http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15984565&query_hl=3
Biometals.
2005 Jun;18(3):207-12.
Exposure to high fluoride concentration
in drinking water will affect spermatogenesis and steroidogenesis
in male albino rats.
Pushpalatha
T, Srinivas M, Sreenivasula Reddy P.
Department
of Biotechnology, Sri Venkateswara University, Tirupati
- 517 502, India.
Sodium
fluoride (NaF) administered orally to adult male rats
at a dose level of 4.5 ppm and 9.0 ppm for 75 days caused
significant decrease in the body
weight, brain index and testicular index. A significant
decrease in sperm count, sperm motility, sperm viability
and sperm function (HOS positive) with increased sperm
abnormalities was also observed in NaF-exposed male rats.
The activity levels of testicular steroidogenic marker
enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD)
and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were
significantly decreased in NaF-treated
rats indicating decreased steroidogenesis and in turn
spermatogenesis in rats exposed to NaF.
PMID:
15984565 [PubMed - in process]
|
From
Toxline at Toxnet
FASEB
J 2005 Mar;19(4):A58
Teratogenicity
Due to Fluoride.
Krupanidhi S, Cherry KN
Biosciences,
Sri Sathya Sai Institute of Higher Learning, Prasanthinilayam,
515 134 AP, India.
The fluoride anion is a natural water contaminant at certain
regions of the globe. Apart from the beneficial attributes
of fluoride at its optimum level in drinking water namely
1.0 to 1.5 ppm in building the skeletal frame of organisms,
there is also a major concern regarding its deleterious
effects particularly at its higher concentrations beyond
4 ppm. Considering the chick embryo, one of the best verbetrate
developing model-system and the embryonic development
of which is entirely independent and also not being interrupted
by the maternal nutrition, the teratogenic
effects of fluoride are demonstrated. The ankle joint
and toe bones articulations and the skeletal materials
involved in this synovial mechanism have been brought
to focus as the target teratogenic sites in the present
investigation.
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16111031&query_hl=13
Wei
Sheng Yan Jiu. 2005 May;34(3):287-8.
[The dose-effect relationship of water fluoride
levels and renal damage in children]
[Article
in Chinese]
Liu
JL, Xia T, Yu YY, Sun XZ, Zhu Q, He W, Zhang M, Wang A.
Health,
Tongji Medical College, Huazhong University of Science
and Technology, Wuhan 430030, China.
OBJECTIVE:
To explore the dose-effect relationship of water fluoride
levels and renal damage in children and observe the difference
of renal function between high-loaded fluoride people
and dental fluorosis people in the same water fluoride
level region.
METHODS: 210 children were divided into seven groups in
term of drinking water fluoride levels and whether they
suffered from dental fluorosis. Fluoride concentrations
in urine and serum and activities of urine NAG and gamma-GT
were determined.
RESULTS: The urine and serum fluoride of high-loaded fluoride
people and dental fluorosis people increased compared
with control, moreover fluoride contents in urine and
serum increased gradually with the increase of fluoride
level in drinking water. Urine NAG and gamma-GT activities
significantly increased in dental fluorosis people from
area of 2.58 mg/L fluoride in drinking water and in those
two groups from area of 4.51 mg/L fluoride in drinking
water. Moreover, there existed an obvious dose-effect
relationship between the drinking water fluoride concentration
and NAG and gamma-GT activity.
CONCLUSION: Over 2.0 mg/L fluoride
in drinking water can cause renal damage in children,
and the damage degree increases with the dinking water
fluoride content. Renal damage degree is not related to
whether the children suffered from dental fluorosis and
mainly due to water fluoride concentration.
PMID:
16111031 [PubMed - in process]
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15993682&query_hl=3
Sci
Total Environ. 2005 Jun 15;346(1-3):56-69.
The impact of the hyperacid Ijen
Crater Lake: risks of excess fluoride to human health.
Heikens
A, Sumarti S, van Bergen M, Widianarko B, Fokkert L, van
Leeuwen K, Seinen W.
Institute
for Risk Assessment Sciences, Yalelaan 2, 3584 CM, The
Netherlands.
The
Asembagus irrigation area (East Java, Indonesia) receives
a high input of fluoride (F) via surface water that partially
originates from the hyperacid crater lake of the Ijen
volcano. Endemic dental fluorosis among local residents
has been ascribed to F in water wells. In this study,
the total F intake by children and adults was estimated,
based on concentrations in well waters and foods throughout
the area. These values were compared with the Lowest Observed
Adverse Effect Level (LOAEL) for dental fluorosis among
children and skeletal fluorosis among adults. Fluorosis
hazard maps were prepared, identifying the most hazardous
locations in the area. It was concluded that there is
not only a high risk of dental fluorosis, but also of
skeletal fluorosis. Based
on the total daily intake, the lowest F concentration
in drinking water that poses a risk of developing fluorosis
is approximately 0.5 mg/l for dental fluorosis and 1.1
mg/l for skeletal fluorosis. This
is below 1.5 mg/l, which is both the guideline value for
drinking water from the World Health Organization (WHO)
and the Indonesian drinking water standard. This
is the first documented case of human health problems
that may be directly associated with natural pollutants
originating from a volcano-hosted crater lake.
PMID:
15993682 [PubMed - as supplied by publisher]
|
Am
J Med. 2005 Jan;118(1):78-82.
Skeletal
fluorosis and instant tea.
Whyte
MP, Essmyer K, Gannon FH, Reinus WR.
Division
of Bone and Mineral Diseases, Washington University School
of Medicine at Barnes-Jewish Hospital, 660 South Euclid,
Box 8301, St. Louis, Missouri 63110, USA. mwhyte@shrinenet.org
No
abstract available
Publication
Types:
• Case Reports
See
a review of this report by Michael Connett at
http://www.fluoridealert.org/science-watch/20.htm
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15862016
Wei Sheng Yan Jiu. 2005
Jan;34(1):32-4.
[Relationship between spermatogenic
cell apoptosis and serum estradiol level in rats exposed
to fluoride]
[Article in Chinese]
Jiang CX, Fan QT, Cheng
XM, Cui LX.
College of Public Health, Zhengzhou University,
Zhengzhou 450052, China.
OBJECTIVE: To observe the relationship
between spermatogenic cell apoptosis and serum estradiol
level in rats exposed to fluoride.
METHODS: A total of 30 male Wistar rats were allocated
into six groups randomly. The six experimental groups
were 28-day control group, 28-day low-dose fluoride treatment
group, 28-day high-dose fluoride treatment group, 38-day
control group, 38-day low-dose fluoride treatment group,
and 38-day high-dose fluoride treatment group. The fluorosis
model was acquired by subcutaneous injection of NaF solution.
The content of NaF in testis was measured by using fluorine
selective electrode. The serum estradiol level was radioimmunochemically
detected. And the apoptotic spermatogenic cells were quantitatively
measured by TUNEL.
RESULTS: The
content of NaF in testis and the ratio of apoptotic spermatogenic
cell in fluoride treatment groups significantly increased
with increased experimental dosage and prolonged experimental
period (P < 0.05). Meanwhile, the serum estradiol level
significantly decreased (P < 0.05), which was negatively
correlated with the content of NaF in testis as well as
the ratio of apoptotic spermatogenic cell (P < 0.05).
CONCLUSION:
Excessive fluoride could lead disturbance to serum estradiol
level during some range of dose and time, which is an
important factor to spermatogenic cell apoptosis.
PMID: 15862016 [PubMed - in process]
|
FASEB
J 2005 Mar;19(4):A58
Teratogenicity
Due to Fluoride.
Krupanidhi S, Cherry KN
Biosciences,
Sri Sathya Sai Institute of Higher Learning, Prasanthinilayam,
515 134 AP, India.
