{"id":2552,"date":"2015-04-26T05:40:38","date_gmt":"2015-04-26T05:40:38","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=2552"},"modified":"2016-11-18T09:55:38","modified_gmt":"2016-11-18T09:55:38","slug":"biomarkers-in-saliva","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol5no2\/biomarkers-in-saliva\/","title":{"rendered":"Biomarkers in Saliva"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Saliva is mainly secreted by 3 major glands (parotid, submandibular and sublingual) and<\/p>\n

many other minor salivary glands, which provides the basic functions like lubrication and<\/p>\n

helps in taste, speech and digestion. The secretions from these glands is mixed with bronchial, nasal secretions, gingival crevicular fluid, blood constituents from bleeding gums, bacteria, virus, fungi, exfoliated epithelial cells and the food debris1, 2<\/sup>.<\/p>\n

It has been used as a diagnostic medium for several years now3, 4, 5<\/sup>. Saliva contains biomarkers derived from serum, gingival crevicular fluid and mucosal transudate. Systemic and oral diseases produce markers that appear in saliva. Unstimulated saliva contains higher concentration of diagnostic biomarkers than stimulated saliva and is used commonly for the diagnostic purpose. It is because, stimulated saliva has low concentrated proteins6, 7<\/sup> and variation in pH, due to the foreign substances (citric acid) that are used to stimulate salivary secretion. Apart from diagnosing various diseases, drug abuse can also be detected through salivary samples under drug monitoring system8<\/sup>.<\/p>\n

The advantages of using saliva as a diagnostic aid are, it is safe, non-invasive, cost effective, time saving and can be used in mass screening5, 9<\/sup>. The salivary biomarkers and their role in diagnosis of various systemic disorders are briefed in this article.<\/p>\n

Discussion<\/strong><\/p>\n

Saliva is used as a diagnostic medium for diseases such as, Oncology (Oral Squamous Cell Carcinoma, Cervical Cancer and Breast Cancer), Cardiovascular Diseases, and Infectious<\/p>\n

Diseases (Viral Diseases, Bacterial Infections, Fungal Infections), Endocrinology, Autoimmune Diseases (Sjogren\u2019s syndrome) and Psychiatry. Biomarkers are defined as cellular, biochemical and molecular characteristics by which normal\/abnormal processes can be recognized and\/or monitored.<\/p>\n

The biomarkers for various diseases are as listed below.<\/p>\n

Oncology<\/strong><\/p>\n

Saliva would be ideal for screening pre-malignant and malignant neoplasms because of its anatomical proximity. The bio markers are p53 antibody which can be detected in oral squamous cell carcinoma10<\/sup>, high level of salivary kallikrein in oral malignant tumors11, 12, 13<\/sup> and Ca-125, a glycoprotein for ovarian cancer14<\/sup>.<\/p>\n

Cardiovascular diseases<\/strong><\/p>\n

Cardio vascular diseases are the major cause for high mortality rate across the world. Salivary markers can be used for follow up after surgery. Determination of salivary amylase activity before and 6hrs after cardiovascular surgery shows more mortality in patients with low salivary amylase pre operatively.15<\/sup><\/p>\n

Infectious diseases<\/strong><\/p>\n

Viral diseases<\/strong><\/p>\n

Beta 2 micro globulin and soluble tumor necrosis factor are high in HIV patients.16, 17<\/sup> Acute hepatitis A & B are diagnosed based on the level of IgM antibodies in saliva.18<\/sup><\/p>\n

Bacterial infections<\/strong><\/p>\n

Presence of helicobacter pylori in saliva is a sign of peptic ulcer19, 20<\/sup>. Saliva can be used as a tool for the detection of dental plaque \u2013 induced diseases, i.e. dental caries and gingivitis21, 22<\/sup>.<\/p>\n

Fungal infections<\/strong><\/p>\n

Saliva can be used for the detection of oral candidiasis and salivary fungal counts23<\/sup>.<\/p>\n

