación básica puede ser comprendido como una dimensión de la valorización profesional (FERREIRA Jr, 2013, GROCHOSKA, 2017, GOUVEIA, 2018). Esta perspectiva amplía dimensiones ya contempladas en la literatura como las de formación, remuneración, carrera y condiciones de trabajo (OLIVEIRA, 2010; CAMARGO; JACOMINI, 2011; GROCHOSKA, 2015; DARLING-HAMMOND, 2017). A partir del análisis de los datos del perfil de los profesores que efectuaron la jubilación en los años 2008 y 2016 cotejados por edad, tiempo de servicio y formación, se problematiza la idea de cambios en el derecho a la jubilación especial dado que los profesores, bajo efecto de las últimas reformas de la previsión, ya han sufrido impactos no evaluados debidamente y han presentado mayor tiempo de permanencia en el sistema y, por lo tanto, mayor edad media. La fuente de información de perfil es la Relación Anual de Información Social (RAIS), registro administrativo anual de empleos formales del Ministerio de Trabajo y Empleo. Se presentan también algunos elementos del debate sindical reciente sobre el derecho a la jubilación especial en Brasil.Palabras-clave: Politicas Educativas. Remuneracion Docente. Jubilación