• Background: Tokyo Guidelines for the management of acute cholangitis and cholecystitis.

      Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Yoshida, Masahiro; Mayumi, Toshihiko; Sekimoto, Miho; Miura, Fumihiko; Wada, Keita; Hirota, Masahiko; Yamashita, Yuichi; et al. (2007-01-25)
      There are no evidence-based-criteria for the diagnosis, severity assessment, of treatment of acute cholecystitis or acute cholangitis. For example, the full complement of symptoms and signs described as Charcot's triad and as Reynolds' pentad are infrequent and as such do not really assist the clinician with planning management strategies. In view of these factors, we launched a project to prepare evidence-based guidelines for the management of acute cholangitis and cholecystitis that will be useful in the clinical setting. This research has been funded by the Japanese Ministry of Health, Labour, and Welfare, in cooperation with the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. A working group, consisting of 46 experts in gastroenterology, surgery, internal medicine, emergency medicine, intensive care, and clinical epidemiology, analyzed and examined the literature on patients with cholangitis and cholecystitis in order to produce evidence-based guidelines. During the investigations we found that there was a lack of high-level evidence, for treatments, and the working group formulated the guidelines by obtaining consensus, based on evidence categorized by level, according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence of May 2001 (version 1). This work required more than 20 meetings to obtain a consensus on each item from the working group. Then four forums were held to permit examination of the Guideline details in Japan, both by an external assessment committee and by the working group participants (version 2). As we knew that the diagnosis and management of acute biliary infection may differ from country to country, we appointed a publication committee and held 12 meetings to prepare draft Guidelines in English (version 3). We then had several discussions on these draft guidelines with leading experts in the field throughout the world, via e-mail, leading to version 4. Finally, an International Consensus Meeting took place in Tokyo, on 1-2 April, 2006, to obtain international agreement on diagnostic criteria, severity assessment, and management.
    • A Baseline Study of Fish Assemblages in a Pristine Georgia Estuary

      Hewett, Melissa; Ong, Claudia; McKittrick, Jacob; Sapp, Mikael; Thiruvaiyaru, Dharma; Sethuraman, Sankara; Moak, Jason; Saul, Bruce; Department of Biological Sciences (2017-03)
      St Catherine’s Island is one of Georgia’s uninhabited barrier islands, and is used strictly for research and conservation purposes. It is approximately seven miles from the mainland, and eighteen miles from the Altamaha River. Due to its location, the surrounding estuary has seen negligible anthropogenic impacts throughout its history. Brunsen Creek, on the southern end of the island, is isolated and considered to be a pristine marine ecosystem. This study is a continuation of an initial 2014 study to collect baseline monthly ichthyofaunal data via trawling. Data presented here contains summary information collected through August 2016. Information collected during this period will provide baseline data for fish assemblage comparisons within the surrounding Georgia estuarine ecosystem. Statistical relationships between Brunsen Creek fish assemblages and environmental factors, such as temperature and salinity, were not established. However, consistent relationships were observed in natural migration and reproduction patterns of key fishes that have also been noted in other studies. Temporal trends among the targeted species in this study reflect a well-established natural pattern along the Georgia coast. Following these trends will provide a baseline of expected life history events, and a reference for further research within southeastern estuaries.
    • A Bayesian Framework To Detect Differentially Methylated Loci in Both Mean And Variability with Next Generation Sequencing

      Li, Shuang; Department of Biostatistics and Epidemiology (2015-07)
      DNA methylation at CpG loci is the best known epigenetic process involved in many complex diseases including cancer. In recent years, next-generation sequencing (NGS) has been widely used to generate genome-wide DNA methylation data. Although substantial evidence indicates that di erence in mean methylation proportion between normal and disease is meaningful, it has recently been proposed that it may be important to consider DNA methylation variability underlying common complex disease and cancer. We introduce a robust hierarchical Bayesian framework with a Latent Gaussian model which incorporates both mean and variance to detect di erentially methylated loci for NGS data. To identify methylation loci which are associated with disease, we consider Bayesian statistical hypotheses testing for methylation mean and methylation variance using a twodimensional highest posterior density region. To improve computational e ciency, we use Integrated Nested Laplace Approximation (INLA), which combines Laplace approximations and numerical integration in a very e cient manner for deriving marginal posterior distributions. We performed simulations to compare our proposed method to other alternative methods. The simulation results illustrate that our proposed approach is more powerful in that it detects less false positives and it has true positive rate comparable to the other methods.
    • Bayesian Functional Clustering and VMR Identification in Methylation Microarray Data

