Trace Elements in Hair: Relevance to Air Pollution

Elemental concentrations of single hair samples taken from 2003 to 2012 had been evaluated by X-ray fluorescence for the assessment of the relation between calcium and cancer. Early results implied a mechanism linking hair and serum element concentrations with a shift in element levels over time. After 2009, pollution-attributable differences were seen in the levels of Ca, Sr, P, Cl, Br, K, S, elements under renal control by parathyroid hormone (PTH), as well as Cu, Zn, Ti. Especially, hair taken from February to March 2011 showed low [Cu] and [Zn] indicating about half of the normal serum level and often three orders of magnitude higher [Ti] than typical. These specimens also showed higher serum [S] than usual, and except for one patient with PTH-related disease, all the subjects had the normal or lower hair calcium than typical for earlier years. Almost all the subjects showed store-operated Ca channel gating. The pollution era is associated with an increase in hair Na, a decrease in K, and abnormally low P, suggesting a functional deterioration of Na+/K+-ATPase. These results can be attributed to increases in serum Ca and S coincident with breathing the polluted air; the incorporated Ca closes the ion channels of hair matrix cells but may be moved with P to bone, resulting in the abnormal P deficiency, likely producing an ATP shortage in serum. This insufficient ATP supply may result in inactivated molecular pumps and hypokalemia contributing to fatal ventricular fibrillation in patients with myocardial infarction. The pollution increase [S] in serum may be excreted by forming sulfide compounds with Cu and Zn, resulting in Cu deficiency necessary for making elastin to repair damage in blood vessels. The K and Cu deficiencies observed appear to account for the reported increase in infarction mortality after high-pollution days

Dioxins and Fatty Acids in Breast Milk of Primiparas in Yonago District, Tottori Prefecture, Japan

We analyzed the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in breast milk collected 1 week after childbirth from 8 primiparas in Yonago district, Tottori Prefecture, and investigated the relationship between PCDDs or PCDFs and fatty acids in concentration, and the relationship between dioxin concentration and kind of daily foods. The mean total content of dioxins (PCDDs and PCDFs) was 0.48 pg-toxic equivalent (TEQ)/g (range 0.12?1.04 pg-TEQ/g) in breast milk, and 16.7 pg-TEQ/g-fat (range 9.6?32.7 pg-TEQ/g-fat) in total lipids of breast milk. The 8 primiparas showed a low mean dioxin concentration: the levels were lower in 6 of them and higher in 2 of them than in primiparas living in other cities in Japan. For 1 of the 2 mothers, the reason for the high level was thought to be her poor intake of vegetables in the diet. The total dioxin content was well correlated with the total lipid content ranging from 1% to 3%. Fatty acids with C16:0 and C18:1 dominated those with C12:0, C14:0, C16:1, C18: 2 and C18:0, which were commonly detected. The amount of fatty acids with C10:0, C20:1, C20:2, C20:3, C20:4, C22:5 and C22:6 was small. Gas chromatograms of these fatty acids generally showed similar distributions in breast milk of the 8 primiparas. The contents of fatty acids ranged from 17.1 to 31.3 mg/g (average 24.0 mg/g) in bulk breast milk. No clear correlation was found in concentration between PCDDs or PCDFs and specific fatty acids in breast milk

Entrance surface dose measurements using a small OSL dosimeter with a computed tomography scanner having 320 rows of detectors

Entrance surface dose (ESD) measurements are important in X-ray computed tomography (CT) for examination, but in clinical settings it is difficult to measure ESDs because of a lack of suitable dosimeters. We focus on the capability of a small optically stimulated luminescence (OSL) dosimeter. The aim of this study is to propose a practical method for using an OSL dosimeter to measure the ESD when performing a CT examination. The small OSL dosimeter has an outer width of 10 mm; it is assumed that a partial dose may be measured because the slice thickness and helical pitch can be set to various values. To verify our method, we used a CT scanner having 320 rows of detectors and checked the consistencies of the ESDs measured using OSL dosimeters by comparing them with those measured using Gafchromic™ films. The films were calibrated using an ionization chamber on the basis of half-value layer estimation. On the other hand, the OSL dosimeter was appropriately calibrated using a practical calibration curve previously proposed by our group. The ESDs measured using the OSL dosimeters were in good agreement with the reference ESDs from the Gafchromic™ films. Using these data, we also estimated the uncertainty of ESDs measured with small OSL dosimeters. We concluded that a small OSL dosimeter can be considered suitable for measuring the ESD with an uncertainty of 30 % during CT examinations in which pitch factors below 1.000 are applied

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL

Influence of Npc1 genotype on the toxicity of hydroxypropyl-β-cyclodextrin, a potentially therapeutic agent, in Niemann–Pick Type C disease models

Hydroxypropyl-β-cyclodextrin (HPBCD) is an attractive drug candidate against Niemann–Pick Type C (NPC) disease. However, the safety of HPBCD treatment for NPC patients remains to be elucidated. In this study, we examined the acute toxicity of HPBCD in Npc1-deficient mice. When treated with HPBCD (20,000 mg/kg, subcutaneously), over half of the wild-type (Npc1+/+) or Npc1+/− mice died by 72 h after the injection. In contrast, all of the Npc1−/− mice survived. Marked pathophysiological changes, such as an elevation in serum transaminase and creatinine levels, hepatocellular necrosis, renal tubular damage, interstitial thickening, and hemorrhages in lungs, were induced by the HPBCD treatment in Npc1+/+ or Npc1+/− mice. However, these pathophysiological changes were significantly alleviated in Npc1−/− mice. In addition, in vitro analysis showed that the Npc1 gene deficiency and treatment with U18666A, an Npc1 inhibitor, remarkably attenuated the cytotoxicity of HPBCD in Chinese hamster ovary cells. These results suggest that the NPC1 genotype exacerbates the cytotoxicity of HPBCD and Npc1−/− mice have substantial resistance to the lethality and the organ injury induced by HPBCD injection compared with Npc1+/+ or Npc1+/− mice. We suggest that the Npc1 genotype should be considered in the safety evaluation of HPBCD using experimental animals and cells