combinatory effect
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Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a bicyclic naphthoquinone naturally distributed among Plumbago species, has been reported to have antimicrobial activity against a wide range of microorganisms. In this study, plumbagin was examined for its combinatory antimicrobial effect with tetracycline or oxacillin against nine strains of Staphylococcus aureus, including its methicillin- and multidrug-resistant strains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated according to the sum of fractional inhibitory concentration (ΣFIC) indices. Additive interactions were obtained for both combinations against most of the strains tested. Synergy was obtained for combination with oxacillin against two out of seven strains (ΣFIC range 0.273-0.281), both were methicillin resistant. Our results proved plumbagin as a compound suitable for anti-Staphylococcal combinatory testing. Moreover, to the best of our knowledge, this is the first report of plumbagin synergy with oxacillin against S. aureus strains, including its resistant forms.
- MeSH
- antibakteriální látky farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- mnohočetná bakteriální léková rezistence MeSH
- naftochinony farmakologie MeSH
- oxacilin farmakologie MeSH
- Staphylococcus aureus klasifikace účinky léků MeSH
- synergismus léků MeSH
- tetracyklin farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chitotriosidase (Chit1) and acidic mammalian chitinase (AMCase) have been implicated in food processing and various pathophysiological conditions such as chronic inflammatory diseases. By combination of the colorimetric analysis and fluorophore-assisted carbohydrate electrophoresis (FACE) method, we directly compared the chitinolytic properties of mouse Chit1 and AMCase and determined their combinatory effects in artificial and natural chitin substrates processing. Chit1 and AMCase display different dynamics of chitinolytic properties through acidic to neutral conditions. At pH2.0, the activity of AMCase was higher than that of Chit1 and stronger or comparable with that of Serratia marcescens chitinase B, a well-characterized bacterium chitinase. Changes of degradation products using different substrates indicate that AMCase and Chit1 have diverse properties under various pH conditions. Exposure of the chitin substrates to both Chit1 and AMCase did not indicate any mutual interference of these enzymes and showed no synergistic effect, in contrast to observations regarding some bacterial chitinases. Our results suggest that Chit1 and AMCase have no synergistic effect under physiological conditions.
- MeSH
- bakteriální proteiny chemie genetika MeSH
- chitin chemie MeSH
- chitinasy chemie genetika MeSH
- hexosaminidasy chemie MeSH
- hydrolýza MeSH
- kolorimetrie MeSH
- koncentrace vodíkových iontů MeSH
- molekulová hmotnost MeSH
- myši MeSH
- rekombinantní proteiny MeSH
- substrátová specifita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: The objective of the study was to evaluate the antimicrobial interactions between two volatile agents, Cinnamomum cassia essential oil (CCEO) and 8-hydroxyquinoline (8-HQ) against Staphylococcus aureus strains in liquid and vapour phases. METHODS AND RESULTS: In vitro antimicrobial effect of CCEO in combination with 8-HQ was evaluated against 12 strains of S. aureus by broth volatilization chequerboard method. Results show additive effects against all S. aureus strains for both phases. In several cases, sums of fractional inhibitory concentration values of our test combinations were lower than 0·6, which can be considered as a strong additive interaction. Moreover, composition of CCEO was analysed by gas chromatography-mass spectrometry analysis. In the CCEO, 26 compounds in total were identified, where (E)-cinnamaldehyde was the predominant compound, followed by cinnamyl acetate, α-copaene, bornyl acetate and caryophyllene. CONCLUSIONS: Results showed additive in vitro growth-inhibitory effect of CCEO and 8-HQ combination against various standard strains and clinical isolates of S. aureus. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on antibacterial effect of 8-HQ and CCEO combination in liquid and vapour phases. Results of the study suggest these agents as potential candidates for development of new anti-staphylococcal applications that can be used in the inhalation therapy against respiratory infections.
- MeSH
- akrolein analogy a deriváty chemie MeSH
- antibakteriální látky farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- oleje prchavé farmakologie MeSH
- oxychinolin farmakologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- skořicovník čínský chemie MeSH
- Staphylococcus aureus účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti-hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti-HCV activity was determined in infected Huh7.5 cells using quantitative real-time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti-HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 μM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd.
