Part 1
2005 Fluoride Abstracts
 
 

2005 Fluoride Abstracts. Part 1.

Abstracts for the following years:
Part 1 - mainly biochemistry and physiology (brain, hormonal, G-proteins, etc.)
Part 2 ("b") - all other

2007

2007-b

2004

2004-b

2001

2001-b

1998

1998-b

1995

1995-b

1992

1992-b

1989

1989-b

1986

1986-b

1983

1982

1976 -
1977
1970 -
1971

2006

2006-b

2003

2003-b

2000

2000-b

1997

1997-b

1994

1994-b

1991

1991-b

1988

1988-b

1985

1985-b

1981

1980

1974 -
1975
1968 -
1969

2005

2005-b

2005-b continued

2002

2002-b

1999

1999-b

1996

1996-b

1993

1993-b

1990

1990 -b

1987

1987-b

1984

1984-b

1979

1978

1972 -
1973
Up to
1967

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 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 - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15877111&query_hl=1

Can J Physiol Pharmacol. 2005 Apr;83(4):367-373.
 
Effects of sodium fluoride on the mechanical activity in mouse gastric preparations.

Amira S, Mule F.

The aim of the present study was to investigate the responses induced by sodium fluoride (NaF) on gastric mechanical activity, using mouse whole-stomach preparations. The mechanical activity was recorded in vitro as changes of intraluminal pressure. In most of the preparations, NaF induced a tetrodotoxin-insensitive biphasic effect characterized by early relaxation followed by slowly developing contractile response. The contraction was dependent on the concentration of NaF, whereas the relaxation was observed at only 10&ndash;30 mmol/L NaF. The contractile effect was significantly reduced by nifedipine (an L-type Ca2+ channel blocker), ryanodine or ruthenium red (inhibitors of Ca2+ release from sarcoplasmic reticulum), and GF109203X (a protein kinase C inhibitor). Moreover, it was abolished by neomycin (an inhibitor of phospholipase C) and potentiated by SQ22536 (an inhibitor of adenylyl cyclase). All the drugs significantly increased the relaxation, except SQ22536, which abolished it. The present results suggest that NaF causes a complex mechanical response in the whole-stomach, which might explain gastric discomfort after fluoride ingestion. The relaxation appears owing to production of cAMP, while the contractile effects imply activation of phospholipase C, protein kinase C, influx of Ca2+, and release of Ca2+ from ryanodine-sensitive intracellular store.

PMID: 15877111 [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=1

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=15901049&query_hl=1

Hum Exp Toxicol. 2005 Mar;24(3):101-8.
 
Inflammatory markers in bronchoalveolar lavage fluid from human volunteers 2 hours after hydrogen fluoride exposure.

Lund K, Dunster C, Ramis I, Sandstrom T, Kelly FJ, Sostrand P, Schwarze P, Skovlund E, Boe J, Kongerud J, Refsnes M.

Department of Respiratory Medicine, National Hospital, University of Oslo, Oslo, Norway. kristin@lund.as

Fluoride has been in focus as a possible causal agent for respiratory symptoms amongst aluminium potroom workers for several decades. Previously, using bronchoalveolar lavage (BAL), we demonstrated airway inflammation in healthy volunteers 24 hours after exposure to hydrogen fluoride (HF). The objective of the present study was to examine early lung responses to HF exposure. Bronchoscopy with BAL was performed 2 hours after the end of 1-hour exposure to HE [sic? HF?] Significant reductions in the total cell number and the number of neutrophils and lymphocytes were observed in bronchoalveolar portion (BAP), whereas there were no significant changes in the bronchial portion (BP). Significantly decreased concentrations of beta2-MG, IL-6 and total protein were found in both BAP and BP. Additionally, IL-8 was significantly reduced in BP, and ICAM-1 and albumin were present in lower concentrations in BAP. Lung function measurements were not affected by HF exposure. These reported effects are presumably transitory, as many were not present in the airways 24 hours after a similar HF exposure.

