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HSDM Theses and Dissertations

Mostrando recursos 1 - 14 de 14

  1. Resolution of Inflammation in Type 2 Diabetes

    Freire, Marcelo
    Unresolved inflammation is a key factor linking metabolic dysregulation and the immune system in type 2 diabetes. Successful regulation of acute inflammation requires biosynthesis of specialized pro-resolving lipid mediators, such as resolvin E1 (RvE1), and activation of cognate g-protein coupled receptors (GPCR). RvE1 binds to BLT-1 on neutrophils and ERV-1/ChemR23 on monocyte/macrophages. The mechanism by which innate immune cells in metabolic diseases fail to respond to endogenous pro-resolution signals is not well understood. The goal of the studies presented was to investigate the expression and function of ERV-1 receptor on neutrophils from type 2 diabetes subjects. Results demonstrate that neutrophils...

  2. Development of Novel Anti-DC-STAMP Monoclonal Antibody Targeting Osteolytic Periodontal Lesion

    Wisitrasameewong, Wichaya
    Background: Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion. This conclusion is supported by evidence showing that osteoclast cell fusion is diminished, while systemic bone mineral density is significantly elevated, in DC-STAMP-KO mice, when compared to their wild-type mice. Clinically available anti-bone loss drugs, such as denosumab (anti-RANKL mAb) and bisphosphonates, cause severe side effects of MRONJ or medication related osteonecrosis of the jaw, presumably by targeting the complete suppression of osteoclastogenesis, which interferes with normal osteoclast-osteoblast coupling, or by interrupting antibacterial immune responses. Therefore, this study aimed to examine the...

  3. Development of Novel Anti-DC-STAMP Monoclonal Antibody Targeting Osteolytic Periodontal Lesion

    Wisitrasameewong, Wichaya
    Background: Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion. This conclusion is supported by evidence showing that osteoclast cell fusion is diminished, while systemic bone mineral density is significantly elevated, in DC-STAMP-KO mice, when compared to their wild-type mice. Clinically available anti-bone loss drugs, such as denosumab (anti-RANKL mAb) and bisphosphonates, cause severe side effects of MRONJ or medication related osteonecrosis of the jaw, presumably by targeting the complete suppression of osteoclastogenesis, which interferes with normal osteoclast-osteoblast coupling, or by interrupting antibacterial immune responses. Therefore, this study aimed to examine the...

  4. Immunomodulation of Macrophages in Periapical Wound Healing

    Andrada, Ana C.
    Background: A periapical lesion is an infection-induced inflammation around the apex of the tooth caused by bacterial invasion and ultimately results in the destruction of bone in the area. To date, the relationship between pathogens and the host immune system in the development of periapical lesions have been extensively investigated. However, a detailed understanding of the host factors that determine successful periapical wound healing is currently lacking. The long-term goal of the present study is to identify the molecular network that regulates wound healing and tissue regeneration in dentoalveolar infections in order to develop rational therapeutic approaches. Although a rodent...

  5. A Two-Pronged Approach to Understanding Quality and Safety Events at the Dental Office

    Obadan-Udoh, Enihomo Mary
    ABSTRACT Objectives: Owing to the limited number and scope of studies in dentistry regarding quality and patient safety, the overarching goal of this thesis was to understand the nature and occurrence of quality and safety events in dentistry using a two-pronged approach – biomedical literature and patient-reported experiences. Methods: I conducted two exploratory studies: the first was a detailed retrospective review of published case reports on dental patient safety events; the second was a cross-sectional study of 450 patients at a large dental teaching practice in South Africa about their quality and safety experiences using a self-adminstered questionnaire. Results: 180 case reports (270...

  6. The Possible Roles of CD73 and Adenosine in the Osteoimmunological Bone Resorption of Periradicular Periodontitis

    Albassam, Abdullah
    Introduction: Periradicular periodontitis is an inflammatory disease caused by perpetual microbial infection in the root canal system which, if left untreated, results in the destruction of tooth supporting tissues. Tenacious infection of virulent bacteria can lead to continuous activation of host immune response which results in excess production of proinflammatory mediators, including the bone resorption factor RANKL. To date, attempts to minimize the destruction of tooth supporting tissues have included laser therapy and phototherapy, but these approaches have been confined to treating and monitoring the exogenous etiology, i.e., bacterial infection. Therefore, to improve the diagnosis and treatment of periradicular periodontitis,...

  7. Evaluation of αLphav Integrin Role in Mouse Model Induced Periapical Periodontitis

    Allahem, Ziyad
    Abstract: Background: alphav (av) integrin is the most common integrin alpha subunit, it is expressed in different cells and involved in many cellular process including adhesion, migration, survival and growth factor signaling. alphav on immune cells has a role in promoting T regulatory (Treg) cells production and differentiation of T helper 17 (Th17) through activating TGF-beta as shown in conditional knockout of alphav in immune cells. Osteopontin (OPN) is a ligand for alphav and involved in modulation of inflammation through its interaction with alphav in immune cells. OPN has been shown to have a protective role in endodontic infection, so we...

