Gastrointestinal Absorption and Renal Excretion of Fluoride After Ingestion of a High-Fluoride Dentifrice

This study aimed to evaluate the gastrointestinal absorption and renal excretion of fluoride after the ingestion of high-fluoride dentifrice. Twelve volunteers participated in this in vivo, crossover, and blinded study. In three experimental phases, the volunteers were randomly assigned to one of three treatment groups, who ingested either the following: distilled and deionized water (control), conventional dentifrice (1100 μg/g), or high-fluoride dentifrice (5000 μg/g). Both dentifrices contained fluoride in the form of NaF/SiO₂. To determine the rate of fluoride absorption, non-stimulated saliva was collected for up to 120 min after ingestion and the area under the curve of the salivary fluoride concentration was plotted as a function of time and the maximum concentration determined. All urine produced during the 24 h before and after ingestion was collected, and urinary excretion was calculated from the difference between the urinary fluoride concentrations in the two periods. A specific ion electrode coupled to an ion analyzer was used to measure fluoride concentrations. Statistical analysis was performed by ANOVA followed by Tukey’s test with p set at 5%. All measured parameters were highest after the ingestion of the dentifrice with 5000 μg/g (p < 0.001), confirming that this has an increased level of bioavailable fluoride compared with the conventional dentifrice. The high-fluoride dentifrice increases the concentration of salivary fluoride, which may explain its greater anticaries effect. However, it poses a potential risk of causing dental fluorosis and so should not be used by children.

     

Influence of coffee on fluoride metabolism in rats

Concomitant intragastric administration of sodium fluoride and coffee resulted in a significantly higher (P less than 0.01) plasma fluoride level than intake of the same amount of fluoride with water. The same result was obtained when coffee was substituted with an equivalent amount of caffeine. Comparison of plasma fluoride levels by total area under the curve of plasma fluoride concentration versus time indicated an almost 2-fold difference. Although the mechanism(s) is not known, it appears that caffeine is responsible for the present observation. This finding could help explain the variations in the incidence of dental fluorosis among people living in optimally fluoridated communities.     

Influence of potassium chloride on alcohol absorption

Simultaneous intragastric administration of large doses of KCl (430 mg/kg and 860 mg/kg) with ethanol (4 g/kg) significantly reduces blood alcohol levels and diminishes manifestations of alcohol intoxication in rats. It was shown with parenteral administration of alcohol that the effect is not related to an acceleration of alcohol metabolism. Analysis of alcohol concentrations of gastric and intestinal content as well as $\text{in situ}$ studies with animals whose stomachs were ligated at the pylorus revealed that KCl interferes with the absorption of alcohol through inhibition of gastric absorption and gastric emptying. The finding that equimolal concentrations of NaCl were unable to duplicate the described effects characterizes them as specific actions of the potassium ion.     

缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响

目的：研究缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响。方法：将30只实验兔随机分为3组,每组10只,即正常对照组：喂以普通饲料;高脂饮食组：喂以高脂饮食（含15%蛋黄粉,0.5%胆固醇和5%猪油的饲料）6周,后给予10 ml/d生理盐水4周;药物干预组：喂以高脂饮食6周,后给予缬沙坦（10 mg/kg/d）治疗4周。饲养6周和10周时分别经兔耳缘静脉取血,通过酶联免疫法检测各组兔血清中IL-8和TNF-α的水平。结果：饲养第6周时,高脂饮食组和药物干预组兔血清TNF-α和IL-8水平均较正常对照组明显升高,差异均具有统计学意义（P〈0.05）,而高脂饮食组与药物干预组比较差异无统计学意义（P〉0.05）。饲养第10周时,即缬沙坦干预4周后,药物干预组与建模6周时比较,血清TNF-α及IL-8水平均明显下降,差异具有统计学意义（P〈0.05）,且与高脂饮食组比较,血清TNF-α及IL-8水平亦明显下降,差异具有统计学意义（P〈0.05）。结论：动脉粥样硬化时,血清IL-8和TNF-α升高,缬沙坦能明显降低动脉粥样硬化中IL-8和TNF-α水平,从而发挥抗动脉粥样硬化作用。     

