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Saliva as a Diagnostic Fluid. Dennis E. Lopatin, Ph.D. University of Michigan. Overview of Lecture. Applications of Sialochemistry Collection of Saliva Examples of Clinical Conditions Gingival Crevicular Fluid (GCF). Historical Background: Diagnostic Testing.

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Saliva as a diagnostic fluid l.jpg

Saliva as a Diagnostic Fluid

Dennis E. Lopatin, Ph.D.

University of Michigan


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Overview of Lecture

  • Applications of Sialochemistry

  • Collection of Saliva

  • Examples of Clinical Conditions

  • Gingival Crevicular Fluid (GCF)


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Historical Background: Diagnostic Testing

  • Rice Test (anxiety=dry mouth=guilt)


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Saliva as a Mirror of the Body

  • Tissue fluid levels of natural substances, as well as molecules introduced for therapeutic, dependency or recreational purposes

  • Emotional status

  • Hormonal status

  • Immunological status

  • Neurological status

  • Nutritional and metabolic influences


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Applications of Sialochemistry

  • Diseases of the salivary glands

  • Systemic diseases where salivary glands are involved

  • Clinical situations in which salivary flow and chemistry are helpful in diagnosis or monitoring patient progress


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Local Diseases

  • Obstructive- neoplastic, mucus plugs, stones

  • Inflammatory- acute viral or bacterial, chronic recurrent bacterial, allergic

  • Irradiation

  • Functional hyper- or hypoactivity


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Systemic Diseases

  • Sjögren’s syndrome- lymphoepithelial lesions

  • Cystic fibrosis

  • Hormonal dysfunction- diabetes, pancreatitis, adrenal-cortex disease, thyroid disease, acromegaly, menopause

  • Hypertension

  • Obesity and hyperlipidemia

  • Alcoholic cirrhosis

  • Malnutrition

  • Neurologic diseases- Parkinson’s disease, Bell’s and cerebral

  • Psychogenic diseases



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Clinical Situations Affecting Salivary Secretions

  • Digitalis toxicity

  • Drug monitoring

  • Environmental pollutants

  • Ovulation

  • Immunodeficiency

  • Pharmacological agents

    • “Dry mouth” side effects, drugs with parasympathetic, sympathetic and ganglionic blocking effects

    • Direct effects- hypersensitivity or idiosyncratic reaction


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Methods of Collection of Saliva

  • Whole Saliva

  • Catheterization

  • Parotid Saliva

  • Submandibular (Submaxillary) Saliva


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Limitations in Use of Whole Saliva

  • An admixture of parotid, submandibular and minor gland secretions mixed with food debris, bacteria, shed cells, leukocytes and other particulate matter.

  • Compositional studies are affected by proportions of secretions from different glands, as well as chemistry of non-salivary elements

  • In studies examining non-salivary components, must take care to exclude GCF, especially where inflammation is present.


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Standardization of Collection

  • Resting secretions

    • need an accommodation period of at least 5 minutes. (Influence of collection procedure as stimulus)

  • Stimulated saliva

    • Consistent gustatory stimulant throughout the study

  • Flow rate

    • Timed, focus on specific gland

  • Time of day

    • Circadian rhythm, time of collection is important


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Salivary Studies in Cystic Fibrosis (CF)

  • CF gene cloned in 1991

  • The gene product is a cyclic AMP-regulated chloride ion channel named CFTR

  • Cystic Fibrosis Transmembrane Conductance Regulator

  • Most investigators felt that chloride and water secretion was the unifying key to explain the abnormalities and consequences of CF.

  • A disease of all exocrine glands.


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Sialochemistry Studies of CF

  • Marked increase in calcium, proteins and phosphate, most evident in submandibular glands

  • Turbidity of the submandibular saliva probably due to precipitation of calcium-binding proteins

  • Too much overlap in calcium levels between CF and asthmatics to serve as screening test

  • Flow rate of saliva from labial salivary glands virtually absent in 90% of CF children, probably due to turbidity and blockage of duct


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Diagnostic Aids in Clinical Situations

  • Digitalis toxicity (calcium and potassium)

  • Affective disorders (prostaglandin)

  • Immunodeficiency (sIgA)

  • Stomatitis in chemotherapy (albumin)

  • Cigarette usage (cotinine)

  • Gastric cancer (nitrates and nitrites)

  • Forensic medicine (blood group substance)

  • Coeliac disease (anti-IgA gliadin)

  • Liver function (caffeine clearance)


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Malignancy

  • P53 Tumor suppressor antigen

    • inactivation in certain cancers leads to accumulation. Oral squamous cell carcinoma leads to anti-p53 antibodies in saliva

  • Salivary Defensin-1 levels elevated in oral SCC (made by PMN’s).

  • C-erbB-2 (erb) Tumor marker associated with breast carcinoma.

  • CA 125 (ovarian cancer marker) associated with elevated salivary levels


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Drug and Hormone Monitoring

  • Psychiatrists studying methadone: advantages using saliva

    • humanitarian- less discomfort

    • clinical- patient acceptance of repeated testing

    • children and patients with limiting coping abilities

    • economic (do it yourself tests)

  • HIV therapy

  • Epilepsy



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Salivary Antibodies and Antigens

  • Advantages in large scale studies

  • Viral Screening

  • Antigen Detection

    • H. pylori (PCR of saliva)

  • Antibody Screening

    • rubella

    • hepatitis A and B

    • Shigella


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Gingival Crevicular Fluid (GCF)

(E) Cervical enamel

(OSE) Oral sulcular epithelium

(JE) Junctional epithelium

(OE) Keratinized oral epithelium


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Collection of GCF

  • Static fluid

  • Timed crevicular fluid flow




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GCF Flow and Menstrual Cycle

  • GCF flow highest at ovulation


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GCF and Tetracycline Levels

Maximum GCF

Minimum GCF

Blood by finger

puncture


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Conclusions

  • Sialochemistry provides important information in a variety of clinical and disease states

  • Greater acceptance by patients

  • Non-invasive in most cases


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