Effects of Dibenzo- p -Dioxins/Dibenzofurans on Acetylcholinesterase Activity and Histopathology of the Body Wall of Earthworm Eisenia andrei : a Potential Biomarker for Ecotoxicity Monitoring

Abstract

The polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) are persistent environmental pollutants. Recently, there have been an increasing demand to assess different biomarkers as early alarming indicators of environmental pollution. This study is the first to investigate the effects of PCDD/Fs on acetylcholinesterase (AChE) activity and histopathology of the body wall (epidermis, circular, and longitudinal muscles) of earthworm Eisenia andrei (Oligochaeta, Lumbricidae) using acute filter paper toxicity test. It is also exploring the selected biomarkers as a potential tool for evaluating soil quality. Earthworms were exposed to 0, 0.5, 1.0, and 1.5 ng/cm² PCDD/Fs. The treated worms expressed progressive abnormal morphological signs with incrementing doses of dioxins, such as coiling, curling, and body swelling. At the highest dose, some worms demonstrated skin discoloration, loss of body segmentation, and body part detachment. The AChE activity was significantly decreased (p < 0.001) in all treated animals compared to control. The mixture induced circular muscle hyperplasia at 0.5 ng/cm². However, the mixture at 1.5 ng/cm² caused epidermal atrophy with cell pyknosis and necrosis in all layers of the body wall. Image analysis revealed significant reduction in the thickness of the epidermis (p < 0.001) at all doses with relative to control. Herein, we report that 48 h of acute exposure of E. andrei to dioxins/furans induced morphological changes, reduced the activity of AChE, and induced histopathological alterations. The outcomes can be utilized as endpoints that could be added to earthworm’s standardized short tests for ecotoxicity studies.

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A meta-analysis of the relationship between ataxia-telangiectasia mutated gene polymorphisms and lung cancer susceptibility

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Yanling Xu, Peng Gao, Xuejiao Lv, Lin Zhang, Wei Li, Jie Zhang
PurposeThis study aimed to analyze the relationship between ataxia-telangiectasia mutated (ATM) gene polymorphisms and lung cancer susceptibility using a meta-analysis.MethodsA literature search of the PubMed and EMBASE databases was performed using keywords such as “ATM gene” and “lung cancer,” and the deadline “October 15 (th), 2016.” After extracting relevant details, each selected literature was evaluated for quality according to the Newcastle–Ottawa Scale (NOS) scores, and Hardy–Weinberg equilibrium and heterogeneity tests were performed. Odds ratios (ORs) and 95% confidence interval (CI) were evaluated using R 3.12 software.ResultsEight eligible studies, published from 2004 to 2013, were identified. The NOS scores of these ranged from 5 to 7. The allele genetic model (OR=1.15; 95% CI, 1.01–1.31); additive genetic model (OR=1.44; 95% CI, 1.09–1.90); recessive genetic model (OR=1.48; 95% CI, 1.16–1.88); and dominant genetic model (OR=1.50; 95% CI, 1.16–1.93) of rs664143 (A>G) were found to be significantly different. For rs664677 (C>T), significant differences were found in the additive genetic model (OR=1.26, 95% CI, 1.01–1.55) and recessive genetic model (OR=1.31; 95% CI, 1.09–1.57). However, the other 2 genetic models (rs609429, rs664982) did not show significant differences.ConclusionThe polymorphisms rs664143 and rs664677 of ATM are associated with lung cancer occurrence.



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A 55-year-old Female with Leukoencephalopathy with Cerebral Calcifications and Cysts: Case Report and Radiopathologic Description

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Jorge Novo, Diana Lin, Megan Shanks, Mehmet Kocak, Leonidas Arvanitis
Adult-onset leukoencephalopathies with increased cerebral volume can present a potentially challenging diagnosis for the pathologist. We present the case of a patient with a rare adult-onset disease called Leukoencephalopathy with cerebral Calcifications and Cysts (LCC). A 55-year-old woman with a history of morning headaches, mild memory loss, diabetes, and hypertension presented to the emergency department with acute onset altered mental status. CT scan revealed multiple small hypodense lesions in the white matter with calcifications in the bilateral cerebral hemispheres, basal ganglia, pons, and cerebellar hemispheres. MRI showed multiple complex/hemorrhagic cystic lesions with partial enhancement in addition to calcifications bilaterally in the frontotemporal white matter, pons, and cerebellar hemispheres, and diffuse white matter signal abnormality. The differential diagnosis included chronic infection, chronic thromboembolic disease, and neoplasm. The biopsy revealed extensive geode-like mineralization as well as smaller calcifications (calcospherites) with associated sclerosis, Rosenthal fibers, angiomatous proliferation of blood vessels with thrombosis and microbleeds. We discuss the differential diagnosis, radiologic and detailed histologic features of LCC.



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A single amino acid in MRGPRX2 necessary for binding and activation by pruritogens

Publication date: Available online 6 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Vemuri B. Reddy, Thomas A. Graham, Ehsan Azimi, Ethan A. Lerner

Teaser

Substance P, a neuropeptide associated with itch, atopic dermatitis and inflammation, activates MRGPRX2, a member of the mas-related GPCR family. A specific amino acid in the receptor has been found to be critical for activity.


