Association of adverse birth outcomes with prenatal uranium exposure: A population-based cohort study.

Uranium (U) is a well-recognized hazardous heavy metal with embryotoxicity and fetotoxicity. However, little is known about its association with adverse birth outcomes. We aimed to investigate the potential correlation between prenatal U exposure and birth outcomes. Urine samples of 8500 women were collected before delivery from a birth cohort in Wuhan, China. Concentrations of urinary U and other metals were measured by inductively coupled plasma mass spectrometry. We used multivariable logistic regressions to evaluate the associations between urinary U concentrations and adverse birth outcomes, such as preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Associations of urinary U concentrations with gestational age, birth weight, and birth length were investigated by linear regressions. The geometric mean of U concentration was 0.03 µg/L. After adjustment for potential confounders, we found each Log2-unit increase in U concentration was associated with a significant decrease in gestational age [adjusted ß = -0.32 day; 95% confidence interval (CI): -0.44, -0.20] and a significant increased likelihood of PTB (adjusted OR = 1.18, 95% CI: 1.07, 1.29). This birth cohort uncovered an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB. Our findings reveal an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB.

Comparison of different sample preparation methods for platinum determination in cultured cells by graphite furnace atomic absorption spectrometry.

BACKGROUND: Platinum-based agents are widely used in chemotherapy against solid tumors and insufficient intracellular drug accumulation is one of the leading causes of platinum resistance which is associated with poor survival of tumor patients. Thus, the detection of intracellular platinum is pivotal for studies aiming to overcome platinum resistance. In the present study, we aimed to establish a reliable graphite furnace atomic absorption spectrometry (GFAAS)-based assay to quantify the intracellular platinum content for cultured cells. METHODS: Several most commonly applied cell preparation methods, including 0.2% HNO3, 0.2% Triton X-100, concentrated nitric acid, RIPA combined with concentrated nitric acid and hydroxide, followed by GFAAS for platinum detection were compared in ovarian, cervical and liver cancer cell lines to obtain the optimal one, and parameters regarding linearity, accuracy, precision and sensitivity were evaluated. Influence of other metals on platinum detection and the storage conditions of samples were also determined. RESULTS: The treatment of cells with 0.2% HNO3 was superior to other approaches with fewer platinum loss and better repeatability. The recovery rate and precision of this method were 97.3%-103.0% and 1.4%-3.8%, respectively. The average recoveries in the presence of other metals were 95.1%-103.1%. The detection limit was 13.23 ug/L. The recovery rate of platinum remained acceptable even in cell samples stored in -20 °C or -80 °C for two months. DISCUSSION: After comparison, we found that 0.2% HNO3 was optimal for intracellular platinum quantification based on GFAAS, which presented values compatible with that of inductively-coupled plasma mass-spectrometry (ICP-MS), and this is partially attributed to the simplicity of this method. Moreover, the assay was proved to be accurate, sensitive, cost-effective and suitable for the research of platinum-based antitumor therapy.

Role of inhibition of osteogenesis function by Sema4D/Plexin-B1 signaling pathway in skeletal fluorosis in vitro.

Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-ß1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-ß1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin (OPG) secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.

Suppression of Sclerostin and Dickkopf-1 levels in patients with fluorine bone injury.

Evidence has been accumulating for the role of Sclerostin and Dickkopf-1 as the antagonists of Wnt/ß-Catenin signaling pathway, which suppresses bone formation through inhibiting osteoblastic function. To get deep-inside information about the expression of the antagonists in patients with fluorine bone injury, a case-control study was conducted in two counties in Hubei Province. Urinary and serum fluoride were significantly higher in patients with fluorine bone injury than in healthy controls. Additionally, patients with fluorine bone injury had significantly lower serum Sclerostin and Dickkopf-1 levels compared with healthy controls (P<0.001). Serum Sclerostin and Dickkopf-1 levels were significantly correlated with serum fluoride in all studied subjects (n=186). Low Sclerostin and Dickkopf-1 levels were associated with a significantly increased risk of fluorine bone injury. In conclusion, serum Sclerostin and Dickkopf-1 might be used as important markers of bone metabolism change and potential therapeutic targets to treat fluorine bone injury.

The influence of fluoride on the expression of inhibitors of Wnt/ß-catenin signaling pathway in rat skin fibroblast Cells.

The effective therapy of fluoride-induced bone diseases requires an understanding of the mechanism of the disorders. Changes in the inhibitors of the Wnt/ß-catenin pathway, Dickkopf-1 (Dkk-1) and Sclerostin (SOST),were studied in supernatants harvested from rat skin fibroblasts cultured with varied doses of fluoride. The contents of SOST and Dkk-1 in fibroblast supernatants were assessed at four exposure time-points and investigated by using the method of ELISA. Compared to the relevant controls(0 mg F(−)/L), a significant decrease of the concentrations of SOST and Dkk-1 was observed as the fluoride concentration increased. Compared to the relevant time controls (24 h), a significant decrease of the concentrations of SOST and Dkk-1 was observed with the extension of time. Our results suggest that the Wnt/ß-catenin pathway inhibitors Dkk-1 and SOST play an important role in skeletal fluorosis. They can be used as important indications for diagnosing bone metabolism changes caused by fluoride exposure and therapeutic targets in diseases resulting from fluoride exposure.

Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP.

