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Polymyxin-b

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https://www.readbyqxmd.com/read/28534936/forsythoside-a-exerts-an-anti-endotoxin-effect-by-blocking-the-lps-tlr4-signaling-pathway-and-inhibiting-tregs-in-vitro
#1
Xiao-Yan Zeng, Wei Yuan, Lin Zhou, Shi-Xiu Wang, Yong Xie, Ying-Jun Fu
Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28533232/potentiation-of-antibiotic-activity-by-a-novel-cationic-peptide-potency-and-spectrum-of-activity-of-spr741
#2
David Corbett, Andrew Wise, Tara Langley, Kirsty Skinner, Emily Trimby, Stephen Birchall, Alain Dorali, Stephanie Sandiford, Jennifer Williams, Peter Warn, Martti Vaara, Troy Lister
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii Of 35 antibiotics tested, the MICs of eight were reduced 32- to 8,000-fold against E...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28526864/a-broad-spectrum-bactericidal-lipopeptide-with-anti-biofilm-properties
#3
Ohad Meir, Fadia Zaknoon, Uri Cogan, Amram Mor
Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526567/synergistic-effects-of-polymyxin-and-ionic-liquids-on-lipid-vesicle-membrane-stability-and-aggregation
#4
Sylvia L Hanna, Jenny L Huang, Alana J Swinton, Gregory A Caputo, Timothy D Vaden
Ionic liquids (ILs) have been investigated for potential antibacterial and antibiotic applications due to their ability to destabilize and permeabilize the lipid bilayers in cell membranes. Bacterial assays have shown that combining ILs with antibiotics can provide a synergistic enhancement of their antibacterial activities. We have characterized the mechanism by which the conventional ILs 1-butyl-3-methylimidazolium chloride (BMICl) and 1-butyl-3-methylimidazolium tetrafluoroborate (BMIBF4) enhance the lipid membrane permeabilization of the well-known antibiotic polymyxin B (PMB)...
May 11, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28505268/pharmacodynamics-of-dose-escalated-front-loading-polymyxin-b-regimens-against-polymyxin-resistant-mcr-1-harbouring-escherichia-coli
#5
Nicholas M Smith, Zackery P Bulman, Arthur O Sieron, Jürgen B Bulitta, Patricia N Holden, Roger L Nation, Jian Li, Gerard D Wright, Brian T Tsuji
Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance. Methods: A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days...
May 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28501124/effects-of-endotoxin-absorber-hemoperfusion-on-microcirculation-in-septic-pigs
#6
Yu-Chang Yeh, Linda Chia-Hui Yu, Chun-Yu Wu, Ya-Jung Cheng, Chen-Tse Lee, Wei-Zen Sun, Jui-Chang Tsai, Tzu-Yu Lin
BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28497462/skin-hyperpigmentation-following-intravenous-polymyxin-b-treatment-associated-with-melanocyte-activation-and-inflammatory-process
#7
K P H Mattos, M L Cintra, I R Gouvêa, L Á Ferreira, P E N F Velho, P Moriel
What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment...
May 11, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28489424/a-novel-ph-responsive-hydrogel-based-on-calcium-alginate-engineered-by-the-previous-formation-of-polyelectrolyte-complexes-pecs-intended-to-vaginal-administration
#8
Natália Noronha Ferreira, Taciane Alvarenga Perez, Liliane Neves Pedreiro, Fabíola Garavello Prezotti, Fernanda Isadora Boni, Valéria Maria de Oliveira Cardoso, Tiago Venâncio, Maria Palmira Daflon Gremião
This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4...
May 10, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28463513/characterization-of-the-polymyxin-d-synthetase-biosynthetic-cluster-and-product-profile-of-paenibacillus-polymyxa-atcc-10401
#9
Charles A Galea, Meiling Han, Yan Zhu, Kade Roberts, Jiping Wang, Philip E Thompson, Jian L, Tony Velkov
The increasing prevalence of polymyxin-resistant bacteria has stimulated the search for improved polymyxin lipopeptides. Here we describe the sequence and product profile for polymyxin D nonribosomal peptide synthetase from Paenibacillus polymyxa ATCC 10401. The polymyxin D synthase gene cluster comprised five genes that encoded ABC transporters (pmxC and pmxD) and enzymes responsible for the biosynthesis of polymyxin D (pmxA, pmxB, and pmxE). Unlike polymyxins B and E, polymyxin D contains d-Ser at position 3 as opposed to l-α,γ-diaminobutyric acid and has an l-Thr at position 7 rather than l-Leu...
