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Chemical pathology

Lorena M Durán-Riveroll, Allan D Cembella
Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogs, are naturally occurring alkaloids with divergent evolutionary origins and biogeographical distribution, but which share the common chemical feature of guanidinium moieties. These guanidinium groups confer high biological activity with high affinity and ion flux blockage capacity for voltage-gated sodium channels (NaV). Members of the STX group, known collectively as paralytic shellfish toxins (PSTs), are produced among three genera of marine dinoflagellates and about a dozen genera of primarily freshwater or brackish water cyanobacteria...
October 13, 2017: Marine Drugs
Mareen Engel, Alon Chen
Covalent RNA modifications were recently rediscovered as abundant RNA chemical tags. Similarly to DNA epigenetic modifications, they have been proposed as essential regulators of gene expression. Here we focus on two of the most abundant adenosine methylations: N6-methyladenosine (m(6) A), N6,2'-O-dimethyladenosine (m(6) Am) and N1-methyladenosine (m(1) A). We review the potential role of these modifications on mature mRNA in regulating gene expression within the adult brain, nervous system function and normal and pathological behavior...
October 13, 2017: Genes, Brain, and Behavior
Leila R Lindeman, Edward A Randtke, Rachel A High, Kyle M Jones, Christine M Howison, Mark D Pagel
PURPOSE: Extracellular pH (pHe) is an important biomarker for cancer cell metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the contrast agent iopamidol to create spatial maps of pHe. Measurements of amide proton transfer exchange rates (kex ) from endogenous CEST MRI were compared to pHe measurements by exogenous acido-CEST MRI to determine whether endogenous kex could be used as a proxy for pHe measurements. METHODS: Spatial maps of pHe and kex were obtained using exogenous acidoCEST MRI and an endogenous CEST MRI analyzed with the omega plot method, respectively, to evaluate mouse kidney, a flank tumor model, and a spontaneous lung tumor model...
October 11, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Youqiang Meng, Li Dong, Biying Sun, Ping Luo, Guohua Zhang, Weifang Rong
Dysfunction of the colonic sensory nerves has been implicated in the pathophysiology of several common conditions, including functional and inflammatory bowel diseases and diabetes. Here, we describe a protocol for the in vitro characterization of the electrophysiological properties of colonic afferents in rats. The colorectum, with the intact pelvic ganglion (PG) attached, is removed from the rat; superfused with carbogenated Krebs solution in the recording chamber; and cannulated at the oral and anal ends to allow for distension...
September 27, 2017: Journal of Visualized Experiments: JoVE
Angeles Canales, Irene Boos, Lukas Perkams, L Karst, Thomas Luber, Theodoros Karagiannis, Gemma Dominguez, F Javier Cañada, Javier Perez-Castells, D Häussinger, Carlo Unverzagt, Jesus Jimenez-Barbero
The biological recognition of complex-type N-glycans is part of many key physiological and pathological events. Despite their importance, the structural characterization of these events remains an unsolved task. The inherent flexibility of N-glycans hampers crystallization and the chemical equivalence of individual branches precludes their NMR characterization. By using a chemoenzymatically synthesized tetraantennary N-glycan conjugated to a lanthanide binding tag, the NMR signals under paramagnetic conditions discriminated all four N-acetyl lactosamine antennae with unprecedented resolution...
October 9, 2017: Angewandte Chemie
Michael W Beck, Jeffrey S Derrick, Jong-Min Suh, Mingeun Kim, Kyle J Korshavn, Richard A Kerr, Woo Jong Cho, Scott D Larsen, Brandon T Ruotolo, Ayyalusamy Ramamoorthy, Mi Hee Lim
Chemical tools have been valuable for establishing a better understanding of the relationships between metal ion dyshomeostasis, the abnormal aggregation and accumulation of amyloid-β (Aβ), and oxidative stress in Alzheimer's disease (AD). Still, very little information is available to correlate the structures of chemical tools with specific reactivities used to uncover such relationships. Recently, slight structural variations to the framework of a chemical tool were found to drastically determine the tool's reactivities toward multiple pathological facets to various extents...
