The present invention relates to methods of using optimized aptamers. In certain embodiments, the present invention provides a method for treating a subject having or being disposed to having a histone-induced injury or disease comprising administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and (i) a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer KU1, KU2, KU3, KU4, KU5, KU6, KU&, KU8, or KU9, wherein the aptamer specifically targets extracellular histones, wherein the nucleotides are RNA; or (ii) a conjugate comprising a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer KU1, KU2, KU3, KU4, KU5, KU6, KU&, KU8, or KU9, wherein the aptamer specifically targets extracellular histones, wherein the nucleotides are RNA, wherein the nucleic acid molecule is linked to a therapeutic molecule.

The present invention relates to methods of using optimized aptamers. In certain embodiments, the present invention provides a method for treating a subject having or being disposed to having a histone-induced injury or disease comprising administering to the subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and (i) a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer KU1, KU2, KU3, KU4, KU5, KU6, KU&, KU8, or KU9, wherein the aptamer specifically targets extracellular histones, wherein the nucleotides are RNA; or (ii) a conjugate comprising a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer KU1, KU2, KU3, KU4, KU5, KU6, KU&, KU8, or KU9, wherein the aptamer specifically targets extracellular histones, wherein the nucleotides are RNA, wherein the nucleic acid molecule is linked to a therapeutic molecule.

The present invention relates to compositions providing improved preservative efficacy. The present invention further relates to polyquaternium compound containing compositions having improved the antifungal activity. In certain embodiments, the present invention relates to ophthalmic compositions comprising a polyquaternium compound, a polyol or combination of polyols, borate compound, and an antimicrobial mixture comprising electrolytes and nutrients.

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R.sup.1 and R.sup.2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

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The present invention provides new methods and kits for treating IBS; treating IBS in females; treating IBS in older subjects; and treating IBS in non-white subjects.

This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNF antagonist. The NGF antagonist and the TNF antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNF antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNF antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNF antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNF antagonist administered alone.

The invention is directed to compounds of formula (I): ##STR00001##
and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.

A dosage form with a first portion and a second portion. The first portion can be an immediate release portion and can comprise a pain reliever, which can be naproxen or naproxen sodium. The second portion can be an extended release portion and can comprise pseudoephedrine or a pharmaceutically acceptable salt thereof and/or dextromethorphan or a pharmaceutically acceptable salt thereof. The dosage form can optionally comprise a stabilizing agent. The dosage form can be adapted to maintain a therapeutically effective amount of pain reliever, pseudoephedrine, or a pharmaceutically acceptable salt thereof, and/or dextromethorphan, or a pharmaceutically acceptable salt thereof, for at least eight hours.

The present invention pertains to novel treatments of neuropathic pain; in particular chemotherapy induced peripheral neuropathic pain (CIPNP). The invention provides antagonists cytochrome P450 epoxygenases (CYP), and more specifically antagonists of CYP2J2, as therapeutics for use in the treatment of neuropathic pain such as CIPNP. CYP2J2 antagonists were identified to alleviate CIPNP in-vivo, and therefore are provided additionally in combination with chemotherapeutics for the treatment of diseases such as cancer or other proliferative disorders. The CYP2J2 antagonists reduce chemotherapeutic induced pain and therefore allow for a higher dosing of the chemotherapeutic during cancer treatment. In addition the invention relates to the use of CYP2J2 agonists, or metabolites of CYP2J2, for sensitizing TRPV1. In this context the invention proposes to use combinations of CYP2J2 agonist or metabolites and transient receptor potential vanilloid 1 (TRPV1) agonists to treat disorders that respond to TRPV1 agonists, such as neuropathic pain.

A medicinal agent for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation is disclosed. A compound having antagonistic activity against the EP.sub.4 receptor is contained as an active ingredient in the medicinal agent. The compound represented by the following general formula (I) as defined in the specification, a salt, an N-oxide, or a solvate thereof, or a prodrug of these is useful as a medicinal component having antagonistic activity against the EP.sub.4 receptor for the prevention and/or treatment of diseases caused by EP.sub.4 receptor activation.

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