PMID: 15901049 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15862015

Wei Sheng Yan Jiu. 2005 Jan;34(1):29-32.

[The effect of high dose fluoride on the rat offspring osteoblasts which ingested by female rats]

[Article in Chinese]

Zhang Y, Liang YJ, Guo XY, Li X.

College of Stomatology, China Medical University, Shenyang 110001, China.

OBJECTIVE: To investigate the effect of high dose fluoride which ingested by female rats on morphologic change in rat offspring's bone and osteoblast, discuss the relation between the mechanism of fluorosis and cell cycle, cell apoptosis.
METHODS: In stock diets condition, Wistar female rats drank distilled water containing 0,50,100,150 mg/L NaF for 2 months, then they are mated with normal rats. The calvarium and osteoblast of offsprings were used to investigate the effects of fluoride on ultrastructure by LM and TEM. FCM was used to analysis cell cycle and apoptosis.
RESULTS: The Electron microscope revealed the number of microvilli of osteoblasts were overall decreased in rat offsprings with fluorosis. There was mitochondrial swelling and dilation of the rough endoplasmic reticulum (RER). The matrix of calvarium was hyperplasia and collagen was accumulated and turbulenced. The nuclear manifested the apoptosis character. NaF at 150 mg/ L increased the osteoblast number of S phase with relative decrease of cell number of G2/M phase, but did not change that in G0/G1 phase. The apoptosis percentage increased in this group.
CONCLUSION: Excessive fluoride can directly through the placental barrier, influence cell structure and cell cycle distribution of fluorosis rat offspring and render the cell cycle stagnant in S phase, induce apoptosis.

PMID: 15862015 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15862017

Wei Sheng Yan Jiu. 2005 Jan;34(1):35-7.

[Effect of fluoride on activities of enzyme and ultrastructure in primary cultured rat hepatocytes]

[Article in Chinese]

Guo XY, Sun YC, Sun GF.

School of Public Health, China Medical University, Shenyang 110001, China.

OBJECTIVE: To study the cell viability, activities of enzyme and ultrastructure changes induced by sodium fluoride in primary cultured rat hepatocytes.
METHODS: Hepatocytes were isolated using half-in situ collagenase digestion method. Cellular viability was determined by MTT method. The activities of ALT and AST were determined by spectrophotography method. The ultrastructure changes of hepatocyte were observed under transmission electron microscope.
RESULTS: After cultured with various concentrations of fluoride for 24 hours, a dose-dependent decrease of cell viability was detected in the hepatocytes. The activities of AST and ALT in the 2 mmol/L and 4 mmol/L groups were significantly higher than the control group (P < 0.05). Transmission electron microscope study showed that in fluoride treated hepatocytes the changes included swollen mitochondria and disordered, disrupted endoplasm reticulum.
CONCLUSION: Excessive fluoride induced significant toxicity in primary cultured hepatocytes which manifested the injuries of membrane and organell plasma membrane.

PMID: 15862017 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15850282

Hum Exp Toxicol. 2005 Feb;24(2):79-87.

Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats.

Cicek E, Aydin G, Akdogan M, Okutan H.

Suleyman Demirel University, Medical School, Dept of Pharmacology, Isparta, Turkey.