October 9, 2017: ChemMedChem
Fatemeh Salimi, Javad Hamedi, Elaheh Motevaseli, Fatemeh Mohammadipanah
AIM: Vascular calcification (VC) is a significant pathological process in some life-threatening diseases. Several pathological mechanisms, including transdifferentiation of vascular smooth muscle cells to osteoblast-like cells and apoptosis are involved in VC. Compounds with an inhibitory effect on these processes are potentially efficient medications. In consideration of the multiple biological activities of Actinobacteria, this research was aimed at finding anti-VC metabolite-producing Actinobacteria...
October 9, 2017: Journal of Applied Microbiology
Longwei He, Xueling Yang, Kaixin Xu, Xiuqi Kong, Weiying Lin
Biothiols, which have a close network of generation and metabolic pathways among them, are essential reactive sulfur species (RSS) in the cells and play vital roles in human physiology. However, biothiols possess highly similar chemical structures and properties, resulting in it being an enormous challenge to simultaneously discriminate them from each other. Herein, we develop a unique fluorescent probe (HMN) for not only simultaneously distinguishing Cys/Hcy, GSH, and H2S from each other, but also sequentially sensing Cys/Hcy/GSH and H2S using a multi-channel fluorescence mode for the first time...
September 1, 2017: Chemical Science
Zhen Li, Yuqing Xu, Hailiang Zhu, Yong Qian
The fluorescence monitoring of formaldehyde in real environmental samples and live plant tissues is of great importance for physiological and pathological studies. However, there is a lack of suitable chemical tools to directly trace and measure the formaldehyde activity in bio-systems, and developing effective and, in particular, selective sensors for mapping formaldehyde in live tissues still remains a great challenge. Here, we demonstrate for the first time that the ratiometric fluorescence monitoring of formaldehyde in live plant tissues is achieved with a newly developed ratiometric fluorescent probe, FAP, which effectively eliminated interference from other comparative analytes...
August 1, 2017: Chemical Science
Yohannes Nigatie
Nowadays, kidney failure is a problem of many peoples in the world. We know that the main function of kidney is maintaining the chemical quality of blood particularly removing urea through urine. But when they malfunction, the pathologic state known as uremia results in a condition in which the urea is retained in the body. Failure of the kidney results in building up of harmful wastes and excess fluids in the body. Kidney diseases (failures) can be due to infections, high blood pressure (hypertension), diabetes, and/or extensive use of medication...
2017: Biomedical Engineering and Computational Biology
G Siracusano, A La Corte, M Gaeta, G Finocchio
Multi-echo Chemical Shift-Encoded (CSE) methods for Fat-Water quantification are growing in clinical use due to their ability to estimate and correct some confounding effects. State of the art CSE water/fat separation approaches rely on a multi-peak fat spectrum with peak frequencies and relative amplitudes kept constant over the entire MRI dataset. However, the latter approximation introduces a systematic error in fat percentage quantification in patients where the differences in lipid chemical composition are significant (such as for neuromuscular disorders) because of the spatial dependence of the peak amplitudes...
October 2, 2017: Magnetic Resonance Imaging
V M Chertok, N V Zakharchuk, A G Chertok
This review presents the data on cellular and molecular mechanisms of angiogenesis regulation linked to the vascular epithelium. According to current conceptions, activated endothelial cells and their predecessors (progenitor cells) are involved in the regulation of angiogenesis. These cells synthesize angiogenic molecules differing by the chemical structure and mechanism of biological effect and allowing a direct or indirect control over each stage of angiogenesis. Both the excess and insufficient angiogenesis can lead to fast and irreversible changes in nervous tissue under certain conditions...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Ahmet Kürşat Bozkurt, Ozan Onur Balkanay
Incidence and severity of both deep vein thrombosis and chronic venous insufficiency are increased with age. Today, however, the significance of these diseases in the elderly patient population are still poorly comprehended. Although most patients have a history of previous treatment, chronic venous insufficiency is usually encountered in the advanced clinical stage. As a result, there is an increase in mobility restrictions, the need for assistance in daily activities and the risk of falls in elderly patients...
September 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Richard Lincoln, Lana E Greene, Wenzhou Zhang, Sheena Louisia, Gonzalo Cosa
Protein and DNA alkylation by endogenously produced electrophiles is associated with the pathogenesis of neurodegenerative diseases, to epigenetic alterations and to cell signaling and redox regulation. With the goal of visualizing, in real-time, the spatiotemporal response of the cell milieu to electrophiles, we have designed a fluorogenic BODIPY-acrolein probe, AcroB, that undergoes a >350-fold fluorescence intensity enhancement concomitant with protein adduct formation. AcroB enables a direct quantification of single post-translational modifications occurring on cellular proteins via recording fluorescence bursts in live-cell imaging studies...
