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https://www.readbyqxmd.com/read/28549219/design-synthesis-and-properties-of-a-potent-inhibitor-of-pseudomonas-aeruginosa-deacetylase-lpxc
#1
Grazia Piizzi, David T Parker, Yunshan Peng, Markus Rolf Dobler, Anup Patnaik, Som Wattanasin, Eugene Liu, Francois Lenoir, Jill Nunez, John Kerrigan, David McKenney, Colin S Osborne, Donghui Yu, Leanne Lanieri, Jade Bojkovic, JoAnne Dzink-Fox, Maria-Dawn Lilly, Elizabeth R Sprague, Yipin Lu, Hongming Wang, Srijan Ranjitkar, Bing Wang, Meir Glick, Lawrence G Hamann, Ruben Tommasi, Xia Yang, Charles R Dean
Over the past several decades the frequency of antibacterial resistance in hospitals, including multi-drug resistance (MDR) and its association with serious infectious diseases, has increased at alarming rates. Pseudomonas aeruginosa is a leading cause of nosocomial infections, and resistance to virtually all approved antibacterial agents is emerging in this pathogen. To address the need for new agents to treat MDR P. aeruginosa, we focused on inhibiting the first committed step in the biosynthesis of lipid A, the deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by the enzyme LpxC...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28544567/chemoproteomics-aided-medicinal-chemistry-for-the-discovery-of-epha2-inhibitors
#2
Stephanie Heinzlmeir, Jonas Lohse, Tobias Treiber, Denis Kudlinzki, Verena Linhard, Santosh Lakshmi Gande, Sridhar Sreeramulu, Krishna Saxena, Xiaofeng Liu, Mathias Wilhelm, Harald Schwalbe, Bernhard Kuster, Guillaume Médard
The receptor tyrosine kinase EPHA2 has gained interest as therapeutic drug target in cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small molecule inhibitors. Here, we report on the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor Dasatinib as a lead structure. We designed hybrid structures of Dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955 and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2...
May 24, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28543438/humanized-mice-a-brief-overview-on-their-diverse-applications-in-biomedical-research
#3
REVIEW
Shigeyoshi Fujiwara
Model animals naturally differ from humans in various respects and results from the former are not directly translatable to the latter. One approach to address this issue is humanized mice that are defined as mice engrafted with functional human cells or tissues. In humanized mice, we can investigate the development and function of human cells or tissues (including their products encoded by human genes) in the in vivo context of a small animal. As such, humanized mouse models have played important roles that cannot be substituted by other animal models in various areas of biomedical research...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28543367/successful-treatment-of-methicillin-susceptible-staphylococcus-aureus-osteomyelitis-with-oritavancin
#4
Dino J Delaportas, Sandy J Estrada, Matthew Darmelio
Staphylococcus aureus remains the most common causative pathogen in osteomyelitis. New or alternate therapies are often needed to adequately treat S. aureus infections in patients with drug allergies, treatment failures, or drug interactions. Oritavancin is a novel long-acting lipoglycopeptide approved by the Food and Drug Administration (FDA) in 2014 for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). With a terminal half-life of 8 to 10 days, oritavancin dosing regimens with infrequent parenteral administration now exist to treat infectious diseases such as osteomyelitis that would otherwise require daily dosing of intravenous antimicrobials for weeks; however clinical experience is lacking...
May 23, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28542223/measuring-changes-in-transmission-of-neglected-tropical-diseases-malaria-and-enteric-pathogens-from-quantitative-antibody-levels
#5
Benjamin F Arnold, Mark J van der Laan, Alan E Hubbard, Cathy Steel, Joseph Kubofcik, Katy L Hamlin, Delynn M Moss, Thomas B Nutman, Jeffrey W Priest, Patrick J Lammie
BACKGROUND: Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays...
