Various systems, devices, NO.sub.2 absorbents, NO.sub.2 scavengers and NO.sub.2 recuperator for generating nitric oxide are disclosed herein. According to one embodiment, an apparatus for converting nitrogen dioxide to nitric oxide can include a receptacle including an inlet, an outlet, a surface-active material coated with an aqueous solution of ascorbic acid and an absorbent wherein the inlet is configured to receive a gas flow and fluidly communicate the gas flow to the outlet through the surface-active material and the absorbent such that nitrogen dioxide in the gas flow is converted to nitric oxide.

Pharmaceuticals compositions comprising the 2S,4R, ketoconazole enantiomer or its pharmaceutically acceptable salts, hydrates, and solvates, that are substantially free of the 2R,4S ketoconazole enantiomer are useful to reduce cortisol synthesis and for the treatment of type 2 diabetes, hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Metabolic Syndrome, and other diseases and conditions, including but not limited to Cushing's Syndrome, depression, and glaucoma.

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. In an exemplary embodiment, the invention relates to a compound represented by formula (I): A-CH.sub.2-B (I) [wherein A is a modifying group comprising one or more polyethylene glycol groups, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is linked to the other moieties through a covalent bond of the nitrogen atom of the N-terminal α-amino group of the peptide moiety B to the carbon atom of the methylene group] or a salt thereof, or a hydrate thereof.

The invention provides a novel adrenomedullin derivative sustainable for a long period which is capable of substantially suppressing unwanted side effects while maintaining pharmacological effects of adrenomedullin. In an exemplary embodiment, the invention relates to a compound represented by formula (I): A-CH.sub.2-B (I) [wherein A is a modifying group comprising one or more polyethylene glycol groups, and B is a peptide moiety derived from adrenomedullin or a modified form thereof with adrenomedullin activity, wherein the peptide moiety B is linked to the other moieties through a covalent bond of the nitrogen atom of the N-terminal α-amino group of the peptide moiety B to the carbon atom of the methylene group] or a salt thereof, or a hydrate thereof.

The present disclosure provides methods for treating sarcoidosis-associated pulmonary hypertension, comprising administering to a patient in need thereof, a therapeutically effective amount of selexipag, wherein the patient is diagnosed with sarcoidosis-associated pulmonary hypertension.

The present invention relates to a compound represented by Formula I, its pharmaceutically acceptable salt, its stereoisomer, its pharmaceutically acceptable hydrate or solvate, or its pharmaceutically acceptable ester, wherein R is selected from heteroaryl, substituted heteroaryl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, alkyl, and substituted alkyl, wherein the substituted heteroaryl, the substituted aryl, the substituted cycloalkyl and the substituted alkyl are each independently substituted with one or more hydroxyalkylene groups. The compound or its pharmaceutically acceptable salt, its stereoisomer, its pharmaceutically acceptable hydrate or solvate, its pharmaceutically acceptable ester of the present invention has agonistic activity on A.sub.2A adenosine receptor and can improve the permeability of blood-brain barrier to promote the delivery of drug across blood-brain barrier, and can also prevent or treat a disease associated with A.sub.2A adenosine receptor agonistic activity.

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The present invention is directed to antibodies and antigen binding fragments thereof having binding specificity for PACAP. The antibodies and antigen binding fragments thereof comprise the sequences of the V.sub.H, V.sub.L, and CDR polypeptides described herein, and the polynucleotides encoding them. Antibodies and antigen binding fragments described herein bind to and/or compete for binding to the same linear or conformational epitope(s) on human PACAP as an anti-PACAP antibody. The invention contemplates conjugates of anti-PACAP antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. Methods of making said anti-PACAP antibodies and antigen binding fragments thereof are also contemplated. Other embodiments of the invention contemplate using anti-PACAP antibodies, and binding fragments thereof, for the diagnosis, assessment, and treatment of diseases and disorders associated with PACAP and conditions where antagonism of PACAP-related activities, such as vasodilation, photophobia, mast cell degranulation, and/or neuronal activation, would be therapeutically beneficial.

Provided herein are microbubble compositions comprising nitro-fatty acids and/or esters thereof, such as amphiphilic esters or allyl esters thereof. Also provided are methods of reducing local inflammation at a site in a patient comprising delivering the microbubbles to a site of inflammation in the patient and applying ultrasound to the microbubbles. The methods may be used to treat fibrosis or cancer.

Described are methods of administering therapeutic gases comprising high concentrations of nitric oxide, particularly concentrations above 2,000 ppm. The therapeutic gas may be administered at a certain dosing rate, such as less than 166 micrograms of nitric oxide per second. Also described are methods of administering a therapeutic gas comprising nitric oxide to a patient, wherein a dose of nitric oxide is administered from a portable device that includes a delivery system and a mini-cylinder. Methods of intermittent administration of nitric oxide pulses are also described.

Proteins that bind IL-1α and IL-1β are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1α and IL-1β in cells, tissues, samples, and compositions.