Effect of drinking waters of high fluorine content on the urinary fluoride level.

The urinary fluoride level has been studied in 307 subjects consuming drinking waters of different fluoride concentrations. The urinary fluoride level was found to increase with the fluoride content of the drinking water. The urinary F level of the population group drinking water of optimum fluoride concentration was 1.14 mg of fluoride per litre. Thus, in regions where the drinking water contains an insufficient amount of fluoride, the fluoride content of domestic salt must be adjusted so as to ensure an about 1.14 mg/litre urinary F level of the population.     

Factors influencing the urinary fluoride level in subjects drinking fluoride-poor waters.

The influence on the urinary F level of the short-term consumption of drinking water of 1 mg/litre fluoride content, of the ingestion of low (1.0 to 2.0 mg) and higher (7.0 and 8.0 mg) fluoride doses and of tea has been studied. Excess fluoride is rapidly excreted with urine, and may disturb the results of urinary fluoride estimation. The urinary F level responds sensitively to the ingestion of fluorine.     

Urinary fluoride levels after consumption of fluoride-poor drinking waters in Hungary.

Fluoride concentration in the urine of subjects drinking fluoride-poor water was investigated. In the first series of experiments, mean F concentration in the urine collected for 24 hours was 0.26 mg/litre, in the second series, 0.28 mg/litre, and in group fractions 0.20 mg/litre. Standard deviations ranged from 0.07 to 0.12 mg/litre. No conclusion could be drawn from the F level of a single urine fraction to the 24-hour F level of the same subject. In group tests, means reflected the expected 24-hour values. There were differences in the urinary F levels of the subjects. Values for the same subject also varied; they were different on different days and the fractions collected on the same day showed variations. Older people excreted more fluoride than young ones. These findings are in good agreement with published data.     

Bone age of children in 2 communities in Hungary with different fluoride levels in the drinking water

The adverse effects of ingested fluoride were investigated. The bone-age of children consuming drinking water containing optimum (about 1 mg/l) fluoride concentration with regard to caries prophylaxis was compared with the bone-age of those consuming drinking water containing low (0.14-0.26 mg/l) fluoride concentration. The examinations were conducted on 7-14-year old Hungarian children. The bone-age was determined by the TW2 method. No significant difference was found between the bone-age of the children belonging to the group consuming water with optimum fluoride concentration and those in the other group consuming water with low fluoride concentration.     

口服苯肼致小鼠慢性贫血模型的建立

目的:应用苯肼建立小鼠急性溶血性贫血的方法已经成熟,但用苯肼建立慢性溶血性贫血模型尚未见报道。本研究试图应用苯肼口服法建立慢性溶血性贫血动物模型并探索最适建模的苯肼浓度。方法:42只C57BL/6小鼠随机分为6组通过口服不同浓度的苯肼溶液,于口服后的第0,1,2,3,4,5,6周目内眦采集小鼠外周血检测,记录相关指标变化比较各组之间的差异,筛选出最佳慢性溶血效果的给药浓度。结果:口服苯肼溶液浓度在250 mg/L以下时C57BL/6小鼠没有出现明显的贫血状态,当浓度调至250mg/L-350mg/L时可使C57BL/6小鼠在5-7周内出现溶血性贫血症状,各组小鼠的皮肤和粘膜颜色苍白,外周血红细胞数量、血红蛋白含量、红细胞压积降低网织红细胞比例增高。但是当浓度达到350 mg/L时小鼠贫血情况过重且达不到慢性贫血的要求。当浓度为300 mg/L时小鼠各项血液指标平稳下降。结论:本实验建立了一种新的小鼠慢性贫血模型,且通过实验发现小鼠口服苯肼致慢性贫血的最佳浓度为300mg/L。据我们所知,这是首次使用苯肼建立慢性贫血的动物模型,此模型对研究人类慢性贫血具有重要价值。     

The effect of diet calcium on fluoride toxicity in growing rats

The effect of dietary Ca in response to fluoride (F) treatment was investigated in rats. Rats were maintained on either adequate (0.5%) or high (2.0%) dietary Ca and given for 5 weeks, NaF in drinking water. The minimum NaF levels that inhibited body growth and reduced survival were 300 mg/L with 0.5% diet Ca and 550 mg/L with 2.0% diet Ca. With these toxic F doses, bone histology showed increased formation surfaces and thickened osteoid seams (osteoid index 6-7%). Fluoride doses 30% below toxic levels (200 and 350 mg/L for 0.5 and 2.0% diet Ca, respectively) had no demonstrable effect on bone. Additional diet Ca reduced F absorption from 76 +/- 3 to 47 +/- 3% for 0.5 and 2.0% diet Ca, respectively. Comparable absorbed doses of F produced comparable effects on bone and body growth but, with additional dietary Ca, these effects were observed with 50% lower serum and bone F levels. Variable response to NaF therapy can be produced in rats by alterations in dietary Ca alone. Results indicate that for clinical treatment the NaF dose needs to be adjusted on an individual basis but neither serum nor bone F levels can be used reliably to establish optimal doses.     

