The State University of New York

Hospital for Joint Diseases

Kuraray Co., Ltd.

University of Rochester

Albert Einstein College of Medicine

Montefiore Medical Center

Robert A Greenwald

Lorne M Golub

Thomas F McNamara

Nangavarum S Ramamurthy

Nungavaram S Ramamurthy

Steven B Abramson

Hsi-Ming Lee

Peter Vadas

Ashok R Amin

Waldemar Pruzanski

Howard Trachtman

Tetsuo Takigawa

Christopher T Ritchlin

Goro Kobayashi

Maria Emanuel Ryan

Hisashi Iwata

Jonathan Maimon

Tsutomu Kawai

Michiya Shimamura

Sally A Haas-Smith

David Brown

Kenneth Gorray

Bruce Schneider

Kavita Desai

Takashi Hamasaki

Susan A Moak

The present invention relates to a method for decreasing elevated serum/plasma LDL-cholesterol levels or LDL-cholesterol levels and CRP levels in a mammal in need thereof. The methods comprises administering an effective amount of a tetracycline formulation. In one embodiment, the tetracycline formulation is a non-antibacterial tetracycline. In another embodiment, the tetracycline formulation is an antibacterial tetracycline at a sub-antibacterial amount.

Method for decreasing low density lipoprotein

A method for treating mammals suffering from conditions associated with excess phospholipase A.sub.2 activity and/or production comprising administering to the mammal an effective amount of a non-antimicrobial tetracycline sufficient to inhibit excess phospholipase A.sub.2 activity and/or production is disclosed. A pharmaceutical composition is also disclosed.

Inhibition of excessive phospholipase A.sub.2 activity and/or production

The invention is a method of enhancing endogenous interleukin-10 production in mammalian cells and tissues, which includes administering an effective amount of a tetracycline derivative. The method also includes enhancing interleukin-10 production by administering an effective amount of the tetracycline derivative to a mammal. Preferred tetracycline compounds are tetracycline compounds which have been modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by excessive IL-1 and TNF .alpha. production.

Method of using tetracycline compounds to enhance interleukin-10

The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Method for inhibiting expression of inducible nitric oxide synthase with

A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

Method of using tetracycline compounds for inhibition of endogenous

A method for treating mammals suffering from conditions associated with excess phospholipase A.sub.2 activity and/or production comprising administering to the mammal an effective amount of a non-antimicrobial tetracycline sufficient to inhibit excess phospholipase A.sub.2 activity and/or production is disclosed.

A method for treating mammals suffering from rheumatoid arthritis and other tissue-destructive (chronic inflammatory or other) conditions associated with excess metalloproteinase activity comprising administering to the mammal an amount of a tetracycline that is effectively anti-metalloproteinase, but that is not effectively antimicrobial, and an amount of non-steroidal anti-inflammatory agent which, when combined with the effectively anti-metalloproteinase amount of tetracycline, results in a significant reduction of tissue destruction and/or bone loss.

Composition comprising indomethacin [non-steroidal anti-inflammatory

Composition comprising fluriprofen and effectively non-antibacterial

A method for treating mammals suffering from rheumatoid arthritis, other tissue-destructive conditions, and chronic inflammatory or other conditions associated with excess metalloproteinase activity comprising administering to the mammal an amount of a tetracycline that is effectively anti-metalloproteinase, but that is not effectively antimicrobial, and an amount of a non-steroidal anti-inflammatory agent which, when combined with the effectively anti-metalloproteinase amount of tetracycline, results in a significant reduction of tissue destruction and/or bone loss.

Composition comprising non-steroidal anti-inflammatory agent tenidap and

Provided is a method of treating humans or animals suffering from a condition or disease characterized by excessive collagen destruction, which comprises administering to said human or animal an effective amount of a 12a-deoxytetracycline represented by the following general formula ##STR1## The method is effective in the treatment of various articular diseases characterized by excessive collagen destruction.

Method to reduce connective tissue destruction

A method for treating mammals suffering from skeletal muscle wasting and/or intracellular protein degradation of skeletal muscle systems by administering to the mammal an amount of tetracycline which results in a significant reduction of the muscle wasting and protein degradation is disclosed. In addition, there is also disclosed a method of increasing the protein content of skeletal muscle systems of mammals by administration of tetracyclines. The tetracyclines useful in the above methods are both antimicrobial and non-antimicrobial. In a preferred embodiment, the method of treatment utilizes a non-antimicrobial tetracycline such as dedimethylaminotetracycline (CMT).

Inhibition of wasting and protein degradation of mammalian muscle by

Growing community of inventors

Melville, NY, United States of America

Robert A Greenwald