10 -ca-p-f


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10 -ca-p-f

  1. 1. Calcium ~ Phosphates ~ Fluorine © Department of Biochemistry, 2011 (J.D.)
  2. 2. Calcium distribution and turnover mineral deposits 25 000 mmol Ca daily intake 25-30 mmol bone remodelation phosphates 7.5 mmol/d oxalates phytates rapid exchange 500 mmol/d absorption < 15 mmol/d ECF ICF 2.5 mmol/l signaling function total only 35 mmol 0.1 µmol/l Ca2+ as second secretion messenger up to 7 mmol/d filtration tubular resorption 240 mmol/d 230 mmol/d excretion fraction max. 5 % decreased by PTH enlarged by calcitonin 17 – 25 mmol/d and high supply of Na+ 5 – 6 mmol/d 2
  3. 3. Recommended intake:Calcium in food Infants Adults 1200 mg 1000 mg Older people 1500 mg Animal food Plant food • milk • broccoli, poppy seed • dairy products • nuts, almonds, dates, legumes • bioavailability ~ 50 % • bioavailability ~ 10 %Intestinal calcium absorption isIncreased by vitamin D, proteins, fermented milk products (yoghurt, kefir)Decreased by phosphates (Coca-Cola, processed cheese), oxalates (leafy vegetables),magnesium (leafy vegetables), the excess of dietary fibre 3
  4. 4. bones, teeth soft tissues ECFCalcium in the body 99 % 0.9 % 0.1 % Ca2+ in blood plasma ∼ 2.5 mmol/l 50 % ionized 40 % with albumin 10 % chelated (citrate, oxalate etc.) Regulation effects – only ionized Ca2+ 4
  5. 5. Effects of ionized Ca2+• neuromuscular excitation(hypocalcemia increases / hypercalcemia decreases excitability of muscles)• contraction of striated and smooth muscles• secretion of signal molecules (neurotransmiters, peptide hormones, catecholamines)• blood clotting• cell adhesion - tight junction – interactions with cadherinsthe changes in Ca2+ concentrations influence all these processes 5
  6. 6. Calcium chelates do not dissociate in aqueous solution CH2 COO- 2 Ca2+ COO- & 2 HO C 2 + CH2 COO- &D , Ca2+ & 2 , CH2 COO- 2 calcium oxalate HO C COO- calcium malate Ca2+ CH2 COO- calcium succinate calcium citrateCompare: Poorly soluble calcium saltsCaCO3 Ca(COO)2 CaSO4 Ca3(PO4)2 CaHPO4 Ca-soaps 6
  7. 7. Blood calcium depends on albumin and pHTotal serum calcium S-Ca, mean value 2.5 mmol/l (2.25 - 2.75 mmol/l)Ionized serum calcium S-[Ca2+], mean value 1.25 mmol/l (1.0 - 1.4 mmol/l)Protein-bound calcium increases if plasma protein concentration is high.Influence of pH can be understood as a competition for Ca2+ binding sitesbetween H+ and Ca2+ ions.[pH value changed by 0.1 corresponds to the change in [Ca2+] by approx. 0.02 mmol/l] 7
  8. 8. Cation exchange in blood: 2H+ from proteins Ca2+acidic environment alkaline environmentH+ bind to all functional groups, where H+ dissociate from acidic groups →it is possible → vacant binding sites bind Ca2+ →the lack of binding sites for Ca2+ → [Ca2+] is low[Ca2+] is higher 8
  9. 9. Calcium ion concentrations ECF ICF10 -3 M 10 -7 M Difference by four orders ! 9
  10. 10. Hormones regulating calcium homeostasisHormone Blood Ca Main actions stimulates bone demineralization (osteoclasts)PTH ↑ stimulates renal Ca resorptionParathyroid hormone (indirect) stimulates synthesis of calcitriol in kidneys inhibits renal Ca resorptionCalcitonin ↓ stimulates bone mineralization stimulates intestinal Ca resorptionCalcitriol ↑ stimulates the action of PTH on kidney1. Maintaining constant Ca2+ plasma concentration (PTH, calcitonin)exchange between bones and ECF, urine excretion of Ca2+, quick regulation2. Maintaining constant calcium content in body (calcitriol)control of calcium intake (intestine), slow regulation 10
  11. 11. increases Ca2+ in plasma intestine PTH decreases phosphates in plasma ↑ Ca resorption* střevo hard tissues kidney stimulation of osteoclasts* indirect actionPTH stimulatesthe hydroxylationcalcidiol → calcitriol hydrolysis of collagenin kidneys and proteoglycans phosphates Ca2+ release of kosti a zuby Ca2+ and phosphates from bones/dentin/cement urine hypocalcemia stimulates the synthesis and secretion of PTH, hypercalcemia (and calcitriol) has the opposite effect 11