The fluoride anion is a natural water contaminant at certain
regions of the globe. Apart from the beneficial attributes
of fluoride at its optimum level in drinking water namely
1.0 to 1.5 ppm in building the skeletal frame of organisms,
there is also a major concern regarding its deleterious
effects particularly at its higher concentrations beyond
4 ppm. Considering the chick embryo, one of the best verbetrate
developing model-system and the embryonic development
of which is entirely independent and also not being interrupted
by the maternal nutrition, the teratogenic effects of
fluoride are demonstrated. The ankle
joint and toe bones articulations and the skeletal materials
involved in this synovial mechanism have been brought
to focus as the target teratogenic sites in the present
investigation.
|
Bulletin
of Environmental Contamination and Toxicology - March 2005;
Vol 74: 566-572
Genotoxic
evaluation of sodium fluoride and sodium perborate in
mouse bone marrow cells
N.
Velazqueq-Guardarrama (1-2), E. Madrigal-Bujaidar (1),
D. Molina (1) G. Chamorro (3)
(1) Laboratory
of Genetics, Escuela Nacional de Ciencias Biologicas (Mexico)
(2) Infantile Hospital Federico Gomez (Mexico)
(3) Prclinical Toxicology Laboratory, Escuela Nacional
de Ciencias Biologicas (Mexico)
Excerpts:
Eight week-old male mice (NIH), weighing 30 g were obtained
from the Mexican National Institute of Health. The animals
were maintained in metallic cages, where they consumed
food (Nutricubos, Purina, Mexico City) and tap water,
ad libitum. The animal room was set at 24 C and a 12 h
dark-light cycle.
To determine
the LD50, we followed a two step assay that calls for
few animals (Lorke 1983). Initially, three mice per group
received 10, 100, and 1000 mg/kg respectively; then depending
on the observed lethality, we also used three other mice
per group to test four new doses for each compound. In
the case of sodium fluoride, we tested 60, 40, 25 and
15 mg/kg...
For the genotoxicity
assay, a BrdU tablet of 50 mg was subcutaneously implanted
to each animal (five mice per dose); one hour later the
tested compounds were ip administered. In the case of
sodium fluoride, 2.0, 4.0, 8.0, 16.0, and 24.0 mg/kg were
applied... The assay also included a negative control
group (0.3 mL of distilled water) and a positive control
group administered with mytomicin C (2 mg/kg). Twenty
one hours after inoculation with these chemicals, the
mice were injected with colchicine (5 mg/kg); three hours
later their femurs were dissected and the bone marrow
dispersed in a tube containing 7mL of KCl 0.075 M at 37
C. ...
RESULTS AND
DISCUSSION
The LD50 was
obtained as the geometric mean of the determined experimental
data on mice lethality. The value for sodium fluoride
was 32 mg/kg and for sodium perborate the result was 775
mg/kg. The results concerning the SCE rate induced by
sodium fluoride are shown in Table 1. Although
no significant increase was observed with the two low
doses tested (from 2 to 4 mg/kg), a significant SCE increase
was found with the three highest doses [8, 16, 24 mg/kg].
The cumulative frequency of these data reveals about 70%
of cells with four SCE in the group treated with the high
dose, a value which is twice the level of the negative
group (Figure 1).
Also, a tendency
for an SCE increase relative to the used doses is observed
in the figure. The cellular proliferation kinetics and
the MI are indicated in Table 1. With respect to the first
parameter, the distribution of the evaluated cell divisions
in the experimental groups gave rise to no significant
variations of the AGT; in regard to the MI, the variability
among the studies groups made it difficult to reach a
conclusion.
... The determination
of the genotoxic potential of compounds that are present
in the environment is necessary before taking the appropriate
and timely preventive measures. The present report includes
two examples of chemicals involved in various human activities,
which have not clearly shown their mutagenic potential.
In the case
of sodium fluoride numerous in vitro studies have produced
contradictory information. The mammalian in vivo approach
is usually considered the final step for determining genotoxicity
and defining risk assessment, before regulatory measures
may be taken. About fifteen in vivo studies using different
research models were made between 1970 and 1998 (Kram
et al. 1978; Mohamet and Chandler 1982; Li et al. 1987;
van Asten et al. 1998). Most of these reports reveal negative
results; in fact, only one of them is clearly positive
showing increases of chromosomal aberrations in somatic
and germ cells of mice that had drunk fluoridated water.
The concern regarding the sodium fluoride hazard is understandable
because of the direct exposure of humans to the chemical
for more than 50 years; however,
most in vivo reports, suggest that only high doses of
the chemical may pose a danger for the genetic material
and that the usual low amounts to which humans are exposed
in the environment are harmless. Our data agree with this
assumption, moreover, if we consider that the highest
daily intake of the chemical in fluoridated water is about
6 mg/kg (Zeiger et al. 1993). In our case, we determined
a genotoxic effect starting with 8 mg/kg, and only 24
mg/kg (75% of the LD50) induced a duplication of the basal
level.
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16519100&query_hl=1&itool=pubmed_docsum
Ann Acad Med Stetin. 2005;51(2):69-85.
In vitro and in vivo effects of fluoride
ions on enzyme activity.
[Article in English, Polish]
Adamek E, Pawlowska-Goral K, Bober K.
Silesian Academy of Medicine, Faculty of Pharmacy, Department
of General and Analytical Chemistry, Sosnowiec.
RESULTS: This work presents mechanisms by which interaction of
fluoride ions with enzymes can take place. The effects of fluoride
on enzymes participating in cellular metabolic pathways, like
energy formation and carbohydrate and lipid turnover, are discussed.
A list of enzymes which are inhibited or
activated in vivo and in vitro by fluoride ions is provided, together
with information on species and organs of origin, fluoride concentration,
and extent of inhibition or activation.
PMID: 16519100 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16463958&query_hl=1&itool=pubmed_DocSum
Toxicol Ind Health. 2005 Nov;21(10):255-8.
Fluorosis and its hematological effects.
Eren E, Ozturk M, Mumcu EF, Canatan D.
Department of Pediatrics, Suleyman Demirel University Medical
School, Isparta, Turkey. erderen@yahoo.com
Although it has been reported that fluoride ingestion has no
influence on various indices of hematopoiesis, some research has
been published that excessive fluoride developed anemia and eosinophilia
of leukocytes. Isparta is situated on the lake region of Turkey
where fluorosis is endemic. Our aim was to explore the hematological
effects in rats induced by fluoride. In this study, Wistar-Albino
rats were used, divided into two groups as control and fluorized.
While the control group was administered commercial water (including
0.07 ppm fluoride), the fluorized group was administered 100 ppm
fluoride in commercial drinking water for four months. At the
end of four months, hematological indices (Hb, Hct, MCV, MCH,
RDW, RBC, WBC, and platelet counts) were measured. In addition,
bone marrow samples were investigated. Mean leukocyte counts (WBC)
in the control group and fluorized group were 7.07 (2.62-12.25)
and 2.76 (3.13-5.24)x 10(3)/mm3, respectively.
We observed displastic changes on granulocytes in the bone marrow
samples of the fluorized group. Although there were significant
statistical changes in WBC, we did not determine red blood cell
and platelet changes in the fluorized group.
PMID: 16463958 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16404888&query_hl=34&itool=pubmed_DocSum
Gig Sanit. 2005 Nov-Dec;(6):53-5.
[The specific features of the development
of iodine deficiencies in children living under environmental
pollution with fluorine compounds]
[Article in Russian]
Gas'kov AIu, Savchenkov MF, Iushkov NN.
Natural iodine deficiency and ambient air pollution with fluorine
compounds were examined for their combined influence on the prevalence
and severity of iodine-deficiency disorders. The excess intake
of fluorine was shown to increase the incidence of thyroid diseases
and to lower anthropometric indices in children. The
preventive measures performed to eliminate iodine-deficiency disorders
under intensive ambient air pollution with fluorine compounds
were found to be insufficiently effective.
PMID: 16404888 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16404888&query_hl=2&itool=pubmed_docsum
Gig Sanit. 2005 Nov-Dec;(6):53-5.
[The specific features of the development
of iodine deficiencies in children living under environmental
pollution with fluorine compounds]
[Article in Russian]
[No authors listed]
Natural iodine deficiency and ambient air pollution with fluorine
compounds were examined for their combined influence on the prevalence
and severity of iodine-deficiency disorders.
The excess intake of fluorine was shown to increase the incidence
of thyroid diseases and to lower anthropometric indices in children.
The preventive measures performed to eliminate iodine-deficiency
disorders under intensive ambient air pollution with fluorine
compounds were found to be insufficiently effective.
