Research Proposal
Author: Randall Bentley, DO, FACOI
1) Effects of Hyperbaric Oxygen Therapy on Mast Cells and Inflammatory Mediators.
Hyperbaric oxygen treatments have previously been shown to prevent the progression of fatty streaks and to enhance the regression of atherosclerotic plaque build-up.
(1) Arterioscler Thromb Vasc Biol. 2000;20:1637-1643.
Mast Cells play a direct role in the development of atherosclerotic plaque by releasing inflammatory cytokines (IL-6 and IFN-gamma, not TNF-alpha) that promote extracellular matrix degradation.
(2) Lipids Online. Nat. Med 2207 Mast cell-derived cytokines promote atherosclerosis. June 7, 2007.
Lesions in mice lacking mast cells had more collagen and preserved fibrous caps compared with mice not lacking mast cells. Mice lacking LDL receptors also showed more collagen in preserved fibrous caps.
Hyperbaric Oxygen (HBO) therapy modifies a variety of growth factor and cytokine effects by regulating their levels and/or receptors.
(3) Physiological and Pharmacological Basis of Hyperbaric Oxygen Therapy. Paul Sheffied, PhD, CHT, Adrianne P.S. Smith, MD. Published as chapter 4 in Hyperbaric Surgery: Perioperative. Care October, 2002.
This study proposes to use male New Zealand white rabbits, with two separate protocols: one for control, cholesterol-fed animals, and one for HBO-exposed cholesterol-fed animals. Levels of inflammatory mediators will be measured before and after a series of HBO treatments: histamine, TNF-alpha, prostaglandin D2, platelet-activating factor, IL1, IL4, IL6, granulocyte-macrophage colony-stimulating factor. Histological evaluation of the aorta and coronary arteries will be performed in both control and experimental animals, looking at the number of mast cells, morphology of mast cells (granulations present or absent), and local atheroma environment/ morphology.
This will be one of several studies to test novel therapies to down-regulate pro-inflammatory cytokines (IL1,IL4, IL5, IL13, TNF alpha) or up-regulate anti-inflammatory cytokines IL10, IL12, INF gamma) or test effects of H1, H2, IL4 and IL1 receptor antagonists on atherosclerosis.
May 19, 2010
Need a different Research Model? What about Starfish and Jellyfish?
Starfish (echinoderms) and Jellyfish (cnidarians) do show internal cellular and physiological signs of a primitive immune response to injury or infection. They do not experience “inflammation” the same way as humans or other vertebrates do.
Starfish response to Injury
*Starfish have a fluid-filled body cavity and specialized blood-like cells called coelomocytes.
*When wounded or infected, these cells move to the injured area.
*The cells surround and phagocytize the bacteria and debris.
*They release stress proteins but lack blood vessels and specific tissues for the classic vertebrate inflammatory response.
Jellyfish Responses to Injury
*Jellyfish have very simple tissue layers and lack a true circulatory or blood cell system.
*They can seal wounds and clear dead tissue using basic cellular repair mechanisms.
*They lack specialized immune organs, blood vessels, or mast cells, meaning they cannot mount a vascular inflammatory response.
Benefits of a study?
Using two experimental models on lower but different rungs of the evolutionary ladder to examine how the innate immune system might play a role in inflammation and better define components other than cytokines and such that are involved in inflammation.
2) Look at the Pacific Salmon for a research model— atherosclerotic plaque. Role of hormones?
3) For Operational Design and Kit Content Priorities (see Tropical Medicine Blog)
Thesis: In Tropical Medicine, the environment is both a heat source and an infectious exposure system. Design must reduce thermal load while interrupting transmission pathways.
