Abstract: Methods for the rapid repression of gene function in eucaryotic cells are disclosed including inducible means for both shutting down a targeted gene's transcription and rapidly removing a targeted gene's polypeptide product.

Abstract: The present invention pertains to novel 7,9-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

Abstract: Mucositis is treated and/or prevented by administrating to a patient a formulation comprising a tetracycline that is poorly absorbed from the gastro-intestinal tract. The tetracycline may be in the form of a pharmaceutically acceptable salt or a base. The formulations may optionally also contain an antifungal agent to prevent fungal overgrowth due to reduction in the normal oral flora by the tetracycline. Such compositions have the advantage of treating the entire gastro-intestinal tract since the active ingredient is not removed from the tract via absorption. Further, such compositions minimize systemic exposure and accompanying side effects.

Abstract: The invention relates to methods for protecting and/or treating a mammal at risk of acquiring a condition associated with bacteria that produce a calmodulin exotoxin, a metalloproteinase exotoxin, or both, by administering a non-antibacterial tetracycline formulation.

Abstract: The present invention provides new chemically modified 4-dedimethylaminotetracycline compounds that can be substituted with aryl, alkenyl, or alkynyl groups. The 7, 8, and/or 9 positions and methods for preparing such compounds. Other tetracycline compounds include the 4-dedimethylaminotetracycline derivatives with an oxime group, NH-Alkyl, or N-NH-Alkyl group substituted at the C4 position as well as C2 Mannich derivatives. The present invention also provides a method of treating a mammal suffering from conditions or diseases by administering to the mammal an effective amount of the new chemically modified tetracycline compounds.

Abstract: The present invention provides an attenuated HIV vaccine comprising an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Additionally, the present invention provides a method for immunization of humans against HIV which comprises administering to a human a vaccine including an HIV virus modified to replicate only in the presence of at least one tetracycline analogue. Simultaneously, at least one tetracycline analogue is administered for a period of time to allow replication of the modified HIV virus in vivo sufficient to produce immunity. Preferably, the tetracycline analogue is doxycycline. A replication competent HIV-DoxT virus genome which can be controlled by the presence or. absence of doxycycline is produced by preparing a promoter, TetopTCAT; producing a provirus, pHIV-DoxT, using the TetopCAT promoter, and transfecting the pHIV-DoxT in cell lines in the presence of doxycycline.

Abstract: The present invention provides a unique approach for the diagnosis and management of infections by Chlamydia species, particularly C. pneumoniae. The invention is based, in part, upon the discovery that a combination of agents directed toward the various stages of the chlamydial life cycle is effective in substantially reducing infection. Products comprising combination of antichlamydial agents, novel compositions and pharmaceutical packs are also described.

Abstract: A method for simultaneously treating ocular rosacea and acne rosacea in a human in need thereof comprising administering systemically to said human a tetracycline compound in an amount that is effective to treat ocular rosacea and acne rosacea but has substantially no antibiotic activity.

Abstract: The invention features methods and reagents for the diagnosis, monitoring, and treatment of multiple sclerosis. The invention is based in part on the discovery that Chlamydia is present in patients with multiple sclerosis, and that anti-chlamydial agents improve or sustain neurological function in these patients.

Abstract: The present invention relates to a composition for the treatment of acne comprising chlorine dioxide or chlorine dioxide generating compounds as acne reduction agents. The invention also relates to a method for treating acne by topically administering one of the compositions in an amount therapeutically effective to reduce the redness and blemishes associated with acne.

Abstract: A means and method for treating pulmonary fibrosis and vaginitis in animals is described. The compositions include surfactant lipids in a pharmaceutically acceptable carrier. Surfactant lipids have been found to suppress the synergistic effect of bleomycin and SP-A in enhancing proinflammatory cytokine production. Surfactant lipids are also effective in the prevention and treatment of pulmonary fibrosis resulting from exposure to inflammatory agents affecting cytokine production. Furthermore, surfactant lipids are effective in treating attenuating the effect of proinflammatory cytokine production in vaginitis.

Abstract: A method of preparing a liposomal bioactive agent comprising infusing an lipid-ethanol mixture with an aqueous or ethanolic solution of the bioactive agent at a temperature below the phase transition of at least one of the lipid components of the lipid and compositions produced by the method of the invention.

Abstract: The present invention provides prophylactic and therapeutic methods of treating the ductal epithelium of an exocrine gland, in particular a mammary gland, for disease, in particular cancer. The methods comprise contacting the ductal epithelium of the exocrine gland with an epithelium-destroying gent, preferably by ductal cannulation, so as to realize a prophylactic or therapeutic effect.