  12. 12. Parathyroid hormone (PTH)PTH is secreted from four parathyroid glands, adjacent to the thyroid gland in the neck.PTH consists of 84 amino acids (prepro-PTH 115 AA, pro-PTH 90 AA).Biological activity is exhibited by the N-terminal sequence, the initial 28 residues.Plasma intact PTH (1-5 pmol/l) is degraded rapidly in the liver (half-life 3-5 min) bysplitting off the inactive C-terminal segments. PTH secretion is regulated by plasma Ca2+ concentration: hypercalcemia inhibits the release of PTH, hypocalcemia stimulates the release of PTH Phosphates do not have a direct influence. The calcium sensor is a receptor cooperating with Gq proteins. In contradistinction to other secreting cells, an increase in intracellular Ca2+ due to IP3 inhibits secretion of PTH. High level of intact PTH is usual in primary hyperparathyroidism, the secretion is not suppressed by hypercalcemia. 12
  13. 13. Biological effects of PTH in bones and kidneysIn bone:PTH stimulates bone resorption through differentiation and activation of osteoclasts.In the renal tubules:the Ca2+ reabsorption increases - elevating so calcemia and decreasing calciuriathe HPO42– reabsorption decreases - so excretion of phosphate increases;Indirect effect on the intestinal mucosa:increased Ca2+ absorption results from stimulation of the 1α-hydroxylation of calcidiolto calcitriol in the renal tubules. 13
  14. 14. Calcitriol In enterocytes: induces conformation changes of calmodulin and the synthesis of calbindin induces the synthesis of Ca2+-ATPase pumping Ca2+ from enterocyte to ECF general effect: facilitates the calcium transport from intestine to blood kidney hard tissuesintestine↑ resorption regulates both resorption and of Ca2+ Ca2+ formation of bonesElevated blood calcium decreases PTH production (= bone resorption)and also decreases calciol hydroxylation in kidneyBeware of vitamin D overdosing – calcification of soft tissues !! 14
  15. 15. Calciol (cholecalciferol, vitamin D3)and ercalciol (ergocalciferol of plant origin, D2) are present in the diet. In addition, calciolis synthesized from 7-dehydrocholesterol in the skin due to UV irradiation.The daily requirement for calciols is 5 – 20 µg/d (200 – 800 IU/d). ≡ Calciol (cholecalciferol, vitamin D3) Ercalciol (ergocalciferol, vitamin D2) The calciols are 9,10-secosteroids, the ring B is opened. Most natural foods have a low content of vitamin D3. It is present in egg yolk, butter, cows milk, animal fat and liver. The most important source of vitamin D2 is fish oil, primarily liver oil. The D-provitamins, 7-dehydrocholesterol and ergosterol, are widely distributed in the animals and plants. Calciols are inactive precursors of calcitriol, a calciotropic steroid hormone. 15
  16. 16. Calciol (vit. D3) is synthesized from 7-dehydrocholesterol by photolysis that is acause of opening of the ring B: Cholesterol THE LIVER CELLS 7,8-Dehydrogenation Lumisterol Tachysterol 7-Dehydrocholesterol Capillaries of the SKIN A high-speed photolysis λmax = 295 nm Slow thermal conversion An intermediate (previtamin) Calciol is slowly released into blood calciol (vit. D3) and bound to serum DBP (D vit. binding protein). 16
  17. 17. The hydroxylation of calciols C-25 The LIVER CELLS The RENAL TUBULAR CELLS 1α 25-hydroxylation 1α-hydroxylation (monooxygenase, cyt P450) (monooxygenase, cyt P450) calciol calcidiol calcitriol (25-hydroxycholecalciferol) (1α,25-dihydroxycholecalciferol) A CALCIOTROPIC STEROID HORMONEIn the liver, calciol is hydroxylated to calcidiol (25-hydroxycalciol). 25-hydroxylation of calcidiol is inhibited by the high concentrations of calcidiol and calcitriol (a negative feed-back control), calcitonin, and a high intake of Ca in the dietIn the proximal renal tubules, calcidiol is transformed by 1α-hydroxylation into calcitriol(1α,25-dihydroxycalciol). 1α-hydroxylation is stimulated by PTH (in hypocalcemia), inhibited by high concentration of calcitriol, calcitonin, and high dietary calcium. 17
