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PubMed1980

[Peripheral regulation of the adrenergic mediator process in the smooth muscles of the rat small intestine].

Under the effect of noradrenaline a physiologically active substance (A-factor) is released from smooth fibres of rat's intestine. A-factor enhances spontaneous activity of an isolated piece of rat's intestine. The A-factor is thermostable, its stimulating action is blocked neither with alpha- nor with beta-adrenolytics which indicates a non-catecholamine nature of this substance. Blocking of the intramural nervous system with novocain does not stop the release of the A-factor which shows that this system is not responsible for the A-factor release. Metabolic adrenoreceptors rather than the functional ones are responsible for the release of this substance. Experiments with metabolic poisons (2,4-dinitrophenol) and sodium fluoride have shown that the release of the A-factor is due to the effect of noradrenaline on glycolysis. The A-factor increases sensitivity of the intestine piece to noradrenaline. Participation of the A-factor in the regulation of the activity of smooth muscle adrenoreceptors of rat's intestine on the principle of positive feedback, is discussed.

Animals↗
PubMed1989

Fluoride and oral health: a story of achievements and challenges.

It's been nearly 45 years since Grand Rapids, MI, approved this country's first citywide fluoridation program. In that time the steady growth of evidence drawn from surveys and other research has yielded inarguable conclusions on fluoride's benefits to oral health. Today, it is one of the country's most heralded public health measures. By 1988, 41 of the 50 largest cities in the United States were served by fluoridated water systems. Yet in some communities the measure still draws fire. Antifluoridationists have charged, among other arguments, that fluoridation proponents are part of a Communist plot, aimed at poisoning the American people and taking over the government. Looking back over the past four decades, fluoride has had a role in a variety of arenas in American life: political, social, medical, and economic. This month's Emphasis takes a look at fluoride's heritage, and considers some of the most recent findings on its safety, benefits, and cost-effectiveness.

Dental Caries↗
PubMed1977

Failure to elicit conditioned taste aversion by severe poisoning.

In an attempt to assess the universal validity of the conditioned taste aversion (CTA) paradigm, various types of poisoning (UC) were associated with the gustatory CS. Water deprived rats were habituated for two days to the drinking box, where water was available for 15 min. On Day 3, access to the CS (0.1% saccharin 15 min) was followed after 30 min by a sublethal dose of the poison (0.15 M LiCl, 4% body weight; 0.1 M sodium malonate, 1% body weight; pyrrolopyrimidine drug BW 58-271, 15 mg/kg; sodium cyanide 4 mg/kg; sodium iodoacetate 40 mg/kg; sodium fluoride 30 mg/kg; gallamine triethiodide 40 mg/kg). Rats injected with the last drug were maintained under artificial respiration until muscular paralysis disappeared. After 4 days of recovery, water deprivation schedule was resumed on Days 8 and 9. During the retention test on Day 10 saccharin consumption dropped by 60% in the LiCl poisoned rats, but not CTA developed in animals poisoned by pyrrolopyrimidine, gallamine, malonate and cyanide. CTA of intermediate intensity was evoked by iodoacetate and fluoride. The absence of CTA was not due to the amnesic effect of poisoning, since LiCl administration to NaCN poisoned rats produced CTA of usual intensity. It is concluded that CTA is not related to the overall severity of poisoning but rather to the effect of the poison on specific interoceptors.

Animals↗
PubMed1994

A prodrug approach to increasing the oral potency of a phenolic drug. 1. Synthesis, characterization, and stability of an O-(imidomethyl) derivative of 17 beta-estradiol.

