Chemical reactivity of the carbon-centered free radicals and ferrous iron in coals: Role of bioavailable Fe2+ in coal workers' pneumoconiosis

Striking differences in the prevalence of coal workers' pneumoconiosis (CWP) exist between different coal mine regions. The major factors responsible for the observed regional differences in CWP have not yet been identified. In the present study, chemical reactivity of the carbon-centered free radicals in coals and lung tissues, as well as ferrous iron in the coals, were studied by ESR techniques. The ESR spectra clearly demonstrated the presence of at least two types of carbon-centered free radical species, which might respectively attribute to the macromolecular phase and the molecular phase of coal. Grinding produced free radicals in coals. Exposure of freshly ground coal to air for 28 h induced a slight increase of free radicals for most of the coals, and a slight decrease after 4 months' exposure. The lung tissue samples of coal workers deceased of CWP showed similar ESR spectra as coal samples, and these radicals were highly stable in the lung. After incubation of coals with glutathione, hydrogen peroxide, sodium formate or oxygen, the coal sample from the Gardanne mine which has never induced CWP, and thus is the least hazardous coal, showed the most significant change in the carbon-centered free radical concentration. No significant changes were observed among other coals reported to induce CWP. On the other hand, we found that the coals released different amounts of Fe²⁺ in an acidic medium. Interestingly, the prevalence of CWP correlates positively with the released Fe²⁺ content in these coals and with the amount of oxygen radicals produced by the interaction of Fe²⁺ with O₂ in the acidified coal filtrates. Our studies indicate that the carbon-centered free radicals may not be biologically relevant to coal dust-induced pneumoconiosis, whereas the acid soluble Fe²⁺, which may be dissolved in the phagolysosomes of macrophages, can then lead to Fe²⁺-induced oxidative stress and eventual CWP development.     

Deferoxamine synergistically enhances iron-mediated AP-1 activation: A showcase of the interplay between extracellular-signal-regulated kinase and tyrosine phosphatase

Deferoxamine (DFO) is a drug widely used for iron overload treatment to reduce body iron burden. In the present study, it was shown in mouse epidermal JB6 cells that all iron compounds transiently induced extracellular signal-regulated kinases (ERK) phosphorylation, whereas DFO further enhanced ERK phosphorylation over long periods. The ERK phosphorylation by DFO treatment appears to be due to the inhibition of MAPK phosphatases (MKP) by DFO. The combined effects of iron-initiated MAPK activation and DFO-mediated MKP inhibition resulted in a synergistic enhancement on AP-1 activities. The results indicate that the interplay between MAPK and MKP is important in regulating the extent of AP-1 activation. It is known that administration of DFO in iron overload patients often results in allergic responses at the injection sites. The results suggest that this synergistic AP-1 activation might play a role in DFO-induced skin immune responses of iron overload patients.     

Verapamil Reverses Myocardial No-Reflow After Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

The present study evaluated the efficacy of intracoronary administration of verapamil to attenuate the no-reflow phenomenon following the primary percutaneous coronary intervention (PCI) in patients with the ST-segment elevation acute myocardial infarction (STEMI). A total of 201 patients with STEMI who underwent primary PCI within 12 h from the beginning of the heart attack were included. The no-reflow phenomenon was defined as substantial coronary anterograde flow of TIMI ≤2. Verapamil (100–200 μg) was injected into coronary artery immediately after no-reflow; the coronary arteriography was repeated later. Hundred and ninety-eight patients with STEMI successfully underwent primary PCI, and 246 stents were implanted with the average of 1.2 stents per patient. No-reflow occurred in 25 out of 198 patients (12.6 %). Twenty-one (84 %) patients developed the flow of TIMI ≥3 after intracoronary administration of verapamil, as revealed by repeated coronary angiography. Two patients developed transient hypotension which normalized without treatment within 3–5 min. Three patients showed sinus bradycardia, in one patient there was transient II sinoatrial block, and one patient developed type 1 atrioventricular block. All adverse effects were alleviated after intravenous injection of atropine (0.5–1 mg). In conclusion, the no-reflow phenomenon following primary PCI in patients with STEMI is significantly improved by intracoronary administration of verapamil which is useful to reduce cardiovascular events during operation.     

