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.

Methods for identifying and optionally treating subjects, e.g., subjects who have Chronic Rhinosinusitis (CRS), based on the detection of elevated levels of soluble P-glycoprotein in nasal secretions. The methods of treatment can include administration of a therapeutically effective amount of a P-glycoprotein inhibitor.

A method is provided that includes intranasally dispensing nasal wash fluid into a nasal cavity of a subject such that the nasal wash fluid washes biological material into an oropharynx of the subject from (a) the nasal cavity, (b) a nasopharynx of the subject, or (c) the nasal cavity and the nasopharynx. The method further includes, thereafter, collecting a specimen sample that passed out of an anterior opening of an oral cavity of the subject and contains at least a portion of the biological material washed into the oropharynx by the nasal wash fluid. Thereafter, information is derived from extracellular vesicles present in the specimen sample. Other embodiments are also described.

The present invention relates to dual delta (δ) and gamma (γ) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of Pi3K kinase mediated diseases or disorders with them.

Provided is a conjugate formed between one or more linear polysaccharide chains and a peptide selected from one or more of the peptide components (a), (b), (c) or (d) as defined below: (a) a peptide component of formula (I), A-Q-B I wherein Q represents a structural fragment of formula (II), wherein: the squiggly lines and m have meanings given in the description and A and B have meanings given in the description, but may represent a peptide component of the amino acid sequence: [W-Lys-X1-Ser-U-X2-Y] n-W-Lys-X1-Ser-U-X2-Y--- (SEQ ID No: 3), wherein the dashed line, n, W, X1, U, X2 and Y have meanings given in the description; (b) a peptide component of the amino acid sequence: [Ala-Lys-X1-Ser-U-X2-Y] p-Ala-Lys-X1-Ser-U-X1-Y-G (SEQ ID No: 4) wherein p, G, X1, U, X2 and Y have meanings given in the description; (c) a peptide component of the amino acid sequence: W-Lys-X1-Ser-U-X2-Y-G (SEQ ID No: 5), wherein W, X1, U, X2, Y and G have meanings given in the description; or (d) a peptide component of the amino acid sequence: K-W1-Lys-X1-Ser-U1-X2-Y1-I-J (SEQ ID No: 6), wherein K, W1, U1, Y1, I, J, X1 and X2 have meanings as well as regioisomers, stereoisomers, and pharmaceutically- or cosmetically-acceptable salts of said conjugates, which conjugates are particularly useful in the treatment of conditions characterised by inflammation, including wounds, burns, and disorders of the mucosa, such as anorectal diseases, inflammatory bowel diseases, gynaecological diseases and dental diseases. Preferred linear polysaccharides include hyaluronic acid.

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The invention provides a chemical entity of Formula (I), and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating treating peripheral disorders, including inflammatory and renal disorders.

A compound of formula (I), and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof can be used as JNK inhibitors. A method for preparing the compound of formula (I) and a pharmaceutical composition comprising the compound of formula (I) are provided. The compound of formula (I) can be used for preparing drugs. The resulting drugs are used for treating diseases that can be treated by inhibiting JNK activity.

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Compositions comprising doses of NSAIDs less than 75 mg are provided. As shown herein, these compositions may be used for the treatment and prophylaxis of inflammatory conditions on the mucosa. In particular, acetyl salicylic acid at doses of less than 75 mg is shown to have therapeutic and prophylactic effect on the mucosa coupled without the adverse effects associated with NSAID administration.

The present invention provides stable topical formulations of cetirizine that provide a comfortable formulation when instilled in the eye and is effective in the treatment of allergic conjunctivitis and/or allergic conjunctivitis. The invention further provides methods of treating allergic conjunctivitis and/or allergic rhinoconjunctivitis in a subject in need of such treatment by topical application of the cetirizine formulations of the invention directly to the eye.

Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.