HEALTH EFFECTS, Fluoride & the Pineal Gland

882019 HEALTH EFFECTS Fluoride amp the Pineal Gland

httpslidepdfcomreaderfullhealth-effects-fluoride-the-pineal-gland 121

FLUORIDE The use of fluoride for health reasons is one of the great insanities of our times Could itbe just by chance that the Germans and Russians both used fluoride to make prisonersstupid and docile or that the US government faced legal action over the toxic effects in theenvironment of this nuclear waste by-product

GERMANS amp RUSSIANS USED FLUORIDE TO MAKE PRISONERS STUPID amp DOCILE

The Fluoride Deception How a Nuclear Waste Byproduct Made Its Way Into the NationsDrinking Water

HEALTH EFFECTS Fluoride amp the Pineal Glandhttpwwwfluoridealertorghealthpineal

Summation - Fluoride amp Pineal Gland

Up until the 1990s no research had ever been conducted to determine the impact of fluorideon the pineal gland - a small gland located between the two hemispheres of the brain thatregulates the production of the hormone melatonin Melatonin is a hormone that helpsregulate the onset of puberty and helps protect the body from cell damage caused by freeradicals

It is now known - thanks to the meticulous research of Dr Jennifer Luke from the Universityof Surrey in England - that the pineal gland is the primary target of fluoride accumulationwithin the body

The soft tissue of the adult pineal gland contains more fluoride than any other soft tissue in

the body - a level of fluoride (~300 ppm) capable of inhibiting enzymes

The pineal gland also contains hard tissue (hyroxyapatite crystals) and this hard tissueaccumulates more fluoride (up to 21000 ppm) than any other hard tissue in the body (egteeth and bone)

After finding that the pineal gland is a major target for fluoride accumulation in humans DrLuke conducted animal experiments to determine if the accumulated fluoride could impactthe functioning of the gland - particulalry the glands regulation of melatonin



Luke found that animals treated with fluoride had lower levels of circulating melatonin asreflected by reduced levels of melatonin metabolites in the animals urine This reduced levelof circulating melatonin was accompanied - as might be expected - by an earlier onset ofpuberty in the fluoride-treated female animals

Luke summarized her human and animal findings as follows

In conclusion the human pineal gland contains the highest concentration of fluoride in thebody Fluoride is associated with depressed pineal melatonin synthesis by prepubertalgerbils and an accelerated onset of sexual maturation in the female gerbil The resultsstrengthen the hypothesis that the pineal has a role in the timing of the onset of pubertyWhether or not fluoride interferes with pineal function in humans requires furtherinvestigation

Online Papers - Fluoride amp the Pineal Gland

FULL TEXT - html Luke J (2001) Fluoride deposition in the aged human pineal glandCaries Research 35125-128

EXCERPT - html Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford

Articles of Interest - Fluoride amp the Pineal Gland

Fluoride amp the Pineal Gland Study Published in Caries Research IFIN Bulletin March 2001

Fluoride amp Oxidative Stress Yet more evidence FAN Science Watch September 30 2004

Summation - Fluoride amp Pineal Gland (back to top)

ldquoThe single animal study of pineal function indicates that fluoride exposure results in alteredmelatonin production and altered timing of sexual maturity Whether fluoride affects pinealfunction in humans remains to be demonstrated The two studies of menarcheal age inhumans show the possibility of earlier menarche in some individuals exposed to fluoride butno definitive statement can be made Recent information on the role of the pineal organ inhumans suggests that any agent that affects pineal function could affect human health in a

variety of ways including effects on sexual maturation calcium metabolism parathyroidfunction postmenopausal osteoporosis cancer and psychiatric diseaserdquoSOURCE National Research Council (2006) Fluoride in Drinking Water A ScientificReview of EPAs Standards National Academies Press Washington DC p221-22

In conclusion the human pineal gland contains the highest concentration of fluoride in thebody Fluoride is associated with depressed pineal melatonin synthesis by prepubertalgerbils and an accelerated onset of sexual maturation in the female gerbil The results



strengthen the hypothesis that the pineal has a role in the timing of the onset of pubertyWhether or not fluoride interferes with pineal function in humans requires furtherinvestigationSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 177

Fluoride amp Pineal Gland - Never Studied before 1990s (back to top)

It is remarkable that the pineal gland has never been analysed separately for F because ithas several features which suggest that it could accumulate F It has the highest calciumconcentration of any normal soft tissue in the body because it calcifies physiologically in theform of hydroxyapatite (HA) It has a high metabolic activity coupled with a very profuseblood supply two factors favouring the deposition of F in mineralizing tissues The fact thatthe pineal is outside the blood-brain barrier suggests that pineal HA could sequester F fromthe bloodstream if it has the same strong affinity for F as HA in the other mineralizingtissues The intensity of the toxic effects of most drugs depends upon their concentration atthe site of action The mineralizing tissues (bone and teeth) accumulate high concentrationsof F and are the first to show toxic reactions to F Hence their reactions to F have beenespecially well studied If F accumulates in the pineal gland then this points to a gap in ourknowledge about whether or not F affects pineal physiology It was the lack of knowledge inthis area that prompted my studySOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 1-2

Fluoride amp Pineal Gland - Accumulation of Fluoride in Soft Tissue of Pineal Gland(back to top)

After half a century of the prophylactic use of fluorides in dentistry we now know thatfluoride readily accumulates in the human pineal gland In fact the aged pineal containsmore fluoride than any other normal soft tissue The concentration of fluoride in the pinealwas significantly higher (p lt0001) than in corresponding muscle ie 296 plusmn 257 vs 05plusmn 04mgkg (wet weight) respectivelySOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 167