赤霉病麦中毒研究Ⅳ.赤霉病麦粗毒素的致畸与致突变研究

通过酒精提取、丙酮浓缩,从天然带毒的赤霉病元麦中制备粗毒素。化学分析表明既含脱氧雪腐镰刀菌烯醇,又含玉米赤霉烯酮。以此粗毒素0,125,250,500,1,000mg/kg体重于孕期7—16天连续灌胃授予Wlstar妊娠大鼠。结果发现:1,000mg/kg有明显的胚胎毒作用;250rag/kg以上有胎儿毒作用和致畸作用。另以不同浓度的粗毒素柱层析纯化物和脱氧雪腐镰刀菌烯醇纯品测试了对鼠伤寒沙门氏菌组氨酸缺陷型菌株的致突变性。结果表明:加与不加S-9混合液均有诱变性,但存在着一定的剂量-反应差异。     

Bone-fracture incidence rate in two Italian regions with different fluoride concentration levels in drinking water.

The effect of the fluoride concentration in drinking water on the prevention of fractures related to osteoporosis has been questioned or contradicted in several recent studies. These studies have been mostly performed using water with artificially added fluoride, at the optimum level of about 1 mg/l. In the present study authors have investigated the effect of equal or greater fluoride concentrations (mean 1.45 mg/l) naturally present in waters supplied for human consumption to a population of 72.756 (Bracciano county), in comparison with a population of 126.189 (Avezzano county), supplied with low fluoride concentration water (mean 0.05 mg/l). The incidence of fractures in the years 1990 and 1991 was evaluated in the two areas (Bracciano and Avezzano), which are located in central Italy and where population have a similar life style, economic and social level and employment structure. The incidence data were obtained from the registers of the public hospital taken as a reference in each district. The authors noticed a significantly greater rate of fracture incidence at several parts of the body, in particular femur fractures (relative risks for males 4.28 and for females 2.64), in the population of the district of Avezzano than in the population of Bracciano. The greater concentration of fluoride in waters distributed for human consumption in Bracciano district seems to have the effect of protecting its inhabitants against fractures.     

The fluoride content of selected foods in relation to the fluoride concentration of water

The F content of foods and beverages comprising a substantial proportion of the Hungarian diet has been determined. Vegetables and fruits grown in three areas where the mean F content of water was 0.09 mg/l, 0.81 mg/l and 1.91 mg/l did not reflect these differences. In contrast, the F content of cooking water has made demonstrable contribution to the F content of cooked foods. Significant elevation in F concentration was also found in some meat products, where the inclusion of bone dust or fragments is suggested by corresponding increase in Ca content.     

Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA–salt hypertensive rats

Although deoxycorticosterone acetate (DOCA)–salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA–salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of α-1 subunit of Na,K–ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA–salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.     

Influence of excessive fluoride consumption on the severity of dystrophic cardiac calcification in DBA/2 mice

Soft tissue calcifications in inbred laboratory mice are frequently observed and are often associated with dystrophic cardiac calcinosis (DCC). We tested the hypothesis that an excessive intake of fluoride would inhibit pathological calcifications in DCC-susceptible mice. A diet containing either a high (200 mg F/kg added to the diet) or low fluoride content (no F added) was fed to both weanling and retired breeder DBA/2 mice. The high-fluoride diet reduced feed intake and body weight gain when given after weaning. It was found that a high fluoride intake effectively reduces soft tissue calcifications in young mice, but not in retired breeders. Because DCC in mice is a pathological finding that could interfere with certain experimental procedures, it is suggested that the optimum fluoride concentration in the diet for mice of susceptible strains should be established.     

