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lead toxicity

Felix Stibany, Stine Nørgaard Schmidt, Andreas Schäffer, Philipp Mayer
The aims of the present study were (1) to develop a passive dosing approach for aquatic toxicity testing of liquid substances with very high Kow values and (2) to apply this approach to the model substance dodecylbenzene (DDB, Log Kow = 8.65). The first step was to design a new passive dosing format for testing DDB exactly at its saturation limit. Silicone O-rings were saturated by direct immersion in pure liquid DDB, which resulted in swelling of >14%. These saturated O-rings were used to establish and maintain DDB exposure exactly at the saturation limit throughout 72-h algal growth inhibition tests with green algae Raphidocelis subcapitata...
October 18, 2016: Chemosphere
Philippe Glorennec, Jean-Paul Lucas, Anne-Camille Mercat, Alain-Claude Roudot, Barbara Le Bot
Children are exposed to toxic metals and metalloids via their diet and environment. Our objective was to assess the aggregate chronic exposure of children aged 3-6years, living in France, to As, Cd, Cr, Cu, Mn, Pb, Sb, Sr, and V present in diet, tap water, air, soil and floor dust in the years 2007-2009. Dietary data came from the French Total Diet Study, while concentrations in residential tap water, soil and indoor floor dust came from the 'Plomb-Habitat' nationwide representative survey on children's lead exposure at home...
October 19, 2016: Environment International
N Gamkrelidze, N Pavliashvili, R Otarashvili
This study describes hematocrit values and quantitative changes in plasma endothelin-1 (ET-1) levels according to the severity of crush syndrome (CS) compression and decompression periods. The experiments were carried out on 50 randomly selected 200-250 gr mass Wistar rats with the use of the standard crush syndrome modeling method. The plasma level of ET-1 was determined by the immuneenzyme method with the use of ELISA REDEAR URIT 660. Hematocrit was determined using the standard method and measured according to tube column divisions...
September 2016: Georgian Medical News
V Lakshma Nayak, Narayana Nagesh, A Ravikumar, Chandrakant Bagul, M V P S Vishnuvardhan, Vunnam Srinivasulu, Ahmed Kamal
Apoptosis is a representative form of programmed cell death, which has been assumed to be critical for cancer prevention. Thus, any agent that can induce apoptosis may be useful for cancer treatment and apoptosis induction is arguably the most potent defense against cancer promotion. In our previous studies, 2-aryl benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity and one of the new molecule (2f) was considered as a potential lead. This lead molecule showed significant antiproliferative activity against human breast cancer cell line, MCF-7...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
Bronwen J Mayo, Andrea M Stringer, Joanne M Bowen, Emma H Bateman, Dorothy M Keefe
PURPOSE: A common side effect of irinotecan administration is gastrointestinal mucositis, often manifesting as severe diarrhoea. The damage to the structure and function of the gastrointestinal tract caused by this cytotoxic agent is debilitating and often leads to alterations in patients' regimens, hospitalisation or stoppage of treatment. The purpose of this review is to identify mechanisms of irinotecan-induced intestinal damage and a potential role for GLP-2 analogues for intervention...
October 21, 2016: Cancer Chemotherapy and Pharmacology
H Mielke, E Di Consiglio, R Kreutz, F Partosch, E Testai, U Gundert-Remy
A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading to the same concentration-time profile as measured in cultured human hepatic cells (Truisi et al. in Toxicol Lett 233(2):172-186, 2015). We parameterized the PBHKM with data from an in vivo study. Tissue partition coefficients were calculated by an algorithm and also derived from the experimental in vitro data for the liver. The predicted concentration-time profile in plasma was in excellent agreement with human experimental data when the liver partition coefficient was calculated by the algorithm (3...
October 21, 2016: Archives of Toxicology
Raghavendra Gowda, Arati Sharma, Gavin P Robertson
Melanoma is a highly drug resistant cancer. To circumvent this problem, a class of synergistically acting drug combinations, which inhibit multiple key pathways in melanoma cells, could be used as one approach for long-term treatment of this deadly disease. A screen has been undertaken on cell lines to identify those that could be combined to synergistically kill melanoma cells. Plumbagin and Celecoxib are two agents that were identified to synergistically kill melanoma cells by inhibiting the COX-2 and STAT3 pathways, which are constitutively activated in up to 70% of melanomas...
October 18, 2016: Cancer Letters
Hongli Li, Victoria M Hitchins, Samanthi Wickramasekara
Bacterial endotoxins are lipopolysaccharides bound to the bacterial cell wall and released when bacteria rupture or disintegrate. Possible contamination of endotoxin in ophthalmic devices can cause a painful eye inflammation or result in toxic anterior segment syndrome after cataract surgery. Measurement of bacterial endotoxin in medical device materials is difficult since endotoxin binds with polymer matrix and some of the materials are very viscous and non-water soluble, where traditional enzyme-based Limulus amebocyte lysate (LAL) assay cannot be applied...
November 2, 2016: Analytica Chimica Acta
Xing-Hai Liu, Wen Zhao, Zhong-Hua Shen, Jia-Hua Xing, Tian-Ming Xu, Wei-Li Peng
A series of novel difluoromethylpyrazole carboxamides derivatives were synthesized by introduction of flexible alkyl chain. Nematicidal bioassay results showed that some of them exhibited good control efficacy against M. incognita, which indicated that these difluoromethylpyrazole carboxamides derivatives might be potential novel lead compounds for discovery new nematicides. The nematicidal activity was affected by the substituted position in the molecule, especially the substitution group on the alkyl chain...