  18. 18. Calciols in bloodCalciol - the blood serum concentration in the range 2.6 - 13 nmol/l.Calciol is transported bound to the specific protein DBP (D-vitamin binding protein)Calcidiol is the major circulating metabolite of calciol. Its biological half-life is ratherlong, approx. 20 - 30 days.The concentration of calcidiol in serum informs of the body calciol accessibility.Seasonal variations are observed:during summer about 75 nmol/l,in winter about 37 nmol/l (a mild deficit).Values < 20 nmol/l have to be taken as a sign of serious vitamin D deficiency.In enormous exposition to sunlight – values up to 250 nmol/l,in hypervitaminosis D up to 1250 - 2500 nmol/l.Calcitriol – its biological half-life is short,serum concentration in children about 160 pmol/l, in adults 3-580 pmol/l 18
  19. 19. Biological effects of calcitriol are mainly in enterocytesIn the enterocytes, it increases resorption of calcium into ECF in all three distinct steps:- Entrance into the cell. There are no special transporters for calcium, calcitriol induces a change in the binding of calmodulin to brush border myosin (it forms a complex with myosin bound to membrane actin). The complex may remove calcium from the brush border after it crosses the membrane.- Calcitriol induces the synthesis of cytosolic protein calbindin (CaBP, calcium-binding protein) after a lag-period about 20 h. CaBP seems to prevent rapid increase in Ca2+ by mediating rapid Ca2+ transport in cytoplasm.- Calcitriol induces the synthesis of Ca2+-ATPase that removes Ca2+ from the cell into ECF.In bone, calcitriol controls both resorption and formation by induction of the synthesis of numerous proteins inosteoblasts and odontoblasts. The control mechanism is not yet quite clear.The effect of calcitriol depends on the degree of osteoblast differentiation:In immature osteoblasts, calcitriol supports differentiation pathway to mature osteoblasts.In mature osteoblasts, calcitriol induces the synthesis of osteocalcin and (besides PTH and certain cytokines)production of osteoclast differentiation factors (ODF) so that it also take part in maintaining of physiologic levelsof Ca2+ and phosphates in ECF. 19
  20. 20. Calcitonin: decreases Ca2+ in plasma antagonist of PTH decreases phosphates in plasmaintestine hard tissues kidneys inhibits osteoclasts activates osteoblasts - phosphates Ca2+ supports mineralization kosti a zubylimited effectsmain function: inhibits bone resorption during gravidity and lactationnasal administration of calcitonin – treatment of hypercalcemia, osteoporosissecretion of calcitonin is mediated by calcemia 20
  21. 21. Calcitoninis a 32 amino acid peptide secreted by the C-cells of the thyroid gland.Calcitonin structure differs in animal species:Rat calcitonin resembles human one (only 2 different AA),the most effective is salmon calcitonin (50 % homology with the human calcitonin).In the therapy of metabolic osteopathies, the salmon, human, or eel calcitonin are used.Plasma calcitonin about 13 - 27 pmol/l,in women over 50 years of age the values are lower (high risk of osteoporosis).Secretion of calcitonin is controlled by calcemia. The calcium sensor is of the same kind asin parathyroid glands, but in the thyroid C-cells the increase in intracellular Ca2+ is the signalfor secretion.Procalcitonin (116 AA) is split to calcitonin and catacalcin in the C-cells and not secreted normally. In sepsis(not in localized infections), procalcitonin is secreted in considerable amount (from neuroendocrine cells of thelung and intestine and mononuclear leukocytes obviously), without an increase in calcitonin. Plasmaprocalcitonin is a reliable marker of sepsis. 21
  22. 22. Biological effects of calcitonin Calcitonin counteracts PTH in the control of Ca metabolism. Under normal conditions, calcitonin exhibits a limited role in calcium metabolism control. Its effect on hypercalcemia results in the blockade of bone resorption. No disturbance of calcium metabolism occurs following removal of the thyroid gland.In bone, calcitonin inhibits bone resorption (if increased) by suppressing the activity ofosteoclasts and supports both synthesis of organic matrix and mineralization of osteoid by arapid activation of osteoblasts.Calcitonin has a special role in pregnancy.Plasma concentration increases till the end of the 2nd trimester up to the double normal values and ismaintained till the end of lactation. Calcitonin primarily supports formation of calcium deposits in thebones of mother (formation of stores for the foetus), later on the effect is diminished due to increasedPTH (increasing the calcium accessibility to the foetus).In the renal tubules, calcitonin inhibits reabsorption of Ca2+ and phosphates increasingtheir excretion in this way.In the GIT, it inhibits the secretion of HCl, pepsin, and pancreatic enzymes.Calcitonin has an analgetic effect, it alleviates bone pain in osteopathies or bone metastases. 22
