Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells

Directory of Open Access Journals (Sweden)

Coffey Matthew C

2009-07-01

Full Text Available Abstract Background Reovirus type 3 Dearing strain (ReoT3D has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC. Results ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell lines examined, with the 50% effective dose, defined as the initial virus dose to achieve 50% cell killing after 48 hours of infection, ranging from 1.46 ± 0.12 ~2.68 ± 0.25 (mean ± SD log10 pfu/cell. Chou-Talalay analysis of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine demonstrated strong synergistic effects on cell killing, but only in cell lines that were sensitive to these compounds. In contrast, the combination of ReoT3D and paclitaxel was invariably synergistic in all cell lines tested, regardless of their levels of sensitivity to either agent. Treatment of NSCLC cell lines with the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose polymerase cleavage and caspase activity compared to single therapy, indicating enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated with the ReoT3D-paclitaxel combination showed increased proportions of mitotic and apoptotic cells, and a more pronounced level of caspase-3 activation was demonstrated in mitotically arrested cells. Conclusion These data suggest that the oncolytic activity of ReoT3D can be potentiated by taxanes and other chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively achieves synergy through accelerated apoptosis triggered by prolonged mitotic arrest.

Synergistic activation of NF-κB by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKKβ-IκBα, and p38 MAPK

International Nuclear Information System (INIS)

Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida; Lim, Jae Hyang; Koga, Tomoaki; Ishinaga, Hajime; Chen, L.-F.; Jono, Hirofumi; Xu Haidong; Li, J.-D.

2006-01-01

In review of the past studies on NF-κB regulation, most of them have focused on investigating how NF-κB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-κB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-κB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKβ-IκBα and p38 MAPK pathways are involved in synergistic activation of NF-κB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-κB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-κB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases

Synergistic antiviral effect in vitro of azidothymidine and amphotericin B methyl ester in combination on HIV infection

DEFF Research Database (Denmark)

Hansen, J E; Nielsen, C; Svenningsen, A

1992-01-01

The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no sig...... synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV....

Preclinical demonstration of synergistic Active Nutrients/Drug (AND combination as a potential treatment for malignant pleural mesothelioma.

Directory of Open Access Journals (Sweden)

Viviana Volta

Full Text Available Malignant pleural mesothelioma (MPM is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug. In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model

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Burkhardt, Melanie A.; Waser, Jasmin; Milleret, Vincent; Gerber, Isabel; Emmert, Maximilian Y.; Foolen, Jasper; Hoerstrup, Simon P.; Schlottig, Falko; Vogel, Viola

2016-02-01

Low correlations of cell culture data with clinical outcomes pose major medical challenges with costly consequences. While the majority of biomaterials are tested using in vitro cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free in vitro cell cultures poorly correlated with in vivo tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, in vitro test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties.

Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation

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Nylander, Sven; Mattsson, Christer; Ramström, Sofia; Lindahl, Tomas L

2004-01-01

The objective of this study was to investigate if there is a synergistic effect of a combination of P2Y12 and P2Y1 inhibition and P2Y12 and thrombin inhibition, on ADP- and thrombin-induced platelet activation, respectively. The rationale being that these combinations will cause a concurrent inhibition of both Gαq and Gαi signalling.Blood from healthy volunteers was preincubated with AR-C69931MX, a reversible P2Y12 antagonist; MRS2179, a reversible P2Y1 antagonist; or melagatran, a direct reversible thrombin inhibitor; alone or in various combinations prior to activation with ADP or thrombin. Platelet function in whole blood was assessed by flow cytometry using the antibody PAC-1 to estimate the expression of active αIIbβ3 (the fibrinogen receptor GPIIb/IIIa). A synergistic effect was evaluated by comparing the concentrations in the different combinations with those of corresponding equipotent concentrations of each single inhibitor alone. The equipotent single concentrations were experimentally obtained from concentration response curves performed in parallel.A synergistic effect regarding inhibition of ADP-induced platelet activation (10 μM) was obtained with different combinations of AR-C69931MX and MRS2179.Inhibition of thrombin-induced platelet activation (2 nM) with combinations of AR-C69931MX and the thrombin inhibitor melagatran did also result in a strong synergistic effect.To our knowledge, this is the first time that data supporting a synergistic effect has been published for the inhibitor combinations described.Whether this synergistic effect in vitro also results in an improved antithrombotic effect in vivo with or without an increased risk of bleeding remains to be studied in well-conducted clinical studies. PMID:15265806

Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.

Science.gov (United States)

Grisin, Tiphany; Bories, Christian; Bombardi, Martina; Loiseau, Philippe M; Rouffiac, Valérie; Solgadi, Audrey; Mallet, Jean-Maurice; Ponchel, Gilles; Bouchemal, Kawthar

2017-05-01

The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity. Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water. The formulation is specifically-engineered for mucosal application by dispersing chitosan micro-platelets into thermosensitive pluronic ® F127 20 wt% hydrogel. The formulation completely cured C. albicans vaginal infection in mice and had a superior activity in comparison with AmB-DOC without addition of chitosan micro-platelets. In vitro studies showed that the platelets significantly enhance AmB-DOC antifungal activity since the IC 50 and the MIC 90 decrease 4.5 and 4.8-times. Calculation of fractional inhibitory concentration index (FICI = 0.198) showed that chitosan micro-platelets act in a synergistic way with AmB-DOC against C. albicans. No synergy is found between spherical nanoparticles composed poly(isobutylcyanoacrylate)/chitosan and AmB-DOC. These results demonstrate for the first time the ability of flattened chitosan micro-platelets to have synergistic activity with AmB-DOC against C. albicans candidiasis and highlight the importance of rheological and mucoadhesive behaviors of hydrogels in the efficacy of the treatment.

Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation

Energy Technology Data Exchange (ETDEWEB)

Borek, C; Zaider, M; Ong, A; Mason, H; Witz, G

1986-09-01

Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear. Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, it is reported for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. The carcinogenic interaction between ozone and ionizing radiation is also reported. Exposure of the cells to 3 or 4 Gy of ..gamma..-rays, 2 h prior to O/sub 3/ treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O/sub 3/ acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model.

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Agarwal, Drishti; Sharma, Manish; Dixit, Sandeep K; Dutta, Roshan K; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

2015-02-05

Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their anti-malarial interaction in combination with artemisinin in vitro, against Plasmodium falciparum 3D7 strain, employing fixed-ratio combination isobologram method. In addition, the efficacy of these compounds was evaluated intraperitoneally in BALB/c mice infected with chloroquine-resistant Plasmodium berghei ANKA strain in the Peters' four-day suppressive test. Promising results were obtained in the form of synergistic or additive interactions. Compounds 10 and 12 were found to have highly synergistic interactions with artemisinin. Antiplasmodial effect was further verified by the convincing ED50 values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW). In vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.

The in vitro synergistic inhibitory effect of human amniotic fluid and gentamicin on growth of Escherichia coli.

Science.gov (United States)

Miglioli, P A; Schoffel, U; Gianfranceschi, L

1996-01-01

The activity of serum and its synergistic effect with many antibiotics against bacteria are well known. Few reports are available on similar phenomena produced by human amniotic fluid (HAF). Thus we investigated the antibacterial activity of HAF and the presence of a synergistic effect with gentamicin (GM) against Escherichia coli strains. Antimicrobial activity was evaluated as a delay of the growth curve, using a turbidimetric method. E. coli ATCC 10798 and E. coli SC 12155 were employed as test micro-organisms in nutrient broth, and GM was used at a subinhibitory concentration. HAF exerted antibacterial activity and, cooperating with GM at subinhibitory concentration, enhanced its antibiotic activity against E. coli. The presence of Schlievert's glycoprotein in HAF could explain these results.

Robust, synergistic regulation of human gene expression using TALE activators.

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Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

2013-03-01

Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

Antifeedant activity of Jatropha gossypifolia and Melia azedarach senescent leaf extracts on Spodoptera frugiperda (Lepidoptera: Noctuidae) and their potential use as synergists.

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Bullangpoti, Vasakorn; Wajnberg, Eric; Audant, Pascaline; Feyereisen, René

2012-09-01

To reduce rates of synthetic insecticide applications, natural product alternatives and synergists are needed. A study has been made of the toxicity of ethanolic senescent leaf extracts (SLEs) of Jatropha gossypifolia and Melia azedarach on larvae of the noctuid pest Spodoptera frugiperda. Their effects as syngergists and inhibitors of several enzyme activities are also reported. When added to the diet, M. azedarach SLE showed lower toxicity than J. gossypifolia SLE. However, after 2 weeks on the diet, the M. azedarach SLE proved to be lethal to 100% of the larval population. Artificial diets with both SLEs have an antifeedant effect on armyworm larvae. Acute toxicity after topical application in a dipping assay was relatively low for both J. gossypifolia and M. azedarach SLEs (LC(50) of 2.6 and 1.4 g L(-1), respectively, after 24 h). However, mixtures of the SLEs of M. azedarach and J. gossypifolia had a strong synergistic effect with cypermethrin. Synergism was higher with the J. gossypifolia SLE, perhaps because it contains several natural products with a methylenedioxyphenyl moiety. Both extracts inhibited P450, general esterase and acetylcholinesterase activities in vitro and in vivo. Both J. gossypifolia and M. azedarach SLEs are antifeedants to armyworm larvae when present in the food, and also have a synergistic effect with cypermethrin in topical assays. Although the synergistic effect is less than with piperonyl butoxide, both SLEs have some inhibitor activity against detoxification enzymes and acetylcholinesterase. Thus J. gossypifolia and M. azedarach SLEs may be considered as ecofriendly approaches for the control of S. frugiperda in order to reduce cypermethrin usage. Copyright © 2012 Society of Chemical Industry.

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Science.gov (United States)

Wu, Bo; Lu, Shu-Ting; Zhang, Liu-Jie; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment. PMID:28331310

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid-polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment.

Science.gov (United States)

Wu, Bo; Lu, Shu-Ting; Zhang, Liu-Jie; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid-polymer hybrid nanoparticles (LPNPs) drug delivery system composed of monomethoxy-poly(ethylene glycol)- S - S -hexadecyl (mPEG- S - S -C 16 ), soybean lecithin, and poly(D,L-lactide-co-glycolide) (PLGA) was used for codelivery of doxorubicin (DOX) and a Chinese herb extract triptolide (TPL). Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs) exhibited a high level of synergistic activation with low combination index (CI) in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells). Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment.

Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung cancers.

Science.gov (United States)

Kim, Bomi; Seo, Bohyung; Park, Sanghyun; Lee, Changkyu; Kim, Jong Oh; Oh, Kyung Taek; Lee, Eun Seong; Choi, Han-Gon; Youn, Yu Seok

2017-10-01

Albumin nanoparticles are well-known as effective drug carriers used to deliver hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin and doxorubicin were fabricated using slightly modified nanoparticle albumin-bound (nab™) technology, and the synergistic effects of these two drugs were examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both curcumin and doxorubicin were prepared using a high pressure homogenizer. The sizes of albumin nanoparticles were ∼130nm, which was considered to be suitable for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles gradually released drugs over a period of 24h without burst effect. To confirm the synergistic effect of two drugs, in vitro cytotoxicity assay was performed using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was highest when co-treated with both curcumin and doxorubicin compared to single treatment of either curcumin and doxorubicin. The combined index calculated by medium-effect equation was 0.6069, indicating a synergistic effect. Results of confocal laser scanning microscopy and fluorescence-activated cell sorting corresponded to results from an in vitro cytotoxicity assay, indicating synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by B16F10 lung metastasis was used to study in vivo therapeutic effects. When curcumin and doxorubicin were simultaneously treated, the metastatic melanoma mass in the lungs macroscopically decreased compared to curcumin or doxorubicin alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to have an effective therapeutic result and would be an excellent way to treat resistant lung cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic induction of apoptosis in multiple myeloma cells by bortezomib and hypoxia-activated prodrug TH-302, in vivo and in vitro.

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Hu, Jinsong; Van Valckenborgh, Els; Xu, Dehui; Menu, Eline; De Raeve, Hendrik; De Bruyne, Elke; De Bryune, Elke; Xu, Song; Van Camp, Ben; Handisides, Damian; Hart, Charles P; Vanderkerken, Karin

2013-09-01

Recently, we showed that hypoxia is a critical microenvironmental factor in multiple myeloma, and that the hypoxia-activated prodrug TH-302 selectively targets hypoxic multiple myeloma cells and improves multiple disease parameters in vivo. To explore approaches for sensitizing multiple myeloma cells to TH-302, we evaluated in this study the antitumor effect of TH-302 in combination with the clinically used proteasome inhibitor bortezomib. First, we show that TH-302 and bortezomib synergistically induce apoptosis in multiple myeloma cell lines in vitro. Second, we confirm that this synergism is related to the activation of caspase cascades and is mediated by changes of Bcl-2 family proteins. The combination treatment induces enhanced cleavage of caspase-3/8/9 and PARP, and therefore triggers apoptosis and enhances the cleavage of proapoptotic BH3-only protein BAD and BID as well as the antiapoptotic protein Mcl-1. In particular, TH-302 can abrogate the accumulation of antiapoptotic Mcl-1 induced by bortezomib, and decreases the expression of the prosurvival proteins Bcl-2 and Bcl-xL. Furthermore, we found that the induction of the proapoptotic BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA is associated with this synergism. In response to the genotoxic and endoplasmic reticulum stresses by TH-302 and bortezomib, the expression of PUMA and NOXA were upregulated in p53-dependent and -independent manners. Finally, in the murine 5T33MMvv model, we showed that the combination of TH-302 and bortezomib can improve multiple disease parameters and significantly prolong the survival of diseased mice. In conclusion, our studies provide a rationale for clinical evaluation of the combination of TH-302 and bortezomib in patients with multiple myeloma.

Interaction of alphamangostin and curcumin with dihydroartemisinin as antimalaria in vitro

Science.gov (United States)

Tjahjani, S.; Syafruddin; Tjokropranoto, R.

2018-03-01

To overcome malarial resistance tendency against the ACT (artemisinin-based combination therapy), several galenic preparations of Garciniamangostana L-rind and alphamangostin as the major xanthone in this rind have been studied, and they had antimalarial activity and showed its synergistic effect with artemisinin in vitro. Curcumin as anactive component of turmeric is also potentially to have antimalarial activity. This study aimed to evaluate the activity as antimalarial of curcumin and dihydroartemisinin, an active metabolite of all artemisinin derivates, and also to study the mechanism of action of aphamangostin, curcumin, and dihydroartemisinin as antimalaria.The interaction between them each other as the antimalarial in vitro was also investigated. The antimalarial activity was studied in in vitro 3D7 Plasmodium falciparum cultivation incubated with these compounds to look for the IC50 and ΣFIC50 of them. The mechanism of action of these compounds was observed electron microscopically. The result of this promising study showed that these compounds were active antimalaria agents which inhibited hemozoin formation and there is synergistic antimalarial activity interaction between alphamangostin and dihydroartemisinin.

In vitro activity of daptomycin combined with dalbavancin and linezolid, and dalbavancin with linezolid against MRSA strains.

Science.gov (United States)

Aktas, Gulseren; Derbentli, Sengul

2017-02-01

Combination therapies have a distinct advantage over monotherapies in terms of their broad spectrum, synergistic effect and prevention of the emergence of drug resistance. In the present study, the in vitro antibacterial activity of daptomycin combinations with linezolid and dalbavancin, and dalbavancin with linezolid were evaluated against 30 clinical MRSA strains. The MICs of all antibiotics were determined using microbroth dilution as described by the CLSI. The in vitro activities of antibiotics in combination were assessed by using a microbroth 'chequerboard' assay. The MIC values of all antibiotics determined were evaluated in accordance with the recommendations of the CLSI for daptomycin and linezolid, and the FDA for dalbavancin. All strains (100%) were found to be susceptible to daptomycin, dalbavancin and linezolid. The MIC 50 , MIC 90 and MIC range values of these antibiotics were determined to be 1, 1 and 0.5-1 mg/L, 0.12, 0.12 and 0.03-0.12 mg/L, and 1, 2 and 1-2 mg/L, respectively. The rates of synergistic effects were 67% for daptomycin combined with dalbavancin and with linezolid, and 60% for dalbavancin combined with linezolid. The results of this study show that in vitro combinations of these new antimicrobials will be effective in the therapy of MRSA infections. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

NARCIS (Netherlands)

Nijholt, W.; Jager-Wittenaar, H.; Visser, M.; Van der Schans, C. P.; Hobbelen, J. S. M.

Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being

Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

NARCIS (Netherlands)

Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

2016-01-01

OBJECTIVES: Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and

Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

NARCIS (Netherlands)

Nijholt, Willemke; Jager, Harriët; Visser, M.; van der Schans, Cees; Hobbelen, Hans

2015-01-01

Objectives: Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and

Codelivery of doxorubicin and triptolide with reduction-sensitive lipid–polymer hybrid nanoparticles for in vitro and in vivo synergistic cancer treatment

Directory of Open Access Journals (Sweden)

Wu B

2017-03-01

Full Text Available Bo Wu,1,2,* Shu-Ting Lu,1,* Liu-Jie Zhang,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Codelivery is a promising strategy to overcome the limitations of single chemotherapeutic agents in cancer treatment. Despite progress, codelivery of two or more different functional drugs to increase anticancer efficiency still remains a challenge. Here, reduction-sensitive lipid–polymer hybrid nanoparticles (LPNPs drug delivery system composed of monomethoxy-poly(ethylene glycol-S-S-hexadecyl (mPEG-S-S-C16, soybean lecithin, and poly(d,l-lactide-co-glycolide (PLGA was used for codelivery of doxorubicin (DOX and a Chinese herb extract triptolide (TPL. Hydrophobic DOX and TPL could be successfully loaded in LPNPs by self-assembly. More importantly, drug release and cellular uptake experiments demonstrated that the two drugs were reduction sensitive, released simultaneously from LPNPs, and taken up effectively by the tumor cells. DOX/TPL-coloaded LPNPs (DOX/TPL-LPNPs exhibited a high level of synergistic activation with low combination index (CI in vitro and in vivo. Moreover, the highest synergistic therapeutic effect was achieved at the ratio of 1:0.2 DOX/TPL. Further experiments showed that TPL enhanced the uptake of DOX by human oral cavity squamous cell carcinoma cells (KB cells. Overall, DOX/TPL-coencapsulated reduction-sensitive nanoparticles will be a promising strategy for cancer treatment. Keywords: triptolide, codelivery, reduction sensitive, synergistic effect

JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C).

Science.gov (United States)

Shami, Paul J; Maciag, Anna E; Eddington, Jordan K; Udupi, Vidya; Kosak, Ken M; Saavedra, Joseph E; Keefer, Larry K

2009-11-01

We have designed prodrugs that release nitric oxide (NO) on metabolism by glutathione S-transferases (GST). This design exploits the upregulation of GST in acute myeloid leukemia (AML) cells. O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-leukemic activity. HL-60 myeloid leukemia cells were used for in vitro studies of the combination of JS-K with daunorubicin (DAUNO), cytarabine (ARA-C) or etoposide (ETOP) using the median effect method to determine synergistic, antagonistic, or additive effects. Combinations of JS-K added simultaneously, 2h before or 2h after the other compounds were used. JS-K and DAUNO were antagonistic in all three drug sequences. JS-K and ETOP were also antagonistic but to a lesser degree. JS-K and ARA-C showed strong synergy. The combination index at the 50% fraction affected was 0.37+/-0.23, 0.24+/-0.27, and 0.15+/-0.11 for simultaneous, JS-K first and ARA-C first additions, respectively. JS-K by itself induced DNA strand breaks at relatively high concentrations. However, at submicromolar concentrations, it significantly augmented ARA-C-induced DNA strand breaks. NMR spectroscopy revealed no evidence of chemical interaction between JS-K and the other chemotherapeutic agents. We conclude that ARA-C and JS-K have synergistic anti-leukemic activity and warrant further exploration in combination.

