1983 Fluoride Abstracts. Fluoride Action Network Pesticide Project.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6627951&dopt=Abstract

Cornell Vet 1983 Oct;73(4):340-62

Dental fluorosis in cattle.

Krook L, Maylin GA, Lillie JH, Wallace RS.

Five expressions of dental fluorosis are described in cattle exposed to industrial fluoride pollution:
1. Hypercementosis with tooth ankylosis, cementum necrosis and cyst formation;
2. Delayed eruption of permanent incisor teeth;
3 Necrosis of alveolar bone with recession of bone and gingiva;
4. Oblique eruption of permanent teeth, hypoplasia of teeth with diastemata; and
5. Rapid progression of dental lesions.
The five entities are not recognized in the "standard for the classification of dental fluorosis" by the National Academy of Sciences. Since this classification it too limited and superficial, adherence to this standard has left severe cases of fluoride intoxication in cattle undetected in field surveys.

PMID: 6627951 [PubMed - indexed for MEDLINE]

ASDC J Dent Child 1983 Mar-Apr;50(2):154-5

As reproduced in Fluoride 1984; 17(1):54-55

Fluorides in mechanically deboned chicken.

Kravitz E, Pollack RL.

Department of Biochemistry and Nutrition, Temple University School of Dentistry, Philadelphia, PA 19140

Publication Types: Letter

To determine the advisability of using mechanically deboned poultry as a food source for children, at least three major factors must be considered:

(1) the likelihood of adverse dental influences following the ingestion of small quantities of fluroide,
(2) the amounts of fluoride likely to be taken into the body from food, water, environmental and other sources,
(3) the fluoride content of various types of poultry following mechanical deboning.

Because of the small margin of safety for fluoride ingestion, the amount consumed should be well below that which may cause harm. Likewise contributions of fluoride from a variety of sources such as chewing gum, medicaments, soot, fertilizers, asbestos, and tobacco products should not be overlooked. Furthermore, significant biologic differences exist among individuals respecting their response to fluorides.

In mechanically deboned poultry, the fluoride content of mature female fowl is very much higher (average 14.38 µg/gm) than that of young chicken (average, 2 ug/gm) or young turkey (average, 1.7 µg/gm) whereas in mature male stage (roosters) fluoride is low (average 1.2 µg/gm) similar to young birds. Following hand-deboning, on the other hand, fluoride concentrations have averaged only 0.7 µg/gm for (mature female) fowl and 0.32-0.9 µg/gm for young chicken parts. Comparison of mature versus young birds revealed that the daily fluoride consumption of infants was projected to be 200-279 µg from mechanically deboned mature poultry; but only 41-57 µg from mechanically deboned young poultry.

Experimental feeding of high fluoride-containing phosphate to young turkeys resulted in high fluroide concentrations (22 µg/gm) following mechanical deboning. Fortunately, the United States governmental regulations help minimize the likelihood of generalized use of such feeds in this country.

Poultry is a good source of dietary protein. It has another desirable nutritional feature: it is lower in saturated fatty acids and higher in polyunsaturated fatty acids than beef or pork products.

At present, mechanically deboned mature female fowl should not be ingested by children. Mechanically deboned poultry intended for consumption by chilren in strained baby, junior, or toddler foods should be obtained exclusively from roosters, young chickens or young turkeys. Only mechanically deboned poultry from birds raised on low-fluoride feeds should be used in such food products. Despite its high fluoride concentration mechanically deboned poultry from mature female fowl may be used, if necessary, in foods preapared for adult consumption exclusively, provided that such mechanically deboned poultry is only a minor ingredient of such food products.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6870909&dopt=Abstract
Biochem Pharmacol 1983 Jun 1;32(11):1693-9

Brain cholinesterases. Differentiation of target enzymes for toxic organophosphorus compounds.

Chemnitius JM, Haselmeyer KH, Zech R.

Cholinesterases in hen brain were characterized with respect to inhibition kinetics and substrate specificity. Three organophosphorus inhibitors were used: diethyl p-nitrophenyl phosphate (Paraoxon, E 600), di-isopropylphosphorofluoridate (DFP), and N,N'-di-isopropylphosphorodiamidic fluoride (Mipafox). The kinetics of irreversible cholinesterase inhibition were studied using two substrates, acetylthiocholine and butyrylthiocholine. The inhibition curves were analysed by the method of iterative elimination of exponential functions. Final classification of the different enzymes was done by combining two inhibitors in sequential inhibition expts. Six cholinesterases were shown to hydrolyse choline esters in hen brain, one was identified as acetylcholinesterase (EC 3.1.1.7) and one as cholinesterase (EC 3.1.1.8). Four enzymes can be classified as intermediate type cholinesterases according to their substrate specificity and to their inhibition constants. The possible role of different brain cholinesterases for the development of atypical symptoms following organophosphate intoxication is discussed.

PMID: 6870909 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6621779&dopt=Abstract
Neurochem Res 1983 Aug;8(8):1059-69

Activation of fluoride-stimulated adenylate cyclase by phospholipase A2 in the caudate nucleus of the rat brain.

Reese JH, Hoss W.

Phospholipase A2 (PLA2) increases adenylate cyclase (AC) activity in the rat caudate nucleus in a dose-dependent manner. After maximal stimulation by fluoride, PLA2 treatment further increases AC activity 2.4 fold. Adenylate cyclase activity is maximal after 45% hydrolysis of the phospholipids. Of the products of PLA2 treatment only lysophosphatidylcholine (LPC) produces such an increase in AC activity. In contrast to PLA2 treatment, LPC solubilizes the enzyme, decreases the Km value for ATP, and requires much larger amounts of LPC than that produced by lipase treatment. After maximal stimulation with fluoride and PLA2, removal of most of the LPC does not reduce the activity of adenylate cyclase. These findings suggest that removal of membrane lipid rather than generation of LPC is responsible for the activation of brain adenylate cyclase by phospholipase A2.

PMID: 6621779 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6865914&dopt=Abstract
Mol Pharmacol 1983 May;23(3):717-23

Inhibition of brain carboxylesterases by neurotoxic and nonneurotoxic organophosphorus compounds.

Chemnitius JM, Zech R.

Carboxylesterases (EC 3.1.1.1) of chicken brain were investigated by applying kinetic analysis of organophosphorus inhibition. By iterative elimination of exponential inhibition curves and by sequential inhibition experiments using a combination of two organophosphorus inhibitors, 11 different carboxylesterases of chicken brain were characterized with respect to their phenyl valerate-hydrolyzing activity (milliunits per gram of brain) and their inhibition by O,O-diethyl O-4-nitrophenyl phosphate (Paraoxon), O,O-diisopropylphosphorofluoridate, and N,N'-diisopropylphosphorodiamidic fluoride (Mipafox). The bimolecular inhibition rate constants (liters . mole-1 . min-1) were calculated for the 11 enzymes and 3 organophosphorus compounds. The corresponding data for acetylcholinesterase (EC 3.1.1.7) in chicken brain were determined. The importance of inhibition rate constants for the development of acute cholinergic symptoms, delayed neurotoxicity, and atypical organophosphate effects is shown.

PMID: 6865914 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6148079&dopt=Abstract
Biochem Int 1983 Jan;6(1):81-91

Separation and properties of a regulatory GTPase activity associated with the adenylate cyclase system in rat brain synaptic plasma membranes.

Enomoto K, Asakawa T.

A GTPase activity having a Km value of 0.5 microM was present in synaptic plasma membranes from rat brain. The activity was inhibited 63% and 24% by NaF and cholera toxin respectively and solubilized from the membranes together with the adenylate cyclase activity. Upon gel chromatography, the solubilized GTPase activity was co-eluted with the GTP-binding regulatory protein of adenylate cyclase. A similar GTPase activity was also associated with the regulatory protein from myelin. The regulatory protein fraction enhanced the activity of the catalytic unit of adenylate cyclase in the presence of 5'-guanylylimidodiphosphate but inhibited the adenylate cyclase activity by 70% in the presence of GTP. These results indicate the possible involvement of the GTPase activity in the regulation of the adenylate cyclase activity.

PMID: 6148079 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6229386&dopt=Abstract
Comp Biochem Physiol B 1983;76(4):869-73

Comparative inhibition profiles of human brain and mouse liver L-hexonate dehydrogenase.

Schofield PJ, Comerford MJ, de Jongh KS.

The inhibition profiles of mouse liver and human brain hexonate dehydrogenase were compared. In general, the pattern for fluoride, lithium, phenobarbital, hydroxylamine and iodoacetate inhibition is similar. Contrary to previous findings, the mouse liver enzyme is potently inhibited by cupric and mercuric ions in sub-millimolar concentrations. The human brain enzyme is also inhibited by these cations. Inhibition of both enzymes by thiol-blocking agents (p-chloromercuribenzoate, iodoacetate) and enzyme protection by the first substrate NADPH but not by the second substrate, glucuronate suggests that both enzymes contain thiol groups essential for catalytic activity.

PMID: 6229386 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6889297&dopt=Abstract
Probl Endokrinol (Mosk) 1983 Jul-Aug;29(4):32-5

[Indices of the pituitary-thyroid system in residents of cities with various fluorine concentrations in drinking water]

[Article in Russian]

Sidora VD, Shliakhta AI, Iugov VK, Kas'ianenko AS, Piatenko VG.

