Research Project: Monitoring of mast cells activation for control of health status in military personnel
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- Gaharwar, Akhilesh
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Background: Mast cells are located in various parts of the body, with the highest likelihood of changes introduced from outside: skin, respiratory system, gut and mesentery, along with blood and lymphatic vessels. Mast cells are sensitive to such changes, which may be induced, but not limited by mechanical stress (compression), increases in tissue fluid volume (edema), pH, abnormal temperatures, harmful dust, and ionizing irradiation. Additionally, mast cells are sensitive to the appearance of various antigens/pathogens, chemical and bacterial toxins, traumatic injury (direct cellular/tissue damage and effects of the products of tissue destruction), inflammation, and allergy. Cumulatively, we believe that monitoring ongoing levels of mast cell activation is especially valuable to evaluate and to monitor the pre-existing and ongoing health status of military personnel.
Objective/Hypothesis: The determination of pre-existing and monitoring of ongoing levels of mast cell activation is able to provide critical information on healthy reserves of the body and its ability to react to acute challenge. The studies in Aim 1 were designed to establish and characterize correlations between individual variations in resting levels of mast cell activation and the ability to respond/resist effectively to acute infectious challenge. The studies in Aim 2 were designed to establish and to characterize an ability to respond/resist effectively to acute infectious challenge in mast cell-stabilized animals with individual variations in resting levels of mast cell activation. The studies in Aim 3 were developed to design and to test the prototype of an implantable mini-sensor to detect changes in blood histamine and mast cell tryptase as the most important indicators of mast cell activation. In perspective, we believe that the portable reader/scanner will allow performance of periodic measurements of these parameters for fast assessment of individual health status of military personnel in missions. We believe that our innovative research directly targets goals of the FY19 AIMM Focus Area "Algorithms/tools for decision support in a deployed or operational environment to: diagnose military-relevant disease, illness, or injury; prescribe mitigation and treatment strategies; and/or determine risk of Warfighter return to duty."
Outcomes of research for military health and medicine:
1. Mast cell activation could be used as an early sign of development of infection. Our approach will provide the ability to start antibacterial therapy even earlier than clinical manifestation of any infection.
2. An ability to monitor mast cell activation in zones contaminated by ionizing irradiation will help to withdraw the most sensitive individuals from such action earlier than the accepted dose of irradiation can be reached. Such ability will help to prevent/diminish the harmful consequences of exposure to irradiation in more sensitive individuals, and to differentiate health risks more precisely on individual basis.
3. Mast cell activation levels could be used as indicators of abnormal reactions to predicted environmental changes (such as harmful dust, extreme heat or cold). In certain situations when personnel cannot be rotated, the therapeutic mast cell stabilization (e.g., masitinib mesylate) could be applied individually with on-time reference to increased levels of histamine and mast cell tryptase.
4. The implantable mini-sensors to detect changes in blood histamine and mast cell tryptase will provide an extremely useful tool to control the health status of military personnel in action. They will permit effective individually based health-oriented decisions in field conditions in accordance with the current situation and therefore diminish the likelihood of a Soldier’s health failure due to unforeseen/unexpected rising health problems.
5. The determination of which level of ongoing mast cell activation and degree of mast cell response could be a useful tool to evaluate the adaptive reserves of the military personnel.
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