Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families

Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy

Inquérito sobre prevalência do tabagismo na classe médica brasileira Survey on prevalence of smoking among Brazilian physicians

OBJETIVOS. Apresentar os resultados do inquérito sobre a prevalência atual de fumantes entre os médicos do Brasil, segundo suas especialidades, realizado no período de maio a outubro de 1996. MÉTODO. A amostra utilizada foi de respostas espontâneas, constituída por 11.909 médicos associados pagantes da Associação Médica Brasileira, das várias Unidades da Federação e especialidades médicas. RESULTADOS. Constatou-se que 759 (6,4%) são fumantes regulares e 11.150 (93,6%) são não-fumantes; 4.085 médicos (34,3%) são ex-fumantes. Os maiores índices de não-fumantes estão entre os associados de sociedades de especialidades que possuem programas efetivos de controle do tabagismo (pneumologia, cancerologia, cardiologia e otorrinolaringologia). As regiões geográficas do Norte, Nordeste e Centro-Oeste apresentaram as maiores prevalências de fumantes. O início do fumar está mais presente no grupo de 10-19 anos (72,6%), com distribuição semelhante entre os sexos. Nenhum médico do sexo feminino iniciou o seu vício de fumar antes dos 10 anos de idade. CONCLUSÃO. É de grande importância os médicos receberem informações sobre tabagismo, bem como a realização de programas de seu controle nas sociedades de especialidades e nas federadas da Associação Médica Brasileira.<br>OBJECTIVES. To present the results of the study of the current prevalence of smoking among Brazilian physicians, according to field of specialization. The study was performed in the period from May to October 1996. METHOD. Data were collected by spontaneous reply from 11,909 physicians registered in Brazilian Medical Association, in the various States of Brazil and medical specializations. RESULTS. The results indicated that 759 (6.4%) are regular smokers, 11,150 (93.6%) are non-smokers and that 4,085 (34.3%) are former smokers. The highest rates of non smoking were found among the societies of specialties that have effetive smoking control programs (pneumology, oncology, cardiology and otorhinolaryngology). The northern, northeastern and mid-western regions of the country presented the highest prevalences of smoking. The onset of smoking occurs more frequently in the 10-19 years age group (72.6%), with similar distribution in both sexes. There were no female physicians who began smoking before 10 years of age. CONCLUSION. It is very important that physicians receive information regarding smoking as well as to have the development of smoking control programs in the specialty societies and in the regional associations federated to the Brazilian Medical Association

In skeletal muscle, advanced glycation end products inhibit insulin action and induce the formation of multimolecular complexes including the receptor for AGEs.

Chronic hyperglycaemia promotes insulin resistance at least in part by increasing the formation of Advanced Glycation End products (AGEs). We have previously shown that, in L6 myotubes, Human Glycated Albumin (HGA) induces insulin resistance by activating PKCalpha. Here we show that HGA-induced PKCalpha activation is mediated by Src. Co-precipitation experiments showed that Src interacts with both RAGE and PKCalpha in HGA-treated L6 cells. A direct interaction of PKCalpha with Src and IRS-1 has also been detected. In addition, silencing of IRS-1 expression abolished HGA-induced RAGE-PKCalpha co-precipitation. AGEs were able to induce insulin resistance also in vivo, as insulin tolerance tests revealed a significant impairment of insulin sensitivity in C57/BL6 mice fed a high AGEs diet (HAD). In tibialis muscle of HAD-fed mice, insulin-induced glucose uptake and PKB phosphorylation were reduced. This was paralleled by a 2.5-fold increase in PKCalpha activity. Similarly to in vitro observations, Src phosphorylation was increased in tibialis muscle of HAD-fed mice and co-precipitation experiments showed that Src interacts with both RAGE and PKCalpha. These results indicate that AGEs impairment of insulin action in the muscle might be mediated by the formation of a multimolecular complex including RAGE/IRS-1/Src and PKCalpha

Trabalho industrial e câncer de pulmão Industrial work and lung cancer

Com base em populações hospitalares, foram entrevistados 316 casos e 536 controles para obtenção de informações sobre histórias de trabalho, tabagismo, tabagismo passivo, ocorrência de outros cânceres na família, migração e situação socioeconômica. Os entrevistadores utilizaram um questionário padronizado. Casos e controles foram emparelhados por hospital, sexo e idade. O estudo foi desenvolvido entre 1º de julho de 1990 e 31 de janeiro de 1991 em 14 hospitais da Região Metropolitana de São Paulo, SP (Brasil). Foi elaborada uma classificação por escores como forma de ordenar os indivíduos estudados segundo suas histórias de exposições ocupacionais a cancerígenos, conhecidos para o pulmão, acumulando informações sobre a exposição nos locais de trabalho durante a vida, considerando o tipo de atividade, setor de trabalho e tempo em cada emprego. A análise de regressão logística não-condicional mostrou odds ratio: 1,97 (95% IC: 1,52 a 2,55) para os trabalhadores com maiores escores de exposição. Os resultados permitiram inferir que trabalhadores ligados aos setores de produção de diferentes ramos industriais têm duas vezes o risco de desenvolverem neoplasia pulmonar quando comparados aos trabalhadores envolvidos em atividades não-industriais.<br>In a hospital-based case-control study, 316 lung cancer cases and 536 controls were interviewed for their occupational, smoking, passive smoking, cancer in the family and residential histories as well as social economic status, by trained interviewers, using a standardized questionnaire. Cases and controls were matched by hospital, sex and age. The study was carried out between 1st July 1990 and 31st January 1991 in 14 hospitals in the Metropolitan Region of S. Paulo, the most highly industrialized and urbanized region in Brazil. Score criteria were developed for the ordering of the individuals of the study by occupational exposure to know carcinogens to the lung, in order to evaluate this exposure during the occupational life of each person. The criteria accumulated information on exposure to carcinogens as regards type, sector of work and time in each employment. The unconditional logistic regression analysis showed an odds ratio of 1.97 (95% IC: 1.52 to 2.55) for the highest exposure group. This result showed that workers linked to the production sectors of several industries have about twice the risk of developing lung cancer as workers involved in non-industrial activities

The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions

International audienc