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["Medicolegal" bone fluorosis. Apropos of 2 cases of possible criminal poisoning].

We report two cases of skeletal fluorosis in two men, 55 and 69 year-old. The physical findings and the roentgenograms were typical and chemical analysis confirmed the diagnosis. Surprisingly, fluoride concentrations in blood and urine were increased at the beginning of the hospitalizations and lower during the hospitalizations. The origin of fluor intake remained unknown, leading to consider a possible criminal poisoning. Then, we discuss the attitude of physician in a case a possible criminal poisoning: denunce the crime to the police or not, as regards french law.

Acute Disease↗

Pediococcus cerevisiae mutant with altered transport of folates.

A Pediococcus cerevisiae mutant that actively accumulated folate (PteGlu), in contrast to the wild-type, was also found to exhibit changes in the pattern of uptake of 5-methyl-tetrahydrofolate (5-CH3-H4PteGlu) and amethopterin. Most of the 5-CH3-H4PteGlue accumulated through a glucose- and temperature-dependent process, and a concentrative uptake was also found in gluocse-starved cells and in cells incubated at OC. About 75% of the accumulated 5-CH3-H4PteGlu exchanged with amethopterin. In contrast to the wild type, the mutant accumulated both diastereoisomers of 5-CH3-H4PteGlue by glucose-dependent and glucose-independent processes. Amethopterin and PteGlue competitively inhibited the uptake in both processes, with an apparent lower affinity of the carrier for PteGlu than for the analogue. p-Chloromercuribenzoate strongly inhibited the uptake (75%). The p-chloromercuribenzoate-nonsusceptible and temperature-independent uptake was also competed by amethopterin. Metabolic poisons like sodium azide, potassium fluoride, iodoacetate, and 2,4-dimitrophenol inhibited the glucose-dependent process. Uptake, in the absence of glucose, was enhanced by sodium azide and potassium fluoride.

Azides↗

REDUCTION OF SELENITE BY INTACT YEAST CELLS AND CELL-FREE PREPARATIONS.

Falcone, Giuseppe (Rutgers, The State University, New Brunswick, N.J.), and Walter J. Nickerson. Reduction of selenite by intact yeast cells and cell-free preparations. J. Bacteriol. 85:754-762. 1963.-Nonproliferating cell suspensions of Candida albicans rapidly reduced selenite to red, metallic selenium in the absence of added substrate. Cell suspensions reduced selenite optimally at pH 4.2. No added metabolite was found to be stimulatory; reduction was inhibited by methionine and formate as well as by fluoride, dinitrophenol, and certain sulfhydryl poisons. Cell-free preparations capable of reducing selenite were obtained from C. albicans and from baker's yeast disintegrated in a Hughes press. The enzymatic system had optimal activity at pH 7 with 10(-2)m selenite. Activity of the system was lost on dialysis but was restored upon the addition of dialyzable substances or of boiled, undialyzed extract.

Candida↗

A superoxide anion induced DNA strand-break metabolic pathway in human leukocytes: effects of vanadate.

Superoxide anion (O2-) is an active oxygen species found in virtually all cells grown in the presence of oxygen. In vivo, the highest concentration of this oxygen radical is found after granulocytes have been exposed to particles or the tumor promoter, phorbol myristate acetate. O2- is released from the cell as a "respiratory burst," which is followed shortly by the appearance of strand breaks in the DNA of the producing cell. In the present report, we have continued our investigation into the mechanism by which extracellular O2- causes breakage of intracellular DNA. Although hydrogen peroxide is present and could also cause strand breaks, its effects are eliminated by the addition of catalase. When the amount of O2- is increased threefold by adding glucose to the medium, the number of breaks increases only slightly, suggesting that the number of breaks that could be induced is limited. The strand-break process is abruptly interrupted by the addition of metabolic poisons such as ionophore A23187, fluoride, or 2-deoxyglucose, but ATP does not appear to be involved. The number of O2(-)-induced strand breaks is increased in the presence of sodium orthovanadate and decreased by A23187. Orthovanadate prevents the inhibition caused by A23187. Reaction of O2- with orthovanadate itself appears not to be responsible for the enhancement of breaks by orthovanadate. We propose that orthovanadate exerts its effect by acting as an inhibitor of a phosphoprotein phosphatase and that A23187 acts to deplete intracellular Ca2+. These data support our hypothesis that the O2- radical causes strand breaks not by attacking the DNA but rather by activating a specific metabolic DNA strand-break pathway.

