scholarly journals Wet leakage resistance development of modules with various backsheet types

2021 ◽  
Author(s):  
Claudia Buerhop ◽  
Oleksandr Stroyuk ◽  
Julian Zöcklein ◽  
Tobias Pickel ◽  
Jens Hauch ◽  
...  
Keyword(s):  
Resistance Development ◽  
Leakage Resistance

The evaluation of lipid peroxidation and oxidative modification of proteins in blood serum under obesity development and the consumption of aqueous kidney beans Phaseolus vulgaris pods extract

2020 ◽  
Vol 33 (1) ◽  
pp. 38-44
Author(s):  
Alona Yurchenko ◽  
Daryna Krenytska ◽  
Olexii Savchuk ◽  
Tetiana Halenova ◽  
Natalia Raksha ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Oxidative Modification ◽  
Resistance Development ◽  
Oxidative Modification Of Proteins ◽  
Kidney Beans ◽  
Calorie Diet ◽  
Diet Control ◽  
High Calorie Diet ◽  
High Calorie

AbstractOur interest has focused on the investigation of the anti-obese potential of kidney beans (P. vulgaris) pods extract. In the course of the study, obesity development in rats was induced with high-calorie diet. Control and obese rats then have consumed with aqueous kidney beans (P. vulgaris) pods extract during 6 weeks (200 mg/kg). Results show that the long-term consumption of P. vulgaris pods extract can lead to the reduction of hyperglycemia and insulin resistance development. Furthermore, we saw a normalization of lipid peroxidation parameters and oxidative modification of protein due to the consumption of the kidney beans (P. vulgaris) pods extract. Our experimental data demonstrate the ability of the kidney beans (P. vulgaris) pod extracts to mitigate obesity development but the details of this mechanism remains to be not fully understood.

Discovery of an Unexpected Similarity in Ligand Binding Between BRD4 and PPARγ

2019 ◽  
Author(s):  
Lina Humbeck ◽  
Jette Pretzel ◽  
Saskia Spitzer ◽  
Oliver Koch
Keyword(s):  
Cancer Therapy ◽  
Drug Targets ◽  
Synergistic Effects ◽  
Complex Structure ◽  
Peroxisome Proliferator ◽  
Resistance Development ◽  
Peroxisome Proliferator Activated Receptor ◽  
Starting Point ◽  
Fundamental Research ◽  
Important Drug

Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. A comprehensive scaffold-based analysis uncovered an unexpected relationship between bromodomain-containing protein 4 (BRD4) and peroxisome-proliferator activated receptor gamma (PPARγ). They are both important drug targets for cancer therapy and many more important diseases. Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such a dual-BRD4-PPARγ-modulator could show synergistic effects with a higher efficacy or delayed resistance development in, for example, cancer therapy. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.

Study of Alnus incana L. Moench fruit extract biologically active substances influence on resistance development in mls-resistant staphylococci skin isolates

2018 ◽  
Vol 22 (2) ◽  
pp. 263-266
Author(s):  
R.V. Kutsyk ◽  
O.I. Yurchyshyn
Keyword(s):  
Selective Pressure ◽  
Biological Response ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Alnus Incana ◽  
Fruit Extract ◽  
Antimicrobial Drugs ◽  
Resistance Development ◽  
Subinhibitory Concentrations ◽  
Active Substances

The emergence of microorganisms resistant strains is a natural biological response to the use of antimicrobial drugs that creates selective pressure, contributing to pathogens selection, survival and reproduction. The purpose of the investigation was to study the resistance development of staphylococci skin isolates to erythromycin and influence on it Alnus incana L. fruit extract subinhibitory concentrations. Development of resistance to erythromycin and influence on it Alnus incana L. fruit extract (extraction by 90% ethanol) subinhibitory concentrations were conducted with S epidermidis strains: sensitive and resistant to 14 and 15-membered macrolides. The study was carried out within 30 days by multiple consecutive passages of staphylococci test strains (concentration 1×107 CFU/ml) into test tubes containing broth and erythromycin ranging from 3 doubling dilutions above to doubling dilutions below the minimum inhibitory concentration. Statistical analysis of the results was carried out by one-and two-factor analysis of variance (ANOVA) and Microsoft Office Excel 2011. Rapid increase of resistance from 32 to 1024 μg/ml (F=34.2804; F> Fstand. max = 5.9874; p=0.0011) for S.epidermidis with a low level of resistance to 14 and 15-membered macrolides resistance to the erythromycine was observed. In the presence of Alnus incana L. fruit extract subinhibitory concentrations (¼ MIC), the initial MIC of erythromycin was decreased by 32 times to 1 μg/ml (F = 9.7497; F> Fstand. max = 5.9874; p = 0.0205). The sensitive strain after 30 passages did not develop resistance to erythromycin. Under the influence of erythromycin selective pressure, S.epidermidis strain with low initial level of MLS-resistance rapidly reaches a high-level resistance. Biologically active substances of the Alnus incana L. fruit extract significantly inhibit the resistance development in S. epidermidis to macrolides and eliminate it phenotypic features.