The thyroid 131I consumption, the hypophyseal thyrotropic hormone content and the blood serum total thyroxin and triiodothyronine concentrations were studied in equal groups of healthy humans and donors, living in two cities with an enhanced or decreased fluorine content in drinking water. Iodine deficiency and adaptive amplification of the hypophyseal-thyroid system, not ensuring an absolute compensation, were found in the citizens, using drinking water with an increased fluorine content, accompanied by an augmented incidence of functional disturbance, which structure remained relatively unchanged.

PMID: 6889297 [PubMed - indexed for MEDLINE]

J Neurosci Methods 1983 Apr;7(4):317-28

An application of neutron activation analysis to small biological samples: simultaneous determination of thirty elements in rat brain regions.

Chan AW, Minski MJ, Lai JC.

Thirty elements in 7 rat brain regions were determined by instrumental neutron activation analysis (INAA). The samples were irradiated by thermal neutrons using 3 different sets of conditions, depending on the nuclear characteristics of the elements. Analysis of the resulting radionuclides was by gamma-ray spectrometry using a high resolution Ge(Li) detector and Nuclear Data 6600 multichannel analyzer, which was fully computerized to give quantitative results for the gamma-ray spectra. This paper demonstrates the use of INAA for small biological samples and to show its potential elements, 7 rat brain regions are listed. It is interesting to note that certain elements, e.g. fluorine and potassium showed high and low regional differences respectively, and hypothalamus and hippocampus had higher elemental concentrations than other brain regions. However, since this paper is essentially an analytical one, no attempt is made to assess these data, which are preliminary, and the possible functional role of these elements will be discussed elsewhere.

PMID: 6865471 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6870792&dopt=Abstract
Biochem J 1983 Mar 1;209(3):817-29

Intramolecular group transfer is a characteristic of neurotoxic esterase and is independent of the tissue source of the enzyme. A comparison of the aging behaviour of di-isopropyl phosphorofluoridate-labelled proteins in brain, spinal cord, liver, kidney and spleen from hen and in human placenta.

Williams DG.

Neurotoxic esterase activity was measured in homogenates of human placenta and hen brain, spinal cord, liver, kidney and spleen. The activity in liver comprised less than 20% of the Paraoxon-resistant esterases, but in the other tissues neurotoxic esterase accounted for over 50%. The same tissues were labelled with [3H]di-isopropyl phosphorofluoridate, and any isopropyl group transferred on to protein during 'aging' of the labelled enzymes (alkali-volatilizable tritium) was measured. No Paraoxon-sensitive labelled sites were found to age in this way in any tissue. In brain, the Paraoxon-resistant alkali-volatilizable-tritium-labelled sites correlated with the number of neurotoxic esterase labelled sites, indicating that 'aging' and isopropyl group transfer were 100% efficient. The site receiving the transferred isopropyl group was characterized by analysing the distribution of radiolabelled proteins on gel-filtration chromatography in the presence of SDS. In particulate preparations from each tissue, the protein-bound alkali-volatilizable tritium (transferred isopropyl group) was attached to a polypeptide of Mr 178 000. This same polypeptide also bore the isopropyl-phosphoryl group of neurotoxic esterase, indicating that aging of neurotoxic esterase is an intramolecular group transfer. The apparent turnover number for the enzyme (average 1.6 X 10(5) min-1) was approximately the same in each hen tissue, confirming that closely similar enzymes were present in brain, spinal cord, liver and spleen. The apparent turnover for the human enzyme was 1.8-fold higher than that for the hen enzyme. The concentration of the neurotoxic esterase phosphorylated subunit in brain, spinal cord, spleen, placenta and liver was 14.6, 3.8, 7.4, 3.3 and 3.8 pmol/g of tissue. The evidence indicated that neurotoxic esterase is present in each tissue except kidney, and that isopropyl group transfer on 'aging' occurs on this enzyme only. This process is an intramolecular transfer of the group within the same polypeptide.

PMID: 6870792 [PubMed - indexed for MEDLINE]

Huanjian Kexue Xuebao 1983; 3:94-100

As cited and abstracted in Fluoride 1986; 19(2):95

Effect of sodium fluoride and fluoroacetamide on sister chromatic exchanges and chromosomal aberrations in cultured red muntjac (Muntjacus muntjak) cells

Weishun He, Aihua Liu, Haixian Bio, et al.

Kunming Inst. Zool., Acad. Sin., Kunming, China

The mutagenicity of fluoride has been confirmed once more. Chromosomal aberrations, sister chromatic exchanges (SCEs) and cell cycle kinetics in cultured cells of Red Muntjac in vitro were used as indices in studying the mutagenic effects of NaF and fluoroaetamid (640-19-7). Both NaF and fluoroacetamid can cause chromosomal breakage, increase SCE frequency and lag cell cycle.

Fluoride 1983; 16(1):37-43
Effect of high fluoride intake on chicken performance, ovulation, spermatogenesis and bone fluoride content

Mehdi AWR, Al-Soudi KA, Al-Jiboori NAJ, Al-Hiti MK

Dept. of Veterinary Physiology and Animal Science, Baghdad University, College of Agriculture and Inst. of Agricultural Technology, Baghdad, Iraq

Summary: Three levels, 150, 300 and 600 ppm, of NaF were added to the basal ration of Hisex breed male and female chickens (98 days old). Body weight gain, total feed consumption, feed conversion and mortality (until 158 days of age) were not influenced. At this age, increased fluoride content of the long bones of the treated groups were observed (P<0.05). Long bones of the male birds tended to accumulate more fluoride than did the long bones of the females.

Egg production started on the 157th and 158th day in all groups. Its rate during a period of 70 days showed a tendency to decrease as the level of added fluoride rose. Although ovulation, as reflected by egg laying, was not influenced, initiation of spermatogenesis was delayed in the testes of the 600 ppm group and giant spermatid cells were observed. Breed variation in the response of chicken to the added level of fluoride was suggested.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6684927&dopt=Abstract
Biochem Pharmacol 1983 Oct 1;32(19):2857-62

Altered hormone sensitivity of adenylate cyclase in myocardial sarcolemma of renal hypertensive rats.

Anand-Srivastava MB, Cantin M, Genest J.

Adenylate cyclase activity was studied in the myocardial sarcolemmal membranes from sham-operated control and renal hypertensive rats (RHR). Basal adenylate cyclase activity was not significantly different in RHR as compared to control rats. The stimulation of adenylate cyclase by adenosine, epinephrine and norepinephrine was diminished in RHR, whereas dopamine-sensitive adenylate cyclase was almost completely abolished. The decreased responsiveness of adenylate cyclase to catecholamines was associated with a decrease in the Vmax. Furthermore, the stimulation of enzyme activity by F- and forskolin was also decreased. The data indicate that, in renal hypertension, the responsiveness of adenylate cyclase to various hormones and to agents (forskolin and F-) which do not act through receptors is impaired.

PMID: 6684927 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6620412&dopt=Abstract
J Toxicol Environ Health 1983 Apr-Jun;11(4-6):799-810

Fluoride stimulation of microsomal benzene metabolism.

Post GB, Snyder R.

Benzene metabolism was examined in hepatic microsomes from male Sprague-Dawley rats. In addition to phenol, a highly polar unidentified component was formed. Fluoride, but not other halides, stimulated in vitro formation of both metabolites. Fluoride did not affect covalent binding of benzene metabolites to protein. Other mixed-function-oxidase reactions, and codeine and ethylmorphine demethylation and benzo[a]pyrene hydroxylation, were not affected by fluoride. The polar metabolite(s) was not retained on either a C-18 reverse-phase or a DEAE-Sephadex anion-exchange column. Thus, although highly polar, this component does not appear to be anionic. These results suggest that an enzyme with high specificity for benzene is responsible for microsomal benzene metabolism. Both phenol and the polar metabolite(s) appear to be formed through a common initial step, which is stimulated by fluoride.

PMID: 6620412 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6620413&dopt=Abstract
J Toxicol Environ Health 1983 Apr-Jun;11(4-6):811-25

Effects of enzyme induction on microsomal benzene metabolism.

Post GB, Snyder R.

The effect of induction by phenobarbital (PB), beta-naphthoflavone (BNF), and benzene on benzene metabolism was studied in hepatic microsomes from male Sprague-Dawley rats. Two distinct forms of mixed-function oxidase activity appeared to metabolize benzene. One form was active at all substrate concentrations in microsomes from control, benzene-treated, and BNF-treated animals, and at benzene concentrations of 0.8 mM and below in microsomes from PB-treated animals. It was saturated at benzene concentrations above 0.4 mM, had a pH optimum of approximately 6.6, and was stimulated by fluoride. Pretreatment with benzene, but not BNF, increased benzene metabolism in these preparations. Benzene metabolism in microsomes from PB-induced rats was less active than in controls at benzene concentrations below 0.8 mM, but increased rapidly at higher benzene concentrations. Further characteristics of the PB-induced enzyme activity were that saturation was not observed at benzene concentrations as high as 4 mM, the pH optimum for benzene metabolism in these preparations was 7.1, metabolism was not stimulated by fluoride, and metabolism was inhibited by metyrapone. Both phenol and an unidentified polar component were formed from benzene in all microsomal preparations. Formation of the polar component was increased by PB pretreatment and inhibited by metyrapone, suggesting that formation of the polar component involves a step requiring cytochrome P-450.

