scholarly journals Brazilian Copaifera Species: Antifungal Activity against Clinically Relevant Candida Species, Cellular Target, and In Vivo Toxicity

2020 ◽  
Vol 6 (3) ◽  
pp. 153
Author(s):  
Géssica Andrade ◽  
Haniel Orlando ◽  
Liliana Scorzoni ◽  
Reginaldo Pedroso ◽  
Fariza Abrão ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Membrane Damage ◽  
Antimicrobial Properties ◽  
Leaf Extracts ◽  
Cell Membrane Damage ◽  
C Elegans ◽  
Cellular Target

Plants belonging to the genus Copaifera are widely used in Brazil due to their antimicrobial properties, among others. The re-emergence of classic fungal diseases as a consequence of antifungal resistance to available drugs has stimulated the search for plant-based compounds with antifungal activity, especially against Candida. The Candida-infected Caenorhabditis elegans model was used to evaluate the in vitro antifungal potential of Copaifera leaf extracts and trunk oleoresins against Candida species. The Copaifera leaf extracts exhibited good antifungal activity against all Candida species, with MIC values ranging from 5.86 to 93.75 µg/mL. Both the Copaifera paupera and Copaifera reticulata leaf extracts at 46.87 µg/mL inhibited Candida glabrata biofilm formation and showed no toxicity to C. elegans. The survival of C. glabrata-infected nematodes increased at all the tested extract concentrations. Exposure to Copaifera leaf extracts markedly increased C. glabrata cell vacuolization and cell membrane damage. Therefore, Copaifera leaf extracts are potential candidates for the development of new and safe antifungal agents.

A reinvestigation of the function of the mammalian urinary bladder

1977 ◽  
Vol 232 (3) ◽  
pp. F187-F195 ◽  
Author(s):  
S. A. Lewis
Keyword(s):  
Urinary Bladder ◽  
Membrane Surface ◽  
Apical Cell ◽  
Membrane Damage ◽  
In Vitro Experiments ◽  
Apical Cell Membrane ◽  
Cell Membrane Damage ◽  
Using Data

The function of adult mammalian urinary bladder is evaluated in light of recent in vitro experiments. The discrepancy between in vivo and in vitro experimental results is examined and a possible solution proposed. Techniques for eliminating edge damage and measuring apical membrane surface area are described. A new chamber design for microelectrode studies is illustrated. The possibility of apical cell membrane damage caused by microelectrodes is critically examined and tested using the polyene antibiotic Nystatin. Using data from transepithelial and microelectrode experiments, a model for net Na+ transport across the bladder is proposed and then critically analyzed. The possible clinical implications of the in vitro experiments are briefly discussed.

scholarly journals Quercetin Rejuvenates Sensitization of Colistin-Resistant Escherichia coli and Klebsiella Pneumoniae Clinical Isolates to Colistin

2021 ◽  
Vol 9 ◽  
Author(s):  
Yishuai Lin ◽  
Ying Zhang ◽  
Shixing Liu ◽  
Dandan Ye ◽  
Liqiong Chen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Alternative Pathway ◽  
Membrane Damage ◽  
New Drugs ◽  
Colistin Resistance ◽  
Cell Membrane Damage ◽  
E Coli

Colistin is being considered as “the last ditch” treatment in many infections caused by Gram-negative stains. However, colistin is becoming increasingly invalid in treating patients who are infected with colistin-resistant Escherichia coli (E. coli) and Klebsiella Pneumoniae (K. pneumoniae). To cope with the continuous emergence of colistin resistance, the development of new drugs and therapies is highly imminent. Herein, in this work, we surprisingly found that the combination of quercetin with colistin could efficiently and synergistically eradicate the colistin-resistant E. coli and K. pneumoniae, as confirmed by the synergy checkboard and time-kill assay. Mechanismly, the treatment of quercetin combined with colistin could significantly downregulate the expression of mcr-1 and mgrB that are responsible for colistin-resistance, synergistically enhancing the bacterial cell membrane damage efficacy of colistin. The colistin/quercetin combination was notably efficient in eradicating the colistin-resistant E. coli and K. pneumoniae both in vitro and in vivo. Therefore, our results may provide an efficient alternative pathway against colistin-resistant E. coli and K. pneumoniae infections.

scholarly journals Intracellular Delivery of Nanoparticles via Microelectrophoresis Technique: Feasibility demonstration

2020 ◽  
Author(s):  
Mengke Han ◽  
Jiangbo Zhao ◽  
Joseph Mahandas Fabian ◽  
Sanam Mustafa ◽  
Yinlan Ruan ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Membrane Damage ◽  
Hydrodynamic Diameter ◽  
Target Cells ◽  
General Strategy ◽  
Human Embryonic Kidney Cells ◽  
Cell Membrane Damage ◽  
Biological Studies

