Identification of genetic determinants associated with susceptibility and therapeutic efficacy in Philadelphia-negative Myeloproliferative Neoplasms

Poster presented at the Scientific Toxomics Meeting, 28 September 2015, Lisbon, Portugal

DNA repair genes polymorphisms and genetic susceptibility to Philadelphia-negative myeloproliferative neoplasms in a Portuguese population: the role of base excision repair genes polymorphisms

Sob uma licença CC-BY-NC-ND - http://creativecommons.org/licenses/by-nc-nd/4.0/The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8‑oxoguanine DNA glycosylase 1, poly (ADP‑ribose) polymerase (PARP) 1, PARP4 and X‑ray repair cross‑complementing 1 (XRCC1)] in a case‑control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN‑MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single‑nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2‑positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN‑MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.info:eu-repo/semantics/publishedVersio

Association between ventilation index and time on mechanical ventilation in infants with acute viral bronchiolitis

OBJECTIVE: To evaluate the association between time on mechanical ventilation and anthropometric, clinical and pulmonary function variables, measured early, in infants on invasive mechanical ventilation with acute respiratory failure due to viral bronchiolitis, and the temporal progression of variables with significant correlations. METHODS: Twenty-nine infants admitted to the pediatric intensive care unit of UNICAMP university hospital were studied. Acute viral bronchiolitis was defined according to clinical and radiological criteria. Children with chronic diseases and those that were hemodynamically unstable were excluded. All measurements were taken after 24 to 72 hours' mechanical ventilation, using volumetric capnography and blood gas analysis. Mechanical ventilation time was divided into: 7 days. Association between time on mechanical ventilation and the variables analyzed was determined by Spearman's Correlation Coefficient (r s). RESULTS: Time on mechanical ventilation showed a significant positive correlation with PaCO2 (r s = 0.45, p = 0.01) and ventilation index (r s = 0.51, p = 0.005), and a negative correlation with pH (r s = -0.40, p = 0.03). Ventilation indices of 37, measured between day one and day five, was associated with a progressively increased risk of more than 7 days on mechanical ventilation (OR = 4.2 on the first day to 15.71 on the fourth day). CONCLUSION: Ventilation index, PaCO2 and pH, measured early, were associated with prolonged mechanical ventilation, reflecting the severity of ventilatory disturbance and the need for support.OBJETIVO: Avaliar a associação entre tempo de ventilação mecânica e variáveis antropométricas, clínicas e de função pulmonar, precocemente, em lactentes com insuficiência respiratória por bronquiolite viral aguda em ventilação mecânica invasiva, e a evolução temporal das variáveis significativamente correlacionadas. MÉTODOS: Foram estudados 29 lactentes admitidos na unidade de terapia intensiva pediátrica do Hospital de Clínicas da UNICAMP, com diagnóstico de bronquiolite viral aguda, definido por critérios clínicos e radiológicos. Lactentes com doenças crônicas ou instabilidade hemodinâmica foram excluídos. Todas as medidas foram feitas entre 24 e 72 horas em ventilação mecânica, usando capnografia volumétrica e análise dos gases sangüíneos. O tempo de ventilação mecânica foi dividido em: menor ou igual que 7 dias e maior que 7 dias. A associação entre o tempo de ventilação e as variáveis analisadas foi determinada pelo coeficiente de correlação de Spearman (r s) RESULTADOS: O tempo de ventilação mecânica apresentou correlação positiva significativa com a PaCO2 (r s = 0,45, p = 0,01) e com o índice de ventilação (r s = 0,51, p = 0,005), e negativa com o pH (r s = -0,40, p = 0,03). Índice de ventilação com valor de 37, avaliado do primeiro ao quinto dia, foi associado a risco progressivamente aumentado de tempo de ventilação mecânica maior que 7 dias (OR = 4,2 no primeiro dia a 15,71 no quarto dia) CONCLUSÕES: Índice ventilatório, PaCO2 e pH, precocemente medidos, foram associados com tempo prolongado em ventilação mecânica, refletindo a gravidade do distúrbio ventilatório e necessidade de suporte.46647

Bioassay-Guided Evaluation of Antinociceptive Effect of N-Salicyloyltryptamine: A Behavioral and Electrophysiological Approach

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management