October 13, 2017: Journal of the American Chemical Society
Sanaz Rasouli, Alireza Abdolvahabi, Corbin M Croom, Devon L Plewman, Yunhua Shi, Jacob I Ayers, Bryan F Shaw
The acylation of lysine residues in superoxide dismutase-1 (SOD1) has been previously shown to decrease its rate of nucleation and elongation into amyloid-like fibrils linked to amyotrophic lateral sclerosis (ALS). The chemical mechanism underlying this effect is unclear, i.e. hydrophobic/steric effects versus electrostatic effects. Moreover, the degree to which the acylation might alter the prion-like seeding of SOD1 in in vivo has not been addressed. Here, we acylated a fraction of lysine residues in SOD1 with groups of variable hydrophobicity, charge, and conformational entropy...
October 3, 2017: Journal of Biological Chemistry
Jon C Cook, Leslie A Obert, Petra Koza-Taylor, Tim Coskran, Alan Opsahl, Daniel Ziemek, Marc Roy, Jessie Qian, Michael P Lawton, Kay Criswell
Pharmaceuticals and chemicals produce hemangiosarcomas (HS) in mice, often by nongenotoxic, proliferative mechanisms. A mode-of-action (MOA) for hemangiosarcoma was proposed based on information presented at an international workshop (Cohen et al., 2009). Five key elements of the MOA were articulated and included hypoxia, macrophage activation, increased angiogenic growth factors, dysregulated angiogenesis/erythropoiesis, and endothial cell proliferation. The goal of the current study was to add to the weight-of-evidence for the proposed MOA by assessing these key elements with three different compounds of varying potency for HS induction: fenretinide (high), troglitazone (intermediate), and elmiron (low)...
September 18, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
J Saarbach, E Lindberg, S Folliet, S Georgeon, O Hantschel, N Winssinger
Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation that enables the detection and imaging of specific kinases. Using two probes that target the nucleotide-binding site and substrate binding site of a target kinase respectively, the reagents appended on the probes are brought within reactive distance thereby enabling the chemical transformation...
July 1, 2017: Chemical Science
Travis W Bainbridge, Diana Ronai Dunshee, Noelyn M Kljavin, Nicholas J Skelton, Junichiro Sonoda, James A Ernst
Fibroblast Activation Protein (FAP) is a membrane-bound serine protease whose expression is often elevated in activated fibroblasts associated with tissue remodeling in various common diseases such as cancer, arthritis and fibrosis. Like the closely related dipeptidyl peptidase DPPIV, the extracellular domain of FAP can be released into circulation as a functional enzyme, and limited studies suggest that the circulating level of FAP correlates with the degree of tissue fibrosis. Here we describe a novel homogeneous fluorescence intensity assay for circulating FAP activity based on a recently identified natural substrate, FGF21...
October 2, 2017: Scientific Reports
Silke Smolders, Sofie Kessels, Sophie Marie-Thérèse Smolders, Florent Poulhes, Olivier Zelphati, Cedric Sapet, Bert Brône
BACKGROUND: Microglia, the resident phagocytic cells of the brain, have recently been the subject of intense investigation given their role in pathology and normal brain physiology. In general, phagocytic cells are hard to transfect with plasmid DNA. The BV2 cell line is a murine cell line of microglial origin which is often used to study this cell type in vitro. Unfortunately, this microglial cell line is, like other phagocytic cells, resistant to transfection. NEW METHOD: Magnetofection is a well-established transfection method that combines DNA with magnetic particles which, under the influence of a magnetic field, ensures a high concentration of particles in proximity of cultured cells...
September 29, 2017: Journal of Neuroscience Methods
Marlene A Tapper, James C Pethick, Lowell L Dilworth, Donovan A McGrowder
INTRODUCTION: The Chemical Pathology Laboratory at the University Hospital of the West Indies (UHWI) processes specimens received from inpatients, the outpatient department and other medical facilities in Jamaica. Specific rejection criteria are used to determine samples unsuitable for analysis. It has been noted that despite efforts to reduce the number of unacceptable samples received in the laboratory, the problem persists. AIM: The study seeks to provide empirical evidence of the inadequacies from which improvements can be formulated...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
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