Linking Material Flow Analysis with Environmental Impact Potential

Technology transition can have significant implications on the evolution of environmental impact potential of disposed electronics over time. Considering technology transition, we quantify the temporal behavior of ecological and human health impact potential from select heavy metals in electronic waste (e‐waste). The case study analyzes product substitution effects in two electronic cohorts from the U.S. market: (1) computers (laptops substituting for desktops) and (2) televisions (flat‐panel liquid crystal displays [LCDs] and plasma displays substituting for cathode‐ray tubes [CRTs]). Quantities of end‐of‐life (EoL) units to year 2030 are forecasted by the unique combination of dynamic material flow analysis, logistic trend analysis, and product lifespan calibration methods. Metal content from EoL units are assessed via a pathway and effect model using USETox? characterization factors to determine the toxicity potential attributed to heavy metal releases into different media (e.g., air, water, and soil) as an indicator of environmental burden. Results show high impact materials such as lead, nickel, and zinc cause changes in human health toxicity potential and copper causes changes in ecological toxicity potential. Effects of dematerialization, such as reduced metal content in laptops over desktops, provide some positive benefits in toxicity potential per product. However, from a market perspective, emerging e‐waste quantities created by increasing per capita penetration rates of electronics and increasing population will offset gains in environmental performance at the product level. The resulting analysis provides guidance on the timing expected for emerging EoL units and an indication of high impact potential materials requiring pollution prevention as product substitution occurs.     

Changes of Sleep Adaptation in Hospitalized Patients with Depression

Sleep adaptation in an unfamiliar environment, the so-called “first-night effect”, is known to occur in healthy individuals. To avoid the confounding effects of the “first-night effect”, the first-night sleep data are not used in most of sleep studies. In the present study, we examined changes of sleep adaptation in hospitalized patients with depression. Polysomnographic recordings were obtained for two consecutive nights from 14 patients, and sleep parameters were compared between both nights. Total sleep time, sleep latency, awakening times, movement awakening time, sleep efficiency, sleep architecture, rapid eye movement (REM) sleep latency, REM intensity, REM density, REM time, REM cycles, and other indicators showed no significant difference (p > 0.05) between the first and second nights. To conclude, hospitalized patients with depression have relatively less change in sleep adaptation, thus, the data from their first night do not need to be discarded.     

Association between Gene Polymorphism of Manganese Superoxide Dismutase and Prostate Cancer Risk

Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species‐induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala‐9Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early‐onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala‐9Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early‐onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:213‐218, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21472     

The Induction of Phagocytic Activation by Mixtures of the Water Chlorination By‐Products,Dichloroacetate‐ and Trichloroacetate,in Mice after Subchronic Exposure

In this study, groups of B6C3F1 male mice were treated with dichloroacetate (DCA), trichloroacetate (TCA), and mixtures of the compounds (Mix I, II, and III) daily by gavage, for 13 weeks. The tested doses were 7.5, 15, and 30 mg DCA/kg/day and 12.5, 25, and 50 mg TCA/kg/day. The DCA: TCA ratios in Mix I, II, and III were 7.5:12.5, 15:25, and 30:50 mg/kg/day, respectively. Peritoneal lavage cells were collected at the end of the treatment period and assayed for the biomarkers of phagocytic activation, including superoxide anion and tumor necrosis factor‐alpha production, and myeloperoxidase activity. The mixtures produced nonlinear effects on the biomarkers of phagocytic activation, with Mix I and II effects were found to be additive, but Mix III effects were found to be less than additive. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:237‐242, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21476     

The Cytotoxic and Proapoptotic Activities of Hypnophilin are Associated with Calcium Signaling in UACC‐62 Cells

Hypnophilin (HNP) is a sesquiterpene that is isolated from Lentinus cf. strigosus and has cytotoxic activities. Here, we studied the calcium signaling and cytotoxic effects of HNP in UACC‐62 cells, a human skin melanoma cell line. HNP was able to increase the intracellular calcium concentration in UACC‐62 cells, which was blocked in cells stimulated in Ca²⁺‐free media. HNP treatment with BAPTA‐AM, an intracellular Ca²⁺ chelator, caused an increase in calcium signals. HNP showed cytotoxicity against UACC‐62 cells in which it induced DNA fragmentation and morphological alterations, including changes in the nuclear chromatin profile and increased cytoplasmatic vacuolization, but it had no effect on the plasma membrane integrity. These data suggest that cytotoxicity in UACC‐62 cells, after treatment with HNP, is associated with Ca²⁺ influx. Together, these findings suggest that HNP is a relevant tool for the further investigation of new anticancer approaches. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:479‐485, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21507