PMID: 16404888 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16356340&query_hl=11&itool=pubmed_DocSum
J Anal Toxicol. 2005
Nov-Dec;29(8):810-3.
Bone surface and whole bone as biomarkers
for acute fluoride exposure.
Buzalaf MA, Caroselli EE, de Carvalho JG,
de Oliveira RC, da Silva Cardoso VE, Whitford GM.
Departamento de Ciencias Biologicas, Faculdade de Odontologia
de Bauru, Universidade de Sao Paulo, Alameda Octavio Pinheiro
Brisolla 9-75, 17012-901, Bauru, SP, Brazil. mbuzalaf@fob.usp.br
This study compares fluoride concentrations ([F]) in surface
and whole bone for up to 27 days following an acute oral dose
of F. Four groups of rats received single oral F dose (50 mg/kg
body weight), and the control group received deionized water (n
= 10/group). Groups were euthanized at 1, 3, 9, or 27 days after
F administration. Plasma and femurs were collected. F on the femur
surface was removed from a circular area (4.52 mm(2)) by immersion
in 0.5M HCl for 15 s. The solution was buffered with total ionic
strength adjustment buffer and analyzed with an electrode. The
subjacent bone was sectioned and ashed at 600 degrees C. Ash and
plasma were analyzed for F with the electrode following hexamethyldisiloxane-facilitated
diffusion. Data were analyzed by Kruskall-Wallis and Dunn's test
and by linear regression (p < 0.05). Peak plasma and bone surface
[F] occurred on day 1 (0.26 +/- 0.14 microg/mL and 1801 +/- 888
microg/g, respectively). Bone surface [F] at 3, 9, and 27 were
not statistically different from control. A significant increase
in whole bone [F] was observed 3 days after F administration and
the [F] remained relatively constant thereafter. The mean (+/-
SD) surface/whole bone [F] ratios for the control and F groups
were 2.45 +/- 0.98, 3.92 +/- 1.32, 1.61 +/- 0.82, 1.73 +/- 0.39,
and 1.09 +/- 0.28, respectively. Plasma and bone surface [F]s
were positively correlated (r = 0.74). Thus, bone surface was
found to be a suitable biomarker for acute, sublethal F exposure
1 day after F administration. Whole bone [F] were significantly
increased at 3, 9, and 27 days after F administration.
PMID: 16356340 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16301964&query_hl=1
Presse Med. 2005
Nov;34(20 Pt 1):1518-20.
[Osteofluorosis caused by excess use of
toothpaste.]
[Article in French]
Roos
J, Dumolard A, Bourget S, Grange L, Rousseau A,
Gaudin P, Calop J,
Juvin R.
Departement de pharmacie.
BACKGROUND: Osteofluorosis
is caused by chronic fluoride intoxication. Fluoride is used in
toothpaste for the prevention of dental caries, and dental fluorosis
has often been reported among children and attributed to ingestion
of fluoride toothpaste. We report a case of chronic fluoride intoxication
caused by excess use of toothpaste in an adult. Case A 45-year-old
woman consulted a rheumatologist for painful swelling of the fingers,
phalangeal rather than articular. She also had brown staining
on her teeth. Radiography of the hands showed
periosteal apposition on the phalanges. Further work-up
ruled out tumoral or thyroid causes. Laboratory tests showed elevated
fluoride levels in the blood (50.9 micromol/L, normal<1.5 micromol/L)
and in the urine (721 micromol/L, normal<46 micromol/L). On
questioning, we found only one cause for chronic fluoride intoxication:
excess and unusual use of toothpaste. The patient brushed her
teeth 18 times a day and swallowed the toothpaste, because she
liked the taste. She consumed a tube of toothpaste every 2 days,
thereby swallowing 68.5 mg of fluoride every day. Suspecting fluorosis
from toothpaste, we asked the patient to use a toothpaste without
fluoride. Sixteen weeks later, the pain had ceased, and laboratory
tests showed massively reduced but still elevated fluoride levels
in the blood (6.9 micromol/L) and urine (92.7 micromol/L).
CONCLUSION: In this rare case of fluoride
intoxication, misuse of a normally innocuous product caused osteofluorosis.
PMID: 16301964 [PubMed
- in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16301964&query_hl=11&itool=pubmed_DocSum
Presse Med. 2005
Nov 19;34(20 Pt 1):1518-20.
[Osteofluorosis caused by excess use of
toothpaste]
[Article in French]
Roos J, Dumolard A, Bourget S, Grange L,
Rousseau A, Gaudin P, Calop J, Juvin R.
Departement de pharmacie, CHU de Grenoble.
BACKGROUND: Osteofluorosis is caused by chronic fluoride intoxication.
Fluoride is used in toothpaste for the prevention of dental caries,
and dental fluorosis has often been reported among children and
attributed to ingestion of fluoride toothpaste. We report a case
of chronic fluoride intoxication caused by excess use of toothpaste
in an adult.
CASE: A 45-year-old woman consulted a rheumatologist for painful
swelling of the fingers, phalangeal rather than articular. She
also had brown staining on her teeth. Radiography of the hands
showed periosteal apposition on the phalanges. Further work-up
ruled out tumoral or thyroid causes. Laboratory tests showed elevated
fluoride levels in the blood (50.9 micromol/L, normal<1.5 micromol/L)
and in the urine (721 micromol/L, normal<46 micromol/L). On
questioning, we found only one cause for chronic fluoride intoxication:
excess and unusual use of toothpaste. The patient brushed her
teeth 18 times a day and swallowed the toothpaste, because she
liked the taste. She consumed a tube of toothpaste every 2 days,
thereby swallowing 68.5 mg of fluoride every day. Suspecting fluorosis
from toothpaste, we asked the patient to use a toothpaste without
fluoride. Sixteen weeks later, the pain had ceased, and laboratory
tests showed massively reduced but still elevated fluoride levels
in the blood (6.9 micromol/L) and urine (92.7 micromol/L).
CONCLUSION: In this rare case of fluoride
intoxication, misuse of a normally innocuous product caused osteofluorosis.
PMID: 16301964 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16341517&query_hl=11&itool=pubmed_DocSum
Pathologe. 2005
Dec 8; [Epub ahead of print]
[Fluorosis - a forgotten entity Case report
of a woman with coxarthrosis and newly diagnosed fluorosis.]
[Article in German]
Busse B, Jobke B, Werner M, Furst M, Ruther
W, Delling G.
Institut fur Osteopathologie, Universitatsklinikum Hamburg-Eppendorf,
.
The clinical manifestation of fluorosis has become rare over
the past years. Although the use of fluoride medication in osteoporosis
therapy remains controversial, past study results have led to
a reduction in fluoride prescriptions. Several studies have shown
minor biomechanical properties of newly built woven bone compared
to original bone. Despite new prescription protocols, fluoride
therapy should not be disregarded in the anamnesis of osteoporosis
patients. In addition to conventional diagnostics in fluorosis,
new techniques such as microanalysis and micro-CT-analysis show
a diagnostic benefit. In this case, the edx-microanalysis results
show an F concentration of over 1.0 wt% in bone. The ratio of
bone to tissue volume, evaluated by micro-CT, is clearly elevated
at 46% BV/TV. The histopathological preparation of the femoral
head has made the possible effects of fluoride medication on bone
visible and quantifiable. A direct causal relationship between
coxarthrosisand fluoride medication,
found both in our patient as well as in the literature, has not
been demonstrated. In order to better understand the broad effects
of fluoride medication in combination with coxarthrosis more studies
are needed.
PMID: 16341517 [PubMed - as supplied by publisher]
coxarthrosis definition:
degenerative joint disease or osteoarthritis of the hip joint.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16329592&query_hl=11&itool=pubmed_DocSum
Wei Sheng Yan Jiu. 2005
Sep;34(5):543-6.
[Screening of environmental response genes
related to dental fluorosis]
[Article in Chinese]
Hou GQ, Liu JL, Yu YY, Xia T.
Henan Centers for Disease Control and Prevention, Zhengzhou 450000,
China.