PMID: 6620413 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6856987&dopt=Abstract
Res Exp Med (Berl) 1983;182(1):7-12

Effect of fluoride on collagen synthesis in the rat.

Uslu B.

Thirty-six young rats were used to determine the effect of the fluoride on collagen synthesis in healing of fracture. Eighteen rats received 100 ppm fluoride per day, the other 18 were not given fluoride and were used as controls. Then the tibiae of the 36 rats were successively fractured and the animals killed. That is, the first 14 animals of either group were killed one a day, and then the remaining four animals were killed on days 21, 28, 35, and 45 as the tibiae were fractured. Collagen synthesis of the callus was examined histochemically and histologically. In the fluoride-treated group, collagen synthesis was found to be defective, while it was normal in the controls.

PMID: 6856987 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6641420&dopt=Abstract
Zhonghua Yu Fang Yi Xue Za Zhi 1983 Jul;17(4):231-3

[X-ray features of workers at an aluminum-producing plant]

[Article in Chinese]

Xu DY, Chen CL.

PMID: 6641420 [PubMed - indexed for MEDLINE]

Fluoride 1983; 16(1):5-10
Periondontal disease, oral hygiene and fluoride content of dental deposits in aluminum workers

M Borysewicz-Lewicka and M Kobylanska

Department of Conservative Dentistry, Dental Institute, Academy of Medicine, Posnan, Poland

Summary: In workers exposed to high concentrations of fluoride, a clinical evaluation of peridontal health and oral hygiene was carried out. Moreover the relationship between periondontal condition and the concentration of fluoride in dental plaque was investigated.

The results point to a prevalence of advanced periodontal disease (mean PI = 5.06-5.92) and to generally unsatisfactory oral hygiene (mean OHI-S = 4.07-4.98). It was found that the progress of periondontal disease is related to age as ell as to the length of employment.

A significant relationship between the concentration of fluoride in dental plaque, measured with the ion-selective fluoride electrode, and the condition of periondontal tissues was established.

Fluoride 1983; 16(1):11-19

Measurement of spinal canal body ratio in fluorotic spine

Kapila AK, Kaur RP, Jolly SS

Dept. of Radiology and Medicine, Government Medical College, Patiala, India

Fluoride 1983; 16(1):20-23

In heavy tea and coffee drinkers "nutritional status" of fluoride in relation to that of other mineral elements

J Skorkowska-Zieleniewska

National Research Institute of Mother and Child, Department of Nutrition, Warsaw, Poland

Summary: Fluoride "nutritional status" or loading was determined by urine test in heavy drinkers of tea and coffee. The level of soluble fluoride was analysed simultaneously in the brews of teas and coffees. These investigations suggest that intake of tea and coffee which contain large amounts of fluoride can, in certain cases, represent a threat to health.

Fluoride 1983; 16(1):23-33

Fluoride ingestion during pregnancy and lactation: morphological effects on maternal rat bone

Ream LJ, Pendergrass PB, Scott JN

Dept. of Anatomy, Wright State University, School of Medicine, Dayton, Ohio

Summary: Anorganic preparations of femurs from female rats, given 150 ppm fluoride in the drinking water for ten weeks prior to and during one subsequent pregnancy and lactation period, were examined by SEM and compared to control rats. The major difference seen was a marked increase in endosteal resorption. Presumably a decreased serum calcium concentration, caused by bone fluoride deposition along with a high demand on calcium under the influence of lactation, resulted in increased bone mineral mobilization from the endosteal surface.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6138892&dopt=Abstract
Virchows Arch B Cell Pathol Incl Mol Pathol 1983;44(1):35-44

Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat.

Ream JL, Hull DL, Scott JN, Pendergrass PB.

Female rats were given 150 ppm fluoride in the drinking water during three successive pregnancy and lactation periods; the femoral diaphyses were then examined for morphological alterations by light and scanning electron microscopy to determine the influence of fluoride ingestion during multiple pregnancies and lactations. The periosteal surface was dominated by areas of woven bone formation with some prolonged resting areas around osteocyte lacunae. The endosteal surface consisted mainly of areas of active bone resorption with some areas of bone formation. The interior of the cortex was characterized by numerous resorption cavities and remodeling in secondary Haversian systems. Fluoride, by the nature of its incorporation into bone crystals and by its direct cytotoxic effect on bone resorbing cells, reduces the availability of calcium from bone. It appears that fluoride ingestion during lactation created a heightened state of calcium homeostatic stress. As a result, bone mineral was mobilized by resorption of the endosteal surface and by cavitation of the interior of the cortex. Secondary hyperparathyroidism is thought to play an integral part in an attempt to maintain calcium homeostasis.

PMID: 6138892 [PubMed - indexed for MEDLINE]

Fluoride 1983; 16(1):33-37
Antidotes in experimental fluorosis on pigs morphological studies

W Seffner and W Teubener

Summary: In pigs fed 5 mg/kg NaF daily for 1 year, cortices of long bones became thicker. On the other hand, in cancellous bone osteopenia resulted. Simultaneous application of high doses of Borax reduced NaF effect on bone cortices, the addition of Mg metasilicate to a lesser extent. Mg oxide caused no such reduction. The parathyroid showed increased activity morphologically following high dose NaF treatment for 4 months.

Fluoride 1983; 16(1):43-47
Fluoride in the groundwater of selected localities in the District of Cottbus [Germany]

KH Miller

Bezirkshygieneinspektion and Institut Cottbus, Germany

Summary: In a survey of fluoride content of groundwater deposits in the Cottbus district, areas were selected with respect to emission loading by brown coal power plants. From the typical hydrogeological formation of a glacial scene, the natural fluoride content in the groundwater level as well as the anthropogenic influences on the fluoride level is taken into consideration. In spite of considerable amounts of fluoride in the environment of the Cottbus district, the average fluoride content in the groundwater-bearing formation is actually relatively low.

Fluoride 1983; 16(1):48-51
Levels of muscle and liver tissue enzymes in Channa punctatus bloch exposed to NaF

Chitra T *, Reddy MM **, Rao JVR **

*Dept. of Zoology, Univ. College for Women
** Dept. of Zoology, Univ. College for Science, Hyderabad, India

Summary: The effect of NaF (10 ppm, LC50) on the muscle and liver tissue enzymes of Channa punctatus (Bloch) was studied at room temperature: 30.22+-0.54¼ C. and at 15¼ C.

Liver GDH and LDH decreased at both termperatures. Inceased activity of AchE, GOT ad GPT in both liver and muscle homogenates were significant. The results are discussed in light of substrate concentrations and metabolic activity.

Fluoride 1983; 16(1):51-54
Comparison of methods used to estimate F in plants

Z Machoy and D Samujlo

Dept. of Biochemistry, Pomeranian Med. Academy, Szczecin, Poland

Summary: The aim of this paper is to evaluate some selected methods being employed to fix fluoride in biological material.

Fluoride 1983; 16(1):54-60
Pharmacokinetic investigations after application of sodium fluoride to chronically exposed persons

Heidelmann G, Klinger J, Schmidt CW

Medical Clinic of the Academy of Medicine, Dresden, and the Internal Dept. of General District Hospital, Heidenau, Germany

Summary: Coated and uncoated sodium fluoride tablets were given in single doses to normal subjects and to those exposed to fluoride for prolonged periods. Twenty-four plasma profiles and 4-day urinary recovery rates were determined by means of a fluorine sensitive electrode. Significant differences were observed between the various preparations and the two gorups of persons. For balance studies, the combination of plasma and urinary fluoride assays are the most useful.

Fluoride 1983; 16(1):60-63
Ionic variations in tissues of Channa punctatus Bloch on exposure to NaF

Chitra T *, Reddy MM **, Rao JVR **

*Dept. of Zoology, Univ. College for Women
** Dept. of Zoology, Univ. College for Science, Hyderabad, India

Summary: Channa Punctatus (Bloch) exhibited the following physiological adjustment by altering its ionic content when treated with 10 ppm sodium fluoride (LC50) at room temperature 30.22+-54¼ C. and at 15¼ C.
1) Increased metabolis rate,
2) Onset of polyuria,
3) A decrease in the potassium level indicating that the cell integrity is under stress,
4) A marked variation in the ionic content which alo suggests kidney dysfunction.

Fluoride 1983; 16(2):72-82
Subacute fluorosis due to airborne fluoride

GL Waldbott

Summary: Three additional cases are described in which prolonged intake of airborne fluoride induced a chronic illness without the skeletal changes which are characteristic of skeletal fluorosis. In one patient, inhalation of sodium fluoride as a fungicide used for preservation of old records, was responsible; in the two others, handling drums of hydrofluosilicic acid from which fumes escaped and leaking containers of uranium fluoride, respectively. Except for the respiratory problems, the multi-symptomatic clinical picture, due to airborne fluoride, is identical with the preskeletal phase of chronic fluoride intoxication.

