Targeting COPD: advances on low-molecular-weight inhibitors of human neutrophil elastase.

Chronic obstructive pulmonary disease (COPD) is a major increasing health problem and the World Health Organization (WHO) reports COPD as the fifth leading cause of death worldwide. COPD refers to a condition of inflammation and progressive weakening of the structure of the lung as well as irreversible narrowing of the airways. Current treatment is only palliative and no available drug halts the progression of the disease. Human neutrophil elastase (HNE) is a serine protease, which plays a major role in the COPD inflammatory process. The protease/anti-protease imbalance leads to an excess of extracellular HNE hydrolyzing elastin, the structural protein that confers elasticity to the lung tissue. Although HNE was identified as a therapeutic target for COPD more than 30 years ago, only Sivelestat (ONO-5046), an HNE inhibitor from Ono Pharmaceutical, has been approved for clinical use. Nevertheless, Sivelestat is only approved in Japan and its development in the USA was terminated in 2003. Other inhibitors in pre-clinical or phase I trials were discontinued for various reasons. Hence, there is an urgent need for low-molecular-weight synthetic elastase inhibitors and the present review discusses the recent advances on this field covering acylating agents, transition-state inhibitors, mechanism-based inhibitors, relevant natural products, and major patent disclosures.

Smokeless Tobacco Use and Cessation Attempts during COVID-19 Lockdown: A Qualitative Study.

BACKGROUND: Smokeless tobacco (SLT) use among women is widely prevalent in Manipur state accounting for 45% users as per Global Adult Tobacco Survey (GATS)-2 India. Studies from India and elsewhere indicate changes in the way people used SLT during COVID-19 lockdown. This study explores individual and economic influences on SLT consumption and cessation attempts by tribal women in Manipur during the first COVID-19 lockdown (March-June, 2020) in India. METHODS: Twenty in-depth interviews, both in-person and telephonically, were conducted among tribal women from Imphal west, Manipur, India, who used any SLT, from April to September 2020. Objective of the study was to understand the use, factors associated with consumption, purchasing behaviors, and cessation attempts of SLT during the lockdown. Thematic content analysis was used to identify core themes and codes. RESULTS: Study participants reported of changes in current SLT use during restrictions imposed to contain COVID-19 pandemic in India. Majority reported of reduction or quit attempts in SLT use. Reasons included inaccessibility due to travel restrictions, limited availability and price rise of SLT products, fear of COVID-19, and disposable income for purchase of SLT products. However, a few women reported of increased consumption due to bulk purchasing, or switching to other SLT products as a result of unavailability or price rise of preferred products or to cope up with social isolation caused by the lockdown. CONCLUSION: Study findings on factors influencing quit attempts and strategies used for reducing SLT use by tribal women in Imphal, Manipur provide valuable insights for development of appropriate intervention for prevention of SLT use among women.

Hemosuccus pancreaticus: a rare complication of chronic pancreatitis.

Hemosuccus pancreaticus is a very rare cause of gastrointestinal bleeding and it should be considered in every patient with history of chronic pancreatitis who presents with acute or intermittent gastrointestinal haemorrhage. A 54-year-old man with a history of chronic alcoholic pancreatitis was admitted to hospital for an acute exacerbation. During hospital stay, he presented with haematemesis and haemodynamic instability. Upper gastrointestinal endoscopy revealed a blood clot on Vater papilla. CT investigation showed a 4 cm cephalopancreatic pseudocyst and angiography identified a large pseudoaneurysm of the right gastroepiploic artery, bleeding into the pseudocyst-hemosuccus pancreaticus. Microcoil transcatheter embolisation was performed with success.