Relationship between Trace Element in Tumor and Prognosis in Lung Cancer Patients.

Background and Objectives: This study aimed to observe the relationship between trace element concentrations in lung tissue from lung non-small cell lung carcinoma (NSCLC) patients and prognosis. Materials and Methods: The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. Eight essential trace elements, Cr, Mn, Fe, Co, Cu, Zn, Se, and Mo, were analyzed. We investigated the relationship between trace element concentrations and disease-free survival (DFS) and overall survival (OS) in NSCLC patients. Results: A total of 129 NSCLC patients and 20 control patients were included in this study. As for DFS, Co was the only element that showed a significant difference, and the high Co group had better DFS (HR: 0.352, 95% CI = 0.128-0.97). No significant difference was observed for Cr, Mn, Fe, Se, or Mo, but DFS tended to be better in the high trace element group. No significant difference was observed for Cu and Zn, but DFS tended to be good in the low trace element group. As for OS, Cr was the only element that showed a significant difference, and the high Cr element group had better OS (HR: 0.477, 95% CI = 0.128-0.97). Conclusions: This study suggests that the prognosis is good in lung cancer cases with high intratumoral concentrations of Co and Cr. The dynamics of trace elements in body and in tumor tissue have not been well established, and we consider that more research is necessary in the future.

Iron treatment inhibits Aß42 deposition in vivo and reduces Aß42/Aß40 ratio.

Alzheimer's disease (AD) is characterized by the formation of extracellular amyloid plaques containing the amyloid ß-protein (Aß) within the parenchyma of the brain. Aß42, which is 42 amino acids in length, is considered to be the key pathogenic factor in AD. Iron deposition is found abundantly in the amyloid plaques of AD patients; however, whether iron intake exacerbates amyloid deposition in vivo is unknown. Here, we treated AD model mice with iron-containing water and found that Aß42 deposition in the brain was significantly inhibited, along with a decrease in iron deposition. Iron treatment did not change the overall levels of iron in the brain or serum. Interestingly, Aß40 generation was significantly increased by iron treatment in amyloid precursor protein (APP)-overexpressing fibroblasts, whereas Aß42 generation did not change, which led to a decreased Aß42/Aß40 ratio. Because Aß40 can inhibit Aß42 aggregation in vitro, and Aß40 inhibits amyloid formation in vivo, our results suggest that iron can selectively enhances Aß40 generation and inhibit amyloid deposition by reducing the Aß42/Aß40 ratio. Thus, iron may be used as a novel treatment for reducing the Aß42/Aß40 ratio and Aß42 deposition in AD.

Study of trace elements in stranded green turtles (Chelonia mydas), hawksbill turtles (Eretmochelys imbricata), and olive ridley turtles (Lepidochelys olivacea) in Gulf of Thailand and Andaman Sea.

The purpose of this study was to survey and compare the amounts of elements in the serum of stranded sea turtles from the Gulf of Thailand and the Andaman Sea. The sea turtles from the Gulf of Thailand had Ca, Mg, P, S, Se, and Si concentrations significantly higher than those in sea turtles from the Andaman Sea. The Ni and Pb concentrations of sea turtles from the Gulf of Thailand was higher, but not significantly so, than in sea turtles from the Andaman Sea. Rb was detected only in sea turtles from the Gulf of Thailand. This may have been related to the industrial activities in Eastern Thailand. The concentration of Br in the sea turtles from the Andaman Sea were significantly higher than those in sea turtles from the Gulf of Thailand. The higher serum concentration of Cu in hawksbill (H) and olive ridley turtles (O) than in green turtles may be due to hemocyanin, as an important component in the blood of crustaceans. The higher Fe concentration in the serum from green turtles than for H and O may be due to chlorophyll, which is an important component of chloroplasts in eel grass. Co was not found in the serum of green turtles but was found in the serum of H and O. The monitoring of important elements in sea turtles may be used as a tool to assess the levels of pollution in marine ecosystems.