Fluoride 1983; 16(2):83-90
Neighborhood fluorosis with skeletal manifestations

CW Schmidt

Department of Internal Medicine, General District Hospital, Heidenau, Germany

Summary: Forty-four persons (about 1% of the population) of a small Saxon town showed x-ray evidence of skeletal fluorosis. Three fluoride-emitting factories which produce hydrofluoric acid, aluminum and graphite are located in this town. The affected persons, although exposed for decades to these emittants, have had no occupational contact with fluoride. Atmospheric floride emissions have been high and fluoride levels in water due to industrial wastes have increased. The subjects have suffered only minor complaints. Their life span is normal. Renal fluoride excretion had increased and, in several persons, bone ash upon analysis showed high fluoride levels. For many years cattle fluorosis, dust damage to plants and dental fluorosis of children was not uncommon in the town. A change in the municipal water system and better technological conditions in industry has led to improved sanitation and hygiene in the area.

Fluoride 1983; 16(2):90-100
Clinical radiological observations among workers of fluoride processing industry

Desai VK, Bhavsar BS, Mehta NR, Krishnamachari AVR *

Government Medical College, Surat, Gujarat and *National Institute of Nutrition, Hyderabad, India

Summary: A fluorspar processing facility which began operations in 1965 producing freezing gas, HF acid, cryolite, NaF, etc., is situated on the West Coast of India, North of Bombay. Four hundred-thirty eight male workers, the majority of whom were employed for more than 9 years without interdepartmental rotation, were interrogated and examined clinically. Two hundred-twenty six random urine samples were analyzed. One hundred-six x-rays (rt., forearm A.P. view) were taken. The overall mean urinary fluoride level was 1.96 ppm. In 11.9% the urinary fluoride level was higher than 4.5 ppm. Although clinical signs suggestive of fluorosis were absent, 34.0% of the workers had complaints. Dental and radiological changes suggestive of fluorosis were present in 9.6% and 21.8% workers respectively. The overall mean urinary value +- 2SE was used to categorize the department according to the degree of exposure risk. The mean urinary fluoride level and complaints were significantly higher whereas the dental and radiological changes were not higher in the high risk groups than in the low risk. Urinary complaints, dental and radiological changes in workers with more than 9 years employment were not higher than in those with less than 9 years employment. In workers of the lower socio-economic group, the mean urinary fluoride level and complaints were significantly higher than in the higher socio-economic group. Under prevailing conditions in the facory, the degree of exposure seems to act independently of duration of exposure and socio-economic status.

Fluoride 1983; 16(2):101-105
Enamel fluorosis in human temporary and permanent teeth from a high fluoride area near Dresden

MEW Pilz

Department of Conservative Dentistry and Dentistry for Children, Medical Academy, Dresden, Germany

Fluoride 1983; 16(2):106-111
Experimental fluorosis in rats: NaF induced changes of bone and bone marrow

M Bely

National Institute of Rheumatology, Budapest, Hungary

Summary: According to recent studies, excess fluoride intake can cause both osteosclerosis and osteoporosis. The effect of fluoride can be influenced by several factors. In our experiments the aim was to demonstrate the alterations in bone and bone marrow caused by sodium fluoride, and to define the realtion beteen the bonelesion and fluoride dosage.

Of 20 white female rats, body weight 200 gr., 10 were administered 0.5 mg NaF, the other 10, 5 mg intraperitoneally for two months. NaF-induced bone changes were analyzed on ribs, vertebrae and femur. The decalcinated specimens were fixed in 8% neutral formalin, imbedded in paraffin, serially sectioned and stained with HE, or investigated by polarization optic methods. Bone and bone marrow alterations were evaluated by the morphometric method.

Fluoride 1983; 16(2):111-117
Production of fluoroacetate by callus tissue from leaves of Acacia georginae

Bennett LW, Miller GW, Yu MN*, Lynn RI

Dept. of Biology, Utah State Uiversity, Logan. *Sabbatical at Utah State University; Huxley College, Western Washingon University, Bellingham

Summary: Callus cultures of Acacia georginae were initiated from leaf discs from young leaves. Growth of callus was slow but predicatable with tissue volumes up to 2.2c3 being formed. Fluoride concentrations up to 80 ppm in the medium produced no adverse effect on callus growth. Reversible growth inhibittion occurred at 160 ppm, whereas apparent death occurred at higher concentrations. Fluoroacetate was detected by gas chromatography in the callus treated with 40, 80, and 160 ppm fluoride.

Fluoride 1983; 16(2):117-128
Effect of fluoroacetate on glucose synthesis in rat liver

Bobyleva-Guarriero V, Dina R, Lauriola P, Masini A

Institute of General Pathology, University of Modena, Italy

Fluoride 1983; 16(3):139-145
Gilbert's disease and fluoride intake

John Lee

Summary: Gilbert's disease, a benign constitutional liver disorder, results in mild unconjugated hyperbilirubinemia due probably to a reduction in hepatocyte glucuronyl transferase activity or possibly to deficient hepatocyte uptake of unconjugated bilirubin. Six such patients found in typical family practices in two fluoridated communities exhibited a return toward normal of their elevated plasma bilirubin levels (2-3 mg/dL to 0.9-1.2 mg/dL) when they switched from fluoridated to unfluoridated water. One patient was observed through three alternating periods of fluoridated and unfluoridated water with consistent results. The pathogenesis of this disease, which involves the unexpetedly strong hydrogen bond found in amide-fluoride systems, is discussed. The author concludes that, in Gilbert's disease, activity of glucuronyl transferase is further inhibited.

Fluoride 1983; 16(3):145-151
Interaction of floroacetamide with rat liver glutathione S-transferases: evidence for a detoxication role by defluorination

PJ Dierickx and JO De Beer

Instituut voor Hygiene en Eidemiologie, Brussels, Belgium

Fluoride 1983; 16(3):152-161
Fluoride-induced secretion from human blood platelets

EH Murer and JL Daniel

Temple University, School of Medicine, Philadelphia, Pennsylvania

Summary: Sodium fluoride induces a wide spectrum of cell activation. Secretion from human platelets has been most thoroughly studied. The duration of secretion is greatly shortened when pH is lowered and the needed concentration is decreased. Maximal effect is found at pH 5.3 suggesting that fluoride is transported into the platelet before secretion begins. Direct evidence for accumulation of fluoride prior to secretin is presented using a fluoride-sensitive electrode. Striking ultrastructural changes accompany fluoride activation: at pH 7.4 centralization of granules is followed by appearance of swollen vacuoles; at pH 5.3 electron-dense material is centralized. W/hen platelets are prelabeled with 32p, and then treated with fluoride, phosphorylation of the 47,000 dalton protein band precedes secretion, while labeling of phosphatidic acid accompanies secretion. Fluorescence of chlortetracycline-treated platelets decreases in response to fluoride, suggesting that calcium moves from a non-polar storage site to the platelet cytoplasm. Fluoride-induced platelet secretion is proposed as a useful model to study the different steps in cell activation, since it bypasses activation via external receptors.

Fluoride 1983; 16(3):162-169
Comparative study of fluoride elimination from guinea pig bone after long and short-term exposure to hydrogen fluoride

Rioufol C, Bourbon P, Vrancken L

Faculte de Pharmacie, Laboratoire Toxicologie, Toulouse, France

Summary: The patterns of fixation and elimination of hydrofluoric acid were studied in guinea pig bone during long and short-term exposure to HF. The results showed the presence of two compartments in the bone: that of easily exchangeable fluoride and that of more tightly bound fluoride.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6837327&dopt=Abstract
Acta Pharmacol Toxicol (Copenh) 1983 Jan;52(1):8-11

The effects of fluoride on cell growth of two human cell lines and on DNA and protein synthesis in HeLa cells.

Imai T, Niwa M, Ueda M.

The effect of sodium fluoride on the growth of two continuous human cell lines, i.e. HeLa cells and human conjunctiva clone 1-5C-4 cells, was studied. The growth of HeLa cells and clone 1-5C-4 cells was arrested nearly completely by the addition of 0.95 and 1,90 mM of sodium fluoride, respectively. DNA synthesis in HeLa cells, determined by incorporation of 3H-thymidine, was not affected appreciably for the first 24-hr period after the addition of sodium fluoride. Markedly reduced incorporation, however, occurred during the next 24-hr period. Thus, there was a discrepancy between the immediate cessation of cell division and the delayed suppression of DNA synthesis. On the other hand, a suppressive effect of sodium fluoride on protein synthesis determined by 14C-leucine incorporation was evident already during the first 24-hr period. The results indicate that the inhibition of protein synthesis is the main cause of growth inhibition.

PMID: 6837327 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6304937&dopt=Abstract
Toxicol Eur Res 1983 Jan;5(1):31-5

[Action of F- on liver metabolism of dimethylnitrosamine and benzo(a)pyrene in the rat]

[Article in French]

Do Phuoc H, Bompart G, Bourbon P, Bouteille L.

The authors carried out this study according to three parameters (dose, level, age of the rats and way of administration) on the action of fluor study in liver metabolism of dimethylnitrosamine and benzo(a)pyrene. The results showed that, in parallel with the increase of the dose level, at certain concentrations, it occurs generally an induction of dimethylnitrosamine-demethylase and a decrease in the amount of cytochrome P450 either by intraperitoneal injection, by ingestion or by inhalation. On the other hand, fluoride does not affect benzo(a)pyrene metabolism. Moreover, inhalation of FH looks the most suitable for this study. It allows to keep a relatively constant rate of F' in the blood and bring about more important changes in the metabolism of dimethylnitrosamine (30 to 70% induction) and in the amount of cytochrome P450 (10 to 40% decrease), as compared to the controls. The results suggest that, in the conditions of our experiments, fluoride would exert an favourable effect on the carcinogenic power of dimethylnitrosamine without affecting benzo(a)pyrene one.