OBJECTIVE: To screen environmental response genes related to
dental fluorosis, and to provide clues for further researches
of the molecular mechanism of fluorosis.
METHODS: The leukocyte gene expression profiles of control group,
high-loaded fluoride group and dental fluorosis group were tested
using the gene chiR HG-U133A from Affymetrix company. The results
were analyzed by bioinformatical methods.
RESULTS: Compared with control group, a total of 1057 genes were
differentially expressed in high-loaded fluoride group. Of these,
148 were robustly up-regulated and 61 were robustly down-regulated.
A total of 964 genes were differentially expressed in dental fluorosis
group as compared with control group, including 71 robustly up-regulated
genes and 60 robustly down-regulated genes. Compared with high-loaded
fluoride group, 633 genes were identified to be differentially
expressed in dental fluorosis group. Of these, the number of robustly
up-regulated genes and robustly down-regulated genes were respectively
15 and 67.
CONCLUSION: Multiple genes are related to
fluorosis.
PMID: 16329592 [PubMed - in process]
Toxicology Letters ; Volume 160, Issue 1 , 30 December 2005,
Pages 69-75
Proteomic analysis of kidney in fluoride-treated
rat
Hui Xu (a), Lin-Sen Hu (b), Ming Chang
(b), Ling Jing (a), Xiu-Yun Zhang (a) and Guang Sheng Li (a)
(a) Institute of Endemic Disease, Jilin University, Changchun
130021, China
(b) Neuroproteomics Laboratory, Department of Neurology, The First
Teaching Hospital, Jilin University, Changchun 130021, China
The recent development of proteomic techniques has enabled investigators
to directly examine the population of proteins present in biological
systems. We first report here the proteomic
changes of renal protein induced by fluoride. To investigate
molecular mechanisms of renal injury induced by fluoride, proteins
were isolated from rat kidney and profiled by two-dimensional
gel electrophoresis (2DE). With the analysis of Image-Master 2D
Elite software, 141 up-regulated and eight down-regulated protein
spots in 2DE gels of fluoride-treated group were gained by comparison
to the control group, 13 of which were identified by matrix-assisted
laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
MS). The identified proteins are mainly related with cell proliferation,
metabolism and oxidative stress, and provide a valuable clue to
explore the mechanism of renal fluorosis. This study also shows
that the proteomic techniques were powerful in fluoride toxical
field.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16183791&query_hl=4
J Dent Res. 2005 Oct;84(10):919-923.
Possible Link between Glycolysis and Apoptosis
Induced by Sodium Fluoride.
Otsuki S, Morshed SR, Chowdhury SA, Takayama
F, Satoh T, Hashimoto K, Sugiyama K, Amano O, Yasui T, Yokote
Y, Akahane K, Sakagami H.
Department of Dental Pharmacology, Meikai Pharmaco-Medical Laboratory
(MPL), Department of Oral Anatomy II, and Department of Oral Health
and Preventive Dentistry, Meikai University School of Dentistry,
Sakado, Saitama 350-0283, Japan; and Faculty of Science, Josai
University, Sakado, Saitama, Japan;
Fluoride has been used to prevent caries in the dentition, but
the possible underlying mechanisms of cytotoxicity induction by
this compound are still unclear. Since fluoride is known as an
inhibitor of glycolytic enzymes, we investigated the possible
connection between NaF-induced apoptosis and glycolysis in human
promyelocytic leukemia HL-60 cells. NaF-induced
apoptotic cell death is characterized by caspase activation, internucleosomal
DNA fragmentation, loss of mitochondrial membrane potential, and
production of apoptotic bodies. Higher activation of caspases-3
and -9, as compared with that of caspase-8, suggested the involvement
of an extrinsic pathway. Utilization of glucose was nearly halted
by NaF, whereas that of glutamine was rather enhanced. NaF enhanced
the expression of Bad protein, but not that of Bcl-2 and Bax proteins,
and reduced HIF-1alpha mRNA expression. Analysis
of these data suggests a possible link between glycolysis and
apoptosis.
PMID: 16183791 [PubMed - as supplied by publisher]
Full free report at http://www.ijoeh.com/pfds/IJOEH_1104_Mullenix.pdf
INT J OCCUP ENVIRON HEALTH 2005;11:404–414
Fluoride poisoning: a puzzle with hidden
pieces
PHYLLIS J. MULLENIX, PHD
Key industry data regarding harm from chronically inhaled fluoride
have been unavailable publicly for decades. Recent unveiling of
unpublished reports reveals three examples of data mishandling
that disguised the need for more stringent occupational standards
for particulate and gaseous fluorides and fluorine. Injury reports
from workers handling chemicals show that unjustifiable reductions
of injury and disability numbers in the process of publication
shifted concern from respiratory to mineralized tissue damage.
Selective editing and data omissions allowed bias that fluoride
reduces caries without detrimental effects. Finally, industry’s
failure to publish an important industry-funded laboratory study
buried knowledge of low thresholds for fluoride-induced lung disease.
Data from that study are presented to clarify the dose- and duration-dependent
changes caused by chronic inhalation of calcium fluoride.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16193231&query_hl=4
Calcif Tissue Int. 2005 Sep 28;
[Epub ahead of print]
Beneficial Effect of Copper Supplementation
on Deposition of Fluoride in Bone in Fluoride- and Molybdenum-Fed
Rabbits.
Khandare AL, Suresh P, Kumar PU, Lakshmaiah
N, Manjula N, Rao GS.
National Institute of Nutrition, Jamai Osmania, Hyderabad, India,
alkhandare@yahoo.com.
Fluorosis is a major public health problem in the world, including
India. The present study was undertaken to investigate the role
of molybdenum (Mo) in the deposition of fluoride (F) in bone and
whether copper (Cu) supplementation has any alleviating role when
F and Mo are ingested together. For this purpose, four groups
of rabbits were used [control (C), fluoride (F), fluoride + molybdenum
(F + Mo), and fluoride + molybdenum + copper (F + Mo + Cu)] to
find out the effect of these treatments on various bone-related
parameters like intact parathyroid hormone (iPTH), alkaline phosphatase
and Cu in serum, hydroxyproline and calcium (Ca) in urine, and
minerals (F, Cu, manganese, and zinc) in femur bone ash. Bone
mineral content (BMC), bone mineral density (BMD) [by dual energy
X-ray absorptiometry (DXA)], and strength of femur bones were
also assessed. F content in the femur was
significantly higher (P < 0.01) in all experimental groups
compared to control group. Mo supplementation increased
F deposition in femur bone in the F + Mo group, whereas supplementation
of Cu reduced F deposition in the F + Mo + Cu group compared to
the F + Mo and F groups. Levels of Cu in femurs of the F + Mo
and F + Mo + Cu groups were significantly higher (P < 0.05,
P < 0.01, respectively) than in the C group, although serum
Cu was significantly lower in the F and F + Mo than the C and
F + Mo + Cu groups. Magnesium levels in the F + Mo group were
significantly higher (P < 0.05) than in the F and F + Mo +
Cu groups. Cu supplementation in the F + Mo + Cu group increased
deposition of zinc significantly (P < 0.05) compared to the
F and F + Mo groups. Serum iPTH, alkaline phosphatase, and urinary
hydroxyproline and Ca were significantly higher (P < 0.01)
in the F and F + Mo than in the C and F + Mo + Cu groups. However,
serum iPTH and urinary hydroxyproline were higher in the F + Mo
group than the F group. Alkaline phosphatase was significantly
higher in the F + Mo group than the F and F + Mo + Cu groups.
Levels of serum Cu in the F and F + Mo groups were lower than
in the C group, though serum Cu was significantly higher in the
F + Mo + Cu than in all other groups. DXA analysis of femur bone
indicated that BMD in the F + Mo group was significantly higher
than in the F (P < 0.05), C (P < 0.01), and F + Mo + Cu
(P < 0.05) groups. However, there was no significant difference
in BMC among the groups. Bone strength was significantly higher
(P < 0.05) in the F + Mo group than in the C group. Results
of the present study show that ingestion of Mo with F does not
create secondary Cu deficiency (due to increased excretion of
Cu through urine). However, Cu concentration was decreased in
serum in this group (F + Mo) compared to the C and F + Mo + Cu
groups. Deposition of F in femur bone was
more (22%) when it was given along with Mo compared to F alone,
while F deposition in femur bone was less in the F + Mo + Cu group
by 80% compared to the F group. Also, deposition of F in the F
+ Mo + Cu group was 120% less compared to the F + Mo group. The
increase in F level due to Mo addition appears to be offset by
supplementation with Cu. Supplementation with Cu showed a beneficial
effect on bone resorption as well as bone formation.