Fluoride amp Pineal Gland - Accumulation of Fluoride in Calcified Tissue of Pineal

Gland (back to top)In terms of mineralized tissue the mean fluoride concentration in the pineal calcificationwas equivalent to that in severely fluorosed bone and more than four times higher than incorresponding bone ash ie 8900 plusmn 7700 vs 2040 plusmn 1100 mgkg respectively Thecalcification in two of the 11 pineals analysed in this study contained extremely high levels offluoride 21800 and 20500 mgkgSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 167



Fluoride amp Pineal Gland - Analagous to Dental Fluorosis (back to top)

Fluoride is now introduced at a much earlier stage of human development than ever beforeand consequently alters the normal fluoride-pharmacokinetics in infants But can one

dramatically increase the normal fluoride-intake to infants and get away with it The safetyof the use of fluorides ultimately rests on the assumption that the developing enamel organ is most sensitive to the toxic effects of fluoride The results from this study suggest that thepinealocytes may be as susceptible to fluoride as the developing enamel organSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 176

Alongside the calcification in the developing enamel organ calcification is also occurring inthe childs pineal It is a normal physiological process A complex series of enzymaticreactions within the pinealocytes converts the essential amino acid tryptophan to a wholefamily of indoles The main pineal hormone is melatonin (MT) If F accumulates in the

pineal gland during early childhood it could affect pineal indole metabolism in much thesame way that high local concentrations of F in enamel organ and bone affect themetabolism of ameloblasts and osteoblastsSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 5

Any adverse physiological effects of fluoride depend upon the concentration at varioustissue sites Can pinealocytes function normally in close proximity to high concentrations offluoride One would predict that a high local fluoride concentration would affect pinealocytefunction in an analogous way that a high local fluoride concentration affects i) bone cellssince histological changes have been observed in bone with 2000 mg Fkg (Baud et al1978) ii) ameloblasts since dental fluorosis develops following fluoride concentrations of

02 mg Fkg in the developing enamel organ (Bawden et al 1992) The consequences aredisturbances in the functions of bone and enamel ie changes in structure (poorlymineralized bone and enamel) If the pineal accumulates fluoride at an earlier age than inprevious decades one would anticipate that a high local concentration of fluoride within thepineal would affect the functions of the pineal ie the synthesis of hormonal productsspecifically melatonin The controlled animal study carried out in this study producecompelling evidence that fluoride inhibits pineal melatonin output during pubertaldevelopment in the gerbilSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 168-169

Fluoride amp Pineal Gland - Earlier Puberty in Animals (back to top)

The section on the effects of fluoride on the physiological signs of sexual maturity in thegerbil was a preliminary pilot study There were not enough subjects to make any firmconclusions so an interpretation of the data is conjectural However the results do suggestthat the HF (High-Fluoride) females had an accelerated onset of puberty as judged byseveral indices of pubertal development in rodents At 7 weeks the HF females were



significantly heavier than the LF females (p lt 0004) as heavy as the HF males and LFmales The ventral gland in the HF female developed significantly earlier than in the LFfemale (p lt 0004) Vaginal opening occurred earlier in the HF female than in the LF female(p lt003)SOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland

PhD Thesis University of Surrey Guildford p 173-174

Fluoride amp Pineal Gland - Earlier Puberty in Humans (back to top)

The first step in assessing a health risk by a substance to humans is the identification of itsharmful effects on animals A health risk to humans is assessed using results from humanepidemiological studies in conjunction with results from animal studies The Newburgh-Kingston Study (Schlesinger et al 1956) showed an earlier age of first menarche in girlsliving in the fluoridated Newburgh than in unfluoridated Kingston The current animal studyindicates that fluoride is associated with an earlier onset of puberty in female gerbilsFurthermore more research was recommended on the effects of fluoride on animal and

human reproduction (USPHS 1991) This project has contributed new knowledge in thisareaSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 177

Fluoride amp Pineal Gland - Mechanism of Action (back to top)

The most plausible hypothesis for the observed significant decrease in the rate of urinaryaMT6s excretion by the HF (High-Fluoride) group is that fluoride affects the pineals ability tosynthesize melatonin during pubertal development in the gerbil Fluoride may affect theenzymatic conversion of tryptophan to melatonin Although melatonin was the hormoneinvestigated in this project fluoride may also affect the synthesis of melatonin precursors(eg serotonin) or other pineal products (eg 5-methoxytryptamine) This would dependon the position(s) of the susceptible enzyme(s) For some unknown reason pinealcalcification starts intracellularly Calcium has been demonstrated in pinealocytemitochondria Therefore it may be a mitochondrial enzyme that is sensitive to the effects offluoride eg tryptophan-5-hydroxylase Alternatively fluoride may affect pinealocyteenzymes which require a divalent co-enzyme because such enzymes are particularlysensitive to fluorideSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 172-173

Fluoride amp Pineal Gland - Discussion (back to top)

Fluoride is now introduced at a much earlier stage of human development than ever beforeand consequently alters the normal fluoride-pharmacokinetics in infants

But can one dramatically increase the normal fluoride-intake to infants and get away with itThe safety of the use of fluorides ultimately rests on the assumption that the developingenamel organ is most sensitive to the toxic effects of fluoride The results from this study



suggest that the pinealocytes may be as susceptible to fluoride as the developing enamelorgan The possibility of a species difference between humans and gerbils does not allowthe extrapolation of the gerbil data to humans However if increased plasma-fluoride levelscause a decline in the levels of circulating melatonin during early human developmentsignificant physiological consequences may have already occurred Changes in plasma

melatonin concentrations are serious functional disturbances because melatonin has manyfunctions in the organism The pinealogists have not completely unravelled the mechanismsby which the pineal gland performs its tasks in the brain The neurochemical phenomenonelicited by melatonin in CNS are unclear