May 2, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28461268/formulation-and-characterisation-of-dissolving-microneedles-for-the-transdermal-delivery-of-therapeutic-peptides
#10
Colin Dillon, Helen Hughes, Niall J O'Reilly, Peter McLoughlin
The highly effective barrier properties of the stratum corneum (SC) limit the application of transdermal delivery to relatively small, lipophilic molecules. Microneedles (MNs) however, offer a route to effectively deliver a wide range of pharmaceuticals through the skin, bypassing the SC in a non-invasive and pain-free manner. This study presents a dissolving MN system composed of polyvinylpyrrolidone (PVP) and trehalose to encapsulate active pharmaceutical peptides within the MN matrix. Rapid systemic delivery is then achieved once the needles have penetrated the SC and dissolved in the interstitial fluid of the skin...
April 28, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28459130/identification-and-characterization-of-multifunctional-cationic-and-amphipathic-peptides-from-soybean-proteins
#11
Masayuki Taniguchi, Kengo Saito, Takafumi Nomoto, Toshiki Namae, Akihito Ochiai, Eiichi Saitoh, Takaaki Tanaka
In the present study, we identified and chemically synthesized three cationic and amphipathic peptides (Glycinin-17, BCAS-16, and BCBS-11) from soybean proteins. These peptides had high isoelectric points, high positive net charges, and included multiple hydrophobic amino acids. Subsequently, we identified multiple functions of these peptides, including antimicrobial, lipopolysaccharide-neutralizing, and angiogenic activities, and examined their cytotoxic activities against mammalian red blood cells. Glycinin-17, BCAS-16, and BCBS-11 exhibited antimicrobial activity against Porphyromonas gingivalis and Candida albicans whereas Glycinin-17 did not possess antimicrobial effects on Propionibacterium acnes and Streptococcus mutans...
April 29, 2017: Biopolymers
https://www.readbyqxmd.com/read/28457834/a-network-perspective-on-antimicrobial-peptide-combination-therapies-the-potential-of-colistin-polymyxin-b-and-nisin
#12
REVIEW
Paula Jorge, Martín Pérez-Pérez, Gael Pérez Rodríguez, Maria Olívia Pereira, Anália Lourenço
Antimicrobial combinations involving antimicrobial peptides (AMPs) attract considerable attention within current antimicrobial and anti-resistance research. The objective of this study was to review the available scientific literature on the effects of antimicrobial combinations involving colistin (polymyxin E), polymyxin B and nisin, which are US Food and Drug Administration (FDA)-approved AMPs broadly tested against prominent multidrug-resistant pathogens. A bioinformatics approach based on literature mining and manual expert curation supported the reconstruction of experimental evidence on the potential of these AMP combinations, as described in the literature...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28455613/polymyxin-b-inhibits-the-chaperone-activity-of-plasmodium-falciparum-hsp70
#13
Tawanda Zininga, Ofentse J Pooe, Pertunia B Makhado, Lebogang Ramatsui, Earl Prinsloo, Ikechukwu Achilonu, Heinrich Dirr, Addmore Shonhai
Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. Hsp70s are also implicated in the survival and pathogenicity of malaria parasites. The main agent of malaria, Plasmodium falciparum, expresses six Hsp70s. Of these, two (PfHsp70-1 and PfHsp70-z) localize to the parasite cytosol. Previously conducted gene knockout studies suggested that PfHsp70-z is essential, and it has been demonstrated that small-molecule inhibitors targeting PfHsp70-1 cause parasite death...
April 28, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28445237/effects-of-polymyxin-b-hemoperfusion-on-mortality-in-patients-with-severe-sepsis-and-septic-shock-a-systemic-review-meta-analysis-update-and-disease-severity-subgroup-meta-analysis
#14
Tzu Chang, Yu-Kang Tu, Chen-Tse Lee, Anne Chao, Chi-Hsiang Huang, Ming-Jiuh Wang, Yu-Chang Yeh
OBJECTIVE: Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2016...