PMID: 6304937 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6623079&dopt=Abstract
Science 1983 Oct 21;222(4621):330-2

Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells.

Farley JR, Wergedal JE, Baylink DJ.

Fluoride is one of the most potent but least well understood stimulators of bone formation in vivo. Bone formation was shown to arise from direct effects on bone cells. Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increased bone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.

PMID: 6623079 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6876776&dopt=Abstract
J Sci Food Agric 1983 May;34(5):523-8

No Abstract available

Dietary intake of fluoride in the United Kingdom and fluoride content of some foodstuffs.

Walters CB, Sherlock JC, Evans WH, Read JI.

PMID: 6876776 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6651785&dopt=Abstract
Biochem Med 1983 Oct;30(2):146-56

Effect of fluoride, silicon, and magnesium on the mineralizing capacity of an inorganic medium and stone formers urine tested by a modified in vitro method.

Anasuya A, Narasinga Rao BS.

An in vitro mineralizing system using bovine achilles tendon developed by Thomas and Tomita (3) was modified to enable quantitative evaluation of mineralization. Using this modified method, the potential effect of various ions on the rate of calcium uptake from inorganic mineralization medium was measured. Of the elements tested, only silicon and fluoride accelerated calcium uptake, whereas magnesium had an inhibitory effect. The simultaneous presence of silicon and fluoride in the medium had a synergistic action on calcium uptake. Urine of stone formers showed high propensity to mineralize tendon collagen, but not the urine of non-stone formers. Total content, and concentration of silicon in urine of stone formers was significantly higher than in normal urine. Addition of silicon to non-stone formers urine enhanced its capacity to mineralize collagen in vitro. These results strongly suggest the possible involvement of silicon and fluoride in the genesis of urinary calculi in man.

PMID: 6651785 [PubMed - indexed for MEDLINE]

Fluoride 1983; 16(3):169-174
Scanning electron microscopy of the rat femur after fluorine ingestion

LJ Ream

Dept. of Anatomy, Wright State University, School of Medicine, Dayton, Ohio

Summary: Anorganic preparations of femurs from rats given 150 ppm fluoride in the drinking water for 10 weeks reveal an increase in periosteal matrix and woven bone formation with a concomitant decrease in endosteal resorptive activity. However, resorption of metaphyseal trabeculae is increased coupled with an inhibition of calcification in the epiphyseal plate.

Fluoride 1983; 16(3):175-181
Effects of airborne fluoride on the fluoride content of rice and vegetables

Sakurai S, Itai K, Tsunoda H

Dept. of Hygiene and Public Health, Iwate Med. Univ., Moriaka, Japan

Summary: The thee most important source of fluoride intake are water, air and food. Since currently fluoridation is not being practiced in Japan, fluoride is consumed mainly from food. Because the staple food in Japan is rice, the present study was undertaken to determine the fluoride content in rice and vegetables from a control area free of sources of fluoride emission and from exposed areas near factories emitting fluoride into the atmosphere. Normal values of the fluoride content in rice ranged from 0.5 to 1.5 ppm, those in green vegetables from 1.0 to 1.5 ppm. The daily fluoride intake from food by Japanese adults is estimated at 1.1 - 1.3 mg.

Assuming that a person ingests polished rice, the fluoride content of which is 19 ppm in the environs of a ceramic factory, intake of fluoride from rice alone is estimated to be 0.6 - 1.0 mg higher than normal.

Fluoride 1983; 16(3):181-186
Fluoride as an activator of enzymatic systems

LS Strochkova and AA Zhavoronkov

Institute of Human Morphology, Moscow, USSR

Summary: The present report provides a brief review of the data on fluoride activation of some enzymatic systems in vivo and in vitro.

Fluoride 1983; 16(4):198-208
Fluorosis and finger ball dermatoglyphics: a comparative study

Batish KL*, Sidhu SS*, Makhni SS*, Batish MK **, Bhatnagar DP ***

Dept. of Anatomy*, Dept. of Pediatrics** of the Government Medical College and Dept. of Human Biology***, Punjabi University, Patiala, India

Fluoride 1983; 16(4):209-213
Light microscopy and scanning electron microscopy of bony tissue in foodborne endemic skeletal fluorosis

Zhan Chongwan, Huo Daijei, and Wang Enshou

Guiyang Medical College, Guizhou, People's Republic of China

Summary: Two cases of foodborne endemic skeletal fluorosis with blockage of the vertebral canal and compression of the spinal cord were subjeced to laminectomy. The vertebral laminae with their neighboring osteophytes, which had been removed, were studied both under light microscopy and scanning electron microscopy.

The diseased bony samples showed active new bone formation. The collagenous fibers had become tortuous, swollen, irregularly oriented, and impregnated with mineral salts. Mineralization of collagenous fibers is believed to be an intermediate stage in the process of new bone formation.

Fluoride 1983; 16(4):214-219
Serum biochemical effects of fluoride in sheep of the Darmous area

Kessabi M, Boudarine B, Braun JP, Lamnaouer D

Laboratoire de Toxicologie, Institut Agronomique et Veterinaire Hassan II, Rabat-Agdal, Maroc and Laboratoire de Biochimie, Ecole National Veterinaire, Toulouse, France

Summary: In 100 sheep in the Darmous (endemic fluorosis) area of Morocco, bone fluoride was about 5 times higher than in controls. Increases of serum potassium, urea creatinine, alkaline phosphatase and sorbitol dehydrogenase were significant whereas serum calcium, magnesium, glucose, cholesterol, total proteins and albumin were decreased. Such disturbances focus attention towards bone, kidneys and liver in the management of sheep herds in fluorosis zones.

Fluoride 1983; 16(4):220-229
Effect of simultaneous action of sulfur dioxide and hydrogen fluoride on stomatal movement in Zea mays and Pelargonim hortorim

Bonte J, Bonte C, de Cormis L

Institut National de la Recherche Agronomique, Laboratoire d'etude de la Pollution Atmospherique, France

Summary: Hydrogen fluoride at concentrations which occur in industrial areas does not modify the degree of stomatal opening and does not affect normal stomatal movement. A study of the simultaneous action of sulfur dioxide and hydrogen fluoride has show that the presence of hydrogen fluoride does not influence movements brought about by sulfur dioxide. The consequences of these observations are discussed in this report.

Fluoride 1983; 16(4):229-234
F concentration in the air of various communities in Japan

Itai K, Sakurai S, Tsunoda H

Dept. of Hygiene and Public Health, School of Medicine, Iwate Medical University, Morioka, Japan

Summary: Atmospheric fluoride concentrations were determined separately for gaseous, soluble and insolube particulate fluorides. In cities with no major industrial sources of fluoride emission atmospheric fluoride levels were mostly below 0.1 ugF/m3. More than 80% of the total fluorides were gaseous.

Ambient air fluoride concentrations in areas with major industrial sources of fluoride emission were highest near aluminum refineries; second highest near brick, tile and pottery factories. About 80% of the total fluorides near brick, tile and pottery factories were gaseous, whereas only 40-50% near aluminum refineries, phosphate fertilizer factories and iron and steel mills were gaseous.

Fluoride 1983; 16(4):235-243
Effects of fluoride pollution on corn plants through phosphatic fertilizer dust fallout

Seth PC, Sahu S, Pandey GS

Dept. of Chemistry, Government College of English and Tech, Raipur, India

Summary: The effecs of particulate fallout from a phosphatic fertilizer factory on corn plants (Zea mays L) have been studied. The progressive effecs of the fallout on the character of the soil, and the morphological characteristics, percentages of nitrogen, phosphorus, potassium, calcium and fluoride in leaves, shoots and roots of the polluted corn plants (Zea mays L) at various stages of their growth have been observed. Changes in grain-characeristics in the polluted plants have also been studied. Definite conclusions with regard to overall pollution effecs of the particulate mater on corn plants have been drawn.

Fluoride 1983; 16(4):243-247
Effect of NaF and mercuric chloride on the unit oxygen consumption of Channa punctatus (Bloch)

Chitra T, Parwathy N, Rao JVR

Dept. of Zoology, University College for Women and University College for Science, Osmania University, Hyderabad, India

Fluoride 1983; 16(4):247-251
Fluoride retention and leach possibilities in Argentine salt-affected soils

Lavado RS, Reinaudi NB, Parodi AA

CISAUA, La Plata, Argentina

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6631559&dopt=Abstract
J Occup Med 1983 Oct;25(10):745-8

The relationship between plasma fluoride, urinary excretion rate and urine fluoride concentration in man.

Ekstrand J, Ehrnebo M.

The fluoride concentration in urine is commonly used for monitoring fluoride exposure, e.g., in aluminium plants. Hitherto this parameter does not seem to have been related to the actual fluoride concentration in plasma following fluoride exposure. In the present study the fluoride concentration in urine, the urinary excretion rate of fluoride and the fluoride concentration in plasma have been studied in five volunteers after intake of 10 mg of fluoride in the form of sodium fluoride (NaF) tablets. In pharmacokinetic analyses of the data calculation of the half-life of fluoride from plasma data and from the urinary excretion rate yielded almost identical results; 5.78 hours (plasma) and 5.11 hours (urine). It was found that plasma fluoride levels were correlated with the fluoride concentration in urine (r = .7532; n = 70), but even more with the urinary excretion rate of fluoride (r = .9651; n = 63). The data suggest that plasma fluoride levels or urinary excretion rates of fluoride may give a more correct picture of occupational fluoride exposure than fluoride concentrations in urine.