Endocrinology<\/strong><\/p>\n

Hormone levels can be monitored with the aid of saliva. Estradiol, Estriol, Cortisol, Testosterone, Salivary Aldosterone, Salivary Progesterone are the hormones that can be accurately assessed from saliva. Diabetes mellitus affects rate of flow & composition of saliva. Salivary alterations include higher levels of IgA, salivary peroxidase, glucose content, potassium, salivary total protein & amylase24<\/sup>.<\/p>\n

Sjogren\u2019s syndrome<\/strong><\/p>\n

It is a chronic autoimmune disorder noted by salivary and lacrimal gland dysfunction along with rheumatoid arthritis. A raised concentration of NaCl, IgA, IgG, lactoferrin, inflammatory mediators such as PGE2, TXB2, interleukin-2 and interleukin-625, 26, 27<\/sup> are noted in the saliva of Sjogren\u2019s syndrome patient.<\/p>\n

Psychiatry<\/strong><\/p>\n

Objective Outcome Measures can be deciphered with the help of saliva during psychiatry. The therapeutic responses in the treatment of anxiety can be measured with salivary MHPG- (3-methyl 4-hydroxyphenyl glycol). 28<\/sup><\/p>\n

Drug monitoring<\/strong><\/p>\n

Saliva can be used to detect and monitor drugs like cocaine, opioids, barbiturates, diazepines, cotinine, cannabinoids and ethanol.29, 30, 31, 32<\/sup><\/p>\n