The effect of mass on the gastrointestinal absorption of plutonium and neptunium

Absorption and retention of plutonium were determined in mice after intragastric administration of either 6 X 10(-4) or 1.5 mg/kg in bicarbonate, citrate, or nitrate media. At the higher concentration, absorption of the citrate was greater than that of the nitrate; at the lower concentration, chemical form was not an important factor in absorption. Concentration and chemical form had much less influence on absorption by the neonatal (versus the adult) rat. The transfer factor (f1) for neonates was between one and two orders of magnitude higher than for adults. Absorption and retention of neptunium were determined in rats and/or mice after intragastric administration at doses ranging from 2.2 X 10(-7) to 43 mg/kg in nitrate solutions of pH 1.5. At the higher concentrations, absorption was 1.5 to 2.7%. For lower concentrations, absorption was 25 to 65 times less. In contrast to results obtained in adult animals, absorption of neptunium by neonates decreased with increasing dose. The data obtained in adult animals suggest that the f1 factor recommended by the ICRP for plutonium should be increased by a factor of 10, but the neptunium f1 factor, in contrast, should be decreased by a factor of 10.     

Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats

Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I mRNA, and ileal proglucagon mRNA. Plasma IGF-I concentration was restored to fed levels with 2 days of ad libitum refeeding but not with 4 days of intravenous or intragastric refeeding. Administration of an inhibitor of endogenous GLP-2 (rat GLP-2 3-33) during ad libitum refeeding partially attenuated mucosal growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas intravenous refeeding had no effect. Intestinal regeneration after 4 days of intragastric or 2 days of ad libitum refeeding was positively associated with increases in plasma concentrations of GLP-2 and jejunal IGF-I mRNA. These data suggest that luminal nutrients stimulate intestinal growth, in part, by increased expression of both GLP-2 and IGF-I.     

Intragastric pH and Pharmacokinetics of Intravenous Ranitidine During Sinusoidal and Constant-Rate Infusions

Six patients with healed duodenal ulcer completed two treatment periods with continuous i.v. infusion ranitidine. A 25-mg i.v. bolus was followed by a constant infusion at 6.25 mg/h or a sinusoidal infusion with infusion rates ranging from 3.125 to 9.375 mg/h. The sinusoidal infusion rate was designed to match the previously observed circadian changes in basal acid secretion. The peak infusion rate occurred at 19:30 h. A pharmacokinetic method was designed to predict the resultant plasma concentrations of ranitidine. Intragastric pH and plasma ranitidine concentration data were fit to a cosine function to evaluate circadian and ultradian rhythms. Plasma concentrations during the sinusoidal infusion exhibited a circadian rhythm according to model predictions. Cosinor analyses of the mean ranitidine plasma concentration data showed a mesor concentration of 237 ng/mL and amplitude of 76 ng/mL (coefficient of determination [CD] = 0.98). The acrophase in plasma concentration occurred at 2223 h, a delay of approximately 2.9 hours from the peak in the infusion rate. The constant-rate infusion resulted in a mean plasma concentration of 222 ± 32 ng/mL. The 24-h mean intragastric pH values for the sinusoidal and constant regimens were 5.4 and 5.1, respectively (p = 0.170). The intragastric pH during the constant-rate infusion exhibited a significant circadian rhythm (CD = 0.52). The minimum pH (bathy-phase) occurred at 2031 h. No circadian rhythm was present during the sinusoidal-rate infusion (CD = 0.08). At the approximate time of the peak basal acid secretion, between 21:00 hours and midnight, the mean pH for the sinusoidal infusion was 5.77 versus 4.5 for the constant-rate infusion (p = 0.112). Sinusoidal infusions or alternate methods of increased doses at the times of peak acid output may improve around-the-clock control of intragastric pH.     

Role of Oxidative Stress in Osteoblasts Exposed to Sodium Fluoride

We investigated the relationship between oxidative stress and osteoblasts viability in osteoblasts exposed to various concentrations of fluoride in this study. Primary calvarial osteoblasts from neonatal Kunming mice were cultured and subcultured to the third generation. Osteoblasts were incubated with sodium fluoride (0, 0.5, 1, 2, 4, 8, 12, and 20 mgF(-)/L) for 24, 48, and 72 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis showed cell viability significantly increased after osteoblasts exposed to low concentrations of fluoride (0.5 to approximately 2 mgF(-)/L) for 24 to approximately 72 h. Oxidative stress analysis showed that low concentration of fluoride excited lipid peroxidation in osteoblasts and increased activity of antioxidant enzymes in varying degrees. We demonstrated that changes of osteoblasts viability of the low-dose fluoride groups are different from those of high-dose fluoride groups; however, both low and high doses of fluoride caused active state of oxidative stress in osteoblasts, which suggesting that oxidative stress may be excited by the active osteoblasts viability induced by a low dose of fluoride.     