PMID: 6631559 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6139128&dopt=Abstract

Biokhimiia 1983 Oct;48(10):1643-53
[Two-stage mechanism of the fluoride inhibition of inorganic pyrophosphatase using the fluoride ion]

[Article in Russian]

Smirnova IN, Baikov AA.

Some kinetic and spectral approaches have been used to study the interactions in the enzyme-Mg2+-F--pyrophosphate (or imidodiphosphate, a non-hydrolyzeable pyrophosphate analog) system underlying the mechanism of yeast inorganic pyrophosphatase inhibition by fluoride. The continuous curves of the enzymatic reaction were obtained with an automatic phosphate analyzer operating on the time scale of seconds. Increasing concentrations of NaF caused an increase in the inactivation rate constant to a constant level of 5.3 min-1 for PPi (pH 6.2-7.2) and 3.9 min-1 for imidodiphosphate, (pH 7.2). At a saturating fluoride concentration, the initial rate of PPi hydrolysis dropped to 10%. NaF and imidodiphosphate changed the protein spectrum at 270-310 nm and strengthened the binding of each other to the protein. The binding of F- required a Mg2+-binding site with Kd = 0.15 mM being filled in. The free enzyme and its Ca2+ complex did not bind F-. The experimental results indicate that pyrophosphatase inhibition by fluoride occurs in two steps. The inhibitor adds first to the Mg2+ ion on the enzyme in a readily reversible reaction causing a 90% decrease of the catalytic activity. Thereafter, a slow isomerization of the enzymesubstrate complex takes place, resulting in a complete loss of activity.

PMID: 6139128 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6846062&dopt=Abstract
Acta Med Scand 1983;213(3):171-6

Risk of myocardial infarction in Finnish men in relation to fluoride, magnesium and calcium concentration in drinking water.

Luoma H, Aromaa A, Helminen S, Murtomaa H, Kiviluoto L, Punsar S, Knekt P.

To study the influence of drinking water composition on the risk of myocardial infarction, the following study was conducted: The cases (C), men 30-64 years of age, had been discharged with a first acute myocardial infarction (AMI) from Kotka Central Hospital. The hospital controls (HC), matched for age and type of community, were selected for each case among surgical patients. Population controls (PC), matched for age and municipality, were drawn for each case from the population register. Subjects submitted a sample of their drinking water and a filled-in questionnaire. After exclusions, a series of 50 C-HC and 50 C-PC pairs was finally constructed. The point estimate of relative risk (RR) for the association between low F (less than or equal to 0.1 ppm) and increased risk of AMI was 3.0 in the C-HC series. In the C-PC comparison, RR was 4.4 RR for low Mg (less than or equal to 1.2 ppm) was 2.0 in the C-HC comparison and 4.7 in the C-PC comparison. The results are consistent with the hypothesis that both a low F and a low Mg intake are conducive to atherosclerosis leading to AMI.

PMID: 6846062 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6685423&dopt=Abstract
Acta Paediatr Scand 1983 Sep;72(5):699-701

Fluoride in human milk.

Spak CJ, Hardell LI, De Chateau P.

Reported contents of fluoride (F) in human milk vary considerably. The aim of this study was to determine the F content in human milk under different levels of F intake using a siliconfacilitated microdiffusion technique, which had a good accuracy and precision. The mean F concentration of colostrum from mothers in a 1.0 ppm and a 0.2 ppm F area was 0.36 +/- 0.02 mumol/l (+/- SEM) and 0.28 +/- 0.02 mumol/l, respectively. The mean F concentration of mature milk from a 1.0 ppm F area was 0.37 +/- 0.04 mumol/l. Within the 1.0 ppm F area, the intra- and interindividual differences in F concentration were very small. No statistically significant difference in milk F concentration between the two areas was found. Consequently, breastfed infants living in a 1 ppm or a 0.2 ppm F area will have an approximately equal F intake of 5-10 micrograms per day, in spite of great differences in F intake among the nursing mothers.

PMID: 6685423 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6311315&dopt=Abstract
Br Med J (Clin Res Ed) 1983 Sep 10;287(6394):723-5

Bilateral fractures of femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis.

Gerster JC, Charhon SA, Jaeger P, Boivin G, Briancon D, Rostan A, Baud CA, Meunier PJ.

Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis. They had been taking sodium fluoride (40-60 mg/day) for 11 and 21 months, respectively. Histological examination of a specimen of the bone showed severe fluorosis in the first case, and quantitative analysis of bone showed osteomalacia and skeletal fluorosis in the other case. These abnormalities were considered to be the consequence of excessive retention of fluoride due to renal insufficiency. As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure.

PMID: 6311315 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6410001&dopt=Abstract
J Neurochem 1983 Sep;41(3):882-5

Adenylate cyclase activity in the superior cervical ganglion of the rat.

Cahill AL, Perlman RL.

Adenylate cyclase activity in cell-free homogenates of the rat superior cervical ganglion (SCG) was assayed under a variety of experimental conditions. Adenylate cyclase activity was decreased by approximately one-half when 1 mM EGTA was included in the homogenization buffer and assay mixture, indicating the presence of a Ca2+-sensitive adenylate cyclase in the ganglion. In the presence of EGTA, basal adenylate cyclase activity in homogenates of the SCG was 12.9 +/- 0.6 pmol cyclic AMP/ganglion/10 min. Enzyme activity was stimulated three- to fourfold by 10 mM NaF or 10 mM MnCl2. Both GTP and its nonhydrolyzable analog guanylylimidodiphosphate (GppNHp) stimulated adenylate cyclase in a concentration-dependent manner over the range of 0.1-10.0 microM. Stimulation by GppNHp was five to six times greater than that produced by GTP at all concentrations tested. Decentralization of the ganglion had no effect on basal or stimulated adenylate cyclase activity. Receptor-linked stimulation of adenylate cyclase was not obtained with any of the following: isoproterenol, epinephrine, histamine, dopamine, prostaglandin E2, or vasoactive intestinal peptide. Thus the receptor-linked regulation of adenylate cyclase activity appears to be lost in homogenates of the ganglion.

PMID: 6410001 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6359948&dopt=Abstract
Anaesth Intensive Care 1983 Nov;11(4):292-320

Anaesthesia and the kidney.

Cousins MJ, Skowronski G, Plummer JL.

Applied anatomy and physiology of the kidney are briefly reviewed. This includes an account of renal blood flow, glomerular filtration rate, juxtaglomerular apparatus, renal autoregulation and intra-renal blood flow distribution, tubular transport mechanisms, solute handling in proximal tubule, function of loop of Henle and distal tubule system. This section concludes with a summary of changes in tubule fluid along the length of the nephron. Acute effects of anaesthesia are reviewed in detail. Indirect effects include those on circulatory and sympathetic nervous systems, autoregulation, endocrine systems such as those involving anti-diuretic hormone, adrenaline and noradrenaline, renin-angiotensin and aldosterone. Direct effects of anaesthesia on renal function have now been confirmed both in vitro and in vivo. Delayed direct nephrotoxicity of anaesthetics relates predominantly to methoxyflurane (MOF) and its metabolism to inorganic fluoride. Other factors are MOF dose, genetics, age, enzyme induction, obesity, other nephrotoxic drugs. Clinical implications are presented. Enflurane nephrotoxicity is rare but aetiologic factors are similar to the foregoing. Isoflurane and halothane are not nephrotoxic. A consideration of the influence of anaesthetic management on the incidence and severity of postoperative acute renal failure concludes the review.

Publication Types:

Review

PMID: 6359948 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6305366&dopt=Abstract
Biochem Pharmacol 1983 May 15;32(10):1627-34

Triphenyltin fluoride in vitro inhibition of rabbit platelet collagen-induced aggregation and ATP secretion and blockade of arachidonic acid mobilization from membrane phospholipids.

Manabe S, Wada O, Matsui H, Takada M, Kobayashi N, Maekawa T.

Recent studies have demonstrated that triphenyltin fluoride (TPTF) inhibits collagen-induced aggregation and ATP secretion of rabbit platelets in vivo [S. Manabe and O. Wada, J. Toxic. Sci. 6, 236 (1981)]. The aim of the present investigation was to test the effects in vitro of TPTF on platelet aggregation and to elucidate the mechanism of the inhibitory action by studying the release and metabolism of arachidonic acid and the cyclic AMP contents of rabbit platelets treated in vitro with TPTF. Although no inhibitory effect of TPTF was found on sodium arachidonate-induced platelet aggregation and ATP secretion, TPTF inhibited both reactions induced by collagen. Triphenylarsine and triphenylantimony did not inhibit, even at a concentration of 10(-3) M. The anti-aggregating concentration (IC50) of TPTF was 6.0 x 10(-6) M against collagen. TPTF had no inhibitory effect on the conversion of exogenous arachidonic acid to malondialdehyde (MDA) by platelets, while the collagen-induced production of arachidonate metabolites [MDA, 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B2] was remarkably inhibited by TPTF. Furthermore, TPTF apparently inhibited the collagen-induced release of arachidonic acid from platelets, although the formation of phosphatidic acid was not inhibited. Total cyclic AMP content after TPTF exposure was not changed significantly. These results indicate that TPTF inhibited the collagen-induced arachidonic acid release from platelet phospholipids, presumably by acting on phospholipase A2. Furthermore, it seems unlikely that the inhibition of arachidonic acid release by TPTF can be explained by the level of cyclic AMP in platelets.