Possible effects of long term exposure (6 months) to sodium fluoride (NaF) through drinking water on the morphology and biochemistry of myocardial tissue in second generation adult male rats were investigated. Wistar strain female and male rats were reared until the second generation of rats obtained, during which they were given 1, 10, 50 and 100 mg/L NaF in drinking water. Of the second generation, 28 male rats were divided into four groups and had the same treatment. All the second generation rats were sacrificed and autopsied at the end of the 6 months. In the samples of myocardial tissues, the levels of serum fluoride and the activities of principal antioxidant enzymes were determined, and a histopathological examination was conducted. Significant histopathological changes were found in the myocardial tissue of rats treated with 50 and 100 mg/L NaF. These were myocardial cell necrosis, extensive cytoplasmic vacuole formation, nucleus dissolution in myosits, swollen and clumped myocardial fibers, fibrillolysis, interstitial oedema, small hemorrhagic areas and hyperaemic vessels. Additionally, the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid-reactive substance (TBARS) levels were observed in the myocardial tissues of rats treated with 10 and 50 mg/L NaF. On the other hand, the activities of SOD, GSH-Px, and CAT decreased, but the TBARS levels increased in the myocardial tissues of rats treated with 100 mg/L. The present results revealed that prolonged ingestion of fluoride through drinking water, particularly with high doses, induced significant histopathological and biochemical changes leading to myocardial tissue damage.

PMID: 15850282 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15842830

Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Mar;39(2):107-10.

[Differential expression of osteopontin and bax, bcl-2 by fluoride.]

[Article in Chinese]

Xu H, Zhang JM, Zhang XY, Li GS.

Department of Pathology, Institute of Frontier Medical Science, Jilin University, Changchun 130021, China.

OBJECTIVE: To study the differential expression of bax, bcl-2 and osteopontin by fluoride in the renal tubular cells in vitro.
METHODS: The renal tubular cells were cultured and exposed to sodium fluoride (NaF) in 1, 5, 7.5, 12.5 mg F(-)/L level. The transcription level of bax, bcl-2 and osteopontin were investigated by reverse transcription - polymerase chain reaction (RT-PCR).
RESULTS: The expression of bax mRNA in 7.5 and 12.5 mgF(-)/L groups (optical absorption ratio value was 2.37 +/- 0.18 and 2.64 +/- 0.19 respectively) was significantly increased (P < 0.01). On the contrary, the level of bcl-2 obviously decreased (5 mg F(-)/L group optical absorption ratio value, 0.80 +/- 0.22, P < 0.05; 7.5 mg F(-)/L group optical absorption ratio value 0.71 +/- 0.22, P < 0.01). The expression mRNA of osteopontin was significantly increased when cells were exposed to fluoride at 7.5 mg F(-)/L (optical absorption ratio value 2.01 +/- 0.40 P < 0.01), in that group the tubular cell apoptotic trend was obvious.
CONCLUSION: NaF might induce tubular cell apoptosis via activation of bax expression and bcl-2 suppression. Osteopontin might protect the tubule against apoptosis in a lower fluoride level, but the function should be decreased in higher fluoride level.

PMID: 15842830 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15794887

Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Jan;39(1):26-9.

[Fluorosis on expression of nicotinic acetylcholine receptors in protein and gene levels in human SH-SY5Y neuroblastoma cells.]

[Article in Chinese]

Guan ZZ, Shan KR, Xiu J, Long YG.

Key Laboratory of Molecular Biology and Department of Pathology, Guiyang Medical College, Guizhou 550004, China.

OBJECTIVE: To investigate the influence of fluorosis on nicotinic acetylcholine receptors (nAChRs) in protein and gene levels in SH-SY5Y cells and the mechanism of the receptor modification.
METHODS: SH-SY5Y cells, a human neuroblastoma cell line, were incubated with different concentrations of fluoride or with antioxidant for 48 hours. The functions of cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method, and protein oxidation detected by carbonyl content; the alpha3 and alpha7 nAChR subunits in protein level were measured by Western blotting and in mRNA level by RT-polymerase chain reaction (RT-PCR).
RESULTS: In high-dose group as compared to the control, the decreased MTT (49%), increased protein oxidation (72%), and lower expression of alpha3 (51%) and alpha7 (47%) nAChR subunit proteins were obviously observed in SH-SY5Y cells. There were no changes in expression of nAChR subunit mRNAs between the cells treated with fluoride and those un-treated in controls. Prior treatment with antioxidant resulted in preventing the decrease of nAChR protein in cells exposed to the high doses of fluoride.
CONCLUSION: Fluorosis should result in damage of cells and the declined expression of nAChRs in protein levels, but no influences on gene expression of the receptors in human neuroblastoma neurons. The decreased nAChR proteins might be involved in the mechanism of oxidative stress induced by fluorosis.