April 25, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28443813/vacuolar-h-atpase-subunit-vma1p-functions-as-the-molecular-ligand-in-the-vacuole-targeting-fungicidal-activity-of-polymyxin-b
#15
Maki Iida, Keiichi Yamada, Yoshiya Nango, Yoshihiro Yamaguchi, Akira Ogita, Ken-Ichi Fujita, Toshio Tanaka
Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the growth of Gram-negative bacteria by disrupting the outer membrane permeability barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae cells, suggesting the presence of a molecular ligand assisting the vacuole-targeting mobilization of the peptide in the organism...
April 2017: Microbiology
https://www.readbyqxmd.com/read/28441858/-development-of-an-eosinophilic-bronchitis-mouse-model-and-the-effects-of-eosinophil-activation-on-airway-hyperresponsiveness-in-eosinophilic-bronchitis-mice
#16
L Li, J T Lin
Objective: To develop a mouse model of eosinophilic bronchitis, and explore the effects of eosinophil activation on airway hyperresponsiveness. Methods: A total of 60 female specific pathogen free BALB/c female mice were divided randomly into four groups: polymyxin B group, normal saline group, polymyxin B+ N-methionine leucine phenylalanine (fMLP) group, normal saline+ fMLP group. All the groups were given corresponding nasal drops for 21 days. The former two groups were given 12 μl 0.5% polymyxin B or normal saline once a day by transnasal administration respectively...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28440556/direct-hemoperfusion-with-polymyxin-b-immobilized-fibre-treatment-for-acute-exacerbation-of-interstitial-pneumonia
#17
Haruhiko Furusawa, Makiko Sugiura, Chieko Mitaka, Naohiko Inase
BACKGROUND AND OBJECTIVE: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is recognized as an important cause of mortality. AE has also been reported in patients with other interstitial lung diseases such as idiopathic non-specific interstitial pneumonia (NSIP) and interstitial pneumonia associated with collagen vascular disease (CVD). Current therapies such as high-dose corticosteroid with immunosuppressive agents have provided little benefit for AE. Direct hemoperfusion (DHP) with a polymyxin B-immobilized fibre column (PMX) was originally developed for the treatment of endotoxaemia...
April 25, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28438930/in-vitro-assessment-of-combined-polymyxin-b-and-minocycline-therapy-against-klebsiella-pneumoniae-carbapenemase-kpc-producing-k-pneumoniae
#18
Dennis Huang, Brenda Yu, John K Diep, Rajnikant Sharma, Michael Dudley, Keith S Kaye, Jason M Pogue, Cely Abboud Saad, Gauri Rao
The multi-drug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes have been reported with intravenous minocycline-based combination treatments for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28433743/the-antibiotic-polymyxin-b-exhibits-novel-antifungal-activity-against-fusarium-species
#19
Li-Hang Hsu, Hsuan-Fu Wang, Pei-Lun Sun, Fung-Rong Hu, Ying-Lien Chen
The genus Fusarium comprises many species, including Fusarium oxysporum, Fusarium solani, Fusarium graminearum and Fusarium verticillioides, and causes severe infections in plants and humans. In clinical settings, Fusarium is the third most frequent mould to cause invasive fungal infections after Aspergillus and the Mucorales. F. solani and F. oxysporum are the most prevalent Fusarium spp. causing clinical disease. However, few effective antifungal drugs are available to treat human and plant Fusarium infections...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28416543/potential-toxicity-of-polymyxins-in-human-lung-epithelial-cells
#20
Maizbha U Ahmed, Tony Velkov, Yu-Wei Lin, Bo Yun, Cameron J Nowell, Fanfan Zhou, Qi Tony Zhou, Kim Chan, Mohammad A K Azad, Jian Li
Inhaled polymyxins are of considerable utility to achieve optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical and often high doses are used which may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial cells (A549). Viability of A549 cells was examined after treatment with polymyxins using flow cytometry. Activation of caspase-3, -8, -9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential and mitochondrial oxidative stress induced by polymyxin B was evaluated...
April 17, 2017: Antimicrobial Agents and Chemotherapy
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