Embodiments of the invention involve treating ophthalmology conditions by the topical or oral use of acetylcholinesterase inhibitors. By effectively reducing or eliminating the population of demodex mites in affected areas and areas where demodex mites may exist, this treatment achieves a more complete remission of clinical signs and symptoms of the ophthalmological afflictions than any previously described method. Embodiments of the invention are useful for treating ocular afflictions caused by demodex-induced inflammatory eye conditions, including meibomian gland dysfunction, conjunctivitis, keratoconjunctivitis, hyperemia, blepharitis and dry eye disease.

The present disclosure provides a method of treating a respiratory disease or disorder in a subject in need thereof, the method comprising: administering a protein having hyaluronidase activity and/or 4-methylumbelliferone (4-MU) to a lung of the subject including, for example, in an aerosolized formulation.

A method for the treatment or prevention of a cardiovascular event in a subject with atherosclerotic vascular disease comprising the step of: b) administering a therapeutically effective amount of a compound of formula (I), a known colchicine derivative and/or a salt thereof ##STR00001##
wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.9, R.sub.10, R.sub.11 and R.sub.12 independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl, halogen, C.sub.1-4 haloalkyl, nitro, amino, C.sub.2-4 acylamino, C.sub.1-4 alkyl or dialkylamino, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, a group of the formula —SO.sub.2N(R.sup.x).sub.2 or SO.sub.2R.sup.x where R.sup.x is C.sub.1-4 alkyl, C.sub.1-4 acyloxy, or optionally substituted phenyl, optionally substituted phenoxy; R.sub.7 and R.sub.8 independently represent hydrogen, C.sub.1-4 alkyl or C.sub.1-4 acyl; and R.sub.5′, R.sub.5″, R.sub.6′ and R.sub.6″ independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl, halogen, C.sub.1-4 haloalkyl, nitro, amino, C.sub.2-4 acylamino, hydroxyl, C.sub.1-4 alkoxy or C.sub.1-4 alkylthio a group of the formula —SO.sub.2N(R.sup.x).sub.2 or SO.sub.2R.sup.x where R.sup.x is C.sub.1-4 alkyl, C.sub.1-4 acyloxy, or optionally substituted phenyl.

A method for the treatment or prevention of a cardiovascular event in a subject with atherosclerotic vascular disease comprising the step of: b) administering a therapeutically effective amount of a compound of formula (I), a known colchicine derivative and/or a salt thereof ##STR00001##
wherein: R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.9, R.sub.10, R.sub.11 and R.sub.12 independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl, halogen, C.sub.1-4 haloalkyl, nitro, amino, C.sub.2-4 acylamino, C.sub.1-4 alkyl or dialkylamino, hydroxyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, a group of the formula —SO.sub.2N(R.sup.x).sub.2 or SO.sub.2R.sup.x where R.sup.x is C.sub.1-4 alkyl, C.sub.1-4 acyloxy, or optionally substituted phenyl, optionally substituted phenoxy; R.sub.7 and R.sub.8 independently represent hydrogen, C.sub.1-4 alkyl or C.sub.1-4 acyl; and R.sub.5′, R.sub.5″, R.sub.6′ and R.sub.6″ independently represent hydrogen, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.3-6 cycloalkyl, halogen, C.sub.1-4 haloalkyl, nitro, amino, C.sub.2-4 acylamino, hydroxyl, C.sub.1-4 alkoxy or C.sub.1-4 alkylthio a group of the formula —SO.sub.2N(R.sup.x).sub.2 or SO.sub.2R.sup.x where R.sup.x is C.sub.1-4 alkyl, C.sub.1-4 acyloxy, or optionally substituted phenyl.

A phosphor-containing drug activator and suspension thereof are provided. The suspension at least includes two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays. The two or more phosphors include Zn2SiO4:M12+ and (3Ca3 (PO4)2Ca(F, Cl)2:Sb3*, Mn2+) at a ratio NP-200:GTP-4300 of from 1:10 to 10:1, and each of the two phosphors have an ethylene cellulose coating and/or a diamond-like carbon coating. The suspension further includes a pharmaceutically acceptable carrier. A system for treating a disease in a subject in need thereof includes a) the above-noted suspension, b) a photoactivatable drug containing 8-methoxypsoralen (8-MOP or UVADEX) untethered from the two or more phosphors, c) one or more devices which infuse the photoactivatable drug and the suspension including the pharmaceutically acceptable carrier into a diseased site in the subject, and d) an x-ray source which is controlled to deliver a dose of x-rays to the subject for production of the ultraviolet light.

A phosphor-containing drug activator and suspension thereof are provided. The suspension at least includes two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays. The two or more phosphors include Zn2SiO4:M12+ and (3Ca3 (PO4)2Ca(F, Cl)2:Sb3*, Mn2+) at a ratio NP-200:GTP-4300 of from 1:10 to 10:1, and each of the two phosphors have an ethylene cellulose coating and/or a diamond-like carbon coating. The suspension further includes a pharmaceutically acceptable carrier. A system for treating a disease in a subject in need thereof includes a) the above-noted suspension, b) a photoactivatable drug containing 8-methoxypsoralen (8-MOP or UVADEX) untethered from the two or more phosphors, c) one or more devices which infuse the photoactivatable drug and the suspension including the pharmaceutically acceptable carrier into a diseased site in the subject, and d) an x-ray source which is controlled to deliver a dose of x-rays to the subject for production of the ultraviolet light.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase 1 and the CMPD is protein transduction domain of the HIV-1 Tat protein.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase 1 and the CMPD is protein transduction domain of the HIV-1 Tat protein.

In one aspect, the invention provides a peptide comprising a chaperone-mediated autophagy (CMA)-targeting signal domain; a protein-binding domain that selectively binds to a target cytosolic protein; and a cell membrane penetrating domain (CMPD). In another aspect, the invention provides methods for reducing the intracellular expression level of an endogenous target protein in vitro and in an animal, wherein the method involves administration of the peptide. Methods are also provided for treating a pathological condition in an animal, the methods comprising administering the peptide to the animal. In one embodiment, the pathological condition is a neurodegenerative disease. In another embodiment of the invention, the target cytosolic protein is death associated protein kinase 1 and the CMPD is protein transduction domain of the HIV-1 Tat protein.

The present invention provides a conjugate of formula (I) and its use in methods of treatment, and also methods for delivering an active agent into a cell. The methods may be used to deliver an active agent into a nematode, flatworm, parasite or bacterium. The conjugate of formula (I) is: (formula (I)), wherein -D- is C.sub.1-4 alkylene or C.sub.2-4 alkenylene, preferably C.sub.2-4 alkenylene, where the alkylene or alkenylene is optionally substituted with alkyl or halo; A- is an active agent for delivery; and —R.sup.A, —R.sup.B, —R.sup.T1, —R.sup.T2, —R.sup.1, —R.sup.2, —R.sup.3, —X— and -L- are as defined herein.

##STR00001##