Abstract: Compositions and methods for vaginal, buccal or nasal transmucosal delivery of drugs and for cryoprotecting of cells and embryos. For cryoprotection, the composition consisting essentially consist of a non-ionizable glycol derivative. For transmucosal delivery, the compositions essentially consist of a non-ionizable glycol derivative in a combination with a pharmaceutically active agent. For transmucosal delivery, the non-ionizable glycol derivative may be further combined with a mucoadhesive agent and/or a penetration enhancer and/or lipophilic or hydrophilic carrier for adhesion to and transport through a mucosa. The compositions are particularly suitable for administration of drugs through a nasal, buccal and vaginal mucosa or for long-term preservation of cell or embryos.

Abstract: The present invention relates to pharmaceutical compositions for the treatment of spinal disorders caused by the liberation of TNF-&agr; comprising an effective amount of a TNF-&agr; inhibitor, as well as a method for treatment of such disorders, and the use of TNF-&agr; inhibitors in the preparation of pharmaceutical compositions for such treatment.

Abstract: A novel oral dosage to be delivered to the stomach comprising a safe and effective amount of an active ingredient selected from the group consisting of emepronium bromidebromide, doxycycline, and other tetracyclines/antibiotics, iron preparations, quinidine, nonsteroidal anti-inflammatory drugs, alprenolol, ascorbic acid, captopril, theophylline, zidovoudine (AZT), bisphosphonates and mixtures thereof and pharmaceutically-acceptable excipients, wherein said oral dosage form is a generally oval form and film coated to facilitate rapid esophageal transit and avoid irritation in the mouth, buccal cavity, pharynx, and esophagus.

Abstract: A stable composition including a water-sensitive pharmacologically active agent, such as an enzyme, an antibiotic or a vitamin, a hydrophilic non-polar primary solvent, an optional hydrophilic non-polar secondary solvent and optional pharmaceutical or cosmetic adjuvants to enhance appearance for topical use. Where the water-sensitive or water-degradable component is L-Ascorbic acid and the principal solvent is N-methyl-2-pyrrolidone (“NMP”) the composition is stable for many months at a concentration of L-Ascorbic acid of up to about 40 % w/v. This composition using NMP as a solvent and enhancer of skin penetration together with appropriate adjuvants is useful for preparing dermatological topical dosage for cosmetic and therapeutic purposes.

Abstract: The invention provides a method of treating certain neurological diseases by administering to a patient in need thereof an effective amount of a tetracycline compound.

Abstract: The present invention provides new chemically modified 4-dedimethylaminotetracycline compounds that can be substituted with aryl, alkenyl, or alkynyl groups. The 7, 8, and/or 9 positions and methods for preparing such compounds. Other tetracycline compounds include the 4-dedimethylaminotetracycline derivatives with an oxime group, NH-Alkyl, or N—NH-Alkyl group substituted at the C4 position as well as C2 Mannich derivatives. The present invention also provides a method of treating a mammal suffering from conditions or diseases by administering to the mammal an effective amount of the new chemically modified tetracycline compounds.

Abstract: A modified release preparation having one or more coated core elements, each core element including an active ingredient and having a modified release coating, wherein a stabilising coat is provided between each core element and its modified release coating so that, upon in vitro dissolution testing, the amount of active ingredient released at any time on a post-storage dissolution profile is within 40 percentage points of the amount of active ingredient released at any time on a pre-storage dissolution profile.

Abstract: The present invention provides new chemically modified 4-dedimethylaminotetracycline compounds that can be substituted with aryl, alkenyl, or alkynyl groups. The 7, 8, and/or 9 positions and methods for preparing such compounds. Other tetracycline compounds include the 4-dedimethylaminotetracycline derivatives with an oxime group, NH-Alkyl, or N—NH-Alkyl group substituted at the C4 position as well as C2 Mannich derivatives. The present invention also provides a method of treating a mammal suffering from conditions or diseases by administering to the mammal an effective amount of the new chemically modified tetracycline compounds.

Abstract: The present invention relates to the identification of lipid oxidising abzymes as a key pathogenic factor in atherosclerotic disorders. Methods and means for the reduction of abzyme mediated lipid oxidation in the vascular system are provided as therapeutic approaches for the treatment of atherosclerotic disorders.

Abstract: Methods of preventing amyloid associated disease comprising preventing protofibril formation using polycyclic compounds related screens and methodologies disclosed.

