The purpose of this proposal is to study the pathogenesis of secondary bacterial infections following influenza infection. This year, the United States has pledged over $334 million dollars in international aid for countries battling influenza. In early 2000, influenza was the 7th leading cause of death in the United States alone, making it a very important public health concern. When addressing the primary cause of mortality, secondary bacterial infections following influenza account for 35- 40% of the mortality observed following viral infection. This is especially germane to the elderly population, where pneumonia alone or as a complication of flu is the leading infectious cause of death. Our objective is to understand the mechanism involved in the pathogenesis of increased susceptibility to secondary bacterial infection and thereby adopt specific therapeutic strategies that impact significant risk reduction in mortality and morbidity from influenza. Research Design and Methods: We will assess the effect of an overactive Th1 response in causing increased susceptibility to secondary bacterial infections, and also study the effects of an over-exuberant Th1 response on various effector cells in the lung. Finally, we will test therapeutic modalities that will target the over-exuberant response to decrease the risk of secondary bacterial infections. To address these objectives we will be using a rodent model for influenza infection, and then study their ability to clear bacteria following viral infection, exposing them to various anesthetics and drugs to modulate the immune response to viral infection. For testing the effect of the viral infection on various effector cells, we will isolate the effector cells from the BAL fluid of the animal and test these cells with various assays developed in the laboratory. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30AG031035-01A1
Application #
7487261
Study Section
Special Emphasis Panel (ZRG1-F07-L (20))
Program Officer
Fuldner, Rebecca A
Project Start
2008-02-28
Project End
2011-02-27
Budget Start
2008-02-28
Budget End
2009-02-27
Support Year
1
Fiscal Year
2008
Total Cost
$39,085
Indirect Cost
Name
State University of New York at Buffalo
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Jacob, Ayden; Chakravarthy, Krishnan; Law, Meng et al. (2014) Neuroradiology, Anesthesia, Bioengineering, and Hardware Programming in the Clinical Applications of Deep Brain Stimulation. Cureus 6:
Jacob, Ayden; Chakravarthy, Krishnan (2014) Engineering Magnetic Nanoparticles for Thermo-Ablation and Drug Delivery in Neurological Cancers. Cureus 6:
Jacob, Ayden (2014) Neuroradiologic Applications in the Assessment of Alzheimer's Disease and the Potential Implications of Brain Imaging in Forensic Psychiatry. Cureus 6:
Jacob, Ayden; Nourafchan, Lorenzo (2013) Radiological Engineering in Brain Dysfunction Imaging Processes and Neuro Informatics. J Nucl Med Radiat Ther 4:157
Chakravarthy, Krishnan V; Davidson, Bruce A; Helinski, Jadwiga D et al. (2011) Doxorubicin-conjugated quantum dots to target alveolar macrophages and inflammation. Nanomedicine 7:88-96
Chakravarthy, Krishnan V; Bonoiu, Adela C; Davis, William G et al. (2010) Gold nanorod delivery of an ssRNA immune activator inhibits pandemic H1N1 influenza viral replication. Proc Natl Acad Sci U S A 107:10172-7