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Results from the 5-year SQ grass SLIT-tablet asthma prevention (GAP) trial in children with grass pollen allergy

Publication date: Available online 6 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Erkka Valovirta, Thomas Houmann Petersen, Teresa Piotrowska, Mette Kongensbjerg Laursen, Jens Strodl Andersen, Helle Frobøse Sørensen, Rabih Klink
BackgroundAllergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease.ObjectiveThe primary objective was to investigate the effect of the SQ grass SLIT-tablet compared to placebo on the risk of developing asthma.Methods812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomised, double-blind, placebo-controlled trial, comprising 3 years treatment and 2 years follow-up.ResultsThere was no difference in time to onset of asthma, defined by pre-specified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass SLIT-tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio=0.66, p<0.036), during the 2-year post treatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22-30% reduced (p<0.005 for all 5 years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, p<0.001). Total IgE, grass pollen specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo.ConclusionTreatment with the SQ grass SLIT-tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma.

Graphical abstract

Teaser

SQ grass SLIT-tablet treatment prevented asthma symptoms and asthma medication use in children with grass pollen ARC and no pre-existing asthma. This disease-modifying effect persisted after end of treatment.


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Functional Role of Kynurenine and Aryl hydrocarbon Receptor Axis in Chronic Rhinosinusitis with Nasal Polyps

Publication date: Available online 6 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Heng Wang, Danh C. Do, Jinxin Liu, Baofeng Wang, Jingjing Qu, Xia Ke, Xiaoyan Luo, Ho Man Tang, Ho Lam Tang, Chengping Hu, Mark E. Anderson, Zheng Liu, Peisong Gao
BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is associated with mast cell-mediated inflammation and heightened oxidant stress. Kynurenine (KYN), an endogenous tryptophan metabolite, can promote allergen-induced mast cell activation through the aryl hydrocarbon receptor (AhR).ObjectivesDetermine the role of the KYN/AhR axis and oxidant stress in mast cell activation and the development of CRSwNP.MethodsWe measured expression of indoleamine 2, 3-dioxygenase 1 (IDO1), tryptophan 2, 3-dioxygenase (TDO2), KYN, and oxidized calmodulin-dependent protein kinase II (ox-CaMKII) in nasal polyps and controls. KYN-potentiated ovalbumin (OVA)-induced reactive oxygen species (ROS) generation, cell activation, and ox-CaMKII expression were investigated in wild type (WT) and AhR deficient (AhR^-/-) mast cells. The role of ox-CaMKII in mast cell activation was further investigated.ResultsNasal polyps in CRSwNP showed an increased expression of IDO1, TDO2, and KYN compared with controls. AhR was predominantly expressed in mast cells in nasal polyps. Activated mast cells and local IgE levels were substantially increased in eosinophilic polyps compared with non-eosinophilic polyps and controls. Furthermore, KYN potentiated OVA-induced ROS generation, intracellular Ca²⁺ levels, cell activation, and expression of ox-CaMKII in WT, but not in AhR^-/- mast cells. Compared with non-eosinophilic polyps and controls, eosinophilic polyps showed increased expression of ox-CaMKII in mast cells. Mast cells from ROS-resistant CaMKII MMVVδ mice or pre-treated with CaMKII inhibitor showed protection against KYN-promoted OVA-induced mast cell activation.ConclusionThese studies support a potentially critical but previously unidentified function of the KYN/AhR axis in regulating IgE-mediated mast cell activation through ROS and ox-CaMKII in CRSwNP.

Teaser

The pathogenesis of chronic rhinosinusitis with nasal polyps is associated with increased levels of kynurenine, a tryptophan metabolite, which potentiated allergen-induced mast cell activation through the aryl hydrocarbon receptor and Calmodulin-dependent protein kinase II.


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Prognostic value of IMP3 expression as a determinant of chemosensitivity in triple-negative breast cancer

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Ryuji Ohashi, Maoka Sangen, Shigeki Namimatsu, Keiko Yanagihara, Koji Yamashita, Takashi Sakatani, Hiroyuki Takei, Zenya Naito
Triple negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis. Neoadjuvant chemotherapy (NAC) is often used to treat TNBC, but some patients are resistant to NAC. We postulated that a subpopulation of TNBC cells expressing IMP3, an oncofetal protein, could be resistant to NAC, contributing to the poor prognosis. We investigated immunohistochemical expression of IMP3 in 42 TNBC patients who underwent NAC in association with clinical outcomes. The patients were divided into IMP3 positive (+) (n=19) and negative (−) (n=23) groups. High Ki67 positivity was detected in 13 patients of the IMP3+group and 8 cases in the IMP3 − group (p=0.03). While 9 patients in the IMP3 − group (39%) were responders, the majority of the IMP3+patients (84.2%) were non-responders (p=0.01). In a Cox proportional hazard model, IMP3 expression was independently associated with poor NAC response and clinical outcomes (p=0.03 and 0.046, respectively). The IMP3+group showed a tendency toward shorter overall survival compared to the IMP3 − group with marginal significance (p=0.07). These findings suggest that IMP3+tumor cells contributed to the poor clinical outcomes by exerting a chemoresistance to NAC, and that IMP3 expression has prognostic value as a biomarker for chemosensitivity and overall survival in TNBC.



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