Contamination Level in Geo-Accumulation Index of River Sediments at Artisanal and Small-Scale Gold Mining Area in Gorontalo Province, Indonesia.

Substances found in watersheds and sediments in artisanal and small-scale gold mining (ASGM) areas contaminated by heavy metals are becoming tremendously critical issues in Asia. This study aimed at clarifying the pollution caused by heavy metals in sediments in river basins near ASGM sites in Gorontalo Province, North Sulawesi, Indonesia. Sediment samples collected from experimental areas were classified into nine clay samples and twenty-seven sand samples, whereas three other samples were collected from the control area. Particle-induced X-ray emission was used to analyze these samples. The Statistical Package for the Social Science and the geo-accumulation index (Igeo) were also used for analysis. Based on the results, Hg, Pb, As, and Zn had a concentration of 0−334 µg/g, 5.5−1930 µg/g, 0−18,900 µg/g, and 0−4923.2 µg/g, respectively, which exceeded limits recommended by the U.S. Environmental Protection Agency consensus (1991) and the Indonesian Government Regulation Number 38, 2011. Furthermore, Igeo showed the order of the pollution degree Hg < Zn < Pb < As and reflected an environment contaminated by heavy metals, ranging from unpolluted to extremely polluted areas. Therefore, sediments contaminated by Hg, Pb, As, and Zn could be found along the river basin of mining areas.

Environmental Survey of the Distribution and Metal Contents of Pteris vittata in Arsenic-Lead-Mercury-Contaminated Gold Mining Areas along the Bone River in Gorontalo Province, Indonesia.

In this paper, we report ecological and environmental investigations on Pteris vittata in the As-Pb-Hg-polluted Bone River area, Gorontalo Province, Indonesia. The density distribution of P. vittata decreases from around the artisanal and small-scale gold mining (ASGM) site to the lower reaches of the Bone River, and it is rarely found near Gorontalo City. The maximum concentrations of As, Hg, and Pb recorded in the soil samples were 401, 36, and 159 mg kg-1, respectively, with their maximum concentrations in P. vittata recorded as 17,700, 5.2, and 39 mg kg-1, respectively. Around the ASGM sites, the concentrations of As, Pb, and Hg in P. vittata were highest in the study area. These data suggest that P. vittata, a hyperaccumulator of As, may be useful as a bioindicator for assessing environmental pollution by Pb and Hg.

Element Rich Area Associated with Human Health Disorders: A Geomedical Science Approach to Potentially Toxic Elements Contamination.

(1) Background: Geomedical science focuses on the relationship between environmental impact and human health. The abundance of elements in a geographic area is reflected accumulation of these elements in humans. This study aims to describe the relationship between concentrations of geologic elements and accumulations in the human body as well as element-related symptoms. (2) Methods: Geogenic sampling was conducted in an Artisanal and Small-Scale Gold Mining (ASGM) area and around residential areas in Indonesia, and samples were analyzed using particle-induced X-ray Emission (PIXE). Head hair was sampled, and health assessments were performed to determine heavy metal exposure, especially to copper and mercury. (3) Results: Results show that potentially toxic elements' accumulation in the human body follows the abundance of these elements in the geographic area, which then affect health and manifest with specific signs and symptoms. East Tulabolo is an area rich in copper (hazard quotient (HQ) in dust = 152.8), and most of the population shows the sign of Kayser-Fleischer rings. Likewise, the Dunggilata area has the highest concentration of mercury, especially in the dust (HQ = 11.1), related to ASGM activity in residential areas. (4) Conclusions: This study concludes that the geogenic concentration of elements parallels the accumulation of human tissue and manifests with element-related signs and symptoms.

Evaluation of the Total Mercury Weight Exposure Distribution Using Tree Bark Analysis in an Artisanal and Small-Scale Gold Mining Area, North Gorontalo Regency, Gorontalo Province, Indonesia.

