Disclosed is a method of treating in a subject of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator. The method comprises administering to the subject Compound (I):

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or pharmaceutically acceptable salts thereof, together with food. Also disclosed are products comprising Compound (I) and the use of such products.

This disclosure provides, among other things, compositions comprising quantities of oltipraz, either in recrystallized or formulated crystal form, and a composition that reduces the rate of cellular oxygen consumption such as atovaquone, as well as methods of making such compositions, and methods of treating patients using such compositions. This disclosure also provides, among other things, compositions comprising quantities of oltipraz, either in recrystallized or formulated crystal form, for use in treating patients who may experience ischemia and/or reperfusion injury.

The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

In asthma, modification of gel-forming respiratory mucins leading to their tethering to the apical pole of epithelial cells, are believed to participate in airway obstruction by mucus plugs. These changes have been linked to local production of Th2 cytokines, resulting in mucus cell hyperplasia and increased MUC5AC production. The inventors showed that severe eosinophil asthma was associated with overexpression of transglutaminase 2 (TG2), an enzyme recently involved in intestinal mucin reticulation. Moreover, the bronchial epithelium from asthmatic patients or control subjects was reconstituted in vitro by culturing cells at the air-liquid interface and the hypersecretory differentiation was modeled by exposing control bronchial epithelial to IL-13. The inventors showed TG2 expression was upregulated upon IL-13-mediated hypersecretory differentiation and correlated with MUC5AC expression. IL-13 promoted MU5AC tethering to in vitro reconstituted hypersecretory epithelium, and this was blocked by a TG2 inhibitor. In conclusion, the inventors showed that TG2 participates in respiratory mucin modifications in asthma, and contribute to mucus tethering to the airway wall, supporting the use of TG2 inhibitors for improving mucociliary clearance in asthma, but more generally in respiratory diseases.

In asthma, modification of gel-forming respiratory mucins leading to their tethering to the apical pole of epithelial cells, are believed to participate in airway obstruction by mucus plugs. These changes have been linked to local production of Th2 cytokines, resulting in mucus cell hyperplasia and increased MUC5AC production. The inventors showed that severe eosinophil asthma was associated with overexpression of transglutaminase 2 (TG2), an enzyme recently involved in intestinal mucin reticulation. Moreover, the bronchial epithelium from asthmatic patients or control subjects was reconstituted in vitro by culturing cells at the air-liquid interface and the hypersecretory differentiation was modeled by exposing control bronchial epithelial to IL-13. The inventors showed TG2 expression was upregulated upon IL-13-mediated hypersecretory differentiation and correlated with MUC5AC expression. IL-13 promoted MU5AC tethering to in vitro reconstituted hypersecretory epithelium, and this was blocked by a TG2 inhibitor. In conclusion, the inventors showed that TG2 participates in respiratory mucin modifications in asthma, and contribute to mucus tethering to the airway wall, supporting the use of TG2 inhibitors for improving mucociliary clearance in asthma, but more generally in respiratory diseases.

The present invention is directed to methods of inhibiting LTA.sub.4-h in a human patient and method of treating a condition ameliorated by the inhibition of leukotriene A.sub.4 hydrolase activity in a human patient comprising administering to said human patient the compound, 4-{5-[4-(4-Oxazol-2-yl-phenoxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl}-benzoic acid.

A particulate substance mixture, preferably for use in the prophylaxis and/or treatment of a respiratory disorder includes a mucolytic substance and amorphous silicon dioxide. The mixture may also have the following characteristics: the amorphous silicon dioxide is hydrophilic silicon dioxide, the amorphous silicon dioxide has a mean particle diameter 20 m, and an amount of the amorphous silicon dioxide is 0.1% by weight to 10% by weight, based on the total weight of the particulate substance mixture.

This invention provides compounds of Formula I

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wherein B, G, A, E, R.sup.1, R.sup.3, R.sup.4, m and n are as defined herein, which are useful as type I receptor tyrosine kinase inhibitors, and methods of use thereof in the treatment of hyperproliferative disorders in mammals.

The present disclosure relates to TGF-beta antibodies and binding fragments thereof, DNA encoding the same, host cells comprising said DNA and methods of expressing the antibody or binding fragment in a host cell. The disclosure also extends to pharmaceutical compositions comprising the antibody or a binding fragment thereof and use of the antibody, binding fragment and compositions comprising the same in treatment of various diseases including fibrosis.