scholarly journals Photo-Disassembly of Membrane Microdomains Revives Conventional Antibiotics against MRSA

2019 ◽  
Author(s):  
Jie Hui ◽  
Pu-Ting Dong ◽  
Lijia Liang ◽  
Taraknath Mandal ◽  
Junjie Li ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Rapid Evolution ◽  
Treatment Strategies ◽  
Pulsed Laser ◽  
Membrane Microdomains ◽  
Carotenoid Pigment ◽  
Drug Resistant ◽  
Development Of Resistance ◽  
Functional Membrane ◽  
Conventional Antibiotics

AbstractConfronted with the rapid evolution and dissemination of antibiotic resistance, there is an urgent need to develop alternative treatment strategies for drug-resistant pathogens. Here, we present an unconventional approach to restore the susceptibility of methicillin-resistant S. aureus (MRSA) to a broad spectrum of conventional antibiotics via photo-disassembly of functional membrane microdomains. The photo-disassembly of microdomains is based on effective photolysis of staphyloxanthin, the golden carotenoid pigment that gives its name. Upon pulsed laser treatment, cell membranes are found severely disorganized and malfunctioned to defense antibiotics, as unveiled by membrane permeabilization, membrane fluidification, and detachment of membrane protein, PBP2a. Consequently, our photolysis approach increases susceptibility and inhibits development of resistance to a broad spectrum of antibiotics including penicillins, quinolones, tetracyclines, aminoglycosides, lipopeptides, and oxazolidinones.One Sentence SummaryUsing photons to crash S. aureus cell membrane and its formidable defense against a broad spectrum of antibiotics.

Disarming the enemy: targeting bacterial toxins with small molecules

2017 ◽  
Vol 1 (1) ◽  
pp. 31-39
Author(s):  
Alejandro Huerta-Uribe ◽  
Andrew J. Roe
Keyword(s):  
Small Molecules ◽  
Pathogenic Bacteria ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Bacterial Toxin ◽  
Bacterial Strains ◽  
Development Of Resistance ◽  
Enterohaemorrhagic Escherichia Coli ◽  
Life Threatening ◽  
Conventional Antibiotics

The rapid emergence of antibiotic-resistant bacterial strains has prompted efforts to find new and more efficacious treatment strategies. Targeting virulence factors produced by pathogenic bacteria has gained particular attention in the last few years. One of the inherent advantages of this approach is that it provides less selective pressure for the development of resistance mechanisms. In addition, antivirulence drugs could potentially be the answer for diseases in which the use of conventional antibiotics is counterproductive. That is the case for bacterial toxin-mediated diseases, in which the severity of the symptoms is a consequence of the exotoxins produced by the pathogen. Examples of these are haemolytic-uraemic syndrome produced by Shiga toxins, the profuse and dangerous dehydration caused by Cholera toxin or the life-threatening colitis occasioned by clostridial toxins. This review focuses on the recent advances on the development of small molecules with antitoxin activity against Enterohaemorrhagic Escherichia coli, Vibrio cholerae and Clostridium difficile given their epidemiological importance. The present work includes studies of small molecules with antitoxin properties that act directly on the toxin (direct inhibitors) or that act by preventing expression of the toxin (indirect inhibitors).

Novel Compound from Flowers of Moringa oleifera Active Against Multi- Drug Resistant Gram-negative Bacilli

2020 ◽  
Vol 20 (1) ◽  
pp. 69-75
Author(s):  
Santi M. Mandal ◽  
Subhanil Chakraborty ◽  
Santanu Sahoo ◽  
Smritikona Pyne ◽  
Samaresh Ghosh ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Moringa Oleifera ◽  
Aqueous Acetic Acid ◽  
Phytochemical Analysis ◽  
Hydroxyl Groups ◽  
Drug Resistant ◽  
Gram Negative ◽  
Isolated Compound ◽  
Conventional Antibiotics

