Term
| Name 3 general attributes of saliva |
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Definition
| Clear fluid, slightly alkaline pH, viscous |
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Term
| Besides contributions from salivary glands what else contributes to saliva? |
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Definition
Gingival crevicular fluid (serum proteins, WBC and their products) Oral epithelial cells and their proteins Oral bacteria and their proteins Food debris |
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Term
| Saliva is what percent water? |
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Definition
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Term
| What ions make up saliva and are their amounts in saliva always the same? |
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Definition
| K+, Na+, Ca2+, Mg2+, H+, Cl-, HCO3-, I-, F-, HPO42- |
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Term
| Name small organic molecules found in saliva |
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Definition
| urea, hormones, lipids, DNA, RNA |
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Term
| What is found in saliva's proteome? |
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Definition
huge glycoproteins (106 Daltons) to smaler peptides (1000D) pI range 11.5-3.0 Secretory products of salivary glands Products of B cells, PMNs, epithelial cells, and bacteria |
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Term
| What protective functions do saliva have? |
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Definition
- Cleansing
- Lubrication
- Buffering (through HCO3-, HPO42-, peptides)
- Maintaining tooth integrity during stages of
- Post-eruptive maturation
- Mineralization equilibrium
- Pellicle forming
- Maintain tissue integrity
- Regulate oral flora
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Term
| How does saliva assist with oral function? |
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Definition
- Food processing
- Speech
- Excretion
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Term
| What are 2 reasons that complicate the study of gland activity? |
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Definition
- Different glands differ in composition (ie parotid, SM/SL, minor)
- Composition affected by level of gland activity (ie during sleep, awake/mouth at rest, awake/eating)
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Term
| Break down the cumulative daily flow rate of saliva |
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Definition
- Spontaneous (asleep): 8 hr at 0.05 mL/min = 25 mL
- Unstimulated (awake): 12 hr at 0.7 mL/min = 504 mL
- Stimulated (eating/talking): 4 hr at 2.0 mL/min = 480 mL
Total = 1009 mL |
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Term
| What happens to saliva composition with stimulation? |
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Definition
- P, K, duct cell proteins, and immunoglobulins dec.
- Ca, Na, Cl, bicarb, secretory cell proteins inc.
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Term
| Which gland dominates output at low level of stimulation? |
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Definition
Submandibular (62%) (with parotid at 25% and sublingual at 5%) [sublingual and minor always maintain at ~5% and 8% respectively, irregardless of level of stimulation] |
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Term
| What happen to saliva makeup as level of stimulation increases? |
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Definition
More parotid and less submandibular (with sublingual and minor the same) - Low stim parotid 25% and SM 62%
- Moderate stimulation parotid 35% and SM 53%
- High stim parotid 44% and SM 44%
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Term
| What are some research design issues working with saliva? |
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Definition
- Glandular (harder to get) or whole (easier to get, messier, more representative)?
- Stimulated or resting?
- What time of day?
- How to control for variation in flow rate?
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Term
| What are causes of profound xerostomia? |
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Definition
Head and neck radiotherapy for cancer Absence or surgical removal of salivary glands Inflammatory disease (Sjogrens, autoimmune, parotitis) |
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Term
| How many drugs have xerostomia as a side effect? |
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Definition
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Term
| Give examples of drugs with xerostomia as a side effect. |
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Definition
- Opiates
- Anti-cholinergics
- Anti-depressives
- Anti-hypertensives
- Anti-histamines
- Bronchodilators
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Term
| Is there a direct correlation between aging and xerostomia? |
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Definition
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Term
| 3 clinical strategies to deal with xerostomia: |
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Definition
- Drugs to stimulate flow
- Artificial salivas
- Gland repair/replacement
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Term
| What type of receptors mediate innervation for salivary stimulation? |
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Definition
| G protein coupled receptors |
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Term
| What type of parasympathetic receptors? What type of sympathetic receptors |
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Definition
| M3 muscarinic receptors; Beta 2 adrenergic receptors |
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Term
What pathway mediates the muscarinic messages and what is its major effector? And for adrenergic messages? |
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Definition
- Phospholipase C - IP3 pathway with Ca2+ as an effector
- Adenylate cyclase -cAMP pathway with effectors activated by phosphorylation cascade
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Term
| How is water secretion driven? |
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Definition
| By osmotic changes (ionic fluxes) from basolateral surface to apex (lumen) |
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Term
| What are some of the ion pumps and channesls in the basolateral and lumenal surfaces? |
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Definition
- Basolateral
- Na-K-ATPase
- Ca2+ activated K+ channel
- Na+-K+-2Cl- cotransporter
- Na-H exchanger
- Cl-HCO3- exchanger
- Lumenal
- Ca activated Cl channel
- HCO3 channel
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Term
| How does water cross the apical membrane? |
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Definition
- Through aquaporin family of water channels (Aqp5 = salivary aquaporin)
- Ca activated open to let water out