      Campbell, Jeff; Department of Biostatistics and Epidemiology (2015-07)
      The study of the relation between DNA and health and disease has had a lot of time, energy, and money invested in it over the years. As more scientific knowledge has accumulated, it has become clear that the relations between DNA and health isn’t just a function of the sequence of nucleotide bases, but also on permanent modifications of DNA that affect DNA transcriptions and thus have a macroscopic effect on an individual. The study of modifications to DNA is known as epigenetics.Epigenetic changes have been shown to play a role in certain diseases, including cancer (Novak 2004). Finding locations of differential methylation in two groups of cells is an ongoing area of research in both science and bioinformatics. The number of developed statistical methods for establishing differential DNA methylation between two groups is limited (Bock 2012). Many developed methods are developed for nextgeneration sequencing data and may not work for microarray data, and vice versa. Bisulfite sequencing, the next-generation sequencing technique for attaining methylation data, often comes with limited sample size and considerations must be made for low and variable coverage, and smoothing the methylation values. The analysis of nextgeneration sequencing data also involves small sample sizes.In addition, these methods can be sensitive to how individual CpG regions are grouped together as a region for analysis. If the DMRs are small relative to the sizes of 5 established regions, then the method may not detect a region as having differential methylation. Robust methods for clustering microarray data have also been an ongoing area of research. It is desirable to have a method that could be applied to microarray data could increase the sample size and mitigate the previous problems if the method used is robust to missing values, outliers, and microarray data noise. Functional clustering has shown to be effective when properly conducted on gene expression data. It can be used when the data have temporal measurements to identify genes that are possibly co-expressed. The clustering of methylation data can also be shown to identify epigenetic subgroups that can potentially be very useful (Wang, 2011). [introduction]
    • BDNF Facilitates L-LTP Maintenance in the Absence of Protein Synthesis through PKMf

      Mei, Fan; Nagappan, Guhan; Ke, Yang; Sacktor, Todd C.; Lu, Bai; Mei, Lin; Department of Neurology (2011-06-29)
      Late-phase long term potentiation (L-LTP) is thought to be the cellular basis for long-term memory (LTM). While LTM as well as L-LTP is known to depend on transcription and translation, it is unclear why brain-derived neurotrophic factor (BDNF) could sustain L-LTP when protein synthesis is inhibited. The persistently active protein kinase f (PKMf) is the only molecule implicated in perpetuating L-LTP maintenance. Here, in mouse acute brain slices, we show that inhibition of PKMf reversed BDNF-dependent form of L-LTP. While BDNF did not alter the steady-state level of PKMf, BDNF together with the L-LTP inducing theta-burst stimulation (TBS) increased PKMf level even without protein synthesis. Finally, in the absence of de novo protein synthesis, BDNF maintained TBS-induced PKMf at a sufficient level. These results suggest that BDNF sustains L-LTP through PKMf in a protein synthesis-independent manner, revealing an unexpected link between BDNF and PKMf.
    • Behavioral Consequences of NMDA Antagonist-Induced Neuroapoptosis in the Infant Mouse Brain

      Yuede, Carla M.; Wozniak, David F.; Creeley, Catherine E.; Taylor, George T.; Olney, John W.; Farber, Nuri B.; Mei, Lin; Department of Neurology (2010-06-29)
      Background: Exposure to NMDA glutamate antagonists during the brain growth spurt period causes widespread neuroapoptosis in the rodent brain. This period in rodents occurs during the first two weeks after birth, and corresponds to the third trimester of pregnancy and several years after birth in humans. The developing human brain may be exposed to NMDA antagonists through drug-abusing mothers or through anesthesia.
    • Benefits and Challenges in the Development and Implementation of a Doctor of Physical Therapy Consortium