Abstract: The present invention relates to intraocular drug delivery for treating ocular diseases. Particularly, the invention relates to particles useful for the delivery of certain pharmacologically active agents to treat ocular diseases. The particles contain calcium phosphate core particles, particularly nanoparticles, as delivery agents and adjuvants. The invention also relates to methods of making such particles and to methods of treating ocular disease by delivery of a therapeutic drug to an ocular surface using the particles of this invention. The invention further relates to methods of regulating ocular pressure using certain formulations according to the present invention.

Abstract: The invention relates to the individualization of therapy on the basis of a phenotypic profile of an individual. More specifically, the present invention relates to the use of metabolic phenotyping for the individualization of treatment with antibiotic agents.

Abstract: A method of administering an antibiotic to an animal in need thereof, including the step of injecting the antibiotic subcutaneously at the junction of a pinna with the cranium of the animal, is disclosed.

Abstract: The present invention relates to a method for prevention or reduction of scar tissue and/or adhesion formation wherein a therapeutically effective amount of a substance that inhibits a pro-inflammatory cytokine such as TNF or IL-1, is administered to a patient in need of said treatment.

Abstract: A method for treating bacterial diseases, including bacterial infections, that are otherwise resistant to antibiotics, such as tetracycline and related compounds, using metal-complexed antibiotics is disclosed. Also disclosed is a method for protecting against such diseases. The metal-complexed antibiotics include tetracyclines complexed with metals such as iron, copper and calcium.

Abstract: The present invention relates to 7-phenyl substituted tetracycline derivatives and compositions thereof.

Abstract: Methods and compositions for treating for the synergistic treatment of fungal associated disorders are discussed.

Abstract: 13-substituted methacycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 13-substituted methacycline compounds are described.

Abstract: A method of treating multiple sclerosis is disclosed. In one embodiment, the method comprises the step of treating a multiple sclerosis patient with a tetracycline derivative, wherein the multiple sclerosis symptoms of the patient are diminished.

Abstract: The invention relates to a prodrug that is capable of being converted into a drug by the catalytic action of human fibroblast activation protein (FAP&agr;), said prodrug having a cleavage site which is recognised by FAP&agr;, and said drug being cytotoxic or cytostatic under physiological conditions.

Abstract: Glucocorticoid blockers, including glucocorticoid receptor antagonists, are effective to prevent glucocorticoid-induced decrease in permeability of the blood-brain barrier and to increase the permeability of the blood-brain barrier. Administration of glucocorticoid blockers, including glucocorticoid receptor antagonists, concomitant with administration of drugs for treating diseases of the central nervous system increases delivery of such drugs into the central nervous system.

Abstract: Therapeutic composition having anti-infective activity. The therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, most preferably one that contains at least 20% alcohol by volume. The therapeutic composition is preferably in local delivery form and is self-administered orally or via the nasal cavity.

Abstract: The invention provides a use of a metalloproteinase inhibitor for the preparation of a pharmaceutical composition for treating human pulmonary emphysema which comprises admixing the metalloproteinase inhibitor in an amount effective to treat human pulmonary emphysema and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition which comprises a metalloproteinase inhibitor in an amount effective to treat human pulmonary emphysema and a pharmaceutically acceptable carrier.

Abstract: This invention relates to an ionic antimicrobial coating. Such a coating may contain (1) a water-insoluble polymer having a first ionized group and (2) an antimicrobial agent having a second ionized group with a charge opposite to that of the first ionized group, in which the antimicrobial agent is attached to the water-insoluble polymer via an ionic bond between the first ionized group and the second ionized group.

Abstract: The ability to incorporate iodoform, tetracycline and a combination of iodoform/tetracycline into root canal gutta percha points is described. The iodoform, tetracycline and iodoform/tetracycline combination are bound within the gutta percha points. They act as a reservoir of antimicrobial that is capable of diffusing onto the surface of the gutta percha thereby inhibiting the colonization of bacteria on the gutta percha points and within the root canal system. Tetracycline is capable of coalescing within the dentinal tubules to inhibit long term microbial growth. These medicated gutta percha points are site specific, surface acting antimicrobial gutta percha points. A method of the usage and delivery of amorphous form iodoform gutta percha, iodoform/tetracycline gutta percha, or tetracycline gutta percha within a heated compule with a pressure plunger by delivering the thermo-softened heat labile amorphous form via a pressure extrusion system through a cannula into the prepared root canal system.

Abstract: This invention relates to compositions, methods, combinations, and kits for treating, preventing, or reducing the risk of developing diarrhea in a mammal; or treating, preventing, or reducing the risk of developing a symptom associated with, or related to, diarrhea in a mammal. In particular, the compositions, methods, combinations, and kits comprise an anti-diarrheal agent and an electrolyte.