It is well known that atmospheric mercury (Hg) contaminates air, water, soil, and living organisms, including trees. Therefore, tree bark can be used for the environmental assessment of atmospheric contamination because it absorbs heavy metals. This study aimed to establish a new biomonitoring for the assessment of atmospheric Hg pollution. Reporting on atmospheric Hg contamination in an artisanal and small-scale gold mining (ASGM) area in North Gorontalo, Indonesia, we calculated the total weight of Hg (THg) and quantitatively measured the concentrations of Hg in the tree bark of Mangifera indica, Syzygium aromaticum, Terminalia catappa, and Lansium domesticum. The THg of Hg in the M. indica tree bark samples ranged from not detected (ND) to 74.6 µg dry weight (DW) per sample. The total Hg in the tree bark of S. aromaticum, T. catappa, and L. domesticum ranged from ND to 156.8, ND to 180, and ND to 63.4 µg DW, respectively. We concluded that topography significantly influences the accumulation of Hg together with local weather conditions. A mapped distribution of the THg suggested that the distribution of THg in the tree bark was not affected by the distance to the amalgamation site. Therefore, tree bark can be used as biomonitoring of atmospheric Hg contamination for the assessment of ASGM areas.

Mercury in Soil and Forage Plants from Artisanal and Small-Scale Gold Mining in the Bombana Area, Indonesia.

Mercury (Hg) contamination in soil and forage plants is toxic to ecosystems, and artisanal and small-scale gold mining (ASGM) is the main source of such pollution in the Bombana area of Indonesia. Hg contamination in soil and forage plants was investigated by particle-induced X-ray emission analysis of samples collected from three savannah areas (i.e., ASGM, commercial mining, and control areas) in the Bombana area. Hg contents of forage plants in the ASGM area (mean 9.90 ± 14 µg/g) exceeded those in the control area (2.70 ± 14 µg/g). Soil Hg contents (mean 390 ± 860 µg/g) were also higher than those in the control area (mean 7.40 ± 9.90 µg/g), with levels exceeding international regulatory limits. The Hg contents of 69% of soil and 78% of forage-plant samples exceeded critical toxicological limits. Thus, the Hg levels observed in this study indicate that contamination extending over large areas may cause major environmental problems.

Sequential changes in serum zinc concentrations in calves with experimentally induced endotoxin shock measured by the particle-induced X-ray emission method.

The aim of the present study was to measure changes in the serum concentrations of some elements in endotoxin-challenged calves using a particle-induced X-ray emission analysis and to screen for elements useful as diagnostic markers. The results obtained revealed that serum Zn concentrations were more accurate diagnostic markers for detecting endotoxin shock in calves than other elements. Serum Zn level in endotoxin-challenged calve was significantly lower from 8 to 12 hr after the endotoxin challenge than pre-challenge values. In addition, serum Zn concentrations in calves from 4 to 24 hr after endotoxin challenges were significantly lower than those of control. Our results indicate that serum Zn concentration has potential as diagnostic markers for detecting inflammation in calves with endotoxin shock.

Elemental and mutational analysis of lung tissue in lung adenocarcinoma patients.

BACKGROUND: This study aimed to observe the association between trace element concentrations in lung tissue from lung adenocarcinoma cancer (LADC) patients and mutations in the epidermal growth factor receptor (EGFR) and KRAS genes. METHODS: LADC patients who had undergone lung resection were included in this study. Furthermore, twenty patients without lung cancer were included in this study as the control group. Samples were separately collected from both tumor and peritumor tissues. The mutational status was assessed for EGFR mutations, ALK rearrangements and KRAS mutations. Based on these analyses, patients were grouped into three groups: EGFR mutation, KRAS mutation and wild-type groups. The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. RESULTS: A total of 110 LADC patients were included in this study. The median age was 70 years, and 60% of the participants were female. Moreover, 18% and 20% of patients were EGFR- and KRAS-positive, respectively. Thirty-two trace elements were measured, and 18 trace elements were detectable. The concentrations of Fe, Co, Ni, Cu, Zn and Br were significantly higher in the KRAS mutation and wild-type groups than in the control group regardless of whether the samples were from tumor or peritumor tissues. For these 6 trace elements, the concentrations were significantly higher in smokers than in non-smokers. Considering the effect of smoking, differences in the trace element concentrations between each mutational group remained. CONCLUSIONS: Trace elements in the lung may play a role in development of LADC in both smokers and never-smokers. However, prospective studies with larger sample sizes are needed to support this hypothesis.