      Keskula, Douglas R; Mishoe, SC; Wark, ET; Department of Physical Therapy (Georgia Regents University, 2013-05-23)
      Educational consortiums provide an opportunity to improve the quality of the educational programs involved through an increase in resources, collaboration, and expertise, both administrative and faculty. This paper addresses the benefits along with the major challenges encountered in the development and implementation of a consortium involving multiple universities within a state system of higher education. The Board of Regents of the University System of Georgia approved the Doctor of Physical Therapy Consortium in 2005. The consortium created a partnership between three existing and successful physical therapy programs. One program was housed in a research university, and two were located in state universities. The primary goal of the consortium was to create an educational alliance within Georgia, which enabled the two state university physical therapy programs to offer doctoral level education to their students. The state university programs were unable to award the doctoral degree due to their institutional missions at that point in time. Forming a collaborative relationship between the state programs built on the excellence of the existing programs, helped to meet the demands of incoming students seeking a degree in physical therapy, produced a steady number of physical therapy graduates, and helped to meet the increasing expectations for practice into the future. The consortium was created to allow each partner to retain their unique mission, curriculum and identity while offering a doctoral degree in physical therapy to all students. Although there were several successful outcomes directly related to the consortium, there were also a variety of challenges that we believe limited the sustainability of the partnership. These challenges included costs relative to benefits, managing ambiguity, the perceived lack of faculty control, and issues related to effective and assertive conflict management.
    • Benefits of International Fieldwork for Occupational Therapy Students

      Vickman, Hannah; Carter, Krissy; Dittmer, Chandler; Nettles, Taylor; Wang, Caroline; McCarley, Trinity; Department of Occupational Therapy (Augusta University, 2020-09-01)
      At the conclusion of this presentation, attendees will: 1) Identify the perceived benefits for international fieldwork ascertained from the research and how that relates to professional and personal development, and 2) Identify the key clinical experience differences between OT students participating in international and domestic fieldwork, as established from the presented research.

      Cantrell, Elroy; Bresnick, Edward; Department of Cellular Biology and Anatomy (1972-02-1)
      Previous studies have implicated the reticuloendothelial cells of the liver in certain aspects of steroid metabolism. The similarity in the metabolism of steroids and polycyclic hydrocarbons suggested that the nonparenchymal cells possibly play a role in these areas . The present study presents evidence that at least one of the microsomal NADPH-requirig enzymes, benzpyrene hydroxylase, is present in nonparenchymal cells and, furthermore, is "inducible ." In adult rats treated with 3-methylcholanthrene or ß-naphthoflavone, the nonparenchymal cells exhibited increases in benzpyrene hydroxylase activity of 17-fold and five-fold, respectively . Treatment with phenobarbital resulted in only a slight increase in enzyme activity . Enzyme activity in parenchymal cells under similar conditions was increased sixfold and fivefold by 3-methylcholanthrene and ß-naphthoflavone, respectively, but not by phenobarbital.
    • Berlin Wall: A Reese Library Environmental Scan Infographic

      Department of English and Foreign Languages (Augusta University, Spr. 2019)
    • beta-Catenin Regulates Intercellular Signalling Networks and Cell-Type Specific Transcription in the Developing Mouse Midbrain-Rhombomere 1 Region

      Chilov, Dmitri; Sinjushina, Natalia; Saarimaki-Vire, Jonna; Taketo, Makoto M.; Partanen, Juha; Mei, Lin; Department of Neurology (2010-06-3)
      b-catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that b-catenin stabilization in mouse midbrain-rhombomere1 region leads to robust upregulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, b-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of b-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop. The changes in signal molecule expression were concomitant with deregulation of anteriorposterior and dorso-ventral patterning. The transcriptional regulatory functions of b-catenin were confirmed by b-catenin loss-of-function experiments. Temporally controlled inactivation of b-catenin revealed a cell-autonomous role for b-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of b-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.
    • Bilateral Hand-Assisted Laparoscopic Renal Surgery in the Supine Position: The Spleen at Risk

      Brown, James A.; Siddiqi, Kashif; Department of Surgery (2011)
    • Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

      Przybycien-Szymanska, Magdalena M.; Mott, Natasha N.; Paul, Caitlin R.; Gillespie, Roberta A.; Pak, Toni R.; Brann, Darrell W; Department of Neurology; College of Graduate Studies (2011-04-13)
      Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.
    • Biocompatibility and mechanical/physical properties of 3D printed, milled, and conventionally processed denture base materials