Abstract: The invention provides Helicobacter polypeptides, designated GHPO 1360 and GHPO 750, which can be used in vaccination methods for preventing or treating Helicobacter infection, and polynucleotides that encode these polypeptides.

Abstract: The present invention relates to cancer, including in cancer and, in particular, to opioid compounds that are inhibitors of drug transporters of the ABC protein superfamily. The invention relates to methods of treating cancer using anti-tumor agents and opioid inhibitors of such transporters. The invention also relates to methods for selecting or designing compounds for the ability to inhibit drug transporter proteins and to methods of inhibiting drug transporter proteins. The invention concerns the new use of opioid receptor antagonists in the treatment of a cancer patient who has developed a resistance to a therapeutically active substance.

Abstract: A method of treating telangiectasia in a human in need thereof comprising administering to said human a tetracycline compound in an amount that is effective to treat telangiectasia, but has substantially no antibiotic activity.

Abstract: In certain embodiments, the present invention is directed to a pharmaceutical formulation for topical administration on a mammal, comprising a unit dose of a therapeutically effective amount of a therapeutic agent and a pharmaceutically acceptable carrier medium therefor, said formulation being solid at ambient temperature and having a softening point of not higher than 35° C., such that when the formulation is placed in continuous contact with the skin of a mammalian patient, it is softened to a consistency to effect substantial application of the unit dose of said therapeutic agent onto a desired skin area of the mammalian patient within a time period of less than 10 minutes.

Abstract: The present invention relates to zero-order sustained release solid dosage forms suitable for administration of a wide range of therapeutically active medicaments, especially those that are water-soluble, and to a process of making same. The solid dosage form comprises (a) a matrix core comprising ethylcellulose and the active agent and (b) a hydrophobic polymer coating encasing the entire matrix core.

Abstract: Methods for treatment of antibiotic-resistant and multi-drug resistant bacterial infections are provided. The methods comprise administration of compositions which mimic plasmid incompatibility in bacteria, resulting in their sensitization to previously resistant drugs. Also provided herein are methods for screening compositions for the ability to mimic plasmid incompatibility by inhibiting Rep protein or by destabilizing RNA/RNA stem loop “kissing” structures. The invention also encompasses compositions identified by the screening methods disclosed herein.

Abstract: The present invention provides compositions and methods for extending the release times and lowering the toxicity of pharmacologically active compounds. The compounds comprise a salt of the pharmacologically active compound with a lipophilic counterion and a pharmaceutically acceptable water soluble solvent combined together to form an injectable composition. The lipophilic counterion may be a saturated or unsaturated C8-C22 fatty acid, and preferably may be a saturated or unsaturated C10-C18 fatty acid. When injected into a mammal, at least a portion of the composition precipitates and releases the active compound over time. Thus, the composition forms a slowly releasing drug depot of the active compound in the mammal. Therefore, the present invention enables one to provide a controlled dose administration of the active compound for a periods of up to 15 days or even longer.

Abstract: A method of treating acne in a human in need thereof comprising administering systemically to said human a tetracycline compound in an amount that is effective to treat acne but has substantially no antibiotic activity, without administering a bisphosphonate compound.

Abstract: The present invention relates to compositions for the protection, treatment and repair of connective tissues in humans and animals comprising any or all of anabolic, anti-catabolic, anti-oxidant and analgesic agents, including aminosugars, S-adenosylmethionine, arachadonic acid, GAGs, including pentosan, collagen type II, tetracyclines or tetracycline-like compounds, diacerin, super oxide dismutase, L-ergothionine, one or more avocado/soybean unsaponifiables, and an analgesic, e.g., acetaminophen, and to methods of treating humans and animals by administration of these novel compositions to humans and animals in need thereof.

Abstract: The present invention relates to microbial multidrug resistance and, in particular, to compounds that microbial drug transporters of the ABC protein superfamily. The invention also relates to methods for selecting or designing compounds for the ability to inhibit drug transporter proteins and to methods of inhibiting drug transporter proteins. The invention concerns the new use of opioid receptor antagonists in the treatment of multidrug resistant microbial infections.

Abstract: The instant invention provides a product of manufacture for retarding the biochemical formation of metalloproteinase, including gelatinase, elastase, collaginase, and the like, within the tissues of the body of a patient who has been inflicted with the HIV virus and/or the HIV virus which has advance to the AIDS virus, through the administration of an effective amount of a non-antimicrobial/non-antibiotic/non-antibacterial, chemically modified tetracycline (CMT) analog, its salts, cojugates and/or derivatives, and combinations thereof.