In Vitro Evaluation of the Activity of Imipenem-Relebactam against 451 Recent Clinical Isolates of Bacteroides Group and Related Species.

Science.gov (United States)

Snydman, David R; Jacobus, Nilda V; McDermott, Laura A

2016-10-01

We evaluated the in vitro activity of imipenem-relebactam (imipenem-MK7655) against 451 recent clinical isolates within the Bacteroides group and related species. Relebactam did not enhance or inhibit the activity of imipenem against Bacteroides fragilis or other Bacteroides species. No synergistic or antagonistic effect was observed. The MICs of imipenem-relebactam were equal to or within one dilution of the MICs of these isolates to imipenem. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

Science.gov (United States)

Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

2014-10-01

Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

Energy Technology Data Exchange (ETDEWEB)

Christen, Verena [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Crettaz, Pierre [Federal Office of Public Health, Division Chemical Products, 3003 Bern (Switzerland); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); ETH Zürich, Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, Universitätsstrasse 16, CH-8092 Zürich (Switzerland)

2014-09-15

Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC{sub 25} and EC{sub 50}. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of

Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

International Nuclear Information System (INIS)

Christen, Verena; Crettaz, Pierre; Fent, Karl

2014-01-01

Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC 25 and EC 50 . Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of pyrethroids and

Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols.

Science.gov (United States)

Seth, Kapileswar; Roy, Sudipta Raha; Pipaliya, Bhavin V; Chakraborti, Asit K

2013-07-04

Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.

In vitro synergistic efficacy of conjugated linoleic acid, oleic acid, safflower oil and taxol cytotoxicity on PC3 cells.

Science.gov (United States)

Kızılşahin, Sadi; Nalbantsoy, Ayşe; Yavaşoğlu, N Ülkü Karabay

2015-01-01

The aim of this study was to determine in vitro synergistic efficacy of conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax) cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic efficacy of oil combinations, PC3 treated with different doses of compounds alone and combined with 10 μg/mL Tax. The MTT results indicated that OLA-Tax combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 μg-Tax, 15 nM+5 μg-Tax and 7.5 nM+2.5 μg-Tax. The treatment of OLA or Tax did not show significant inhibition on PC3, while OLA-Tax combinations showed effective cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect on PC3 as combined form with 45.72% versus the alone form as 74.51% viability. Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3 which might be used in the therapy of prostate cancer.

Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin- sensitive and resistant Staphylococcus aureus in vitro and in vivo.

Science.gov (United States)

Cunningham-Oakes, Edward; Soren, Odel; Moussa, Caroline; Rathor, Getika; Liu, Yingjun; Coates, Anthony; Hu, Yanmin

2015-01-01

Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are prevalent. MRSA infections are difficult to treat and there are no new classes of antibiotics produced to the market to treat infections caused by the resistant bacteria. Therefore, using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. Nordihydroguaiaretic acid (NDGA) is an antioxidant compound found in extracts from plant Larrea Tridentata. It exhibits antimicrobial activity and may target bacterial cell membrane. Combination efficacies of NDGA with many classes of antibiotics were examined by chequerboard method against 200 clinical isolates of MRSA and MSSA. NDGA in combination with gentamicin, neomycin, and tobramycin was examined by time-kill assays. The synergistic combinations of NDGA and aminoglycosides were tested in vivo using a murine skin infection model. Calculations of the fractional inhibitory concentration index (FICI) showed that NDGA when combined with gentamicin, neomycin, or tobramycin displayed synergistic activities in more than 97% of MSSA and MRSA, respectively. Time kill analysis demonstrated that NDGA significantly augmented the activities of these aminoglycosides against MRSA and MSSA in vitro and in murine skin infection model. The enhanced activity of NDGA resides on its ability to damage bacterial cell membrane leading to accumulation of the antibiotics inside bacterial cells. We demonstrated that NDGA strongly revived the therapeutic potencies of aminoglycosides in vitro and in vivo. This combinational strategy could contribute major clinical implications to treat antibiotic resistant bacterial infections.

Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro.

Science.gov (United States)

Prescott, Matthew; Mitchell, James; Totti, Stella; Lee, Judy; Velliou, Eirini; Bussemaker, Madeleine

2018-01-01

The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100μM sanguinarine or 1mM of GRE with 15s sonication at 500kHz and 10W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

Science.gov (United States)

Oh, Euna; Jeon, Byeonghwa

2015-01-01

The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

Comparison of the antibacterial activity and synergistic activity towards antibiotics of different mammalian sera.

Science.gov (United States)

Miglioli, P A; Pea, F; Mazzo, M; Berti, T

1993-02-01

The antibacterial activity against Escherichia coli ATCC 10798 and Staphylococcus aureus Mag 90 of normal sera from nine species of mammals was investigated by Avantage (Abbott). Human and rat sera showed the highest antibacterial activity against E. coli ATCC 10798, while all investigated sera did not exhibit, till the maximum concentration tested (20%), spontaneous antibacterial activity against S. aureus Mag 90. Heat inactivated sera (56 degrees C for 30 min) of all investigated species lost their antibacterial activity, but maintained their synergistic effect with sub-MICs of some antibacterial drugs, principally against E. coli ATCC 10798.

In-vitro evaluation of anti-trichomonal activities of Eugenia uniflora leaf.

Science.gov (United States)

Ibikunle, Gabriel Femi; Adebajo, Adeleke Clement; Famuyiwa, Funmilayo Gladys; Aladesanmi, Adetunji Joseph; Adewunmi, Clement Oladapo

2011-01-01

Eugenia uniflora, used ethnomedically in some tropical countries as an anti-infective, has shown anti-malarial and anti-trypanocidal activities. Therefore using bioactivity guided fractionation, anti-trichomonal activity of E. uniflora leaf was investigated. Anti-trichomonal activities of leaf methanol extract and its fractions against Trichomonas gallinae as well as their cytotoxicities using an in vitro haemaglutination assay were determined. Anti-trichomonacidal activities of the extract improved on purification up to a stage. Subfractions E(2-5) had LC(50) and LC(90) values of 4.77 - 5.28, 18.49 - 25.00 and 4.53 - 5.18, 18.32 - 19.07 µg/ml at 24 and 48 hrs, respectively that were better than those of metronidazole. Further purification of E(2-5) led to loss of activity suggesting that the active components were probably working synergistically and additively. Demonstration of low haemaglutination titre values of 0.00 - 5.33 by methanolic extract and its partition fractions suggested their low toxicity profile. The established safety of the leaf indicated that its anti-trichomonal activity was not due to non-specific cytotoxicity, hence could be used in ethnomedicine as an anti-trichomonal agent.

In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

Science.gov (United States)

Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

2016-01-11

Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Targeting both IGF-1R and mTOR synergistically inhibits growth of renal cell carcinoma in vitro

International Nuclear Information System (INIS)

Cardillo, Thomas M; Trisal, Preeti; Arrojo, Roberto; Goldenberg, David M; Chang, Chien-Hsing

2013-01-01

Advanced or metastatic renal cell carcinoma (RCC) has a poor prognosis, because it is relatively resistant to conventional chemotherapy or radiotherapy. Treatments with human interferon-α2b alone or in combination with mammalian target of rapamycin (mTOR) inhibitors have led to only a modest improvement in clinical outcome. One observation made with mTOR inhibitors is that carcinomas can overcome these inhibitory effects by activating the insulin-like growth factor-I (IGF-I) signaling pathway. Clinically, there is an association of IGF-I receptor (IGF-IR) expression in RCC and poor long-term patient survival. We have developed a humanized anti-IGF-IR monoclonal antibody, hR1, which binds to RCC, resulting in effective down-regulation of IGF-IR and moderate inhibition of cell proliferation in vitro. In this work, we evaluate the anti-tumor activity of two novel IGF-1R-targeting agents against renal cell carcinoma given alone or in combination with an mTOR inhibitor. hR1 was linked by the DOCK-AND-LOCK™ (DNL™) method to four Fabs of hR1, generating Hex-hR1, or to four molecules of interferon-α2b, generating 1R-2b. Eight human RCC cell lines were screened for IGF-1R expression and sensitivity to treatment with hR1 in vitro. Synergy with an mTOR inhibitor, temsirolimus, was tested in a cell line (ACHN) with low sensitivity to hR1. Hex-hR1 induced the down-regulation of IGF-IR at 10-fold lower concentrations compared to the parental hR1. Sensitivity to growth inhibition mediated by hR1 and Hex-hR1 treatments correlated with IGF-1R expression (higher expression was more sensitive). The potency of 1R-2b to inhibit the in vitro growth of RCC was also demonstrated in two human cell lines, ACHN and 786-O, with EC 50 –values of 63 and 48 pM, respectively. When combined with temsirolimus, a synergistic growth-inhibition with hR1, Hex-hR1, and 1R-2b was observed in ACHN cells at concentrations as low as 10 nM for hR1, 1 nM for Hex-hR1, and 2.6 nM for 1R-2b. Both Hex-hR1

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

Science.gov (United States)

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2016-02-15

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. Copyright © 2016 Leggett et al.

Natamycin and Azithromycin are Synergistic in vitro against Ocular Pathogenic Aspergillus flavus species complex and Fusarium solani species complex Isolates.

Science.gov (United States)

Guo, Haoyi; Zhou, Lutan; He, Yi; Gao, Chuanwen; Han, Lei; Xu, Yan

2018-05-07

The interaction of natamycin-azithromycin combination against 60 ocular fungal isolates was tested in vitro The combination produced 100% synergistic interactions when natamycin added azithromycin at 20, 40, 50 μg/ml against Aspergillus flavus species complex (AFSC) isolates and added azithromycin at 50 μg/ml against Fusarium solani species complex isolates. The combination with 50 μg/ml azithromycin enhanced natamycin's effect against AFSC isolates by reducing natamycin MICs from MIC 90 64μg/ml to MIC 90 0.031μg/ml. No antagonism was observed. Copyright © 2018 American Society for Microbiology.

Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

Science.gov (United States)

Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

2016-01-01

Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being physically active with cognitive functioning. Cross-sectional study. Data from the Longitudinal Aging Study Amsterdam (LASA) were used. We analyzed data from 2,165 community dwelling adults who were aged 55-85 years, 56% of whom were female. Cognitive functioning was assessed by the Mini-Mental State Examination (MMSE), an MMSE score of >26 indicates good cognitive functioning. Physical activity was assessed by the LASA Physical Activity Questionnaire and was considered sufficient if the person engaged in moderately intense physical activity ≥ 20 min/day. A healthy diet score was based on the intake of fruit, vegetables and fish. Each of the food groups was assigned a score that ranged from 1 (well below the Dutch guideline for a healthy diet) to 4 (well above the Dutch guideline for a healthy diet), and the scores were aggregated to determine a healthy diet (healthy ≥ 9 points). Multiple logistic and linear regression analyses were used to examine the (synergistic) association among physical activity, a healthy diet and cognitive functioning. All analyses were adjusted for potential chronic diseases and lifestyle confounders. Of all of the participants, 25% were diagnosed with a cognitive impairment (MMSE ≤26), 80% were physically active and 41% had a healthy diet. Sixty three percent of the participants both adhered to a healthy diet and were physically active. Sufficient daily physical activity (OR=2.545 phealthy diet (OR=1.766 p=.002) were associated with good cognitive functioning. After adjusting for confounding factors, sufficient physical activity was not significantly related to cognitive functioning (p=.163); however adherence to a healthy diet remained

Synergistic mutual potentiation of antifungal activity of Zuccagnia punctata Cav. and Larrea nitida Cav. extracts in clinical isolates of Candida albicans and Candida glabrata.

Science.gov (United States)

Butassi, Estefanía; Svetaz, Laura A; Ivancovich, Juan J; Feresin, Gabriela E; Tapia, Alejandro; Zacchino, Susana A

2015-06-01

Zuccagnia punctata Cav. (Fabaceae) and Larrea nitida Cav. (Zygophyllaceae) are indistinctly or jointly used in traditional medicine for the treatment of fungal-related infections. Although their dichloromethane (DCM) extract have demonstrated moderate antifungal activities when tested on their own, antifungal properties of combinations of both plants have not been assessed previously. The aim of this study was to establish with statistical rigor whether Z. punctata (ZpE) and L. nitida DCM extract (LnE) interact synergistically against the clinically important fungi Candida albicans and Candida glabrata and to characterize the most synergistic combinations. For synergism assessment, the statistical-based Boik's design was applied. Eight ZpE-LnE fixed-ratio mixtures were prepared from four different months of 1 year and tested against Candida strains. Lϕ (Loewe index) of each mixture at different fractions affected (ϕ) allowed for the finding of the most synergistic combinations, which were characterized by HPLC fingerprint and by the quantitation of the selected marker compounds. Lϕ and confidence intervals were determined in vitro with the MixLow method, once the estimated parameters from the dose-response curves of independent extracts and mixtures, were obtained. Markers (four flavonoids for ZpE and three lignans for LnE) were quantified in each extract and their combinations, with a valid HPLC-UV method. The 3D-HPLC profiles of the most synergistic mixtures were obtained by HPLC-DAD. Three over four IC50ZpE/IC50LnE fixed-ratio mixtures displayed synergistic interactions at effect levels ϕ > 0.5 against C. albicans. The dosis of the most synergistic (Lϕ = 0.62) mixture was 65.96 µg/ml (ZpE = 28%; LnE = 72%) containing 8 and 36% of flavonoids and lignans respectively. On the other hand, one over four IC50ZpE/IC50LnE mixtures displays synergistic interactions at ϕ > 0.5 against C. glabrata. The dosis of the most synergistic (Lϕ = 0.67) mixture was 168

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

International Nuclear Information System (INIS)

Jiménez-Medina, Eva; Berruguilla, Enrique; Romero, Irene; Algarra, Ignacio; Collado, Antonia; Garrido, Federico; Garcia-Lora, Angel

2008-01-01

Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G 0 /G 1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells

Synergistic Effect of Pleuromutilins with Other Antimicrobial Agents against Staphylococcus aureus In Vitro and in an Experimental Galleria mellonella Model

Science.gov (United States)

Dong, Chun-Liu; Li, Lin-Xiong; Cui, Ze-Hua; Chen, Shu-Wen; Xiong, Yan Q.; Lu, Jia-Qi; Liao, Xiao-Ping; Gao, Yuan; Sun, Jian; Liu, Ya-Hong

2017-01-01

Invasive infections due to Staphylococcus aureus, including methicillin-resistant S. aureus are prevalent and life-threatening. Combinations of antibiotic therapy have been employed in many clinical settings for improving therapeutic efficacy, reducing side effects of drugs, and development of antibiotic resistance. Pleuromutilins have a potential to be developed as a new class of antibiotics for systemic use in humans. In the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in combination of all three study pleuromutilins with tetracycline (TET) by standard checkerboard and/or time-kill assays. In addition, the combination of pleuromutilins with ciprofloxacin or enrofloxacin showed antagonistic effects, while the rest combinations presented indifferent effects. Importantly, all study pleuromutilins in combination with TET significantly enhanced survival rates as compared to the single drug treatment in the G. mellonella model caused by S. aureus strains. Taken together, these results demonstrated synergy effects between pleuromutilins and TET against S. aureus both in vitro and in vivo. PMID:28874907

Synergistic Effect of Pleuromutilins with Other Antimicrobial Agents against Staphylococcus aureus In Vitro and in an Experimental Galleria mellonella Model

Directory of Open Access Journals (Sweden)

Chun-Liu Dong

2017-08-01

Full Text Available Invasive infections due to Staphylococcus aureus, including methicillin-resistant S. aureus are prevalent and life-threatening. Combinations of antibiotic therapy have been employed in many clinical settings for improving therapeutic efficacy, reducing side effects of drugs, and development of antibiotic resistance. Pleuromutilins have a potential to be developed as a new class of antibiotics for systemic use in humans. In the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in combination of all three study pleuromutilins with tetracycline (TET by standard checkerboard and/or time-kill assays. In addition, the combination of pleuromutilins with ciprofloxacin or enrofloxacin showed antagonistic effects, while the rest combinations presented indifferent effects. Importantly, all study pleuromutilins in combination with TET significantly enhanced survival rates as compared to the single drug treatment in the G. mellonella model caused by S. aureus strains. Taken together, these results demonstrated synergy effects between pleuromutilins and TET against S. aureus both in vitro and in vivo.

Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p

DEFF Research Database (Denmark)

Moreira, José Manuel Alfonso; Remacle, J E; Kielland-Brandt, Morten

1998-01-01

A cis-acting element required for GCN4-independent basal-level transcription of ILV1 was previously identified in our laboratories as a binding site for the REB1 protein (Reb1p). Further deletion analysis of the ILV1 promoter region identified a second element also required for GCN4-independent...... basal-level ILV1 expression. This second element is an A.T-rich tract (26 As out of 32 nucleotides) situated 15 bp downstream of the Reb1p-binding site. Deletion of both the Reblp site and the poly(dA:dT) element totally eliminates basal activity of the ILV1 promoter. We show that the two elements act...... synergistically to control ILV1 expression and that the synergistic effect is distance dependent. We demonstrate that (i) datin (Dat1p), the only known poly (dA:dT)-binding protein in yeast, specifically binds to the ILV1 poly(dA:dT) element in vitro; (ii) Dat1p functions as a trans-activating factor in the ILV1...

Design, synthesis, and evaluation of caffeic acid amides as synergists to sensitize fluconazole-resistant Candida albicans to fluconazole.

Science.gov (United States)

Dai, Li; Zang, Chengxu; Tian, Shujuan; Liu, Wei; Tan, Shanlun; Cai, Zhan; Ni, Tingjunhong; An, Maomao; Li, Ran; Gao, Yue; Zhang, Dazhi; Jiang, Yuanying

2015-01-01

A series of caffeic acid amides were designed, synthesized, and their synergistic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The title caffeic acid amides 3-30 except 26 exhibited potent activity, and the subsequent SAR study was conducted. Compound 3, 5, 21, and 34c, at a concentration of 1.0 μg/ml, decreased the MIC₈₀ of fluconazole from 128.0 μg/ml to 1.0-0.5 μg/ml against the fluconazole-resistant C. albicans. This result suggests that the caffeic acid amides, as synergists, can sensitize drug-resistant fungi to fluconazole. The SAR study indicated that the dihydroxyl groups and the amido groups linking to phenyl or heterocyclic rings are the important pharmacophores of the caffeic acid amides.

Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

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Kasim, Vivi, E-mail: vivikasim78@gmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Yang, Li [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Miyagishi, Makoto [Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566 (Japan); Wu, Shourong, E-mail: shourongwu@hotmail.com [The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

2014-07-04

Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73.