The first step in assessing a health risk by a substance to humans is the identification of itsharmful effects on animals A health risk to humans is assessed using results from humanepidemiological studies in conjunction with results from animal studies The Newburgh-Kingston Study (Schlesinger et al 1956) showed an earlier age of first menarche in girlsliving in the fluoridated Newburgh than in unfluoridated Kingston The current animal studyindicates that fluoride is associated with an earlier onset of puberty in female gerbilsFurthermore more research was recommended on the effects of fluoride on animal andhuman reproduction (USPHS 1991) This project has contributed new knowledge in thisarea

I do not intend to discuss the relative merits of the claims made by the anti-fluoridationiststhat chronic ingestion of low levels of fluoride has harmful effects on human health ieincreases the risk of cancer affects the immune system and hastens the aging processThese claims could be associated with the effects of fluoride on the pineal because thegland has been linked to oncogenesis immunocompetence and in recent years to theprocess of aging

In conclusion the human pineal gland contains the highest concentration of fluoride in thebody Fluoride is associated with depressed pineal melatonin synthesis by prepubertal

gerbils and an accelerated onset of sexual maturation in the female gerbil The resultsstrengthen the hypothesis that the pineal has a role in the timing of the onset of pubertyWhether or not fluoride interferes with pineal function in humans requires furtherinvestigationSOURCE Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford p 176-177



[ httpwwwgarynullcomDocumentsDentalFluoridefluoride13htm ]

Another concern is fluorides effect on the pineal gland a small but powerful structurelocated between the right and left hemispheres of the brain The pineal gland secretesmelatonin a hormone that affects such functions as sleep cycles jet lag hybernation inanimals immunity and the onset of puberty Jennifer Luke PhD found that the pinealgland attracts fluoride and thereby interferes with melatonins functions(180) In autopsystudies she discovered extremely high concentrations of fluoride in the gland averaging9000 ppm going up to 21000 ppm in some cases(181) And in an accompanying study offluoride-treated Mongolian gerbils (the animal considered most favorable for studying effectson the pineal gland) Luke found lower levels of melatonin and earlier onset of puberty

This research is highly suggestive People with insomnia could be suffering as a result offluorides interference with melatonin production Currently more than half the population ofthe United States suffers from some form of sleep disturbance(182) Sleep deprivationpromotes reduced immunity Sleep-challenged people are more likely to suffer depressionstroke or heart disease than their well-rested peers Numerous studies have correlated

insufficient melatonin production with an earlier-than-usual onset of puberty(183 184)

This recalls the 1955 Newburgh-Kingston study which produced some extremely puzzlingresults that scientists have yet to explain One was the finding that girls in fluoridatedNewberg were reaching menstruation five months earlier on average than the girls inunfluoridated Kingston This raises the question does fluoride contribute to the alarmingrates of early puberty that we are seeing(185) Premature menstruation is associated with avariety of ills including breast cancer and obesity A 2001 study published in the AmericanJournal of Public Health reveals that early maturation nearly doubled the odds of beingobese(186)



Fluoride Deposition in the Aged Human Pineal GlandJennifer Luke

httpwwwicnrcomjlukefluoridedepositionhtml

School of Biological Sciences University of Surrey Guildford UK

Department of Obstetrics and Gynaecology The Royal London Hospital

Original Paper

Caries Res 299135125-128

Copyright copy 2001 S Karger AG BaselPresented by permission of the author

Key Words

Calcium Distribution Fluoride Human pineal gland Hydroxyapatite Pineal concretions

Abstract

The purpose was to discover whether fluoride (F) accumulates in the aged human pineal

gland The aims were to determine (a) F-concentrations of the pineal gland (wet)

corresponding muscle (wet) and bone (ash) (b) calcium-concentration of the pineal Pineal

muscle and bone were dissected from 11 aged cadavers and assayed for F using the

HMDS-facilitated diffusion F-ionspecific electrode method Pineal calcium was determined

using atomic absorption spectroscopy Pineal and muscle contained 297plusmn257 and 05plusmn04

mg Fkg wet weight respectively bone contained 2037plusmn1095 mg Fkg ash weight The

pineal contained 16000plusmn11070 mg Cakg wet weight There was a positive correlation

between pineal F and pineal Ca (r = 073 plt002) but no correlation between pineal F and

bone F By old age the pineal gland has readily accumulated F and its FCa ratio is higher

than bone

The pineal gland is a small organ situated near the centre of the brain It is intimately related

to the third ventricle It is composed of pinealocytes and neuroglial cells amongst which

ramifies a rich network of capillaries and postganglionic nerve fibres The pineal gland is a

mineralizing tissue Its calcified concretions range from a few micrometres to several



millimetres in diameter The larger ones are identifiable on skull X-rays cranial CT and MRI

scans The concretions are composed of hydroxyapatite (HA) [Angervall et al 1958 Earle

1965 Mabie and Wallace 1974 Galliani et al 1990 Bocchi and Valdre 1993] whose

chemical composition morphology and unit cell dimensions are similar to HA in bone and

teeth [Mabie and Wallace 1974 Bocchi and Valdre 1993] The pineal (calcified and

uncalcified) has a high trace element content (zinc iron manganese magnesium strontium

and copper) in humans [Krstic 1976 Michotte et al 1977] and in rats [Humbert and Peacutevet