  23. 23. Hypercalcemia disturbs renal functionsMild hypercalcemia (< 3 mmol/l) usually do not have clinical symptoms.Defects of renal tubular functions, particularly polyuria, may occur.Hypercalcemia > 3.5 - 4 mmol/l is a serious menace.If hypercalcaemia is chronic, renal functions are impaired, soft tissue calcificationsand kidney stones develop.In turn, chronic renal failure in chronic hypercalcemia disturbs Ca homeostasis:Decrease in GFR to about one third is the cause of phosphate retention andhyperphosphatemia, FE(Ca) increases, calcium loss follows, calcidiol is hydroxylatedinsufficiently, and intestinal calcium resorption diminished.The consequence is hypocalcemia that induces secondary hyperparathyroidism. 23
  24. 24. The causes of hypercalcemiaPrimary hyperparathyroidism is usually caused by a solitary adenoma.It is detected mostly (up to 50 %) as calcium urolithiasis or nephrocalcinosis, polyuria,osteopathy (osteodystrophy, pathological bone fractures), etc.The diagnosis is supported by hypophosphatemia resulting from phosphate losses,and mild metabolic acidosis from losses of HCO3–. Increased PTH is conclusive.Malignancy-related hypercalcemia– osteolytic metastases of solid tumours (lung, breast, kidney) resorb bone either directly,or (breast carcinoma) activate osteoclasts by means of local release of humoral factors.– multiple myeloma (and some lymphomas)– tumours producing PTHrP (namely squamous cell carcinomas of the bronchus).Other causes:Calciol intoxication in excessive intake of calciol (e.g. long-lasting treatment ofhypoparathyroidism, calciol overdose is released from the adipose tissue slowly, in thecourse of several weeks) or when calcitriol is used (immediate effect).Long-lasting immobilization intensifies osteoresorption, namely in teenagers due to highbone turnover. A complete immobilization can cause about 30 % loss of bone minerals. 24
  25. 25. HypocalcemiaClinical symptoms appear when total calcium is lower than approx. 1.9 mmol/l.Hypocalcemia is accompanied by typical neuromuscular manifestations – paresthesiae,increased neuromuscular excitability and tetany.The most common causes of hypocalcemia:Alkalosis – hyperventilation (artificial, hysteric reaction), too rapid infusion of HCO3–.Acute complexation – multiple blood transfusions (citrate or EDTA form complexes with Ca2+)Reduced parathyroid hormone action – rare primary hypoparathyroidism,secondary hypoparathyroidism – surgery on the neck (destruction of the glands) Insufficient supply of calcium, impairment of intestinal calcium absorption, failure to produce calcitriol: inadequate dietary intake of calcium or calciol, limited exposure to sunlight (this sometimes occurs in elderly subjects) malabsorption of liposoluble compounds (diseases of pancreas, insufficient bile production chronic renal failure (insufficient 1α-hydroxylation of calcidiol). In adults, insufficient calcium intake results in osteomalacia (bands of decalcification, affecting particularly the pelvis, femur, and scapula), in children in rickets (rachitis, skeletal deformities and muscle weakness). 25
  26. 26. Biochemical features of phosphates 30 - 80 mmol/dayIntake most foods, phospholipids (meat, eggs), phytates (cereals), phosphoproteins (milk - casein) ICF: mostly phosphoesters (metabolism of glucose, fructose etc.), macroergic compounds (ATP), nucleotides (~ 20 % of P) Nucleus: DNADistribution Ribosomes: RNAin body Cell membranes: phospholipid bilayer ECF: hydrogen phosphate buffer, phospholipid monolayer of lipoproteins Hard tissues (bones, teeth): biological apatites (~ 80 % of P)Urine H2PO4- (30 - 50 mmol/day)excretion 26