OBJECTIVE: To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism. METHODS: In the animal study, rats were allowed free access to drinking water containing different concentrations (10, 150, or 400 mg/L) of sodium fluoride. Serum ALP and BALP activity and serum BGP content were assessed at three exposure time-points. In the spot study, serum ALP and BALP activity and serum BGP content were assessed in workers exposed to fluoride in their working environment for different periods of time. RESULTS: Compared with the control group, on days 15 and 30, the activity of serum ALP in the low- and medium-dose group was significantly higher (p < 0.05), while in the high-dose group it was significantly lower (p < 0.05). Only on day 30 was the activity of serum BALP in the medium-dose group significantly higher than that of the control group (p < 0.05). BGP content was lower in the high-dose group than in the control group (p < 0.05) on days 30 and 90, but it was higher in the medium-dose group on day 90. Compared with the control group, BGP content in the fluoride-exposed group was higher (p < 0.05). In the spot study, serum ALP activity and serum BGP content in the medium working-age group were higher than that in the short working-age group (p < 0.05). However, serum ALP activity and serum BGP content were lower in the long working-age group than in the medium working-age group (p < 0.05). CONCLUSIONS: Our results suggest that serum fluoride and urinary fluoride can be used as reference indications to provide an overall reflection of the body's fluoride-load and fluoride exposure level. Serum ALP activity and serum BGP content can be used as important reference indications for diagnosing bone metabolism changes resulting from fluoride exposure.

Interactive effect of fluoride burden with calcitonin receptor gene polymorphisms on the risk of F bone injury.

PURPOSE: This study aims to examine the interactive effect of fluoride burden with calcitonin receptor (CTR) gene polymorphisms on the risk of fluoride (F) bone injury and provide the basis for determination of F bone injury risk factors. METHODS: In this case-control study, a total of 119 cases and 126 controls were enrolled from 2 aluminum plants in Hubei province. F burden (UF) was measured by F ion-selective electrode method. The CTR gene polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios, 95% confidence intervals (CI). RESULTS: The odds of developing F bone injury for participants in the moderate F burden group versus the mild F burden group were 4.1 (95% CI: 1.9, 8.7); the heavy F burden group versus the mild F burden group were 14.1 (95% CI: 6.5, 30.6). The odds of developing F bone injury for participants with the TC & TT genotypes versus the CC genotype were 2.6 (95% CI: 1.4, 4.7). The interactions between TC & TT genotypes and moderate, heavy F burden were significant (OR = 14.4; OR = 40.3). CONCLUSION: The interactive effect of F burden and CTR genotype was significant, which increased the F bone injury risk.

[Method for concentration determination of mineral-oil fog in the air of workplace].

OBJECTIVE: To study the method of concentration determination of mineral-oil fog in the air of workplace. METHODS: Four filter films such as synthetic fabric filter film, beta glass fiber filter film, chronic filter paper and microporous film were used in this study. Two kinds of dust samplers were used to collect the sample, one sampling at fast flow rate in a short time and the other sampling at slow flow rate with long duration. Subsequently, the filter membrane was weighed with electronic analytical balance. According to sampling efficiency and incremental size, the adsorbent ability of four different filter membranes was compared. RESULTS: When the flow rate was between 10 approximately 20 L/min and the sampling time was between 10 approximately 15 min, the average sampling efficiency of synthetic fabric filter film was 95.61% and the increased weight ranged from 0.87 to 2.60 mg. When the flow rate was between 10 approximately 20 L/min and sampling time was between 10 approximately 15 min, the average sampling efficiency of beta glass fiber filter film was 97.57% and the increased weight was 0.75 approximately 2.47 mg. When the flow rate was between 5 approximately 10 L/min and the sampling time between 10 approximately 20 min, the average sampling efficiency of chronic filter paper and microporous film was 48.94% and 63.15%, respectively and the increased weight was 0.75 approximately 2.15 mg and 0.23 approximately 0.85 mg, respectively. When the flow rate was 3.5 L/min and the sampling time was between 100 approximately 166 min, the average sampling efficiency of filter film were 94.44% and 93.45%, respectively and the average increased weight was 1.28 mg for beta glass fiber filter film and 0.78 mg for beta glass fiber filter film and synthetic fabric synthetic fabric filter film. The average sampling efficiency of chronic filter paper and microporous film were 37.65% and 88.21%, respectively. The average increased weight was 4.30 mg and 1.23 mg, respectively. CONCLUSION: Sampling with synthetic fabric filter film and beta glass fiber filter film is credible, accurate, simple and feasible for determination of the concentration of mineral-oil fog in workplaces.

[Study on metabolism of preventive anti-fluorine agent on rats].

In order to study the metabolism of preventive anti-fluorine agent, 30 rats are randomly divided into high-dose, low-dose and a control groups. The high dose (400 mg/kg.d) and low dose (16 mg/kg.d) are orally administrated respectively, and the content of boron and/or zinc in urine, dung, serum, bone, liver, muscles, brain tissues is determined. The results showed that during the administration of this agent, the content of boron in urine and the content of zinc in dung increases obviously in both high-dose and low-dose groups and their discharge rate is consistent with the dose given. The content of boron and zinc in bone, liver, and zinc in serum, muscles, brain tissues increases evidently compared to that in control group but decreases rapidly after administration of the agent. The findings revealed that there is a rapid metabolism of boron and zinc in the body of rats. The highest content of the agent is observed in bones. The content ranks second in liver and muscles but no accumulative effects are observed.