氟化泡沫预防青少年固定正畸过程中釉质脱矿的临床研究

目的观察固定正畸过程中应用氟化泡沫对年轻恒牙形成釉质脱矿的影响。方法选取60例固定正畸患者（年龄11～14岁）,分为3组,分别采取3个月应用一次氟化泡沫,6个月应用一次氟化泡沫,及未使用氟化泡沫。记录治疗12个月后牙面的釉质脱矿指数（EDI）,计算平均EDI,进行统计学分析。结果 3个月应用一次氟化泡沫组平均EDI为0.144,明显低于其他两组,存在统计学差异;6个月应用一次氟化泡沫组平均EDI为0.256,与未使用氟化泡沫组平均EDI为0.350相比无明显统计学差异。结论 3个月应用一次氟化泡沫能有效预防固定正畸过程中年轻恒牙的釉质脱矿。     

Integral pharmacokinetics of multiple lignan components in normal, CCl4-induced hepatic injury and hepatoprotective agents pretreated rats and correlations with hepatic injury biomarkers

Although pharmacokinetic alternations by hepatic injury have been extensively studied, little is known about the potential influence of hepatoprotective agent's treatment. This study was aimed to investigate the holistic pharmacokinetics of multiple lignans, CYP3A regulations, and their correlations with hepatic injury biomarkers, in hepatic injured rats pretreated with or without schisandra lignan extract (SLE) and dimethyl-diphenyl-bicarboxylate (DDB). Integral pharmacokinetics of multiple lignans based on an AUC-weighting approach was determined in normal, CCl4 induced hepatic injury rats pretreated with or without SLE and DDB. Protein expression and activities of CYP3A were determined. Pharmacokinetic parameters and CYP3A activities were correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. CCl4 induced acute hepatic injury resulted in a nearly 8-fold enhancement of integral plasma exposures of multiple lignans, which was caused by the significant down-regulation of CYP3A. SLE and DDB pretreatment exhibited potent hepatoprotective effects, accompanied with the restored expression and activity of CYP3A, and the recovery of the respective and integral pharmacokinetics of lignans components. The integral AUC_0-tn and CYP3A activities correlated well with ALT and AST. This study suggested that the pharmacokinetic regulating effects of hepatoprotective agent's on themselves and co-prescribed drugs should be of concern, and hepatic injury biomarkers may serve as good predictors.     

Fluoride-induced IL-8 release in human epithelial lung cells: relationship to EGF-receptor-, SRC- and MAP-kinase activation

Exposure of human epithelial lung cells to fluorides is known to induce a marked increase in the release of interleukin (IL)-8, a chemokine involved in neutrophil recruitment. In the present study, the involvement of mitogen-activating protein kinases (MAPKs), the role of upstream activation of Src family kinases (SFKs), epidermal growth factor receptor (EGFR) activation and the interrelationships between these pathways in fluoride-induced IL-8 were examined in a human epithelial lung cell line (A549). Sodium fluoride strongly activated MAPK, in particular JNK1/2 and p38. The ERK1/2-inhibitor PD98059, the p38-inhibitor SB202190 and the JNK1/2-inhibitor SP600125 partially inhibited the fluoride-induced IL-8 response. Combinations of these inhibitors reduced the responses nearly to basal levels. Treatment with siRNA against JNK2 also reduced the IL-8 response to fluoride. Furthermore, fluoride activated SFKs, which was abolished by the SFK-inhibitor PP2. PP2 substantially inhibited the increased levels of IL-8, and partially reduced the fluoride-induced activation of ERK1/2, p38 and JNK1/2. Fluoride exposure also led to a phosphorylation of the EGFR, that was partially inhibited by PP2. AG1478, an EGFR-inhibitor, partially reduced the fluoride-induced IL-8 response and the phosphorylation of JNK1/2 and ERK1/2, but less the phosphorylation of p38. The effects of AG1478 were less than that of PP2. In conclusion, our findings suggest that the fluoride-induced IL-8 release involves the combined activation of ERK1/2, JNK1/2 and p38, and that the phosphorylation of these kinases, and in particular JNK1/2 and ERK1/2, partly, is mediated via a SFK-dependent EGFR-linked pathway. SFK-dependent, but EGFR-independent mechanisms seem important, and especially for phosphorylation of p38.     

Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices containing perfluoroheptane

Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from repaired Althane dialysers was found to be the most probable reason for the deaths of 53 dialysis patients reported in the year 2001. This study focuses on toxic decomposition products generated due to gamma and beta sterilisation of hexadecafluoroheptane. The responsible dialysers were sterilised with a maximum dose of 45 kGy gamma irradiation. We investigated the influence of both 20-500 kGy gamma and beta irradiation on perfluoroheptane. Analysis of the irradiated samples verified the decomposition of perfluoroheptane in dependence on the dose of irradiation. Beta irradiation resulted in a higher degree of decomposition than the same dose of gamma irradiation. As decomposition products, hydrogen fluoride, CO2, and one saturated fluorinated hydrocarbon which could not be analysed exactly were identified. Even at 20 kGy gamma irradiation hydrogen fluoride was detectable. Our results provide evidence that hydrogen fluoride is generated as a highly toxic decomposition product when perfluoroheptane is sterilised with gamma irradiation as it was applied on the affected dialysers. There is no evidence of other toxic degradation products especially perfluoroisobutylene. Therefore, hydrogen fluoride or the dissociated fluoride ions might act as a toxic agent when medical devices containing liquid perfluorocarbons are sterilised by irradiation.     

Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss

Fluorosis, caused by drinking water contamination with inorganic fluoride, is a public health problem in many areas around the world. The aim of the study was to evaluate the effect of environmentally relevant doses of fluoride on in vitro fertilization (IVF) capacity of spermatozoa, and its relationship to spermatozoa mitochondrial transmembrane potential (DeltaPsi(m)). Male Wistar rats were administered at 5 mg fluoride/kg body mass/24 h, or deionized water orally for 8 weeks. We evaluated several spermatozoa parameters in treated and untreated rats: i) standard quality analysis, ii) superoxide dismutase (SOD) activity, iii) the generation of superoxide anion (O(2)(-)), iv) lipid peroxidation concentration, v) ultrastructural analyses of spermatozoa using transmission electron microscopy, vi) DeltaPsi(m), vii) acrosome reaction, and viii) IVF capability. Spermatozoa from fluoride-treated rats exhibited a significant decrease in SOD activity (~33%), accompanied with a significant increase in the generation of O(2)() (~40%), a significant decrease in DeltaPsi(m) (~33%), and a significant increase in lipid peroxidation concentration (~50%), relative to spermatozoa from the control group. Consistent with this finding, spermatozoa from fluoride-treated rats exhibited altered plasmatic membrane. In addition, the percentage of fluoride-treated spermatozoa capable of undergoing the acrosome reaction was decreased relative to control spermatozoa (34 vs. 55%), while the percentage fluoride-treated spermatozoa capable of oocyte fertilization was also significantly lower than the control group (13 vs. 71%). These observations suggest that subchronic exposure to fluoride causes oxidative stress damage and loss of mitochondrial transmembrane potential, resulting in reduced fertility.     

西南某铝业周边人群环境氟暴露健康影响现状

目的了解某铝业对周边居民健康影响现状,为政府及企业制定相关防治对策提供科学依据。方法于2015年对西南某地一处有近20年生产历史并停产1年的综合性铝业公司,在其周边选择3个行政村作为污染区,同时选择1个行政村作为对照区。采集8~12岁儿童和18~70岁居民尿液及其家中粮食、蔬菜等食物,以及饮用水和所在村空气样本,检测样本氟含量及尿样肌酐,应用点评估方法计算居民环境氟暴露量,评价暴露风险和健康危害水平。结果 8~15岁和18~70岁居民经食物、饮水和空气摄入氟化物量依次分别为污染区0.243 1mg/d、0.321 1mg/d和对照区0.274 6mg/d、0.410 5mg/d,总氟摄入量均低于《人群总摄氟量卫生标准》规定。但污染区儿童和成人群体尿氟几何均值分别为0.46 mg/L、0.58 mg/L,虽未超过国家有关标准限值,但显著高于对照区儿童(0.34 mg/L)和成人(0.32 mg/L),并且污染区儿童氟斑牙患病率(14.11%)明显高于对照区(1.76%),最高的B村小学儿童氟斑牙检出率高达38.36%。结论该企业周边饮用水、食物和空气等环境介质总体安全,但应持续关注居民尿氟高负荷和儿童氟斑牙高患病率问题,企业在后续的技术改造升级过程中应采取有效措施,确保周边居民身体健康。     

The Inhibitory Effect of Shikonin on the Agonist-Induced Regulation of Vascular Contractility

Shikonin, a natural flavonoid found in the roots of Lithospermum erythrorhizon, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of shikonin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Shikonin significantly relaxed fluoride-, thromboxane A₂- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, shikonin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and the inhibition of MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of shikonin on agonist-induced vascular contraction regardless of endothelial function.     