  27. 27. Phosphate distribution and turnover mineral deposits 15 000 – 25 000 mmol PO43- Daily intake (80 – 85 % total P) 30 - 80 mmol/d exchange Al3+ and 8 - 15 mmol/d calcium absorption ICF 15- 20 % of total P ECF 15 - 55 mmol/d 1.0 mmol/l Pi ~ 1 mmol/l Pi 2.5 mmol/l phosphate esters up 100 mmol/l organic esters filtration tubular reabsorption > 130 - 200 mmol/d > 110 - 150 mmol/d Excretion fraction < 25 % (children < 15 %)10 – 40 mmol/d increased by PTH or calcitonin 30 – 50 mmol/d 27
  28. 28. Compare: phosphate species in solutionLiquid pH Prevailing species !Blood 7.4 HPO42- [HPO42-] : [H2PO4-] ≈ 4 : 1Urine 5.0 H2PO4- [HPO42-] : [H2PO4-] ≈ 1 : 63Coca-Cola 2.5 H3PO4 28
  29. 29. Phosphate homeostasisis maintained by urinary excretion of phosphatethat depends on reabsorption of phosphate in renal tubules.Filtration of free Pi is complete, 50 – 70 % is reabsorbed in the proximal tubule (specific active co-transport with Na+, inhibited by PTH), about 10 – 20 % in the distal parts of the nephron.Of the 240 mmol of phosphate filtered daily, about 85 % (80 – 97 %) is reabsorbed.Excretion fraction EF(phosphate) – in adults less than 20 %, in children less than 15 %.Increased phosphate excretion (decrease in tubular phosphate reabsorption) is caused by PTH and calcitonin, – by acidosis (hyperphosphatemia, protons excreted as H2PO4–), – and indirectly (through hypocalcemia that stimulates PTH secretion) by alkalosis or increased ECF volume.Retention (decreased excretion) of phosphate (increased tubular phosphate reabsorption)is caused– by somatotropin (decrease in ECF volume) and corticosteroids,– to a lesser degree, by calcitriol and phosphate deficiency. 29
  30. 30. Fasting serum inorganic phosphate in adults is 0.7 – 1.6 mmol/lPlasma concentration is by 0.06 – 0.10 mmol/l lower than that of serum due to the releaseof intracellular phosphate from platelets and erythrocytes during clotting:(serum should be separated from the coagulum without delay).In healthy adults, there is a marked diurnal variation of phosphatemia – the lowest being inthe morning and the highest during the night (this variation is abolished by fasting).Postprandially, phosphate concentration tends to decrease presumably because of insulinrelease (anabolic action of insulin). Therefore, samples for serum phosphate estimation shouldbe taken in the fasting state in the morning.Great and rapid changes in serum phosphate concentration may have their causes inthe shifts of phosphates between ICF and ECF that depend on the nutritional status(the energy charge of the cells).Urinary phosphate excretion depends on dietary intake of phosphates.At the average daily intake of phosphate (about 50 mmol/d),dU-Pi is in the range 30-50 mmol/d in healthy adults. 30
  31. 31. HyperphosphatemiaEven a mild form (> 1.6 mmol/l) is a rare finding among hospital patients.Consequences – Acute hyperphosphatemia can lead to hypocalcemia.In chronic hyperphosphatemia, the low production of calcitriol may lead to bone changes(osteomalacia or rickets) or to soft tissue calcification in myocardium, lungs, and the liver.Artificial (false) hyperphosphatemia may result from hemolysis due to the release of intracellularphosphate from red blood cells and platelets.Causes of hyperphosphatemiaReduced urinary excretionRenal failure accounts for more than 90 % in hospital patients; retention of phosphate occurswhen the GFR falls below 20–30 % of normal and may be a cause of secondaryhyperparathyroidism.Hypoparathyroidism – increased tubular phosphate reabsorption.Excess phosphate administration to patients on parenteral and enteral nutrition, also in sucklings nourished with undiluted cows milk.Shift of intracellular phosphate into the ECF is seen in- hypercatabolic states and in metabolic acidosis (untreated lactic acidosis and diabeticketoacidosis) due to increased ATP breakdown and tissue hypoxia,- excessive hemolysis. 31
