Browsing by Author "Kowolik, Michael"

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    The Effects of Etidronate on Healing of Implant-Supporting Bone
    (2000) de la Rosa, Ana Marcela; Garetto, Lawrence P.; Katona, Thomas R.; Kowolik, Michael; Roberts, W. Eugene; Shanks, James C.
    The bisphosphonate etidronate, a drug commonly used to treat osteolytic bone disorders, produces a long lasting inhibition of bone resorption. Since continual bone remodeling appears crucial for the long-term success of endosseous implants, the effects of this drug on the bone surrounding implants were investigated. The specific objective was to quantify the static and dynamic histomorphometric properties of bone surrounding implants placed in 12 beagle dogs treated with this drug. The dogs were divided into three groups (4 dogs/group) based on the bisphosphonate treatment dose: 0, 0.5 and 5.0 mg/kg/day. Since remodeling is different at distinct sites around implants, we analyzed bone at different distances (<1, 1-2 and 2-3 mm from the implant) and in different regions (periosteal and endosteal calluses and intracortical bone). Factorial ANOVA with repeated measures was used to compare site and regional differences in the dose groups. Results show that etidronate treatment produced a decrease in remodeling activity in the treated groups. The high dose group had impaired bone formation and a complete inhibition of remodeling. Low dose produced the same trend, but was not statistically different from controls. The significant differences (p < 0.05) were shown by the high dose group compared to controls for Mineralizing Surface (MS/BS), Activation Frequency (AcF), Mineral Apposition Rate (MAR), Bone Formation Rate (BFR), Formation Period (FP), Mineralization Lag Time (MLT), Adjusted Apposition Rate (AjAr) and Bone Volume (BV/TV), while Osteoid Volume (OV/TV) and Osteoid Thickness (OTh) were higher (p < 0.05) in the high dose group. Since it has been suggested that a remodeling rate of 500 percent per year is achieved in the first millimeter around an implant in successful osseointegration, the area within the first millimeter, as expected, was more affected by all the parameters than further away. These results agree with earlier studies in which areas of high remodeling were shown to be more affected by bisphosphonate therapy than areas of low remodeling. The area closest to the implant showed significantly greater BV/TV, Void Volume (VV/TV), Osetoid Volume over Bone volume (OV/BV), Osteoid Surface (OS/BS), MS/BS, BFR, FP, AcF and MLT while OV/TV was significantly increased in the area most distant from the implant. It was found that etidronate interfered with normal bone mineralization, since there was a decrease in MLT and an accumulation of osteoid. If remodeling is high around implants so as to repair or prevent microdamage, then etidronate could impair this from happening, thereby resulting in eventual implant failure. Though these high doses are not ordinarily used for the clinical treatment of osteoporosis, a low dose might still be harmful if given long-term. These data confirm our hypothesis that etidronate affects bone resorption and mineralization around an implant, when given at the high dose. Two hypotheses were rejected, since in this study, the effect of etidronate was not dose-dependent. This study was supported by NIH 2PO1AG05793, Merck and CO., and Procter and Gamble Pharmaceuticals.
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    Empowering Department Chairs to Facilitate Faculty Mentoring
    (Office of Academic Affairs, IUPUI, 2017-11-14) Edwards, Paul; Kowolik, Michael; Chu, Gabe; Calvert, Danielle; Hemmerlein, Scott; Kolar, N.
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    Green tea catechin inhibits the activity and neutrophil release of Matrix Metalloproteinase-9.