Plasma insulin concentration during physiological variations in immunoreactive plasma secretin.

The effect of endogenous and exogenous secretin on fasting plasma insulin and glucose concentrations in peripheral venous blood was studied. In 10 non-diabetic subjects intragastric instillation of 300 ml 0.1 mol/l hydrochloric acid increased the plasma secretin concentration significantly. This increment did not influence insulin or glucose concentration. Control experiments with intragastric instillation of 300 ml of isotonic saline did not influence the plasma concentration of secretin, insulin or glucose. In four other non-diabetic persons no significant changes were found in plasma insulin or glucose concentration during an i.v. infusion of pure natural porcine secretin in doses of 0.1, 0.3, 1.0 and 3.0 clinical units/kg/h. The results suggest that secretin is without effect on insulin secretion in the fasting normal subject.     

Plasma concentrations of choline in man following choline chloride

Plasma choline levels were measured in patients being treated with choline chloride for movement disorders. Following single doses of 5 g given orally in aqueous solution, plasma concentrations rose to a peak within four hours and then rapidly declined. The degree of increase was variable both between and within patients. During chronic treatment, plasma choline concentrations tended to rise as the dose increased, although the relationship was not strong. The highest concentrations attained by patients were always at a dose of 16 or 20 g daily. Following chronic treatment, the disappearance of choline from plasma was rapid, with most patients reaching baseline by four days. Choline chloride is generally given in four divided doses, which seems reasonable in the early stages of treatment. Most therapeutic effect is seen when patients are treated with daily doses in the 12 to 20 g range, doses likely to produce substantial increases in plasma choline concentration. However, the relationship of plasma choline concentration to clinical efficacy may be tenuous. Following discontinuation of treatment, clinical improvement tends to persist long after plasma choline has returned to baseline concentrations.     

Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride

Summary Micromolar concentrations of aluminum sulfate consistently stimulated [³H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D₃ significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D₃-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.     

不同剂量的多乐氟对学龄前儿童尿氟浓度的影响

目的:观察儿童使用不同剂量的多乐氟氟化钠护齿剂(Duraphat)对其尿氟浓度的影响,为Duraphat应用于群防群治提供理论依据。方法:采用氟离子选择电极法,将53名3~4岁儿童按班别分成三组,分别使用0.2 m L及0.05 m L Duraphat涂布儿童牙齿,检测涂氟前和涂氟后1、2、3 d的尿氟浓度,并进行组内和组间比较。结果:各组使用Duraphat后尿氟浓度逐渐增加,涂氟后2 h开始与涂氟前比较差异均有统计学意义(P0.05),涂氟后3~4 h尿氟浓度达到高峰,至21 h后与涂氟前比较差异无统计学意义(P0.05);3岁0.2 m L组与0.05 m L组在涂氟后2~4 h的尿氟浓度比较差异有显著性(P0.05),其他时间比较均无显著性差异(P0.05);0.05 m L3岁组与4岁组比较尿氟浓度无明显差别(P0.05);3岁初次用氟组和4岁多次用氟组涂氟前尿氟无显著差异(P0.05)。结论:儿童口腔局部用氟对其尿氟浓度有影响,随局部用氟剂量的增加而增加;年龄对儿童尿氟浓度无明显影响;Duraphat在体内无远期氟蓄积,在一定剂量内使用Duraphat可起到较好的防龋效果。     

Quantitative investigation of copper(II) and zinc(II) complexes with S-carboxymethyl-L-cysteine and computer-simulated appraisal of their potential significance in vivo

S-carboxymethyl-L-cysteine (SCC) is a mucolytic agent extensively used in the treatment of respiratory tract disorders. Some of the undesirable side effects observed during SCC therapy being reminiscent of symptoms characteristic of copper and zinc imbalances, the objective of this paper was to test the possible interference of SCC with the metabolism of these two metals. Copper(II)- and zinc(II)-SCC complex equilibria have thus been investigated under physiological conditions by means of classical potentiometry combined with computer-assisted calculation techniques. Formation constants derived from these studies have then been used to simulate 1) the potential influence of SCC on the distribution of the above metals in blood plasma and 2) the extent to which gastrointestinal interactions between the drug and each metal ion in turn are likely to affect the bioavailability of each other. The results of these simulations show that 1) plasma therapeutic levels of SCC are not likely to induce dramatic changes in the distributions of copper(II) and zinc(II) low molecular weight fractions, 2) the gastrointestinal distribution of the drug is not affected by standard dietary doses of these metals, and 3) in contrast, therapeutic concentrations of SCC are capable of mobilizing significant fractions of both metals into tissue-diffusible electrically neutral complexes. In conclusion significant depletions of neither copper nor zinc are to be expected from oral administration of SCC. While the drug may to some extent facilitate the excretion of Cu2+ and Zn2+ ions from blood plasma, its gastrointestinal influence is, on the contrary, favorable to a better absorption of these two metals.     

