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https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#1
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28332430/preparation-of-pva-amino-multi-walled-carbon-nanotubes-nanocomposite-microspheres-for-endotoxin-adsorption
#2
Wenhui Zong, Jian Chen, Wenyan Han, Guanghui Cheng, Jie Chen, Yue Wang, Weichao Wang, Lailiang Ou, Yaoting Yu, Jie Shen
A novel polyvinyl alcohol-amino multi-walled carbon nanotube (PVA-AMWCNT) nanocomposite microsphere was prepared successfully for the first time and used for endotoxin removal. The resulting AMWCNT modified PVA microsphere was characterized by SEM, Raman spectrum and fluorescence image, which indicated AMWCNT was dispersed into the macropores of PVA microsphere uniformly. The PVA-AMWCNT microspheres showed better adsorption capability and faster adsorption equilibrium for endotoxin in aqueous solution when compared to the PVA microsphere with polymyxin B (PMB) as ligand...
March 23, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28332318/a-novel-bispecific-molecule-delivered-by-recombinant-aav2-suppresses-ocular-inflammation-and-choroidal-neovascularization
#3
Yiming Li, Ping Zhu, Amrisha Verma, Tuhina Prasad, Hongxin Deng, Dechao Yu, Qiuhong Li
Elevated vascular endothelial growth factor (VEGF) and complement activation are implicated in the pathogenesis of different ocular diseases. The objective of this study was to investigate the hypothesis that dual inhibition of both VEGF and complement activation would confer better protection against ocular inflammation and neovascularization. In this study, we engineered a secreted chimeric VEGF inhibitor domain (VID), a complement inhibitor domain (CID) and a dual inhibitor (ACVP1). Vectors expressing these three inhibitors were constructed and packaged into AAV2 (sextY-F) particles...
March 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28330277/classical-and-bayesian-predictions-applied-to-bacillus-toxin-production
#4
Karim Ennouri, Rayda Ben Ayed, Maura Mazzarello, Ennio Ottaviani, Fathi Hertelli, Hichem Azzouz
Bacillus thuringiensis is a bacterium with unusual properties that make it useful for pest control in ecoagriculture. It can form a parasporal crystal containing polypeptides (also called delta-endotoxins). These entomopathogenic toxins are made during the stationary phase of the bacterial growth cycle and were initially characterized as an insect pathogen. Nowadays, the use of saturated two-level designs is very popular. This method is especially used in industrial applications where the cost of experiments is expensive...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330137/biotechnological-production-of-hyaluronic-acid-a-mini-review
#5
REVIEW
Jun Hui Sze, Jeremy C Brownlie, Christopher A Love
Hyaluronic acid (HA) is a polysaccharide found in the extracellular matrix of vertebrate epithelial, neural and connective tissues. Due to the high moisture retention, biocompatibility and viscoelasticity properties of this polymer, HA has become an important component of major pharmaceutical, biomedical and cosmetic products with high commercial value worldwide. Currently, large scale production of HA involves extraction from animal tissues as well as the use of bacterial expression systems in Streptococci...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329851/short-tslp-attenuates-toluene-diisocyanate-tdi-induced-airway-inflammation-and-inhibits-hmgb1-rage-and-long-tslp-expression
#6
Yanhong Wang, Yanqing Le, Wenqu Zhao, Yun Lin, Yue Wu, Changhui Yu, Jing Xiong, Fei Zou, Hangming Dong, Shaoxi Cai, Haijin Zhao
Short thymic stromal lymphopoietin (short TSLP), one of TSLP variants, exerts anti-inflammatory activities in endotoxin shock and colitis mouse models. Our latest work reported that short TSLP prevented house dust mite (HDM)-induced epithelial barrier disruption. Yet the role of short TSLP in toluene diisocyanate (TDI)-induced asthma is unknown. Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthma model. Synthetic short TSLP peptides were given intranasally (i.n.) or intraperitoneally (i...
February 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329379/the-lysis-of-pathogenic-escherichia-coli-by-bacteriophages-releases-less-endotoxin-than-betalactams
#7
Nicolas Dufour, Raphaëlle Delattre, Jean-Damien Ricard, Laurent Debarbieux
Background: Beside numerous experimental data assessing phage therapy efficacy, questions regarding safety of this approach are not sufficiently addressed. In particular, as phages can kill bacterial cells within less than 10 minutes, the associated endotoxin release (ER) in severe infections caused by Gram-negative bacteria could be a matter of concern. Methods: Two therapeutic virulent phages and four reference antibiotics were studied in vitro for their ability to kill two pathogenic strains of Escherichia coli and generate an ER...