      Ulmer, Mallory; Biomedical Sciences (Augusta University, 2019-12)
      According to the American College of Prosthodontists, over 36 million people in the USA are edentulous with a 2:1 predilection for geriatric patients1. Each year, an estimated 15% of edentulous Americans will seek denture treatment1. Conventional dentures require multiple visits and lab processing time. 3D printing technology offers the potential to reduce the number of appointments and speed up the time until patient rehabilitation. However, the newly FDA-certified 3D printer denture resins, featuring secretive and proprietary formulae, lack studies concerning their biocompatibility/safety and mechanical strength. This study aims to investigate the biocompatibility and physical properties of one such 3D printer resin, NextDent® Base (Vertex, Soesterberg, The Netherlands), and compare it to pre-existing conventional polymethyl methacrylate (PMMA) denture base (Lucitone 199, Dentsply Sirona, York, Pennsylvania) and milled PMMA denture base (IvoBase CAD®, Ivoclar Vivadent AG, Schaan, Liechtenstein). The cytotoxicity was examined using of 12 discs: conventional PMMA, milled PMMA, as-printed 3D printer resin, post-cured 3D printer resin, and Teflon controls. An MTT assay using human periodontal ligament (900L) cells was employed, and specimens were aged for 1, 3, 7, 10, and 14 days. After day 7, there were no statistically significant differences among the groups, excluding the Teflon control, which showed significantly less cell viability on day 14. Bars of conventional PMMA, milled PMMA, as-printed 3D printer resin, and post-cured 3D printer resin were subjected to a 3-point bend test to examine flexural strength and moduli differences. The mean flexural strength was 63.8 ± 3.06, 82.6 ± 1.9, 5.1 ± 0.4, and 22.1 ± 6.4 MPa, respectively, while the flexural moduli were 1757.3 ± 109.5, 2226.7 ± 76.3, 110.3 ± 20.3, and 537.0 ± 210.6 MPa, respectively. The flexural strength and modulus were significantly different among all groups. Weibull analyses for conventional PMMA, milled PMMA, as-printed 3D printer resin, and post-cured 3D printer resin revealed a Weibull modulus of 23.5, 42.8, 16.6, and 3.7, respectively, and a characteristic strength of 65.2, 83.5, 5.3, and 24.5 MPa, respectively. The characteristic strength was significantly different among all groups as well. The Weibull modulus was significantly different between all groups, except for conventional vs. as-printed, which were not significantly different. In summary, milled PMMA featured significantly greater mechanical properties. Both 3D printed groups proved to be very weak, with the as-printed group being the weakest of all. The differences between the as-printed and post-cured groups highlight the importance of properly post-curing the resin. While the biocompatibility results showed promise, the mechanical testing results were disappointing. Unfortunately, the findings suggest that 3D-printed denture base resin is not yet ready for clinical use.
    • Biomechanical behavior related to structure in normal and congenitally disordered elastic arteries

      Beall, Arthur C.; Department of Pharmacology and Toxicology (Augusta University, 1992-12)
    • Bionanofabrication: engineering biomaterials for in situ remodeling and drug delivery

      Batt, Carl A.; Cornell University (2016-02-26)
      The bionanofabrication of smart materials presents opportunities in fields as far ranging as food science and medicine. The tools of molecular biology allow for the in vivo and in vitro production of unique biomolecules enabling not only the direct(ed) creation of novel proteins but also catalysts that can then produce other non-protein polymers. An example is the biodegradable polymer, polyhydroxyalkanoate (PHA), which is normally produced by a number of different bacteria. It is synthesized through a series of three enzymes but only one, polyhydroxalkanoate synthetase (PHAC) is required for the conversion of a soluble CoA-substrate into an insoluble hydrophobic polymer. Our laboratory has pioneered the in situ formation of PHA by engineering PHAC and targeting it toward fabricated and native substrates. Once on-site polymer formation can be initiated by introducing the substrate. Alternatively polymers can be formed in vitro and then delivered to the target site. Beyond the localized impact by the introduction of significant quantities of a highly hydrophobic polymer, PHA can also be used as a vehicle for the delivery of therapeutic drugs and once there release their cargo through its normal degradation process. Applications to cancer therapy and in situ engineering of microvasculature will be presented.
    • Biosynthesis and Modification of Helicobacter pylori Lipid A