An O-(saccharinylmethyl) prodrug was synthesized to improve the poor oral potency of the phenolic drug 17 beta-estradiol. This O-(imidomethyl) type of prodrug was designed to undergo chemical hydrolysis and to be a poor substrate for enzymatic hydrolysis. At 37 degrees C, it was found to exhibit half-lives of about 13 min in 50% methanol:pH 7.0 (v/v) phosphate buffer, about 3 min in rat plasma, about 15 min in human plasma, and about 50 min in 20% rat liver homogenate. Introduction of the enzyme poison tetraethyl pyrophosphate or the protein denaturant sodium fluoride into rat plasma had no significant effect on the half-life. Thus, the observed increased rate of hydrolysis in biological media is not due to enzymatic catalysis but to a nonspecific solventlike effect. The fact that the rate of hydrolysis in the methanol:buffer exhibited a first-order dependence on the hydroxide ion concentration and that the rate of hydrolysis increased with increasing methanol concentrations up to 70% supported an SN2 mechanism of hydrolysis for the prodrug. These results suggest that an O-(imidomethyl) type prodrug is insensitive to enzymatic catalysis of hydrolysis yet may hydrolyze quickly enough to release 17 beta-estradiol faster than 17 beta-estradiol is conjugated and excreted.

Administration, Oral↗
PubMed1998

The biochemical toxicology of 1,3-difluoro-2-propanol, the major ingredient of the pesticide gliftor: the potential of 4-methylpyrazole as an antidote.

Administration to rats of 1,3-difluoro-2-propanol (100 mg kg-1 body weight), the major ingredient of the pesticide gliftor, resulted in accumulation of citrate in the kidney after a 3 hour lag phase. 1,3-Difluoro-2-propanol was found to be metabolized to 1,3-difluoroacetone and ultimately to the aconitate hydratase inhibitor (-) erythrofluorocitrate and free fluoride. The conversion of 1,3-difluoro-2-propanol to 1,3-difluoroacetone was found to be catalyzed by an NAD(+)-dependent alcohol dehydrogenase, while the defluorination was attributed to microsomal monooxygenase activity induced by phenobarbitone and inhibited by piperonyl butoxide. 4-Methylpyrazole was found to inhibit both of these processes in vitro and when administered (90 mg kg-1 body weight) to rats, 2 hours prior to 1,3-difluoro-2-propanol, eliminated signs of poisoning, prevented (-) erythrofluorocitrate synthesis, and markedly decreased citrate and fluoride accumulation in vivo. 4-Methylpyrazole also appeared to diminish (-) erythrofluorocitrate synthesis from fluoroacetate in vivo, and this was attributed to its capacity to inhibit malate dehydrogenase activity. The antidotal potential of 4-methylpyrazole and the potential for 1,3-difluoro-2-propanol to replace fluoroacetate (compound 1080) as a vertebrate pesticide is discussed.

Animals↗
PubMedDate not supplied

Fluoride accumulation and bone strength in wild black-crowned night-herons.

Fluoride was measured in femurs of black-crowned night-herons (Nycticorax nycticorax) living adjacent to a phosphate processing complex near Pocatello, Idaho. Fluoride (ash wt.) in femurs ranged from 540 micrograms/g to 11,000 micrograms/g and increased (P = 0.0001) with age, but with no difference (P = 0.80) between sexes. Adult males (greater than or equal to 4 years) contained 5,409 micrograms/g compared to 6,042 micrograms/g for adult females. The tibiotarsus (= tibiae in text) increased in diameter with age (P = 0.015) in this study; fluoride was nearly related (P = 0.065) to the increase. As the diameter increased with age, wall thickness decreased (P = 0.011) suggesting excessive internal bone resorption, but fluoride concentrations were not implicated in the relationship (p = 0.64). The apparent increase in diameter and decrease in wall thickness may have partially neutralized each other's effects on strength. Although significantly higher concentrations of fluoride were present in adults than in Third Year herons, no significant change in bone strength (maximum load or modulus of rupture) was detected between the two age classes, but three of the four comparisons showed adults with less strength (i.e., a hint of diminished strength with age). The tibiae of Hatch Year birds were significantly weaker than documented in older age classes, but incomplete growth was thought responsible. The strong relationship between age and fluoride concentrations reduced our ability to separate a "fluoride effect" from an "age effect." Other authors believed fluoride was responsible for an increase in bone diameter and the fluoride residues encountered in adults were within the range indicative of poisoning in cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2005

Effect of soman poisoning on populations of bone marrow and peripheral blood cells in mice.