1991 1996] Michotte et al [1977] suggested that within the pineal there are areas which

are heavily loaded with calcium and which attract trace elements even though these

calcium-rich areas are not yet identifiable as concretions Calcium is distributed throughout

the pinealocytes in the mitochondria Golgi apparatus cytoplasm and nucleus [Krstic

1976 1995 Welsh 1984 Pizarro et al 1989 Lewczuk et al 1994]

Fluoride does not accumulate in brain Of all tissues brain has the lowest fluoride

concentration [Jenkins 1991 Whitford 1996 Ekstrand 1996] It is generally agreed that the

blood-brain barrier restricts the passage of fluoride into the central nervous system The

human pineal gland is outside the blood-brain barrier [Arendt 1995] It is one of a few

unique regions in the brain (all midline structures bordering the third and fourth ventricles)

where the blood-brain barrier is weak Cells in these regions require direct and unimpeded

contact with blood [Rapoport 1976] Therefore pinealocytes have free access to fluoride in

the bloodstream This fact coupled with the presence of HA suggest that the pineal gland

may sequester fluoride from the bloodstream

The purpose of this study was to discover whether fluoride accumulates in the aged pineal

gland Its objectives were to determine (a) the fluoride concentrations of the pineal gland

(wet) corresponding muscle (wet) and bone (ash) (b) the pineal concentrations of calcium

and HA

Materials and Methods

The pineal glands and corresponding bone and muscle samples were dissected from I Iaged cadavers (7 females and 4 males) in the Anatomy Department UCL The mean age

was 82 years (range 70-100)

Preparation of the Samples

The pineal glands were blotted dry with tissue paper weighed to the nearest milligram



homogenized in I ml double-distilled water using an agate pestle and mortar and sonicated

for 10 min Each pineal was divided into two portions that were analysed separately Muscle

samples weighing about 100 mg were treated likewise Bone samples were cleaned of any

adherent soft tissue with a razor blade dried overnight at 110C in an oven and ashed (in

porcelain crucibles with no fixatives) at 550-600degC in a muffle furnace for 8 h Bone ash was

pulverized into a fine powder using an agate pestle and mortar Bone solutions were made

by dissolving known weights of bone ash in 3 ml 2 M HC104 Bone solutions were analysed

for fluoride in replicates of six and the mean fluoride concentrations in bone were calculated

Determination of the Fluoride Concentrations

The homogenized pineal homogenized muscle and bone solutions were assayed for

fluoride using the HMDS-facilitated diffusion F-ion-specific electrode method originally

described by Taves [19681 and modified by Whitford and Reynolds [1979] The protocolwas further modified for use with the pineal glands The concentration and volume of the

base trap were increased to 05 M NaOH and 100 microl respectively the strength of the

acetate buffer was increased to 50 microl 2 M acetic acid and the volume of the analysed

solution was adjusted to 150 microl with double-distilled water Diffusion time for pineal and

muscle was 3 days for bone 18 h

Standards pineal 1000 2500 and 5000 nmol F muscle 5 50 and 500 nmol F bone 10

50 100 and 500 nmol F

Determination of the Concentration of Total Calcium in the Human Pineal Gland

The acid digests which remained in the Petri dishes following the separation of fluoride from

the pineal glands were wet-acid ashed to decompose the organic component The acid

digests were placed in clean glass tubes and I ml conc HN03 was added The tubes were

heated slowly to 50degC and maintained at 50degC for 30 min in a fume cupboard The

procedure was repeated using I ml 60 HC104 Two millilitre of double-distilled water was

added to each tube and the volumes were measured Calcium concentration was

determined using atomic absorption spectroscopy

Statistical Methods

Results were expressed as means plusmn SD Differences between the groups were tested for

significance using unpaired Students t-test Differences were regarded as statistically

significant when plt005



Pearsons correlation coefficient was used to test association between pineal fluoride and

pineal calcium and pineal fluoride and bone fluoride

Fig 1 The relationship between the calcium and fluoride contents of ten aged human pineal

glands

Results

The aged pineal gland weighed 112plusmn52 mg (56-198 mg) Pineal had a significantly higher F

concentration than muscle 297 plusmn 257 (14-875) vs 05 plusmn 04 (02-15) mg Fkg wet weight

(plt0001) Bone contained 2037plusmn 1095 (838-3711) mg Fkg ash weight The mean

coefficient of variation between the replicates of F contents of bone solutions was 25 plusmn 1 1

There was no correlation between pineal F and bone F The pineal gland contained

16000plusmn11070 (4600-37250) mg Cakg wet weight Pineal fluoride and pineal calcium

were directly correlated r = 073 p lt 002 n = 10 slope= 002 (fig 1) Assuming

stoichiometric HA the pineal contained an estimated 40000 plusmn 27700 mg HAkg wet weight

(11600-93200 mg HAkg) The estimated F concentration of pineal HA was 9000 plusmn 7800

mgkg (650-21800 mgkg) Figure 2 shows that the Fcalcium ratio was higher in pineal HA

than in corresponding bone HA

Discussion

This study has added new knowledge on the fate and distribution of fluoride in the body It

has shown for the first time that fluoride readily accumulates in the human pineal gland

although there was considerable inter-individual variation (14-875 mg Fkg) By old age the

average pineal gland contains about the same amount of fluoride as teeth (300 mg Fkg)

since dentine and whole enamel contain 300 and 100 mg Fkg respectively [Newbrun



1986] Unlike brain capillaries pineal capillaries allow the free passage of fluoride through

the endothelium If there had been a bloodbrain barrier in the pineal it would have

prevented the passage of fluoride into the pinealocytes and the pineal fluoride content would

have been similar to or lower than muscle This was obviously not the case the fluoride

concentration of the pineal was significantly higher (plt0001) than muscle The high fluoride

levels in the pineal are presumably due to the large surface area of the HA crystallites both

intra- and extracellularly In addition the pineal has a profuse blood flow and high capillary

density pineal blood flow (4 mlming) is second only to the kidney [Arendt 19951

The extent of pineal calcification also varied between individuals ranging from 4600 to