  32. 32. Hypophosphatemia is more frequent than hyperphosphatemiaMild hypophosphatemia (~ 0.6 mmol/l) is quite common in hospital patients (acutely ill,malnourished, or with diabetic ketoacidosis), but it is rather exceptional in out-patients.Moderate hypophosphatemia of long duration leads to skeletal changes (rickets/osteomalacia)Severe hypophosphatemia (< 0.3 mmol/l) is rare, but in few days - serious consequences:hemolysis due to decreased 2,3-BPG and ATP in erythrocytes,muscular weakness that may result in respiratory failure,impaired cardiac contractility and nervous system disorders.Hypophosphatemia does not always indicate intracellular phosphate deficiency,phosphate depletion may be present with normal or even increased phosphatemia. 32
  33. 33. The most common causes of hypophosphatemiaHemodilution – water retention, parenteral nutritionReduced absorptionlow dietary intake is unusual (strict vegetarians) as phosphate occurs widely in foodsoral phosphate-binding agents (Al3+ antacids in excess)diarrhoea or long-lasting vomitingmalabsorptionIncreased uptake of phosphate into cellsAdministration of glucose (both intravenous and enteral) or hyperalimentation leads toincreased insulin concentration, increased formation of phosphorylated intermediates leads tothe shift of phosphate into the cells. Life-threatening hypophosphatemia may occur in rapidrealimentation of starved patients (refeeding syndrome), treatment of diabetic ketoacidosis,alcoholics during alcohol withdrawal and glucose refeeding.Increased phosphate eliminationDecreased renal tubular reabsorption due to high PTH secretion in hyperparathyroidism, rickets, and osteomalacia.Hemodialysis 33
  34. 34. Fluorine in the bodyDaily intake 0.3-0.5 mg (tap water, mineral waters, tea, sea food)95 % of fluorine occurs in hard tissues, concentration increases with ageBones: 0.5 - 2 g/kg (more in trabecular bones)Teeth: 0.1- 5 g/kg (especially in dentin and enamel surface)Total in body: 3.5 - 4 g .... mainly as fluorapatite Ca5(PO4)3FFluoride ions in crystal structureFluoride ions substitute one or two OH- ions on crystal surfaceto form fluorapatite Ca10(PO4)6(OH,F).Other OH- in other layers (above, below) make with F- hydrogen bondswhich stabilize crystal structure 34
  35. 35. Fluorine is important for hard tissuesFluorine deficitdefects in hard tissues, growth retardation, impaired tooth development↑ caries predispositionFluorine excessskeletal fluorosis↑ collagen synthesis↑ bone mineralization, calcification of tendonsdental fluorosisdamage of ameloblasts (vacuolization, calcium globules in cytoplasm)enamel is more porous, mottled, stained, easily affected with various lesions 35
  36. 36. Toxic mechanism of fluoridesfluoride ions inhibit enzymes which need divalent metal cationsas cofactors / activatorsMg (ATP-dependent enzymes)Mn (hydrolases, transferases, decarboxylases)Ca (phospholipases, α-amylase)Cu (numerous oxidases)Fe (heme enzymes, e.g. catalase, peroxidases) metal cations are associated with flurides: Me2+ + 2 F- → MeF2 36
  37. 37. Caries prevention - fluoridation• fluorides increase the enamel resistance against acids• fluorides support the remineralization of enamel: 5 Ca2+ + 3 HPO42- + F- → Ca5(PO4)3F + 3 H+• fluorapatite is less soluble than hydroxylapatite and other phosphates, especially under lower pH values Ks (hydroxylapatite) = 2.3 × 10-59 Ks (fluorapatite) = 3.1 × 10-60 37
  38. 38. Exogenous sources of fluorine• tap water (~ 0.2 mg/l) upper limit value for drinking water is 1.5 mg/l• mineral waters (1-6 mg/l)• extract of tea (Camellia sinensis), at least 3-5 min (1-3 mg/l)• sea food• food made with Teflon utensils• NaF (natrii fluoridum) tablets – only on prescription!• fluoridated food products (salt, milk, baby food ...)Brno tap water comes from the spring area in Cretaceous stratanear Březová nad Svitavou, fluoride concentration is below 0.1 mg/l 38
  39. 39. Local application of fluorides in oral health products (exogenous fluoridation) tooth pastes, gels,• inorganic fluorides: NaF, CaF2, SnF2, ZnF2, AlF3 varnishes, mouth rinses, dental flosses etc.• organic fluorides: alkylammonium fluoride (olaflur, dectaflur) organic cation has the nature of tenside – makes monomolecular layer on tooth surface ⇒ long-term fluoride deposition ¡ ¡   ¢ ¡ dectaflur (9-octadecenylammonium fluoride)• covalently bound fluorine: sodium monofluorophosphate (MFP), its hydrolysis relases F- ion O Na O P F O Na 39