Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features

Because of its involvement in the progression of several malignant tumors, the histone lysine-specific demethylase 1 (LSD1) has become a prominent drug target in modern medicinal chemistry research. We report on the discovery of two classes of noncovalent inhibitors displaying unique structural features. The antibiotics polymyxins bind at the entrance of the substrate cleft, where their highly charged cyclic moiety interacts with a cluster of positively charged amino acids. The same site is occupied by quinazoline-based compounds, which were found to inhibit the enzyme through a most peculiar mode because they form a pile of five to seven molecules that obstruct access to the active center. These data significantly indicate unpredictable strategies for the development of epigenetic inhibitors

Determinant Factors of Dividend Payments in Brazil

This study identifies factors that shaped cash disbursement distribution policies employed by Brazilian public companies listed on the Brazilian Securities, Commodities and Futures Exchange (BM&FBOVESPA) from 1995 to 2011. Relationships between Dividends/Total Assets and potential determinants discussed in the literature, including firm size, corporate governance, profitability, leverage, market to book, liquidity, investment, risk, profit growth, information asymmetry and agency conflict, are examined. The following econometric methods are employed: (1) Tobit, given the nature of the dividend data, and (2) the Generalized Method of Moments (GMM) to control for endogenous regressors. Significant positive variables found include size, return on assets (ROA), market to book, liquidity and profit growth. It can thus be inferred that larger firm size, profitability, market value, liquidity and profit growth correlate with greater firm pro pensity to distribute money to shareholders, thus supporting the theory of corporate finance. Significant negative variables found include leverage, liquidity squared, capex, beta and tag along 100%. It is thus inferred that more significantly leveraged companies that invest more heavily in fixed assets and that exhibit high liquidity, higher risk and less conflict between controlling and minority shareholders will be less likely to pay dividends to shareholders.</p

Drenagem endoscópica transmural de pseudocisto pancreático: resultados a longo prazo Transmural endoscopy drainage of pancreatic pseudocyst: long-term outcome

RACIONAL: Os pseudocistos pancreáticos são complicações relativamente comuns em pacientes adultos com pancreatite. OBJETIVO: Avaliar os resultados a longo prazo da drenagem endoscópica transmural, estabelecendo seu papel no manejo do pseudocisto pancreático. MÉTODOS: Foram estudados 14 pacientes com pseudocisto de pâncreas, cuja principal queixa à apresentação foi dor no andar superior do abdome e massa abdominal palpável, submetidos a cistogastrostomia (n = 12) e cistoduodenostomia (n = 2), acompanhados clinicamente e com tomografia computadorizada de abdome por até 51 meses. A colangiopancreatografia endoscópica retrógrada era tentada em todos os casos para estudo do ducto pancreático e classificação dos cistos. RESULTADOS: A pancreatite crônica alcoólica agudizada foi responsável por 10 casos (71,5%) e a biliar por 4 (28,5%). As duas formas de drenagens (cistogastrostomia e cistoduodenostomia) endoscópicas foram efetivas. Não houve mudança na conduta terapêutica proposta; em dois pacientes a migração da órtese para o interior do pseudocisto, no momento da inserção, foi a principal complicação, sendo possível sua retirada no mesmo ato, com o uso da cesta de Dormia, sob o auxílio de fluoroscopia. Não houve mortalidade, nem recidiva até o momento. O tempo médio de permanência hospitalar foi de 3 dias. CONCLUSÃO: A drenagem endoscópica transmural se apresentou como terapêutica eficaz, com baixo índice de complicações, mortalidade nula e pequeno tempo de internação hospitalar.<br>BACKGROUND: Pancreatic pseudocysts are relatively common complications of pancreatitis in adults. OBJECTIVE: To evaluate the long-term results from transmural endoscopic drainage and thus to establish its role in managing pancreatic pseudocyst. METHODS: Fourteen patients with pancreatic pseudocyst were studied. Their main complaint was pain in the upper levels of the abdomen. They presented palpable abdominal mass and underwent cystogastrostomy (n = 12) and cystoduodenostomy (n = 2), with clinical follow-up using abdominal computed tomography for up to 51 months. Retrograde endoscopic cholangiopancreatography was attempted in all cases to study the pancreatic duct and classify the cysts. RESULTS: There were 10 cases (71.5%) of chronic pancreatitis that had become acute through alcohol abuse and 4 (28.5%) that had become acute through biliary disorders. Both types of endoscopic drainage (cystogastrostomy and cystoduodenostomy) were effective. There was no change in the therapeutic management proposed. Migration of the orthesis into the pseudocyst at the time of insertion (two cases) was the principal complication, and these could be removed during the same operation, by means of a Dormia basket, with the aid of fluoroscopy. There has so far not been any mortality or relapse. The mean hospital stay was 3 days. CONCLUSION: Transmural endoscopic drainage was an efficacious form of therapy, presenting a low complication rate and no mortality, and only requiring a short stay in hospital