37250 mg Cakg wet weight One of the aged pineals had very little precipitation This

supports the age independence of pineal calcification and agrees with previous studies

[Cooper 1932 Arieti 1954 Tapp and Huxley 197 1 Hasegawa et aL 1987 Galliani et al1990] The estimated fluoride concentration of pineal HA was 9000 plusmn 7800 mgkg The

FCa ratio was higher in pineal HA than in corresponding bone (fig 2) The extremely high

level of substitution in the crystal structure of pineal HA by fluoride illustrates the readiness

with which fluoride replaces the hydroxyl ion in the HA crystal By old age pineal HA has a

higher fluoride content than other biological apatites Unlike pineal concentrations of

magnesium manganese zinc and copper which although very high were generally within

the limits found in bone and teeth [Michotte et al 1977]

Fig 2 A comparison of the FCa ratio in aged pineal HA and corresponding bone ash (microg

F100 microg calcium) Calcium content of bone determined stoichiometrically

There was no corTelation between pineal fluoride and bone fluoride Therefore unlike bone

pineal fluoride concentrations are not indicators of long-term fluoride exposure and body



burden Pineal fluoride however was significantly correlated with pineal calcium

The methodology used in this project was accurate because the F values obtained for bone

and muscle agreed with literature values For example the mean fluoride concentration of

bone from elderly subjects was 2000 mgkg ash weight which agrees with previous studies

using bone from subjects of a similar age [Ebie et al 1992 Charen et al 1979 Zipkin et

al 1958] In this study muscle contained 05 mg Fkg wet weight a typical fluoride

concentration for soft tissue [WHO 1984] The pineal and bone were treated differently

during sample preparation (the pineal was wet-acid ashed bone was dry ashed) which may

somewhat obscure a direct comparison of the fluoride contents of pineal HA and bone

However it is unlikely that there would be a significant analytical error

In conclusion this study presented evidence that fluoride readily accumulates in the agedpineal Fluoride may also accumulate in a childs pineal because significant amounts of

calcification have been demonstrated in the pineals from young children [Cooper 1932

Wurtman 1968 Kereacutenyi and Sarkar 1968 Tapp and Huxley 197 1 Doskocil 1984] In fact

calcification of the developing enamel organs and the pineal gland occur concurrently If

fluoride does accumulate in the childs pineal (this needs verification) the pinealocytes will

be exposed to relatively high local concentrations of fluoride This could affect pineal

metabolism in much the same way that high local concentrations of fluoride in the

developing enamel organ affect ameloblast function Research is presently underway to

discover whether fluoride affects pineal physiology during childhood specifically pineal

synthesis of melatonin

Acknowledgements

I acknowledge the Anatomy Deptartment UCL for providing the pineal glands Prof Gary

Whitford Medical College of Georgia USA and Gordon Hartman University of Surrey for

their assistance with the fluoride analysis Nicholas Porter The Royal Surrey County

Hospital Guildford for help with the determination of pineal-calcium concentrations The

Colt Foundation The Heinz and Anna Kroch Foundation and The New Moorgate Trustfunded the research References

1 Angervall L Berger S Roumlckert H A microradiographic and X-ray crystallographic

study of calcium in the pineal body and intracranial tumours Acta Pathol Microbiol

Scand 195844 113-119



2 Arendt J Melatonin and the Mammalian Pineal Gland ed 1 London Chapman amp

Hall 1995 p 17

3 Arieti S The pineal gland in old age J Neuropathol Exp Neurol 1954 13482-49 1

4 Bocchi G Valdre G Physical chemical and mineralogical characterization of

carbonate-hydroxyapatite concretions of the human pineal gland J Inorg Biochem

199349209-220

5 Charen J Taves DR Stamm JW Parkins FM Bone fluoride concentrations

associated with fluoridated drinking water Calcif Tiss Int 197927 95-99

6 Cooper ERA The human pineal gland and pineal cysts J Anat (Lond) 19326728-

46

7 Doskocil M Development of concrements in the human pineal body Folia Morphol

(Praha) 19843216-26

8 Earle KM X-ray diffraction and other studies of the calcareous deposits in human

pineal glands J Neuropathol Exp Neurol 19654 108-118

9 Ebie DM Deaton TG Wilson FC Bawden JW Fluoride concentrations in human and

rat bone J Public Health Dent 199252288-29)

10 Ekstrand J Fluoride metabolism in Fejerskov 0 Ekstrand J Burt B (eds) Fluorides

in Dentistry Munksgaard Copenhagen 1996 pp 55-68

11 Galliani 1 Falcieri E Giangaspero F Valdre G Mongiorgi R A preliminary study of

human pineal gland concretions Structural and chemical analysis Boll Soc Ital Biol

