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https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#1
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29146135/multivalent-oleanolic-acid-human-serum-albumin-conjugate-as-nonglycosylated-neomucin-for-influenza-virus-capture-and-entry-inhibition
#2
Yang Yang, Hao-Jie He, Hao Chang, Yao Yu, Mei-Bing Yang, Yun He, Zhen-Chuan Fan, Suri S Iyer, Peng Yu
We report the synthesis of multivalent oleanolic acid (OA) protein conjugates as nonglycosylated neomucin mimic for the capture and entry inhibition of influenza viruses. Oleanolic acid derivatives bearing an amine-terminated linker were synthesized by esterification of carboxylic acid and further grafted onto the human serum albumin (HSA) via diethyl squarate method. The binding of hemagglutinin (HA) on the virion surface to the synthetic neomucin was evaluated by hemagglutination inhibition assay. The influenza virus capture ability of the PEGylated OA-HSA conjugate was further investigated by Dynamic Light Scattering (DLS), virus capture assay and Isothermal Titration Calorimeter (ITC) techniques...
October 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29143719/microbial-protein-targets-towards-understanding-and-intervention
#3
Paul W Denny
The rise of antimicrobial resistance, coupled with a lack of industrial focus on antimicrobial discovery over preceding decades, has brought the world to a crisis point. With both human and animal health set to decline due to increased disease burdens caused by near untreatable microbial pathogens, there is an urgent need to identify new antimicrobials. Central to this is the elucidation of new, robustly validated, drug targets. Informed by industrial practice and concerns, the use of both biological and chemical tools in validation is key...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29143311/interleukin-12-and-its-procoagulant-effect-on-erythrocytes-platelets-and-fibrin-ogen-the-lesser-known-side-of-inflammation
#4
Martin J Page, Janette Bester, Etheresia Pretorius
Inflammation, with its associated inflammatory molecules, is integral to most chronic diseases, including the various cardiovascular diseases. Interleukin 12 (IL12) is one of the inflammatory cytokines that is upregulated during inflammation; however, we know very little about its exact effect on red blood cells (RBCs), platelets and fibrin(ogen). IL12 is an important pleiotropic cytokine in early inflammatory responses and has potent immunomodulatory, antitumour and anti-infection activity. Here we investigate how low levels of circulating IL12, comparable to levels found during chronic inflammation, affect coagulation parameters, platelets and RBCs...
November 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/29141696/use-of-a-trigger-tool-to-detect-adverse-drug-reactions-in-an-emergency-department
#5
Silvana Maria de Almeida, Aruana Romualdo, Andressa de Abreu Ferraresi, Giovana Roberta Zelezoglo, Alexandre R Marra, Michael B Edmond
BACKGROUND: Although there are systems for reporting adverse drug reactions (ADR), these safety events remain under reported. The low-cost, low-tech trigger tool method is based on the detection of events through clues, and it seems to increase the detection of adverse events compared to traditional methodologies. This study seeks to estimate the prevalence of adverse reactions to drugs in patients seeking care in the emergency department. METHODS: Retrospective study from January to December, 2014, applying the Institute for Healthcare Improvement (IHI) trigger tool methodology for patients treated at the emergency room of a tertiary care hospital...
November 15, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29140690/new-sesquiterpenoids-from-eugenia-jambolana-seeds-and-their-anti-microbial-activities
#6
Feifei Liu, Chengbin Liu, Wei Liu, Zhanjun Ding, Hang Ma, Navindra P Seeram, Li Xu, Yu Mu, Xueshi Huang, Liya Li
Twenty four sesquiterpenoids, 1-24, including 11 new sesquiterpenoids, jambolanins A-K, and two new norsesquiterpenoids, jambolanes A and B, along with six known triterpenoids, were isolated from the seeds of Eugenia jambolana fruit. Their structures were elucidated on the basis of NMR and MS spectrometry data analysis. Among the isolates, compound 13 possessed a rare 6,7-seco-guaiene skeleton, and compounds 14 and 15 were norsesquiterpenoids containing a spiro[4.4]nonane skeleton. Antimicrobial assay evaluation revealed that sesquiterpenoids, 4, 5/6, 17, 19, 21, 23, and 24 inhibited the growth of the Gram-positive bacterium, Staphylococcus aureus...
November 15, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29140595/modulation-of-quorum-sensing-in-a-gram-positive-pathogen-by-linear-imprinted-copolymers-with-anti-infective-properties
#7
Anfal Motib, Antonio Guerreiro, Firas Al-Bayati, Elena Piletska, Irfan Manzoor, Sulman Shafeeq, Anagha Kadam, Oscar Kuipers, Luisa Hiller, Todd Cowen, Sergey Piletsky, Peter Andrew, Hasan Yesilkaya
Here we describe the development, characterization and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as anti-infective by blocking the quorum sensing (QS) mechanism and so preventing virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches no cross-linker is used. This results in soluble low molecular weight polymer that can act as drug agent in vitro and in vivo...