March 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328802/curative-effect-of-neutral-macroporous-resin-hemoperfusion-on-treating-hemodialysis-patients-with-refractory-uremic-pruritus
#8
Wen-Hong Li, Yu-Min Yin, Hao Chen, Xiao-Dan Wang, He Yun, Hui Li, Jie Luo, Jin-Wen Wang
This study aims to investigate the efficacy and safety of neutral macroporous resin hemoperfusion in treating maintenance hemodialysis (MHD) patients with refractory uremic pruritus (RUP).Ninety patients were enrolled and were randomly divided into 3 groups: control group, experiment 1 group, and experiment 2 group. Clinical symptom scores of skin itching were recorded before and at 4 and 8 weeks after the treatment. In addition, serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and C-reactive protein (CRP) were detected; and the calcium-phosphorus product ([Ca] × [P]) was calculated to compare the curative effect...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28323272/constipation-predominant-irritable-bowel-syndrome-females-have-normal-colonic-barrier-and-secretory-function
#9
Stephanie A Peters, Shoko Edogawa, Wendy J Sundt, Roy B Dyer, Daniel A Dalenberg, Amelia Mazzone, Ravinder J Singh, Natalie Moses, Thomas C Smyrk, Christopher Weber, David R Linden, Wallace K MacNaughton, Jerrold R Turner, Michael Camilleri, David A Katzka, Gianrico Farrugia, Madhusudan Grover
OBJECTIVES: The objective of this study was to determine whether constipation-predominant irritable bowel syndrome (IBS-C) is associated with changes in intestinal barrier and secretory function. METHODS: A total of 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g (13)C mannitol and 1 g lactulose), measurements of duodenal and colonic mucosal barrier (transmucosal resistance (TMR), macromolecular and Escherichia coli Bio-Particle translocation), mucosal secretion (basal and acetylcholine (Ach)-evoked short-circuit current (Isc)), in vivo duodenal mucosal impedance, circulating endotoxins, and colonic tight junction gene expression...
March 21, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28322834/anti-human-cd14-monoclonal-antibody-improves-survival-following-sepsis-induced-by-endotoxin-but-not-following-polymicrobial-infection
#10
Masaki Nakamura, Takashi Takeuchi, Kamon Shirakawa, Shoji Furusako
Cluster of differentiation 14 (CD14), a pattern recognition receptor expressed on myeloid cells and a critical component of the innate immune system, mediates local and systemic host responses to gram-negative bacterial products, including lipopolysaccharide (LPS). Therefore, CD14 is an attractive target for development of sepsis therapies, and several monoclonal anti-CD14 antibodies have been reported. In this study, we prepared an anti-human CD14 monoclonal antibody, F1024-1-3, which suppressed LPS-induced upregulation of pro-inflammatory cytokines and an adhesion molecule in human peripheral mononuclear cells and human vascular endothelial cells...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322791/lps-depletes-phlpp-levels-in-macrophages-through-the-inhibition-of-sp1-dependent-transcriptional-regulation
#11
Neeraja P Alamuru-Yellapragada, Sanghamitra Vundyala, Soma Behera, Kishore V L Parsa
We have previously reported that bacterial endotoxin LPS attenuates expression of PHLPP, a ser/thr phosphatase, at both transcript and protein levels in different immune cells, however the underlying molecular mechanism is unknown and is of significant interest. Here, in line with the decreased transcript levels upon LPS treatment, we observed that LPS caused significant reduction in PHLPP promoter activity. We observed that SP1, a transcription factor frequently associated with inflammation, was recruited to the PHLPP promoter region...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322133/rosiglitazone-regulates-tlr4-and-rescues-ho-1-and-nrf2-expression-in-myometrial-and-decidual-macrophages-in-inflammation-induced-preterm-birth
#12
Leena Kadam, Nardhy Gomez-Lopez, Tara Mial, Hamid-Reza Kohan-Ghadr, Sascha Drewlo
INTRODUCTION: Elevated inflammation accounts for approximately 30% of preterm birth (PTB) cases. We previously reported that targeting the peroxisome proliferator-activated receptor gamma (PPARγ) pathway reduced the incidence of PTB in the mouse model of endotoxin-induced PTB. The PPARγ has proven anti-inflammatory functions and its activation via rosiglitazone significantly downregulated the systemic inflammatory response and reduced PTB and stillbirth rate by 30% and 41%, respectively, in our model...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28320525/reducing-indoor-air-pollutants-with-air-filtration-units-in-wood-stove-homes
#13
Marcy L McNamara, Jonathon Thornburg, Erin O Semmens, Tony J Ward, Curtis W Noonan
BACKGROUND: Biomass burning has been shown to be a major source of poor indoor air quality (IAQ) in developing and higher income countries across the world. Specifically, wood burning for cooking and heating contributes to high indoor concentrations of fine (particles with aerodynamic diameters<2.5μm; PM2.5) and coarse (particles with aerodynamic diameters <10μm and >2.5μm; PMc) particulate matter. Endotoxin, predominantly found within the coarse fraction of airborne particulate matter, is associated with proinflammatory effects and adverse outcomes among susceptible populations...