Detection of sarin in plasma of rats after inhalation intoxication

Abstract

Presently used methods for detection and diagnosis of the severity of intoxication with organophosphorus (OP) compounds are mostly those that quantify inhibition of blood cholinesterases. It was found that when plasma inhibited with OP compounds is incubated in the presence of a high concentration of fluoride ions, the organophosphate is released from the enzyme thus yielding a phosphofluoridate, which can be analyzed by gas chromatography and NP detection. In our study, the concentration of sarin released after fluoride ions were added to the plasma of sarin-poisoned rats was determined. Sarin amounts in plasma measured after refluoridation and plasma butyrylcholinesterase activity in ten rats, that were exposed to sarin vapors at concentration of 1.25 μg/L (E1 group) and 2.5 μg/L (E2 group) respectively, for 60 min. In the E2 group the concentration of sarin in plasma was nearly 2-fold higher than in the E1 group. These results correspond well with the concentrations of sarin vapors to which the animals were exposed. Both experimental groups of animals showed significant decreases in butyrylcholinesterase activity by more than 30%–36.4% (E1 group) and 47.0% (E2 group). The method of fluoride-induced reactivation provides a very good marker for monitoring sarin intoxication in laboratory animals determined previously mostly by ChE determination which does not allow any information on sarin amounts in plasma.     

High Concentration of Fluoride Can Be Increased Risk of Abortion

The presence of fluoride in drinking water can be either beneficial or harmful for human health, depending on its concentration. Most adverse effects of fluoride are observed at high concentrations (above 1.5 mg/L). This study was aimed to evaluate the effect of fluoride concentrations in drinking water on spontaneous abortion in two regions: one with low fluoride concentration and another with high fluoride concentration. The results showed that there is a relationship between the concentration of fluoride in drinking water and abortion, so that the risk of abortion increased at high concentrations of fluoride. However, further studies are needed to clarify this relationship due to the small area and population in this study.     

Detection of sarin in plasma of rats after inhalation intoxication

Presently used methods for detection and diagnosis of the severity of intoxication with organophosphorus (OP) compounds are mostly those that quantify inhibition of blood cholinesterases. It was found that when plasma inhibited with OP compounds is incubated in the presence of a high concentration of fluoride ions, the organophosphate is released from the enzyme thus yielding a phosphofluoridate, which can be analyzed by gas chromatography and NP detection. In our study, the concentration of sarin released after fluoride ions were added to the plasma of sarin-poisoned rats was determined. Sarin amounts in plasma measured after refluoridation and plasma butyrylcholinesterase activity in ten rats, that were exposed to sarin vapors at concentration of 1.25 microg/L (E1 group) and 2.5 microg/L (E2 group) respectively, for 60 min. In the E2 group the concentration of sarin in plasma was nearly 2-fold higher than in the E1 group. These results correspond well with the concentrations of sarin vapors to which the animals were exposed. Both experimental groups of animals showed significant decreases in butyrylcholinesterase activity by more than 30%-36.4% (E1 group) and 47.0% (E2 group). The method of fluoride-induced reactivation provides a very good marker for monitoring sarin intoxication in laboratory animals determined previously mostly by ChE determination which does not allow any information on sarin amounts in plasma.     

Mechanism of hypocalcemia induced by intraperitoneal, intragastric, and intravenous administration of ethanol to the rat