Synergistic cooperation of MDM2 and E2F1 contributes to TAp73 transcriptional activity

International Nuclear Information System (INIS)

Kasim, Vivi; Huang, Can; Zhang, Jing; Jia, Huizhen; Wang, Yunxia; Yang, Li; Miyagishi, Makoto; Wu, Shourong

2014-01-01

Highlights: • MDM2 is a novel positive regulator of TAp73 transcriptional activity. • MDM2 colocalizes together and physically interacts with E2F1. • Synergistic cooperation of MDM2 and E2F1 is crucial for TAp73 transcription. • MDM2 regulates TAp73 transcriptional activity in a p53-independent manner. - Abstract: TAp73, a structural homologue of p53, plays an important role in tumorigenesis. E2F1 had been reported as a transcriptional regulator of TAp73, however, the detailed mechanism remains to be elucidated. Here we reported that MDM2-silencing reduced the activities of the TAp73 promoters and the endogenous TAp73 expression level significantly; while MDM2 overexpression upregulated them. We further revealed that the regulation of TAp73 transcriptional activity occurs as a synergistic effect of MDM2 and E2F1, most probably through their physical interaction in the nuclei. Furthermore, we also suggested that MDM2 might be involved in DNA damage-induced TAp73 transcriptional activity. Finally, we elucidated that MDM2-silencing reduced the proliferation rate of colon carcinoma cells regardless of the p53 status. Our data show a synergistic effect of MDM2 and E2F1 on TAp73 transcriptional activity, suggesting a novel regulation pathway of TAp73

Synergistic antioxidant activity of milk sphingomyeline and its sphingoid base with α-tocopherol on fish oil triacylglycerol.

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Shimajiri, Junki; Shiota, Makoto; Hosokawa, Masashi; Miyashita, Kazuo

2013-08-21

The effects of milk phospholipids (PLs), sphingolipids (SLs), and their sphingoid backbone on the oxidation of fish oil triacylglycerol (TAG) were examined with or without α-tocopherol. All compounds had little effect on the TAG oxidation in the absence of α-tocopherol. On the other hand, they could act synergistically with α-tocopherol. The highest synergistic activity was shown by sphingoid bases, followed by sphingomyelin (SPM) and other amine-containing PLs and SLs. This result showed that the synergistic activity increased with an increasing concentration of amine group of PLs, SLs, or sphingoid bases in the reaction mixture. The comparison of changes in α-tocopherol content in fish oil TAG and tricaprylin suggested that antioxidant compounds would be formed from the amine group and the lipid oxidation products in a mild oxidation condition controlled by α-tocopherol.

Synergistic activity of synthetic N-terminal peptide of human lactoferrin in combination with various antibiotics against carbapenem-resistant Klebsiella pneumoniae strains.

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Morici, P; Florio, W; Rizzato, C; Ghelardi, E; Tavanti, A; Rossolini, G M; Lupetti, A

2017-10-01

The spread of multi-drug resistant (MDR) Klebsiella pneumoniae strains producing carbapenemases points to a pressing need for new antibacterial agents. To this end, the in-vitro antibacterial activity of a synthetic N-terminal peptide of human lactoferrin, further referred to as hLF1-11, was evaluated against K. pneumoniae strains harboring different carbapenemase genes (i.e. OXA-48, KPC-2, KPC-3, VIM-1), with different susceptibility to colistin and other antibiotics, alone or in combination with conventional antibiotics (gentamicin, tigecycline, rifampicin, clindamycin, and clarithromycin). An antimicrobial peptide susceptibility assay was used to assess the bactericidal activity of hLF1-11 against the different K. pneumoniae strains tested. The synergistic activity was evaluated by a checkerboard titration method, and the fractional inhibitory concentration (FIC) index was calculated for the various combinations. hLF1-11 was more efficient in killing a K. pneumoniae strain susceptible to most antimicrobials (including colistin) than a colistin-susceptible strain and a colistin-resistant MDR K. pneumoniae strain. In addition, hLF1-11 exhibited a synergistic effect with the tested antibiotics against MDR K. pneumoniae strains. The results of this study indicate that resistance to hLF1-11 and colistin are not strictly associated, and suggest an hLF1-11-induced sensitizing effect of K. pneumoniae to antibiotics, especially to hydrophobic antibiotics, which are normally not effective on Gram-negative bacteria. Altogether, these data indicate that hLF1-11 in combination with antibiotics is a promising candidate to treat infections caused by MDR-K. pneumoniae strains.

Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma.

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Jeannot, Victor; Busser, Benoit; Vanwonterghem, Laetitia; Michallet, Sophie; Ferroudj, Sana; Cokol, Murat; Coll, Jean-Luc; Ozturk, Mehmet; Hurbin, Amandine

2016-01-01

Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated. The effects of the synergistic drug combinations were also studied in human lung adenocarcinoma and hepatocarcinoma cells in vivo. The combination of gefitinib and vorinostat synergistically reduced cell growth and strongly induced apoptosis through inhibition of the insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT)-dependent signaling pathway. Moreover, the gefitinib and vorinostat combination strongly inhibited tumor growth in mice with lung adenocarcinoma or hepatocarcinoma tumor xenografts. In contrast, the combination of sorafenib and vorinostat did not inhibit cell proliferation compared to a single treatment and induced G 2 /M cell cycle arrest without apoptosis. The sorafenib and vorinostat combination sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent signaling pathways. These results showed that there was synergistic cytotoxicity when vorinostat was combined with gefitinib for both lung adenocarcinoma and hepatocarcinoma with mutant KRAS in vitro and in vivo but that the combination of vorinostat with sorafenib did not show any benefit. These findings highlight the important role of the IGF-1R/AKT pathway in the resistance to targeted therapies and support the use of histone deacetylase inhibitors in combination with EGFR-tyrosine kinase inhibitors, especially for

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

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Garrido Federico

2008-03-01

Full Text Available Abstract Background Protein-bound polysaccharide (PSK is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin.

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Christen, Verena; Crettaz, Pierre; Fent, Karl

2014-09-15

Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose-response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC25 and EC50. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Our evaluation provides an appropriate "proof of concept", but whether it equally translates to in vivo effects should further be investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

Schedule dependent synergy of gemcitabine and doxorubicin: Improvement of in vitro efficacy and lack of in vitro-in vivo correlation.

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Vogus, Douglas R; Pusuluri, Anusha; Chen, Renwei; Mitragotri, Samir

2018-01-01

Combination chemotherapy is commonly used to treat late stage cancer; however, treatment is often limited by systemic toxicity. Optimizing drug ratio and schedule can improve drug combination activity and reduce dose to lower toxicity. Here, we identify gemcitabine (GEM) and doxorubicin (DOX) as a synergistic drug pair in vitro for the triple negative breast cancer cell line MDA-MB-231. Drug synergy and caspase activity were increased the most by exposing cells to GEM prior to DOX in vitro. While the combination was more effective than the single drugs at inhibiting MDA-MB-231 growth in vivo, the clear schedule dependence observed in vitro was not observed in vivo. Differences in drug exposure and cellular behavior in vivo compared to in vitro are likely responsible. This study emphasizes the importance in understanding how schedule impacts drug synergy and the need to develop more advanced strategies to translate synergy to the clinic.

In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

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Eberlin Marcos N

2011-05-01

Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

Potent synergistic in vitro interaction between nonantimicrobial membrane-active compounds and itraconazole against clinical isolates of Aspergillus fumigatus resistant to itraconazole.

NARCIS (Netherlands)

Afeltra, J.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

2004-01-01

To develop new approaches for the treatment of invasive infections caused by Aspergillus fumigatus, the in vitro interactions between itraconazole (ITZ) and seven different nonantimicrobial membrane-active compounds--amiodarone (AMD), amiloride, lidocaine, lansoprazole (LAN), nifedipine (NIF),

Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation of MAP Kinases and NFκB

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Ángela Dávila-Grana

2018-01-01

Full Text Available In recent years, there has been an increase in the production of several types of nanoparticles (Nps for different purposes. Several studies have been performed to analyse the toxicity induced by some of these individual Nps, but data are scarce on the potential hazards or beneficial effects induced by a range of nanomaterials in the same environment. The purpose of the study described here was to evaluate the toxicological effects induced by in vitro exposure of human cells to ZnO Nps in combination with different concentrations of other metal oxide Nps (Al2O3, CeO2, TiO2 and Y2O3. The results indicate that the presence of these Nps has synergistic or antagonistic effects on the cell death induced by ZnO Nps, with a quite marked beneficial effect observed when high concentrations of Nps were tested. Moreover, analysis by Western blot of the main components of the intracellular activation routes (MAPKs and NFκB again showed that the presence of other Nps can affect cell activation. In conclusion, the presence of several Nps in the same environment modifies the functional activity of one individual Np. Further studies are required in order to elucidate the effects induced by combinations of nanomaterials.

Synergistic Manganese(I) C-H Activation Catalysis in Continuous Flow: Chemoselective Hydroarylation.

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Wang, Hui; Pesciaioli, Fabio; Oliveira, João C A; Warratz, Svenja; Ackermann, Lutz

2017-11-20

Chemoselective hydroarylations were accomplished by a novel synergistic Brønsted acid/manganese(I)-catalyzed C-H activation manifold. Thus, alkynes bearing O-leaving groups could, for the first time, be employed for C-H alkenylations without concurrent β-O elimination, thereby setting the stage for versatile late-stage diversifications. Also described is the first manganese-catalyzed C-H activation in continuous flow, thus enabling efficient hydroarylations within only 20 minutes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Seasonal variation of Brazilian red propolis: Antibacterial activity, synergistic effect and phytochemical screening.

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Regueira, M S; Tintino, Saulo Relison; da Silva, Ana Raquel Pereira; Costa, Maria do Socorro; Boligon, Aline Augusti; Matias, Edinardo F F; de Queiroz Balbino, Valdir; Menezes, Irwin R A; Melo Coutinho, Henrique Douglas

2017-09-01

The aim of this study was to investigate the effect of the dry and rainy season on the antibacterial activity and chemical composition of the Brazilian red propolis. The samples were collected in rainy (RP-PER) and dry (RP-PED) seasons and analyzed by HPLC-DAD. The extracts were tested alone and in association with antibiotics against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The HPLC analysis identified luteolin and quercetin as the main compounds. Seasonal variation was observed according to concentrations of the compounds. The MIC values against E. coli ranged from 128 μg/mL to 512 μg/mL (EC 06 and EC ATCC). The red propolis showed MIC values of 512 μg/mL against both strains of P. aeruginosa used in our study (PA03 and PA24) and against strains of Gram-positive bacteria S. aureus the MICs ranged from 64 μg/mL to ≥1024 μg/mL (SA10). A synergistic effect was observed when we combined the RP-PED with gentamicin against all the strains tested. When we combined the RP-PED with Imipenem, we only observed synergistic effect against P. aeruginosa. According to our synergistic activity results, the utilization of red propolis collected in the drier periods can be used as an adjuvant against multiresistant bacterial infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printer-based technology.

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Brennan-Krohn, Thea; Truelson, Katherine A; Smith, Kenneth P; Kirby, James E

2017-10-01

Synergistic combination antimicrobial therapy may provide new options for treatment of MDR infections. However, comprehensive in vitro synergy data are limited and facile methods to perform synergy testing in a clinically actionable time frame are unavailable. To systematically investigate a broad range of antibiotic combinations for evidence of synergistic activity against a collection of carbapenem-resistant Enterobacteriaceae (CRE) isolates. We made use of an automated method for chequerboard array synergy testing based on inkjet printer technology in the HP D300 digital dispenser to test 56 pairwise antimicrobial combinations of meropenem, aztreonam, cefepime, colistin, gentamicin, levofloxacin, chloramphenicol, fosfomycin, trimethoprim/sulfamethoxazole, minocycline and rifampicin, as well as the double carbapenem combination of meropenem and ertapenem. In a screening procedure, we tested these combinations against four CRE strains and identified nine antibiotic combinations that showed potential clinically relevant synergy. In confirmatory testing using 10 CRE strains, six combinations demonstrated clinically relevant synergy with both antimicrobials at the minimum fractional inhibitory concentration (FICI-MIN) in the susceptible or intermediate range in at least one trial. These included two novel combinations: minocycline plus colistin and minocycline plus meropenem. In 80% of strains at least one combination demonstrated clinically relevant synergy, but the combinations that demonstrated synergy varied from strain to strain. This work establishes the foundation for future systematic, broad-range investigations into antibiotic synergy for CRE, emphasizes the need for individualized synergy testing and demonstrates the utility of inkjet printer-based technology for the performance of automated antimicrobial synergy assays. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights

Assessment of bioelectrical activity of synergistic muscles during pelvic floor muscles activation in postmenopausal women with and without stress urinary incontinence: a preliminary observational study.

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Ptaszkowski, Kuba; Paprocka-Borowicz, Małgorzata; Słupska, Lucyna; Bartnicki, Janusz; Dymarek, Robert; Rosińczuk, Joanna; Heimrath, Jerzy; Dembowski, Janusz; Zdrojowy, Romuald

2015-01-01

Muscles such as adductor magnus (AM), gluteus maximus (GM), rectus abdominis (RA), and abdominal external and internal oblique muscles are considered to play an important role in the treatment of stress urinary incontinence (SUI), and the relationship between contraction of these muscles and pelvic floor muscles (PFM) has been established in previous studies. Synergistic muscle activation intensifies a woman's ability to contract the PFM. In some cases, even for continent women, it is not possible to fully contract their PFM without involving the synergistic muscles. The primary aim of this study was to assess the surface electromyographic activity of synergistic muscles to PFM (SPFM) during resting and functional PFM activation in postmenopausal women with and without SUI. This study was a preliminary, prospective, cross-sectional observational study and included volunteers and patients who visited the Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Forty-two patients participated in the study and were screened for eligibility criteria. Thirty participants satisfied the criteria and were categorized into two groups: women with SUI (n=16) and continent women (n=14). The bioelectrical activity of PFM and SPFM (AM, RA, GM) was recorded with a surface electromyographic instrument in a standing position during resting and functional PFM activity. Bioelectrical activity of RA was significantly higher in the incontinent group than in the continent group. These results concern the RA activity during resting and functional PFM activity. The results for other muscles showed no significant difference in bioelectrical activity between groups. In women with SUI, during the isolated activation of PFM, an increased synergistic activity of RA muscle was observed; however, this activity was not observed in asymptomatic women. This may indicate the important accessory contribution of these muscles in the mechanism of continence.

Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro.

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Yang, Jun; Liu, Rui Hai

2009-09-23

Breast cancer is the most frequently diagnosed cancer in women. An alternative strategy to reduce the risk of cancer is through dietary modification. Although phytochemicals naturally occur as complex mixtures, little information is available regarding possible additive, synergistic, or antagonistic interactions among compounds. The antiproliferative activity of apple extracts and quercetin 3-beta-d-glucoside (Q3G) was assessed by measurement of the inhibition of MCF-7 human breast cancer cell proliferation. Cell cytotoxicity was determined by the methylene blue assay. The two-way combination of apple plus Q3G was conducted. In this two-way combination, the EC(50) values of apple extracts and Q3G were 2- and 4-fold lower, respectively, than those of apple extracts and Q3G alone. The combination index (CI) values at 50 and 95% inhibition rates were 0.76 +/- 0.16 and 0.42 +/- 0.10, respectively. The dose-reduction index (DRI) values of the apple extracts and Q3G to achieve a 50% inhibition effect were reduced by 2.03 +/- 0.55 and 4.28 +/- 0.39-fold, respectively. The results suggest that the apple extracts plus Q3G combination possesses a synergistic effect in MCF-7 cell proliferation.

In-vitro activity of ciprofloxacin combined with flomoxef against Bacteroides fragilis, compared with that of ciprofloxacin combined with clindamycin.

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Kato, Komei; Iwai, Shigetomi; Sato, Takeshi; Harada, Tomohide; Nakagawa, Yoshiteru; Iwanaga, Hitomi; Ito, Yumiko; Takayama, Tadatoshi

2002-06-01

Using checkerboard and time-kill assays, the in-vitro activity of ciprofloxacin alone and in combination with flomoxef against clinical Bacteroides fragilis strains was evaluated. In addition, the microbiological efficacy of this combination was compared with that of ciprofloxacin plus clindamycin. In 88% of the 25 strains tested, the combination of ciprofloxacin plus flomoxef exhibited a synergistic or an additive effect, whereas only 56% of the 25 strains ( Pflomoxef was observed in all 7 strains. In conclusion, the combination of ciprofloxacin plus flomoxef is very active against B. fragilis, suggesting that this combination may be very useful in the treatment of aerobic and B. fragilis mixed infections, because ciprofloxacin has an expanded spectrum against aerobes.

Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus

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Karla Morán-Santibañez

2016-01-01

Full Text Available Sulfated polysaccharides (SPs extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera, Eisenia arborea, Pelvetia compressa, Ulva intestinalis, and Solieria filiformis were tested in this study in order to evaluate their effect on measles virus in vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation and low cytotoxicity (MTT assay at inhibitory concentrations. SPs from Eisenia arborea and Solieria filiformis showed the highest antiviral activities (confirmed by qPCR and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL of E. arborea and S. filiformis SPs, resp., which exhibited by far a higher inhibitory effect (96% syncytia reduction in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL of E. arborea and S. filiformis, resp.. Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents.

Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer

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Prestwich Robin

2011-06-01

Full Text Available Abstract Background Reovirus type 3 Dearing (T3D has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication. Methods The effects of reovirus and chemotherapy on in vitro cytotoxicity were investigated in PC3 and Du 145 cells and the interactions between agents were assessed by combination index analysis. An Annexin V/propidium iodide fluorescence-activated cell sorting-based assay was used to determine mode of cell death. The effects of reovirus and docetaxel administered as single agent or combination therapy were tested in vivo in a murine model. The effects of docetaxel and reovirus, alone and together, on microtubule stabilisation were investigated by Western blot analysis. Results Variable degrees of synergistic cytotoxicity were observed in PC3 and Du 145 cells exposed to live reovirus and several chemotherapy agents. Combination of reovirus infection with docetaxel exposure led to increased late apoptotic/necrotic cell populations. Reovirus/docetaxel combined therapy led to reduced tumour growth and increased survival in a PC3 tumour bearing mouse model. Microtubule stabilization was enhanced in PC3 cells treated with reovirus/docetaxel combined therapy compared to other reovirus/chemotherapy combinations. Conclusions The co

Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

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Laura Bedin Denardi

2015-03-01

Full Text Available In vitro interaction between tacrolimus (FK506 and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%, followed by that of the combination with ketoconazole (37%, against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%, itraconazole (73%, voriconazole (63% and fluconazole (60%. The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

Anti-tumor effect of cisplatin in human oral squamous cell carcinoma was enhanced by andrographolide via upregulation of phospho-p53 in vitro and in vivo.

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Chen, Songjie; Hu, Hui; Miao, Shushu; Zheng, Jiayong; Xie, Zhijian; Zhao, Hui

2017-05-01

Oral squamous cell carcinoma is one of the most common neoplasm in the world. Despite the improvements in diagnosis and treatment, the outcome is still poor now. Thus, the development of novel therapeuticapproaches is needed. The aim of this study is to assess the synergistic anti-tumor effect of andrographolide with cisplatin (DDP) in oral squamous cell carcinoma CAL-27 cells in vitro and in vivo. We performed Cell Counting Kit-8 proliferation assay, apoptosis assay, and western blotting on CAL-27 cells treated with andrographolide, DDP or the combination in vitro. In vivo, we also treated CAL-27 xenografts with andrographolide or the combination, and performed terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay and immunohistochemical analysis of Ki-67. The results showed the combination of andrographolide and DDP synergistically inhibited CAL-27 cell proliferation in vitro and caused tumor regression in vivo in the CAL-27 xenografts. In addition, the synergistic anti-tumor effect of andrographolide with synergistic was due to an enhanced apoptosis. Moreover, the combination therapy upregulated the expression level of p-p53 in vitro and decreased Ki-67 expression in vivo. Our data indicate that the combination treatment of andrographolide and DDP results in synergistic anti-tumor growth activity against oral squamous cell carcinoma CAL-27 in vitro and in vivo. These results demonstrated that combination of andrographolide with DDP was likely to represent a potential therapeutic strategy for oral squamous cell carcinoma.