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Term
| When saliva enters the lumen is it isotonic or hypotonic? And the mouth? |
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Definition
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Term
| What happens in the striated ducts? |
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Definition
| Reabsorption of Na and Cl |
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Term
| At what point in the modification of saliva do drugs usually interfere and what is a key receptor in this? |
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Definition
| During water secretion; M3 |
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Term
| How is M3 involved in xerostomia? |
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Definition
- Autoantibodies to M3 in some Sjogren's patients
- Agonists can be useful in profound xerostomia treatment
- Anti-cholinergics will most likely induce xerostomia side effects
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Term
| What is one approach to repairing damaged salivary glands? How is it carried out |
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Definition
| Gene therapy; through viral transfection of genes into host cells |
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Term
| Why are genes transfused into ducts? |
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Definition
| Because ducts are best preserved in Sjogren's and radition |
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Term
| What was the effect of transfecting aquaporin into rat duct cells? |
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Definition
| Increased salivary flow, but only short term and only replaced water; would need to replace many genes for full repair |
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Term
| What are 3 steps in tissue engineering? |
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Definition
- Create biocompatible scaffold (with ductlike structure)
- Seed with cells that function like secretory/duct cells or induce differntiation in stem cells
- Implant into patient
- This must induce vasclarization and innervation
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Term
| What are the steps in exocytosis? |
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Definition
- Endoplasmic reticulum - translation/glycosylation
- Golgi - more extensive glycosylation
- Condensing vaculole- packaging, condensation
- Immature granule - sorting, major branching pt
- Secretory granule - protein storage
- Beta adrenergic stimulation
- Docking, membrane fusion, and exocytosis
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Term
| What is the immediate and long term response to noradrenaline? |
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Definition
Immediate - docking and fusion to release granules Long-term - transcription, translation, glycosylation, new granules |
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Term
| What membrane proteins mediate docking and fusion of secretory granules? |
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Definition
V(esicle)-SNARES on granule T(arget)-SNARES on inner apical membrane (this process is Ca dependent) |
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Term
| What protein pathways are sources of proteins in basal/resting secretions? |
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Definition
| Constitutive-like pathway ad minor regulated pathway |
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Term
| What protein pathway is always activated (no stim required)? |
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Definition
| Constitutive-like pathway; branches from immature granules |
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Term
| How is the minor regulated pathway stimulated? |
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Definition
| Low levles of M3 cholinergic agonists and vesicle membrane contains t-SNARES |
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Term
| What is the goal of proteomics? |
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Definition
| Identify and catalog every protein in a biological system |
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Term
| Why is the proteome useful? |
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Definition
| Can compare proteome patterns in cancer vs. control; virulent vs. avirulent bacteria; subjects w/ and w/o disease |
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Term
| What does amphifunctional mean? |
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Definition
| Helps both host and microbe |
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Term
| What are 3 key proteomics technologies? |
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Definition
- Separating along 2 dimensions
- Mass spec
- Bioinformatics
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Term
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Definition
| computer based identification of digested peptide patterns taken from info from human and all other genomes |
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Term
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Definition
| Gives exact MW of peptides in a trypsin digest |
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Term
| Differntiate between 1D and 2D. |
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Definition
- 1D - bands based on MW only
- 2D - separated based on MW and isoelectric pt (IEP)
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Term
| Why is saliva good for use as a biomarker? |
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Definition
- Non-invasive collection
- Broad range of potential analytes
- Bacteria
- Salivary ions
- Secreted salivary proteins
- Inflammatory mediators
- Proteins, metabolites from other parts of body
- Nucleic acids
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Term
| A biomarker must be associated with: |
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Definition
| active presence of disease or future risk of disease (no direct etiological relationship need occur) |
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Term
| What bacteria are biomarkers for caries risk in some tests? |
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Definition
| Lactobacilli and s. mutans |
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Term
| What is the general problem for biomarkers for caries? |
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Definition
| High sensitivity (ability to detect people with caries risk), low specificity (lots of false positives) |
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Term
| What other oral diseases besides caries have tests aimed at identifying biomarkers? |
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Definition
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Term
| What is the biomarker focus for perio? |
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Definition
| Givngival crevicular fluid |
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