Sper 199066 615-622

12 Hasegawa A Ohtsubo K Mori W Pineal gland in old age quantitative and qualitative

morphological study of 168 human autopsy cases Brain Res 1987409343-349

13 Humbert W Peacutevet P Calcium content and concretions of pineal glands of young and

old rats Cell Tissue Res 199 1263593-596

14 Humbert W Peacutevet P Electron probe x-ray microanalysis of the elemental



composition of the pineal gland of young adults and aged rats J Pineal Res

19962039-44

15 Jenkins GN Physiology of fluoride in Murray JJ Rugg-Gunn AJ Jenkins GN (eds)

Fluorides in Caries Prevention ed 3 London Butterworth-Heinemann 199 1 pp262-294

16 Kereacutenyi NA Sarkar K The postnatal transformation of the pineal gland Acta Morphol

Acad Sci Hung 1968 16223-236

17 Krstic R A combined scanning and transmission electron microscopic study and

electron probe microanalysis of human pineal acervuli Cell Tiss Res 1976 174129-

137

18 Krstic R Ultracytochemical localization of calcium in the superficial pineal gland of

the Mongolian gerbil J Pineal Res 1985221-37

19 Lewczuk B Przybylska B Wyrzykowski Z Distribution of calcified concretions and

calcium ions in the pig pineal gland Folia Histochem Cytobiol 199432243-249

20 Mabie CP Wallace BM Optical physical and chemical properties of pineal gland

calcifications Calcif Tissue Res 1974 1659-7 1

21 Michotte Y Lowenthal A Knaepen L Collard M Massart DL A morphological and

chemical study of calcification of the pineal gland J Neurol 1977215209-219

22 Newbrun E Fluorides and Dental Caries ed 3 Springfield Thomas 1986

23 Pizarro MDL Gil JAL Vasallo JL Munoz Barragan L Distribution of calcium in the

pineal glands of normal rats Adv Pineal Res 1989 339-42

24 Rapoport SI Blood-Brain Barrier in Physiology and Medicine New York Raven

Press 1976 p 77-78

25 Tapp E Huxley M The weight and degree of calcification of the pineal gland J

Pathol 197 1 10531-39

26 Taves DR Separation of F by rapid diffusion using hexamethyldisiloxane Talanta



196815969-974

27 Welsh MG Cytochemical analysis of calcium distribution in the superficial pineal

gland of the Mongolian gerbil J Pineal Res 19841305-316

28 Whitford GM The Metabolism and Toxicity of Fluoride Monogr Oral Sci 16 ed 2

Basel Karger 1996

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during chronic acid-base disturbances J Dent Res 1979582058-2065

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1984

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740

Facts About Fluoridation You Did Not Know

By Fluoride Action Network

98 Of Western Europe Has Rejected Water Fluoridation This includes AustriaBelgium Denmark Finland France Germany Italy Luxembourg NetherlandsNorway and Sweden The predominant reason for Europes rejection is the belief thatpublic drinking water is NOT the appropriate vehicle with which to deliver medication toa population

Fluoride Is Not An Essential Nutrient which means that no human disease (includingdental decay) has ever been linked to a fluoride deficiency (1)

The fluoride used to fluoridate water is an industrial waste product from the phosphatefertilizer industry It is an unprocessed hazardous waste contaminated with a numberof toxins particularly arsenic

Fluoridation adds between 01 and 16 parts per billion (ppb) Arsenic to drinking water



and therefore violates the EPAs Maximum Contaminant Level Goal for arsenic - whichis 0 ppb (2)

Hydrofluosilicic acid amp sodium silicofluoride which are the chemicals used to fluoridate91 of fluoridated water in the US have Never Been Tested for safety and

effectivenessAccording to a November 16 2000 letter from the EPA to answer your question onwhether we have in our possession empirical scientific data on the effects of fluosilicicacid or sodium silicofluoride on health and behavior the answer is no

Most dental authorities are now conceding that there is little if any benefit fromswallowing fluoride and that fluorides benefits (whatever they are) come from topicalapplication

When water fluoridation began 50 years ago it was believed that fluoride needed to beingested in order to be effective This is NO longer the view of the dental establishment

which now generally concedes that fluorides benefits are derived primarily from topical application (3)

According for instance to the US Centers for Disease Control Laboratory andepidemiologic research suggests that fluoride prevents dental caries predominatelyafter eruption of the tooth into the mouth and its actions primarily are topical for bothadults and children

All fluoride products designed to be ingested (eg fluoride supplements) are availableby prescription only No fluoride products designed for ingestion have ever beenapproved as safe or effective by the US Food amp Drug Administration (4)

By Logical Extension Fluoridated Water Can Appropriately Be Classified As AnUnapproved Prescription Drug

The dental community concedes that fluoride is ineffective at preventing the mostcommon type of dental decay - pit amp fissures Pit amp fissure decay - which is the decayfound in the crevices of the chewing surfaces - accounts for upwards of 85 of dentaldecay now experienced in the US (5)

New evidence suggests that fluoridation is either unnecessary or doesnt workCavities have declined at similarly impressive rates throughout the entire westernindustrialized world over the past half century

This decline has occurred irrespective of a countrys fluoridation status WesternEurope which is 98 unfluoridated has experienced the SAME decline in cavities asthe heavily fluoridated US and today enjoys the SAME low level of tooth decay (6)

The largest dental survey ever conducted in the US found virtually no differencein dental decay between children living in fluoridated vs unfluoridated areas

The study which was conducted by the National Institute Of Dental Research (NIDR)



found that the average difference in tooth decay (06 tooth surfaces) between childrenliving in fluoridated vs unfluoridated areas amounted to LESS than 05 of the 128 totaltooth surfaces in a childs mouth (7)

Five peer-reviewed studies published in the last 2 years have found that dental

decay DOES NOT increase when communities stop fluoridation (8) The rhetoric supporting fluoridation is increasingly centered around the notion thatfluoridation benefits the neediest in society the most This claim flies in the face of theexperience of most US inner cities over the past 50 years