Enhanced antitumor activity of 3-bromopyruvate in combination with rapamycin in vivo and in vitro.

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Zhang, Qi; Pan, Jing; Lubet, Ronald A; Komas, Steven M; Kalyanaraman, Balaraman; Wang, Yian; You, Ming

2015-04-01

3-Bromopyruvate (3-BrPA) is an alkylating agent and a well-known inhibitor of energy metabolism. Rapamycin is an inhibitor of the serine/threonine protein kinase mTOR. Both 3-BrPA and rapamycin show chemopreventive efficacy in mouse models of lung cancer. Aerosol delivery of therapeutic drugs for lung cancer has been reported to be an effective route of delivery with little systemic distribution in humans. In this study, 3-BrPA and rapamycin were evaluated in combination for their preventive effects against lung cancer in mice by aerosol treatment, revealing a synergistic ability as measured by tumor multiplicity and tumor load compared treatment with either single-agent alone. No evidence of liver toxicity was detected by monitoring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. To understand the mechanism in vitro experiments were performed using human non-small cell lung cancer (NSCLC) cell lines. 3-BrPA and rapamycin also synergistically inhibited cell proliferation. Rapamycin alone blocked the mTOR signaling pathway, whereas 3-BrPA did not potentiate this effect. Given the known role of 3-BrPA as an inhibitor of glycolysis, we investigated mitochondrial bioenergetics changes in vitro in 3-BrPA-treated NSCLC cells. 3-BrPA significantly decreased glycolytic activity, which may be due to adenosine triphosphate (ATP) depletion and decreased expression of GAPDH. Our results demonstrate that rapamycin enhanced the antitumor efficacy of 3-BrPA, and that dual inhibition of mTOR signaling and glycolysis may be an effective therapeutic strategy for lung cancer chemoprevention. ©2015 American Association for Cancer Research.

A synergistic effect of artocarpanone from Artocarpus heterophyllus L. (Moraceae) on the antibacterial activity of selected antibiotics and cell membrane permeability.

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Septama, Abdi Wira; Xiao, Jianbo; Panichayupakaranant, Pharkphoom

2017-01-01

Artocarpanone isolated from Artocarpus heterophyllus L. (Moraceae) exhibits antibacterial activity. The present study investigated synergistic activity between artocarpanone and tetracycline, ampicillin, and norfloxacin, respectively, against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Escherichia coli . A broth microdilution method was used for evaluating antibacterial susceptibility. Synergistic effects were identified using a checkerboard method, and a bacterial cell membrane disruption was investigated by assay of released 260 nm absorbing materials following bacteriolysis. Artocarpanone exhibited weak antibacterial activity against MRSA and P. aeruginosa with minimum inhibitory concentrations values of 125 and 500 μg/mL, respectively. However, the compound showed strong antibacterial activity against E. coli (7.8 μg/mL). The interaction between artocarpanone and all tested antibiotics revealed indifference and additive effects against P. aeruginosa and E. coli (fractional inhibitory concentration index [FICI] values of 0.75-1.25). The combination of artocarpanone (31.2 μg/mL) and norfloxacin (3.9 μg/mL) resulted in synergistic antibacterial activity against MRSA, with an FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time-kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, the combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. These findings suggest that artocarpanone may be used to enhance the antibacterial activity of norfloxacin against MRSA.

Evaluation of synergistic activity of bovine lactoferricin with antibiotics in corneal infection.

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Oo, Thein Zaw; Cole, Nerida; Garthwaite, Linda; Willcox, Mark D P; Zhu, Hua

2010-06-01

The objectives of this study were to determine whether a synergistic effect could be obtained in vitro between bovine lactoferricin (B-LFcin) and antibiotics against Pseudomonas aeruginosa and Staphylococcus aureus isolates from ocular infections, and to evaluate the use of B-LFcin as an adjunct to the antibiotic treatment of corneal infection in vivo. Chequerboard and time-kill assays were performed to investigate the combined effects of B-LFcin and conventional antibiotics, including ciprofloxacin, ceftazidime and gentamicin, against 17 strains of P. aeruginosa (8) and S. aureus (9) isolated from ocular infection and inflammation, and 1 reference strain of S. aureus. Corneas of C57BL/6 mice were topically challenged with a multidrug-resistant strain of P. aeruginosa. Nine hours post-challenge, mice were treated topically and hourly with either vehicle, B-LFcin, ciprofloxacin or ciprofloxacin containing B-LFcin for 8 h. Corneas were then clinically examined, and bacterial numbers and levels of myeloperoxidase (MPO) evaluated. Synergy between B-LFcin and ciprofloxacin or ceftazidime was identified in most P. aeruginosa isolates, including multidrug-resistant strains, whereas no synergistic effect was seen between B-LFcin and gentamicin. Synergy was only observed with B-LFcin and ciprofloxacin against 2/10 S. aureus strains, and there was no synergy between B-LFcin and any of the other antibiotics tested. Combined B-LFcin and ciprofloxacin treatment significantly improved the clinical outcome, and reduced bacterial numbers and MPO in infected mouse corneas. B-LFcin alone was also able to reduce levels of MPO in infected corneas. These findings indicate that B-LFcin may have advantages as an adjunct therapy with both antimicrobial and anti-inflammatory properties in the treatment of corneal infection.

In vitro synergistic effects of fisetin and norfloxacin against aquatic isolates of Serratia marcescens.

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Dong, Jing; Ruan, Jing; Xu, Ning; Yang, Yibin; Ai, Xiaohui

2016-01-01

Serratia marcescens is a common pathogenic bacterium that can cause infections in both humans and animals. It can cause a range of diseases, from slight wound infections to life-threatening bacteraemia and pneumonia. The emergence of antimicrobial resistance has limited the treatment of the diseases caused by the bacterium to a great extent. Consequently, there is an urgent need to develop novel antimicrobial strategies against this pathogen. Synergistic strategy is a new approach to treat the infections caused by drug-resistant bacteria. In this paper, we isolated and identified the first multi-resistant pathogenic Serratia marcescens strain from diseased soft-shelled turtles (Pelodiscus sinensis) in China. We then performed a checkerboard assay; the results showed that out of 10 tested natural products fisetin had synergistic effects against S. marcescens when combined with norfloxacin. The time-kill curve assay further confirmed the results of the checkerboard assay. We found that this novel synergistic effect could significantly reduce the dosage of norfloxacin against S. marcescens. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simple method for assembly of CRISPR synergistic activation mediator gRNA expression array.

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Vad-Nielsen, Johan; Nielsen, Anders Lade; Luo, Yonglun

2018-05-20

When studying complex interconnected regulatory networks, effective methods for simultaneously manipulating multiple genes expression are paramount. Previously, we have developed a simple method for generation of an all-in-one CRISPR gRNA expression array. We here present a Golden Gate Assembly-based system of synergistic activation mediator (SAM) compatible CRISPR/dCas9 gRNA expression array for the simultaneous activation of multiple genes. Using this system, we demonstrated the simultaneous activation of the transcription factors, TWIST, SNAIL, SLUG, and ZEB1 a human breast cancer cell line. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of bioelectrical activity of synergistic muscles during pelvic floor muscles activation in postmenopausal women with and without stress urinary incontinence: a preliminary observational study

Directory of Open Access Journals (Sweden)

Ptaszkowski K

2015-09-01

Full Text Available Kuba Ptaszkowski,1 Małgorzata Paprocka-Borowicz,2 Lucyna Słupska,2 Janusz Bartnicki,1,3 Robert Dymarek,4 Joanna Rosińczuk,4 Jerzy Heimrath,5 Janusz Dembowski,6 Romuald Zdrojowy6 1Department of Obstetrics, 2Department of Clinical Biomechanics and Physiotherapy in Motor System Disorders, Wroclaw Medical University, Wroclaw, Poland; 3Department of Obstetrics and Gynecology, Health Center Bitterfeld/Wolfen gGmbH, Bitterfeld-Wolfen, Germany; 4Department of Nervous System Diseases, 5Department of Gynaecology and Obstetrics, Faculty of Health Science, 6Department and Clinic of Urology, Faculty of Postgraduate Medical Training, Wroclaw Medical University, Wroclaw, Poland Objective: Muscles such as adductor magnus (AM, gluteus maximus (GM, rectus abdominis (RA, and abdominal external and internal oblique muscles are considered to play an important role in the treatment of stress urinary incontinence (SUI, and the relationship between contraction of these muscles and pelvic floor muscles (PFM has been established in previous studies. Synergistic muscle activation intensifies a woman’s ability to contract the PFM. In some cases, even for continent women, it is not possible to fully contract their PFM without involving the synergistic muscles. The primary aim of this study was to assess the surface electromyographic activity of synergistic muscles to PFM (SPFM during resting and functional PFM activation in postmenopausal women with and without SUI.Materials and methods: This study was a preliminary, prospective, cross-sectional observational study and included volunteers and patients who visited the Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Forty-two patients participated in the study and were screened for eligibility criteria. Thirty participants satisfied the criteria and were categorized into two groups: women with SUI (n=16 and continent women (n=14. The bioelectrical activity of PFM and SPFM (AM, RA, GM was

Epilobi Hirsuti Herba Extracts Influence the In Vitro Activity of Common Antibiotics on Standard Bacteria

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Pirvu Lucia

2016-01-01

Full Text Available Epilobium genus has been confirmed as an effective source of natural antimicrobials. However, the influence of Epilobi hirsuti herba derived products on usual antibiotics activity has not been studied. In this study, several standardized Epilobi hirsuti herba extracts (EHE were evaluated in order to asses their potential effects on usual antibiotics tested on standard Gram-positive and Gram-negative bacterial strains in vitro. The results emphasized that the bacterial strains ranged from sensitive (MIC values between 50–200 μg GAE mL-1 (S. epidermidis ATCC 12228 to very resistant (E. coli strains, E. faecalis ATCC 29212 being practically immune to EHE. In terms of synergistic interaction, Tetracycline and Ampicillin combinations lead to the most important stimulatory effects, the diameters of the inhibition zone being even 60% bigger compared to the antibiotic alone. Synergistic effects between myricetin(galloyl derivates and Tetracycline were also revealed on P. aeruginosa and E. coli strains. Together, it clearly demonstrated not only EHE’s own antimicrobial properties, but also their capacity to influence the antimicrobial potency of some common antibiotics. These results could be useful for the area of herbal medicines and as potential candidates in managing microbial resistance, but also for physicians and pharmacists using combined antibacterial therapy.

The amino acid sequences and activities of synergistic hemolysins from Staphylococcus cohnii.

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Mak, Pawel; Maszewska, Agnieszka; Rozalska, Malgorzata

2008-10-01

Staphylococcus cohnii ssp. cohnii and S. cohnii ssp. urealyticus are a coagulase-negative staphylococci considered for a long time as unable to cause infections. This situation changed recently and pathogenic strains of these bacteria were isolated from hospital environments, patients and medical staff. Most of the isolated strains were resistant to many antibiotics. The present work describes isolation and characterization of several synergistic peptide hemolysins produced by these bacteria and acting as virulence factors responsible for hemolytic and cytotoxic activities. Amino acid sequences of respective hemolysins from S. cohnii ssp. cohnii (named as H1C, H2C and H3C) and S. cohnii ssp. urealyticus (H1U, H2U and H3U) were identical. Peptides H1 and H3 possessed significant amino acid homology to three synergistic hemolysins secreted by Staphylococcus lugdunensis and to putative antibacterial peptide produced by Staphylococcus saprophyticus ssp. saprophyticus. On the other hand, hemolysin H2 had a unique sequence. All isolated peptides lysed red cells from different mammalian species and exerted a cytotoxic effect on human fibroblasts.

Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.

Science.gov (United States)

Lin, Ming-Te; Lin, Chia-Liang; Lin, Tzu-Yu; Cheng, Chun-Wen; Yang, Shun-Fa; Lin, Chu-Liang; Wu, Chih-Chien; Hsieh, Yi-Hsien; Tsai, Jen-Pi

2016-05-01

Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.

Potential synergistic effects of human placental extract and minoxidil on hair growth-promoting activity in C57BL/6J mice.

Science.gov (United States)

Kwon, T-R; Oh, C T; Park, H M; Han, H J; Ji, H J; Kim, B J

2015-08-01

Human placenta extract (HPE) has been used to alleviate tiredness and promote wound healing, and for its antiageing functions; however, it has not yet been studied for its effects on hair growth. In the present study, we evaluated the in vitro effect of HPE on hair growth by observing its actions on human dermal papilla cells (DPCs). To define how HPE promotes induction of anagen hair growth during the telogen phase, and to understand the synergistic molecular mechanisms of HPE and minoxidil (MXD) actions on hair growth. We examined the effects of HPE and MXD on C57BL6/J mice using haematoxylin and eosin staining, quantitative histomorphometry, hair growth scoring, immunohistochemistry and immunofluorescence on the dorsal skins of C57BL/6J mice. We found that HPE synergistically augmented the effects of MXD, a promoter of hair growth. In particular, histomorphometric analysis data indicated that subcutaneous injection of HPE induced an earlier anagen phase and prolonged the anagen phase. It also stimulated increases in both the number and size of hair follicles in groups treated with HPE alone and HPE + MXD. From our data, we conclude that HPE increases β-catenin and Wnt3a expression levels. Overall, our findings suggest that HPE in combination with MXD has hair growth-promoting activity and is a potential novel therapeutic treatment for alopecia or baldness in humans. © 2015 British Association of Dermatologists.

Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1

International Nuclear Information System (INIS)

Oiwa, Ako; Kakizawa, Tomoko; Miyamoto, Takahide; Yamashita, Koh; Jiang, Wei; Takeda, Teiji; Suzuki, Satoru; Hashizume, Kiyoshi

2007-01-01

Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as a repressor for wide variety of nuclear hormone receptors. We demonstrated here that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian clock components, bound to E-box (CACGTG), and stimulated the promoter activity by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated promoter activity, but strongly repressed the synergistic activation of CLOCK-BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of direct protein-protein interaction between LRH-1 and CLOCK. In summary, this study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene to generate the circadian oscillation. The cyclic expression of mSHP may affect daily activity of other nuclear receptors and contribute to circadian liver functions

Effects of Polysaccharides from Platycodon grandiflorum on Immunity-Enhancing Activity In Vitro

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Xiaona Zhao

2017-11-01

Full Text Available The study is aimed at investigating the immunoenhancement activity of polysaccharides from Platycodon grandiflorum polysaccharides (PGPSs in vitro. In this study, some research on lymphocyte proliferation, cell cycle, and the levels of CD4+ and CD8+ T cells were performed. Four different concentrations of PGPSs (PGPStc, PGPS60c, PGPS80c, and PGPStp were harvested and added to peripheral blood T lymphocytes. We observed significant increases in T lymphocyte proliferation at PGPStc groups individually or synergistically with phytohemagglutinin (PHA at most concentrations, and their lymphocyte proliferation rates were the highest. The active sites of PGPStc and PGPS60c were subsequently chosen. Then, we utilized flow cytometry to determine lymphocyte cell cycle distribution and levels of CD4+ and CD8+ T cells. At most time points, PGPStc could facilitate lymphocyte cell cycle progression from the G0/G1 phase to the S and G2/M phases and, simultaneously, increase the levels of CD4+ and CD8+ T cells. These results indicate that PGPStc enhances the immune functions, suggesting that PGPStc could be a potential immunopotentiator for further in vivo and clinical trial experiments.

In vitro activity of flomoxef and cefazolin in combination with vancomycin.

Science.gov (United States)

Simon, C; Simon, M

1991-01-01

207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

Increased incidence of urolithiasis and bacteremia during Proteus mirabilis and Providencia stuartii coinfection due to synergistic induction of urease activity.

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Armbruster, Chelsie E; Smith, Sara N; Yep, Alejandra; Mobley, Harry L T

2014-05-15

Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI.

A Cumulative Spore Killing Approach: Synergistic Sporicidal Activity of Dilute Peracetic Acid and Ethanol at Low pH Against Clostridium difficile and Bacillus subtilis Spores.

Science.gov (United States)

Nerandzic, Michelle M; Sankar C, Thriveen; Setlow, Peter; Donskey, Curtis J

2016-01-01

Background.  Alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with pH 1.5-2 that were as effective as soap and water washing in reducing levels of C difficile spores on hands. We hypothesized that the addition of dilute peracetic acid (PAA) to acidified ethanol would enhance sporicidal activity while allowing elevation of the pH to a level likely to be well tolerated on skin (ie, >3). Methods.  We tested the efficacy of acidified ethanol solutions alone or in combination with PAA against C difficile and Bacillus subtilis spores in vitro and against nontoxigenic C difficile spores on hands of volunteers. Results.  Acidification of ethanol induced rapid sporicidal activity against C difficile and to a lesser extent B subtilis. The addition of dilute PAA to acidified ethanol resulted in synergistic enhancement of sporicidal activity in a dose-dependent fashion in vitro. On hands, the addition of 1200-2000 ppm PAA enhanced the effectiveness of acidified ethanol formulations, resulting in formulations with pH >3 that were as effective as soap and water washing. Conclusions.  Acidification and the addition of dilute PAA induced rapid sporicidal activity in ethanol. Our findings suggest that it may be feasible to develop effective sporicidal ethanol formulations that are safe and tolerable on skin.

Antioxidant, antimicrobial and synergistic activities of tea polyphenols

African Journals Online (AJOL)

Microbial resistance to antibiotics has become an increasing global problem and there is a need to find out novel potent antimicrobial agents with alternative modes of action as accessories to antibiotic therapy. This study investigated the antioxidant, antimicrobial and synergistic properties of tea polyphenols. The tea ...

Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model.

Science.gov (United States)

Wei, Wenjuan; Yang, Haifei; Hu, Lifen; Ye, Ying; Li, Jiabin

2017-12-01

Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB) and the lack of novel agents. Although recent data suggest that levofloxacin (LVX) may have unique activity against MDR-AB in combination with colistin (CST), further preclinical work is needed. We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115) of MDR-AB to investigate the in vitro and in vivo efficacy of LVX-CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time-kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied in vitro. A simple invertebrate model (Galleria mellonella) has been used to assess the in vivo activity of antimicrobial therapies. The LVX-CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624). In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p < 0.05). In summary, a synergistic or additive effect between CST and LVX was observed in vitro and in vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones. Copyright © 2015. Published by Elsevier B.V.

Synergistic effects of hollow structure and surface fluorination on the photocatalytic activity of titania

International Nuclear Information System (INIS)

Lv Kangle; Yu Jiaguo; Deng Kejian; Sun Jie; Zhao Yanxi; Du Dongyun; Li Mei

2010-01-01

To study the synergistic effects of hollow structure and surface fluorination on the photoactivity of TiO 2 , TiO 2 hollow microspheres were synthesized by a hydrolysis-precipitate method using sulfonated polystyrene (PS) as templates and tetrabutylorthotitanate (TBOT) as precursor, and then calcined at 500 o C for 2 h. The calcined samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and N 2 sorption. Photocatalytic activity was evaluated using reactive brilliant red X3B, an anionic organic dye, as a model pollutant in water. The results show that the photocatalytic activity of TiO 2 hollow microspheres is significantly higher than that of TiO 2 nanoparticles prepared in the same experimental conditions. At pH 7 and 3, the apparent rate constants of the former exceed that of the latter by a factor of 3.38 and 3.15, respectively. After surface fluorination at pH 3, the photoactivity of hollow microspheres and nanoparticles further increases for another 1.61 and 2.19 times, respectively. The synergistic effect of surface fluorination and hollow structure can also be used to prepare other highly efficient photocatalyst.

Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections.

Science.gov (United States)

Wang, Yao; Ding, Xiali; Chen, Yuan; Guo, Mingquan; Zhang, Yan; Guo, Xiaokui; Gu, Hongchen

2016-09-01

Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Controlled synthesis of ordered mesoporous TiO{sub 2}-supported on activated carbon and pore-pore synergistic photocatalytic performance

Energy Technology Data Exchange (ETDEWEB)

Liu, Chen; Li, Youji, E-mail: bcclyj@163.com; Xu, Peng; Li, Ming; Zeng, Mengxiong

2015-01-15

Ordered mesoporous titania/activated carbon (OMTAC) were prepared by the template technique with the aid of an ultrasonic method. To explore the relationship between the structure and properties of OMTAC, the ultrasonic-sol-gel technique was applied to synthesize titania dioxide/activated carbon (USTAC). The obtained material structure was characterized by X-ray diffraction (XRD), nitrogen adsorption – desorption, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance (DRS) and Photoluminescence (PL) emission spectra. OMTAC photocatalytic performance was evaluated by means of acid red B (ARB) degradation. The pore-pore synergistic amplification mechanism of photocatalysis was proposed and the effects of catalytic conditions on synergistic amplification were explored. The results show that compared to OMT, OMTAC has a small particle size, low electron-hole recombination rate and high surface areas, due to the hindering effect of activated carbon on crystalline grain growth and an ordered mesoporous structure of titania. OMTAC has higher catalytic activity than USTAC, OMT and P25, due to pore-pore synergistic amplification effect of photocatalysis. The OMT content is strongly affected OMTAC photocatalytic activity, and OMTAC-3 (loading 3 times of OMT on AC) has the highest photocatalytic activity due to high hydroxyl concentration, surface area and low electron-hole recombination rate. When ARB is degraded by OMTAC-3, the optimum catalytic conditions are a catalyst concentration of 1 g/L, an ARB concentration of 15 mg/L and a pH of 5. - Graphical abstract: We investigate the influence of mesoporous titania content upon the photocatalytic performance of OMTAC in acid red B degradation. - Highlights: • OMTAC were fabricated by a template technique with the aid of an ultrasonic method. • OMTAC show high photoactivity for acid red B (ARB) degradation. • OMTAC also show pore-pore synergistic photocatalytic

Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

International Nuclear Information System (INIS)

Kammerer, Cornelia; Getoff, Nikola

2001-01-01

Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N 2 O (converting e aq - into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N 2 O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e aq - , H and OH- species with aspirin were also determined

Cytostatic action of aspirin and its effect on mitomycin C activity. A study in vitro under irradiation

Energy Technology Data Exchange (ETDEWEB)

Kammerer, Cornelia; Getoff, Nikola E-mail: nikola.getoff@univie.ac.at

2001-04-01

Experiments in vitro using E. coli bacteria (AB 1157) proved that aspirin possesses a cytostatic ability under various experimental condition (pH=7.4) in airfree, aerated as well as in media containing N{sub 2}O (converting e{sub aq}{sup -} into OH- radicals). In the last case the highest effect of aspirin was observed. The combination of aspirin with the well-known cytostaticum, mitomycin C (MMC) leads in airfree as well as in aerated media to a significant decrease of the MMC activity. However, the mixture of aspirin and MMC in the presence of N{sub 2}O causes a synergistic effect, resulting in an enhancement of the MMC activity by a factor of 1.5. Probable reaction steps are presented and discussed. Using the pulse radiolysis method the rate constants for the reactions of e{sub aq}{sup -}, H and OH- species with aspirin were also determined.

Studying the synergistic damage effects induced by 1.8 GHz radiofrequency field radiation (RFR) with four chemical mutagens on human lymphocyte DNA using comet assay in vitro

International Nuclear Information System (INIS)

Wang Baohong; He Jiliang; Jin Lifen; Lu Deqiang; Zheng Wei; Lou Jianlin; Deng Hongping

2005-01-01

The aim of this investigation was to study the synergistic DNA damage effects in human lymphocytes induced by 1.8 GHz radiofrequency field radiation (RFR, SAR of 3 W/kg) with four chemical mutagens, i.e. mitomycin C (MMC, DNA crosslinker), bleomycin (BLM, radiomimetic agent), methyl methanesulfonate (MMS, alkylating agent), and 4-nitroquinoline-1-oxide (4NQO, UV-mimetic agent). The DNA damage of lymphocytes exposed to RFR and/or with chemical mutagens was detected at two incubation time (0 or 21 h) after treatment with comet assay in vitro. Three combinative exposure ways were used. Cells were exposed to RFR and chemical mutagens for 2 and 3 h, respectively. Tail length (TL) and tail moment (TM) were utilized as DNA damage indexes. The results showed no difference of DNA damage indexes between RFR group and control group at 0 and 21 h incubation after exposure (P > 0.05). There were significant difference of DNA damage indexes between MMC group and RFR + MMC co-exposure group at 0 and 21 h incubation after treatment (P 0.05). The experimental results indicated 1.8 GHz RFR (SAR, 3 W/kg) for 2 h did not induce the human lymphocyte DNA damage effects in vitro, but could enhance the human lymphocyte DNA damage effects induced by MMC and 4NQO. The synergistic DNA damage effects of 1.8 GHz RFR with BLM or MMS were not obvious

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-γ ligand, rosiglitazone

International Nuclear Information System (INIS)

Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki; Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru

2010-01-01

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-α, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPARα ligand, bezafibrate, and a PPARγ ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPARγ, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-α-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists

Science.gov (United States)

Urso, Loredana; Biasini, Lorena; Zago, Giulia; Calabrese, Fiorella; Conte, Pier Franco; Ciminale, Vincenzo; Pasello, Giulia

2017-01-01

Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL. In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs. In vivo studies were conducted on a sarcomatoid MPM mouse model. In all the cell lines tested (with the exception of ZL55, which carries a biallelic loss-of-function mutation of p53), Nutlin 3a enhanced p21, MDM2 and DR5 expression, and decreased survivin expression. These changes were associated to cell cycle arrest but not to a significant induction of apoptosis. A synergistic pro-apoptotic effect was obtained through the association of rhTRAIL in all the cell lines harboring functional p53. This synergistic interaction of MDM2 inhibitor and TRAIL agonist was confirmed using a mouse preclinical model. Our results suggest that the combined targeting of MDM2 and TRAIL might provide a novel therapeutic option for treatment of MPM patients, particularly in the case of sarcomatoid MPM with MDM2 overexpression and functional inactivation of wild-type p53. PMID:28562336

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

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Shang Weihu

2011-12-01

Full Text Available Abstract Background Botanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU. Methods Components of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA. Results TC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI TC extract did not affect the pharmacokinetics of 5-FU in rats. Conclusions The combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.

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Gadjeva, V; Koldamova, R

2001-01-01

A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

The In Vitro Antimicrobial Activity of Lavandula angustifolia Essential Oil in Combination with Other Aroma-Therapeutic Oils

Science.gov (United States)

de Rapper, Stephanie; Kamatou, Guy; Viljoen, Alvaro

2013-01-01

The antimicrobial activity of Lavandula angustifolia essential oil was assessed in combination with 45 other oils to establish possible interactive properties. The composition of the selected essential oils was confirmed using GC-MS with a flame ionization detector. The microdilution minimum inhibitory concentration (MIC) assay was undertaken, whereby the fractional inhibitory concentration (ΣFIC) was calculated for the oil combinations. When lavender oil was assayed in 1 : 1 ratios with other oils, synergistic (26.7%), additive (48.9%), non-interactive (23.7%), and antagonistic (0.7%) interactions were observed. When investigating different ratios of the two oils in combination, the most favourable interactions were when L. angustifolia was combined with Cinnamomum zeylanicum or with Citrus sinensis, against C. albicans and S. aureus, respectively. In 1 : 1 ratios, 75.6% of the essential oils investigated showed either synergistic or additive results, lending in vitro credibility to the use of essential oil blends in aroma-therapeutic practices. Within the field of aromatherapy, essential oils are commonly employed in mixtures for the treatment of infectious diseases; however, very little evidence exists to support the use in combination. This study lends some credence to the concomitant use of essential oils blended with lavender. PMID:23737850

The In Vitro Antimicrobial Activity of Lavandula angustifolia Essential Oil in Combination with Other Aroma-Therapeutic Oils

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Stephanie de Rapper

2013-01-01

Full Text Available The antimicrobial activity of Lavandula angustifolia essential oil was assessed in combination with 45 other oils to establish possible interactive properties. The composition of the selected essential oils was confirmed using GC-MS with a flame ionization detector. The microdilution minimum inhibitory concentration (MIC assay was undertaken, whereby the fractional inhibitory concentration (ΣFIC was calculated for the oil combinations. When lavender oil was assayed in 1 : 1 ratios with other oils, synergistic (26.7%, additive (48.9%, non-interactive (23.7%, and antagonistic (0.7% interactions were observed. When investigating different ratios of the two oils in combination, the most favourable interactions were when L. angustifolia was combined with Cinnamomum zeylanicum or with Citrus sinensis, against C. albicans and S. aureus, respectively. In 1 : 1 ratios, 75.6% of the essential oils investigated showed either synergistic or additive results, lending in vitro credibility to the use of essential oil blends in aroma-therapeutic practices. Within the field of aromatherapy, essential oils are commonly employed in mixtures for the treatment of infectious diseases; however, very little evidence exists to support the use in combination. This study lends some credence to the concomitant use of essential oils blended with lavender.

Synergistic use of active and passive microwave in soil moisture estimation

Science.gov (United States)

O'Neill, P.; Chauhan, N.; Jackson, T.; Saatchi, S.

1992-01-01

Data gathered during the MACHYDRO experiment in central Pennsylvania in July 1990 have been utilized to study the synergistic use of active and passive microwave systems for estimating soil moisture. These data sets were obtained during an eleven-day period with NASA's Airborne Synthetic Aperture Radar (AIRSAR) and Push-Broom Microwave Radiometer (PBMR) over an instrumented watershed which included agricultural fields with a number of different crop covers. Simultaneous ground truth measurements were also made in order to characterize the state of vegetation and soil moisture under a variety of meteorological conditions. A combination algorithm is presented as applied to a representative corn field in the MACHYDRO watershed.

Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: structure-activity relationship and synergistic potential.

Science.gov (United States)

Ben Hmidene, Asma; Smaoui, Abderrazak; Abdelly, Chedly; Isoda, Hiroko; Shigemori, Hideyuki

2017-03-01

O-Methylated and glucuronosylated flavonoids were isolated from Tamarix gallica as α-glucosidase inhibitors. Structure-activity relationship of these flavonoids suggests that catechol moiety and glucuronic acid at C-3 are factors in the increase in α-glucosidase inhibitory activity. Furthermore, rhamnetin, tamarixetin, rhamnazin, KGlcA, KGlcA-Me, QGlcA, and QGlcA-Me exhibit synergistic potential when applied with a very low concentration of acarbose to α-glucosidase from rat intestine.

Antifungal activity of secondary plant metabolites from potatoes (Solanum tuberosum L.): Glycoalkaloids and phenolic acids show synergistic effects.

Science.gov (United States)

Sánchez-Maldonado, A F; Schieber, A; Gänzle, M G

2016-04-01

To study the antifungal effects of the potato secondary metabolites α-solanine, α-chaconine, solanidine and caffeic acid, alone or combined. Resistance to glycoalkaloids varied among the fungal species tested, as derived from minimum inhibitory concentrations assays. Synergistic antifungal activity between glycoalkaloids and phenolic compounds was found. Changes in the fluidity of fungal membranes caused by potato secondary plant metabolites were determined by calculation of the generalized polarization values. The results partially explained the synergistic effect between caffeic acid and α-chaconine and supported findings on membrane disruption mechanisms from previous studies on artificial membranes. LC/MS analysis was used to determine variability and relative amounts of sterols in the different fungal species. Results suggested that the sterol pattern of fungi is related to their resistance to potato glycoalkaloids and to their taxonomy. Fungal resistance to α-chaconine and possibly other glycoalkaloids is species dependent. α-Chaconine and caffeic acid show synergistic antifungal activity. The taxonomic classification and the sterol pattern play a role in fungal resistance to glycoalkaloids. Results improve the understanding of the antifungal mode of action of potato secondary metabolites, which is essential for their potential utilization as antifungal agents in nonfood systems. © 2016 The Society for Applied Microbiology.

Synergistic mosquito-repellent activity of Curcuma longa, Pogostemon heyneanus and Zanthoxylum limonella essential oils.

Science.gov (United States)

Das, N G; Dhiman, Sunil; Talukdar, P K; Rabha, Bipul; Goswami, Diganta; Veer, Vijay

2015-01-01

Mosquito repellents play an important role in preventing man-mosquito contact. In the present study, we evaluated the synergistic mosquito-repellent activity of Curcuma longa, Pogostemon heyneanus and Zanthoxylum limonella essential oils. The mosquito repellent efficacies of three essential oils were evaluated separately and in combination under laboratory and field conditions. N,N-Diethylphenylacetamide (DEPA) and dimethylphthalate (DMP) were used for comparison of the protection time of the mixture of essential oils. At an optimum concentration of 20%, the essential oils of C. longa, Z. limonella and P. heyneanus provided complete protection times (CPTs) of 96.2, 91.4 and 123.4 min, respectively, against Aedes albopictus mosquitoes in the laboratory. The 1:1:2 mixture of the essential oils provided 329.4 and 391.0 min of CPT in the laboratory and field trials, respectively. The percent increases in CPTs for the essential oil mixture were 30 for DMP and 55 for N,N-diethylphenylacetamide (DEPA). The synergistic repellent activity of the essential oils used in the present study might be useful for developing safer alternatives to synthetic repellents for personal protection against mosquitoes. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Trimethoprim in vitro antibacterial activity is not increased by adding sulfamethoxazole for pediatric Escherichia coli urinary tract infection.

Science.gov (United States)

Nguyen, Hiep T; Hurwitz, Richard S; Defoor, W Robert; Minevich, Eugene; McAdam, Alexander J; Mortensen, Joel E; Novak-Weekley, Susan M; Minnillo, Brian J; Elder, Jack S

2010-07-01

The combination of trimethoprim/sulfamethoxazole is often used to treat uncomplicated urinary tract infections in children. The rationale for combining trimethoprim and sulfamethoxazole is that they may act synergistically to increase antibacterial activity. However, approximately 3% of patients show allergic reactions to sulfamethoxazole, of which some are serious (liver failure and Stevens-Johnson syndrome). We determined whether adding sulfamethoxazole is necessary to increase in vitro antibacterial activity for pediatric urinary tract infection compared to that of trimethoprim alone. We prospectively identified 1,298 children with urinary tract infection (greater than 100,000 cfu/ml Escherichia coli) from a total of 4 American regions. In vitro susceptibility of bacterial isolates to sulfamethoxazole, trimethoprim and trimethoprim/sulfamethoxazole was determined using disk diffusion. Ampicillin susceptibility was tested at 2 sites. At 1 site all uropathogens from consecutive urinary isolates were evaluated. E. coli susceptibility to trimethoprim was 70%, comparable to the 70% of trimethoprim/sulfamethoxazole (p = 0.9) and higher than the 56.9% of sulfamethoxazole (p trimethoprim was significantly higher than to ampicillin. At 1 site the susceptibility of other uropathogens to trimethoprim and trimethoprim/sulfamethoxazole was similar to that of E. coli. In children with urinary tract infection in vitro susceptibility to trimethoprim was comparable to that to trimethoprim/sulfamethoxazole and significantly higher than to sulfamethoxazole. This finding was similar at all sites. Adding sulfamethoxazole appears unnecessary and may represent a risk to patients. Trimethoprim can be used as an alternative to trimethoprim/sulfamethoxazole based on in vitro antibacterial susceptibility. Routine trimethoprim/sulfamethoxazole use for urinary tract infection should be carefully reevaluated. Copyright (c) 2010 American Urological Association Education and Research, Inc

Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of Three Different Cyanobacterial Pigment Extracts

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Chetan Paliwal

2015-08-01

Full Text Available Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC50 values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± 1.57 mg·mg−1 DPPH and Lyngbya methanol (LM, 59.56 ± 37.38 mg·mg−1 DPPH extracts. Iso-bolographic analysis revealed most of the combinations of extracts were antagonistic to each other, although LM—Spirulina methanol (SM 1:1 had the highest synergistic rate of 86.65%. In vitro digestion studies showed that DPPH scavenging activity was considerably decreased in all extracts except for Pseudanabaena methanol (PM and LM after the simulated digestion. All of the extracts were effective in reducing the calcium oxalate crystal size by nearly 60%–65% compared to negative control, while PM and Spirulina water (SW extracts could inhibit both nucleation and aggregation of calcium oxalate by nearly 60%–80%.

Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM)

DEFF Research Database (Denmark)

Xiong, Kai; Zhou, Yan; Hyttel, Poul

2016-01-01

Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4...... a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes....

Increased Incidence of Urolithiasis and Bacteremia During Proteus mirabilis and Providencia stuartii Coinfection Due to Synergistic Induction of Urease Activity

Science.gov (United States)

Armbruster, Chelsie E.; Smith, Sara N.; Yep, Alejandra; Mobley, Harry L. T.

2014-01-01

Background. Catheter-associated urinary tract infections (CaUTIs) are the most common hospital-acquired infections worldwide and are frequently polymicrobial. The urease-positive species Proteus mirabilis and Providencia stuartii are two of the leading causes of CaUTIs and commonly co-colonize catheters. These species can also cause urolithiasis and bacteremia. However, the impact of coinfection on these complications has never been addressed experimentally. Methods. A mouse model of ascending UTI was utilized to determine the impact of coinfection on colonization, urolithiasis, and bacteremia. Mice were infected with P. mirabilis or a urease mutant, P. stuartii, or a combination of these organisms. In vitro experiments were conducted to assess growth dynamics and impact of co-culture on urease activity. Results. Coinfection resulted in a bacterial load similar to monospecies infection but with increased incidence of urolithiasis and bacteremia. These complications were urease-dependent as they were not observed during coinfection with a P. mirabilis urease mutant. Furthermore, total urease activity was increased during co-culture. Conclusions. We conclude that P. mirabilis and P. stuartii coinfection promotes urolithiasis and bacteremia in a urease-dependent manner, at least in part through synergistic induction of urease activity. These data provide a possible explanation for the high incidence of bacteremia resulting from polymicrobial CaUTI. PMID:24280366

Synergistic Efficacy of Aedes aegypti Antimicrobial Peptide Cecropin A2 and Tetracycline against Pseudomonas aeruginosa

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Zheng, Zhaojun; Tharmalingam, Nagendran; Liu, Qingzhong; Kim, Wooseong; Fuchs, Beth Burgwyn; Zhang, Rijun; Vilcinskas, Andreas

2017-01-01

ABSTRACT The increasing prevalence of antibiotic resistance has created an urgent need for alternative drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are promising candidates that could address the spread of multidrug-resistant bacteria, either alone or in combination with conventional antibiotics. We studied the antimicrobial efficacy and bactericidal mechanism of cecropin A2, a 36-residue α-helical cationic peptide derived from Aedes aegypti cecropin A, focusing on the common pathogen Pseudomonas aeruginosa. The peptide showed little hemolytic activity and toxicity toward mammalian cells, and the MICs against most clinical P. aeruginosa isolates were 32 to 64 μg/ml, and its MICs versus other Gram-negative bacteria were 2 to 32 μg/ml. Importantly, cecropin A2 demonstrated synergistic activity against P. aeruginosa when combined with tetracycline, reducing the MICs of both agents by 8-fold. The combination was also effective in vivo in the P. aeruginosa/Galleria mellonella model (P < 0.001). We found that cecropin A2 bound to P. aeruginosa lipopolysaccharides, permeabilized the membrane, and interacted with the bacterial genomic DNA, thus facilitating the translocation of tetracycline into the cytoplasm. In summary, the combination of cecropin A2 and tetracycline demonstrated synergistic antibacterial activity against P. aeruginosa in vitro and in vivo, offering an alternative approach for the treatment of P. aeruginosa infections. PMID:28483966

ANTIMICROBIAL AND SYNERGISTIC ACTIVITY OF INGREDIENTS OF BETEL QUID ON ORAL AND ENTERIC PATHOGENS

OpenAIRE

Niraj A Ghanwate; Prashant Thakare

2012-01-01

In this study, antimicrobial and synergistic activity of ingredients of betel quid i.e. kattha, lime, betel leaf, betel nut, cardamom, clove and fennel seeds was tested against microbial population of oral cavity and four enteric pathogens namely Staphylococcus aureus, Salmonella typhi, Escherichia coli and Shigell flexneri. For this purpose two methods were used. Pour plate method was used for calculating the reduction in microbial population in oral cavity and disk diffusion method was u...

