A method and apparatus for controlled hydrolysis. The method can comprise hydrolyzing a first reagent in a first hydrolysis reaction and deactivating a first enzyme catalyzing the first hydrolysis reaction. The deactivating step can occur in about 10 seconds or less; the deactivating step can comprise adding a deactivating fluid to a composition comprising the first enzyme and heating the first enzyme using a deactivating mechanism. In other aspects, hydrolyzing the first reagent and deactivating the first enzyme can occur in a conduit, and the first hydrolysis reaction can occur in a composition that is at least 50% water by weight. The apparatus can provide a hydrolysis reactor comprising: a conduit; a composition inlet in the conduit for a composition; a first enzyme inlet in the conduit downstream of the composition inlet; and a first deactivating mechanism downstream of the first enzyme inlet to deactivate the first enzyme.

The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

Compounds and related compositions and methods as can be used to selectively inhibit neuronal nitric oxide synthase and as can be employed in the treatment of various neurodegenerative diseases.

Compounds and related compositions and methods as can be used to selectively inhibit neuronal nitric oxide synthase and as can be employed in the treatment of various neurodegenerative diseases.

Provided is a humanized monoclonal antibody or an antibody fragment thereof that selectively inhibits the enzymatic activity of vascular endothelial lipase and pharmaceutical compositions containing the same as an active ingredient useful for the treatment of arteriosclerosis or metabolic syndrome.

The present invention provides useful compounds for HIV protease inhibitor. A compound represented by the following formula or its pharmaceutically acceptable salt:

##STR00001##

wherein ring A is

##STR00002## R.sup.4 is —Y—Z, hydrogen atom, halogen, hydroxy and the like, R.sup.5 is hydrogen atom, halogen, hydroxy and the like, R.sup.6 is each independently halogen, hydroxy, carboxy and the like, ring A may be substituted with said R.sup.6 at any substitutable position(s), a is an integer of 0 to 7, ring B is substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, ring C is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, R.sup.1 is —Y—Z, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and the like, R.sup.2 and R.sup.3 are each independently —Y—Z or hydrogen atom, provided that at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is a group represented by formula: —Y—Z, Y is a bond, or a spacer of any combination selected from the group consisting of —O—, —S—, —NR.sup.7—, —C(═O)—, —SO—, —SO.sub.2—, —NR.sup.7—C(═O)—, —C(═O)—NR.sup.7—, —NR.sup.7—C(═O)—NR.sup.7—, —O—C(═O)—NR.sup.7—, —NR.sup.7—C(═O)—O—, —SO.sub.2—NR.sup.7—, —NR.sup.7—SO.sub.2—, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted aromatic carbocyclediyl, substituted or unsubstituted non-aromatic carbocyclediyl, substituted or unsubstituted aromatic heterocyclediyl and substituted or unsubstituted non-aromatic heterocyclediyl, R.sup.7 are each independently hydrogen atom, hydroxy, carboxy and the like, and Z is substituted aromatic carbocyclyl, substituted non-aromatic carbocyclyl, substituted aromatic heterocyclyl or substituted non-aromatic heterocyclyl.

In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.