In Vivo Study Of Diabetic Hyperglycemia And Inflammation
Robert Gyurko
Periodontology And Oral Biologyboston University Medical Campus
Grant 5R01DE016933-05 from National Institute Of Dental & Craniofacial Research IRG: ODCS
Abstract: Diabetes increases the susceptibility to infectious diseases, including periodontal disease. Periodontal disease is initiated by bacteria, but components of the host immune response are thought to contribute significantly to periodontal tissue damage. Of particular interest, free radicals such as superoxide play a prominent role both in diabetic complications and in periodontal tissue damage. Free radicals are produced in large quantities by polymorphonuclear (PMN) leukocytes, and abnormal PMN function is detected both in diabetes and in periodontal disease. This proposal is intended to help elucidate the molecular mechanisms that link diabetes and periodontal disease. The chief hypothesis to be tested is that elevated blood glucose activates PMN leukocytes, which in turn release excess superoxide causing tissue damage in the periodontium and in other tissues. A second focal point of these experiments is the evaluation of novel endogenous anti-inflammatory lipids, such as lipoxins, resolvins and docosatrienes. These molecules are formed locally during inflammation, and they antagonize the effect of PMN leukocytes and promote resolution of inflammation. Experiments are designed to test the effectiveness of stable analogs of lipoxins, defensins and docosatrienes in decreasing inflammatory tissue damage in diabetes and periodontal disease. These experiments employ a novel animal model of insulin-dependent diabetes, the Akita mice, and another mouse line, the Ncfl mice, whose PMN are deficient in superoxide generation. Akita and Ncf1 mice will be crossed to generate a double mutant experimental model in which the contribution of superoxide to diabetic tissue damage can be analyzed in alveolar bone and in soft tissue. The findings from these experiments might be important not only from the view of periodontal health, but also for diabetes research. Moreover, findings on novel lipid inhibitors of inflammation will be important in evaluating the therapeutic potential of these compounds in resolving inflammation in periodontal and other inflammations
Project start date: 2005-09-01
Project end date: 2010-07-31
Sponsored Links Excellgen http://Excellgen.com
In Vivo Study Of Diabetic Hyperglycemia And Inflammation
Robert Gyurko
Periodontology And Oral Biologyboston University Medical Campus
85 East Newton Street, M-921
boston, Ma 021182394
Grant 5R01DE016933-04 from National Institute Of Dental & Craniofacial Research IRG: ODCS
Abstract: Diabetes increases the susceptibility to infectious diseases, including periodontal disease. Periodontal disease is initiated by bacteria, but components of the host immune response are thought to contribute significantly to periodontal tissue damage. Of particular interest, free radicals such as superoxide play a prominent role both in diabetic complications and in periodontal tissue damage. Free radicals are produced in large quantities by polymorphonuclear (PMN) leukocytes, and abnormal PMN function is detected both in diabetes and in periodontal disease. This proposal is intended to help elucidate the molecular mechanisms that link diabetes and periodontal disease. The chief hypothesis to be tested is that elevated blood glucose activates PMN leukocytes, which in turn release excess superoxide causing tissue damage in the periodontium and in other tissues. A second focal point of these experiments is the evaluation of novel endogenous anti-inflammatory lipids, such as lipoxins, resolvins and docosatrienes. These molecules are formed locally during inflammation, and they antagonize the effect of PMN leukocytes and promote resolution of inflammation. Experiments are designed to test the effectiveness of stable analogs of lipoxins, defensins and docosatrienes in decreasing inflammatory tissue damage in diabetes and periodontal disease. These experiments employ a novel animal model of insulin-dependent diabetes, the Akita mice, and another mouse line, the Ncfl mice, whose PMN are deficient in superoxide generation. Akita and Ncf1 mice will be crossed to generate a double mutant experimental model in which the contribution of superoxide to diabetic tissue damage can be analyzed in alveolar bone and in soft tissue. The findings from these experiments might be important not only from the view of periodontal health, but also for diabetes research. Moreover, findings on novel lipid inhibitors of inflammation will be important in evaluating the therapeutic potential of these compounds in resolving inflammation in periodontal and other inflammations
Keywords: comorbidity, eicosanoid, free radical oxygen, hyperglycemia, immunomodulator, inflammation, insulin dependent diabetes mellitus, medical complication, periodontitis Bacteroides gingivalis, animal breeding, bacteria infection mechanism, chemical structure function, disease /disorder model, gene mutation, laboratory mouse, leukocyte activation /transformation, model design /development, neutrophil, pathologic bone resorption, superoxide fluorescence microscopy, liquid chromatography mass spectrometry
Project start date: 2005-09-01
Project end date: 2010-07-31
5R01DE016933-04 (2008): $251780
5R01DE016933-03 (2007): $254581
5R01DE016933-02 (2006): $262184
Grants awarded to Robert Gyurko
Nitric Oxide Defense Against Porphyromonas Gingivalis
