Current developments in salivary diagnostics

Abstract

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 ...

Utility of Salivary Biomarkers for Demonstrating Acute Myocardial Infarction

“…Saliva is rapidly, easily, and non-invasively procured and contains thousands of biomolecules that are derived from the local capillary bed (Hu et al, 2005;Xiao and Wong, 2011). Several biomarkers associated with CHD and AMI [i.e., TnI, TnT, CK-MB, active matrix metalloproteinase (MMP)-8, and C-reactive protein (CRP)] can be detected in saliva at concentrations distinct from those in healthy individuals and that correlate with serum concentrations (Floriano et al, 2009;Miller et al, 2010;Buduneli et al, 2011;MirzaiiDizgah and Jafari-Sabet, 2011;Foley et al, 2012b;Mirzaii-Dizgah et al, 2012;Mirzaii-Dizgah and Riahi, 2013a,b). However, the clinical utility of these biomarkers for AMI assessment, alone or as a multimarker panel, is not fully understood.…”

Salivary microRNAs Show Potential as a Noninvasive Biomarker for Detecting Resectable Pancreatic Cancer

“…These molecules come from the capillary beds in the mouth, and they enter the saliva from the blood circulating in the salivary glands by passing through the spaces between cells by transcellular (passive intracellular diffusion and active transport) or paracellular routes (extracellular ultrafiltration; ref. 36). Thus, in health examinations, saliva may be used in place of plasma/serum to monitor variations of molecules in the blood (28).…”

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

“…aminoácidos, proteínas e lipídeos) (Miller, Foley et al 2010). A água da saliva tem origem do leito capilar local e entram nas glândulas salivares por difusão intracelular, canais de aquaporina e outras vias extracelulares (Haeckel and Hanecke 1996;Verkman, Yang et al 2000).…”

“…A redução da placa bacteriana em decorrência da raspagem pode levar a menor liberação de citocinas pró-inflamatórias (Miller, Foley et al 2010) vezes menor que o monômero e sua estrutura é mais estável (Olson, Bernardo et al 2000). Assim, a baixa atividade dessa espécie de MMP-9 forneceria apenas uma manutenção pequena, lenta e sustentada da proteólise in vivo (Marcaccini, Meschiari et al 2010).…”

“…É encontrado na literatura que citocinas pró-inflamatórias como IL-1, IL-6, TNF-α e TGF-β podem inibir a expressão do TIMP-1, e os níveis destas citocinas estão aumentadas na saliva de pacientes com DP (Pietruska, Pietruski et al 2009;Miller, Foley et al 2010).…”