  8. Cellular Response to Expansion and Compression Forces in Mouse Midpalatal Suture and Surrounding Structures

    Katebi, Negin
    Objectives – To investigate the anatomy of the mouse palate, the midpalatal suture, and the cellular characteristics in the sutures before and immediately after midpalatal suture expansion, and as well as, to study the effects of compression force on the midpalatal suture. Materials and Methods – Wild-type C57BL ⁄ 6 male mice, aged between 6 weeks and 12 months, were chosen for all the experiments. The complete palate of the non-operated group and the midpalatal suture-expanded or -compressed group at different ages was used for histological, micro-CT, immunohistochemistry, and sutural cell analyses. Animals in the experimental group for compression were...

  9. Longitudinal Clinical Outcomes and Cost- Effectiveness Evaluation of a Comprehensive School- Based Dental Prevention Program – ForsythKids

    Bukhari, Omair M.
    We aimed to evaluate longitudinal clinical outcomes and cost-effectiveness of a comprehensive school-based caries prevention program, ForsythKids. In collaboration with the Massachusetts Department of Health, we solicited all principals and nurses from Massachusetts’s elementary schools in which greater than 50% of students received free or reduced meals, to participate. Dentists were calibrated at baseline and hygienists trained to deliver standardized dental care. Dentists clinically examined children following guidelines provided by the National Institute of Dental and Craniofacial Research. We assessed trends in the proportion of sound surfaces (PrSS) and teeth (PrST) remaining sound over subjects' number of visits in the program. We...

  10. Topical Clonazepam and Placebo Effect in Burning Mouth Syndrome

    Kuten-Shorrer, Michal
    Burning mouth syndrome (BMS) is a chronic pain condition reported to affect up to 7.9% of the general population, with associated detrimental impact on patients’ quality of life. Currently employed treatment regimens follow therapy for other neuropathic pain conditions. Very few placebo-controlled randomized trials (RCTs) have been conducted to evaluate the efficacy of these regimens, with a wide range of placebo responses documented. Low-dose clonazepam is considered first-line therapy for BMS, either in a topical or systemic mode of administration. An innovative formulation of topical clonazepam in the form of a compounded oral solution has been used at the Division...

  11. Short Sleep Duration as a Risk Factor for Obesity and Gingivitis in Kuwaiti Children: A Longitudinal Multilevel Analysis

    Alqaderi, Hend Ebrahim
    Objectives: It has been shown that inadequate sleep has negative effect on health including obesity, diabetes, and cardiovascular diseases. Current evidence showed that little sleep impairs immunity, promotes systemic inflammation, and increases the risk of pathological change in many body organs. Aims of this study were to assess the relations between insufficient sleep in developing obesity and gingivitis among a cohort of Kuwaiti children. We also identified the risk behaviors contributed to decreased sleep among those children. This is the first study that has examined the relation between sleep duration and the oral inflammatory condition; gingivitis. In addition, the majority...

  12. Saturation of the Biological Response to Orthodontic Forces and Its Effect on the Rate of Tooth Movement

    Chou, Michelle Yuching
    Objectives: The objectives of this research are to investigate the biological response of the body to different magnitude of force, and to investigate if the response varies among individuals. Therefore this research has 3 Specific Aims: Aim 1 is to investigate the biological response to different magnitudes of orthodontic forces at molecular and cellular levels in animals; Aim 2 is to investigate whether an equal magnitude of force can stimulate different levels of biological response among individuals; Aim 3 is to investigate whether the limit of biological response to different magnitudes of orthodontic force varies among individuals. Methods and Materials: For...

  13. Saturation of the Biological Response to Orthodontic Forces and Its Effect on the Rate of Tooth Movement

    Chou, Michelle Yuching
    Objectives: The objectives of this research are to investigate the biological response of the body to different magnitude of force, and to investigate if the response varies among individuals. Therefore this research has 3 Specific Aims: Aim 1 is to investigate the biological response to different magnitudes of orthodontic forces at molecular and cellular levels in animals; Aim 2 is to investigate whether an equal magnitude of force can stimulate different levels of biological response among individuals; Aim 3 is to investigate whether the limit of biological response to different magnitudes of orthodontic force varies among individuals. Methods and Materials: For...

  14. Biologic Significance of 5-Hydroxymethylcytosine Expression in Oral Mucosal Epithelial Dysplasia and Oral Squamous Cell Carcinoma

    Cuevas-Nunez, Maria C.
    Current modeling postulates that the development of cancer is driven by the accumulation of genetic mutations and epigenetic modifications, resulting in a clonal population of cells with deregulated growth characteristics. Three epigenetic mechanisms have been well documented, including DNA methylation, histone modifications and non-coding RNAs. Of these, DNA methylation is the best studied epigenetic alteration in cancer. Characterization of the expression of the epigenetic marker 5-hydroxymethylcytosine (5-hmC) in human and experimental melanoma and its precursors has established it as an important functionally relevant epigenetic biomarker in cancer. We therefore posited that 5-hmC in oral premalignant lesions and oral squamous cell...

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