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Chemical pathology

Michael H Smolensky, Alain E Reinberg, Linda Sackett-Lundeen
The circadian time structure (CTS) and its disruption by rotating and nightshift schedules relative to work performance, accident risk, and health/wellbeing have long been areas of occupational medicine research. Yet, there has been little exploration of the relevance of the CTS to setting short-term, time-weighted, and ceiling threshold limit values (TLVs); conducting employee biological monitoring (BM); and establishing normative reference biological exposure indices (BEIs). Numerous publications during the past six decades document the CTS substantially affects the disposition - absorption, distribution, metabolism, and elimination - and effects of medications...
December 7, 2017: Chronobiology International
А Romaniuk, M Lyndin, V Sikora, Y Lyndina, S Romaniuk, K Sikora
Background: Breast cancer is the most frequent localization of malignant process in American women and women of European countries. To date it is not possible to control the morbidity growth due to lack of effective ways of primary prevention. Comparing the incidence of breast cancer in developed countries with the countries of Asia and Africa, there is the fact of population predominance lesion in more urbanized countries. This suggests that the environment along with other factors, occupies a significant place in the initiation and progression of breast neoplasia...
2017: Journal of Occupational Medicine and Toxicology
Liang Ma, Yudan Zhao, Yuchen Chen, Biao Cheng, Anlin Peng, Kun Huang
Over the past decades, C. elegans has been widely used as a model system because of its small size, transparent body, short generation time and lifespan (~3 days and 3 weeks, respectively), completely sequenced genome and tractability to genetic manipulation. Protein misfolding and aggregation are key pathological features in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Animal models, including Caenorhabditis elegans (C...
December 2, 2017: European Journal of Pharmacology
Stefanie Dichtl, David Haschka, Manfred Nairz, Markus Seifert, Chiara Volani, Oliver Lutz, Günter Weiss
Iron is essential for many biological functions including neurotransmitter synthesis, where the metal is a co-factor of tyrosine hydroxylase, which converts tyrosine to dopamine and further to norepinephrine. As the shared chemical structure, called catechol, may potentially bind iron we questioned whether tyrosine derived hormones would impact on cellular iron homeostasis in macrophages, which are central for the maintenance of body iron homeostasis. Using murine bone marrow-derived macrophages (BMDMs), we investigated the effect of catecholamines and found that only dopamine but neither tyrosine, nor norepinephrine, affected cellular iron homeostasis...
December 2, 2017: Biochemical Pharmacology
Geert Peeters, Charlotte Debbaut, Adrian Friebel, Pieter Cornillie, Winnok H De Vos, Kasper Favere, Ingrid Vander Elst, Tim Vandecasteele, Tim Johann, Luc Van Hoorebeke, Diethard Monbaliu, Dirk Drasdo, Stefan Hoehme, Wim Laleman, Patrick Segers
Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited...
December 4, 2017: Journal of Anatomy
Dorothee Rose, Annette Schmidt, Matthias Brandenburger, Tabea Sturmheit, Marietta Zille, Johannes Boltze
Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects...
December 1, 2017: Toxicology Letters
Hui-Min Li, Ying-Lu Shi, Di Wen, Huan-Min Luo, Xi Lin, Fei Xiao
There is no effective drug for the therapy of acute carbon monoxide (CO) poisoning. The purpose of the present study was to investigate the potential preventive and therapeutic effects of hemin on an animal model of acute CO poisoning and to provide a potential therapeutic candidate drug. A total of 80 Kunming mice were randomly divided into four groups, namely the air control, acute CO poisoning, hemin-treatment + CO and hemin-pretreatment + CO groups (n=20 each). Furthermore, the mortality rate of mice, blood carboxyhaemoglobin (HbCO) concentration and serum malondialdehyde (MDA) concentration were measured, and pathological changes of the hippocampal area were determined using histochemical staining...
November 2017: Experimental and Therapeutic Medicine
Mauricio A Retamal, Manuel A Riquelme, Jimmy Stehberg, Julio Alcayaga
In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia). It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons...
2017: Frontiers in Molecular Neuroscience
Abraham M Vidal-Limon, Oscar Daniel Luna-Martinez, Fausto Rojas-Durán, Thuluz Meza-Menchaca, Maria Elena Hernández-Aguilar, Angel Trigos, Jorge Suárez-Medellín
Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library...