According to recent reports, brain lesions resulting from ischemia, mechanical injury or neurodegenerative diseases can be partially treated using bone marrow-derived stromal cell (BMSC) engraftment approaches. Nevertheless, for brain lesions resulting from organophosphate poisoning, nerve agents such as soman (pinacolyl methylphosphono-fluoridate) could affect blood and bone marrow (BM) micro-environments, thus preventing efficient BMSC migration and engraftment. It is therefore necessary to verify the hematologic response to soman exposure. To assess this issue, the survival of BM cells, in particular hematopoietic progenitor and precursor cells (HPC), as well as distribution of the different populations of peripheral blood cells, were investigated in soman-intoxicated mice. Nine-week-old adult male B6D2F1 mice were treated with 110 microg/kg soman and 5.0 mg/kg methyl nitrate atropine. BM and peripheral blood (PB) samples were collected 1, 4, 8 and 22 days after poisoning. Various parameters were determined such as PB cell counting or, for BM samples, myelogram, in vitro colony-forming cells and phenotypic flow cytometry analysis. On post-soman day 1, a significant decrease in numbers of white blood cells and an increase in erythrocyte and platelet counts were noted. On post-soman day 4, the number of HPC decreased significantly, probably due to reduction of the replication rate of these immature cells. However, the number of more immature cells (Sca1+/Lin- phenotype) remained unchanged. On post-soman day 8 and day 22, the number of monocytes and granulocytes in the blood had considerably increased, probably due to a strong inflammatory reaction in response to soman poisoning. In conclusion, PB cell and BM-derived HPC populations are affected by acute soman poisoning, suggesting particular care, mainly for graft kinetic aspects, during future development of autologous BM stem cell therapy strategy to treat nerve agent-induced brain damage.

Animals↗
PubMed2005

[Study of contents of nitrates, fluorides, aluminium in dialysis water in Tunisia].

Nitrates, fluorides and aluminum have often been incriminated in cases of poisoning sometimes life threatening such as methaemoglobinaemia, dental and skeletal fluorosis, and myoclonal encephalopathy in patients undergoing haemodialysis. The three elements mentioned have something in common: their water origin (drinking water and dialysis water). To study the situation in Tunisia in this respect we propose to determinate the contents of nitrates, fluorides, and aluminum in drinking water and dialysis water supplied by the water board (SONEDE). 540 samples of drinking water and dialysis water were taken from 95 centers of haemodialysis scattered all over the country, between January 2000 and December 2001. These samples are divided in three parts (drinking water, soften water, and dialysis water ). Results show levels of fluorides < 1.5 ppm in most areas with the exception of zones rich in phosphate where the mean level is 1.61 +/- 1.22. the levels of nitrates are in most regions < 50mg/l and those of aluminum < 100microg/l. The levels of fluorides, nitrates and aluminum in dialysis water were within acceptable national and international limits excepting a few centers where the levels of the these contaminants are high, exposing patients on haemodialysis to acute and chronic intoxication. This contamination is caused in majority of cases by a dysfunction of water dialysis treatment chain, therefore caution is necessary and strict measures of control should be introduced.

Aluminum↗
PubMed1996

[Cariostatic mechanisms of fluoride and its effects on human beings].

Fluorine is ubiquitous in man's environment, rocks, soil, water, air, etc, and mainly is in the form of inorganic fluoride (compounds of fluorine) and utilized extensively for industrial and medical purposes. It is also known that fluoride has both beneficial and toxic effects in man. One of the most beneficial effects of fluorine on human health is the application of fluoride solution for the prevention or reduction the incidence of dental caries. The major cariostatic mechanisms is believed to be that fluoride reduces dental caries through influencing the morphology of teeth by reducing the solubility of the enamel and promoting remineralization, and through its effect on oral cariogenic bacteria. Recently, the possible beneficial effects of fluoride on osteoporosis have been studied. Chronic effects of fluoride, described by many epidemiological studies, are only dental fluorosis and skeletal fluorosis. Most cases of acute poisoning in human subjects have been associated with the suicidal, accidental or experimental (by researcher himself) ingestion of a fluoride solution.

Dental Caries↗