Hemokinin-1 (HK-1) is a novel neuropeptide produced by human bronchial cells and macrophages and causes contraction of human bronchi ex vivo. It is also generated by antigen/IgE-activated murine mast cells (MCs) and contributes to experimental chronic allergic airway inflammation via the activation of the neurokinin receptor-1 (NK-1R) expressed on murine MCs. We found elevated MC numbers in the lungs of individuals who died from asthma (asthma) when compared to lungs of individuals who died from other causes (non-asthma). Mas-related G Protein coupled receptor X2 (MRGPRX2) is a novel G-protein coupled receptor (GPCR) that is expressed predominantly on human MCs. We detected low level of MRGPRX2 in non-asthma lung MCs but its expression was significantly upregulated in asthma lung MCs. HK-1 caused degranulation in a human MC line (LAD2) and RBL-2H3 cells stably expressing MRGPRX2 and this response was resistant to inhibition by an NK-1R antagonist. However, knockdown of MRGPRX2 in LAD2 cells resulted in substantial inhibition of HK-1-induced degranulation. These findings suggest that while HK-1 contributes to the development of experimental asthma in mice via NK-1R on murine MCs the effect of this neuropeptide on human bronchoconstriction likely reflects the activation of MRGPRX2 on lung MCs. Thus, development of selective MRGPRX2 antagonists could serve as novel target for the modulation of asthma.
Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression.
Objective. To prepare pharmacy and dental students to collaborate as members of an interprofessional team by participating in an interprofessional practice experience. Methods. An interprofessional practice experience was implemented within a dental admissions clinic. Pharmacy and dental students collaboratively conducted medical histories and provided tobacco cessation education. Pharmacy student performance was measured using a standardized assessment rubric; pharmacy and dental student perceptions were measured using the SPICE-R tool; and faculty feedback was captured for evaluation purposes. Results. Pharmacy students achieved performance expectations upon completion. There was a statistically significant increase in the mean scores for a majority of the SPICE-R factors for pharmacy and dental students. Overall, faculty perceptions of the practice experience were positive. Conclusion. A collaboration between pharmacy and dental schools is a novel approach to meeting interprofessional and experiential curricular goals. Evaluating performance in practice experiences and perceptions can be used to demonstrate learner outcomes within interprofessional education. Furthermore, faculty feedback should be used to improve practice experiences.
Thrombocytopenia Absent Radius (TAR) syndrome is a rare genetic disorder characterized by thrombocytopenia and bilateral absence of radii with both thumbs present. Multiple organ systems may be affected in patients with TAR syndrome, including hematologic, skeletal, cardiovascular, and gastrointestinal systems. This article describes a 35-year-old Caucasian male with TAR syndrome receiving comprehensive dental care and reviews the pertinent aspects of this disease, as well as dental management considerations, for patients with TAR syndrome.
Oral medicine is concerned with the diagnosis and nonsurgical management of medically related disorders of the oral and maxillofacial region as well as the oral health management of medically compromised patients. Oral diseases have a wide range of clinical presentations and can manifest either as a local oral disease or as a sign of an underlying systemic condition. Therefore, oral health is a vital component of overall systemic health and an oral lesion may in certain situations be the initial presentation of a systemic disorder. Consequently, it is imperative that oral health-care providers and physicians are adequately trained to accurately diagnose and manage diseases affecting the oral and maxillofacial region. This chapter addresses the systematic approach required for the evaluation of patients who present with oral diseases. This includes the process of
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