Salivary diagnostics is an emerging field that has progressed through several important developments in the past decade, including the publication of the human salivary proteome and the infusion of federal funds to integrate nanotechnologies and microfluidic engineering concepts into developing compact point-of-care devices for rapid analysis of this secretion. In this article, we discuss some of these developments and their relevance to the prognosis, diagnosis and management of periodontitis, as an oral target, and cardiovascular disease, as a systemic example for the potential of these biodiagnostics. Our findings suggest that several biomarkers are associated with distinct biological stages of these diseases and demonstrate promise as practical biomarkers in identifying and managing periodontal disease, and acute myocardial infarction. The majority of these studies have progressed through biomarker discovery, with the identified molecules requiring more robust clinical studies to enable substantive validation for disease diagnosis. It is predicted that with continued advances in this field the use of a combination of biomarkers in multiplex panels is likely to yield accurate screening tools for these diagnoses in the near future. Keywordsacute myocardial infarction; lab-on-a-chip; periodontitis; salivary diagnosis Overview of the field of salivary diagnosisThe analysis of blood and its components has been the mainstay for laboratory diagnostic procedures for several decades. However, other biological fluids are also utilized frequently for the diagnosis of disease, for example urine and cerebrospinal fluid, and thus, saliva could offer some distinct advantages in select situations [1][2][3][4][5][6]. Saliva is a hypotonic fluid NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript composed mostly of water, electrolytes and organic molecules (i.e., amino acids, proteins and lipids). The water component is derived largely from the local capillary bed via intracellular diffusion, aquaporin water channels and extracellular routes [7,8]. Small neutral molecules from the serum enter by passive diffusion from the dense beds of capillaries surrounding and bathing the salivary glands. Electrolytes enter the saliva via osmotic gradients and are regulated by the rate of secretion, nature of the stimulus and level of mineralocorticoids in the circulation. The organic components of glandular saliva are derived largely from protein synthesis and are stored as granules within the acinar cells [4]. Because serum components of saliva are derived primarily from the local vasculature that originates from the carotid arteries [9], saliva has a prodigious fluid source that provides many, if not most, of the same molecules found in the systemic circulation. This makes saliva a potentially valuable fluid for the diagnosis of various systemic diseases (Figure 1).The recent cataloguing of the salivary proteome has availed considerable information that is potentially important for diagnostic applications ...

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Following the widespread use of immunosuppressive therapy and broad-spectrum antimycotic prophylaxis, C. glabrata has emerged as an important opportunistic pathogen in the oral mucosa. In the past, studies on the virulence factors and host-pathogen interactions of this organism were scarce, but continued to rise in recent years. Denture-wearing, immunosuppression, antibiotic therapy, and aging are risk factors for oral colonization or infection with C. glabrata. Compared with C. albicans, C. glabrata exhibits lower oral keratinocyte-adherence capacity, but higher denture-surface-adherence ability. The role of extracellular hydrolase production in the virulence of this organism does not appear to be as important as it is in C. albicans pathogenesis. Although traditionally thought of as a non-transforming yeast organism, both phenotypic switching and pseudohyphal formation have recently been identified in C. glabrata, but their role in pathogenesis is not known. With the exception of granulocyte monocyte colony-stimulating factor, C. glabrata triggers a lower proinflammatory cytokine response in oral epithelial cells than does C. albicans, in a strain-dependent manner. C. glabrata is less susceptible to killing by human beta-defensins than is C. albicans and exhibits various degrees of resistance to the antifungal activity of salivary histatins and mucins. In addition, C. glabrata possesses both innate and acquired resistance against antifungal drugs, due to its ability to modify ergosterol biosynthesis, mitochondrial function, or antifungal efflux. This resistance allows for its relative overgrowth over other susceptible species and may contribute to the recent emergence of C. glabrata infections in chronically immunocompromised populations. Further investigations on the virulence and host-pathogen interactions of C. glabrata are needed to better define the pathogenesis of oral C. glabrata infection in susceptible hosts.

We describe a patient with recurrent episodes of oropharyngeal candidiasis who required progressively higher doses of fluconazole to control and infection. The patient was treated for 14 infections over a 2-year period with doses of fluconazole that ranged from 100 to 800 mg per day. Clinical response, two methods of in vitro susceptibility testing, and molecular epidemiologic techniques were evaluated for 12 of the 14 episodes. Ultimately, the patient became unresponsive clinically to a dose of 800 mg of fluconazole per day. In vitro susceptibility testing of isolates obtained during these successive episodes of infection revealed the development of resistance to fluconazole, and molecular epidemiologic techniques confirmed the persistence of the same Candida albicans strain throughout all 12 episodes.