[Biodistribution of ultrafine particles of titanium dioxide by intratracheal administration to mice].

TiO2 ultrafine particles are used as photo-catalysis. When ultrafine particles are exposed to hosts, they are invaded in alveolar, transferred to organs through blood vessels and may express biological effects. We administered TiO2 ultra-fine particles (5 nm, 100 nm) intratracheally to mice, and collected whole blood and removed organs (liver, lung, kidney, spleen and brain) after 1, 4 and 24 hours. The quantity of Ti in the blood and these organs was analyzed by PIXE (Particle Induced X-Ray Emission) or ICP/MS (Inductively Coupled Plasma-Mass Spectrometry). Compared to control mice, the quantity of Ti in the exposed mice was not different. Consequently, we observed the solution of dissolved TiO2 ultrafine particles by Scanning Electron Microscope, and observed the particles which aggregated. That diameter was about 1 microm. We concluded that the particles had aggregated before administration to mice, so they didn't invade the blood vessels or organs from the pulmonary alveolus in the lung.

Lung Function Assessment as an Early Biomonitor of Mercury-Induced Health Disorders in Artisanal and Small-Scale Gold Mining Areas in Indonesia.

The evaluation of mercury impact on humans is currently nonspecific because the body characteristics (homeostasis) of each human being varies. Therefore, in the early diagnosis of mercury toxicity, one of the most important monitoring parameters is the respiratory function examination. In this study, respiratory function was examined with a portable spirometer and correlated with the mercury levels in hair from the noses and heads of subjects. Samples were taken from artisanal and small-scale gold mining (ASGM) areas (villages of East Tulabolo and Dunggilata) and control areas (villages of Bongo and Longalo) in Gorontalo Province, Indonesia. A statistical analysis with the Mann⁻Whitney test (alternative) showed significant differences in lung function between the polluted and control areas (α = 0.03). The analysis of nasal and head hair samples with particle-induced X-ray emissions (PIXE) showed that the mercury levels in the ASGM area were considerably higher than in the more homogeneous control areas. This study confirms that a pulmonary function test is a quick and precise alternative way to monitor the impact of mercury on humans, especially atmospheric mercury, because we detected a negative correlation between pulmonary function and the level of mercury in hair.

Statistical resolutions for large variabilities in hair mineral analysis.

Measuring biomaterials is usually subject to error. Measurement errors are classified into either random errors or biases. Random errors can be well controlled using appropriate statistical methods. But, biases due to unknown, unobserved, or temporary causes, may lead to biased conclusions. This study describes a verification method to examine whether measurement errors are random or not and to determine efficient statistical methods. A number of studies have dealt with associations between hair minerals and exposures such as health, dietary or environmental conditions. Most review papers, however, emphasize the necessity for validation of hair mineral measurements, since large variations can cause highly variable results. To address these issues, we answer the following questions: How can we ascertain the reliability of measurements?How can we assess and control the variability of measurements?How do we efficiently determine associations between hair minerals and exposures?How can we concisely present the reference values? Since hair minerals all have distinctive natures, it would be unproductive to examine each mineral individually to find significant and consistent answers that apply to all minerals. To surmount this difficulty, we used one simple model for all minerals to explore quantitative answers. Hair mineral measurements of six-year-old children were analyzed based on the statistical model. The analysis verified that most of the measurements were reliable, and their inter-individual variations followed two-parameter distributions. These results allow for sophisticated study designs and efficient statistical methods to examine the effects of various kinds of exposures on hair minerals.