Conclusion<\/strong><\/p>\n

Although challenges remain ahead, the use of saliva – based oral fluid diagnostics appear promising for future application to diagnose diseases and to prognosticate treatment outcomes. More case controlled and longitudinal studies are needed in near future to validate these biomarkers and impregnate these into regular clinical practice, in a cost effective way for the benefit of mankind.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. Mandel, I.D., \u201cThe functions of saliva\u201d. <\/em>J. Dent. Res<\/em>. 66: 623\u20137. (1987).<\/li>\n
  2. Sreebny, L.M.., \u201cSalivary flow in health and disease\u201d. Compend. Suppl<\/em>.13: 461\u20139 (1989).<\/li>\n
  3. Kaufman, E., and Lamster, I., \u201cThe diagnostic applications of saliva: A Review\u201d. Crit. Rev. Oral. Biol. Med<\/em>. 13: 197\u2013212. (2002).<\/li>\n
  4. Streckfus, C.F., Bigler, L., Navazesh, M., Al-Hashimi, L., \u201cCytokine concentrations in stimulated whole saliva among patients with primary Sjogren’s, secondary Sjogren’s syndrome, and primary Sjogren’s syndrome receiving varying doses of interferon for symptomatic treatment of the condition: A preliminary study\u201d. J. Clin. Oral Invest. <\/em>5: 133. (2001).<\/li>\n
  5. Malamud, D., \u201cSaliva as a diagnostic fluid\u201d. Br. Med. J<\/em>. 8: 207\u20138. (1992).<\/li>\n
  6. Oberg, S.G., Izutsu, K.T., Truelove, E.L.,. \u201cHuman parotid saliva protein composition: Dependence on physiological factors\u201d. Am. J. Physiol<\/em>. 242(3): 231-236. (1982)<\/li>\n
  7. Rudney, J. D., Kajander, K.C., Smith, Q.T., \u201cCorrelations between human salivary levels of lysozyme, lactoferrin, salivary peroxidase and secretory immunoglobulinA with therapies\u201d. Caries Res<\/em>. 38: 241\u20136. (2004).<\/li>\n
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  11. Jenzano, J.W., Courts, N.F., Timko, D.A., Lundblad, R.L., \u201cLevels of glandular kallikrien in whole saliva obtained from patients with solid tumors remote from the oral cavity\u201d. J. Dent. Res. <\/em>65: 67-70. (1986a).<\/li>\n
  12. Jenzano, J.W., Daniel, P.A., Kent, R.T., Leal, J.L., Koth, D.L., \u201cEvaluation of kallikrein in human parotid and submandibular saliva\u201d. Arch. Oral. Biol. <\/em>31: 627-628. (1986b).<\/li>\n
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  15. Adam, D.J., Milne, A.A., Evans, S.M., \u201cSerum amylase Isoenzymes in patients undergoing operation for ruptured and non-ruptured abdominal aortic aneurysm\u201d. <\/em>J .Vasc.Surg.<\/em> 30: 229-235. (1999 ).<\/li>\n
  16. Grant, R.M., Piwowar, E.M., Katongole-Mbidde, E., \u201cComparison of saliva and serum for human immunode\u00ae- Ciency virus Type 1 antibody testing in uganda using a rapid recombinant assay\u201d. Clin. Diag. Lab. Immunol. <\/em>3: 640-644. (1996).<\/li>\n
  17. Nishanian, P., Aziz, N., Chung, J., Detels, R., Fahey, J.L., \u201cOral \u00afuids as an alternative to serum for measurement of markers of Immune activation\u201d. Clin. Diagn. Lab.Immunol<\/em>. 5: 507-512. (1998).<\/li>\n
  18. Bello, P.Y., Pasquier, C., Gourney, P., Puel, J., Izopet, J., \u201cAssessment of a Hepatitis C virus antibody assay in saliva for epidemiological studies\u201d. Eur J Clin Microbiol Infect Dis<\/em> 17: 570-572. ( 1998).<\/li>\n
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  20. Kountoruras, J., \u201cDiagnostic tests for Helicobacter Pylori\u201d. Gut. <\/em>42: 900-901. (1998).<\/li>\n
  21. Togelius, J., Kristoffersson, K., Anderson, H., Bratthall, D.,\u201cStreptococcus mutans.saliva: Intra individual variations and relation to the number of colonized sites\u201d.<\/em>Acta Odontol. Scand. <\/em>42: 157-163. (1984).<\/li>\n
  22. Stecksen-Blicks, C., \u201cSalivary counts of Lactobacilli <\/em>and Streptococcus Mutans<\/em>. Caries prediction\u201d. <\/em>Scand. J. Dent. Res. <\/em>93: 204-212. (1985).<\/li>\n
  23. Herenia, P., Lawrence., \u201cSalivary markers of systemic disease: Non\u2013 invasive diagnosis of disease and monitoring of general health\u201d. Can.<\/em> Dent. Assoc<\/em>. 68(3): 170-4. (2002).<\/li>\n
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  26. Rhodus, N., Dahmer, L., Lindemann, K., Rudney, J., Mathur, A., Bereuter, J., \u201cSiga and cytokine levels in whole saliva of Sjogren’s syndrome patients before and after oral pilocarpine hydrochloride administration: A Pilot study\u201d. Clin. Oral Invest<\/em>. 2: 191-196. (1998).<\/li>\n
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  28. Schramm, W., Pomerleau, O.F., Pomerleau, C.S., Grates, H.E., \u201cCotinine in an ultra\u00aeltrate of saliva\u201d. Prev. Med. <\/em>21: 63-73. (1992a).<\/li>\n
  29. Schramm, W., Smith, R.H., Craig, P.A., Kidwell, D.A., \u201cDrugs of abuse in saliva: A review\u201d. <\/em>J. Anal. Tox. <\/em>16: 1-9. (1992b).<\/li>\n
  30. Schramm, W., Smith, R.H., Craig, P.A., \u201cMethods of simpli\u00aeed saliva collection for the measurement of drugs of abuse, therapeutic drugs, and other molecules\u201d. <\/em>Ann.<\/em> Ny<\/em>. Acad. Sci<\/em>. 694: 311-313. (1993).<\/li>\n
  31. Smolle, K.H., Hofmann, G., Kaufmann, P., Lueger, A., Brunner, G., \u201cQ.E.D. Alcohol test: A simple and quick method to detect ethanol in saliva of patients in emergency departments. Comparison with the conventional determination in blood\u201d. Intensive Care Med<\/em> .25: 492-495. (1999).<\/li>\n
  32. Yamada, S., Yajima, J., Harano, M. \u00a0\u201cSaliva level of free 3-methoxy-4 hydroxyphenylglycol in psychiatric outpatients with anxiety\u201d. Int. Clin. Psychopharmacol. <\/em>13: 213-217. (1998).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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