Myosin light chain mono- and di-phosphorylation differentially regulate adhesion and polarity in migrating cells

A high carbohydrate-high fat (HC-HF) diet-associated with hyperinsulinemia has been previously reported to induce accelerated growth of prostate cancer in a xenograft model. High energy supply and insulin/insulin growth factor-1 axis are two of the mechanisms proposed. We hypothesize that metformin may have a protective effect against prostate cancer progression by affecting metabolisms associated with high energy intake. In the present study, animals were randomized into five groups, receiving a HC-HF diet with 50, 100, or 250 mg/kg body weight (mg/kg) metformin in drinking water, a standard diet or HC-HF diet alone. Animals on the HC-HF diet developed obesity and insulin resistance. They had significantly higher body weight, fasting blood glucose at an upper level of normal range, higher insulin secretion and utilization, and fatty degeneration of the liver. Metformin at the doses employed significantly reduced food and water consumption; however, only a dose of 250 mg/kg showed a significant reduction in body weight gain and suppression of gluconeogenesis as well remarkably reduced insulin secretion. There was no observed metformin-related hepato-toxicity in any of the groups. In summary, metformin at various doses exhibits protective effects on the metabolic disorder caused by the HC-HF diet with the most effective protection at a dose of 250 mg/kg. These effects may explain its translational role relating to its anti-neoplastic potential.     

Involvement of p38 Mapkinase in attenuation of antinociceptive effect of morphine in diabetic mice

Experimental diabetes induced by streptozotocin (200 mg/kg, ip) markedly decreased the antinociceptive effect of morphine and significantly increased the urinary nitrite concentration. Administration of FR-167653 (a selective p38MAPKinase inhibitor) in a dose of 4 mg/kg improved the antinociceptive effect of morphine and attenuated the increase in urinary nitrite concentration in diabetic mice. It may be concluded that diabetes-induced decrease in antinociceptive effect of morphine may be due to induction of p38 MAPKinase activity.     

Studies on the Utilization of Levulinic Acid

The single injection of levulinic acid oxime (250 mg/rat) or α-ketoglutaric acid oxime (250 mg/rat) on rats, carrying radioactive cesium, promoted both urinary and fecal excretion of this radionuclide. The administration of levulinic acid oxime (sodium salt) decreased the cesium retention by liver. The administration of the oxime did not have influence on the urinary excretion of sodium and potassium in normal rats. The toxicity of the oxime was low. The LD₅₀ of α-ketoglutaric acid oxime was 3500 mg/kg (mice, intraperitoneally). (The LD₅₀ of levulinic acid oxime has already been indicated as 2040 mg/kg (mice, intravenously).     

Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice

Arsenic and fluoride are potent toxicants, widely distributed through drinking water and food and often result in adverse health effects. The present study examined the effects of sodium meta-arsenite (100 mg/l in drinking water) and sodium fluoride (5 mg/kg, oral, once daily), administered either alone or in combination for 8 weeks, on various biochemical variables indicative of tissue oxidative stress and cell injury in Swiss albino male mice. A separate group was first exposed to arsenic for 4 weeks followed by 4 weeks of fluoride exposure. Exposure to arsenic or fluoride led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by increased level of blood and tissues reactive oxygen species (ROS) level. An increase in the level of liver and kidney thiobarbituric acid reactive substance (TBARS) along with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and reduced GSH content were observed in both arsenic and fluoride administered mice. The changes were significantly more pronounced in arsenic exposed animals than in fluoride. It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone. In some cases antagonistic effects were noted following co-exposure to arsenic and fluoride. Arsenic and fluoride concentration increased significantly on exposure. Interestingly, their concentration decreased significantly on concomitant exposure for 8 weeks. However, the group which was administered arsenic for 4 weeks followed by 4 weeks of fluoride administration showed no such protection suggesting that the antagonistic effect of fluoride on arsenic or vice versa is possible only during interaction at the gastro intestinal sites. These results are new and interesting and require further exploration.     

Effect of high dietary copper on weight gain and neuropeptide Y level in the hypothalamus of pigs