Nanobiotics: Challenging the anti-microbial perspective - The game changer?

2017 ◽  
Vol 6 (10) ◽  
pp. 5518 ◽  
Author(s):  
Deepak Narang ◽  
Jeevan Singh Tityal ◽  
Amit Jain ◽  
Reena Kulshreshtra ◽  
Fatima Khan
Keyword(s):  
Bacterial Resistance ◽  
Public Health Problem ◽  
Drug Resistant ◽  
European Science Foundation ◽  
Resistance Development ◽  
Bacterial Diseases ◽  
European Science ◽  
Tremendous Impact ◽  
New Strategies ◽  
Game Changer

Antibiotics are the most important medical inventions in human history and are the invaluable weapons to fight against various infectious diseases. Multi drug resistant microorganisms are becoming a serious issue and increasingly public health problem in present day scenario. Antibiotics are becoming less useful due to increasing bacterial resistance. Development of new and more powerful antibiotics leading to drastic pathogens response by developing resistance to the point where the most powerful drugs in our arsenal are no longer effective against them. New strategies for the management of bacterial diseases are urgently needed and nanomaterials can be a very promising approach. Nanobiotics uses nano-sized tools for the successful management bacterial diseases and to gain increased understanding of the complex underlying patho-physiology of disease. (European Science Foundation. Forward Look Nanomedicine: An EMRC Consensus Opinion 2005. Available online: http://www.esf.org (accessed on 15 July 2017). The application of nanotechnologies to medicine, or nanomedicine, which has already demonstrated its tremendous impact on the pharmaceutical and biotechnology industries, is rapidly becoming a major driving force behind ongoing changes in the antimicrobial field. Present review providing important insights on nanobiotics, and their preparation, mechanism of action, as well as perspectives on the opportunities and challenges in nanobiotics.

scholarly journals 44. Antibiotic Class-Based Distribution and Analysis of Reported Beta-Lactam Allergies amongst Hospitalized Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S45-S45
Author(s):  
Joseph Patrik Hornak ◽  
David Reynoso
Keyword(s):  
Bacterial Infections ◽  
Drug Resistant ◽  
Beta Lactam ◽  
Resistance Development ◽  
Texas Medical ◽  
University Of Texas ◽  
Icd 10 ◽  
Mrsa Infection ◽  
The University ◽  
Alternative Antibiotic

Abstract Background Reported β-lactam allergy (BLA) is very common, yet less than 10% of these patients exhibit true hypersensitivity. When faced with reported BLAs, physicians often choose alternative antibiotics which can be associated with C. difficile infection, drug-resistance development, poorer outcomes, & increased costs. Effective identification of these patients is necessary for subsequent, appropriate BLA “de-labeling.” Here, we conducted a single-center analysis of alternative antibiotic utilization amongst patients reporting BLA and compare the frequency of drug-resistant infections and C. difficile infection in allergic & non-allergic patients. Methods This is a retrospective review of adult patients hospitalized at The University of Texas Medical Branch from 1/1/2015 to 12/31/2019. Pooled electronic medical records were filtered by antibiotic orders and reported allergies to penicillins or cephalosporins. Patients with drug-resistant and/or C. difficile infection (CDI) were identified by ICD-10 codes. Microsoft Excel & MedCalc were used for statistical calculations. Results Data were available for 118,326 patients and 9.3% (11,982) reported a BLA, with the highest rates seen in those receiving aztreonam (85.9%, 530/617) & clindamycin (33.7%, 3949/11718). Amongst patients reporting BLA, high ratios-of-consumption (relative to all patients receiving antibiotics) were seen with aztreonam (7.0), clindamycin (2.7), cephalosporin/β-lactamase inhibitors (2.4), & daptomycin (2.1). Compared to the non-BLA population, BLA patients more frequently experienced MRSA infection (3.0% vs 1.5%, OR 1.99, 95% CI 1.79–2.23, p< 0.0001), β-lactam resistance (1.2% vs 0.6%, OR 2.07, 95% CI 1.72–2.49, p< 0.0001), and CDI (1.2% vs 0.7%, OR 1.85, 95% CI 1.54–2.23, p< 0.0001). Conclusion Our measured BLA rate matches approximate expectations near 10%. Moreover, these patients experienced significantly higher frequencies of drug-resistant bacterial infections and CDI. Targeted inpatient penicillin allergy testing stands to be particularly effective in those patients receiving disproportionately utilized alternative agents (e.g. aztreonam, clindamycin, daptomycin). β-lactam allergy “de-labeling” in these patients is likely a valuable antimicrobial stewardship target. Disclosures All Authors: No reported disclosures

scholarly journals Structural and Thermodynamic Analysis of the Resistance Development to Pimodivir (VX-787), the Clinical Inhibitor of Cap Binding to PB2 Subunit of Influenza A Polymerase

