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https://www.readbyqxmd.com/read/29458133/artesunate-derived-monomeric-dimeric-and-trimeric-experimental-drugs-their-unique-mechanistic-basis-and-pronounced-antiherpesviral-activity
#1
Friedrich Hahn, Tony Fröhlich, Theresa Frank, Luca D Bertzbach, Stephan Kohrt, Benedikt B Kaufer, Thomas Stamminger, Svetlana B Tsogoeva, Manfred Marschall
Human cytomegalovirus (HCMV) is a major human pathogen and is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Currently, antiviral therapy is still hampered by a considerable toxicity of the available drugs and induction of viral resistance. Recently, we and others reported the very potent antiviral activity of the broad antiinfective drug artesunate in vitro and in vivo. Here, we investigated further optimized analogs including monomeric, dimeric and trimeric derivatives belonging to this highly interesting chemical group of experimental drugs (sesquiterpenes/trioxanes) and compared these to the previously identified trimeric artesunate compound TF27...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29457543/greener-chemicals-for-the-future-qsar-modelling-of-the-pbt-index-using-eta-descriptors
#2
P De, K Roy
Persistent, bioaccumulative and toxic (PBT) chemicals symbolize a group of substances that are not easily degraded; instead, they accumulate in different organisms and exhibit an acute or chronic toxicity. The limited empirical data on PBT chemicals, the high cost of testing together with the regulatory constraints and the international push for reduced animal testing motivate a greater reliance on predictive computational methods like quantitative structure-activity relationship (QSAR) models in PBT assessment...
April 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29456798/-18-f-radiolabeled-panobinostat-allows-for-positron-emission-tomography-guided-delivery-of-a-histone-deacetylase-inhibitor
#3
Harikrishna Kommidi, Umberto Tosi, Uday B Maachani, Hua Guo, Christopher S Marnell, Benedict Law, Mark M Souweidane, Richard Ting
Histone deacetylase (HDAC) inhibition is becoming an increasingly popular approach to treat cancer, as HDAC overexpression is common in many malignancies. The blood-brain barrier (BBB) prevents systemically delivered drugs from reaching brain at effective concentration, making small-molecule-HDAC inhibition in brain tumors particularly challenging. To circumvent the BBB, novel routes for administering therapeutics are being considered in the clinic, and a need exists for drugs whose deliveries can be directly imaged, so that effective delivery across the BBB can be monitored...
February 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29456531/first-occurrence-of-plasmablastic-lymphoma-in-adenosine-deaminase-deficient-severe-combined-immunodeficiency-disease-patient-and-review-of-the-literature
#4
Maddalena Migliavacca, Andrea Assanelli, Maurilio Ponzoni, Roberta Pajno, Federica Barzaghi, Fabio Giglio, Francesca Ferrua, Marta Frittoli, Immacolata Brigida, Francesca Dionisio, Roberto Nicoletti, Miriam Casiraghi, Maria Grazia Roncarolo, Claudio Doglioni, Jacopo Peccatori, Fabio Ciceri, Maria Pia Cicalese, Alessandro Aiuti
Adenosine deaminase-deficient severe combined immunodeficiency disease (ADA-SCID) is a primary immune deficiency characterized by mutations in the ADA gene resulting in accumulation of toxic compounds affecting multiple districts. Hematopoietic stem cell transplantation (HSCT) from a matched donor and hematopoietic stem cell gene therapy are the preferred options for definitive treatment. Enzyme replacement therapy (ERT) is used to manage the disease in the short term, while a decreased efficacy is reported in the medium-long term...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29455149/influence-of-process-variables-in-a-continuous-treatment-of-non-sterile-hospital-wastewater-by-trametes-versicolor-and-novel-method-for-inoculum-production
#5
Josep Anton Mir-Tutusaus, Glòria Caminal, Montserrat Sarrà
Micropollutants such as pharmaceutical active compounds, present at high concentration in hospital wastewater (HWW), pose both environmental and human health challenges. Fungal reactors can effectively remove such contaminants and produce non-toxic effluents, but their ability to operate for a long period of time is yet to be demonstrated in real hospital wastewater. Several process variables need to be studied beforehand. Here, variables: pellet size, aeration and carbon-to-nitrogen ratio are studied in continuous operations with real HWW...