Robert Gyurko
Boston University Medical Campus 715 Albany St, 560 Boston, Ma 021182394
Grant 5K22DE014568-04 from National Institute Of Dental And Craniofacial Research IRG: DSR
Abstract: Periodontal disease, the leading cause of tooth loss in the adult population, is an inflammatory disease which is triggered by bacteria, but it is thought that periodontal tissue damage is primarily inflicted by the host s own defense reaction. Nitric oxide (NO) is a multifunctional molecule present in periodontal tissues, which can be toxic to bacteria as well as to cells of the periodontal tissue. NO is released in response to Porphyromonas gingivalis (P. gingivalis) infection, a bacterium which is clinically and experimentally associated with periodontal disease. We propose experiments to elucidate the role of NO in the defense against P. gingivalis infection. In preliminary studies we have compared P. gingivalis-induced periodontal bone loss in normal mice and in mutant mice which do not produce NO in response to bacteria (iNOS KO mice). We found that iNOS KO mice are resistant to P. gingivalis induced bone loss. To investigate the mechanisms by which NO participates in antimicrobial defense, the role of NO in inflammatory reaction is evaluated in an implant chamber model of P. gingivalis infection. We study the interaction of NO with other antibacterial molecules, such as superoxide, by testing mutant mice deficient in NO, superoxide, or both NO and superoxide. To assess the importance of NO in regulating bone destruction, isolated bone tissue from normal and iNOS KO mice is tested for a series of signaling molecules which are known to cause bone loss. The role of NO in bone development at various ages of normal and iNOS KO mice is also tested. Robert Gyurko, DDS, PhD is currently conducting research on the role of NO in cardiovascular diseases at the Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA. He is applying for the NIDCR Scholar Development and Faculty Transition Award to pursue scientific career as an independent investigator at Boston University School of Dental Medicine.
Keywords: Bacteroides gingivalis, antibacterial agent, host organism interaction, nitric oxide, periodontium disorder, bone development, inflammation, longitudinal animal study, nitric oxide synthase, pathologic bone resorption, superoxide, genetically modified animal, laboratory mouse
Project start date: 2003-01-01
Project end date: 2006-12-31
5K22DE014568-04 (2006): $147361
5K22DE014568-03 (2005): $143068
5K22DE014568-02 (2004): $138900
1K22DE014568-01A1 (2003): $134854
In Vivo Study Of Diabetic Hyperglycemia And Inflammation
Robert Gyurko
Boston University Medical Campus 715 Albany St, 560 Boston, Ma 021182394
Grant 1R01DE016933-01 from National Institute Of Dental And Craniofacial Research IRG: ODCS
Abstract: Diabetes increases the susceptibility to infectious diseases, including periodontal disease. Periodontal disease is initiated by bacteria, but components of the host immune response are thought to contribute significantly to periodontal tissue damage. Of particular interest, free radicals such as superoxide play a prominent role both in diabetic complications and in periodontal tissue damage. Free radicals are produced in large quantities by polymorphonuclear (PMN) leukocytes, and abnormal PMN function is detected both in diabetes and in periodontal disease. This proposal is intended to help elucidate the molecular mechanisms that link diabetes and periodontal disease. The chief hypothesis to be tested is that elevated blood glucose activates PMN leukocytes, which in turn release excess superoxide causing tissue damage in the periodontium and in other tissues. A second focal point of these experiments is the evaluation of novel endogenous anti-inflammatory lipids, such as lipoxins, resolvins and docosatrienes. These molecules are formed locally during inflammation, and they antagonize the effect of PMN leukocytes and promote resolution of inflammation. Experiments are designed to test the effectiveness of stable analogs of lipoxins, defensins and docosatrienes in decreasing inflammatory tissue damage in diabetes and periodontal disease. These experiments employ a novel animal model of insulin-dependent diabetes, the Akita mice, and another mouse line, the Ncfl mice, whose PMN are deficient in superoxide generation. Akita and Ncf1 mice will be crossed to generate a double mutant experimental model in which the contribution of superoxide to diabetic tissue damage can be analyzed in alveolar bone and in soft tissue. The findings from these experiments might be important not only from the view of periodontal health, but also for diabetes research. Moreover, findings on novel lipid inhibitors of inflammation will be important in evaluating the therapeutic potential of these compounds in resolving inflammation in periodontal and other inflammations.
Keywords: comorbidity, eicosanoid, free radical oxygen, hyperglycemia, immunomodulator, inflammation, insulin dependent diabetes mellitus, medical complication, periodontitis, Bacteroides gingivalis, animal breeding, bacteria infection mechanism, chemical structure function, disease /disorder model, gene mutation, laboratory mouse, leukocyte activation /transformation, model design /development, neutrophil, pathologic bone resorption, superoxide, fluorescence microscopy, liquid chromatography mass spectrometry
Project start date: 2005-09-01
Project end date: 2010-07-31
1R01DE016933-01 (2005): $268494