Current Mercury Exposure from Artisanal and Small-Scale Gold Mining in Bombana, Southeast Sulawesi, Indonesia-Future Significant Health Risks.

The rapid expansion of the artisanal and small-scale gold mining (ASGM) industry in developing countries has marginalized the local communities in poverty, and resulted in occupational exposure to mercury via the gold extraction process. We investigated the mercury exposure of the mining workers lived inside and outside the mining area. Based on the occupations of the contributors, the hair samples were divided into three subgroups: directly exposed, indirectly exposed, and a control. A total of 81 hair samples were analyzed by particle-induced X-ray emission spectrometry. The median mercury concentration was highest in the hair from the directly exposed group (12.82 µg/g hair) (control group median: 4.8 µg/g hair, p < 0.05), and the concentrations in hair from 45 respondents exceeded the Human Biomonitoring I (HBM I) threshold limit. Mercury concentrations were also elevated in the hair from the indirectly exposed group (median 7.64 µg/g hair, p < 0.05), and concentrations in hair from 24 respondents exceeded the HBM I threshold limits. Exposure to mercury during ASGM presents health risks and is harmful for the miners; mercury is also at hazardous levels for people who live in the mining area but who are not engaged in mercury-based gold extraction.

Total Calcium and Albumin Are Decreased in the Deeper Epidermis of Patients with Chronic Kidney Disease-Associated Pruritus.

BACKGROUND/AIMS: In our earlier studies, we reported high concentrations of intra- and extracellular calcium ions (Ca2+) in the deeper epidermis of patients with chronic kidney disease (CKD) and associated pruritus. To determine the cause of this phenomenon, we measured total calcium (TCa) concentrations in the deeper epidermis and performed immunostaining of epidermal albumin, which binds to Ca2+. METHODS: This study included 45 patients with CKD-stage 5, which was defined as severely reduced kidney function (i.e., estimated glomerular filtration rate less than 15 mL/min or on dialysis). Subjects were divided into the pruritus group, consisting of patients with mild, moderate, or severe uremic pruritus, and the non-pruritus group, consisting of patients with no or slight pruritus. The particle-induced X-ray emission method was used to measure elements including TCa. Furthermore, we have immunostained epidermal albumin using anti-albumin antibodies and compared the results in the pruritus and non-pruritus groups. RESULTS: The TCa concentration in the spinous layer of patients with CKD with CKD-associated pruritus was lower than in patients with CKD without pruritus (median [range], 395 [235-1,063] vs. 476 [342-1,243] µg/g). The intensity of epidermal albumin expression in the spinous layer was weaker in patients with CKD with CKD-associated pruritus than in those without. CONCLUSION: Patients with CKD with CKD-associated pruritus demonstrated higher Ca2+ concentrations but lower TCa concentrations than patients without CKD-associated pruritus. This could be in part due to low concentrations of epidermal albumin, which binds to Ca2+, in those with CKD-associated pruritus. These results clarify the pathophysiology of CKD-associated pruritus, providing a valuable foundation for the future development of treatments for this condition.

Plasma lead, silicon and titanium concentrations are considerably higher in green sea turtle from the suburban coast than in those from the rural coast in Okinawa, Japan.

The purpose of this study was to compare the concentration of trace elements in the plasma of sea turtles that inhabited the suburban (Okinawa Main Island, n=8) and the rural coast (Yaeyama Island, n=57) in Okinawa, Japan. Particle induced X-ray emission allowed detection of 20 trace and major elements. The wild sea turtles in the suburban coast in Okinawa were found to have high concentrations of Pb, Si and Ti in the plasma when compared to the rural area but there were no significant changes in the Al, As and Hg concentrations. These results may help to suggest the status of some elements in a marine environment. Further, monitoring the plasma trace and major element status in sea turtles can be used as a bio-monitoring approach by which specific types of elements found here could indicate effects that are related to human activities.