October 10, 2016: European Journal of Medicinal Chemistry
Richard A Manderville, Stacey D Wetmore
The formation of DNA adducts by the attack of intermediates derived from toxic substances at the C8 position of 2-deoxyguanosine (dG) is a common damaging event. Although the majority of studies on C8-dG adducts have focused on lesions containing a C8-N-C tether between the bulky moiety and the nucleobase, the formation of O-linked lesions with a similar tether topology and C-linked adducts involving direct C8-C connectivity have also been uncovered. Several studies have been done to try to better understand the structural impact and mutagenicity of O-linked and C-linked aryl C8-dG adducts, including lesions arising from unsubstituted and chloro substituted phenols, and the food mutagen ochratoxin A (OTA)...
October 21, 2016: Chemical Research in Toxicology
Christopher D Morrone, Lynsie A M Thomason, Mary E Brown, Isabelle Aubert, JoAnne McLaurin
Although it is recognized that multi-drug therapies may be necessary to combat AD, there is a paucity of preclinical proof of concept studies. We present a combination treatment paradigm, which temporally affects different aspects of Alzheimer's disease (AD)-like pathology, specifically Aβ-toxicity and neurogenesis. At early stages of AD-like pathology, in TgCRND8 mice, we found that combating Aβ pathology with scyllo-inositol ameliorated deficits in neurogenesis. Older TgCRND8 mice with established amyloid load had decreased progenitor cell proliferation and survival compared to non-transgenic mice, regardless of scyllo-inositol treatment...
2016: PloS One
Charlotte Rombaut, Katrien Faes, Ellen Goossens
PURPOSE: Previous studies have shown that the removal of one testis leads to a compensatory mechanism in the contralateral one, but this was species and age dependent. The aim of this study was to check whether this compensation would still occur after the combination of a unilateral orchiectomy and gonadotoxic treatment, since this resembles the clinical situation of patients who have to undergo highly toxic cancer treatment and therefore choose to cryopreserve a testicular biopsy for fertility restoration purposes...
2016: PloS One
Si Hyung Lee, Eun Min Kang, Gyu Ah Kim, Seung Woo Kwak, Joon Mo Kim, Hyoung Won Bae, Gong Je Seong, Chan Yun Kim
BACKGROUND: To investigate the association between heavy metal levels and open-angle glaucoma (OAG) with low- and high-teen baseline intraocular pressure (IOP) using a population-based study design. METHODS: This cross-sectional study included 5,198 participants older than 19 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2012 and had blood heavy metal levels available. The OAG with normal baseline IOP (IOP ≤ 21 mmHg) subjects were stratified into low-teen OAG (baseline IOP ≤ 15 mmHg) and high-teen OAG (15 mmHg < baseline IOP ≤ 21 mmHg), and the association between blood lead, mercury, and cadmium levels and glaucoma prevalence was assessed for low- and high-teen OAG...
2016: PloS One
Nina Holland
Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma...
October 21, 2016: Reviews on Environmental Health
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
Ke Yuan, Sang Soo Lee, Vincent De Andrade, Neil C Sturchio, Paul Fenter
The mobility of toxic elements, such as lead (Pb) can be attenuated by adsorption, incorporation, and precipitation on carbonate minerals in subsurface environments. Here, we report a study of the bulk transformation of single-crystal calcite (CaCO3) into polycrystalline cerussite (PbCO3) through reaction with acidic Pb-bearing solutions. This reaction began with the growth of a cerussite shell on top of calcite surfaces followed by the replacement of the remaining calcite core. The external shape of the original calcite was preserved by a balance between calcite dissolution and cerussite growth controlled by adjusting the Pb(2)(+) concentration and pH...
October 21, 2016: Environmental Science & Technology
Marta Polkowska, Edyta Czepielewska, Małgorzata Kozłowska-Wojciechowska
Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach...
December 2016: Current Treatment Options in Oncology
Alexander S Falk, Ansgar B Siemer
Several amyloid fibrils have cores framed by highly dynamic, intrinsically disordered, domains that can play important roles for function and toxicity. To study these domains in detail using solid-state NMR spectroscopy, site-specific resonance assignments are required. Although the rapid dynamics of these domains lead to considerable averaging of orientation-dependent NMR interactions and thereby line-narrowing, the proton linewidths observed in these samples is far larger than what is regularly observed in solution...
October 20, 2016: Journal of Biomolecular NMR
Christoph Funk, Adrian Roth
Drug-induced liver injury (DILI) is a major concern for drug developers, regulators and clinicians. It is triggered by drug and xenobiotic insults leading to liver impairment or damage, in the worst-case liver failure. In contrast to acute "intrinsic" hepatotoxicity, DILI typically manifests in a very small subset of the population under treatment with no clear dose relationship and inconsistent temporal patterns and is therefore termed an idiosyncratic event. Involved are multifactorial, compound-dependent mechanisms and host-specific factors, making the prediction in preclinical test systems very challenging...
October 20, 2016: Archives of Toxicology
Arathi Kizhedath, Simon Wilkinson, Jarka Glassey
Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few...
October 20, 2016: Archives of Toxicology
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