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C

International Nuclear Information System (INIS)

Ferir, Geoffrey; Palmer, Kenneth E.; Schols, Dominique

2011-01-01

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4 + MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC 95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

Synergistic effects in threshold models on networks

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Juul, Jonas S.; Porter, Mason A.

2018-01-01

Network structure can have a significant impact on the propagation of diseases, memes, and information on social networks. Different types of spreading processes (and other dynamical processes) are affected by network architecture in different ways, and it is important to develop tractable models of spreading processes on networks to explore such issues. In this paper, we incorporate the idea of synergy into a two-state ("active" or "passive") threshold model of social influence on networks. Our model's update rule is deterministic, and the influence of each meme-carrying (i.e., active) neighbor can—depending on a parameter—either be enhanced or inhibited by an amount that depends on the number of active neighbors of a node. Such a synergistic system models social behavior in which the willingness to adopt either accelerates or saturates in a way that depends on the number of neighbors who have adopted that behavior. We illustrate that our model's synergy parameter has a crucial effect on system dynamics, as it determines whether degree-k nodes are possible or impossible to activate. We simulate synergistic meme spreading on both random-graph models and networks constructed from empirical data. Using a heterogeneous mean-field approximation, which we derive under the assumption that a network is locally tree-like, we are able to determine which synergy-parameter values allow degree-k nodes to be activated for many networks and for a broad family of synergistic models.

Synergistic activity of antibiotics combined with ivermectin to kill body lice.

Science.gov (United States)

Sangaré, Abdoul Karim; Rolain, Jean Marc; Gaudart, Jean; Weber, Pascal; Raoult, Didier

2016-03-01

Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a Parafilm™ membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P≤10(-3)), with a significant difference between groups in the production of nits (P=0.019, Kruskal-Wallis test). A high lethal effect of ivermectin alone (50ng/mL) was observed compared with the control group (log-rank test, P≤10(-3)). Fluorescence of bacteriocytes in lice treated with 20μg/mL doxycycline was lower than in untreated lice (PKruskal-Wallis test). In the second series with antibiotic-ivermectin combinations, a synergistic lethal effect on treated lice (log-rank test, PKruskal-Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log-rank test, P=0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-{gamma} ligand, rosiglitazone

Energy Technology Data Exchange (ETDEWEB)

Wakui, Yuta; Inoue, Jun [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan); Fukushima, Koji; Kondo, Yasuteru; Kakazu, Eiji; Obara, Noriyuki; Kimura, Osamu; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574 (Japan)

2010-05-28

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.

Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model

DEFF Research Database (Denmark)

Christensen, Louise; van Gennip, Maria; Jakobsen, Tim H

2012-01-01

Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended...

Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma

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Jeannot V

2016-11-01

apoptosis. The sorafenib and vorinostat combination sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent signaling pathways. These results showed that there was synergistic cytotoxicity when vorinostat was combined with gefitinib for both lung adenocarcinoma and hepatocarcinoma with mutant KRAS in vitro and in vivo but that the combination of vorinostat with sorafenib did not show any benefit. These findings highlight the important role of the IGF-1R/AKT pathway in the resistance to targeted therapies and support the use of histone deacetylase inhibitors in combination with EGFR-tyrosine kinase inhibitors, especially for treating patients with mutant KRAS resistant to other treatments. Keywords: targeted therapy, combined treatments, non-small cell lung cancer, hepatocarcinoma

Biochemical evaluation of interactions between synergistic molecules and phase I enzymes involved in insecticide resistance in B- and Q-type Bemisia tabaci (Hemiptera: Aleyrodidae).

Science.gov (United States)

Panini, Michela; Tozzi, Francesco; Zimmer, Christoph T; Bass, Chris; Field, Linda; Borzatta, Valerio; Mazzoni, Emanuele; Moores, Graham

2017-09-01

Metabolic resistance is an important consideration in the whitefly Bemisia tabaci, where an esterase-based mechanism has been attributed to pyrethroid resistance and over-expression of the cytochrome P450, CYP6CM1, has been correlated to resistance to imidacloprid and other neonicotinoids. In vitro interactions between putative synergists and CYP6CM1, B and Q-type esterases were investigated, and structure-activity relationship analyses allowed the identification of chemical structures capable of acting as inhibitors of esterase and oxidase activities. Specifically, methylenedioxyphenyl (MDP) moieties with a polyether chain were preferable for optimum inhibition of B-type esterase, whilst corresponding dihydrobenzofuran structures were potent for the Q-esterase variation. Potent inhibition of CYP6CM1 resulted from structures which contained an alkynyl chain with a terminal methyl group. Synergist candidates could be considered for field control of B. tabaci, especially to abrogate neonicotinoid resistance. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Evaluation of Bioelectrical Activity of Pelvic Floor Muscles and Synergistic Muscles Depending on Orientation of Pelvis in Menopausal Women with Symptoms of Stress Urinary Incontinence: A Preliminary Observational Study

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Tomasz Halski

2014-01-01

Full Text Available Objectives. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles (PFM and the synergistic muscles, depending on the orientation of the pelvis, in anterior (P1 and posterior (P2 pelvic tilt. Design. Preliminary, prospective observational study. Setting. Department and Clinic of Urology, University Hospital in Wroclaw, Poland. Participants. Thirty-two menopausal and postmenopausal women with stress urinary incontinence were recruited. Based on inclusion and exclusion criteria, sixteen women aged 55 to 70 years were enrolled in the study. Primary Outcome Measures. Evaluation of resting and functional bioelectrical activity of the pelvic floor muscles by electromyography (sEMG and vaginal probe. Secondary Outcome Measures. Evaluation of activity of the synergistic muscles by sEMG and surface electrodes. Results. No significant differences between orientations P1 and P2 were found in functional and resting sEMG activity of the PFM. During resting and functional PFM activity, higher electrical activity in P2 than in P1 has been recorded in some of the synergistic muscles. Conclusions. This preliminary study does not provide initial evidence that pelvic tilt influences PFM activation. Although different activity of synergistic muscles occurs in various orientations of the pelvic tilt, it does not have to affect the sEMG activity of the PFM.

Enhanced visible light-responsive photocatalytic activity of LnFeO3 (Ln = La, Sm) nanoparticles by synergistic catalysis

International Nuclear Information System (INIS)

Li, Li; Wang, Xiong; Zhang, Yange

2014-01-01

Highlights: • LnFeO 3 (Ln = La, Sm) nanoparticles were prepared by a facile sol–gel method. • The samples exhibit superior visible-light-responsive photocatalytic activity. • Synergistic effect will enhance the photodegradation of RhB under visible light. - Abstract: LnFeO 3 (Ln = La, Sm) nanoparticles were prepared by a facile sol–gel method with assistance of glycol at different calcination temperatures. The as-synthesized LnFeO 3 was characterized by X-ray diffraction, transmission electron microscopy, differential scanning calorimeter and thermogravimetric analysis, and UV–vis absorption spectroscopy. The photocatalytic behaviors of LnFeO 3 nanoparticles were evaluated by photodegradation of rhodamine B under visible light irradiation. The results indicate that the visible light-responsive photocatalytic activity of LnFeO 3 nanoparticles was enhanced remarkably by the synergistic effect between the semiconductor photocatalysis and Fenton-like reaction. And a possible catalytic mechanism was also proposed based on the experimental results

Herbicidal Activities of Some Allelochemicals and Their Synergistic Behaviors toward Amaranthus tricolor L.

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Nawasit Chotsaeng

2017-10-01

Full Text Available Seven allelochemicals, namely R-(+-limonene (A, vanillin (B, xanthoxyline (C, vanillic acid (D, linoleic acid (E, methyl linoleate (F, and (±-odorine (G, were investigated for their herbicidal activities on Chinese amaranth (Amaranthus tricolor L.. At 400 μM, xanthoxyline (C showed the greatest inhibitory activity on seed germination and seedling growth of the tested plant. Both vanillic acid (D and (±-odorine (G inhibited shoot growth, however, apart from xanthoxyline (C, only vanillic acid (D could inhibit root growth. Interestingly, R-(+-limonene (A lightly promoted root length. Other substances had no allelopathic effect on seed germination and seedling growth of the tested plant. To better understand and optimize the inhibitory effects of these natural herbicides, 21 samples of binary mixtures of these seven compounds were tested at 400 μM using 0.25% (v/v Tween® 80 as a control treatment. The results showed that binary mixtures of R-(+-limonene:xanthoxyline (A:C, vanillin:xanthoxyline (B:C, and xanthoxyline:linoleic acid (C:E exhibited strong allelopathic activities on germination and seedling growth of the tested plant, and the level of inhibition was close to the effect of xanthoxyline (C at 400 µM and was better than the effect of xanthoxyline (C at 200 µM. The inhibition was hypothesized to be from a synergistic interaction of each pair of alleochemicals. Mole ratios of each pair of allelochemicals ((A:C, (B:C, and (C:E were then evaluated, and the best ratios of the binary mixtures A:C, B:C and C:E were found to be 2:8, 2:8, and 4:6 respectively. These binary mixtures significantly inhibited germination and shoot and root growth of Chinese amaranth at low concentrations. The results reported here highlight a synergistic behavior of some allelochemicals which could be applied in the development of potential herbicides.

Synergistic effect of interaction between perceived health and social activity on depressive symptoms in the middle-aged and elderly: a population-based longitudinal study.

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Chun, Sung-Youn; Han, Kyu-Tae; Lee, Seo Yoon; Kim, Chan Ok; Park, Eun-Cheol

2015-03-13

To examine the synergistic effect of interaction between perceived health and social activity on depressive symptoms. We investigated whether the interaction between perceived health and social activity has a synergistic effect on depressive symptoms in the middle-aged and elderly using data from 6590 respondents aged 45 and older in the Korean Longitudinal Study on Aging (KLoSA), 2006-2012. A generalised linear mixed-effects model was used to investigate the association in a longitudinal data form. Depressive symptoms were measured using the Center for Epidemiological Studies Depression 10 Scale (CES-D10). Perceived health and level of social activity were categorical variables with three values. Participation in six social activities was assessed. Interactions between perceived health status and social activity were statistically significant for almost all social activity/perceived health combinations. Addition of the interaction term significantly decreased CES-D10 scores, confirming the synergistic effect of the interaction between perceived health status and social activity ('normal×moderate', β=-0.1826; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In addition, we performed stratified analyses by region: urban or rural. In urban respondents, the additional effect of the interaction term decreased CES-D10 scores and all social activity/perceived health combinations were statistically significant ('normal×moderate', β=-0.2578; 'normal×active', β=-0.3945; 'poor×moderate', β=-0.5739; 'poor×active', β=-0.8935). In rural respondents, only one social activity/perceived health combination was statistically significant, and the additional effect of the interaction term showed no consistent trend on CES-D10 scores. The interaction between perceived health and social activity has a synergistic effect on depressive symptoms; the additional effect of the interaction term significantly decreased CES-D10 scores in our models. Published by the BMJ

Synergistic in-vitro effects of combining an antiglycolytic, 3-bromopyruvate, and a bromodomain-4 inhibitor on U937 myeloid leukemia cells.

Science.gov (United States)

Kapp, Nicolette; Stander, Xiao X; Stander, Barend A

2018-06-01

This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth. Cell growth studies determined the IC50 after 48 h exposure for 3-BrP and ITH-47 to be 6 and 2 μmol/l, respectively. When combined, 2.4 and 1 μmol/l of 3-BrP and ITH-47, respectively, inhibited 50% of the cell population, yielding a synergistic combination index of 0.9. Subsequent mechanistic studies showed that the IC50 concentrations of ITH-47 and 3-BrP and the combination increased observable apoptotic bodies and cell shrinkage in U937 cells treated for 48 h. Cell cycle analysis showed an increase in the sub-G1 fraction in all treated cells, suggesting that cell death was increased in the treated samples. Annexin-V-FITC apoptosis analysis showed a statistically significant increase in the number of cells in early and late apoptosis, indicating that cell death occurred through apoptosis and not necrosis. Only U937 cells exposed to ITH-47 showed a decrease in mitochondrial membrane potential compared with the vehicle control. Reactive oxygen species production was decreased in all treated samples. ITH-47-exposed cells showed a decrease in c-Myc, Bcl-2, and p53 gene expressions. 3-BrP-treated cells showed an increase in c-myc and p53 gene expressions. The combination of ITH-47 and 3-BrP lead to downregulation of c-myc and Bcl-2 genes. ITH-47 exposure conditions yielded a marked decrease

Synergistic Effects of Cabozantinib and EGFR-Specific CAR-NK-92 Cells in Renal Cell Carcinoma

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Qing Zhang

2017-01-01

Full Text Available The chimeric antigen receptor-modified immune effector cell (CAR-T and CAR-NK therapies are newly developed adoptive treatments of cancers. However, their therapeutic efficacy against solid tumors is limited. Combining CAR-T or CAR-NK cells with chemotherapeutic drugs to treat solid tumor may be a promising strategy. We developed an epidermal growth factor- (EGFR- specific third-generation CAR. NK-92 cells were modified with the CAR by lentivirus infection. The specific killing ability of the CAR-modified NK-92 cells (CAR-NK-92 against renal cell carcinoma (RCC cell lines was confirmed in vitro. The synergistic effects of cabozantinib and EGFR-specific CAR-NK-92 cells were investigated in vitro and in vivo. Our results showed that the CAR-NK-92 cells lyse RCC cells in an EGFR-specific manner. Treatment with cabozantinib could increase EGFR and decrease PD-L1 membrane surface expression in RCC cells and enhance the killing ability of CAR-NK-92 cells against the RCC cells in vitro. Furthermore, the CAR-NK-92 cells show synergistic therapeutic efficacy with cabozantinib against human RCC xenograft models. Our results provided the basis for combination with chemotherapy as a novel strategy for enhancing the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

Role of Muramyl Dipeptide in Lipopolysaccharide-Mediated Biological Activity and Osteoclast Activity

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Hideki Kitaura

2018-01-01

Full Text Available Lipopolysaccharide (LPS is an endotoxin and bacterial cell wall component that is capable of inducing inflammation and immunological activity. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is another inflammation-inducing molecule that is ubiquitously expressed by bacteria. Several studies have shown that inflammation-related biological activities were synergistically induced by interactions between LPS and MDP. MDP synergistically enhances production of proinflammatory cytokines that are induced by LPS exposure. Injection of MDP induces lethal shock in mice challenged with LPS. LPS also induces osteoclast formation and pathological bone resorption; MDP enhances LPS induction of both processes. Furthermore, MDP enhances the LPS-induced receptor activator of NF-κB ligand (RANKL expression and toll-like receptor 4 (TLR4 expression both in vivo and in vitro. Additionally, MDP enhances LPS-induced mitogen-activated protein kinase (MAPK signaling in stromal cells. Taken together, these findings suggest that MDP plays an important role in LPS-induced biological activities. This review discusses the role of MDP in LPS-mediated biological activities, primarily in relation to osteoclastogenesis.

Simultaneous silencing of ACSL4 and induction of GADD45B in hepatocellular carcinoma cells amplifies the synergistic therapeutic effect of aspirin and sorafenib

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Xia, Hongping; Lee, Kee Wah; Chen, Jianxiang; Kong, Shik Nie; Sekar, Karthik; Deivasigamani, Amudha; Seshachalam, Veerabrahma Pratap; Goh, Brian Kim Poh; Ooi, London Lucien; Hui, Kam M

2017-01-01

Sorafenib is currently the only US Food and Drug Administration (FDA)-approved molecular inhibitor for the systemic therapy of advanced hepatocellular carcinoma (HCC). Aspirin has been studied extensively as an anti-inflammation, cancer preventive and therapeutic agent. However, the potential synergistic therapeutic effects of sorafenib and aspirin on advanced HCC treatment have not been well studied. Drug combination studies and their synergy quantification were performed using the combination index method of Chou-Talalay. The synergistic therapeutic effects of sorafenib and aspirin were evaluated using an orthotopic mouse model of HCC and comprehensive gene profiling analyses were conducted to identify key factors mediating the synergistic therapeutic effects of sorafenib and aspirin. Sorafenib was determined to act synergistically on HCC cells with aspirin in vitro. Using Hep3B and HuH7 HCC cells, it was demonstrated that sorafenib and aspirin acted synergistically to induce apoptosis. Mechanistic studies demonstrated that combining sorafenib and aspirin yielded significant synergistically anti-tumor effects by simultaneously silencing ACSL4 and the induction of GADD45B expression in HCC cells both in vitro and in the orthotopic HCC xenograft mouse model. Importantly, clinical evidence has independently corroborated that survival of HCC patients expressing ACSL4highGADD45Blow was significantly poorer compared to patients with ACSL4lowGADD45Bhigh, thus demonstrating the potential clinical value of combining aspirin and sorafenib for HCC patients expressing ACSL4highGADD45Blow. In conclusion, sorafenib and aspirin provide synergistic therapeutic effects on HCC cells that are achieved through simultaneous silencing of ACSL4 and induction of GADD45B expression. Targeting HCC with ACSL4highGADD45Blow expression with aspirin and sorafenib could provide potential synergistic therapeutic benefits. PMID:28900541

Mechanical properties and osteogenic activity of poly(l-lactide) fibrous membrane synergistically enhanced by chitosan nanofibers and polydopamine layer.

Science.gov (United States)

Liu, Hua; Li, Wenling; Wen, Wei; Luo, Binghong; Liu, Mingxian; Ding, Shan; Zhou, Changren

2017-12-01

To synergistically improve the mechanical properties and osteogenic activity of electrospinning poly(l-lactide) (PLLA) membrane, chitosan (CS) nanofibers were firstly introduced to prepare sub-micro and nanofibers interpenetrated PLLA/CS membrane, which was further surface modified with a polydopamine (PDA) layer to obtain PLLA/CS-PDA. Surface morphology, porosity, surface area and hydrophilicity of the obtained fibrous membranes were studied in detail. As compared to pure PLLA, the significant increase in the mechanical properties of the PLLA/CS, and especially of the PLLA/CS-PDA, was confirmed by tensile testing both in dry and wet states. Cells culture results indicated that both the PLLA/CS and PLLA/CS-PDA membranes, especially the latter, were more beneficial to adhesion, spreading and proliferation, as well as up-regulating alkaline phosphate activity and calcium deposition of MC3T3-E1 cells than PLLA membrane. Results suggested there was a synergistic effect of the CS nanofibers and PDA layer on the mechanical properties and osteogenic activity of PLLA membrane. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression profiling of Bombyx mori gloverin2 gene and its synergistic antifungal effect with cecropin A against Beauveria bassiana.