PMID: 6305366 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6410022&dopt=Abstract
J Nutr 1983 Aug;113(8):1576-82

Glycosaminoglycan alterations in rat bone due to growth and fluorosis.

Prince CW, Navia JM.

Evidence in the literature has suggested that alterations in bone glycosaminoglycans (GAGs) are at least partially responsible for the defective calcification in skeletal fluorosis. The major objectives of this study were to quantitate the GAGs of bone from normal and fluorotic rats and to characterize the change in bone GAGs that occurred during maturation. Weanling male rats were fed a semipurified diet and deionized water with or without fluoride (125 ppm) for 1 or 2 months. Also, a control group of rats was pair-fed to the rats receiving fluoride. GAGs were isolated from dry, fat-free tibias and then quantitated by digestion with chondroitinases and chondrosulfatases. Chondroitin-4-sulfate (C4S) comprised 90% of the bone GAGs, while chondroitin-6-sulfate (C6S), dermatan sulfate (DS) and hyaluronic acid (HA) together comprised about 10% of the total bone GAGs. With increasing age, total GAGs, C4S and HA decreased in amount, but DS remained constant. Fluorotic bone (containing in excess of 5000 ppm of fluoride) had three times as much C6S and twice as much DS as bone from weight- and age-matched control rats. Thus, using a controlled experimental animal model, we have demonstrated that specific alterations of bone GAGs result from fluorosis independently of changes in body weight and age.

PMID: 6410022 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6641020&dopt=Abstract
Clin Exp Pharmacol Physiol 1983 Sep-Oct;10(5):615-9

Urinary excretion of glycosaminoglycans, hydroxyproline and hydroxylysine in rabbits after excessive ingestion of fluoride.

Jha M, Koacher J, Susheela AK.

Urinary levels of glycosaminoglycans (GAG) and hydroxyproline from normal and fluoride treated rabbits were estimated. The hydroxylysine content of serum and urine of rabbits after excessive ingestion of fluoride was also investigated. There was a progressive decrease in GAG content, reduction in hydroxylysine, whereas the hydroxyproline content was increased after fluoride ingestion. Enhanced hydroxyproline in urinary excretion is due to collagen breakdown after fluoride ingestion. The reduction in hydroxylysine content is due to reduced collagen cross-link formation. The report suggests the possibility of using the urinary levels of GAG or hydroxyproline or hydroxylysine as an index of fluoride intoxication.

PMID: 6641020 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6311563&dopt=Abstract
Eur J Clin Invest 1983 Aug;13(4):339-46

Differences in beta-adrenergic receptor density and adenylate cyclase activity between normal and leukaemic leukocytes.

Paietta E, Schwarzmeier JD.

An identical class of high-affinity binding sites for the 125I-labelled beta-adrenergic antagonist hydroxybenzylpindolol, was identified on intact human normal and leukaemic peripheral blood leukocytes. On normal unfractionated lymphocytes, polymorphonuclear leukocytes, and monocytes, receptor density did not differ significantly (1200-1400 receptors per cell; P greater than 0.3), but it was higher on B- than on T-lymphocytes (P less than 0.05). In leukaemia, monocytic blast cells expressed highest receptor numbers, whereas very low receptor density was seen on the pathologic B-cells from chronic lymphocytic leukaemia. Among normal leukocytes, adenylate cyclase activation by hormones (isoproterenol, prostaglandin E1, histamine) and sodium fluoride was strongest in plasma membranes from monocytes, but very weak in polymorphonuclear leukocytes either due to uncoupling of hormone receptors from adenylate cyclase or to low catalytic activity. In T-cells, enzyme activity was significantly lower than in B-cells. Loss of adenylate cyclase sensitivity to hormones and fluoride occurred in leukaemic cells from chronic and acute lymphocytic leukaemia.

PMID: 6311563 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6623890&dopt=Abstract
Vet Hum Toxicol 1983 Aug;25(4):253-4

Toxicosis in cattle from contaminated well water.

Hibbs CM, Thilsted JP.

PMID: 6623890 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6226972&dopt=Abstract
Presse Med 1983 Oct 15;12(36):2262

[Fluoride osteosis caused by chronic poisoning with Vichy Saint-Yorre water]

[Article in French]

Chambourlier P, Teissier M, Domange C, Amarger J, Vacher G.

Publication Types: Letter

PMID: 6226972 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6861996&dopt=Abstract
Farmakol Toksikol 1983 May-Jun;46(3):97-9

[Effect of chronic fluorine poisoning on oxidative processes in body tissues]

[Article in Russian]

Genkin AI, Glotov NA, Zhdakhina KS, Maevskii EI, Kolmogortseva VM.

PMID: 6861996 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6578726&dopt=Abstract
Arch Toxicol Suppl 1983;6:228-31

Fluoroacetamide poisoning in man: the role of ionized calcium.

Taitelman U, Roy A, Hoffer E.

Two cases are reported of severe acute fluoroacetamide poisoning in man, with successful treatment of the life-threatening cardiac arrhythmias by the administration of calcium chloride. The arrhythmias were preceded by prolongation of the QT interval in the ECG. Calcium chloride therapy restored to normal the markedly prolonged QT interval.

PMID: 6578726 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6676316&dopt=Abstract
Indian Pediatr 1983 Sep;20(9):637-42

Chronic ingestion of natural fluoride and endemic bladder stone disease.

Teotia M, Teotia SP, Singh DP, Singh CV.

PMID: 6676316 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6407795&dopt=Abstract
Clin Orthop 1983 Jul-Aug;(177):274-82

The microscopic morphology of fluoride-induced bone.

Vigorita VJ, Suda MK.

To characterize further the bone changes in osteoporotic patients treated by a combined calcium, vitamin D, and sodium fluoride therapy regimen, full-thickness transilial undecalcified bone biopsy specimens from ten postmenopausal white women treated for idiopathic osteoporosis for 18-24 months were compared with those from ten age-, sex-, and race-matched untreated control subjects using standard light microscopy and histomorphometry. Statistically significant bone changes in the treated group consisted of cortical and trabecular new bone formation juxtaposed on underlying normal lamellar bone (p less than 0.001). The new bone showed increased osteocytic cellularity (p less than 0.001), irregular arrangement of osteocytes (p less than 0.001), enlarged osteocyte lacunae (p less than 0.001), and periosteocytic hematoxylinophilic staining intensity (p less than 0.001). Increases were also noted in trabecular bone volume (p less than .025), trabecular osteoid surface (p less than 0.001), and trabecular osteoid volume (p less than 0.001). Osteoid calculations were significantly less than those in the clinical and chemical osteomalacia observed in the authors' laboratory (p less than 0.01). Osteoclastic resorptive activity was increased (p less than .001), but no evidence of hyperparathyroidism was noted. These histologic and histomorphometric changes indicate accretion of new bone but with distinctly abnormal matrix characteristics. These are changes considered characteristic of the treatment and are pathologic markers of fluoride-induced abnormal bone formation.

PMID: 6407795 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6313153&dopt=Abstract
Can J Biochem Cell Biol 1983 Jul;61(7):569-78

The interactive effects of fluoride and N-formyl-L-methionyl-L-leucyl-L-phenylalanine on superoxide production and cAMP levels in human neutrophils.

Wong K.

The kinetics of superoxide (O2-) production and intracellular cAMP levels were monitored in human neutrophils incubated in vitro with sodium fluoride and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). F- activation of both the O2- -generating system, NAD(P)H oxidase, and adenylate cyclase was characterized by a prolonged lag period of 8 to 10 min at 37 degrees C. Adenylate cyclase agonists or cAMP analogues which inhibited FMLP-induced O2- bursts did not affect O2- production of F- -activated cells. Prior treatment of cells with F- suppressed the short rapid burst elicited by FMLP but not the binding of the tripeptide. FMLP reciprocally decreased the lag period of the F- -induced burst by 40 to 50% and, in the case of cells incubated at temperatures below 37 degrees C, increased the rate of O2- production. A similar potentiating effect of FMLP on F- -induced elevation of intracellular cAMP levels was observed.

PMID: 6313153 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6682657&dopt=Abstract
Biochem Biophys Res Commun 1983 May 16;112(3):911-8

The dual effects of aluminum as activator and inhibitor of adenylate cyclase in the liver fluke Fasciola hepatica.

Mansour JM, Ehrlich A, Mansour TE.

The liver fluke, Fasciola hepatica, has a very active adenylate cyclase which can be stimulated by NaF or by serotonin and guanine nucleotides. Micromolar amounts of AlCl3 augment the activation by F-. In contrast, when the enzyme is activated with serotonin and guanine nucleotides, AlCl3 inhibits the activation. Aluminum also inhibits the activation by forskolin. Gallium mimics the effects of aluminum.

