Browsing by Subject "Periodontal Disease"

Now showing 1 - 4 of 4
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    Effects of tobacco on human gingival fibroblasts
    (2011) Zhang, Weiping; Windsor, L. Jack; Song, Fengyu; Kowolik, Michael J.; Lee, Chao-Hung; Subramaniam, Denise Rogers
    The negative heath consequences of smoking are widely recognized, but there are still about 20% of the people in United States using tobacco products. Cigarette smoke condensate (CSC), the particulate matter of cigarette smoke, is comprised of thousands of chemicals (e.g., nicotine). Secondary only to bacterial plaque, cigarette smoking is a major risk factor for periodontal disease. Human gingival fibroblasts (HGFs) are the main cellular component of periodontal connective tissues. During the development of periodontal disease, collagen degradation occurs. Collagen is the major extracellular matrix component of the gingiva. The major extracellular matrix degrading enzymes produced by the HGFs are the matrix metalloproteinases (MMPs). The MMPs are mainly modulated by the tissue inhibitors of metalloproteinases (TIMPs). In this dissertation, three studies aimed at understanding the effects of tobacco on human gingival fibroblasts and their mechanisms have been conducted: the effects of CSC on HGF-mediated collagen degradation; comparison of the effects of CSC on HGFs with that of nicotine; and the combined effects of CSC and bacteria on HGFs. The cell proliferation of HGFs decreased and cytotoxicity increased in HGFs treated with increasing concentrations of CSC. CSC increased the collagen degrading ability of the HGFs by altering the production and localization of MMPs and TIMPs. Nicotine is one of the major components and the most pharmacologically active agent in tobacco. The percentage of nicotine in the CSC was 2.4%. CSC (100 µg/ml) increased the collagen degrading ability of the HGFs by affecting membrane associated MMP-2, MMP-14, and TIMP-2, but the level of nicotine in the CSC may only play a limited role in this process. Porphyromonas gingivalis (P. gingivalis) is an opportunistic pathogen involved in periodontal disease. The combined effects of CSC and P. gingivalis supernatant increased HGF-mediated collagen degradation by destroying the balance between the MMPs and TIMPs at the protein and mRNA levels. This project demonstrated that tobacco (with or without P. gingivalis) increased HGF mediated collagen degradation, as seen in the periodontal disease, through altering the MMPs and TIMPs.
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    Peptidoglycan Recognition Proteins in the Pathogenesis of Preeclampsia and Periodontal Disease
    (2015) Dukka, Himabindu; John, Vanchit; Reiter, Jill; Blanchard, Steven B.; Zunt, Susan; Kowolik, Michael
    Background: Pre-eclampsia a potentially life threatening hypertensive disorder occurring in 3-14% of pregnancies. Its etiology is multifactorial involving the placenta. The only “cure” that currently exists is the delivery of the baby, which is often pre-term. There is no early pregnancy screening test to recognize those at risk. Recently, an altered immune-inflammatory responses at the placental level in response to infectious agents (eg., periodontal pathogens) have been proposed to be etiological for this pregnancy complication. A new class of Pattern Recognition Receptors called Peptidoglycan Recognition Proteins (PGRPs) constituting 4 distinct molecules PGRP 1-4 is emerging as a key player in modulating host responses to peptidoglycan and its breakdown products. A critical knowledge gap exists on the role of PGRPs in the innate immune responses that occur at the maternal-fetal interface in response to pathogens and their components that may be present in maternal circulation secondary to chronic infections. Aim: The aim of this pilot study is to investigate the expression PGRPs in the placenta of pre-eclamptic women. The overall goal is to better understand the association of periodontal disease and adverse pregnancy outcomes. Methods and Materials: This case control study consisted of subjects with: (1) normal term pregnancies (n=7) (2) pre-eclampsia (n=7). Preeclampsia was defined as hypertension (systolic blood pressure of ≥ 140 mm Hg or diastolic blood pressure of ≥ 90 mm Hg on at least 2 occasions, 4 hours to 1 week apart) and proteinuria (≥ 300 mg in a 24-hour urine collection or one dipstick measurement of ≥ 2+). A real time quantitative PCR array was used to analyze the relative mRNA expression of TLR2, TLR4, NOD1, NOD2, PGRP1, PGRP2, PGRP3, and PGRP4. Immunohistochemistry was performed to determine the cell type(s) expressing the PGRP proteins in the placental tissue. Summary statistics (mean, standard deviation, range, 95% confidence interval for the mean) were calculated for PGRP 1-4 expression for each group. Results and conclusions: The PCR data showed the expression of PGRPs 1, 3 and 4 in the placental samples. There was an up-regulation of PGRP-1 (1.4 fold) and down regulation of PGRP-3 (1.3 fold) and PGRP-4 (1.6 fold). TLR2, TLR4 and NOD2 mRNA were also elevated in the placental samples. Immunohistochemistry demonstrated positive staining for PGRPs 3 and 4 in the trophoblasts. The results from this novel research could lead to development of salivary and/or plasmatic biomarkers for early detection of PE and warrants further investigation.