PMID: 16193231 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200454&query_hl=1
J Mol Histol. 2005 May;36(4):225-33.
Localisation of high Acid phosphotyrosine
phosphatase activity in afferent arterioles and glomeruli of human
kidney.
Partanen S.
Department of Pathology, Helsinki University Central Hospital,
Jorvi Hospital, Turuntie 150, FIN-02740, Espoo, Finland, seppo.partanen@hus.fi.
Endothelial cells contain a variety of specific protein tyrosine
phosphatases and an acid phosphatase differing from other known
phosphatases. The highest activity of this
acid phosphatase with artificial or unspecific substrates is present
in the afferent arterioles and glomeruli of human kidney, and
the activity is inhibited by nephrotoxic fluoride concentrations,
suggesting that it plays a role in circulatory regulation.
Here the activity was characterised with physiological substrates.
An incubation mixture containing phosphotyrosine or phosphoserine
was stable at pH 5 when phosphate-precipitating lead was chelated
with tartrate. The activities were studied in frozen sections.
Only phosphotyrosine was hydrolysed by some cells. High activity
of tartrate-resistant phosphotyrosine phosphatase was present
in lymphocytes, endothelial cells of afferent arterioles, and
glomerular mesangial cells of kidney, decidual cells, and alveolar
macrophages. In lymphocytes the activity was fluoride-resistant
and vanadate-sensitive, in other cells fluoride- and vanadate-sensitive.
In decidual cells and alveolar macrophages, the activity is due
to specific osteoclastic/macrophagic tartrate-resistant acid phosphatase,
in lymphocytes to specific protein tyrosine phosphatases, and
in endothelial and mesangial cells to a protein tyrosine phosphatase-like
acid phosphatase. The results suggest that in endothelial cells
of the afferent arterioles, mesangial cells, and lymphocytes the
cellular activities are regulated by high constitutive phosphotyrosine
phosphatase activity and this may be related to the exceptional
cyclosporin A sensitivity of these cells.
PMID: 16200454 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16193236&query_hl=4
Calcif Tissue Int. 2005 Sep 28;
[Epub ahead of print]
The Effect of Fluoridation and Its Discontinuation
on Fluoride Profiles in the Alveolar Bone of Rat.
Ohmi K, Nakagaki H, Tsuboi S, Okumura A,
Sugiyama T, Thuy TT, Robinson C.
Depertment of Preventive Dentistry and Dental Public Health,
School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho,
Nagoya, 464-8650, Japan, nakagaki@dpc.aichi-gakuin.ac.jp.
We investigated the effect of fluoridation and its discontinuation
on fluoride content in the alveolar portion of the mandible in
rats. Drinking water with three different fluoride contents (0,
50, 100 ppmF) was given to rats for three different periods (4,
13 and 25 weeks). Fluoride concentrations were measured in the
crest, the middle, and the apical parts of the alveolar bone and
in the body of the mandible. Furthermore, after fluoridated drinking
water was given to rats for 4 or 13 weeks, distilled water was
given to them for 21 or 12 weeks respectively; and the effect
of the discontinuation on fluoride profiles was investigated.
Layer samples were analyzed by abrasive microsampling. Fluoride
and phosphorus concentrations were determined by ion-specific
electrode and colorimetric procedures, respectively. There
was an increase in fluoride concentrations in the mandible in
proportion to the fluoride content in the drinking water and the
duration of fluoridation. After fluoridation was discontinued,
fluoride concentrations in the surface layers of the mandible
presented a decrease. Among the four different parts of the mandible,
the upper part of the alveolar bone and the alveolar crest part
presented the highest rates of reduction. The relative reduction
rate of fluoride concentration was closely related to the duration
of discontinuation. The alveolar crest was affected most by the
discontinuation of fluoridation, presenting the greatest reduction.
PMID: 16193236 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16200454&query_hl=4
J Mol Histol. 2005 May;36(4):225-33.
Localisation of high Acid phosphotyrosine
phosphatase activity in afferent arterioles and glomeruli of human
kidney.
Partanen S.
Department of Pathology, Helsinki University Central Hospital,
Jorvi Hospital, Turuntie 150, FIN-02740, Espoo, Finland, seppo.partanen@hus.fi.
Endothelial cells contain a variety of specific protein tyrosine
phosphatases and an acid phosphatase differing from other known
phosphatases. The highest activity of this acid phosphatase with
artificial or unspecific substrates is present in the afferent
arterioles and glomeruli of human kidney,
and the activity is inhibited by nephrotoxic fluoride concentrations,
suggesting that it plays a role in circulatory regulation. Here
the activity was characterised with physiological substrates.
An incubation mixture containing phosphotyrosine or phosphoserine
was stable at pH 5 when phosphate-precipitating lead was chelated
with tartrate. The activities were studied in frozen sections.
Only phosphotyrosine was hydrolysed by some cells. High activity
of tartrate-resistant phosphotyrosine phosphatase was present
in lymphocytes, endothelial cells of afferent arterioles, and
glomerular mesangial cells of kidney, decidual cells, and alveolar
macrophages. In lymphocytes the activity
was fluoride-resistant and vanadate-sensitive, in other
cells fluoride- and vanadate-sensitive. In decidual cells and
alveolar macrophages, the activity is due to specific osteoclastic/macrophagic
tartrate-resistant acid phosphatase, in lymphocytes to specific
protein tyrosine phosphatases, and in endothelial and mesangial
cells to a protein tyrosine phosphatase-like acid phosphatase.
The results suggest that in endothelial cells of the afferent
arterioles, mesangial cells, and lymphocytes the cellular activities
are regulated by high constitutive phosphotyrosine phosphatase
activity and this may be related to the exceptional cyclosporin
A sensitivity of these cells.
PMID: 16200454 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16161253&query_hl=9
Anticancer Res. 2005 May-Jun;25(3B):2085-90.
Changes in fluoride sensitivity during
in vitro senescence of normal human oral cells.
Satoh R, Kishino K, Morshed SR,
Takayama F, Otsuki S, Suzuki F, Hashimoto K, Kikuchi H, Nishikawa
H, Yasui T, Sakagami H.
Department of Dental Pharmacology, Meikai University School of
Dentistry, Sakado, Saitama 350-0283, Japan.
We have previously reported that sodium fluoride (NaF) showed
slightly higher cytotoxicity against human oral tumor cell lines
than normal human oral cells. Possible changes in the NaF sensitivity
of three normal human oral cell types (gingival fibroblast HGF,
pulp cell HPC, periodontal ligament fibroblast HPLF) during in
vitro ageing were investigated in the present study. When these
cells were subcultured at 1:4 split ratio every week, their saturation
density declined with increasing population doubling level (PDL),
and they ceased to divide when they reached 20 PDL. Mitochondrial
function, evaluated by MTT stainability per cell basis, was elevated
at the terminal phase. NaF dose-dependently reduced the viable
cell number, but did not show any beneficial (growth promoting)
effect (so-called "hormesis") at lower concentrations.
NaF produced large DNA fragments, without induction of internucleosomal
DNA fragmentation, possibly due to weak activation of caspases
-3, -8 and -9. Higher concentrations of
NaF were required to reduce the number of viable senescent cells
than younger cells, indicating that cells become resistant to
cytotoxicity of NaF with in vitro ageing.
PMID: 16161253 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16149713&query_hl=9
Arzneimittelforschung. 2005;55(8):455-60.
Effect of fluoride on the secretion of
insulin in the rat.
Menoyo I, Rigalli A, Puche RC.
Laboratorio de Biologia Osea, Facultad de Ciencias Medicas, Rosario,
Argentina.