Background: The need for suitable antibacterial agents effective against Multi-drug resistant Gram-negative bacteria is acknowledged globally. The present study was designed to evaluate the possible antibacterial potential of an extracted compound from edible flowers of Moringa oleifera. Methods: Five different solvents were used for preparing dried flower extracts. The most effective extract was subjected to fractionation and further isolation of the active compound with the highest antibacterial effect was obtained using TLC, Column Chromatography and reverse phase- HPLC. Approaches were made for characterization of the isolated compound using FTIR, NMR and Mass spectrometry. Antibacterial activity was evaluated according to the CLSI guidelines. Results: One fraction of aqueous acetic acid extract of M. oleifera flower was found highly effective and more potent than conventional antibiotics of different classes against Multi-drug resistant Gram-negative bacilli (MDR-GNB) when compared. The phytochemical analysis of the isolated compound revealed the presence of hydrogen-bonded amine and hydroxyl groups attributable to unsaturated amides. Conclusion: The present study provided data indicating a potential for use of the flowers extract of M. oleifera in the fight against infections caused by lethal MDR-GNB. Recommendations: Aqueous acetic acid flower extract of M. oleifera is effective, in-vitro, against Gram-negative bacilli. This finding may open a scope in pharmaceutics for the development of new classes of antibiotics.

scholarly journals Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 400 ◽  
Author(s):  
Seiichiro Mitani ◽  
Hisato Kawakami
Keyword(s):  
Gastroesophageal Junction ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Drug Conjugates ◽  
Gastroesophageal Junction Cancer ◽  
Development Of Resistance ◽  
Epidermal Growth ◽  
Antibody Drug

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies.

scholarly journals AB1267 ONLINE CASE-BASED EDUCATION SIGNIFICANTLY IMPROVED RHEUMATOLOGISTS’ KNOWLEDGE AND CONFIDENCE IN MANAGING PATIENTS WITH RA

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1925.2-1925
Author(s):  
E. Bell ◽  
A. Sendaydiego ◽  
P. C. Taylor
Keyword(s):  
Rapid Evolution ◽  
Safety Data ◽  
Treatment Strategies ◽  
Further Education ◽  
Learning Activity ◽  
Tnf Inhibitor ◽  
Jak Inhibitors ◽  
Significance Level ◽  
Average Percentage ◽  
Post Assessment

Background:With the rapid evolution in treatment strategies and the increasing range of available therapeutics for rheumatoid arthritis (RA), keeping pace with advances can be a challenge for busy physicians.Objectives:We assessed whether online CME can improve rheumatologists’ knowledge of RA management focusing on the assessment and monitoring of RA, the selection of appropriate treatments and the clinical efficacy and safety data for JAK inhibitors.Methods:Rheumatologists participated in a text-based activity featuring two patient cases with questions that “tested” knowledge and discussion of the main “teaching” points. Educational effect was assessed using a repeated-pair design, pre-/post-assessment. A Chi-square test of independence determined if a statistically significant improvement (5% significance level,P<.05) existed in the number of correct responses between the pretest and posttest scores. Cramer’s V estimated the effect size of the education. The activity launched on 15 December 2018 with data collection through 27 February 2019.Results:•Significant improvement in average percentage of correct responses, rising from 47% at baseline to 92% post-activity (P<.001) and extensive educational impact (Cramer’s V=0.496)•Significant increase in percentage of rheumatologists (n=111) answering all 3 questions correctly (9% at baseline rising to 78% post assessment)•Significant improvements in knowledge of EULAR/ACR assessment criteria (86% improvement,P<.001), EULAR treatment recommendations for a patient failing on MTX and a TNF inhibitor (100% improvement,P<.001), and the VTE risk associated with having RA or receiving RA treatments (108% improvement,P<.001)•46% of rheumatologists reported greater confidence in their ability to appropriately incorporate JAK inhibitors into the treatment of patients with RA (average confidence shift 20%)Conclusion:Overall, this learning activity was highly successful in improving rheumatologists’knowledge and confidence in managing patients with RA, particularly with regard to the appropriate use of JAK inhibitors in patients for whom such treatment is suitable. The extensive impact of this interactive ‘test then teach’ activity is likely to directly translate into patient benefit. Further education on this topic would be useful to enhance and reinforce this knowledge and to support physician confidence in the use of JAK inhibitors in clinical practice.References:[1]https://www.medscape.org/viewarticle/906202Disclosure of Interests:Elaine Bell: None declared, Anne Sendaydiego: None declared, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB

scholarly journals Single cell-derived clonal analysis of human glioblastoma links functional and genomic heterogeneity