November 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29138583/efficacy-of-intravenous-tigecycline-in-patients-with-acinetobacter-complex-infections-results-from-14-phase-iii-and-phase-iv-clinical-trials
#8
Hal Tucker, Michele Wible, Ashesh Gandhi, Alvaro Quintana
Background: Acinetobacter infections, especially multidrug-resistant (MDR) Acinetobacter infections, are a global health problem. This study aimed to describe clinical outcomes in patients with confirmed Acinetobacter spp. isolates who were treated with tigecycline in randomized clinical trials. Materials and methods: Data from 14 multinational, randomized (open-label or double-blind), and active-controlled (except one) Phase III and IV studies were analyzed using descriptive statistics...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29133557/a-novel-mechanism-of-inactivating-antibacterial-nitro-compounds-in-the-human-pathogen-staphylococcus-aureus-by-overexpression-of-a-nadh-dependent-flavin-nitroreductase
#9
Ebaa M El-Hossary, Konrad U Förstner, Patrice François, Damien Baud, Karin Streker, Jacques Schrenzel, Knut Ohlsen, Ulrike Holzgrabe
Recently, the nitro substituted bisquaternary bisnaphthalimides were reported to have substantial anti-infective activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Here, we selected resistant S. aureus clones by cultivation in increasing concentrations of the most active compound MT02. Interestingly, MT02 resistant variants induced a diffusible red color of the broth. Chromatographic and spectroscopic investigations revealed a stepwise reduction of the bisquaternary bisnaphthalimides̀ nitro groups to amino groups...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29131269/clinical-analysis-of-urinary-tract-infection-in-patients-undergoing-transurethral-resection-of-the-prostate
#10
Y-H Li, G-Q Li, S-M Guo, Y-N Che, X Wang, F-T Cheng
OBJECTIVE: To analyze the related influencing factors of urinary tract infection in patients undergoing transurethral resection of the prostate (TURP). PATIENTS AND METHODS: A total of 343 patients with benign prostatic hyperplasia admitted to this hospital from January 2013 to December 2016, were selected and treated by TURP. Patients were divided into infection group and non-infection group according to the occurrence of urinary tract infection after operation...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29127020/does-the-use-of-antifungal-agents-in-agriculture-and-in-food-foster-polyene-resistance-development-a-reason-for-concern
#11
REVIEW
Axel Dalhoff
Environmental fungicides are used in agriculture to reduce fungal spoilage of crop to a minimum and the polyene macrolide natamycin is used as a food preservative. The use of natamycin in yoghurt has recently been authorized in the USA and some other countries. However, resistance development is a serious risk associated with the use of antimicrobials as food additives and environmental fungicides. Cross-resistance between agricultural and medical azoles and amphothericin B, respectively, not being used in agriculture has been demonstrated in clinical and environmental isolates...
November 7, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29124063/a-review-of-the-combination-therapy-of-low-frequency-ultrasound-with-antibiotics
#12
REVIEW
Yun Cai, Jin Wang, Xu Liu, Rui Wang, Lei Xia
Single antimicrobial therapy has been unable to resist the global spread of bacterial resistance. Literatures of available in vitro and in vivo studies were reviewed and the results showed that low frequency ultrasound (LFU) has a promising synergistic bactericidal effect with antibiotics against both planktonic and biofilm bacteria. It also can facilitate the release of antibiotics from medical implants. As a noninvasive and targeted therapy, LFU has great potential in treating bacterial infections. However, more in-depth and detailed studies are still needed before LFU is officially applied as a combination therapy in the field of anti-infective treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29119936/recent-patents-on-light-based-anti-infective-approaches
#13
Imran Ahmed, Yanyan Fang, Min Lu, Quan Yan, Ahmed Mohamed Kamel El-Hussein, Michael R Hamblin, Tianhong Dai
BACKGROUND: Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains...