    (Elsevier, 2016-10) Kim-Park, Wan K.; Allam, Eman S.; Palasuk, Jadesada; Kowolik, Michael; Park, Kichuel K.; Windsor, L. Jack; Department of Biomedical and Applied Sciences, IU School of Dentistry
    Green tea (Camellia sinensis; 綠茶 lǜ chá) extracts have been shown to possess anti-oxidant and anti-inflammatory effects in various cell types. Green tea extract (GTX) has been shown to significantly inhibit the activity of collagenase-3 (matrix metalloproteinase-13 (MMP-13)) in vitro. MMPs, such as
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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 Oxidative Response of Human Monocytes to Surface Modified Commercially Pure Titanium
    (Frontiers Media, 2021-06-02) De Poi, Robert P.; Kowolik, Michael; Oshida, Yoshiki; El Kholy, Karim; Periodontology, School of Dentistry
    Cellular responses to implanted biomaterials are key to understanding osseointegration. The aim of this investigation was to determine the in vitro priming and activation of the respiratory burst activity of monocytes in response to surface-modified titanium. Human peripheral blood monocytes of healthy blood donors were separated, then incubated with surface-modified grade 2 commercially pure titanium (CPT) disks with a range of known surface energies and surface roughness for 30- or 60-min. Secondary stimulation by phorbol 12-myrisate 13-acetate (PMA) following the priming phase, and luminol-enhanced-chemiluminescence (LCL) was used to monitor oxygen-dependent activity. Comparison among groups was made by incubation time using one-way ANOVA. One sample from each group for each phase of the experiment was viewed under scanning electron microscopy (SEM) and qualitative comparisons made. The results indicate that titanium is capable of priming peripheral blood monocytes following 60-min incubation. In contrast, 30 min incubation time lead to reduced LCL on secondary stimulation as compared to cells alone. At both time intervals, the disk with the lowest surface energy produced significantly less LCL compared to other samples. SEM examination revealed differences in surface morphology at different time points but not between differently surface-modified disks. These results are consistent with the hypothesis that the titanium surface characteristics influenced the monocyte activity, which may be important in regulating the healing response to these materials.
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    Use of an Orthodontic Bracket as a Fiduciary Marker for Digital Subtraction Radiography
    (2004) Silverman, Michael J.; Parks, Edwin T.; Roberts, W. Eugene; Hohlt, William F.; Kowolik, Michael; Shanks, James C.
    Radiography is an essential diagnostic technique for the detection of hard tissue changes over time. Digital subtraction radiography allows a significant improvement in the ability to detect subtle changes in hard tissues and has been used for many applications including assessment and monitoring of root resorption, caries, periodontal disease, periapical disease and implants. Subtraction radiography requires two identical images taken at different times. The subtracted image is a composite, representing the changes in density. The ability to accurately detect changes is dependent on the reproducibility of the projection geometry between images and the ability to register or superimpose those images. Historically, this has been difficult to achieve and clinical application of this technique has been limited. Many approaches have been suggested to address this problem. To date, no investigators have used an orthodontic bracket as a fiduciary marker for digital subtraction. The purpose of the study was to investigate the use of an orthodontic bracket with and without additional fiduciary markers for digital subtraction radiography. The hypothesis is that, by virtue of its geometry and stable position, an orthodontic bracket will provide more accurate subtractions than controls using anatomic reference points. This laboratory study examined digital subtraction images obtained from human mandibular incisors with and without brackets. Direct digital images of forty teeth were taken at no angulation and 10 and 15 degrees of labial and lingual tip. The images were reconstructed and subtracted using the Emago/Advanced v3.5 program. The standard deviations of the subtraction histograms were evaluated with an ANO VA model to test the null hypothesis of no significant difference in the accuracy of digital subtractions between groups. An exploratory analysis of the length and width of the reconstructed images was also performed. Ten teeth were randomly selected to have their reconstructions repeated to assess intra and inter operator repeatability with this method. Subtractions performed using the brackets alone or the brackets with additional fiduciary markers were significantly more accurate than those performed with anatomic landmarks (p < 0.05). Reconstruction length of the no bracket group was closer in length to the reference images while length of the bracket groups were closer to the reference image length for labial tipping and closer to the tipped image for lingual tipping. Differences in width between groups were negligible. Improving the accuracy of digital subtraction by using orthodontic brackets as fiduciary markers will assist in research applications of interest to orthodontists, particularly root resorption, and may contribute to the improvement of clinical applications, such as monitoring patients genetically susceptible to root resorption. The use of an orthodontic bracket provides another tool to facilitate the application of digital subtraction radiography.
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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.