RESUMO
Ten synthetic analogs of the marine alkaloids tambjamines, bearing aromatic enamine moieties, have been synthesized. These compounds proved to be highly efficient transmembrane anion transporters in model liposomes. Changes in the electronic nature of the substituents of the aromatic enamine or the alkoxy group of the central pyrrole group did not affect this anionophore activity. The in vitro activity of these compounds has also been studied. They trigger apoptosis in several cancer cell lines with IC50 values in the low micromolar range as well as modify the intracellular pH, inducing the basification of acidic organelles.
Assuntos
Alcaloides/metabolismo , Ânions/metabolismo , Pirróis/metabolismo , Alcaloides/toxicidade , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Transporte de Íons , Espectroscopia de Ressonância Magnética , Pirróis/toxicidade , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The regulators of complement activation (RCA) gene cluster in 1q31-1q32 includes most of the genes encoding complement regulatory proteins. Genetic variability in the RCA gene cluster frequently involve copy number variations (CNVs), a type of chromosome structural variation causing alterations in the number of copies of specific regions of DNA. CNVs in the RCA gene cluster often relate with gene rearrangements that result in the generation of novel genes, carrying internal duplications or deletions, and hybrid genes, resulting from the fusion or exchange of genetic material between two different genes. These gene rearrangements are strongly associated with a number of rare and common diseases characterized by complement dysregulation. Identification of CNVs in the RCA gene cluster is critical in the molecular diagnostic of these diseases. It can be done by bioinformatics analysis of DNA sequence data generated by massive parallel sequencing techniques (NGS, next generation sequencing) but often requires special techniques like multiplex ligation-dependent probe amplification (MLPA). This is because the currently used massive parallel DNA sequencing approaches do not easily identify all the structural variations in the RCA gene cluster. We will describe here how to use the MLPA assays and two computational tools to analyze NGS data, NextGENe and ONCOCNV, to detect CNVs and gene rearrangements in the RCA gene cluster.
Assuntos
Ativação do Complemento/genética , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Aberrações Cromossômicas , Enzimas Ativadoras do Complemento/genética , Via Alternativa do Complemento/genética , Via Clássica do Complemento/genética , Proteínas do Sistema Complemento/genética , Variações do Número de Cópias de DNA , Rearranjo Gênico , Testes Genéticos/métodos , Humanos , Família Multigênica/genética , Análise de Sequência de DNARESUMO
The objective of this study is to describe the characteristics of the caregivers of patients with Parkinson's disease (PD) and to analyze the association between these characteristics and caregiver burden, perceived health and mood status, and identify their predictors. A multicenter, nationwide, observational, cross-sectional study that included 289 patient-caregiver pairs was conducted. Caregiver self-assessments were the Hospital Anxiety and Depression Scale (HADS), EuroQol (EQ), and Zarit Caregiver Burden Inventory (ZCBI). Most caregivers in the study were women aged 60 years or thereabouts. Over two thirds were gainfully employed or housewives, 75% were patients' spouses, and the majority (96.5%) had been permanently taking care of the patient for 6 +/- 5.4 years. Less than 5% of patients were in the most advanced stages of disease, and direct costs were 6,350 euros per patient per year. Caregivers had more mood disorders and worse health-related quality of life (HRQol; EQ-Tariff) than did the general population. Caregiver HADS and EuroQol scores displayed a weak correlation (r(S) = 0.01-0.28) with patient-related variables (disease duration, HY, SCOPA-Motor, SCOPA-AUT, HADS, PPRS, and CISI-PD) whereas the ZCBI correlated moderately (r(S) = 0.27-0.47). Among caregivers, the EQ-Tariff was significantly lower and the HADS-Anxiety scores significantly higher for women. ZCBI and HADS-depression, though not EuroQol and HADS-anxiety, scores significantly increased with increasing PD severity levels. Caregivers' affective status proved the most important factor influencing their burden and perceived health, whereas patient-related variables influenced caregiver burden and mood but not health status. In PD, prevalence of affective disorders among patients' caregivers is high and influences both burden and HRQoL.