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1007
Author(s):  
Jiří Gregor ◽  
Kateřina Radilová ◽  
Jiří Brynda ◽  
Jindřich Fanfrlík ◽  
Jan Konvalinka ◽  
...  
Keyword(s):  
Thermodynamic Analysis ◽  
Influenza A ◽  
Polymerase Activity ◽  
Second Phase ◽  
Missense Mutations ◽  
Wild Type ◽  
Resistance Development ◽  
Third Phase ◽  
Major Mutation ◽  
Control And Prevention

Influenza A virus (IAV) encodes a polymerase composed of three subunits: PA, with endonuclease activity, PB1 with polymerase activity and PB2 with host RNA five-prime cap binding site. Their cooperation and stepwise activation include a process called cap-snatching, which is a crucial step in the IAV life cycle. Reproduction of IAV can be blocked by disrupting the interaction between the PB2 domain and the five-prime cap. An inhibitor of this interaction called pimodivir (VX-787) recently entered the third phase of clinical trial; however, several mutations in PB2 that cause resistance to pimodivir were observed. First major mutation, F404Y, causing resistance was identified during preclinical testing, next the mutation M431I was identified in patients during the second phase of clinical trials. The mutation H357N was identified during testing of IAV strains at Centers for Disease Control and Prevention. We set out to provide a structural and thermodynamic analysis of the interactions between cap-binding domain of PB2 wild-type and PB2 variants bearing these mutations and pimodivir. Here we present four crystal structures of PB2-WT, PB2-F404Y, PB2-M431I and PB2-H357N in complex with pimodivir. We have thermodynamically analysed all PB2 variants and proposed the effect of these mutations on thermodynamic parameters of these interactions and pimodivir resistance development. These data will contribute to understanding the effect of these missense mutations to the resistance development and help to design next generation inhibitors.

scholarly journals Phenotypic and Genotypic Properties of Fluoroquinolone-Resistant, qnr-Carrying Escherichia coli Isolated from the German Food Chain in 2017

2021 ◽  
Vol 9 (6) ◽  
pp. 1308
Author(s):  
Katharina Juraschek ◽  
Carlus Deneke ◽  
Silvia Schmoger ◽  
Mirjam Grobbel ◽  
Burkhard Malorny ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Point Mutations ◽  
Beta Lactamase ◽  
Resistance Development ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
German Food ◽  
Sequence Types ◽  
Ammonium Compounds ◽  
Additional Point

Fluoroquinolones are the highest priority, critically important antimicrobial agents. Resistance development can occur via different mechanisms, with plasmid-mediated quinolone resistance (PMQR) being prevalent in the livestock and food area. Especially, qnr genes, commonly located on mobile genetic elements, are major drivers for the spread of resistance determinants against fluoroquinolones. We investigated the prevalence and characteristics of qnr-positive Escherichia (E.) coli obtained from different monitoring programs in Germany in 2017. Furthermore, we aimed to evaluate commonalities of qnr-carrying plasmids in E. coli. We found qnr to be broadly spread over different livestock and food matrices, and to be present in various sequence types. The qnr-positive isolates were predominantly detected within selectively isolated ESBL (extended spectrum beta-lactamase)-producing E. coli, leading to a frequent association with other resistance genes, especially cephalosporin determinants. Furthermore, we found that qnr correlates with the presence of genes involved in resistance development against quaternary ammonium compounds (qac). The detection of additional point mutations in many isolates within the chromosomal QRDR region led to even higher MIC values against fluoroquinolones for the investigated E. coli. All of these attributes should be carefully taken into account in the risk assessment of qnr-carrying E. coli from livestock and food.

scholarly journals Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 877
Author(s):  
Ana Mafalda Pinto ◽  
Alberta Faustino ◽  
Lorenzo M. Pastrana ◽  
Manuel Bañobre-López ◽  
Sanna Sillankorva
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Chronic Infections ◽  
Swarming Motility ◽  
Resistance Development ◽  
Healthcare Settings ◽  
Time Kill

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application.

scholarly journals Risk factors for antibiotic resistance development in healthcare settings in China: A systematic review

2021 ◽  
pp. 1-30
Author(s):  
Qi Chen ◽  
Duguang Li ◽  
Claudia Beiersmann ◽  
Florian Neuhann ◽  
Babak Moazen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Antibiotic Resistance ◽  
Resistance Development ◽  
Healthcare Settings
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