May 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28539723/antimicrobial-and-anti-inflammatory-effects-of-ethanol-extract-of-corylopsis-coreana-uyeki-flos
#6
Da-Eon Park, In-Soo Yoon, Jung-Eun Kim, Ji-Hye Seo, Jin-Cheol Yoo, Chun-Sik Bae, Chang-Dai Lee, Dae-Hun Park, Seung-Sik Cho
BACKGROUND: Corylopsis coreana Uyeki (Hamamelidaceae) is a medicinal plant cultivated in Northeast Asia. Previously, we have reported that an ethanol extract of Corylopsis coreana Uyeki flos (ECCF) contains four active compounds with antioxidant activity. OBJECTIVE: The aim of this study was to investigate the antimicrobial spectrum against infectious bacteria and anti-inflammatory effect of ECCF in a mouse model of acute local inflammation. MATERIALS AND METHODS: In vitro antimicrobial susceptibility was evaluated using standard plate assay technique...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28538389/antimicrobial-resistance-patterns-clinical-features-and-risk-factors-for-septic-shock-and-death-of-nosocomial-e-coli-bacteremia-in-adult-patients-with-hematological-disease-a-monocenter-retrospective-study-in-china
#7
Jie Ma, Ning Li, Yajie Liu, Chong Wang, Xiaoyan Liu, Shengmei Chen, Xinsheng Xie, Silin Gan, Meng Wang, Weijie Cao, Fang Wang, Yanfan Liu, Dingming Wan, Ling Sun, Hui Sun
The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28537720/chromone-as-a-privileged-scaffold-in-drug-discovery-recent-advances
#8
Joana Reis, Alexandra Gaspar, Nuno Milhazes, Fernanda M Borges
The use of privileged structures in drug discovery has proven to be an effective strategy allowing the generation of innovative hits/leads and successful optimization processes. Chromone is actually recognized as a privileged structure and a valid template for the design of novel compounds with potential pharmacological interest, particularly in the field of neurodegenerative, inflammatory and infectious diseases as well as diabetes and cancer. Within this framework, this review provides the reader with a literature update following the preceding article entitled Chromone: a valid scaffold in Medicinal Chemistry...
May 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28537216/regulation-of-drug-metabolizing-enzymes-in-infectious-and-inflammatory-disease-implications-for-biologics-small-molecule-drug-interactions
#9
Pankajini Mallick, Guncha Taneja, Bhagavatula Moorthy, Romi Ghose
Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment...
June 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28535936/lipids-in-infectious-diseases-the-case-of-aids-and-tuberculosis
#10
REVIEW
Fabrice Dumas, Evert Haanappel
Lipids play a central role in many infectious diseases. AIDS (Acquired Immune Deficiency Syndrome) and tuberculosis are two of the deadliest infectious diseases to have struck mankind. The pathogens responsible for these diseases, Human Immunodeficiency Virus-1 and Mycobacterium tuberculosis, rely on lipids and on lipid membrane properties to gain access to their host cells, to persist in them and ultimately to egress from their hosts. In this Review, we discuss the life cycles of these pathogens and the roles played by lipids and membranes...
May 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28534957/grape-seed-proanthocyanidin-inhibits-inflammatory-responses-in-hepatic-stellate-cells-by-modulating-the-mapk-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#11
Jin-Woo Lee, Young Il Kim, Youngchul Kim, Minji Choi, Seoyeon Min, Yong Hoon Joo, Sung-Vin Yim, Namhyun Chung
In the present study, we aimed to investigate the molecular mechanisms and prophylactic effects of grape seed proanthocyanidin (GSP) on lipopolysaccharide (LPS)-stimulated human hepatic stellate cells (HSCs). Cell counting and MTT assays were used to assess cell viability in the absence or presence of GSP. Reverse transcription-quantitative PCR (RT-qPCR) was performed for several inflammation-related genes (NOD1, NOD2, TLR2, TLR4, IL-1 β, IL-6, IL-8, iNOS and COX-2). The expression of anti-inflammatory cell signaling molecules, including c-Jun N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), Akt, nuclear factor-κB (NF-κB), inhibitory-κBα (IκBα), iNOS and COX-2, was evaluated by western blot analysis...
May 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28533657/esophagitis-and-its-causes-who-is-guilty-when-acid-is-found-not-guilty
#12
EDITORIAL
Laurino Grossi, Antonio Francesco Ciccaglione, Leonardo Marzio
Esophagitis is mainly a consequence of gastroesophageal reflux disease, one of the most common diseases affecting the upper digestive tract. However the esophageal mucosa can also be targeted by some infectious, systemic or chemical conditions. Eosinophilic esophagitis (EoE) is an immune-mediated inflammatory disease, characterized by eosinophilic infiltration in the mucosa. Esophageal localization of Crohn's disease is not very common, but it should always be considered in patients with inflammatory bowel disease complaining of upper digestive tract symptoms...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28532790/a-safe-and-molecular-tagged-brucella-canis-ghosts-confers-protection-against-virulent-challenge-in-mice
#13
Jing Qian, Zhaoyang Bu, Xulong Lang, Guangmou Yan, Yanling Yang, Xiuran Wang, Xinglong Wang
Canine brucellosis, caused by Brucella canis, is a persistent infectious reproductive disease in dogs. The absence of effective treatment to the intracellular pathogen and the irreversible consequence of infection makes the need of a specific vaccine urgent. Bacterial ghosts (BGs) are the empty envelopes of bacteria with no genome content inside, which emerge as a proper vaccine candidate due to its intact outer antigen. It is generally derived from a genetically engineered strain, through the expression of Bacteriophage phiX174 lysis E gene upon induction...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28530057/-hansen-s-disease-in-israel
#14
REVIEW
Leon Gilead, Ruth Wexler
Hansen's disease (HD) is an anthropophylic, infectious, chronic disease, caused by Mycobacterium leprae. The systemic disease, affecting both males and females at any age, involves mainly the skin and the peripheral nerves located in the limbs close to the skin. Traditionally the treatment of HD patients was entrusted to dermatologists. Current drug therapy given at an early stage can prevent many of the complications, and enables patients to go on with life. In 95% of the population there is an innate immunity, which following exposure, enables the development of an effective immune response preventing the development of overt clinical disease...
