Metals detected by ICP/MS in wound tissue of war injuries without fragments in Gaza

<p>Abstract</p> <p>Background</p> <p>The amount and identity of metals incorporated into "weapons without fragments" remain undisclosed to health personnel. This poses a long-term risk of assumption and contributes to additional hazards for victims because of increased difficulties with clinical management. We assessed if there was evidence that metals are embedded in "wounds without fragments" of victims of the Israeli military operations in Gaza in 2006 and 2009.</p> <p>Methods</p> <p>Biopsies of "wounds without fragments" from clinically classified injuries, amputation (A), charred (C), burns (B), multiple piercing wounds by White Phosphorus (WP) (M), were analyzed by ICP/MS for content in 32 metals.</p> <p>Results</p> <p>Toxic and carcinogenic metals were detected in folds over control tissues in wound tissues from all injuries: in A and C wounds (Al, Ti, Cu, Sr, Ba, Co, Hg, V, Cs and Sn), in M wounds (Al, Ti, Cu, Sr, Ba, Co and Hg) and in B wounds (Co, Hg, Cs, and Sn); Pb and U in wounds of all classes; B, As, Mn, Rb, Cd, Cr, Zn in wounds of all classes, but M; Ni was in wounds of class A. Kind and amounts of metals correlate with clinical classification of injuries, exposing a specific metal signature, similar for 2006 and 2009 samples.</p> <p>Conclusions</p> <p>The presence of toxic and carcinogenic metals in wound tissue is indicative of the presence in weapon inducing the injury. Metal contamination of wounds carries unknown long term risks for survivors, and can imply effects on populations from environmental contamination. We discuss remediation strategies, and believe that these data suggest the need for epidemiological and environmental surveys.</p

Obesity and male breast cancer: Provocative parallels?

While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21st century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence

Endocrine disruptors and obesity

The purpose of this review is to summarise current evidence that some environmental chemicals may be able to interfere in endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine disrupting chemicals, termed “obesogens”, can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer

Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study

Abstract Background Exposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt. Methods We measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure. Results Urban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA. Conclusions Despite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.http://deepblue.lib.umich.edu/bitstream/2027.42/112495/1/12940_2011_Article_523.pd

Non-randomness of the anatomical distribution of tumors

Background: Why does a tumor start where it does within an organ? Location is traditionally viewed as a random event, yet the statistics of the location of tumors argues against this being a random occurrence. There are numerous examples including that of breast cancer. More than half of invasive breast cancer tumors start in the upper outer quadrant of the breast near the armpit, even though it is estimated that only 35 to 40% of breast tissue is in this quadrant. This suggests that there is an unknown microenvironmental factor that significantly increases the risk of cancer in a spatial manner and that is not solely due to genes or toxins. We hypothesize that tumors are more prone to form in healthy tissue at microvascular ‘hot spots’ where there is a high local concentration of microvessels providing an increased blood flow that ensures an ample supply of oxygen, nutrients, and receptors for growth factors that promote the generation of new blood vessels. Results: To show the plausibility of our hypothesis, we calculated the fractional probability that there is at least one microvascular hot spot in each region of the breast assuming a Poisson distribution of microvessels in two-dimensional cross sections of breast tissue. We modulated the microvessel density in various regions of the breast according to the total hemoglobin concentration measured by near infrared diffuse optical spectroscopy in different regions of the breast. Defining a hot spot to be a circle of radius 200 μm with at least 5 microvessels, and using a previously measured mean microvessel density of 1 microvessel/mm2, we find good agreement of the fractional probability of at least one hot spot in different regions of the breast with the observed invasive tumor occurrence. However, there is no reason to believe that the microvascular distribution obeys a Poisson distribution. Conclusions: The spatial location of a tumor in an organ is not entirely random, indicating an unknown risk factor. Much work needs to be done to understand why a tumor occurs where it does. Electronic supplementary material The online version of this article (10.1186/s41236-017-0006-7) contains supplementary material, which is available to authorized users

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease

BACKGROUND: Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of metastatic breast cancers providing support for blockade of AR-signalling. However, clinical studies with abiraterone, which blocks cytochrome P450 17A1 (CYP17A1) showed limited benefit. METHODS: In order to address this, we assessed the impact of abiraterone on cell-viability, cell-death, ER-mediated transactivation and recruitment to target promoters. together with ligand-binding assays in a panel of ER+ breast cancer cell lines that were either oestrogen-dependent, modelling endocrine-sensitive disease, or oestrogen-independent modelling relapse on an aromatase inhibitor. The latter, harboured wild-type (wt) or naturally occurring ESR1 mutations. RESULTS: Similar to oestrogen, abiraterone showed paradoxical impact on proliferation by stimulating cell growth or death, depending on whether the cells are hormone-dependent or have undergone prolonged oestrogen-deprivation, respectively. Abiraterone increased ER-turnover, induced ER-mediated transactivation and ER-degradation via the proteasome. CONCLUSIONS: Our study confirms the oestrogenic activity of abiraterone and highlights its differential impact on cells dependent on oestrogen for their proliferation vs. those that are ligand-independent and harbour wt or mutant ESR1. These properties could impact the clinical efficacy of abiraterone in breast cancer