Science.gov (United States)

Lü, Dingding; Geng, Tao; Hou, Chengxiang; Qin, Guangxing; Gao, Kun; Guo, Xijie

2017-02-05

Gloverin2 is a cationic and glycine-rich antimicrobial peptide whose expression can be induced in fat body of silkworm (Bombyx mori) larvae exposed to bacteria. The purpose of this study is to identify the roles of Bombyx mori gloverin2 (Bmgloverin2) during entomopathogenic fungus Beauveria bassiana infection. Fluorescent quantitative real-time PCR analysis indicated that the relative expression level of Bmgloverin2 gene was up-regulated in the silkworm larvae infected by B. bassiana. The cDNA of Bmgloverin2 was cloned from the silkworm by RT-PCR and the DNA segment of the Bmgloverin2 peptide (without signal peptide sequence) was inserted into pCzn1 expression plasmid and expressed in E. coli ArcticExpress (DE3). SDS-PAGE results revealed that soluble recombinant Bmgloverin2 was successfully expressed and purified. Polyclonal antibody against the Bmgloverin2 was successfully produced with the expressed recombinant protein. Western blot analysis indicated that Bmgloverin2 could be detected in the fat body of silkworm larvae infected with B. bassiana, suggesting that the expression of Bmgloverin2 could be induced by B. bassiana infection in silkworm. Antifungal assays indicated that the Bmgloverin2 had a synergistic antifungal activity with B. mori cecropin A (BmCecA) to entomopathogenic fungus B. bassiana both in vitro and in vivo in the silkworm larvae. This is the first report that Bmgloverin2 exhibits synergistic effect with BmCecA in antifungal activity against B. bassiana. The study demonstrates that Bmgloverin2 is an antifungal protein which plays an important role in synergistic antifungal activity with other antimicrobial peptide in silkworm. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancing effect of negative polypropylene electret on in vitro transdermal delivery of cyclosporine A solution and its synergistic effect with ethyl oleate

International Nuclear Information System (INIS)

Cui, L L; Liu, H Y; Ma, L; Liang, Y Y; Guo, X; Jiang, J

2013-01-01

In this study, the corona charged electrets at voltages of −500 V, −1000 V and −2000 V were made from polypropylene (PP) film. The cyclosporine A (CsA) and 10% ethyl oleate were chosen as the model drug and chemical enhancer, respectively. The charge storage stability of the electrets and the in vitro transdermal behaviour of the model drug in solution under different conditions were studied. The results indicate that the external electrostatic field of the negative PP electrets could penetrate through the rat skin and enhance the transdermal delivery of cyclosporine A. A synergistic effect on enhancing the transdermal delivery of cyclosporine A was observed by combining different surface potential negative PP electrets with 10% ethyl oleate, and the amount of transdermal delivery of CsA was greatly increased comparing with only application of electrets. Therefore, the combination application of electret and chemical enhancer could be a feasible strategy in enhancing transdermal delivery of small peptide drugs or some large molecular drugs.

In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida spp. and Probiotic Vaginal Microbiota.

Science.gov (United States)

Di Vito, Maura; Mattarelli, Paola; Modesto, Monica; Girolamo, Antonietta; Ballardini, Milva; Tamburro, Annunziata; Meledandri, Marcello; Mondello, Francesca

2015-10-01

The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO-VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R-215 and Lactobacillus acidophilus R-52) was tested. Both TTO-VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo-VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations vaginal microbiota. In vivo studies are needed to confirm the efficacy to prevent acute or recurrent vaginal candidiasis. Copyright © 2015 John Wiley & Sons, Ltd.

In vitro activity of commercial formulation and active principle of ...

African Journals Online (AJOL)

The in vitro trypanocidal activities of 4 commercial formulations Ornidyl®, Pentamidine isethionate®, Germanin® and Lampit® and their corresponding active principles (Dl-difluoromethylornithine, pentamidine isethionate, suramine and 5-nitrofuran) were compared against Trypanosoma brucei gambiense. Differences of ...

Bioinspired green synthesis of copper oxide nanoparticles from Syzygium alternifolium (Wt.) Walp: characterization and evaluation of its synergistic antimicrobial and anticancer activity

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Yugandhar, Pulicherla; Vasavi, Thirumalanadhuni; Uma Maheswari Devi, Palempalli; Savithramma, Nataru

2017-10-01

In recent times, nanoparticles are attributed to green nanotechnology methods to know the synergistic biological activities. To accomplish this phenomenon, present study was aimed to synthesize copper oxide nanoparticles (CuO NPs) by using Syzygium alternifolium stem bark, characterized those NPs using expository tools and to elucidate high prioritized antimicrobial and anticancer activities. Synthesized particles exhibited a color change pattern upon synthesis and affirmed its respective broad peak at 285 nm which was analyzed through UV-vis spectroscopy. FT-IR study confirmed that phenols and primary amines were mainly involved in capping and stabilization of nanoparticles. DLS and Zeta potential studies revealed narrow size of particles with greater stability. XRD studies revealed the crystallographic nature of particles with 17.2 nm average size. Microscopic analysis by using TEM revealed that particle size range from 5-13 nm and most of them were spherical in shape, non-agglomerated and poly-dispersed in condition. Antimicrobial studies of particles showed highest inhibitory activity against E. coli and T. harzianum among bacterial and fungal strains, respectively. The scope of this study is extended by examining anticancer activity of CuO NPs. This study exhibited potential anticancer activity towards MDA-MB-231 human breast cancer lines. Overall, these examinations relate that the S. alternifolium is described as efficient well-being plant and probabilistically for the design and synthesis of nanoparticles for human health. This study paves a way to better understand antimicrobial and anticancer therapeutic drug potentials of nanoparticles to design and analysis of pharmaceuticals by in vivo and in vitro approaches.

In vitro and in vivo antioxidant activities of inulin

OpenAIRE

Shang, Hong-Mei; Zhou, Hai-Zhu; Yang, Jun-Yan; Li, Ran; Song, Hui; Wu, Hong-Xin

2018-01-01

This study was designed to investigate the in vitro and in vivo antioxidant activities of inulin. The in vitro assays demonstrated that the antioxidant activities of inulin, including the DPPH radical scavenging activity, ABTS scavenging activity and ferric reducing power, were weak and significantly lower than those of Vitamin C (P < 0.05). The influence of dietary supplementation with inulin on the antioxidant status of laying hens was evaluated with in vivo antioxidant assays. The results ...

One-pot solvothermal synthesis of highly efficient, daylight active and recyclable Ag/AgBr coupled photocatalysts with synergistic dual photoexcitation

International Nuclear Information System (INIS)

Zhang, Caihong; Ai, Lunhong; Li, Lili; Jiang, Jing

2014-01-01

Highlights: • Ag/AgBr photocatalysts were controllably synthesized by solvothermal process. • Ag/AgBr composites showed excellent daylight driven photocatalytic activity. • The remarkable activity is attributed to the synergistic dual photoexcitation. -- Abstract: Efficient light harvesting has been considered to be critical for manipulating the photocatalytic behavior of photocatalysts, because it directly determines the generation of reactive redox charge carriers involved in photoreaction process. In this study, we present a successful example on efficient conversion of solar energy by Ag/AgBr coupled photocatalysts that hold unique synergistic dual photoexcitation. A series of Ag/AgBr coupled photocatalysts were controllably synthesized by an easily manipulated mild solvothermal process. The physicochemical properties of the as-prepared Ag/AgBr coupled photocatalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS) and UV–vis diffuse reflectance spectroscopy (DRS). The results showed the solvothermal reaction time played key role for control of crystalline structure, morphology, composition, and visible light absorption ability of the resulting photocatalysts. The as-prepared Ag/AgBr coupled photocatalysts exhibited remarkable photocatalytic performance and good reusability for decomposing organic dyes in aqueous solution under the irradiation of commercial 20 W cool daylight fluorescent lamp, owing to the synergistic dual photoexcitation cooperating between plasmonic Ag nanoparticles and narrow-band-gap AgBr

Muscle Shear Moduli Changes and Frequency of Alternate Muscle Activity of Plantar Flexor Synergists Induced by Prolonged Low-Level Contraction

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Ryota Akagi

2017-09-01

Full Text Available During prolonged low-level contractions, synergist muscles are activated in an alternating pattern of activity and silence called as alternate muscle activity. Resting muscle stiffness is considered to increase due to muscle fatigue. Thus, we investigated whether the difference in the extent of fatigue of each plantar flexor synergist corresponded to the difference in the frequency of alternate muscle activity between the synergists using muscle shear modulus as an index of muscle stiffness. Nineteen young men voluntarily participated in this study. The shear moduli of the resting medial and lateral gastrocnemius muscles (MG and LG and soleus muscle (SOL were measured using shear wave ultrasound elastography before and after a 1-h sustained contraction at 10% peak torque during maximal voluntary contraction of isometric plantar flexion. One subject did not accomplish the task and the alternate muscle activity for MG was not found in 2 subjects; therefore, data for 16 subjects were used for further analyses. The magnitude of muscle activation during the fatiguing task was similar in MG and SOL. The percent change in shear modulus before and after the fatiguing task (MG: 16.7 ± 12.0%, SOL: −4.1 ± 13.9%; mean ± standard deviation and the alternate muscle activity during the fatiguing task (MG: 33 [20–51] times, SOL: 30 [17–36] times; median [25th–75th percentile] were significantly higher in MG than in SOL. The contraction-induced change in shear modulus (7.4 ± 20.3% and the alternate muscle activity (37 [20–45] times of LG with the lowest magnitude of muscle activation during the fatiguing task among the plantar flexors were not significantly different from those of the other muscles. These results suggest that the degree of increase in muscle shear modulus induced by prolonged contraction corresponds to the frequency of alternate muscle activity between MG and SOL during prolonged contraction. Thus, it is likely that, compared with

Caffeine and contraction synergistically stimulate 5′-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle

Science.gov (United States)

Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

2015-01-01

5′-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr172 phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser473 phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. PMID:26471759

Synergistic effect of single-electron-trapped oxygen vacancies and carbon species on the visible light photocatalytic activity of carbon-modified TiO2

International Nuclear Information System (INIS)

Wang, Xiaodong; Xue, Xiaoxiao; Liu, Xiaogang; Xing, Xing; Li, Qiuye; Yang, Jianjun

2015-01-01

Carbon-modified TiO 2 (CT) nanoparticles were prepared via a two-step method of heat treatment without the resorcinol-formaldehyde (RF) polymer. As-prepared CT nanoparticles were characterized by means of X-ray diffraction (XRD), UV–Vis diffuse reflectance spectroscopy (UV–Vis/DRS), transmission electron microscopy (TEM), N 2 adsorption–desorption isotherms, thermal analysis (TA), electron spin resonance (ESR), and X-ray photoelectron spectroscopy (XPS). The visible light photocatalytic activities were evaluated on the basis of the degradation of methyl orange (MO). The synergistic effect of single-electron-trapped oxygen vacancies (SETOVs) and the carbon species on the visible light photocatalytic activities of the CT nanoparticles were discussed. It was found that the crystalline phase, the morphology, and particle size of the CT nanoparticles depended on the second heat-treatment temperature instead of the first heat-treatment temperature. The visible light photocatalytic activities were attributed to the synergistic effect of SETOVs and the carbon species, and also depended on the specific surface area of the photocatalysts. - Highlights: • Carbon-modified TiO 2 particles have been prepared without RF polymer. • The visible light photocatalytic activities of the particles have been evaluated. • The band gap energy structure of the carbon-modified TiO 2 has been proposed. • Synergistic effect of SETOVs and carbon species has been discussed. • The activities also depend on the specific surface area of the catalysts

Caffeine and contraction synergistically stimulate 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

Science.gov (United States)

Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

2015-10-01

5'-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr(172) phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser(473) phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

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Takayuki Kondo

2017-11-01

Full Text Available In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD. Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ, a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.

Silver oxide nanoparticles embedded silk fibroin spuns: Microwave mediated preparation, characterization and their synergistic wound healing and anti-bacterial activity.

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Babu, Punuri Jayasekhar; Doble, Mukesh; Raichur, Ashok M

2018-03-01

The synergistic wound healing and antibacterial activity of silver oxide nanoparticles embedded silk fibroin (Ag 2 O-SF) spuns is reported here. UV-Vis spectro photometric analysis of these spuns showed the surface plasmon resonance (SPR) confirming the formation of the silver oxide nanoparticles (Ag 2 O NPs) on the surface of the silk fibroin (SF). Scanning electron microscope (SEM) and Differential scanning calorimetry (DSC) also confirmed the presence of Ag 2 O NPs on surface of SF. X-ray diffraction (XRD) analysis revealed the crystalline nature of both SF and Ag 2 O-SF. Fourier transform infrared spectroscopy (FT-IR) results showed the different forms of silk (I and II) and their corresponding protein (amide I, II, III) confirmations. Biodegradation study revealed insignificant changes in the morphology of Ag 2 O-SF spuns even after 14 days of immersion in phosphate buffered saline (PBS). Ag 2 O-SF spuns showed excellent antibacterial activity against both pathogen (S. aureus and M. tuberculosis) and non-pathogen (E. coli) bacteria. More importantly, In vitro wound healing (scratch assay) assay revealed fast migration of the T3T fibroblast cells through the scratch area treated with extract of Ag 2 O-SF spuns and the area was completely covered within 24 h. Cytotoxicity assay confirmed the biocompatible nature of the Ag 2 O-SF spuns, thus suggesting an ideal material for wound healing and anti-bacterial applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

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Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

2012-01-01

In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs

Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model

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Wenjuan Wei

2017-12-01

Full Text Available Background/Purpose: Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB and the lack of novel agents. Although recent data suggest that levofloxacin (LVX may have unique activity against MDR-AB in combination with colistin (CST, further preclinical work is needed. Methods: We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115 of MDR-AB to investigate the in vitro and in vivo efficacy of LVX–CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time–kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied in vitro. A simple invertebrate model (Galleria mellonella has been used to assess the in vivo activity of antimicrobial therapies. Results: The LVX–CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of < 0.5 was observed between CST and LVX in GN0624. The combination had antibiofilm properties on the preformed biofilms of four tested strains and could prevent the emergence of CST-resistant A. baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p < 0.05. Conclusion: In summary, a synergistic or additive effect between CST and LVX was observed in vitro and in vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones. Keywords: Acinetobacter baumannii, antimicrobial synergy, invertebrate model, levofloxacin, polymyxins

Synergistic responses of superficial chemistry and micro topography of titanium created by wire-type electric discharge machining.

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Kataoka, Yu; Tamaki, Yukimichi; Miyazaki, Takashi

2011-01-01

Wire-type electric discharge machining has been applied to the manufacture of endosseous titanium implants as this computer associated technique allows extremely accurate complex sample shaping with an optimal micro textured surface during the processing. Since the titanium oxide layer is sensitively altered by each processing, the authors hypothesized that this technique also up-regulates biological responses through the synergistic effects of the superficial chemistry and micro topography. To evaluate the respective in vitro cellular responses on the superficial chemistry and micro topography of titanium surface processed by wire-type electric discharge, we used titanium-coated epoxy resin replica of the surface. An oxide layer on the titanium surface processed by wire-type electric discharge activated the initial responses of osteoblastic cells through an integrin-mediated mechanism. Since the mRNA expression of ALP on those replicas was up-regulated compared to smooth titanium samples, the micro topography of a titanium surface processed by wire-type electric discharge promotes the osteogenic potential of cells. The synergistic response of the superficial chemistry and micro topography of titanium processed by wire-type electric discharge was demonstrated in this study.

Synergistic gene and drug tumor therapy using a chimeric peptide.

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Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2013-06-01

Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Critical Synergistic Concentration of Lecithin Phospholipids Improves the Antimicrobial Activity of Eugenol against Escherichia coli

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Zhang, Haoshu; Dudley, Edward G.

2017-01-01

ABSTRACT In this study, the effect of individual lecithin phospholipids on the antimicrobial properties of eugenol against Escherichia coli C600 was investigated. We tested five major phospholipids common in soy or egg lecithin (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine [DPPC], 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine [DSPC], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine [DPPE], 1,2-dihexadecanoyl-sn-glycero-3-phosphate [sodium salt] [DPPA], and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine [DPPS]) and one synthetic cationic phospholipid (1,2-dioctadecanoyl-sn-glycero-3-ethylphosphocholine [18:0 EPC]). Among the six phospholipids, DPPC, DSPC, DPPE, DPPA, and the cationic 18:0 EPC showed critical synergistic concentrations that significantly improved the inactivation effect of eugenol against E. coli after 30 min of exposure. At the critical synergistic concentration, an additional ca. 0.4 to 1.9 log reduction (ca. 0.66 to 2.17 log CFU/ml reduction) in the microbial population was observed compared to eugenol-only (control) treatments (ca. 0.25 log reduction). In all cases, increasing the phospholipid amount above the critical synergistic concentration (which was different for each phospholipid) resulted in antimicrobial properties similar to those seen with the eugenol-only (control) treatments. DPPS did not affect the antimicrobial properties of eugenol at the tested concentrations. The critical synergistic concentration of phospholipids was correlated with their critical micelle concentrations (CMC). IMPORTANCE Essential oils (EOs) are naturally occurring antimicrobials, with limited use in food due to their hydrophobicity and strong aroma. Lecithin is used as a natural emulsifier to stabilize EOs in aqueous systems. We previously demonstrated that, within a narrow critical-concentration window, lecithin can synergistically enhance the antimicrobial properties of eugenol. Since lecithin is a mixture of different phospholipids, we aimed to

Critical Synergistic Concentration of Lecithin Phospholipids Improves the Antimicrobial Activity of Eugenol against Escherichia coli.

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Zhang, Haoshu; Dudley, Edward G; Harte, Federico

2017-11-01

In this study, the effect of individual lecithin phospholipids on the antimicrobial properties of eugenol against Escherichia coli C600 was investigated. We tested five major phospholipids common in soy or egg lecithin (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine [DPPC], 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine [DSPC], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine [DPPE], 1,2-dihexadecanoyl-sn-glycero-3-phosphate [sodium salt] [DPPA], and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine [DPPS]) and one synthetic cationic phospholipid (1,2-dioctadecanoyl-sn-glycero-3-ethylphosphocholine [18:0 EPC]). Among the six phospholipids, DPPC, DSPC, DPPE, DPPA, and the cationic 18:0 EPC showed critical synergistic concentrations that significantly improved the inactivation effect of eugenol against E. coli after 30 min of exposure. At the critical synergistic concentration, an additional ca. 0.4 to 1.9 log reduction (ca. 0.66 to 2.17 log CFU/ml reduction) in the microbial population was observed compared to eugenol-only (control) treatments (ca. 0.25 log reduction). In all cases, increasing the phospholipid amount above the critical synergistic concentration (which was different for each phospholipid) resulted in antimicrobial properties similar to those seen with the eugenol-only (control) treatments. DPPS did not affect the antimicrobial properties of eugenol at the tested concentrations. The critical synergistic concentration of phospholipids was correlated with their critical micelle concentrations (CMC). IMPORTANCE Essential oils (EOs) are naturally occurring antimicrobials, with limited use in food due to their hydrophobicity and strong aroma. Lecithin is used as a natural emulsifier to stabilize EOs in aqueous systems. We previously demonstrated that, within a narrow critical-concentration window, lecithin can synergistically enhance the antimicrobial properties of eugenol. Since lecithin is a mixture of different phospholipids, we aimed to identify

In Vitro Antibacterial and Antibiotic Resistance Modifying Effect of Bioactive Plant Extracts on Methicillin-Resistant Staphylococcus epidermidis

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Romana Chovanová

2013-01-01

Full Text Available The crude extracts of plants from Asteraceae and Lamiaceae family and essential oils from Salvia officinalis and Salvia sclarea were studied for their antibacterial as well as antibiotic resistance modifying activity. Using disc diffusion and broth microdilution assays we determined higher antibacterial effect of three Salvia spp. and by evaluating the leakage of 260 nm absorbing material we detected effect of extracts and, namely, of essential oils on the disruption of cytoplasmic membrane. The evaluation of in vitro interactions between plant extracts and oxacillin described in terms of fractional inhibitory concentration (FIC indices revealed synergistic or additive effects of plant extracts and clearly synergistic effects of essential oil from Salvia officinalis with oxacillin in methicillin-resistant Staphylococcus epidermidis.