Despite the fact that nearly all large US cities have been fluoridated for decades dentaldecay is currently rampant in virtually all poor urban areas

One of the major dental health problems experienced in poor communities is adebilitating condition known as baby bottle tooth decay which is also referred to asearly childhood caries

This condition which results from excessive consumption of sweetened liquids at ayoung age is not prevented by water fluoridation (9) According to a study in PediatricNursing Data from Head Start surveys show the prevalence of baby bottle tooth decayis about three times the national average among poor urban children even incommunities with a fluoridated water supply

Fluoride Is A Very Toxic Substance which is why it is the active ingredient in anumber of pesticides Just 2 grams of fluoride is enough to kill an adult and just 500mg is enough to kill a child (11) In the US people have died and many have becomesick when faltering fluoridation equipment has pumped excess fluoride into the waterPoor nutrition exacerbates the toxic effects of fluoride exposure which is a further

reason why its wrong to target poor communities with fluoridation (as poor nutrition ismore prevalent in low income communities)

According to the Agency for Toxic Substances and Disease Registry Existing dataindicate that subsets of the population may be unusually susceptible to the toxic effectsof fluoride and its compounds These populations include the elderly people withdeficiencies of calcium magnesium andor vitamin C and people with cardiovascularand kidney problems (12)

Contaminated Food Chain - Many of the processed beverages and foods sold in theUS contain elevated levels of fluoride due to the use of fluoridated water duringmanufacturing and the presence of fluoride pesticides

Total fluoride exposure has increased substantially since the early days of fluoridation(13) When fluoridation first began exposure to fluoride from sources other thanfluoridated water was minimal

Today that is not the case

People now receive fluoride from a whole host of sources including pesticide residues



fluoridated dental products mechanically deboned meat fluoride air pollution andprocessed foods amp beverages prepared with fluoridated water (eg soda juice beercereal etc)

It has now reached the point where most people receive the optimal 1 mgday of

fluoride (which fluoridated water was designed to deliver) without ever drinking a glassof fluoridated water

Despite the increase in total fluoride exposure the concentration of fluoride added todrinking water (07-12 mgL) as prescribed by the US Government is still the same asit was back in the 1940s

Due to the increase in total fluoride exposure there has been a major increase in therate of dental fluorosis found among American children According to the USGovernment approximately 1 in 3 children living in fluoridated areas have dentalfluorosis on at least 2 teeth (14)

Dental fluorosis is the first visible sign that fluoride has poisoned enzymes in thebody

Approximately half of the fluoride we ingest each day accumulates in our bodiesprimarily in the bones but also in soft tissues (15)

High levels of naturally occurring fluoride causes a crippling bone disease known asskeletal fluorosis According to UNICEF skeletal fluorosis is endemic in at least 25countries across the globe (16) with the problem particularly acute in India China andother developing countries

Skeletal fluorosis comes in varying degrees of severity depending on the level of

exposure The earliest symptoms are characterized by joint pain that is difficult if notimpossible to distinguish from arthritis

According to a review on fluoridation by Chemical amp Engineering News Because someof the clinical symptoms mimic arthritis the first two clinical phases of skeletal fluorosiscould be easily misdiagnosed [as arthritis] The World Health Organization states thatearly cases [of skeletal fluorosis] may be misdiagnosed as rheumatoid orosteoarthritis (17)

It is estimated that approximately 40 million Americans suffer from arthritis themost common type being osteoarthritis

Fluoride stimulates abnormal bone development Clinical trials published in the NewEngland Journal of Medicine and Journal of Bone and Mineral Research (18) report thathigh dose fluoride treatment increases bone mass but that the newly formed bone isstructurally unsound (19) Thus instead of reducing hip fracture the studies foundthat high doses of fluoride increase hip fracture

There is concern that low doses of fluoride taken over long periods of time (egfluoridated water) may also increase the rate of hip fracture Approximately 20 recent



studies have investigated the relationship between fluoridated water and hip fracturewith approximately half of the studies finding an association (20)

A 1995 study in the journal Neurtoxicology and Teratology found that fluorideaccumulated in the brain of rats and produced age-specific behavioral deficits typical of

most neurotoxic agents (21)In the study fluoride induced damage to the hippocampal region of the brain Damageto the hippocampal region has been linked to hyperactivity and cognitive deficits Basedon the results the lead author of the study Dr Phyllis Mullenix has come out andadvised against water fluoridation

Five recent peer reviewed studies from China have found an association betweenelevated fluoride exposure and decreased IQs in children - an effect that would beexpected based on Mullenixs research (22)

In the late 1990s a British scientist discovered that fluoride accumulates to very high

levels (avg = 9000 ppm) in the crystallized tissue of the human pineal glandA subsequent animal study found that fluoride interferes with the pineal glandsproduction of melatonin a hormone which helps regulate the onset of PUBERTY Inthe study animals dosed with fluoride had reduced levels of melatonin metabolites intheir urine and had earlier onsets of puberty than the controls (23)

Up until the 1950s European doctors used fluoride to reduce the activity of the thyroidgland for people suffering from overactive thyroid (hyperthyroidism) (24) The dailydose of fluoride which people are now receiving in fluoridated communities (16 to 66mgday) (25) actually exceeds the dose of fluoride which was found to depress thethyroid gland (23 to 45 mgday) (26)

Hypothyroidism (under-active thyroid) is currently one of the most common medicalproblems in the United States Synthroid the drug doctors prescribe to treathypothyroidism was the fourth most prescribed drug in the US in the year 2000Symptoms of hypothyroidism include depression fatigue weight gain muscle and jointpains increased cholesterol levels and heart disease