February 15, 2018: Journal of Environmental Management
https://www.readbyqxmd.com/read/29455116/linking-mode-of-action-of-the-model-respiratory-and-photosynthesis-uncoupler-3-5-dichlorophenol-to-adverse-outcomes-in-lemna-minor
#6
Li Xie, Tânia Gomes, Knut Asbjørn Solhaug, You Song, Knut Erik Tollefsen
Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers...
February 10, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29455092/internet-pseudoscience-testing-opioid-containing-formulations-with-tampering-potential
#7
Jennifer P Pascali, Paolo Fais, Fabio Vaiano, Nicola Pigaiani, Stefano D'Errico, Sandra Furlanetto, Diego Palumbo, Elisabetta Bertol
Drug tampering practices, with the aim to increase availability of drug delivery and/or enhance drug effects, are accessible on Internet and are practiced by some portion of recreational drug users. Not rarely, recreational misuse may result in toxic and even fatal results. The aim of the present study was to assess the tampering risk of medicaments containing different formulations of an opioid in combination with paracetamol or dexketoprofen, following the procedures reported in dedicated forums on the web...
February 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29454199/benthic-nitrite-exchanges-in-the-seine-river-france-an-early-diagenetic-modeling-analysis
#8
Zahra Akbarzadeh, Anniet M Laverman, Fereidoun Rezanezhad, Mélanie Raimonet, Eric Viollier, Babak Shafei, Philippe Van Cappellen
Nitrite is a toxic intermediate compound in the nitrogen (N) cycle. Elevated concentrations of nitrite have been observed in the Seine River, raising questions about its sources and fate. Here, we assess the role of bottom sediments as potential sources or sinks of nitrite along the river continuum. Sediment cores were collected from two depocenters, one located upstream, the other downstream, from the largest wastewater treatment plant (WWTP) servicing the conurbation of Paris. Pore water profiles of oxygen, nitrate, nitrite and ammonium were measured...
February 14, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29453596/effectiveness-of-the-sesquiterpene-%C3%AE-bisabolol-in-dogs-with-naturally-acquired-canine-leishmaniosis-an-exploratory-clinical-trial
#9
V Corpas-López, G Merino-Espinosa, C Acedo-Sánchez, V Díaz-Sáez, M C Navarro-Moll, F Morillas-Márquez, J Martín-Sánchez
The use of natural products is a promising approach for treating visceral leishmaniosis. (-)-α-Bisabolol is a sesquiterpene that have been proved active in vivo on Leishmania infantum-infected mice without showing toxicity. A single-centre, parallel-group, randomized, exploratory study was designed to assess its efficacy in a canine leishmaniosis model involving naturally infected dogs. In this clinical trial, 12 dogs were allocated into two groups and were treated with either meglumine antimoniate (100 mg/kg) through subcutaneous route or (-)-α-bisabolol (30 mg/kg) through oral route for two treatment series of 30 days, separated by a 30-day interval...
February 16, 2018: Veterinary Research Communications
https://www.readbyqxmd.com/read/29453252/ecology-and-biotechnological-potential-of-bacteria-belonging-to-the-pseudovibrio-genus
#10
Stefano Romano
Bacteria belonging to the genus Pseudovibrio have been isolated worldwide from a great variety of marines sources as both free living and host associated. So far, the available data depict a group of Alphaproteobacteria characterized by a versatile metabolism, which allows them to use a variety of substrates to meet their carbon, nitrogen, sulfur, and phosphorous requirements. Additionally, Pseudovibrio -related bacteria have been shown to proliferate under extreme oligotrophic conditions, tolerate high heavy metal concentrations, and metabolize potentially toxic compounds...