Evaluation of urinary 8-hydroxydeoxyguanine in healthy Japanese people.

The urinary concentration of 8-hydroxydeoxyguanine (8-OHdG), which is a biomarker of oxidative DNA damage, was measured in 248 healthy Japanese, and its correlations with life style, urinary metal elements, serum antioxidants, and other plasma or serum factors were investigated. The mean urinary concentration of 8-OHdG was 15.2+/-5.71 ng/mg creatinine. Mean urinary 8-OHdG was not significantly different in terms of age (<45, >or=45), gender, smoking (no, <20, >or=20), and alcohol consumption (no, occasionally, sometimes and usually). Moreover, multiple regression analysis showed a significant association between urinary 8-OHdG and urinary arsenic (As) or chromium (Cr), and a tendency for association between the former and aluminum (Al) and nickel (Ni). Age, gender and plasma or serum factors including antioxidants, lipid peroxide, HbA1c, BUN, and iron did not show such an association. The present study suggests that natural exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative DNA damage in healthy people under usual environmental management. Therefore, the measurement of urinary metals such as As, Ni and Cr is prerequisite for the study of the relationship between urinary 8-OHdG and other variable factors.

Effects of formalin-preservation on element concentrations in animal tissues.

Determination of the exposure level of environmental pollutants is essential in studies on environmental toxicology. If concentrations of exposed pollutants in tissues are not affected by formalin-preservation, a preserved specimen will provide not only histopathological information but also the exposure level of environmental pollutants. In the present study, concentrations of nine elements in the liver and kidney were compared between fresh and formalin- or neutral formalin-preserved specimens to validate the ultimate analysis of the preserved specimens. After one year of preservation, various elements had diffused from the specimens into the solutions. The concentrations of iron, copper, zinc (in the case of neutral formalin) and selenium in the central region of the specimens showed no alterations, suggesting that the diffusions of these elements were limited to the surface of the specimens. Therefore, preserved specimens may be available for the determination of these elements if the specimens are large enough for their surface to be removed. Concentrations of other elements in the preserved specimens were different from the original ones, because the diffusion or infiltration also occurred in the deep region of the specimens.

Relationship between trace elements status in mane hair and atrial fibrillation in horse.

To investigate the relationships between trace elements concentrations in hair and atrial fibrillation (AF) in horses, concentrations of nineteen trace elements were detected in hair using the particle induced X-ray emission (PIXE) method. The horses were assigned to either control (n=22, no abnormalities) or AF groups (n=5) based on electrocardiograph findings. The mean concentrations of Ca and Zn in the hair of the AF group were significantly higher than those in the control group. The Zn/Cu ratio of the hair in the AF group (29.8 +/- 5.5) was significantly higher than that in the control group (23.4 +/- 2.2, P<0.05). The results of the present study suggest that there is a relationship between elevated concentrations of Ca and Zn in hair and AF.

Correlation between 25 element contents in mane hair in riding horses and atrioventricular block.

The influence of atrioventricular block (AV-block) on the trace elemental status in a horse hair was studied. The particle-induced X-ray emission (PIXE) method has provided a reliable, rapid, easy, and relatively inexpensive diagnostic method. Twenty-five elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Hg, K, Mg, Mn, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, Y, and Zn) in mane hair and serum were measured by the PIXE method. A horse hair with first- and second-degree AV-block contained significantly greater amounts of Br, Ca, Sr, and Zn than those of horses without electrocardiographic abnormalities, whereas there was no significant differences in the elemental contents of the serum of the both groups. Those results in contents of a horse hair suggest that the evaluation of the degree of ionic imbalance by this method might be used to predict the susceptibility of a horse to heart disease much before symptoms appear.