A recent study published in the journal Brain Research found that 1 PPM fluoride inwater facilitated the uptake of aluminum into the brain of rats producing the type ofbrain tangles (amyloid deposits) that are associated with Alzheimers disease and othertypes of dementia (27)

An epidemiological study published in the December 2000 issue of the journalNeurotoxicology found that fluoridated water was associated with elevated levels oflead in childrens blood (28)

The studys findings parallel the findings of an earlier study published in the September1999 issue of the International Journal of Environmental Studies (29) Lead in the bloodis associated with a variety of neurological problems including reduced intelligence



aggression and hyperactivity

Dozens of laboratory studies have found that fluoride is a mutagen - a classificationwhich frequently indicates that a substance is carcinogenic (ie that it causes cancer)(30) A cancer bioassay conducted by the National Toxicology Program found that rats

dosed with fluoride had a statistically significant increase in bone tumors (osteosarcomas) which were not found among the controls

The initial review of the study also reported that the fluoride-dosed rats had tumors ofthe thyroid oral cavity and rare tumors of the liver however these tumors were laterdowngraded under conspicuous and controversial circumstances According to DrWilliam Marcus the Chief Toxicologist at the EPAs Office of Drinking Water thedowngrading of the tumors was politically motivated and not scientifically defensible(31)

A recent epidemiological study conducted by a scientist from the US Public HealthService found that female infertility was associated with elevated levels of fluoride (

gt3ppm) in drinking water The study concluded that more emphasis needs to be givento the effects on health from total fluoride exposure - not just exposure to fluoridateddrinking water (32)

In light of the recent research indicating health risks from low level fluoride exposurethe Union of Scientists and professionals at EPA headquarters has voted to opposefluoridation (33) and has called upon Congress to issue a national moratorium on thefifty year old policy According to the Vice President of the Union Dr J William Hirzy

In summary we hold that fluoridation is an unreasonable risk That is the toxicity offluoride is so great and the purported benefits associated with it are so small - if thereare any at all - that requiring every man woman and child in America to ingest it

borders on criminal behavior on the part of governmentsAfter years of overlooking the problems with fluoride amp fluoridation the environmentalcommunity is finally beginning to address the issue In September of 2001 the SierraClub announced that

There are now valid concerns regarding the potential adverse impact of fluoridation onthe environment wildlife and human health The Sierra Club therefore supports givingcommunities the option of rejecting mandatory fluoridation of their water supplies

To protect sensitive populations and because safer strategies and methods forpreventing tooth decay are now available we recommend that these safer alternativesbe made available and promoted



Luke found that animals treated with fluoride had lower levels of circulating melatonin asreflected by reduced levels of melatonin metabolites in the animals urine This reduced levelof circulating melatonin was accompanied - as might be expected - by an earlier onset ofpuberty in the fluoride-treated female animals

Luke summarized her human and animal findings as follows

In conclusion the human pineal gland contains the highest concentration of fluoride in thebody Fluoride is associated with depressed pineal melatonin synthesis by prepubertalgerbils and an accelerated onset of sexual maturation in the female gerbil The resultsstrengthen the hypothesis that the pineal has a role in the timing of the onset of pubertyWhether or not fluoride interferes with pineal function in humans requires furtherinvestigation

Online Papers - Fluoride amp the Pineal Gland

FULL TEXT - html Luke J (2001) Fluoride deposition in the aged human pineal glandCaries Research 35125-128

EXCERPT - html Luke J (1997) The Effect of Fluoride on the Physiology of the Pineal Gland PhD Thesis University of Surrey Guildford

Articles of Interest - Fluoride amp the Pineal Gland

Fluoride amp the Pineal Gland Study Published in Caries Research IFIN Bulletin March 2001

Fluoride amp Oxidative Stress Yet more evidence FAN Science Watch September 30 2004

Summation - Fluoride amp Pineal Gland (back to top)

ldquoThe single animal study of pineal function indicates that fluoride exposure results in alteredmelatonin production and altered timing of sexual maturity Whether fluoride affects pinealfunction in humans remains to be demonstrated The two studies of menarcheal age inhumans show the possibility of earlier menarche in some individuals exposed to fluoride butno definitive statement can be made Recent information on the role of the pineal organ inhumans suggests that any agent that affects pineal function could affect human health in a

variety of ways including effects on sexual maturation calcium metabolism parathyroidfunction postmenopausal osteoporosis cancer and psychiatric diseaserdquoSOURCE National Research Council (2006) Fluoride in Drinking Water A ScientificReview of EPAs Standards National Academies Press Washington DC p221-22

In conclusion the human pineal gland contains the highest concentration of fluoride in thebody Fluoride is associated with depressed pineal melatonin synthesis by prepubertalgerbils and an accelerated onset of sexual maturation in the female gerbil The results






















































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740





































































































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740




























































































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740

















































































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740





































































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740





























































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740






















































































Original Paper

Caries Res 299135125-128


Key Words


Abstract











than bone































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740










































































































and HA

























50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740



































































































50 100 and 500 nmol F









Statistical Methods









glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740





















































































glands

Results












Discussion




















































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740






























































































































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740






































































































Acknowledgements








Scand 195844 113-119




Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740



















































































Hall 1995 p 17




199349209-220




46


(Praha) 19843216-26









Sper 199066 615-622









19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740



















































































19962039-44




Acad Sci Hung 1968 16223-236



137













Press 1976 p 77-78


Pathol 197 1 10531-39




196815969-974




Basel Karger 1996




1984




740


















































































196815969-974




Basel Karger 1996




1984




740

































































































































































































































































