氟化钠对L02人正常肝细胞衰老及相关蛋白表达影响的实验研究

目的 研究氟化钠（NaF）是否会诱导人肝细胞 L02衰老及衰老相关标志蛋白水平的改变。方法 不同浓度 (0、1、2、3、4、5、6、7和8mmol/L) NaF 处理 L02人正常肝细胞,CCK-8 法检测细胞存活率的变化以筛选 NaF 的作用浓度;衰老标志物 β-半乳糖苷酶 (β-galactosidase, β-Gal) 染色检测衰老阳性细胞;实时荧光定量 PCR (Real-time PCR) 和蛋白免疫印迹 (Western Blot) 测定细胞衰老标志蛋白 p16,p21 mRNA 和蛋白的表达水平;流式细胞术分析细胞周期的变化情况。结果 CCK-8 结果显示,NaF 浓度为 1、4、7mmol/L时 L02细胞的存活率（87.38±0.93、66.72±2.81、52.17±2.04）均低于对照组［(100.00±0.00),均 P<0.01］,且每组之间的细胞存活率差异存在统计学意义（均 P<0.01）,因此 NaF 选用1、4、7 mmol/L 处理L02细胞作为低氟组、中氟组、高氟组开展研究;β-半乳糖苷酶染色结果显示,低、中、高氟组中细胞衰老率 (23.15±0.23、36.06±0.40、65.36±0.82)均高于正常组［(3.27±0. 27),P<0.01］;Real-time PCR 结果显示,p16、p21 mRNA在低、中、高氟组中表达(2.29±0.19、3.44±0.30、5.25±0.32;1.88±0.22、3.22±0.24、7.33±0.30)表达均高于正常对照组［(1.00±0.00;1.00±0.00),均P<0.01］。低、中、高氟组中p16蛋白水平(93.68±3.40、116.25±7.30、122.31±3.00)均高于对照组［(78.07±4.17),P<0.05,P<0.01,P<0.01),低、中、高氟组中p21蛋白水平(87.61±5.22、121.62±4.27、147.95±7.81)均高于对照组［(61.32±4.56),均P<0.01)］;流式结果显示,低、中、高氟组 L02 细胞周期均停滞在 G2 期,与对照组相比,差异具有统计学意义 (P<0.01)。结论 NaF 处理的人肝细胞 L02 中细胞衰老率及衰老标志蛋白 p16、p21 的 mRNA 和蛋白表达升高,这可能提示了 NaF 可导致 L02 细胞衰老,进一步说明细胞衰老在氟化物诱导的肝损伤中可能具有重要作用。     

某燃煤型氟病区儿童血清骨吸收生物标志浓度变化

目的探讨某燃煤型氟中毒病区8～14岁儿童血清骨吸收标志物Ⅰ型胶原交联氨基末端肽(NTX)和抗酒石酸酸性磷酸酶5b(TRACP-5b)的浓度及其与年龄的关系,为氟骨症的发病机制研究提供数据资料。方法整群随机抽取贵州省六盘水市燃煤型氟病区陡菁乡的2所小学8～14岁在校儿童为暴露组(123人),随机抽取非病区花嘠乡某小学学生为对照组(64人),调查氟斑牙情况并检测血清NTX和TRACP-5b的浓度。结果氟病组儿童氟斑牙检出率为94.3%,对照组儿童未检出氟斑牙。氟病组血清NTX、TRACP-5b浓度[13.39(69.99,32.63),280.32(152.06,651.63) nmol/L]低于对照组。氟病组儿童血清NTX在青春早期、青春中期浓度为13.04(10.76,15.64)、14.82(12.15,18.26) nmol/L,低于对照组的15.73(14.36,18.61)、16.45(15.45,22.02) nmol/L(Z值分别为-4.12,-5.40,P值均<0.05);氟病儿童血清TRACP-5b在青春前期、青春早期和青春中期浓度为276.74(237.63,3...     

Fluoride in drinking water and diet: the causative factor of chronic kidney diseases in the North Central Province of Sri Lanka

A significant number of people in the North Central Province of Sri Lanka suffer from chronic kidney diseases (CKD), and the author revisits existing literature related to CKD to find its causative factor. There is a direct connection between high fluoride levels in drinking water and kidney disease, and there are unhealthy levels of fluoride in the groundwater in Sri Lanka’s CKD-affected areas. Based on the following observations, the author believes with confidence that excess fluoride in drinking water and in the locally grown food in the affected areas are the culprits of CKD in Sri Lanka.

• Fluoride excretion rate is considerably lower in children than adults, leading to renal damage of children living in areas with high fluoride.
• Adults who had renal damage due to fluoride in childhood are vulnerable to CKD with continued consumption of water from the same source.
• Patients with chronic renal insufficiency are at an increased risk of chronic fluoride toxicity.
• High content of fluoride in groundwater paves the way to excess fluoride in local food crops, consequently adding more fluoride to the systems of the consumers.
• People who work outdoors for prolonged periods consume excess water and tea, and are subjected to additional doses of fluoride in their system.
• In the mid-1980s, the increase in water table levels of the affected areas due to new irrigation projects paved the way to adding more fluorides to their system through drinking water and locally grown foods.