PMID: 15794887 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15796194

In Vivo. 2005 Mar-Apr;19(2):327-34.

Inhibition of branching morphogenesis of mouse fetal submandibular gland by sodium fluoride--protection by epidermal growth factor.

Naka T, Maruyama S, Nagao T, Takayama F, Maki J, Yasui T, Sakagami H, Ohkawa S.

Department of Prosthodontics, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan.

As an initial step to study the effect of sodium fluoride on the oral environment, we investigated how sodium fluoride (NaF) affects the branching morphogenesis of fetal mouse submandibular gland (SMG). When mouse SMG was prepared from the embryo at 13 days post prenatal stage and cultured, gradual development of branching morphogenesis was observed. Addition of NaF affected this morphological change in bimodal fashions. At a lower concentration of NaF (< 2 microM), the branching morphogenesis was slightly enhanced, whereas at a higher concentration of NaF (4 - 8 microM), it was almost completely inhibited. The inhibitory effect of NaF at the higher concentration was abrogated by stimultaneous addition of epidermal growth factor (EGF), but not by 5alpha-dihydrotestosterone (DHT) or insulin-like growth factor (IGF). These data demonstrate that EGF can effectively reduce the cytotoxic activity of NaF at micromolar concentration.

PMID: 15796194 [PubMed - in process]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15827647

Org Biomol Chem. 2005 Apr 21;3(8):1495-500. Epub 2005 Mar 10.

Urea vs. thiourea in anion recognition.

Gomez DE, Fabbrizzi L, Licchelli M, Monzani E.

Dipartimento di Chimica Generale, Universita di Pavia, via Taramelli 12, 27100, Pavia, Italy. luigi.fabbrizzi@unipv.it.

Neutral anion receptors (LH) form stable 1 : 1 H-bond [LHX](-) complexes with carboxylates, halides and phosphate (X(-)). Some of the [LHX](-) complexes, in presence of an excess of X(-), release an HX fragment, with formation of [HX(2)](-) and the deprotonated receptor L(-). The tendency towards deprotonation increases with the acidity of the receptor and with the stability of the [HX(2)](-) self-complex. Thus, the more acidic thiourea containing receptor deprotonates in the presence all the investigated anions except chloride, whereas the less acidic urea containing receptor undergoes deprotonation only in the presence of fluoride, due to the high stability of [HF(2)](-).

PMID: 15827647 [PubMed - in process]

•• Note from FAN: Deprotonation is the removal of a proton (H+) from an atom, molecule, or ion.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15728705

Toxicol Sci. 2005 Feb 23;
 
No increase of apoptosis in regressing mouse liver after withdrawal of growth stimuli or food restriction.

Bursch W, Wastl U, Hufnagl K, Schulte-Hermann R.

Medizinische Universitat Wien, Univ. Klinik fur Innere Medizin I Abtl. Institut fur Krebsforschung, Borschkegasse 8a, A-1090 Wien.

In short-term in vivo experiments, liver growth and regression in mice with high (C3H/He), intermediate (B6C3F1) or low (C57BL/6J) susceptibility to hepatocarcinogenesis was compared. Liver growth was induced by dietary administration of phenobarbital (PB; 750 ppm) or nafenopin (NAF; 500 ppm). The following results were obtained:
1. PB or NAF treatment for 7 days produced moderate increases of liver DNA (15% or 25-28%, resp.) along with pronounced hypertrophy. Liver growth was strongest in C3H/He mice
2. Cessation of PB or NAF treatment led to a rapid regression of liver hypertrophy. However, the enhanced hepatic DNA content persisted for at least 2 weeks in all mouse strains.