October 2016: Harefuah
https://www.readbyqxmd.com/read/28529116/italian-consensus-guidelines-for-the-management-of-hepatitis-b-virus-infections-in-patients-with-rheumatoid-arthritis
#15
Marco Sebastiani, Fabiola Atzeni, Laura Milazzo, Luca Quartuccio, Carlo Scirè, Giovanni Battista Gaeta, Giovanni Lapadula, Orlando Armignacco, Marcello Tavio, Ignazio Olivieri, Pierluigi Meroni, Laura Bazzichi, Walter Grassi, Alessandro Mathieu, Claudio Mastroianni, Evangelista Sagnelli, Teresa Santantonio, Caterina Uberti Foppa, Massimo Puoti, Loredana Sarmati, Paolo Airò, Oscar Massimiliano Epis, Rossana Scrivo, Miriam Gargiulo, Agostino Riva, Andreina Manfredi, Giovanni Ciancio, Gianguglielmo Zehender, Gloria Taliani, Luca Meroni, Salvatore Sollima, Piercarlo Sarzi-Puttini, Massimo Galli
OBJECTIVES: Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations. METHODS: The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations...
May 18, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28528519/il-6-blockade-in-the-management-of-non-infectious-uveitis
#16
Giuseppe Lopalco, Claudia Fabiani, Jurgen Sota, Orso Maria Lucherini, Gian Marco Tosi, Bruno Frediani, Florenzo Iannone, Mauro Galeazzi, Rossella Franceschini, Donato Rigante, Luca Cantarini
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases...
May 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28526311/dramatic-effects-of-a-new-antimicrobial-stewardship-program-in-a-rural-community-hospital
#17
Claudia R Libertin, Stephanie H Watson, William L Tillett, Joy H Peterson
BACKGROUND: New Joint Commission antimicrobial stewardship requirements took effect on January 1, 2017, promoted as a central strategy for coping with the emerging problems of antimicrobial resistance and Clostridium difficile infection. Our objective was to measure the effects of a new antimicrobial stewardship program (ASP) in a rural community hospital with no prior ASP, in the context of having a new infectious disease specialist on staff. METHODS: An ASP team was formed to implement a prospective audit with health care provider feedback and targeting 12 antimicrobial agents in a rural hospital in Georgia...
May 16, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28521338/klebsiella-pneumoniae-a-major-worldwide-source-and-shuttle-for-antibiotic-resistance
#18
Shiri Navon-Venezia, Kira Kondratyeva, Alessandra Carattoli
Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28521337/perspectives-for-clinical-use-of-engineered-human-host-defense-antimicrobial-peptides
#19
María Eugenia Pachón-Ibáñez, Younes Smani, Jerónimo Pachón, Javier Sánchez-Céspedes
Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28516869/recommendations-for-infectious-disease-screening-in-migrants-to-western-europe-with-inflammatory-arthropathies-before-starting-biologic-agents-results-from-a-multidisciplinary-task-force-of-four-european-societies-sir-ser-simet-semtsi-facing-the-lar
#20
Filippo Bartalesi, Carlo Scirè, Ana Requena-Méndez, Miguel Angel Abad, Dora Buonfrate, Roberto Caporali, Fabrizio Conti, Federico Diaz-Gonzalez, Cruz Fernández-Espartero, Carmen Martinez-Fernandez, Marta Mascarello, Elena Generali, Giovanni Minisola, Aldo Morrone, Jose Muñoz, Patricia Richi, Gariffalia Sakellariou, Joaquin Salas Coronas, Michele Spinicci, Francesco Castelli, Alessandro Bartoloni, Zeno Bisoffi, Francisco Gimenez-Sanchez, Santiago Muñoz-Fernandez, Marco Matucci-Cerinic
OBJECTIVES: Inflammatory arthritis needs infectious disease screening before starting a biologic agent, however, few data are known about migrant patients, who represent a peculiar population which requires a multidisciplinary approach among international health specialists and should also be considered by health authorities. For this reason, the Italian and Spanish Societies of Rheumatology (SIR and SER) and Tropical Medicine (SIMET and SEMTSI) promoted a multidisciplinary task force in order to produce specific recommendations about screening and advices to be considered in migrant patients with inflammatory arthritis candidate to receive biological therapy, according to their geographical origin...
May 8, 2017: Clinical and Experimental Rheumatology
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