An experiment was performed to examine the effect of dietary copper supplementation on weight gain, neuropeptide Y (NPY) concentration and NPY mRNA expression level in the hypothalamus of pigs. Forty-five crossbred pigs were randomly assigned to three groups of 15 pigs, each comprising five replicates of 3 animals. Pigs were allocated to diets that contained 10 mg/kg (as a control), 125 and 250 mg/kg copper as CuSO₄. Live weight gain and feed conversion efficiency was determined at the end of the experiment and five pigs, selected at random from each group, were slaughtered and the hypothalami collected for determination of NPY concentration and NPY mRNA expression level. The results showed that average daily gain (ADG) and average daily feed intake (ADFI) were higher and feed:gain (F:G) ratio was lower in pigs fed the diets with 125 and 250 mg/kg copper (P<0.05), respectively, than in pigs fed a diet with 10 mg/kg copper, but that there was no statistically significant difference in growth performance between animals of the 125 mg/kg and the 250 mg/kg copper groups. Furthermore, pigs fed diets with 125 and 250 mg/kg copper had higher NPY concentrations and NPY mRNA expression levels in their hypothalamus than control animals. The data indicated that 125 and 250 mg/kg copper gave similar responses in terms of weight gain, whilst high dietary copper could enhance NPY concentration and NPY mRNA expression level in the hypothalamus of pigs. High dietary copper appears to increase feed intake and promote weight gain by enhancing NPY concentration and NPY mRNA expression level in the hypothalamus of pigs.     

Drinking water quality and arsenic health risk assessment in Sistan and Baluchestan,Southeastern Province,Iran

Access to drinking water is one of the most important indicators determined by the World Health Organization (WHO). This investigation surveyed the concentration of various pollutants in drinking water and its health risk attribute to Arsenic in Sistan and Baluchistan province, Iran. Water samples were collected from ground water and analyzed for physical parameters, anions, and heavy metals using the standard procedures. The concentrations of sulfate (269 ± 127 mg/l) in five sites exceeded the permissible limit (250 mg/l), while chlorine concentrations (223 ± 100 mg/l) in four sites exceeded the permissible limit (250 mg/l) set by WHO. Similarly, the concentrations of Mg (30 ± 11 mg/l) in four sites exceeded the permissible limit (30 mg/l), while Na concentrations (222 ± 99 mg/l) in five sites exceeded the permissible limit (200 mg/l) set by Institute of Standards and Industrial Research of Iran (ISIRI). In addition, arsenic was in acceptable levels recommended by WHO and local regulations. Based on the calculated indices of hazard qutient (HR) and excess lifetime cancer risk (ELCR), the in-use drinking water has no adverse effects on the consumer's health. Excessive use of fertilizers and pesticides, unsuitable sewerage systems, and inappropriate sludge and solid waste disposal in this province can lead to drinking water pollution. Also, excessive pumping of ground water should be managed as an effective method for supply of safe drinking water.     

The determination of urinary fluoride/creatinine ratio (Q) in monitoring fluoride intake

Linear correlation (r = 0.6811, p less than 0.001) was found between the 24 hour urinary excreted fluoride quantity and fluoride/creatinine ratio (Q) of the morning urine sample of 21 school children living in a children's home in Hungary. The mean value of fluoride/creatinine ratio (Q) in groups of children from eight different parts of Hungary, also showed linear correlation (r = 0.9720, p less than 0.001) with the measured fluoride concentration of drinking water. The urinary fluoride/creatinine ratio (Q) seems sufficiently informative for controlling fluoride intake in the course of caries preventive field studies.     

Modelling of fish contamination with 90Sr in relation to the calcium concentrations in water

A set of data on the equilibrium concentration factors of 90Sr in fish in relation to the Ca concentrations in water was collected and analyzed. An empiric relationship was obtained on the basis of statistical processing of this dataset: CF(90Sr, Bq/kg w.w.) = 3940(1770-6110)/[Ca, mg/L]water. The range of observed data on the concentration factors of 90Sr in fish is from 20 to 4000 L/kg (about 200 times). The statistical relationship obtained in the paper allows one to reduce this uncertainty by more than 50 times. The formula adequately describes equilibrium concentration factors of 90Sr both in freshwater and in marine fish. A dynamics model approach is described for the cases of accidental contamination of water bodies, when the equilibrium approaches are not appropriate.     

Method for endogenous formaldehyde evaluation in animal organism

A method for endogenous formaldehyde (FA) level evaluation has been worked out. The method involves the administration of dimedone, which forms the stable complex with FA, and the determination of formaldimedone concentration in biological samples by the fluorescence approach. The method was tested on rat's models of FA metabolism modulation. Animals received FA (10 mg/kg); or methylamine - substrate of FA-generating enzyme SSAO, (250 mg/kg); or semicarbazide - SSAO inhibitor, (200 mg/kg). Concentration of FA bound with dimedone in the liver tissue were, correspondingly: 7.5 +/- 1.5 mkg/kg; 5.4 +/- 0.9 mkg/kg; 2.4 +/- 0.7 mkg/kg; control - 4.2 +/- 1.4 mkg/kg. Obtained data indicate, that the elaborated method gives reliable information about FA level.