3. Apoptosis was not increased at any time after cessation of treatment in all strains.
4. Food restriction to 60% of the ad libitum intake did neither amplify regression of liver hyperplasia nor the occurrence of apoptosis.
In conclusion, the highly susceptible C3H/He mice exhibited the strongest liver growth response to PB. No strain difference in the occurrence of apoptosis was detected. Mouse hepatocytes in liver regressing after mitogen withdrawal do not enter apoptosis as readily as rat hepatocytes.

PMID: 15728705 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15748797

Regul Toxicol Pharmacol. 2005 Apr;41(3):228-39.

Toxicological profile of hydrofluoropolyethers

G. Malinvernoa, I. Colombob, , and M. Viscab

(a) Solvay S.A., European Public Affairs Brussels, Belgium
(b) Solvay Solexis R&D Centre, Regulatory Affairs and Industrial Toxicology, Bollate, Italy

Received 14 June 2004.  Available online 20 January 2005.

Hydrofluoropolyethers (HFPE) are a family of linear oligomeric fluorinated fluids comprising a chain of difluoromethoxy and tetrafluoroethoxy repeating units with terminal OCF2H end groups, each of which contains an isolated hydrogen atom. These fluids have been designed as low environmental impact substitutes for perfluorinated organic substances in a number of applications including heat transfer and fire suppression agents, and as a solvent. The toxicological profile of these new fluids has been evaluated and is presented in this paper. Acute toxicity tests have been performed on Sprague–Dawley Crl: CD (SD) BR rats using oral, dermal, and inhalation routes. No deaths were recorded even at the highest tested concentrations, and the resultant LD50/LC50 values were >5000 mg/kg (oral), >2000 mg/kg (dermal), and >26,411 ppm (inhalation: reversible anaesthetic effects, e.g., lethargy, seen at this exposure concentration). Other short-term tests (skin and eye irritation, skin sensitisation, genotoxicity tests in vitro and in vivo, cardiac sensitisation) were also performed, and no hazardous properties were identified. Effects of repeated exposure by inhalation were examined in rats over test periods of 5, 14, 28, and 90 days. Effects on embryo–foetal development in the rat have also been studied. The 28-day, 90-day and developmental studies were performed using nominal HFPE concentrations of 1000, 3300, and 10,000 ppm (6 h/day: actual exposures confirmed by test atmosphere analysis), and the highest tested concentration proved to be an NOAEL in each study. Major observed effects were elevated urinary (inorganic) fluoride levels and increased liver weights with centrilobular hepatocyte hypertrophy (considered an adaptive response, linked to hepatic metabolism of absorbed material).


From Science Direct

Fish & Shellfish Immunology Volume 18, Issue 2 , February 2005, Pages 149-162

Signal transduction of the prophenoloxidase activating system of prawn haemocytes triggered by CpG oligodeoxynucleotides

Che-Pei Chuo (a), Shu-Mei Liang (b) and Hung-Hung Sung (a)

a Department of Microbiology, Soochow University, Taipei, Taiwan, ROC
b Institute of Bioagricultural Sciences, Academia Sinica, Taipei, Taiwan, ROC