2017: International Journal of Medicinal Mushrooms
Richard Pougnet, Brice Loddé, Marie Uguen, Bénédicte Sawicki, Laurence Pougnet
The trade of laboratory technician (TL) exposes to many risks to health, because of biological or chemical or physical exposures. But the TL occupation is constantly evolving, the techniques are constantly changing. The purpose of this article is to take stock of the occupational TL pathologies which were recently described in the literature. This is a literature review, based on Medline® and Scopus® medical databases, on publications between 01/01/2006 and 31/12/2016. The research was conducted in French and English...
December 1, 2017: Annales de Biologie Clinique
Iulia Pinzaru, Dorina Coricovac, Cristina Dehelean, Elena-Alina Moacă, Marius Mioc, Flavia Baderca, Ioana Sizemore, Seth Brittle, Daniela Marti, Cornelia Daniela Calina, Aristidis M Tsatsakis, Codruţa Şoica
The present study was purported to assess the toxicological profile of bare and polyethylene glycol (PEG) coated spherical silver nanoparticles (AgNPs) by means of in vitro (on human keratinocytes - HaCat cells) and in vivo non-invasive tests (after intraperitoneal - i.p. administration to mice). Bare and PEG-coated AgNPs were synthesized by applying Turkevich's method slightly modified. The physico-chemical characterization revealed the formation of stable, spherical AgNPs and PEG-AgNPs, with narrow size distributions and mean hydrodynamic sizes in the range of 19 nm and 50 nm, respectively...
November 27, 2017: Food and Chemical Toxicology
Marlet Martinez, Benjamin Garcia, Brenda Colin, M Bello, Berenice Prestegui, Alma Chavez, Alfonso Duenas, Jonathan Fragoso, Jessica Mendieta, Edgar Rojano, David Ordaz, Rocio Garcia, D Castillo-Bautista, Jose Correa
Estrogen (17β-estradiol) is essential for normal growth and differentiation in the mammary gland. Previous investigations have revealed that estrogen receptor alpha (ERα) plays a critical role in breast cancer. More recently, observations regarding the widespread expression of ERβ-like proteins in normal and neoplastic mammary tissues have suggested that ERβ is also involved in the mentioned pathology. Design of new drugs both steroidal and nonsteroidal that target any of these receptors represents a promise to treat breast cancer...
November 29, 2017: Anti-cancer Agents in Medicinal Chemistry
Michael Wormald, Gangling Liao, Martha Kimos, James Barrow, Huijun Wei
Inositol pyrophosphates have been implicated in a wide range of cellular processes. Inositol hexakisphosphate kinase 1 catalyzes the pyrophosphorylation of inositol hexakisphosphate into inositol 5-diphospho-1,2,3,4,6-pentakisphosphate which is important in numerous areas of cell physiology such as DNA repair and glucose homeostasis. Furthermore, inositol 5-diphospho-1,2,3,4,6-pentakisphosphate is implicated in the pathology of diabetes and other human diseases. As such there is a demonstrated need in the field for a robust chemical probe to better understand the role of inositol hexakisphosphate kinase 1 and inositol pyrophosphate in physiology and disease...
2017: PloS One
Norman A Lapin, Leoncio A Vergara, Yuri Mackeyev, Jared M Newton, Sean A Dilliard, Lon J Wilson, Steven A Curley, Rita E Serda
[60]Fullerene is a highly versatile nanoparticle (NP) platform for drug delivery to sites of pathology owing to its small size and both ease and versatility of chemical functionalization, facilitating multisite drug conjugation, drug targeting, and modulation of its physicochemical properties. The prominent and well-characterized role of the enhanced permeation and retention (EPR) effect in facilitating NP delivery to tumors motivated us to explore vascular transport kinetics of a water-soluble [60]fullerene derivatives using intravital microscopy in an immune competent murine model of breast adenocarcinoma...
2017: International Journal of Nanomedicine
M Zuluaga, V Gueguen, D Letourneur, G Pavon-Djavid
Oxidative stress induced by Reactive Oxygen Species (ROS) was shown to be involved in the pathogenesis of chronic diseases such as cardiovascular pathologies. Particularly, oxidative stress has proved to mediate abnormal platelet function and dysfunctional endothelium-dependent vasodilatation representing a key factor in the progression of ischemic injuries. Antioxidants like carotenoids have been suggested to contribute in their prevention and treatment. Astaxanthin, a xanthophyll carotenoid produced naturally and synthetically, shows interesting antioxidant and anti-inflammatory properties...