ABSTRACTNanoparticles with desirable properties and functions have been actively developed for various bio-medical research, such as in vivo and in vitro sensors, imaging agents and delivery vehicles of therapeutics. However, an effective method to deliver nanoparticles into the intracellular environment is a major challenge and critical to many biological studies. Current techniques, such as intracellular uptake, electroporation and microinjection, each have their own set of benefits and associated limitations (e.g., aggregation and endosomal degradation of nanoparticles, high cell mortality and low throughput). Here, the well-established microelectrophoresis technique is applied for the first time to deliver nanoparticles into target cells, which overcomes some of these delivery difficulties. Semiconductive quantum dots, with average hydrodynamic diameter of 24.4 nm, have been successfully ejected via small electrical currents (−0.2 nA) through fine-tipped glass micropipettes as an example, into living human embryonic kidney cells (roughly 20 - 30μm in length). As proposed by previous studies, micropipettes were fabricated to have an average tip inner diameter of 206 nm for ejection but less than 500 nm to minimize the cell membrane damage and cell distortion. In addition, delivered quantum dots were found to stay monodispersed within the cells for approximately one hour. We believe that microelectrophoresis technique may serve as a simple and general strategy for delivering a variety of nanoparticles intracellularly in various biological systems.

scholarly journals Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 903
Author(s):  
Miklós Nagy ◽  
Gábor Szemán-Nagy ◽  
Alexandra Kiss ◽  
Zsolt László Nagy ◽  
László Tálas ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Clinical Strain ◽  
Control Group ◽  
Multiple Drug ◽  
Species Structure ◽  
In Vivo Experiments

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.

Abstract 130: Ox-LDL Impairs The Survival Of Bone Marrow Stem Cells Partially Through Membrane Damage Independent Of ROS Production In Vitro

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xin Li ◽  
Yuan Xiao ◽  
Yuqi Cui ◽  
Hua Zhu ◽  
Chandrakala A Narasimhulu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Death ◽  
Membrane Damage ◽  
Final Concentration ◽  
Bone Marrow Stem Cells ◽  
Cell Membrane Damage ◽  
Cell Based Therapy

Aims: cell-based therapy with bone marrow stem cells (MSCs) remains a viable option for tissue repair and regeneration. One of the major challenges for cell-based therapy is the limited survival of the cells after in vivo administration. The exact mechanism(s) for impaired in vivo survival of the implanted MSCs remains to be defined. Oxidized low-density lipid protein (ox-LDL) is a natural product in human blood, and the major contributor to the development of atherosclerosis. The present study was to investigate the effect of ox-LDL on the survival of bone marrow stem cells and the mechanisms in vitro. Methods and Results: Rat bone marrow multipotent adult progenitor cells (MAPCs) were treated with ox-LDL (with the final concentration of 10 and 20 ug/ml) for up to 48 hours. Exposure to ox-LDL resulted in significant cell death and apoptosis of MAPCs in association with a significant increase in LDH release in the conditioned media in a dose- and time-dependent manner, indicating significant cell membrane damage. The membrane damage was further confirmed with the rapid entry of the small fluorescent dye FM1-43 as detected using confocal microscope. Ox-LDL generated a significant amount of reactive oxygen species (ROS) in the culture system as measured with electron paramagnetic resonance spectroscopy. The antioxidant N-acetylcysteine (NAC, 0.1 mM) completely inhibited the production of ROS from ox-LDL. However, it didn’t prevent ox-LDL-induced cell death or apoptosis. However, pre-treatment of the cells with the specific membrane protective recombinant human MG53 protein (rhMG53)(66 ug/ml, final concentration) significantly, reduced LDH release and the entry of FM1-43 dye into the cells exposed to ox-LDL. Conclusion: Ox-LDL enhanced cell death and apoptosis of MAPCs with a mechanism independent of ROS generation in vitro. Ox-LDL impaired the survival of MAPCs partially through cell membrane damage in vitro.

