Disclosed are pharmaceutical compositions and related methods for treating a subject with a viral or retroviral infection. The disclosed compositions and methods comprise and utilize an effective amount of one or more vanadium-containing compounds and an effective amount of one or more sulfonylureas. In certain embodiments, the viral infection is human immunodeficiency virus (HIV) and the compositions and methods improve one or more immunologic cellular parameters, such as viral load, CD4 counts and CD4/CD8 lymphocyte cell ratios in a subject. Also disclosed are methods of improving one or more immunologic cellular parameters that are associated with viral infections such as HIV in a subject, including viral load, CD4 counts and CD4/CD8 lymphocyte cell ratios.

A composition comprising a novel Ca.sup.2+-activated, [ATP].sub.i-sensitive nonspecific cation (NC.sub.Ca-ATP) channel is described. The channel is found in mammalian neural cells and exhibits a different sensitivity to block by various adenine nucleotides, and is activated by submicromolar [Ca].sub.i. The NC.sub.Ca-ATP channel is activated under conditions of ATP depletion, which causes severe cell depolarization, followed by cell swelling. The NC.sub.Ca-ATP channel is regulated by a sulfonylurea receptor and is inhibited by sulfonylurea compounds glibenclamide and tolbutamide. Methods employing compositions comprising the NC.sub.Ca-ATP channel to screen for compounds that block the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described. In addition, methods employing compositions comprising the Kir2.3 channel to screen for compounds that open the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described.

A composition comprising a novel Ca.sup.2+-activated, [ATP].sub.i-sensitive nonspecific cation (NC.sub.Ca-ATP) channel is described. The channel is found in mammalian neural cells and exhibits a different sensitivity to block by various adenine nucleotides, and is activated by submicromolar [Ca].sub.i. The NC.sub.Ca-ATP channel is activated under conditions of ATP depletion, which causes severe cell depolarization, followed by cell swelling. The NC.sub.Ca-ATP channel is regulated by a sulfonylurea receptor and is inhibited by sulfonylurea compounds glibenclamide and tolbutamide. Methods employing compositions comprising the NC.sub.Ca-ATP channel to screen for compounds that block the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described. In addition, methods employing compositions comprising the Kir2.3 channel to screen for compounds that open the channel and the use of such antagonists as therapeutics in preventing brain swelling and damage are described.

The present invention provides compounds of Formula I,

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pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated as FXR modulators. Specifically, the present invention relates to isoxazole derivatives useful as agonists for FXR, and methods for their preparation and use.

The present invention provides compounds of Formula I,

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pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated as FXR modulators. Specifically, the present invention relates to isoxazole derivatives useful as agonists for FXR, and methods for their preparation and use.

Modulators of intracellular chloride concentration for treating down syndrome The present invention relates to a modulator of a chloride transporter for use in the treatment of Down syndrome.

Modulators of intracellular chloride concentration for treating down syndrome The present invention relates to a modulator of a chloride transporter for use in the treatment of Down syndrome.

Modulators of intracellular chloride concentration for treating down syndrome The present invention relates to a modulator of a chloride transporter for use in the treatment of Down syndrome.

The invention relates to process for the preparation of grapiprant and its intermediates thereof. The invention also relates to grapiprant having a purity 98% or more and compounds of Formula (A), (B), (C) and (D) in an amount of 0.5 or less, relative to grapiprant, by area percentage of HPLC. The invention also relates to an amorphous form of grapiprant and process for preparation thereof.

The invention relates to process for the preparation of grapiprant and its intermediates thereof. The invention also relates to grapiprant having a purity 98% or more and compounds of Formula (A), (B), (C) and (D) in an amount of 0.5 or less, relative to grapiprant, by area percentage of HPLC. The invention also relates to an amorphous form of grapiprant and process for preparation thereof.