5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6-hydroxydopamine, a well-known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, -synuclein (-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and -Syn expression. -Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation. (c) 2013 Wiley Periodicals, Inc

Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies

In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra®) has been developed and has replaced Vivaglobin® (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra® would affect frequency of infusions, number of infusion sites, patients' satisfaction, and tolerability in patients previously treated with Vivaglobin® or intravenous immunoglobulins (IVIG). Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra® with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra®, with respect to the medicinal product formerly used, and the variations in patients' therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded. Eighty-two patients switched to Hizentra®: 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin®. The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra®). A decrease in the number of infusion sites with Hizentra® was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra®; no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported

Immunophenotype Anomalies Predict the Development of Autoimmune Cytopenia in 22q11.2 Deletion Syndrome

Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients

Clinical features and follow-up in patients with 22q11.2 deletion syndrome

OBJECTIVE: To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease. STUDY DESIGN: A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis. RESULTS: The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis. CONCLUSIONS: Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management

III Diretrizes para Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

Diariamente novos artigos científicos sobre tuberculose (TB) são publicados em todo mundo. No entanto, é difícil para o profissional sobrecarregado na rotina de trabalho acompanhar a literatura e discernir o que pode e deve ser aplicado na prática diária juntos aos pacientes com TB. A proposta das "III Diretrizes para TB da Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)" é revisar de forma crítica o que existe de mais recente na literatura científica nacional e internacional sobre TB e apresentar aos profissionais da área de saúde as ferramentas mais atuais e úteis para o enfrentamento da TB no nosso país. As atuais "III Diretrizes para TB da SBPT" foram desenvolvidas pela Comissão de TB da SBPT e pelo Grupo de Trabalho para TB a partir do texto das "II Diretrizes para TB da SBPT" (2004). As bases de dados consultadas foram LILACS (SciELO) e PubMed (Medline). Os artigos citados foram avaliados para determinação do nível de evidência científica, e 24 recomendações sobre TB foram avaliadas, discutidas por todo grupo e colocadas em destaque. A primeira versão das "III Diretrizes para TB da SBPT" foi colocada no website da SBPT para consulta pública durante três semanas, e as sugestões, críticas e o nível de evidência da referência científica que as embasavam foram avaliados e discutidos antes de serem incorporadas ou não ao texto final