Acute hypocalcemic effects of intraperitoneal administration of 3 and 5 g ethanol/kg body weight; intragastric administration of 3, 5, and 7 g ethanol/kg body weight; and intravenous administration of 2.5 a ethanol/kg body weight were investigated in 20 h fasted female Wistar rats. Dose-dependent hypocalcemia was similarly induced by intraperitoneal and intragastric routes of administration. Net calcium efflux from plasma, as indicated by the plasma 45Ca activity, was unaffected by 3 g ethanol/kg body weight but was delayed at higher doses of ethanol. Intragastric, but not intraperitoneal, administration of ethanol increased the gastrointestinal luminal calcium content partly by enhancing calcium secretion. Significantly increased tissue 45Ca content 30 min after ethanol administration was evident in the duodenum (31%), jejunum (27%), and colon (33%) in the intragastric ethanol-treated group and in the duodenum (40%), jejunum (38%), ileum (45%), colon (39%), and liver (25%) in the intraperitoneal ethanol-treated group. Thus, the hypocalcemia induced by both intraperitoneal and intragastric administration of ethanol could be partly accounted for by the suppression of calcium efflux from some soft tissues. In contrast, intravenous administration of ethanol was found to enhance the calcium efflux from plasma without affecting the net 45Ca content in the soft tissues. The mechanism(s) by which ethanol affects calcium transport has yet to be elucidated.     

The influence of citrate, maltolate and fluoride on the gastrointestinal absorption of aluminum at a drinking water-relevant concentration: A 26Al and 14C study

The objectives were to test the null hypotheses that (1) citrate, maltolate, and fluoride do not significantly influence oral Al bioavailability, C(max) or T(max) at an Al dose relevant to drinking water exposure; and (2) Al citrate and maltolate are absorbed intact from the gastrointestinal tract. Male Fisher rats were given 1ml of solution intra-gastrically containing 1 nCi (26)Al (65nmol total Al) as the Al(3+) ion, or as complexes with (14)C-citrate, (14)C-maltolate or fluoride, during concurrent (27)Al iv infusion. Blood was repeatedly collected for serum (26)Al, total Al and (14)C quantification. Absorption parameters were estimated using WinNonlin. Al bioavailability, C(max) and T(max) from the ion, citrate, maltolate, and fluoride were 0.29+/-0.11%, 0.61+/-0.31%, 0.50+/-0.25%, and 0.35+/-0.10%; 659+/-195, 1073+/-250, 881+/-356, and 880+/-295fg/ml; and 1.2+/-0.9, 1.0+/-1.1, 1.3+/-1.0, and 1.0+/-0.9h (X+/-SD) respectively. Serum (14)C was approximately 100 times higher than (26)Al. The results suggest a non-significant enhancement of oral Al bioavailability by citrate and maltolate, some Al complex dissociation in the GI tract, and less absorption of Al than citrate or maltolate. The presence of citrate, maltolate and fluoride, at a similar molar concentration to Al, would not be expected to greatly influence Al absorption from drinking water.     

Effect of delayed gastric emptying on fluoride absorption in the rat

The rate and site of fluoride (F) absorption were compared in fasted 350 g male rats given 50 micrograms F (as NaF) in either water or a 7.5% pectin solution. Absorption was measured at intervals up to 2 h following gastric intubation. Gastric emptying was measured by inclusion of 14C-PEG in the F solution. The extent of gastric F absorption was derived from rates of gastric emptying (14C-PEG loss) and F loss. Pectin markedly slowed gastric emptying, but by 2 h, more than 90% of the solution had passed into the small intestine in both groups, and F absorption exceeded 90% in both groups. The rate of F absorption was initially much slower in the pectin group than in the group given F in water, and plasma F concentration increased more slowly and reached a lower maximum value. Absorption from the stomach was greater in the pectin group, but still accounted for only approx 25% of total gastrointestinal absorption. The reduced rate of F absorption and slower rise in plasma F concentration accompanying delayed gastric emptying indicate that passage of F into the small intestine is the major factor in rapid F absorption.     

The effect of sodium fluoride on cereal seed germination and seedling growth

Abstract. Fluoride has been shown to inhibit germination and seedling establishment in barley cv. Natasha, wheat cv. Axona and rice cv. Ishikari. The concentrations of fluoride were selected so as to give a satisfactory dose-response relationship and also to relate to levels of fluoride present under natural conditions. Concentrations used were zero, 0.5, 1.0, 10 and 40 mol m⁻³ sodium fluoride. In germination studies, barley was found to be least tolerant and rice most tolerant of fluoride. The inhibition was found to be a response to fluoride itself and the observed effects were not due to pH, sodium or an unspecific effect of halide ion. Phosphate, applied at two concentration levels, was unable to overcome the inhibition. Fluoride was also shown to inhibit seedling growth. The inhibitory effects of fluoride may be accounted for by a wide range of metabolic effects including inhibition of gibberellic acid–triggered alpha amylase activity during germination, and later on to inhibition of chlorophyll synthesis in the developing leaves.