February 16, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29452189/roasted-and-green-coffee-extracts-show-antioxidant-and-cytotoxic-activity-in-myoblast-and-endothelial-cell-lines-in-a-cell-specific-manner
#11
Alexandros Priftis, Eleftheria-Maria Panagiotou, Konstantinos Lakis, Christina Plika, Maria Halabalaki, Georgia Ntasi, Aristidis S Veskoukis, Dimitrios Stagos, Leandros A Skaltsounis, Dimitrios Kouretas
Coffee is one of the most highly consumed beverages with potential beneficial health implications, however its molecular mechanism of action has not been completely elucidated yet. To that cause, the polyphenolic composition of different coffee extracts (from Light, Medium and Dark roasts as well as green beans) was examined by UHPLC-HRMS analysis, indicating chlorogenic acids isomers as the main constituents. In the following step, the toxicity of the extracts was tested in myoblasts and endothelial cells and differential toxicity of green and roasted samples was displayed as the myoblasts were more sensitive to green coffee extracts, in contrast to the endothelial cells...
February 13, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29451361/development-of-a-focused-library-of-triazole-linked-privileged-structure-based-conjugates-leading-to-the-discovery-of-novel-phenotypic-hits-against-protozoan-parasitic-infections
#12
Elisa Uliassi, Lorna Piazzi, Federica Belluti, Andrea Mazzanti, Marcel Kaiser, Reto Brun, Carolina B Moraes, Lucio H Freitas-Junior, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Chiara Borsari, Maria Paola Costi, Maria Laura Bolognesi
Protozoan infections caused by Plasmodium, Leishmania, and Trypanosoma spp. contribute significantly to the burden of infectious diseases worldwide, causing severe morbidity and mortality. The inadequacy of available treatments calls for cost- and time-effective drug discovery endeavors. To this end, we envisaged the triazole linkage of privileged structures as an effective drug design strategy to generate a focused library of high-quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME-tox profiling...
February 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29449485/volatile-chemical-products-emerging-as-largest-petrochemical-source-of-urban-organic-emissions
#13
Brian C McDonald, Joost A de Gouw, Jessica B Gilman, Shantanu H Jathar, Ali Akherati, Christopher D Cappa, Jose L Jimenez, Julia Lee-Taylor, Patrick L Hayes, Stuart A McKeen, Yu Yan Cui, Si-Wan Kim, Drew R Gentner, Gabriel Isaacman-VanWertz, Allen H Goldstein, Robert A Harley, Gregory J Frost, James M Roberts, Thomas B Ryerson, Michael Trainer
A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products-now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements...
February 16, 2018: Science
https://www.readbyqxmd.com/read/29448893/arsenic-species-in-rice-and-rice-based-products-consumed-by-toddlers-in-switzerland
#14
Roxane Guillod-Magnin, Beat J Brüschweiler, Rafael Aubert, Max Haldimann
Inorganic arsenic (iAs) is a contaminant present in food, especially in rice and rice-based products. Toxicity of arsenic compounds (As) depends on species and oxidative state. Inorganic arsenic species, such as arsenite (As(III)) and arsenate (As(V)), are more bioactive and toxic than organic arsenic species, like methylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) or arsenosugars and arsenobetaine. An ion chromatography-inductively coupled plasma-mass spectroscopy (IC-ICP-MS) method was developed to separate the four following arsenic anions: As(III), As(V), MMA(V) and DMA(V)...