- MeSH
- amfotericin B farmakologie terapeutické užití MeSH
- antifungální látky farmakologie terapeutické užití MeSH
- Candida albicans účinky léků MeSH
- Hepacivirus účinky léků MeSH
- lidé MeSH
- naftochinony aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The successful application of mesenchymal stem cells (MSCs) remains a major challenge in stem cell therapy. Currently, several in vitro studies have indicated potentially beneficial interactions of MSCs with immunosuppressive drugs. These interactions can be even more complex in vivo, and it is in this setting that we investigate the effect of MSCs in combination with Cyclosporine A (CsA) on transplantation reaction and allogeneic cell survival. Using an in vivo mouse model, we found that CsA significantly promoted the survival of MSCs in various organs and tissues of the recipients. In addition, compared to treatment with CsA or MSCs alone, the survival of transplanted allogeneic cells was significantly improved after the combined application of MSCs with CsA. We further observed that the combinatory treatment suppressed immune response to the alloantigen challenge and modulated the immune balance by harnessing proinflammatory CD4+T-bet+ and CD4+RORγt+ cell subsets. These changes were accompanied by a significant decrease in IL-17 production along with an elevated level of IL-10. Co-cultivation of purified naive CD4+ cells with peritoneal macrophages isolated from mice treated with MSCs and CsA revealed that MSC-educated macrophages play an important role in the immunomodulatory effect observed on distinct T-cell subpopulations. Taken together, our findings suggest that CsA promotes MSC survival in vivo and that the therapeutic efficacy of the combination of MSCs with CsA is superior to each monotherapy. This combinatory treatment thus represents a promising approach to reducing immunosuppressant dosage while maintaining or even improving the outcome of therapy.
- MeSH
- alografty účinky léků imunologie MeSH
- cyklosporin farmakologie terapeutické užití MeSH
- cytokiny metabolismus MeSH
- imunosupresiva farmakologie terapeutické užití MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- preklinické hodnocení léčiv MeSH
- přežívání štěpu účinky léků imunologie MeSH
- T-lymfocyty účinky léků metabolismus MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Bioorthogonal chemistry provides one of the possibilities to modify various biomolecules in their native environment. The combination of Click chemistry with the BONCAT method (bioorthogonal non-canonical amino acid tagging) is widely used for tagging and analysis of newly synthesized proteins, which are clearly distinguishable from the pre-existing protein pool. However, the commonly used procedure results in low quality 2D electrophoretic profiles. We put a lot of effort into obtaining clear results using a standard Click protocol, with a negligible effect. Here we describe a Click-on-membrane approach which we successfully used not only to monitor de novo protein synthesis but also to detect newly synthesized RNA.
Context The increasing problem of drug-resistant strains has led to the failure of current treatment regimens of Helicobacter pylori (HP) infection. Recently, a new treatment strategy has been developed to overcome the problem by using natural products in combination with antibiotics to enhance the treatment efficacy. Objective The antimicrobial combinatory effect of the aqueous extract of Hibiscus sabdariffa L. (Malvaceae) (AEHS) with antibiotics (clarithromycin, CLA; amoxicillin, AMX; metronidazole, MTZ) has been evaluated in vitro against HP strains. Materials and methods Hibiscus calyces (35 g) were brewed in 250 mL of boiled water for 30 min, and minimum inhibitory concentrations (MICs) were determined by agar dilution method. The checkerboard assay was used to evaluate the antimicrobial combinatory effect according to the sum of fractional inhibitory concentration (∑FIC) indices. Results In this study, AEHS exerted remarkable bacteriostatic effect against all HP strains tested with MICs values ranging from 9.18 to 16.68 μg/mL. Synergy effect of AEHS with CLA or MTZ was obtained against four of seven HP strains tested with ∑FIC ranging from 0.21 to 0.39. The additive effect of AEHS with AMX was obtained against five of seven HP strains tested with ∑FIC ranging from 0.61 to 0.91. Conclusion This study presents AEHS as a potent therapeutic candidate alone, or in combination with antibiotics for the treatment of HP infection.
