7. Conclusion

different antiepileptic drugs (namely phenytoin, valproate, and carbamazepine), were found to be increased and were compared with protein levels in the saliva of healthy control subjects. It was also found that, for all patient groups, the specific amylase activity was increased up to twofold. On the other side, absolute and relative concentrations of cystatin S were diminished in all samples, but particularly strong in patients using either valproate or phenytoin. These data suggest that use of antiepileptic drugs over long periods may cause a decrease of salivary proteins such as sIgA and cystatins, which are involved in the protection of the oral cavity against microbial infections and, therefore, these patients suffer more complications related to

Ngounou Wetie et al. [77] have investigated the use of salivary proteins as possible markers for early onset of Autism Spectrum Disorders (ASDs). Authors have identified increased levels of apolipoproteins apoA1 and apoA4 and of serum paraoxonase/arylesterase 1 (PON1) in ASD sera compared to healthy controls in blood serum and have tested the hypothesis that levels of these peptides might also be elevated in saliva. Authors found statistically significant differences in expression of a number of salivary proteins such as elevated prolactin-inducible protein, lactotransferrin, Ig kappa chain C region, Ig gamma-1 chain C region, Ig lambda-2 chain C regions, neutrophil elastase, polymeric immunoglobulin receptor and deleted in malignant brain tumors 1. Identifications made support the hypothesis that immune system

Castagnola et al. [78, 79] have applied a proteomics approach for studying the naturally occurring peptidome of human saliva in children diagnosed with ASDs. The study revealed that naturally occurring peptides in the saliva of children with ASD can bear multiple phosphorylations. The phosphorylation level of four specific salivary phosphopeptides, identified in this study, statherin, histatin 1, and acidic proline-rich proteins for both entire and truncated isoforms, was found to be significantly lower in autistic patients, with hypophosphorylation of at least one peptide observed in 18 ASD subjects (66%). Authors suggest that different phosphorylation and hypophosphorylation of salivary peptides suggest potential asynchronies in the phosphorylation of other secretory proteins. These proteins could be relevant in the development of central nervous system during embryonic development or in early infancy. Furthermore, obtained results suggest that naturally occurring salivary phosphopeptides might help

Saliva has a continuous and intensive contact and interaction with human teeth and plays an important role in cleaning the tooth surface and antimicrobial defense. Salivary proteomics and its role in dentistry have been studied in a number of experiments. Some of these have addressed the role of salivary proteins in edentulous patients diagnosed with DM. Byrd et al. and Border et al. [80, 81] have addressed the problem of edentulous patients with Denture

Denture stomatitis refers to an inflammatory condition of the mucosal tissue underneath the denture, which could lead to severe health problems. Clinical classification of DS distinguishes

gingiva and oral cavity in general.

80 Salivary Glands - New Approaches in Diagnostics and Treatment

disturbances may be present in individuals with ASDs.

to detect and discriminate a subgroup of ASD patients.

6.4. Application of salivary proteomics for dentistry

stomatitis (DS) and DM type-2.

In summary, salivary proteomics is an upcoming approach for both basic and clinical research with a significant potential for use in fast diagnostic approaches. Not only the analysis of salivary proteins but also the analysis of endogenous peptides in saliva and their posttranslational modifications shall be addressed and targeted. Although a number of studies have been published and more are to come, more research is required to validate the discovered putative biomarkers so far.

Current proteomics approach for the analysis of oral fluid is not yet suited for daily routine in clinical diagnostics. However, it can help discovering biomarkers for which immunological tests such as ELISA can be developed.

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Furthermore, it is essential to develop and curate a comprehensive database for the salivary proteome and establish standard conditions for sample collection and processing until the MS analysis.

The space was scarce in this chapter to address more of the clinical approach of salivary proteomics, but the researcher is encouraged to stay focused and follow the further development.

Current development shows that, without any doubt, this process will continue and will yield more biomarker candidates in the future.