Sodium fluoride (CAS 7681-49-4) 5-20 micromol/L in the extracellular
space inhibited insulin secretion by isolated Langerhans islets
stimulated with glucose. Insulin secretion followed a negative
exponential function. This phenomenon is rapidly reversible. Perfusion
of pancreatic tissue (rat) in vivo with stimulatory levels of
glucose revealed that 20 micromol/L fluoride in the perfusion
fluid inhibited the initial and sustained phases of insulin secretion
to 15% of that of controls. The stimulatory effects of the ionophore
A23187, phorbol-ester and forskolin on the secretion of insulin
of isolated rat Langerhans islets in vitro were inhibited by 20
micromol/L fluoride. The results suggested
that fluoride affects some stage of insulin secretion situated
below the cascade of events that include the participation of
calmodulin, protein-kinase C and cyclic AMP.
PMID: 16149713 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16140906&query_hl=9
J Nutr. 2005 Sep;135(9):2247-52.
Elevated serum fluoride concentrations
in women are not related to fractures and bone mineral density.
Sowers M, Whitford GM, Clark MK, Jannausch
ML.
Department of Epidemiology, University of Michigan, Ann Arbor,
MI 48104;
Epidemiologic studies of the relations between drinking-water
fluoride levels and bone mineral density (BMD) and fracture are
characterized by disparate conclusions and an absence of information
about individual circulating fluoride levels. This study relates
serum fluoride concentrations, which reflect individual fluoride
exposures, to BMD and bone fractures. Data are from 1300 female
residents of 3 small communities in which the water fluoride concentrations
were 52.6 or 210.4 mumol/L. Circulating serum fluoride concentrations
were assessed by ion-specific electrode. Fluoride intake was estimated
from interviews describing water and water-based beverage consumption
and duration of residence in the community. BMD was measured by
dual-energy X-ray densitometry and single-photon densitometry.
Self-reported fractures were confirmed by medical record abstraction.
The mean serum fluoride concentration in the high-fluoride community,
2.11 +/- 0.05 mumol/L, was significantly higher than serum fluoride
concentrations in the control and high-calcium communities with
water fluoridation to 52.6 mumol/L. The mean serum fluoride concentrations
in these latter 2 communities were 1.6 +/- 0.04 and 1.22 +/- 0.05
mumol/L, respectively. Serum fluoride was not significantly related
to BMD after adjusting for covariates including age and body size.
The mean distal radius BMD, however, was significantly higher
in the high-fluoride community. Serum fluoride concentrations
were not related to incident osteoporotic fractures with 4
y of observation. Serum fluoride concentrations were not
associated with BMD or osteoporotic fractures among female residents
of communities with water fluoride concentrations of 52.6 or 210.4
mumol/L.
PMID: 16140906 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16136339&query_hl=9
Arch Toxicol. 2005 Sep 1;:1-7 [Epub
ahead of print]
Evaluation of caspase-dependent apoptosis
during fluoride-induced liver lesion in pigs.
Zhan XA, Wang M, Xu ZR, Li WF, Li JX.
Feed Science Institute, College of Animal Science, Zhejiang University,
No. 268, Kaixuan Road, HangZhou, 310029, People's Republic of
China, wing_mail@hotmail.com.
Sixteen barrows (DurocxLandracexYorkshire) were randomly divided
into two groups, each consisting eight pigs. The groups received
the same basal diet supplemented with 0 and 400 mg/kg fluoride,
respectively. Histological examinations, including in situ terminal
deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL),
Haematoxylin and Eosin staining (HE) and transmission electron
microscopy observation, found apoptotic hepatocytes 50 days after
additional 400 mg/kg fluoride treatment. The obvious DNA ladder
and the significantly increased both hepatic caspase-9 and caspase-3
activity indicated that fluoride induced caspase-dependent apoptosis
in vivo. In addition, serum glutamate pyruvate transaminase (GPT)
activity and hepatic lipid peroxides (LPO) concentration was significantly
increased. The activity of serum glutamate oxaloacetate transaminase
(GOT) showed an increased trend. The results
suggest that fluoride induces apoptosis by elevating the oxidative
stress-induced lipid peroxidation, causing mitochondrial dysfunction
and further activating caspase-9 and caspase-3.
PMID: 16136339 [PubMed - as supplied by publisher]
Free Full Report at
http://www.jbc.org/cgi/reprint/M505259200v1
J Biol Chem. 2005 Aug 29; [Epub
ahead of print]
Heterotrimeric G-protein alpha -subunit
adopts a 'pre-activated' conformation when associated with beta
gamma -subunits.
Abdulaev NG, Ngo T, Zhang C, Dinh A, Brabazon
DM, Ridge KD, Marino JP.
Center for Membrane Biology, Department of Biochemistry and Molecular
Biology, University of Texas Health Science Center at Houston,
Houston, TX 77030.
Activation of a heterotrimeric G-protein by an agonist-stimulated
G-protein coupled receptor requires the propagation of structural
signals from the receptor binding interface to the guanine nucleotide
binding pocket of the G-protein. To probe the molecular basis
of this signaling process, we are applying high-resolution NMR
to track structural changes in an isotope-labeled, full length
G-protein alpha-subunit (Galpha) chimera (ChiT) associated with
G-protein betagamma-subunit (Gbetagamma) and activated receptor
(R*) interactions. Here, we show that ChiT can be functionally
reconstituted with Gbetagamma as assessed by aluminum fluoride
dependent changes in intrinsic tryptophan fluorescence, and light-activated
rhodopsin catalyzed guanine nucleotide exchange. We further show
that (15)N-ChiT can be titrated with Gbetagamma to form stable
heterotrimers at NMR concentrations. To assess structural changes
in ChiT upon heterotrimer formation, HSQC spectra of the (15)N-ChiT
reconstituted heterotrimer have been acquired and compared with
spectra obtained for GDP/Mg(2+)-bound (15)N-ChiT in the presence
and absence of aluminum fluoride, and GTPgammaS/Mg(2+)-bound (15)N-ChiT.
As anticipated, Gbetagamma association with (15)N-ChiT results
in (1)HN, (15)N chemical shift changes relative to the GDP/Mg(2+)-bound
state. Strikingly, however, most (1)HN, (15)N chemical shift changes
associated with heterotrimer formation are the same as those observed
upon formation of the GDP*AlF(4)(super-}/Mg(2+)- and GTPgammaS/Mg(2+)-bound
states. Based on these comparative analyses, assembly of the heterotrimer
appears to induce structural changes in the switch II and carboxyl-terminal
regions of Galpha ('pre-activation') that may facilitate the interaction
with R* and subsequent GDP/GTP exchange.
PMID: 16129667 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16044843&query_hl=9
Vopr Pitan. 2005;74(3):50-4.
[Stability
of ascorbic acid at it contract alloy in presence of fluoride
ions]
[Article in Russian]
.
Aluminum utensils are considered as potentiAl source of dietary
Aluminums. Report suggests that acidic food cooked or stored in
presence of Aluminum foil contain high concentrations of Aluminum.
Study on fluoride induced leaching of Aluminum from different
pH. Higher concentrations of fluoride and
lower pH enhance Aluminum leaching to a great extent. Evidence
was obtained showing that after a 2-dyas exposure at room temperature
in presence of floride NaF, Aluminum foil liberated nearly 1 mg/l
of Aluminum, compared with less than 0.04 mg/l in absence of fluoride.
There is reason to believe that in experiments
with ascorbic acid NaF prevents the oxidation of ascorbic acid.
PMID: 16044843 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16043314&query_hl=1
Toxicol Lett. 2005 Jul 22; [Epub
ahead of print]
Proteomic analysis of kidney in fluoride-treated
rat.
Xu H, Hu LS, Chang M, Jing L, Zhang XY,
Li GS.
Institute of Endemic Disease, Jilin University, Changchun 130021,
China.