Abstract 8: GTPase-Activating Protein for Rho Associated with FAK (GRAF) Regulates Cardiomyocyte Membrane Integrity

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Thomas J O'Neill ◽  
Kaitlin Lenhart ◽  
Jason Doherty ◽  
Mauricio Rojas ◽  
Mack P Christopher ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Muscle Pathology ◽  
Blue Dye ◽  
Membrane Repair ◽  
Cell Membrane Damage ◽  
Deficient Mice

Cardiac myocytes are unique in their requirement to sustain continuous repetitive contraction in the setting of intense mechanical stress while simultaneously maintaining high membrane integrity for an appropriate electrical gradient. The consequence of failure of the membrane repair response has been highlighted in recent reports linking cardiomyocyte membrane fragility with cardiac degeneration in patients as well as in their analogous mouse models. Herein, we describe a novel role for GTPase activator for Rho associated with Focal Adhesion Kinase (GRAF) in regulating cardiomyocyte membrane integrity. We previously published that disruption of GRAF in Xenopus laevis resulted in progressive skeletal muscle degeneration. We now show that GRAF-depleted tadpoles exhibit defective cardiac formation and function. Interestingly, damage of muscle cells in vivo and in vitro led to a translocation of GRAF to the sarcolemma, suggesting that GRAF may be an important component of the cardiac membrane repair machinery. To further explore this possibility, we generated GRAF hypomorphic mice that exhibit greater than 99% reduction of endogenous GRAF expression. While GRAF deficient mice show normal Mendelian birth distribution and are viable, they exhibit a modest skeletal muscle pathology. Although baseline cardiac integrity was not compromised in GRAF deficient mice, treatment either with cardiotoxin or intraperitoneal injection of isoproterenol led to elevated cardiomyocyte membrane damage (assessed by Evan’s blue dye uptake) in GRAF deficient compared to control mice (19% vs 2% of myocytes within afflicted ventricular area for cardiotoxin, 18% vs 8% for isoproterenol respectively). Moreover, cultured GRAF null myocytes exhibited a significantly attenuated membrane resealing response following laser-mediated disruption compared to GRAF-containing control cells as assessed by accumulation of the membrane impermeable dye, FM-143. As well, the survival rate after injury of GRAF-deficient cells was markedly attenuated (20% vs 85% in control cells). While cardiac cell membrane damage is likely a frequent and important event, the repair process is currently understudied, and this is the first report to implicate a Rho regulator in this response.

scholarly journals Addition of Ceftaroline to Daptomycin after Emergence of Daptomycin-Nonsusceptible Staphylococcus aureus during Therapy Improves Antibacterial Activity

2012 ◽  
Vol 56 (10) ◽  
pp. 5296-5302 ◽  
Author(s):  
Warren E. Rose ◽  
Lucas T. Schulz ◽  
David Andes ◽  
Rob Striker ◽  
Andrew D. Berti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Membrane Damage ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Content Type ◽  
Cell Membrane Damage

ABSTRACTAntistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory methicillin-resistantStaphylococcus aureus(MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves the daptomycin potency comparably to other beta-lactams. We report a complex patient case of endocarditis who was treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. Anin vitropharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment. Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivityin vivoand resulted in clearance of persistent blood cultures. Daptomycin susceptibilityin vitrowas increased in the presence of either ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC, 2 to 4 μg/ml) with continued monotherapy. The addition of ceftaroline at 200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Bothin vivo- andin vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity was restored to the level of the initialin vivoisolate. Daptomycin-resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline combined with daptomycin was effective in eliminating daptomycin-resistant MRSA, and these results further justify the potential use of daptomycin plus beta-lactam therapy for these refractory infections.

Antifungal activity of plant extracts against Colletotrichum musae, the post harvest anthracnose pathogen of banana cv. Martaman

2016 ◽  
Vol 46 (1) ◽  
pp. 2-15 ◽  
Author(s):  
Dawa Dolma Bhutia ◽  
Yeka Zhimo ◽  
Ramen Kole ◽  
Jayanta Saha
Keyword(s):  
Antifungal Activity ◽  
Plant Species ◽  
Plant Extract ◽  
Mycelial Growth ◽  
Disease Incidence ◽  
Leaf Extracts ◽  
Content Type ◽  
Colletotrichum Musae