PMID: 6682657 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6858260&dopt=Abstract
Z Gesamte Hyg 1983 Feb;29(2):74-9

[Contribution to the occupational toxicologic problems of fluorine exposure at the place of work]

[Article in German]

Melson F.

PMID: 6858260 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6306967&dopt=Abstract
Acta Biochim Pol 1983;30(2):213-22

Peroxidative oxidation of halides catalysed by myeloperoxidase. Effect of fluoride on halide oxidation.

Zgliczynski JM, Stelmaszynska T, Olszowska E, Krawczyk A, Kwasnowska E, Wrobel JT.

It was found that all halides can compete with cyanide for binding with myeloperoxidase. The lower is the pH, the higher is the affinity of halides. The apparent dissociation constants (Kd) of myeloperoxidase-cyanide complex were determined in the presence of F-, Cl-, Br- and I- in the pH range of 4 to 7. In slightly acidic pH (4 - 6) fluoride and chloride exhibit a higher affinity towards the enzyme than bromide and iodide. Taking into account competition between cyanide and halides for binding with myeloperoxidase the dissociation constants of halide-myeloperoxidase complexes were calculated. All halides except fluoride can be oxidized by H2O2 in the presence of myeloperoxidase. However, since fluoride can bind with myeloperoxidase, it can competitively inhibit the oxidation of other halides. Fluoride was a competitive inhibitor with respect to other halides as well as to H2O2. Inhibition constants (Ki) for fluoride as a competitive inhibitor with respect to H2O2 increased from iodide oxidation through bromide to chloride oxidation.

PMID: 6306967 [PubMed - indexed for MEDLINE]

NOTE: AG Gilman, co-author of this report, shared the 1994 Nobel Prize for the discovery of "G-proteins and the role of these proteins in signal transduction in cells."
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6309844&dopt=Abstract

J Biol Chem 1983 Sep 25;258(18):11369-76

The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution of the activated 45,000-dalton (alpha) subunit.

Northup JK, Smigel MD, Sternweis PC, Gilman AG.

Activation of the stimulatory guanine nucleotide-binding regulatory component (G/F) of adenylate cyclase by guanine nucleotides or by Al3+, Mg2+, and F-stabilizes the protein to thermal denaturation or to inactivation by LiBr, guanidine HCl, or urea. Such activation allows the resolution of the active 45,000-Da alpha subunit from the 35,000-Da beta subunit by a high performance gel filtration procedure. Separation of the active alpha subunit has allowed definitive evaluation of the subunit dissociation model for the activation of G/F. The resolved alpha subunit is sufficient to reconstitute the adenylate cyclase activity of the cyc-S49 cell mutant. The alpha subunit alone is also sufficient to activate a preparation of the catalyst of adenylate cyclase that had been resolved from all other identified components of the enzyme system. The resolved alpha subunit displays hydrodynamic properties characteristic of activated G/F. The alpha subunit contains a high affinity guanine nucleotide-binding site. Activation of G/F by guanine nucleotides or by Al3+ + Mg2+ + F- allows resolution of the activated alpha subunit. Reversal of the activated state of the resolved alpha subunit occurs only slowly. Addition of beta subunit enhances the rate of deactivation. Deactivation of the activated alpha subunit by the beta subunit changes the S20,w for G/F activity from 2.0 to 4.0 (in Lubrol), consistent with a formation of the alpha X beta heterodimer. These data, taken in aggregate, constitute proof for the proposed mechanism of activation of G/F by non-hydrolyzable analogs of GTP and by Al3+, Mg2+, and F-. They are analogous to data obtained for transducin, the GTP-binding regulatory protein from vertebrate rod outer segment discs, and for the putative inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase (the substrate for islet-activating protein). The model provides several powerful tests for study of mechanisms of hormonal regulation of adenylate cyclase in membranes.

PMID: 6309844 [PubMed - indexed for MEDLINE]

NOTE: AG Gilman, co-author of this report, shared the 1994 Nobel Prize for the discovery of "G-proteins and the role of these proteins in signal transduction in cells."
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6309843&dopt=Abstract

J Biol Chem 1983 Sep 25;258(18):11361-8

The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution, activity, and properties of the 35,000-dalton (beta) subunit.

Northup JK, Sternweis PC, Gilman AG.

The stimulatory guanine nucleotide-binding regulatory component (G/F) of adenylate cyclase is activated by exposure to guanine nucleotide analogs or to Al3+ + F-. Activated G/F can reconstitute adenylate cyclase activity when mixed with the catalytic moiety of the enzyme system in the absence of an effective free concentration of stimulatory ligand. Activation is explained by dissociation of the alpha (45,000-Da) and beta (35,000-Da) subunits of G/F. The beta subunit of G/F facilitates reversal of the activated state of the regulatory protein. This phenomenon, which has been exploited as an assay for the resolved beta subunit, has the following properties.
1) Addition of the resolved beta subunit to fluoride-activated G/F increases the initial rate of deactivation from a t 1/2 of 10 min to less than 0.5 min.
2) The enhancement of the rate of deactivation is a saturable process with a K 1/2 value of 60 ng/ml (approximately 2 nM).
3) G/F does not display beta subunit activity unless the alpha subunit has been inactivated or the subunits have been resolved. beta Subunit activity is measurable in detergent extracts of rabbit liver membranes or plasma membranes from S49 cell clones. The activity in such extracts is similar to that found with purified G/F, in that incubation at 30 degrees C in the presence of Mg2+ is required for its expression. However, cyc-, UNC, and H21a (S49 cell mutants with deficient or altered G/F activity) have amounts of beta subunit activity similar to that found in wild type S49 cells. Furthermore, the amount of beta subunit activity exceeds by 5- to 10-fold the amount expected based on the quantity of G/F in wild type extracts. All of the beta subunit activity in detergent extracts of liver membranes can be purified as a 35,000-Da polypeptide that is indistinguishable from the beta subunit of G/F. The beta subunit activity in extracts of cyc- membranes is expressed after incubation with guanine nucleotide analogs, implying association of the beta subunit with a GTP-binding protein. By analysis of the chromatographic behavior of G/F and the recently identified 41,000/35,000-Da heterodimeric substrate for the islet-activating protein from Bordetella pertussis, we have identified the 41,000-Da subunit of the substrate for islet-activating protein as the GTP-binding protein with which the majority of the beta subunit activity associates. These data have direct bearing on the mechanisms of hormonal activation and inhibition of adenylate cyclase.

PMID: 6309843 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6860619&dopt=Abstract
Br J Nutr 1983 May;49(3):295-301

Dietary intake of fluoride ashed (total fluoride) v. unashed (inorganic fluoride) analysis of individual foods.

Taves DR.

Fluoride content in ninety-three individual food items from a hospital in a fluoridated area was determined by ashing (total fluoride) v. unashing (inorganic fluoride) analysis. No discrepancy between the two methods was found by food group but two dry cereals and black pepper did show significantly more fluoride after ashing. The reason for the unavailability before ashing was not determined. Daily fluoride intake was estimated at 1.783 mg which is midway between the 1.211 and 2.201 mg reported from studies in which composite diets were analysed. Daily intake from food at 0.4 mg was one-quarter of the daily total intake 1.8 mg; a ratio consistent with those previously reported in serum, urine and bone between residents from a non-fluoridated v. fluoridated community.

PMID: 6860619 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6312063&dopt=Abstract
J Toxicol Environ Health 1983 Apr-Jun;11(4-6):765-82

Cardiopulmonary response to sodium fluoride infusion in the dog.

Gaugl JF, Wooldridge B.

Because humans are occasionally acutely exposed to high levels of fluoride (F-), and cardiac and especially pulmonary tissue accumulate higher concentrations of F- than do the other soft tissues, the present study was undertaken to investigate the effects of acute exposure to toxic plasma levels of F- on cardiopulmonary hemodynamics. Anesthetized dogs were instrumented with right and left cardiac catheters to measure pulmonary arterial and wedge pressures, left ventricular and aortic pressures, left ventricular dP/dt, and cardiac output. An intravenous loading dose of NaF followed by a 3-h infusion produced a plasma F- level of 800 microM in the "low" group of 6 animals, and 1300 microM in the "high" group. The mean pulmonary arterial pressure peaked at 1 h, 83% above preinfusion values in the high group, while that of the low group attained the same level by the end of the infusion period. Impaired pulmonary gas exchange, as indicated by an increased alveolar-arterial PO2 gradient, occurred in half the animals, and an obvious hyperventilation was reflected in a decreased PCO2 value; there was no change in arterial pH, ECG T-wave peaking was common. The central venous pressure declined steadily, while there were no significant changes from controls in systemic arterial pressure, heart rate, cardiac output, or myocardial contractility (dP/dt). Thus, pulmonary hemodynamics and the systemic capacitance vessels are more affected by acute exposure to F- than is cardiac function.

PMID: 6312063 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6661583&dopt=Abstract

Bull Environ Contam Toxicol 1983 Dec;31(6):692-8

Acute and sublethal effects of 1080 on starlings.

Balcomb R, Bowen CA 2nd, Williamson HO.

PMID: 6661583 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6582956&dopt=Abstract
Josai Shika Daigaku Kiyo 1983;12(1):71-82

[An abstract of this report is available in Fluoride 1985; 18(4):228]

[An analysis of fluoride in rice]

[Article in Japanese]

Hara S.

PMID: 6582956 [PubMed - indexed for MEDLINE]

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