- MeSH
- amoxicilin farmakologie MeSH
- antibakteriální látky izolace a purifikace farmakologie MeSH
- fytoterapie MeSH
- Helicobacter pylori účinky léků růst a vývoj izolace a purifikace MeSH
- Hibiscus chemie MeSH
- infekce vyvolané Helicobacter pylori farmakoterapie mikrobiologie MeSH
- klarithromycin farmakologie MeSH
- kombinovaná farmakoterapie MeSH
- květy MeSH
- léčivé rostliny MeSH
- lidé MeSH
- metronidazol farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- rostlinné extrakty izolace a purifikace farmakologie MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A 2-D method was developed for separation of phenolic acids and flavone compounds combining LC with MEKC. The effect of substituted neutral and anionic CD additives to the background electrolyte on the quality of MEKC separation was investigated. The best selectivity of the MEKC separation was achieved in 25 mmol/L borate background buffer at pH 9.05 with the addition of 10 g/L SDS and 1.85 g/L heptakis (6-O-sulfo)-beta-CD. These conditions were used in the second dimension of 2-D combination of LC and MEKC separation in combination with a PEG column in the first dimension, providing the best orthogonality (the lowest degree of correlation between the selectivity of separation) in the two dimensions. A CE autosampler was employed as the interface between LC and MEKC steps based on automated fraction collection before the re-analysis of the collected LC fractions in the second, MEKC dimension. The 2-D method under optimized conditions was applied for the separation of natural antioxidants in the samples of green tea.
- MeSH
- beta-cyklodextriny chemie MeSH
- chromatografie kapalinová metody MeSH
- chromatografie micelární elektrokinetická kapilární metody MeSH
- flavonoidy analýza chemie izolace a purifikace MeSH
- hydroxybenzoáty analýza chemie izolace a purifikace MeSH
- koncentrace vodíkových iontů MeSH
- techniky kombinatorické chemie metody MeSH
- výpočetní biologie metody MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study evaluated the effect of low-molecular weight chitosan on Staphylococcus epidermidis, a common colonizer of joint implants and other prosthetic devices. We have also attempted to elucidate its mechanism of action. Chitosan was found to be effective against both the planktonic and biofilm cells (MIC80 35-40 mg/L; MBIC80 40-150 mg/L), in contrast to the antibiotics erythromycin and tetracycline with no antibiofilm activity (MBIC80 not found). In combination, chitosan had an additive effect with antibiotics on suspension growth of S. epidermidis (FICi 0.7-1.0), and the combinatory action caused a complete inhibition of biofilm metabolic activity in some cases. In addition, chitosan caused rapid cellular damage and enhanced antihaemolytic activity of tetracycline in combination towards S. epidermidis biofilm cells. Chitosan efficiently inhibited S. epidermidis growth acting via cell membrane damage, yet the extent of antimicrobial and antibiofilm activities was quite strain-specific. It was proved to be a very efficient antimicrobial agent worth further examination as a potent candidate in pharmaceutical research. Apart from antimicrobial activity, it also acted as antivirulence enhancing agent which is a very promising strategy for alternative infectious diseases treatment.
Carvacrol and thymol, both plant-derived volatile compounds, have extensively been studied individually as well as in combination with other agents for their antimicrobial activity in liquid phase. However, in contrast to well-established assays for testing of antimicrobial combinatory effects in liquid media, there are no standardized methods for evaluation of interactions between volatile compounds in vapour phase. The objective of this study was to verify new broth volatilization chequerboard method by testing the combination of carvacrol and thymol and to determine in vitro inhibitory effect of these compounds in liquid and vapour phase against twelve Staphylococcus aureus strains. The new method, based on combination of standard microdilution chequerboard and new broth volatilization tests allowing calculation of fractional inhibitory concentrations (FICs), was used. Combination of carvacrol and thymol produced the additive antimicrobial effect against all strains tested. In several cases, they reached ΣFIC values lower than 0.6, which can be considered as a strong additive interaction. The best result was found in vapour phase against one standard strain at combination of 128 μg/mL of carvacrol and 16-256 μg/mL of thymol (ΣFIC = 0.51) and in liquid phase against one clinical isolate at combination of 256 μg/mL of carvacrol and 256 μg/mL of thymol (ΣFIC = 0.53). The study verified that the new technique is suitable for simple and rapid high-throughput combinatory antimicrobial screening of volatile compounds simultaneously in vapour and liquid phase and that it allows determination and comparison of MIC and FIC values in both, liquid and solid media.
