The pharmacological activity of CBD and CBD-DMH in HEK293A cells and their modelled binding sites at CB and CB receptors may explain their in vivo effects and illuminates the difficulties associated with the development of allosteric modulators for CB and CB receptors.
Significance
Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease caused by the failure to clear bacteria. Bacterial clearance depends on a layer of airway surface liquid (ASL) covering the airways, rich in antimicrobial compounds and mucins, that removes bacteria from the airway through mucociliary clearance. This study provides the first demonstration that inhalation of bacteria triggers CFTR-dependent ASL secretion. We suggest that this response to inhaled pathogens is an important but previously unknown part of the innate immune response that would be missing in CF patients, resulting in reduced bacterial killing and facilitating infection.
Water buffalo are an ancient component of Turkey's domestic livestock resources. Commonly referred to as the Anatolian buffalo the animal is part of the Mediterranean group which includes Syrian, Egyptian and Southeast European animals. Once quite numerous, there have been drastic reductions in their numbers since the 1970s due to intensification of dairy activities, agricultural mechanization and changing consumer preferences. The main areas of distribution are in northwest Turkey in the Marmara and Black Sea Regions. Buffalo are kept in small herds by livestock and mixed crop-livestock farmers. Milk is the main product, meat is largely a by-product of the dairy function and provision of the once-important draught power is now a minor output. Buffalo milk is used to prepare a variety of speciality products but output of both milk and meat is very low in comparison to cattle. Conditions of welfare and health status are not optimal. Internal parasites are a constraint on productivity. Some buffalo are being used for conservation grazing in the Black Sea area to maintain optimal conditions for bird life in a nature reserve. Long neglected by government there are recent activities to establish conservation herds, set up in vitro banks and undertake molecular characterization. More effort is needed by government to promote buffalo production and to engage the general public in conservation of their national heritage.
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR−/− swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.
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