The recent development of proteomic techniques has enabled investigators
to directly examine the population of proteins present in biological
systems. We first report here the proteomic changes of renal protein
induced by fluoride. To investigate molecular mechanisms of renal
injury induced by fluoride, proteins were isolated from rat kidney
and profiled by two-dimensional gel electrophoresis (2DE). With
the analysis of Image-Master 2D Elite software, 141 up-regulated
and eight down-regulated protein spots in 2DE gels of fluoride-treated
group were gained by comparison to the control group, 13 of which
were identified by matrix-assisted laser desorption ionization-time
of flight mass spectrometry (MALDI-TOF MS). The
identified proteins are mainly related with cell proliferation,
metabolism and oxidative stress, and provide a valuable clue to
explore the mechanism of renal fluorosis. This study also
shows that the proteomic techniques were powerful in fluoride
toxical field.
PMID: 16043314 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921192&query_hl=19
Med Tr Prom Ekol. 2005;(4):35-9.
[Hemostasis disorders in patients with
occupational fluorosis are risk factors for IHD]
[Article in Russian]
Filimonov SN, Luk'ianova MV, Razumov VV,
Koriakin AM, Gorbatovskii IaA, Epifantseva NN, Danilov IP.
The studies covered hemostasis changes in workers with occupational
fluorosis. The disorders diagnosed could be a risk factor for
IHD in aluminium production workers
PMID: 15921192 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15865257&query_hl=19
Drug Chem Toxicol. 2005;28(2):135-58.
Subchronic toxicity of a fluoroalkylethanol
mixture in rats.
Ladics GS, Stadler JC, Makovec GT, Everds
NE, Buck RC.
DuPont Company Haskell Laboratory for
Health and Environmental Sciences, Newark, Delaware 19714, USA.
Gregory.S.Ladics@usa.dupont.com
The objective of this study was to evaluate the subchronic toxicity
of a commercial fluoroalkylethanol mixture, which is an intermediate
in the production of fluoroorganic compounds that are used
as protectants and surfactants. The test substance was
administered daily by gavage to Sprague-Dawley rats as a suspension
in aqueous methylcellulose. The dosages were 0, 25, 100, or 250
mg kg(-1) day(-1). A 1- and 3-month recovery period was included
to evaluate the reversibility of toxic effects. No test substance-related
mortality or neurotoxicity occurred. Body weights and/or nutritional
parameters were significantly reduced at 100 and 250 mg kg(-1)
day(-1), and these effects were reversible. Broken and absent
teeth were observed in rats dosed with 250 mg kg(-1) day(-1),
and microscopic tooth lesions (ameloblast degeneration/disorganization)
occurred at 100 and 250 mg kg(-1) day(-1) and persisted with decreased
severity throughout recovery. Decreased red cell mass parameters
occurred at 90 days in the 250 mg kg(-1) day(-1) group, but red
cell counts were normal thereafter during recovery. A persistent
elevation of liver weights was seen in groups given > or =100
mg kg(-l) day(-1). The increased weights correlated with microscopic
hepatocellular hypertrophy only in males and females administered
250 mg kg(-1) day(-1). Hepatic beta-oxidation was increased in
a dose-dependent manner and persisted through 1 month of recovery
at 250 mg kg(-1) day(-1). Increased kidney weights were observed
at 25 (females only), 100, and 250 mg kg(-1) day(-1). These elevated
weights persisted in the high dose after recovery and correlated
with microscopic tubular hypertrophy (males only). Thyroid
follicular hypertrophy was present at 100 and 250 mg kg(-1)
day(-1) but was not present after recovery. Total
fluorine in whole blood increased with continuous dosing and achieved
steady state in approximately 42 days. Both
plasma and urine fluoride levels were elevated in a dose-dependent
manner. Under the conditions of the study, the no-observed adverse
effect level for this mixture was 25 mg kg(-1) day(-1) for subchronic
toxicity.
PMID: 15865257 [PubMed - indexed for MEDLINE]
Experimental and Toxicologic Pathology Volume 57, Issue 1 , 1 August
2005, Pages 59-64
Effect of sodium fluoride on gastric emptying
and intestinal transit in mice
Smain Amira, , Sihem Soufane and Kamel
Gharzouli
Faculté des Sciences, Département de Biologie,
Université Ferhat Abbas, 19000 Setif, Algeria
Fluoride, a well-recognised harmful substance, is easily absorbed
by the gastrointestinal mucosa. It is therefore conceivable that
any alteration of the gastrointestinal motility can affect the
rate of absorption of fluoride and leads to aggravation of its
toxic effects. The effects of fluoride on gastric emptying and
intestinal transit were studied in the mouse using a carboxymethyl
cellulose (CMC) solution as a non-nutrient meal. The participation
of the cholinergic and nitrergic systems in these effects was
also evaluated. Oral gavage of 5 mM NaF had no significant
effect on gastric emptying and intestinal transit of the CMC meal,
whereas a decrease of gastric emptying (-33%,
P<0.05) and an increase in intestinal transit (+20.7%, P<0.05)
were observed with 20 mM NaF. Atropine injection induced
a significant decrease of gastric emptying. Combined treatment
of atropine with 20 mM NaF brought about a further, but not
significant decrease in gastric emptying. N-G-nitro-l-arginine-methyl
ester (L-NAME) treatment with or without oral administration of
NaF decreased gastric emptying. Atropine treatment significantly
depressed intestinal transit from 56.5% to 37.7% in the absence
of NaF and from 70.1% to 42.8% in its presence. In contrast, L-NAME
administration either alone or with fluoride increased intestinal
transit (P<0.05). The present results
suggest that fluoride alter gastrointestinal motility, an effect
that may partly involve the cholinergic pathway.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15949378&query_hl=6
Zhonghua Yi Xue Za Zhi. 2005 Mar
23;85(11):738-42.
[Impacts of osteoclast-like cells cultured
on bone wafer and their sub-cellular structures on osteoblast.]
[Article in Chinese]
Zhu M, Zhang P, Zhang X, Lu B, Dai CL,
Li YM, Qiu MC.
Department of Endocrinology, General Hospital of Tianjin Medical
University, Tianjin 300052, China.
OBJECTIVE: To investigate the effects of osteoclast-like cells
(OLC) and its sub-cellular structures on the osteoblast
(OB) differentiation and function.
METHODS: Spleen cells from C57 mice administrated with 5-fluorouracil
were induced by IL-3, 6 and granulocyte-macrophage colony stimulating
factor (GM-CSF), and 1alpha, 25-(OH)(2)D(3) to obtain massive
OLCs. These OLC cells were cultured in culture fluid and on bone
wafers (called bolcs). Osteoblasts were
cultured and added with NaF, OLCs of two kinds, culture
fluid free of OLC, and sub-unit structures such as nucleus, mitochondria,
and cytoplasma from OLCs for 5 days. The proliferation rate of
OBs was measured by MTT method and the alkaline phophatase (ALP)
activity was measured by PNPP method. Immunochemistry was used
to detect the core-binding factor alpha1 (Cbfalpha1) in the OBs,
Enzyme linked immunosorbent assay was used to measure the osteocalcin.
RESULTS: The OB number was lower in the OLC (1.288 +/- 0.039),
OLC cytoplasm (1.138 +/- 0.024), 50% OLC culture fluid (1.203
+/- 0.033), 50% OLC culture medium of OLCs cultured on bone wafer
(1.128 +/- 0.028) in comparison with the pure OB group (1.393
+/- 0.016, all P < 0.05). The increase functions of OBs by
OLC cultured on bone wafer and their nucleus and mitochondria
were all more significant than those of the OLCs not cultured
on bone wafer. The ALP activity was increased
in the NaF (1.027 +/- 0.024), OCL cytoplasm (1.850 +/-
0.033), 50% OLC medium (2.074 +/- 0.065), 50% OLC medium of OLCs
cultured on bone wafer (1.718 +/- 0.048), and mitochondria and
cytoplasm of the OLC cultured on bone wafer groups (1.246 +/-
0.037, all P < 0.05). NaF (0.0825 +/-
0.0025), OLCs (0.0775 +/- 0.0025), nucleus (0.0775 +/-
0.0025), mitochondria (0.0875 +/- 0.0025), and cytoplasm of OLCs
(0.1100 +/- 0.0007), 50% OLC medium (0.0900 +/- 0.0000), 50% OLC
medium of OLCs cultured on bone wafer (0.1200 +/- 0.0041), OLCs
cultured on bone wafer and nucleus, mitochondria, and cytoplasm
of OLCs cultured on bone wafer all significantly
increase the oeteocalcin activity of OBs (0.525 +/- 0.0063,
all P < 0.05). NaF (57.6% +/- 2.6%),
OLC cytoplasm (45.3% +/- 4.7%), 50% OLC medium (46.6% +/- 3.3%),
50% medium of OLCs cultured on bone wafer (54.0% +/- 2.1%), OLCs
cultured on bone wafer (44.8% +/- 3.0%), and cytoplasm of OLCs
cultured on bone wafer (48.7% +/- 3.5%) all
significantly increased the Cbfalpha1 protein in the OBs
(32.8% +/- 4.5%, all P < 0.05).