November 7, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/29119720/phage-display-on-anti-infective-target-dxs-led-to-an-acceptor-substrate-competitive-peptidic-inhibitor
#14
Alessio Marcozzi, Tiziana Masini, Di Zhu, Diego Pesce, Boris Illarionov, Markus Fischer, Andreas Herrmann, Anna Katharina Herta Hirsch
Enzymes of the 2-C-methyl-d-erythritol-4-phosphate pathway for the biosynthesis of isoprenoid precursors are validated drug targets. By performing phage display on 1-deoxy-d-xylulose 5-phosphate synthase (DXS), which catalyzes the first step of this pathway, we discovered several peptide hits and recognized false positive hits. The enriched peptide binder P12 emerged as substrate (d-glyceraldehyde 3-phosphate) competitive against Deinococcus radiodurans DXS. The result indicates possible overlapping of cofactor- and acceptor-substrate-binding pockets, and provides inspiration for the design of inhibitors of DXS with a unique and novel mechanism...
November 8, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29114245/the-selective-interaction-of-pistacia-lentiscus-oil-vs-human-streptococci-an-old-functional-food-revisited-with-new-tools
#15
Germano Orrù, Cristina Demontis, Antonello Mameli, Enrica Tuveri, Pierpaolo Coni, Giuseppina Pichiri, Ferdinando Coghe, Antonella Rosa, Paola Rossi, Guy D'hallewin
Pistacia lentiscus berry oil (LBO) represents a typical vegetal product of the Mediterranean basin that has been formally used in traditional cuisine for 100s of years. In addition to its interesting alimentary properties, this product could represent an interesting candidate in the field of research on the study of new anti-infective agents. In fact, in Mediterranean countries, lentisk oil still continues to be widely used in folk medicine for oral and skin affections, in particular, acute gingivitis, pediatric skin infections such as impetigo and foot plaques, and biofilm related infections often associated with Streptococcus spp...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29112080/%C3%AE-lactam-therapeutic-drug-management-in-the-picu
#16
Jeffrey J Cies, Wayne S Moore, Adela Enache, Arun Chopra
OBJECTIVES: To determine whether contemporary β-lactam anti-infective dosing recommendations in critically ill children achieve concentrations associated with maximal anti-infective activity. The secondary objective was to describe the microbiological and clinical outcomes associated with β-lactam therapeutic drug management. DESIGN: Electronic Medical Record Review. SETTING: A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA...
November 3, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29109684/antimicrobial-anthelmintic-and-antiviral-activity-of-plants-traditionally-used-for-treating-infectious-disease-in-the-similipal-biosphere-reserve-odisha-india
#17
Sujogya K Panda, Laxmipriya Padhi, Pieter Leyssen, Maoxuan Liu, Johan Neyts, Walter Luyten
In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial (E. coli, S. aureus, C. albicans); anthelmintic (C. elegans); and antiviral (enterovirus 71) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29108108/antibacterial-aryl-crowned-polyketide-from-bacillus-subtilis-associated-with-seaweed-anthophycus-longifolius
#18
Kajal Chakraborty, Bini Thilakan, Vinaya Kizhakkepatt Kizhakkekalam
AIMS: Microbiological, biotechnological and chemical characterization of a previously undescribed aryl-crowned polyketide from Bacillus subtilis MTCC 10403 isolated from brown seaweed Anthophycus longifolius with activity against opportunistic Gram-negative food-borne pathogenic bacterial strains. METHODS AND RESULTS: A culture-dependent method was used to isolate heterotrophic B. subtilis associated with A. longifolius, and assessed for its antimicrobial properties...
November 6, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29091809/pharmacological-agents-preceding-a-diagnosis-of-immune-thrombocytopenia-in-adult-patients-developing-the-chronic-form-a-swedish-national-register-study
#19
Lukas Löfling, Marie Linder, Charlotta Ekstrand, Honar Cherif, Helle Kieler, Shahram Bahmanyar
Patients with primary chronic immune thrombocytopenia (cITP) have been reported to use more anti-infective medications, even before diagnosis of immune thrombocytopenia (ITP). The more common use of anti-infective medications may be due to general health problems, requiring medication in the early stages of cITP and before the diagnosis is set, rather than infections preceding the disease. Accordingly, cITP may not only be associated with use of anti-infective medications but also with medications for more general symptoms...
October 23, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29079968/prediction-of-drug-drug-interaction-potential-using-physiologically-based-pharmacokinetic-modeling
#20
REVIEW
Jee Sun Min, Soo Kyung Bae
The occurrence of drug-drug interactions (DDIs) can significantly affect the safety of a patient, and thus assessing DDI risk is important. Recently, physiologically based pharmacokinetic (PBPK) modeling has been increasingly used to predict DDI potential. Here, we present a PBPK modeling concept and strategy. We also surveyed PBPK-related articles about the prediction of DDI potential in humans published up to October 10, 2017. We identified 107 articles, including 105 drugs that fit our criteria, with a gradual increase in the number of articles per year...
October 27, 2017: Archives of Pharmacal Research
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