2015 ◽  
Vol 112 (3) ◽  
pp. 851-856 ◽  
Author(s):  
Mona Meyer ◽  
Jüri Reimand ◽  
Xiaoyang Lan ◽  
Renee Head ◽  
Xueming Zhu ◽  
...  
Keyword(s):  
Functional Significance ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Clonal Analysis ◽  
Specific Drug ◽  
Drug Resistant ◽  
Naive Patient ◽  
Functional Behavior ◽  
Proliferation And Differentiation ◽  
Genomic Analyses

Glioblastoma (GBM) is a cancer comprised of morphologically, genetically, and phenotypically diverse cells. However, an understanding of the functional significance of intratumoral heterogeneity is lacking. We devised a method to isolate and functionally profile tumorigenic clones from patient glioblastoma samples. Individual clones demonstrated unique proliferation and differentiation abilities. Importantly, naïve patient tumors included clones that were temozolomide resistant, indicating that resistance to conventional GBM therapy can preexist in untreated tumors at a clonal level. Further, candidate therapies for resistant clones were detected with clone-specific drug screening. Genomic analyses revealed genes and pathways that associate with specific functional behavior of single clones. Our results suggest that functional clonal profiling used to identify tumorigenic and drug-resistant tumor clones will lead to the discovery of new GBM clone-specific treatment strategies.

A quest to the therapeutic arsenal: Novel strategies to combat multidrug-resistant bacteria

2021 ◽  
Vol 21 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal
Keyword(s):  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antimicrobial Drugs ◽  
Short Palindromic Repeat ◽  
Prevention Of Infections ◽  
Resistant Bacterial Strain ◽  
Conventional Antibiotics ◽  
Drug Resistant Strains

: The increasing resistance of the disease-causing pathogens to antimicrobial drugs is a public health concern and a socio-economic burden. The emergence of multi-drug resistant strains has made it harder to treat and combat infectious diseases with available conventional antibiotics. There are currently few effective therapeutic regimens for the successful prevention of infections caused by drug-resistant microbes. The various alternative strategies used in the recent past to decrease and limit antibiotic resistance in pathogens include bacteriophages, vaccines, anti-biofilm peptides, and antimicrobial peptides. However, in this review, we focus on the novel and robust molecular approach of antisense RNA (asRNA) technology and the clustered regulatory interspaced short palindromic repeat (CRISPR)-based antibiotic therapy, which can be exploited to selectively eradicate the drug-resistant bacterial strain in a sequence-specific fashion establishing opportunities in the treatment of multi-drug resistant related infections.

Fruits for Seizures? A Systematic Review on the Potential Anti- Convulsant Effects of Fruits and its Phytochemicals

2021 ◽  
Vol 19 ◽  
Author(s):  
Lee Hsien Siang ◽  
Alina Arulsamy ◽  
Yeong Keng Yoon ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Critical Appraisal ◽  
Treatment Strategies ◽  
Alternative Methods ◽  
Drug Resistant ◽  
Future Studies ◽  
Seizure Models ◽  
Epileptic Patients ◽  
Anti Oxidant ◽  
Excitatory Neurotransmission ◽  
Harmful Effects

: Epilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant and anti-inflammatory activities. However, some fruits may also elicit harmful effects. This review aims to summarize and elucidate the anti- or pro- convulsant effects of fruits used in relation to seizures, in hopes to provide a good therapeutic reference to epileptic patients and their carers. Three databases; SCOPUS, ScienceDirect and PubMed were utilized for the literature search. Based on the PRISMA guidelines, a total of 40 articles were selected for critical appraisal in this review. Overall, the extracts and phytochemicals of fruits managed to effectively reduce seizure activities in various preclinical seizure models, acting mainly through the activation of the inhibitory neurotransmission and blocking the excitatory neurotransmission. Only star fruit has been identified as a pro-convulsant fruit, which was attributed to the its caramboxin and oxalate compounds. Future studies should focus more on utilizing these fruits as possible treatment strategies for epilepsy.

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