CONCLUSION: The sub-cellular elements of OLC and the supernatant
of OLC culture media free of OLC promote the functions of OB,
especially the OLCs cultured on bone wafer.
PMID: 15949378 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15950406&query_hl=1
Toxicol Lett. 2005 Jun 9; [Epub
ahead of print]
Effects on protein and mRNA expression
levels of p53 induced by fluoride in human embryonic hepatocytes.
Wang AG, Chu QL, He WH, Xia T, Liu JL,
Zhang M, Nussler AK, Chen XM, Yang KD.
Department of Environmental Health, School of Public Heath, Tongji
Medical College, Huazhong University of Science and Technology,
Wuhan 430030, Hubei, PR China.
We investigated the effects of protein and mRNA expression levels
on p53 induced by fluoride in human embryo hepatocyte L-02 cells.
The protein and mRNA levels of p53 in L-02 cells were measured
after in vitro cultured L-02 was exposed to sodium fluoride at
different doses (40, 80, and 160mug/ml) for 24h.
The results showed that the cell survival rate of L-02 cells in
the high dose fluoride group was significantly lower than that
of the control group. The protein expression levels of p53 in
the middle and high dose fluoride group were significantly higher
than in the control group and elevated with increasing fluoride
concentration. The mRNA expression levels of p53 in the fluoride
groups were markedly higher than in the control group. The
mRNA expression level of p53 in the high dose fluoride group was
however lower compared to the middle dose fluoride group, but
similar to the low dose fluoride group. These
finding suggest that fluoride can decrease the L-02 cells survival
rate and induce protein and mRNA expressions of p53; however,
there is no consistency between the protein expression level of
p53 and the mRNA expression level.
PMID: 15950406 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15950921&query_hl=1
Arch Biochem Biophys. 2005 Jun 9;
[Epub ahead of print]
Human tartrate-resistant acid phosphatase
becomes an effective ATPase upon proteolytic activation.
Mitic N, Valizadeh M, Leung EW, de Jersey
J, Hamilton S, Hume DA, Cassady AI, Schenk G.
School of Molecular and Microbial Sciences, The University of
Queensland, St. Lucia, Qld 4072, Australia.
Proteolytic cleavage in an exposed loop of human tartrate-resistant
acid phosphatase (TRAcP) with trypsin leads to a significant increase
in activity. At each pH value between 3.25 and 8.0 the cleaved
enzyme is more active. Substrate specificity is also influenced
by proteolysis. Only the cleaved form is able to hydrolyze unactivated
substrates efficiently, and at pH >6 cleaved TRAcP acquires
a marked preference for ATP. The cleaved enzyme also has altered
sensitivity to inhibitors. Interestingly,
the magnitude and mode of inhibition by fluoride depends not only
on the proteolytic state but also pH. The combined kinetic
data imply a role of the loop residue D158 in catalysis in the
cleaved enzyme. Notably, at low pH this
residue may act as a proton donor for the leaving group.
In this respect the mechanism of cleaved TRAcP resembles that
of sweet potato purple acid phosphatase.
PMID: 15950921 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15895280&query_hl=2
Calcif Tissue Int. 2005 May 19;
[Epub ahead of print]
Severe Bone Deformities in Young Children
From Vitamin D Deficiency and Fluorosis in Bihar-India.
Khandare AL, Harikumar R, Sivakumar B.
National Institute of Nutrition (ICMR), Jamia Osmania P.O., 500007,
Hyderabad, India, alkhandare@yahoo.com.
A case-control study was undertaken to understand the etiopathology
of the bone deformities among young children in a fluoride-affected
village of the Bihar State. Two villages were selected: one village
with high fluoride in drinking water (7.9 +/- 4.15 ppm), and the
other village with normal levels of fluoride (0.6 +/- 0.31 ppm)
as the control village. The source of drinking water was bore
wells in both the villages. Two hundred and forty subjects from
54 households (HHs) of
the high-fluoride village (HFV)
and 1443 subjects from 197 HHs of the control village were selected
for the study. Dental mottling (DM) was
observed in 50% and skeletal deformities of various forms were
observed in 20% of the total population of HFV, whereas, in the
control village, DM was 6% and skeletal deformities were absent.
The prevalence of both, DM and skeletal deformities was
high in the younger age group of 1.5 to 14 years. Genu
valgum, genu varum, bowing of tibia, saber shin, and widening
of the lower ends of long bones at the wrist were the typical
skeletal deformities observed among affected children in the HFV.
X-rays of the children with deformities revealed varying degrees
of bending of bones and enlargement of epiphyseal ends of metaphyses
with fraying of bone and ligamental calcification. A survey indicated
significantly low calcium and high phosphorus intake among the
population of the HFV as compared to that of the control village,
possibly resulting from low intake of milk and high intake of
potatoes, respectively. The mean urinary
fluoride level was significantly higher in the children of the
HPV, both with and without deformities, as compared to that of
the control village. The mean serum 25 OHD(3) (25 HYDROXY
Vitamin D) and calcium levels were significantly lower and alkaline
phophatase activity was significantly higher among the children
with deformities as compared to those without deformities from
the HFV and the control village. Serum intact
parathyroid hormone (IPTH) levels were high in children both with
and without deformities in the HFV as compared to those in the
control village. No significant differences were observed
in the concentration of serum and urinary creatinine, and Cu,
and Mg levels between the HFV and the control village. It can
be concluded that some of the children from the HFV manifested
severe bone deformities (rickets), which were confirmed by the
existence of low serum calcium and vitamin D levels.
PMID: 15895280 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15921192&query_hl=2
Med Tr Prom Ekol. 2005;(4):35-9.
[Hemostasis disorders in patients with
occupational fluorosis are risk factors for IHD]
[Article in Russian]
[No authors listed]
The studies covered hemostasis changes
in workers with occupational fluorosis. The disorders diagnosed
could be a risk factor for IHD in aluminium production workers
PMID: 15921192 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15865257&query_hl=21
Drug Chem Toxicol. 2005;28(2):135-58.
Subchronic toxicity of a fluoroalkylethanol
mixture in rats.
Ladics GS, Stadler JC, Makovec GT, Everds
NE, Buck RC.
DuPont Company Haskell Laboratory
for Health and Environmental Sciences, Newark, Delaware 19714,
USA. Gregory.S.Ladics@usa.dupont.com
The objective of this study was to evaluate the subchronic toxicity
of a commercial fluoroalkylethanol mixture, which is an intermediate
in the production of fluoroorganic compounds that are used as
protectants and surfactants. The test substance was administered
daily by gavage to Sprague-Dawley rats as a suspension in aqueous
methylcellulose. The dosages were 0, 25, 100, or 250 mg kg(-1)
day(-1). A 1- and 3-month recovery period was included to evaluate
the reversibility of toxic effects. No test substance-related
mortality or neurotoxicity occurred. Body weights and/or nutritional
parameters were significantly reduced at 100 and 250 mg kg(-1)
day(-1), and these effects were reversible. Broken
and absent teeth were observed in rats dosed with 250 mg kg(-1)
day(-1), and microscopic tooth lesions (ameloblast degeneration/disorganization)
occurred at 100 and 250 mg kg(-1) day(-1) and persisted
with decreased severity throughout recovery. Decreased red cell
mass parameters occurred at 90 days in the 250 mg kg(-1) day(-1)
group, but red cell counts were normal thereafter during recovery.
A persistent elevation of liver weights was seen in groups given
> or =100 mg kg(-l) day(-1). The increased weights correlated