February 16, 2018: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/29448253/lycorine-suppresses-endplate-chondrocyte-degeneration-and-prevents-intervertebral-disc-degeneration-by-inhibiting-nf-%C3%AE%C2%BAb-signalling-pathway
#15
Gangliang Wang, Kangmao Huang, Yangxin Dong, Shuai Chen, Jianfeng Zhang, Jiying Wang, Ziang Xie, Xianfeng Lin, Xiangqiang Fang, Shunwu Fan
BACKGROUND/AIMS: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. METHODS: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29448125/a-critical-review-of-histopathological-findings-associated-with-endocrine-and-non-endocrine-hepatic-toxicity-in-fish-models
#16
REVIEW
Jeffrey C Wolf, James R Wheeler
Although frequently examined as a target organ for non-endocrine toxicity, histopathological evaluation of the liver is becoming a routine component of endocrine disruption studies that utilize various fish species as test subjects. However, the interpretation of microscopic liver findings can be challenging, especially when attempting to distinguish adverse changes associated with endocrine disrupting substances from those caused by systemic or direct hepatic toxicity. The purpose of this project was to conduct a critical assessment of the available peer-reviewed and grey literature concerning the histopathologic effects of reproductive endocrine active substances (EAS) and non-endocrine acting substances in the livers of fish models, and to determine if liver histopathology can be used to reliably distinguish endocrine from non-endocrine etiologies...
February 12, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29448040/comparing-the-therapeutic-efficacy-of-different-amphotericin-b-carrying-delivery-systems-against-visceral-leishmaniasis
#17
Débora V C Mendonça, Vívian T Martins, Daniela P Lage, Daniel S Dias, Patrícia A F Ribeiro, Ana Maria R S Carvalho, Anna Letícia T Dias, Carolina K Miyazaki, Daniel Menezes-Souza, Bruno M Roatt, Carlos A P Tavares, José Mário Barichello, Mariana C Duarte, Eduardo A F Coelho
Amphotericin B (Amp) has been well-successfully used to treat against Leishmania infection, although high toxicity has been found in patients. In the present study, Amp was administered in Leishmania infantum-infected BALB/c mice by three distinct delivery systems aiming to compare their efficacy against challenge infection, as well as their side effects in a murine visceral leishmaniasis (VL) model. This product was administered in a Poloxamer P407 (Pluronic ® F127)-based polymeric micelle system (Amp/M), in the Ambisome ® formulation (Lip-Amp) or in a free format (free Amp)...
February 12, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29446726/metal-organic-framework-mof-based-nanomaterials-for-biomedical-applications
#18
Zhidong Luo, Shuran Fan, Chuying Gu, Weicong Liu, Baohong Li, Jianqiang Liu
Metal-organic frameworks (MOFs) are compounds consisting of metal ions or clusters coordinated to organic ligands to form one-, two-, or three-dimensional structures. They are a subclass of coordination polymers (CPs), with the special feature that they are often porous. The organic ligands are sometimes referred to as second building structs. The new porous materials have paid great attention because of the variety of advantages such as tunable components, structural diversity, high loading performance and favorable biodegradability...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29445624/dioxin-exposure-in-the-manufacture-of-pesticide-production-as-a-risk-factor-for-death-from-prostate-cancer-a-meta-analysis
#19
REVIEW
Ali Kabir, Rezvan Zendehdel, Raana Tayefeh-Rahimian
Background: In pesticide exposure groups such as farmers, the risk of prostate cancer was increased, although the report of the cause of evidence is limited. We selected chlorophenol compounds as an important group of the contaminated pesticide with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). This meta-analysis, the risk of death from prostate cancer was analyzed. Methods: PubMed, Scopus, Scholar Google and web of Sciences until 2016 were searched...
February 2018: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29445138/non-toxic-engineered-carbon-nanodiamond-concentrations-induce-oxidative-nitrosative-stress-imbalance-of-energy-metabolism-and-mitochondrial-dysfunction-in-microglial-and-alveolar-basal-epithelial-cells
#20
Claudia G Fresta, Aishik Chakraborty, Manjula B Wijesinghe, Angela M Amorini, Giacomo Lazzarino, Giuseppe Lazzarino, Barbara Tavazzi, Susan M Lunte, Filippo Caraci, Prajnaparamita Dhar, Giuseppe Caruso
Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism...
February 14, 2018: Cell Death & Disease
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