Methods to prevent and treat diseases

Abstract

This invention discloses methods and compositions that can treat a variety of tissue injuries and infections. Tissue-derived leukocyte chemotactic factors are rapidly released after injury to mammalian tissue and can act as the initial signal leading to the initiation and amplification of acute and chronic inflammation associated with injury and infection. The present invention generally provides methods and compositions to prevent and treat injury of cells, tissue, or organs by blocking or inhibiting the release of leukocyte chemotactic factors, by administering certain effective compositions to the tissue.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application relies on the disclosures of and claims the benefit of the filing dates of U.S. provisional patent application No. 60 / 818,806, filed 5 Jul. 2006, U.S. provisional patent application No. 60 / 835,748, filed 3 Aug. 2006, U.S. provisional patent application No. 60 / 846,684, filed 21 Sep. 2006, and U.S. provisional patent application No. 60 / 876,457, filed 20 Dec. 2007, the entire disclosures of all of which are hereby incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to the field of human and veterinarian medicine. More specifically, the invention relates to prevention and treatment of tissue and organ injury and infection in animals, such as mammals. [0004] 2. Discussion of Related Art [0005] Tissue-derived leukocyte chemotactic factors (LCFs) are a group of approximately 3 KDa peptides that are rapidly released by local tissues (within about 5 m...

AI Technical Summary

Benefits of technology

[0018] In some embodiments relating to creatine analogues, a method of treating animal (e.g., mammalian) tissue subject to injury comprises the step of administering to the mammal a creatine analogue in an amount between 0.01 g and 0.1 g creatine analogue per kg of mammal body weight. In certain embodiments, the administered dose of creatine analogue is in the 0.03-0.08 g / kg range. In these embodiments, the creatine analogue (e.g., cyclocreatine and cyclocreatine phosphate) can reduce intracellular cAMP production in the tissue. Tissue apoptosis can be significantly reduced or eliminated.

[0020] In preferred embodiments of the invention, the anti-inflammatory response arises from one or more actions of the tissue-protective agent. Such actions can be, among other things, delaying the depletion of adenosine triphosphate in the tissue, conserving the total adenylate pool in the tissue, buffering a decrease in the ratio of adenosine triphosphate to free adenosine diphosphate in the tissue, delaying exhaustion of high-energy phosphates in the tissue, maintaining cell-membrane integrity in the tissue, inhibiting caspase enzyme activity in the tissue, and reducing intracellular edema in the tissue.

[0021] In some embodiments, the tissue-protective agent crosses the blood-brain barrier of the animal (e.g., mammal). In certain embodiments, the agent accumulates in nerve tissue of the animal. In some embodiments, the agent reduces lactic acidosis in the tissue. The agent can also reduce the level of malondialdehyde in the tissue.

Problems solved by technology

Uncontrolled inflammation, on the other hand, can cause potentially destructive biological responses.

In the case of reperfusion after ischemia, neutrophils could also be deleterious to injured tissues because of their large size.

Neutrophils can plug tissue capillaries during reperfusion resulting in what is known as the “no-reflow” phenomenon with resultant impaired perfusion.

Furthermore, activated neutrophils induce extended cell injury during “early reperfusion” after ischemia.

Vaccines and viral medications are the two most common approaches generally used to prevent and treat viral infections, but neither can control the excessive host inflammatory response including cytokine storms, which occur secondary to Avian viral influenza infections and can cause death.

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