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    The Responses of Human Neutrophils to Tobacco Smoke Components
    (2012) Al-Shibani, Nouf Khider; Windsor, L. Jack; Song, Fengyu; Kowolik, Michael J.; Goodpaster, John V. (John Vincent); Subramaniam, Danise Rogers
    Tobacco smoking is considered a major modifiable risk factor for periodontal disease. Tobacco contains about 6700 compounds and almost 4000 compounds of these have been identified in tobacco smoke. Nicotine is the addictive ingredient in tobacco and has been shown to affect multiple cellular processes. Cigarette smoke condensate (CSC) is the particulate matter of smoke. It is believed to be a powerful inducer of inflammatory responses. Neutrophils are the first line of host defense and are critical cells in the maintenance of periodontal health through their role in the control of bacteria, but they can also contribute to the progression of periodontal disease by the production and release of reactive oxygen species (ROS). Virulence factors from periodontal pathogens, such as Porphyromonas gingivalis (P. gingivalis), stimulate the respiratory burst of neutrophils. In this dissertation, three studies aimed at understanding the oxidative activity of neutrophils when stimulated with either nicotine, cigarette smoke condensate (CSC) or four other components of tobacco smoke (2-naphthylamine, hydroquinone, acrolein, and acetaldehyde) with or without P. gingivalis supernatant. The release of matrix metalloproteinase-9 (MMP-9) was also examined. ROS production increased significantly when the neutrophils were stimulated with nicotine. P. gingivalis induced the maximum ROS production when compared to all the other components examined. The combination of nicotine and P. gingivalis did not have an additive effect on ROS production. Nicotine significantly increased the MMP-9 release from the neutrophils. On the contrary, CSC inhibited ROS production at all the concentrations examined. The combination of CSC and P. gingivalis resulted in the inhibition of ROS production. MMP-9 release was also increased from the CSC-treated neutrophils. The four other tobacco smoke components examined affected ROS production and MMP-9 release differently. These projects demonstrated that CSC inhibited the ROS production from neutrophils, which can be attributed to several components in tobacco smoke that may include acrolein and hydroquinone. More research is needed to determine the mechanisms of inhibition and if other tobacco components are involved in ROS inhibition
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    Utilizing Electronic Dental Record Data to Track Periodontal Disease Change
    (2020-07) Patel, Jay Sureshbhai; Jones, Josette; Thyvalikakath, Thankam Paul; Palkal, Mathew; Kowolik, Michael; Nagarajan, Radha
    Periodontal disease (PD) affects 42% of US population resulting in compromised quality of life, the potential for tooth loss and influence on overall health. Despite significant understanding of PD etiology, limited longitudinal studies have investigated PD change in response to various treatments. A major barrier is the difficulty of conducting randomized controlled trials with adequate numbers of patients over a longer time. Electronic dental record (EDR) data offer the opportunity to study outcomes following various periodontal treatments. However, using EDR data for research has challenges including quality and missing data. In this dissertation, I studied a cohort of patients with PD from EDR to monitor their disease status over time. I studied retrospectively 28,908 patients who received comprehensive oral evaluation at the Indiana University School of Dentistry between January 1st-2009 and December 31st-2014. Using natural language processing and automated approaches, we 1) determined PD diagnoses from periodontal charting based on case definitions for surveillance studies, 2) extracted clinician-recorded diagnoses from clinical notes, 3) determined the number of patients with disease improvement or progression over time from EDR data. We found 100% completeness for age, sex; 72% for race; 80% for periodontal charting findings; and 47% for clinician-recorded diagnoses. The number of visits ranged from 1-14 with an average of two visits. From diagnoses obtained from findings, 37% of patients had gingivitis, 55% had moderate periodontitis, and 28% had severe periodontitis. In clinician-recorded diagnoses, 50% patients had gingivitis, 18% had mild, 14% had moderate, and 4% had severe periodontitis. The concordance between periodontal charting-generated and clinician-recorded diagnoses was 47%. The results indicate that case definitions for PD are underestimating gingivitis and overestimating the prevalence of periodontitis. Expert review of findings identified clinicians relying on visual assessment and radiographic findings in addition to the case definition criteria to document PD diagnosis.