March 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28317862/biological-activity-of-masked-endotoxin
#14
Harald Schwarz, Jan Gornicec, Theresa Neuper, Maria Alejandra Parigiani, Michael Wallner, Albert Duschl, Jutta Horejs-Hoeck
Low endotoxin recovery (LER) is a recently discovered phenomenon describing the inability of limulus amebocyte lysate (LAL)-based assays to detect lipopolysaccharide (LPS) because of a "masking effect" caused by chelators or detergents commonly used in buffer formulations for medical products and recombinant proteins. This study investigates the masking capacities of different buffer formulations and whether masked endotoxin is biologically active. We show that both naturally occurring endotoxin as well as control standard endotoxin can be affected by LER...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316108/cry1a-b-16-toxin-from-bacillus-thuringiensis-theoretical-refinement-of-three-dimensional-structure-and-prediction-of-peptides-as-molecular-markers-for-detection-of-genetically-modified-organisms
#15
Alexandra Plácido, Andreia Coelho, Lucas Abreu do Nascimento, Andreanne Gomes Vasconcelos, Maria Fátima Barroso, Joilson Ramos-Jesus, Vladimir Costa, Francisco das Chagas Alves Lima, Cristina Delerue-Matos, Ricardo Martins Ramos, Mariela M Marani, José Roberto de Souza de Almeida Leite
Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, e.g., biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures...
March 18, 2017: Proteins
https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#16
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28314100/attenuated-mtor-signaling-and-enhanced-glucose-homeostasis-by-dietary-supplementation-with-lotus-seedpod-oligomeric-procyanidins-in-streptozotocin-stz-induced-diabetic-mice
#17
Xiaopeng Li, Yong Sui, Qian Wu, Bijun Xie, Zhida Sun
This study investigated the protective role of lotus seedpod oligomeric procyanidins (LSOPC) and synbiotics (Bifidobacterium Bb-12 and xylo-oligosaccharide) against high fat and streptozotocin (STZ)-induced diabetes. Administration of LSOPC or synbiotics have no effect on blood glucose in normal mice. Treatments with LSOPC for 12 weeks markedly reduced blood glucose, FFA, endotoxin, GHbA1c and improved glucose homeostasis, lipid metabolism and insulin level. In addition, administration of LSOPC significantly reversed the increase of mTOR and p66Shc in liver, skeletal muscle and white adipose tissue (WAT)...
March 17, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28303896/phospholipid-imprinted-polymers-as-selective-endotoxin-scavengers
#18
Robert Sulc, Gyorgy Szekely, Sudhirkumar Shinde, Celina Wierzbicka, Filipe Vilela, David Bauer, Börje Sellergren
Herein we explore phospholipid imprinting as a means to design receptors for complex glycolipids comprising the toxic lipopolysaccharide endotoxin. A series of polymerizable bis-imidazolium and urea hosts were evaluated as cationic and neutral hosts for phosphates and phosphonates, the latter used as mimics of the phospholipid head groups. The bis-imidazolium hosts interacted with the guests in a cooperative manner leading to the presence of tight and well defined 1:2 ternary complexes. Optimized monomer combinations were subsequently used for imprinting of phosphatidic acid as an endotoxin dummy template...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296884/increased-von-willebrand-factor-decreased-adamts13-and-thrombocytopenia-in-melioidosis
#19
Emma Birnie, Gavin C K W Koh, Ester C Löwenberg, Joost C M Meijers, Rapeephan R Maude, Nicholas P J Day, Sharon J Peacock, Tom van der Poll, W Joost Wiersinga
BACKGROUND: Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. We hypothesized that changes in Von Willebrand factor (VWF) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin in melioidosis, and investigated whether this impacted on outcome...
March 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28294970/krill-oil-in-water-emulsion-protects-against-lipopolysaccharide-induced-proinflammatory-activation-of-macrophages-in-vitro
#20
Gabriel A Bonaterra, David Driscoll, Hans Schwarzbach, Ralf Kinscherf
BACKGROUND: Parenteral nutrition is often a mandatory therapeutic strategy for cases of septicemia. Likewise, therapeutic application of anti-oxidants, anti-inflammatory therapy, and endotoxin lowering, by removal or inactivation, might be beneficial to ameliorate the systemic inflammatory response during the acute phases of critical illness. Concerning anti-inflammatory properties in this setting, omega-3 fatty acids of marine origin have been frequently described. This study investigated the anti-inflammatory and LPS-inactivating properties of krill oil (KO)-in-water emulsion in human macrophages in vitro...
March 15, 2017: Marine Drugs
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