      Stead, Christopher Michael; Department of Biochemistry and Molecular Biology (2010-05)
      The secondary acylation steps of Helicobacter pylori lipid A biosynthesis are poorly understood because H. pylori only has one homolog (Jhp0265) to the Escherichia coli secondary acyl transferases LpxL and LpxM. Jhp0265 was shown to be responsible for the transfer of a secondary C18 acyl chain to the 2′-linked acyl chain of lipid A, making Jhp0265 homologous to LpxL. An activity was also demonstrated for the addition of a secondary acyl chain to the 3′-linked acyl chain of H. pylori lipid A, although the enzyme responsible for the transfer remains unknown. After synthesis, H. pylori lipid A is modified by the action of five enzymes. Mutation of the candidate modification enzyme Jhp0634 demonstrated that the enzyme catalyzes the removal of the 3′-linked acyl chains of H. pylori lipid A, producing a tetra-acylated lipid A species. Continuing with the characterization of H. pylori lipid A modification enzymes, we were also able to demonstrate an activity for a Kdo trimming enzyme in vitro. Requirement for a Kdo hydrolase in vivo was confirmed after the Kdo transferase of H. pylori was shown to be bifunctional despite the presence of only one Kdo sugar in H. pylori lipopolysaccharide. Attempted identification of the Kdo hydrolase revealed that both Hp0579 and Hp0580 were required for the removal of the Kdo sugar, which occurred in the periplasm. A Kdo hydrolase mutant revealed two unexpected phenotypes related to interaction with the innate immune system. The first was an increased sensitivity to cationic antimicrobial peptides, which was explained by a downstream effect on modification to the 4′- phosphate group of lipid A. The second phenotype related to the expression of Oantigen on the bacterial cell surface. The Kdo hydrolase mutants produced a reduced amount of fully extended lipopolysaccharide and conversely, an increased amount of core-lipid A. The type of O-antigen epitope displayed was also affected by a Kdo hydrolase mutation, in a strain specific manner.
    • Biosynthesis of the Vibrio cholerae Kdo-lipid A Domain and its Role in Pathogenesis

      Hankins, Jessica V.; Department of Biochemistry and Molecular Biology (2011-05)
      Bacteria assemble remarkable surface structures that interface with their surrounding environment. One such structure is the glycolipid lipopolysaccharide (LPS) that covers the surface of Gram-negative bacteria. LPS is anchored to the bacterial cell by its lipid anchor known as lipid A. Since lipid A is the bioactive component of LPS, modulation of its structure can have a profound impact on disease by altering the host immune response. Additionally, LPS structure directly impacts the outer membrane permeability barrier and bacterial resistance to host antimicrobial peptides. Although the lipid A domain of Escherichia coli has been well characterized, the Vibrio cholerae lipid A biosynthetic pathway has received little attention. The late stages of lipid A biosynthesis include the transfer of the 3-deoxy-Dmanno- octulosonic acid (Kdo) sugars and the secondary acyl chains to the lipid A backbone. Here, the V. cholerae Kdo transferase (Vc0233) was shown to be monofunctional, transferring one Kdo residue to the lipid A precursor, lipid IVA. V. cholerae encode a Kdo kinase (Vc0227) responsible for the phosphorylation of the Kdo residue. The functionality of Vc0227 was shown to be required for the activity of the V. cholerae lipid A LpxL homologue, Vc0213. Interestingly, the addition of the phosphate group on the Kdo sugar was shown to be essential for lipid A secondary acylation in Haemophilus influenzae and Bordetella pertussis. Vc0213 was shown to catalyze the transfer of a myristate (C14:0) to the 2′-position of the V. cholerae phosphorylated Kdolipid A domain. A second protein, Vc0212, acts as an LpxM homologue and transfers 3- hydroxylaurate (3-OH C12:0) to the 3′-position creating hexa-acylated V. cholerae lipid A domain. Although lipid A secondary acyltransferases have been characterized among various Gram-negative bacteria, this is the first report of a lipid A secondary hydroxyacyltransferase. Further, the transfer of 3-hydroxylaurate (3-OH C12:0) was demonstrated to be essential for antimicrobial peptide resistance in V. cholerae and required for activation of the innate immune receptor TLR4.
    • Bisphenol A (BPA) Contamination in Yellow-Bellied Sliders (Trachemys scripta scripta)