Adenosine Triphosphate↗

Drug-induced erythrocyte membrane internalization.

In vitro erythrocyte membrane internalization, resulting in the formation of membrane-lined vacuoles, can be quantified by a radioisotopic method. A complex of (37)Co-labeled vitamin B(12) and its plasma protein binders is first adsorbed to the cell surface, and after vacuoles are formed, the noninternalized label is removed by washing and trypsin treatment. The residual radioactivity represents trapped label and can be used to measure the extent of membrane internalization. Using this method, it was found that in addition to primaquine, a group of membrane-active drugs, specifically hydrocortisone, vinblastine, and chlorpromazine can induce membrane internalization in erythrocytes. This is a metabolic process dependent on drug concentration, temperature, and pH. Vacuole formation by all agents tested can be blocked by prior depletion of endogenous substrates or by poisoning the erythrocytes with sodium fluoride and sulfhydryl blocking agents. This phenomenon resembles in some respects the previously reported membrane internalization of energized erythrocyte ghosts. It is suggested that membrane internalization is dependent on an ATP-energized state and is influenced by the balance between the concentrations of magnesium and calcium in the membrane. This study provides a basis for proposing a unifying concept of the action of some membrane-active drugs, and for considering the role of erythrocyte membrane internalization in pathophysiologic events.

Adenosine Triphosphate↗

Pharmacy: a unique opportunity to participate in education.

Health education and health maintenance are part of the traditional role of the pharmacist, particularly for those engaged in general practice (retail) pharmacy, writes J. W. Barnett, APhO Hereford and Worcester AHA, in the last of our series. Pharmaceutical officers have many opportunities to exercise this professional role themselves either by direct contact with the public, or indirectly by helping and advising others. Although this generally involves educating the public on medicines, wider issues are also involved -- for example, fluoridation and the risk of poisoning from household chemicals.

Community Pharmacy Services↗

[Dynamics of protein synthesis in several organs of mice with fluorosis].

Proceeding from the time course of 3H-leucine incorporation during chronic fluoride administration the mouse organs were distributed conventionally into three groups. The first group included the organs which did not manifest significant alterations in protein synthesis. On the contrary, the second group of the organs manifested pronounced oscillations in the synthetic activity during poisoning. However, the majority of the organs studied (the third group) was characterized by a sharp inhibition of isotope incorporation.

Animals↗

Intracellular transfer of phospholipids in the yeast, Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, unlike in higher eukaryotic cells, most of the reactions involved in phospholipid biosynthesis occur both in mitochondria and in the endoplasmic reticulum. Some of the key enzymes involved, however, are restricted to one compartment. Thus, the formation of phosphatidylethanolamine by decarboxylation of phosphatidylserine occurs only in mitochondria, while phosphatidylcholine synthesis via methylation of phosphatidylethanolamine is restricted to microsomes. When yeast cells were pulse labelled with [3H]serine,[3H] phosphatidylethanolamine formed in mitochondria was found not only in the organelle but also, with even higher specific radioactivity, in the endoplasmic reticulum. Translocation of phosphatidylethanolamine between organelles was blocked immediately after poisoning cells with cyanide, azide and fluoride. Part of the [3H]phosphatidylcholine formed in the endoplasmic reticulum by methylation of [3H]phosphatidylethanolamine was transferred to mitochondria. This process continued in deenergized cells, although at a lower rate as compared to metabolizing cells. This result indicates rapid movement of both phosphatidylethanolamine and phosphatidylcholine requires metabolic energy, but that phosphatidylinositol-specific phospholipid transfer protein that has been found in saccharomyces cerevisiae (Daum, G. and Paltauf, F. (1984) Biochim. Biophys. Acta 784, 385-391). The mechanism of movement of phospholipids from internal membranes to the cell surface was studied with temperature-sensitive secretory mutants (Schekman, R. (1982) Trends Biochem. Sci. 7, 243-246) of Saccharomyces cerevisiae. A shift from the permissive to the restrictive temperature, which blocks the flow of vesicles involved in the secretion of proteins, had no effect on the transfer of phosphatidylinositol to the plasma membrane.

Biological Transport↗

[Hydrofluorosis].

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Fluorides↗