November 24, 2017: Chemico-biological Interactions
Fabiana Bettoni, Fernanda Christtanini Koyama, Paola de Avelar Carpinetti, Pedro Alexandre Favoretto Galante, Anamaria Aranha Camargo, Paula Fontes Asprino
Next generation sequencing (NGS) has become an informative tool to guide cancer treatment and conduce a personalized approach in oncology. The biopsy collected for pathologic analysis is usually stored as formalin-fixed paraffin-embedded (FFPE) blocks and then availed for molecular diagnostic, resulting in DNA molecules that are invariably fragmented and chemically modified. In an attempt to improve NGS based diagnostics in oncology we developed a straightforward DNA integrity assessment assay based on qPCR, defining clear parameters to whether NGS sequencing results is accurate or when it should be analyzed with caution...
November 21, 2017: Experimental and Molecular Pathology
Beatriz Balsera, José Mulet, Salvador Sala, Francisco Sala, Roberto de la Torre-Martínez, Sara González-Rodríguez, Adrián Plata, Lieve Naesens, Asia Fernández-Carvajal, Antonio Ferrer-Montiel, Manuel Criado, María Jesús Pérez de Vega, Rosario González-Muñiz
α7 Nicotinic acetylcholine receptors (nAChRs) are ion channels implicated in a number of CNS pathological processes, including pain and psychiatric, cognitive and inflammatory diseases. Comparing with orthosteric agonism, positive allosteric modulation of these channels constitutes an interesting approach to achieve selectivity versus other nicotinic receptors. We have recently described new chalcones and 1,3-diphenylpropanones as positive allosteric modulators (PAMs) of α7 nAChRs, which proved to have good analgesic activities but poor pharmacokinetic properties...
November 2, 2017: European Journal of Medicinal Chemistry
Jinwook Kim, Sueun Lee, Sohi Kang, Sung-Ho Kim, Jong-Choon Kim, Miyoung Yang, Changjong Moon
Neurotoxicity induced by stress, radiation, chemicals, or metabolic diseases, is commonly associated with excitotoxicity, oxidative stress, and neuroinflammation. The pathological process of neurotoxicity induces neuronal death, interrupts synaptic plasticity in the brain, and is similar to that of diverse neurodegenerative diseases. Animal models of neurotoxicity have revealed that clinical symptoms and brain lesions can recover over time via neuroregenerative processes. Specifically, brain-derived neurotropic factor (BDNF) and gamma-aminobutyric acid (GABA)-ergic transmission are related to both neurodegeneration and neuroregeneration...
October 2017: Neural Regeneration Research
Marcello Rossi, Daniela Saverioni, Michele Di Bari, Simone Baiardi, Afina Willemina Lemstra, Laura Pirisinu, Sabina Capellari, Annemieke Rozemuller, Romolo Nonno, Piero Parchi
Amyloid plaques formed by abnormal prion protein (PrPSc) aggregates occur with low frequency in Creutzfeldt-Jakob disease, but represent a pathological hallmark of three relatively rare disease histotypes, namely variant CJD, sporadic CJDMV2K (methionine/valine at PRNP codon 129, PrPSc type 2 and kuru-type amyloid plaques) and iatrogenic CJDMMiK (MM at codon 129, PrPSc of intermediate type and kuru plaques). According to recent studies, however, PrP-amyloid plaques involving the subcortical and deep nuclei white matter may also rarely occur in CJDMM1 (MM at codon 129 and PrPSc type 1), the most common CJD histotype...
November 23, 2017: Acta Neuropathologica Communications
Kun Dou, Guang Chen, Fabiao Yu, Yuxia Liu, Lingxin Chen, Ziping Cao, Tao Chen, Yulin Li, Jinmao You
As a notorious toxin, formaldehyde (FA) poses an immense threat to human health. Aberrantly elevated FA levels lead to serious pathologies, including organ damage, neurodegeneration, and cancer. Unfortunately, current techniques limit FA imaging to general comparative studies, instead of a mechanistic exploration of its biological role, and this is presumably due to the lack of robust molecular tools for reporting FA in living systems. More importantly, despite being reductive, FA, however, can induce oxidative damage to organisms, thus providing a challenge to the mechanistic study of FA using fluorescence imaging...
November 1, 2017: Chemical Science
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