      McDavid, Kayla; Department of Biological Sciences (Augusta University, 2017-05)
      Bisphenol A, also known as BPA, is a chemical that is recognized for being in a variety of consumer products, particularly to make plastic food containers and drink bottles (Makinwa, 2015). It was estimated in 2011 that about 5.5 million metric tons of BPA have been consumed globally (Flint, 2011). This is cause for alarm because it is classified as moderately toxic to aquatic life by the Environmental Protection Agency (EPA) (Flint, 2011). BPA can negatively affect gene expression and hormone pathways. It is also known for triggering sex changes during embryonic stages in turtles and caiman (Flint, 2011). A major source of BPA is littering of plastics, which enter ponds and wetlands and may become incorporated into the food web of aquatic species (Campani, 2013). When plastic products degrade, BPA is leached into the soil and can potentially flow into neighboring waterways (Makinwa, 2015). Animals acquire BPA through direct ingestion of plastic particles or through consuming plants or animals that have accumulated BPA. Previous research has shown that Bisphenol A acts as an endocrine disruptor on painted turtles, caiman, fish, and amphibians (Jandegian, 2015). It mimics the hormone estrogen, which at sufficient concentrations, may cause developing male embryos to produce female reproductive tissue. Snails have been observed to undergo “superfeminization” when exposed to about 1 μg/L (Flint, 2011). This superfeminization caused “additional female organs, enlarged sex organs, and oviduct deformities” (Flint, 2011). There is evidence that Bisphenol A causes feminization in most animals that have been studied, although the mechanism has yet to be found (Krüger, 2005). Turtles are often used as environmental indicators because they are omnivorous and tend to be long-lived. Their longevity makes them more likely than short-lived species to bioaccumulate toxins.If BPA concentrations are high in turtles, then it is likely that humans have absorbed a certain amount that may contribute to unknown biological consequences. Research has shown that there are links between this contaminant and the rates of cancer development, obesity, and the probability of a child developing neurological problem when exposed. According to the analysis of 315 urine samples “93% of people had detectable levels of BPA” (Kinch, 2015). The objective of my research was to quantify BPA concentrations in Yellow-bellied sliders (Trachemys scripta scripta) and their habitat. Blood samples were collected from the subcarapacial or dorsal coccygeal vein of each turtle captured. Additionally, soil samples were taken at the edge of the water. Study Areas Blood samples were collected from 9 turtles trapped at Reed Creek Park. Additional samples were collected from 22 turtles from Brick Pond Park. Reed Creek Park is in Martinez, Georgia (33.53375598, -82.08555523) (Google maps, 2016). Brick Pond Park is in North Augusta, South Carolina (33.4874273, -81.9786814) (Google maps, 2016). Ten soil samples were collected at each location. The soil samples were analyzed for BPA quantities and compared with the amounts of BPA that were recorded from the blood samples taken from the captured turtles. [Introduction]
    • Bisphosphonate-Related Osteonecrosis of the Jaw: From Mechanism to Treatment

      Howie, Rebecca; Department of Cellular Biology and Anatomy (2015-04-20)
      With 55 million prescriptions issued each year, bisphosphonates are the second most prescribed class of drug in the United States. They are widely used to treat diseases with excessive osteoclastic resorption, including post-menopausal osteoporosis, Paget’s disease, and tumor metastasis to bone. Unfortunately, with long term intravenous administration of nitrogen-containing bisphosphonates some patients develop bisphosphonate-related osteonecrosis of the jaw (BRONJ). This debilitating disease has limited treatment options once it has manifested and no mechanism for its development has been elucidated. This dissertation explores the novel concept that bisphosphonates cause osteonecrosis of the jaw by impairing osteocyte-induced osteoclastogenesis and, through the physical accumulation of bisphosphonates in bone, impairing the ability of recruited osteoclasts to attach thereby arresting bone healing. Furthermore, it explores the possibility that chelating agents can be used for the removal of bisphosphonate attachment from bone systemically and locally during extractions, potentially leading to a future preventive treatment. It was found that 13 weeks of 80µg/kg intravenous tail vein injections of Zoledronate followed by two mandibular molar extractions caused the clinical presentation of BRONJ as analyzed by the gross, radiographic, and histological methods. Bone dynamic parameters and TRAP staining suggested an impaired ability for the bone to remodel and defective osteoclast attachment in treated groups that persisted eight weeks after the cessation of treatment. Additionally, it was found through the use of a fluorescently tagged bisphosphonate, that the decalcifying agents cadmium, EDTA, and citric acid all had the ability to cause the significant release of bound bisphosphonate from bone. Finally, this dissertation showed that the migration of monocytes treated with low doses of Zoledronate had increased migration, while their migration to conditioned media of osteocytes treated with Zoledronate was impaired. Collectively, these data suggest that invasive trauma by itself consistently precipitated massive bone necrosis in Zoledronate treated animals, possibly through a bisphosphonate driven alteration of monocyte migration and that the use of decalcifying agents could acutely remove bisphosphonate from bone both systemically and locally. This study establishes and effective rodent model for BRONJ and a possible preventive strategy for the side-effects of bisphosphonates during high-risk situations.