Intracellular phenoloxidase (PO) activity in haemocyte lysate supernatant (HLS) of giant freshwater prawn (Macrobrachium rosenbergii) was shown to be enhanced by CpG oligodeoxynucleotide (ODN) 2006, but not by so-ODN13. When haemocytes were treated in vitro with 50 ?g/ml of ODN2006 for 30 min, the increases in both intra- and extracellular stimulated PO activity (POS) and extracellular total PO activity (POT) and the reduction of POT suggest that the PO activity of haemocytes is enhanced by ODN2006 stimulation, but new prophenoloxidase (proPO) is not synthesised. In an attempt to determine which signal transduction pathway is involved in the activation of the proPO system, haemocytes were separately treated with activators or inhibitors of specific signalling components. The results show that there was an increase in both intra- and extracellular POT of haemocytes treated with sodium fluoride (a G-protein activator); the addition of phosphokinase A (PKA)-activating 8-bromo-cAMP to haemocytes only increased intracellular POT, and the addition of either phorbol-12-myristate-13-acetate (PMA; a phosphokinase C (PKC) activator) or caffeine (a phosphodiesterase inhibitor) only increased extracellular POT. When PMA-stimulated haemocytes were treated with chelerythrine (a PKC inhibitor), the induced extracellular POT was significantly reduced. Furthermore, the study of ODN2006-stimulated haemocytes treated with chelerythrine or palmitoyl-DL-carnitine (a PKC inhibitor) showed that the enhancement effects of ODN2006 on the intra- and extracellular POS and extracellular POT were significantly decreased. ODN-stimulated haemocytes treated with genistein (an inhibitor of protein tyrosine kinase) showed a further increase in extracellular POT, but the other PO activities remained the same as those of the ODN-stimulated group. These results suggest that the activation of the proPO system of prawn haemocytes, including degranulation and PO activity, is induced by ODN2006 via a PKC-activating signalling pathway, but negatively regulated via the tyrosine kinase pathway.


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15846740

Cochrane Database Syst Rev. 2005 Apr 18;2:CD005015.

Interventions for preventing bone disease in kidney transplant recipients.

Palmer S, McGregor D, Strippoli G.

Department of Nephrology, Christchurch Hospital, Private Bag 4710, Christchurch, NEW ZEALAND, 8001.

BACKGROUND: Patients with chronic kidney disease have significant abnormalities of bone remodelling and calcium homeostasis and are at increased risk of fracture. The fracture risk for a kidney transplant recipient is four times that of the general population and higher than that for a patient on dialysis. Trials reporting the use of bisphosphonates, vitamin D analogues, calcitonin, and hormone replacement therapy to treat bone disease following engraftment exist.
OBJECTIVES: To evaluate the use of interventions for the treatment of bone disease following kidney transplantation.
SEARCH STRATEGY: The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library - Issue 3 2004), MEDLINE (1966 to August 2004), EMBASE (1980- August 2004) and reference lists were searched without language restriction.
SELECTION CRITERIA: Randomised trials of treatment of bone disease following kidney transplantation were included. Trials of recipients of any transplant other than a kidney transplant including trials of kidney-pancreas transplants were excluded.
DATA COLLECTION AND ANALYSIS: Two authors assessed independently trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI) for dichotomous variables. For continuous variables the weighted mean difference (WMD) and its 95% CI was used.
MAIN RESULTS: Twenty-three eligible trials (1,209 patients) were identified. Seven trials compared more than two interventions. Nineteen trials compared active treatment with placebo, five vitamin D analogue and calcium, six vitamin D analogue alone, twelve bisphosphonates, and four nasal calcitonin. Eight trials compared two active treatments, one 17-beta oestradiol and medroxyprogesterone versus vitamin D analogue, five bisphosphonate versus vitamin D analogue, two vitamin D analogue and calcium versus calcium and one bisphosphonate versus calcitonin.Methodological quality was suboptimal. There were no significant differences between any treatment group for risk of fracture. Bisphosphonate, administered by any route, vitamin D analogue and calcitonin all had a beneficial effect on the bone mineral density at the lumbar spine. Bisphosphonates and vitamin D analogue had a beneficial effect on the bone mineral density at the femoral neck. Few or no data were available for combined hormone replacement, testosterone, selective oestrogen receptor modulators, fluoride or anabolic steroids. All-cause mortality and drug-related toxicity were reported infrequently and there was no statistical difference between treatment groups.
AUTHORS' CONCLUSIONS: No benefit from any intervention known to reduce risk of fracture from bone disease could be demonstrated to reduce fracture incidence in kidney transplant recipients.

PMID: 15846740 [PubMed - as supplied by publisher]


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