fluoride metabolism - elitegyetem · fluoride inhibits na+/k+ -atpase, which may lead to...
TRANSCRIPT
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Fluoride metabolism
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Importance
CariespreventionCariesprevention
Haemopoesis
Reproduction
Hard tissue
Mineralisation
-
•
Most important sources:
–
food–
water
–
air
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Supplementary
sourcesMilk
Salt
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Fluoridemetabolism
•
Absorption•
Distribution
•
Storage•
Excretion/elimination
„ADME”
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Absorption•
GI tract–
Oral
mucosa
(toothpaste, mouth
water…)
•
5-8% absorbed, concentration
important
–
GI tract:•
Passive
transport
of
HF (gastric
juice
H+)
–
Depending
on
physico-chemical
features:•
solvability
(NaF
CaF2
, AlF3
)
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Milk, calcium lowers the absorption!
fasting
with milk
after a calcium rich breakfast
Plas
ma
fluor
ide
cc. (μm
ol/l)
Hours
-
bone surface
blood vessel
Readily excangable fluorid
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BoneDentine
Enamel
Fluoride content of different hard tissues
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before fluoride after fluoride
a, c : healty enamel
b: caries
Caries and fuoride treatment
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Plasma and saliva fluoride levels
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A fluoridreabsorption pH dependent
acidic urine
Alkalic urine
Acidic urine
BLOOD
Fluoride elimination
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Fluoride balance
•
Measuring
fluoride
intake
and
excretion–
Absorption
< excretion
negative
•
example: childhood–
Absorption
> excretion
positive
–
Absorption
= excretion
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Acute toxicity• Probably toxic dose: ~5mg/kg somewhere
1-10mg• Estimated lethal dose: 32-64mg/kg
– Pl. Elmex gel (highest fluoride content – registered as drug!!) 12,5 mg/g fluorid (12.500 ppm!) (25 és 125 g)
– Pl. Parodontax fluoride – 1400 ppm
• Symptoms from lower doses!– as low as 0.3 mg/kg (Gessner, 1994)
(http://content.nejm.org/cgi/content/full/330/2/95)
How much is toxic from these for a 12 kg child?
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• Once absorbed, fluoride binds calcium ions and may lead to hypocalcemia. Fluoride has direct cytotoxic effects and interferes with a number of enzyme systems; it disrupts oxidative phosphorylation, glycolysis, coagulation, and neurotransmission (by binding calcium). Fluoride inhibits Na+/K+ -ATPase, which may lead to hyperkalemia by extracellular release of potassium. Fluoride inhibits acetylcholinesterase, which may be partly responsible for hypersalivation, vomiting, and diarrhea (cholinergic signs). Seizures may result from both hypomagnesemia and hypocalcemia. Severe fluoride toxicity will result in multiorgan failure. Central vasomotor depression as well as direct cardiotoxicity also may occur. Death usually results from respiratory paralysis, dysrhythmia, or cardiac failure.
• Severity of symptoms depends upon the amount of fluoride ingested. These include abdominal pain, diarrhea, dysphagia, hypersalivation, , nausea, vomiting. Electrolyte abnormalities including hyperkalemia, hypocalcemia, hypoglycemia, and hypomagnesemia may occur. Neurological symptoms include headache, muscle weakness, hyperactive reflexes, muscular spasms, paresthesia seizures, tetanic contractions, and tremors. In severe cases, multiorgan failure will occur. Death typically results from cardiac arrest, shock, widening of QRS, and various arrhythmias occur.
http://emedicine.medscape.com/article/767546-overviewhttp://emedicine.medscape.com/article/767260-overviewhttp://en.wikipedia.org/wiki/Abdominal_painhttp://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Dysphagiahttp://en.wikipedia.org/wiki/Hypersalivationhttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Electrolytehttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Hypocalcemiahttp://en.wikipedia.org/wiki/Hypoglycemiahttp://en.wikipedia.org/wiki/Hypomagnesemiahttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Muscle_weaknesshttp://en.wikipedia.org/wiki/Spasmhttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Seizureshttp://en.wikipedia.org/wiki/Tetanic_contractionhttp://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Cardiac_arresthttp://en.wikipedia.org/wiki/Cardiac_arresthttp://en.wikipedia.org/wiki/Shock_(circulatory)http://en.wikipedia.org/wiki/Electrical_conduction_system_of_the_hearthttp://en.wikipedia.org/wiki/Arrhythmia
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Hard tissue
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Goal
• Patomechanism of caries
• Diagnosis of caries
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Quantitative Light-induced Fluorescence
• Based on the autofluorescence of the teeth• High energy blue light emission in green• proportional of mieralisation
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• Physical– structure
• Chemical– organic – anorganic components– acid solvability
• Other
Properties
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Physical
• Hardness – Vickers hardness
• Cristall structure – X-ray diffraction
• Mineralisation, distribution – μCT
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ChemischStep 1: pulverisation
Step 2: resuspending in bromoform-aceton mix
Separation of dentin and enamel with centrifugation
Step 3: centrifugation
Step 4: wash with aceton and dry
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Solvability in acid
• measuring demineralisation– standardisation:
• acid cc.• time• surface area
– measuring Ca2+ cc.
Importance: GERD
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acid proof lack
free enamel surface
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Vickers hardness
rat upper incisors
protein poor food109261326
normal food129320398
Dentindeepenamel
surface enamel
diamond
enamel surface
impression on the surface
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SkyScan-1172 High-resolution desk-top micro-CT systemX-ray detector: 1.3 Megapixel (1280x1024) 12-bit digital CCD-camera,Maximum object size for scanning and reconstruction: 20-37 mmComputer for 3D-reconstruction and image analysis: Dual Intel Xeon 3.6 GHz,2GB RAM, internal Writer, 320GB HDD, 128MB graphical cardReconstruction time: 0.42-1.1 sec per cross sectionReconstruction algorithms: Cone-beam volumetric reconstruction (Feldkamp)
Fluoride metabolismImportanceSlide Number 3Slide Number 4FluoridemetabolismAbsorption�Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Fluoride balanceAcute toxicitySlide Number 18Hard tissueGoalQuantitative Light-induced Fluorescence Slide Number 22Slide Number 23PhysicalChemischSolvability in acidSlide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31