Purpose – The purpose of this paper was to determine the antifungal activities of different solvent extracts of common plants in vitro and in vivo against banana anthracnose fungus Colletotrichum musae (Berk & M.A. Curtis) Arx, and to investigate its effects on the pathogen and identify the bio active component(s). Design/methodology/approach – Extracts were obtained from leaves, tender shoots, rhizomes, bulbs, seeds and fruits of 42 naturally growing plant species following hot sequential extraction. Preliminary screening of the solvent extracts was done based on the inhibition of radial mycelial growth of C. musae following poison food technique and conidial germination inhibition by cavity slide technique. The selected extracts were assessed for their effect on harvested banana in reducing anthracnose during storage. The active components in the bio-active fractions of plant extract were identified by gas chromatography-mass spectroscopy. Findings – Methanol extracted a larger quantity of material (between 6.9 and 12.5 per cent) than hexane or chloroform, and all its extracts were active against the test pathogen with mycelial growth inhibition ranging from 13.70 to 88.89 per cent. Zingiber officinale rhizome extract as well as Polyalthia longifolia and Clerodendrum inerme leaf extracts exhibited more than 80 per cent inhibition of mycelial growth. Total inhibition of spore germination of C. musae was recorded in Z. officinale and P. longifolia extracts at 0.3 per cent w/v and 0.5 per cent w/v concentration, respectively, while only 68 per cent spore inhibition was recorded in C. inerme at 0.5 per cent w/v concentration. Of the three plant species, Z. officinale had the best antifungal activity (18.0 per cent disease incidence; 2.2 disease severity scale) when banana fruits were dipped in the extract at a concentration of 0.5 per cent w/v at 5 days of storage in ambient condition (80-82 per cent R.H., 27 ± 1°C). The bio-active compounds in the extract of Z. officinale were identified as alpha-curcumene and zingerone. Originality/value – Based on the antifungal activity, plant extract of Z. officinale can be used as an effective alternative to chemicals in controlling anthracnose pathogen in harvested banana.

scholarly journals Curtisia dentata (Cornaceae) leaf extracts and isolated compounds inhibit motility of parasitic and free-living nematodes

2009 ◽  
Vol 76 (2) ◽  
Author(s):  
L.J. Shai ◽  
E.S. Bizimenyera ◽  
V. Bagla ◽  
L.J. McGaw ◽  
J.N. Eloff
Keyword(s):  
Medicinal Plant ◽  
Betulinic Acid ◽  
Small Ruminants ◽  
Anthelmintic Activity ◽  
Parasitic Nematodes ◽  
Leaf Extracts ◽  
Free Living ◽  
C Elegans

Haemonchus contortus and Trichostrongylus colubriformis are among the most important parasitic nematodes of small ruminants. Caenorhabditis elegans, a free-living nematode, is used as a model for evaluating anthelmintic activity of a variety of test substances. Extracts of several medicinal plants are useful in vitro and in vivo against nematode development. Extracts of Curtisia dentata, a South African medicinal plant, and compounds isolated from leaves of this plant were investigated for anthelmintic activity against T. colubriformis, H. contortus and C. elegans. The acetone and dichloromethane extracts were active against all nematodes at concentrations as low as 160 μg/mℓ. Betulinic acid and lupeol were active against the parasitic nematodes only at the high concentrations of 1 000 and 200 μg/mℓ, respectively. All compounds were effective against C. elegans with active concentrations as low as 8 μg/mℓ. Betulinic acid was less active than lupeol and ursolic acid against C. elegans. The acetone and dichloromethane extracts were also active against C. elegans with a concentration of 0.31 mg/mℓ resulting in almost 80 % inhibition of larval motility. The use of free-living nematodes may provide information on the activity of potential anthelmintics against parasitic nematodes. Extracts of various medicinal plant species may provide solutions to ill-health of small ruminants caused by parasitic nematodes in poor communities of southern Africa.

scholarly journals Nanohole-boosted electron transport between nanomaterials and bacteria as a concept for nano–bio interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tonglei Shi ◽  
Xuan Hou ◽  
Shuqing Guo ◽  
Lei Zhang ◽  
Changhong Wei ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Electron Transport ◽  
Bacterial Infection ◽  
Membrane Damage ◽  
Extracellular Dna ◽  
High Electron ◽  
Cell Membrane Damage ◽  
Antibiotic Drug

AbstractBiofilms contribute to bacterial infection and drug resistance and are a serious threat to global human health. Antibacterial nanomaterials have attracted considerable attention, but the inhibition of biofilms remains a major challenge. Herein, we propose a nanohole-boosted electron transport (NBET) antibiofilm concept. Unlike known antibacterial mechanisms (e.g., reactive oxygen species production and cell membrane damage), nanoholes with atomic vacancies and biofilms serve as electronic donors and receptors, respectively, and thus boost the high electron transport capacity between nanomaterials and biofilms. Electron transport effectively destroys the critical components (proteins, intercellularly adhered polysaccharides and extracellular DNA) of biofilms, and the nanoholes also significantly downregulate the expression of genes related to biofilm formation. The anti-infection capacity is thoroughly verified both in vitro (human cells) and in vivo (rat ocular and mouse intestinal infection models), and the nanohole-enabled nanomaterials are found to be highly biocompatible. Importantly, compared with typical antibiotics, nanomaterials are nonresistant and thereby exhibit high potential for use in various applications. As a proof-of-principle demonstration, these findings hold promise for the use of NBET in treatments for pathogenic bacterial infection and antibiotic drug resistance.

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