Binding of Gallic Acid and Epigallocatechin Gallate to Heat-Unfolded Whey Proteins at Neutral pH Alters Radical Scavenging Activity of in Vitro Protein Digests.

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Cao, Yanyun; Xiong, Youling L

2017-09-27

Preheated (80 °C for 9 min) whey protein isolate (HWPI) was reacted with 20, 120, and 240 μmol/g (protein basis) gallic acid (GA) or epigallocatechin gallate (EGCG) at neutral pH and 25 °C. Isothermal titration calorimetry and fluorometry showed a similar trend that GA binding to HWPI was moderate but weaker than EGCG binding. However, the shift of maximal fluorescence emission wavelength in opposite directions in response to GA (blue) and EGCG (red) suggests discrepant binding patterns. Electrophoresis results showed that EGCG induced formation of HWPI complexes while GA only had a marginal effect. Both free and phenolic-bound HWPI exhibited mild antiradical activity. However, when subjected to in vitro digestion, synergistic radical-scavenging activity was produced between the phenolics and peptides with the highest synergism being observed on 120 μmol/g phenolics.

Bortezomib interactions with chemotherapy agents in acute leukemia in vitro.

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Horton, Terzah M; Gannavarapu, Anurhadha; Blaney, Susan M; D'Argenio, David Z; Plon, Sharon E; Berg, Stacey L

2006-07-01

Although there is effective chemotherapy for many patients with leukemia, 20% of children and up to 65% of adults relapse. Novel therapies are needed to treat these patients. Leukemia cells are very sensitive to the proteasome inhibitor bortezomib (VELCADE(R), PS-341), which enhances the in vitro cytotoxic effects of dexamethasone and doxorubicin in multiple myeloma. To determine if bortezomib enhances the cytotoxicity of agents used in leukemia, we employed an in vitro tetrazolium-based colorimetric assay (MTT) to evaluate the cytotoxic effects of bortezomib alone and in combination with dexamethasone, vincristine, doxorubicin, cytarabine, asparaginase, geldanamycin, trichostatin A, and the bcl-2 inhibitor HA14.1. We demonstrated that primary leukemia lymphoblasts and leukemia cell lines are sensitive to bortezomib, with an average IC(50) of 12 nM. Qualitative and quantitative bortezomib-drug interactions were evaluated using the universal response surface approach (URSA). Bortezomib was synergistic with dexamethasone in dexamethasone-sensitive leukemia cells, and additive with vincristine, asparaginase, cytarabine, and doxorubicin. The anti-leukemic activity of bortezomib was also additive with geldanamycin and HA14.1, and additive or synergistic with trichostatin A. These results were compared to analysis using the median-dose effect method, which generated complex drug interactions due to differences in dose-response curve sigmoidicities. These data suggest bortezomib could potentiate the cytotoxic effects of combination chemotherapy in patients with leukemia.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

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Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

Cross-talk between PKA-Cβ and p65 mediates synergistic induction of PDE4B by roflumilast and NTHi

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Susuki-Miyata, Seiko; Miyata, Masanori; Lee, Byung-Cheol; Xu, Haidong; Kai, Hirofumi; Yan, Chen; Li, Jian-Dong

2015-01-01

Phosphodiesterase 4B (PDE4B) plays a key role in regulating inflammation. Roflumilast, a phosphodiesterase (PDE)4-selective inhibitor, has recently been approved for treating severe chronic obstructive pulmonary disease (COPD) patients with exacerbation. However, there is also clinical evidence suggesting the development of tachyphylaxis or tolerance on repeated dosing of roflumilast and the possible contribution of PDE4B up-regulation, which could be counterproductive for suppressing inflammation. Thus, understanding how PDE4B is up-regulated in the context of the complex pathogenesis and medications of COPD may help improve the efficacy and possibly ameliorate the tolerance of roflumilast. Here we show that roflumilast synergizes with nontypeable Haemophilus influenzae (NTHi), a major bacterial cause of COPD exacerbation, to up-regulate PDE4B2 expression in human airway epithelial cells in vitro and in vivo. Up-regulated PDE4B2 contributes to the induction of certain important chemokines in both enzymatic activity-dependent and activity-independent manners. We also found that protein kinase A catalytic subunit β (PKA-Cβ) and nuclear factor-κB (NF-κB) p65 subunit were required for the synergistic induction of PDE4B2. PKA-Cβ phosphorylates p65 in a cAMP-dependent manner. Moreover, Ser276 of p65 is critical for mediating the PKA-Cβ–induced p65 phosphorylation and the synergistic induction of PDE4B2. Collectively, our data unveil a previously unidentified mechanism underlying synergistic up-regulation of PDE4B2 via a cross-talk between PKA-Cβ and p65 and may help develop new therapeutic strategies to improve the efficacy of PDE4 inhibitor. PMID:25831493

A Synergistic effect of artocarpanone from Artocarpus heterophyllus Lam. (Moraceae on the antibacterial activity of some antibiotics and their effect on membrane permeability

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Abdi Wira Septama

2017-06-01

Full Text Available Aim/backgrounds: Artocarpanone isolated from Artocarpus heterophyllus Lam. (Moraceae possesses antibacterial activity. The present study investigated any interaction between artocarpanone and some antibiotics including tetracycline, ampicillin and norfloxacin against Methicillin-resistant Staphylococcus aureus (MRSA, Pseudomonas aeruginosa and Escherichia coli, as well as determining any disruptive effect on bacterial membranes. Materials and methods: A broth microdilution method was used for the susceptibility assay. Any synergistic effect was determined using a checerboard method, and any membrane disruption effect was investigated using a bacteriolysis assay and a measurement of the released 260 nm absorbing materials. Results and discussion: Artocarpanone exhibited weak antibacterial activities against MRSA and P. aeruginosa with MIC values of 125 and 500 µg/mL, respectively. However, it showed the strong antibacterial activity against E. coli (7.8 µg/mL. The interaction between artcarpanone with all tested antibiotics against P. aeruginosa and E. coli only revealed indifference and additive effects (FICI values of 0.75-1.25. The interaction between artocarpanone (31.2 µg/mL and norfloxacin (3.9 µg/mL exhibited a synergistic antibacterial activity against MRSA, with a fractional inhibitory concentration index (FICI of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, a combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. Conclusion: These findings suggested that artocarpanone may be considered as an adjuvant to enhance the antibacterial activity of norfloxacin against MRSA. [J Complement Med Res 2017; 6(2.000: 186-191

Halloysite Nanotubes Supported Ag and ZnO Nanoparticles with Synergistically Enhanced Antibacterial Activity

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Shu, Zhan; Zhang, Yi; Yang, Qian; Yang, Huaming

2017-02-01

Novel antimicrobial nanocomposite incorporating halloysite nanotubes (HNTs) and silver (Ag) into zinc oxide (ZnO) nanoparticles is prepared by integrating HNTs and decorating Ag nanoparticles. ZnO nanoparticles (ZnO NPs) and Ag nanoparticles (Ag NPs) with a size of about 100 and 8 nm, respectively, are dispersively anchored onto HNTs. The synergistic effects of ZnO NPs, Ag NPs, and HNTs led to the superior antibacterial activity of the Ag-ZnO/HNTs antibacterial nanocomposites. HNTs facilitated the dispersion and stability of ZnO NPs and brought them in close contact with bacteria, while Ag NPs could promote the separation of photogenerated electron-hole pairs and enhanced the antibacterial activity of ZnO NPs. The close contact with cell membrane enabled the nanoparticles to produce the increased concentration of reactive oxygen species and the metal ions to permeate into the cytoplasm, thus induced quick death of bacteria, indicating that Ag-ZnO/HNTs antibacterial nanocomposite is a promising candidate in the antibacterial fields.

In vitro effectiveness of triterpenoids and their synergistic effect with antibiotics against Staphylococcus aureus strains.

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Hamza, Muhammad; Nadir, Maha; Mehmood, Nadir; Farooq, Adeel

2016-01-01

The aim of this study is to evaluate the effect of four triterpenoids such as oleanolic acid, ursolic acid, cycloastragenol, and beta-boswellic acid alone and in combination with antibiotics against Staphylococcus aureus strains. Sixteen clinical strains of S. aureus from infected wounds were isolated. Eight were methicillin-sensitive S. aureus (MSSA), and the other eight were methicillin-resistant S. aureus (MRSA). The activity was also seen in reference S. aureus American Type Culture Collection ™ strains. The activity of all the triterpenoids and antibiotics against S. aureus was evaluated by broth microdilution method. The effectiveness was judged by comparing the minimum inhibitory concentrations (MICs) of the compounds with antibiotics. The combination of antibiotics with compounds was evaluated by their fractional inhibitory concentrations (FIC). Against both clinical and reference MSSA strains, none of the compounds exhibited comparable activity to antibiotics vancomycin or cefradine except for ursolic acid (MIC 7.8 μg/ml). Against MRSA, all compounds (MIC 16-128 μg/ml) showed lesser activity than vancomycin (MIC 5.8 μg/ml). Among triterpenoid-antibiotic combinations, the most effective were ursolic acid and vancomycin against clinical strain MSSA (FIC S 0.17). However, overall, different combinations between triterpenoids and antibiotics showed 95%-46% ( P antibiotics compared to when antibiotics were used alone. Cefradine, a drug not suitable for treating MRSA (MIC = 45 μg/ml), showed a remarkable decrease in its MIC (87% Pantibiotics. However, when used in combination with antibiotics, they showed remarkable synergistic effect and thus can help in prolonging the viability of these antibiotics against S. aureus infections. Furthermore, reduction in MIC of cefradine with oleanolic acid indicates their potential use against MRSA.

In vitro and in vivo antioxidant activities of inulin.

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Shang, Hong-Mei; Zhou, Hai-Zhu; Yang, Jun-Yan; Li, Ran; Song, Hui; Wu, Hong-Xin

2018-01-01

This study was designed to investigate the in vitro and in vivo antioxidant activities of inulin. The in vitro assays demonstrated that the antioxidant activities of inulin, including the DPPH radical scavenging activity, ABTS scavenging activity and ferric reducing power, were weak and significantly lower than those of Vitamin C (P inulin on the antioxidant status of laying hens was evaluated with in vivo antioxidant assays. The results indicated that inulin supplementation quadratically improved the egg production rate of the laying hens (P inulin levels increased (P inulin levels increased (P inulin has the potential to improve the antioxidant status of laying hens.

Antioxidant and immunostimulatory activities in vitro of polysaccharides from pomegrante peels

International Nuclear Information System (INIS)

Ke, C.L.; Wang, D.; Yao, X.; Xu, H.

2015-01-01

In the present study, the crude polysaccharides from pomegranate peels(CPP) were prepared by water-extraction technology. In vitro antioxidant assay, CPP showed strong inhibition of lipid peroxidation and reducing ability, moderate 1,1-diphenyl-2-picryldydrazyl(DPPH) radical scavenging activity. The immunostimulatory activity of CPP was also evaluated by using in vitro cell models. The results demonstrated that CPP could promote the splenocyte proliferation, increase the activity of acid phosphatase in peritoneal macrophages and strengthen peritoneal macrophages to devour neutral red in vitro. (author)

Human milk inactivates pathogens individually, additively, and synergistically.

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Isaacs, Charles E

2005-05-01

Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

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Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

2016-03-01

Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole. Copyright © 2015 Elsevier B.V. All rights reserved.

Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

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Li-Xia Feng

2014-03-01

Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

Synergistic induction of astrocytic differentiation by factors secreted from meninges in the mouse developing brain.

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Kawamura, Yoichiro; Katada, Sayako; Noguchi, Hirofumi; Yamamoto, Hiroyuki; Sanosaka, Tsukasa; Iihara, Koji; Nakashima, Kinichi

2017-11-01

Astrocytes, which support diverse neuronal functions, are generated from multipotent neural stem/precursor cells (NS/PCs) during brain development. Although many astrocyte-inducing factors have been identified and studied in vitro, the regions and/or cells that produce these factors in the developing brain remain elusive. Here, we show that meninges-produced factors induce astrocytic differentiation of NS/PCs. Consistent with the timing when astrocytic differentiation of NS/PCs increases, expression of astrocyte-inducing factors is upregulated. Meningeal secretion-mimicking combinatorial treatment of NS/PCs with bone morphogenetic protein 4, retinoic acid and leukemia inhibitory factor synergistically activate the promoter of a typical astrocytic marker, glial fibrillary acidic protein. Taken together, our data suggest that meninges play an important role in astrocytic differentiation of NS/PCs in the developing brain. © 2017 Federation of European Biochemical Societies.

A multi-functional nanoplatform for tumor synergistic phototherapy

Science.gov (United States)

Zhang, Huijuan; Jiao, Xiaojing; Chen, Qianqian; Ji, Yandan; Zhang, Xiaoge; Zhu, Xing; Zhang, Zhenzhong

2016-02-01

Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform.

A multi-functional nanoplatform for tumor synergistic phototherapy

International Nuclear Information System (INIS)

Zhang, Huijuan; Jiao, Xiaojing; Chen, Qianqian; Ji, Yandan; Zhang, Xiaoge; Zhu, Xing; Zhang, Zhenzhong

2016-01-01

Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO 2 @MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO 2 @MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO 2 @MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform. (paper)

Synergistic Interaction Between Phage Therapy and Antibiotics Clears Pseudomonas Aeruginosa Infection in Endocarditis and Reduces Virulence.

Science.gov (United States)

Oechslin, Frank; Piccardi, Philippe; Mancini, Stefano; Gabard, Jérôme; Moreillon, Philippe; Entenza, José M; Resch, Gregory; Que, Yok-Ai

2017-03-01

Increasing antibiotic resistance warrants therapeutic alternatives. Here we investigated the efficacy of bacteriophage-therapy (phage) alone or combined with antibiotics against experimental endocarditis (EE) due to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection. In vitro fibrin clots and rats with aortic EE were treated with an antipseudomonas phage cocktail alone or combined with ciprofloxacin. Phage pharmacology, therapeutic efficacy, and resistance were determined. In vitro, single-dose phage therapy killed 7 log colony-forming units (CFUs)/g of fibrin clots in 6 hours. Phage-resistant mutants regrew after 24 hours but were prevented by combination with ciprofloxacin (2.5 × minimum inhibitory concentration). In vivo, single-dose phage therapy killed 2.5 log CFUs/g of vegetations in 6 hours (P 6 log CFUs/g of vegetations in 6 hours and successfully treating 64% (n = 7/11) of rats. Phage-resistant mutants emerged in vitro but not in vivo, most likely because resistant mutations affected bacterial surface determinants important for infectivity (eg, the pilT and galU genes involved in pilus motility and LPS formation). Single-dose phage therapy was active against P. aeruginosa EE and highly synergistic with ciprofloxacin. Phage-resistant mutants had impaired infectivity. Phage-therapy alone or combined with antibiotics merits further clinical consideration. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

International Nuclear Information System (INIS)

Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

2012-01-01

Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

THE SYNERGISTIC SYLLABUS FOR TEACHING READING IN 32 TOURISM VOCATIONAL HIGH SCHOOL

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Ahlis Qoidah Noor

2017-12-01

Full Text Available The new Syllabus at 2013 Curriculum for vocational high school created many problems to apply in the class. Based on the Need Analysis, the writer develops a Synergistic Syllabus for teaching Reading in vocational high school. It contains the syllabus combined from Task- Based Learning, Situational Syllabus, Program of International Student Assessment ( PISA item test and Character Building. It is a R and D research uses three phases of Observation, Developing and Try Out. It is in a True Experimental Research. The main findings are Reading Skill cannot be taught effectively for some reasons. There is no appropriate syllabus for teaching Reading; most teachers need some models in a syllabus. The results are the Synergistic Syllabus for teaching Reading, a set of Reading Material for Teaching Reading and a set of the lesson plan for one semester at Grade X of Tourism VHS. It is measured through mean, median and t- Test. To Sum up Synergistic Syllabus can develop many aspects, the systematic and meaningful activities in the class, motivation and good attitude. The standardized item of assignment, and a sense of competition in Reading activities and the Synergistic Syllabus assist teachers in teaching Reading using 2013 curriculum in the class effectively.

Halloysite Nanotubes Supported Ag and ZnO Nanoparticles with Synergistically Enhanced Antibacterial Activity

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Zhan Shu

2017-02-01

Full Text Available Abstract Novel antimicrobial nanocomposite incorporating halloysite nanotubes (HNTs and silver (Ag into zinc oxide (ZnO nanoparticles is prepared by integrating HNTs and decorating Ag nanoparticles. ZnO nanoparticles (ZnO NPs and Ag nanoparticles (Ag NPs with a size of about 100 and 8 nm, respectively, are dispersively anchored onto HNTs. The synergistic effects of ZnO NPs, Ag NPs, and HNTs led to the superior antibacterial activity of the Ag-ZnO/HNTs antibacterial nanocomposites. HNTs facilitated the dispersion and stability of ZnO NPs and brought them in close contact with bacteria, while Ag NPs could promote the separation of photogenerated electron-hole pairs and enhanced the antibacterial activity of ZnO NPs. The close contact with cell membrane enabled the nanoparticles to produce the increased concentration of reactive oxygen species and the metal ions to permeate into the cytoplasm, thus induced quick death of bacteria, indicating that Ag-ZnO/HNTs antibacterial nanocomposite is a promising candidate in the antibacterial fields.

Chimeric anti-staphylococcal enterotoxin B antibodies and lovastatin act synergistically to provide in vivo protection against lethal doses of SEB.

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Mulualem E Tilahun

Full Text Available Staphylococcal enterotoxin B (SEB is one of a family of toxins secreted by Staphylococcus aureus that act as superantigens, activating a large fraction of the T-cell population and inducing production of high levels of inflammatory cytokines that can cause toxic shock syndrome (TSS and death. Extracellular engagement of the TCR of T-cells and class II MHC of antigen presenting cells by SEB triggers the activation of many intracellular signaling processes. We engineered chimeric antibodies to block the extracellular engagement of cellular receptors by SEB and used a statin to inhibit intracellular signaling. Chimeric human-mouse antibodies directed against different neutralizing epitopes of SEB synergistically inhibited its activation of human T-cells in vitro. In the in vivo model of lethal toxic shock syndrome (TSS in HLA-DR3 transgenic mice, two of these antibodies conferred significant partial protection when administered individually, but offered complete protection in a synergistic manner when given together. Similarly, in vivo, lovastatin alone conferred only partial protection from TSS similar to single anti-SEB antibodies. However, used in combination with one chimeric neutralizing anti-SEB antibody, lovastatin provided complete protection against lethal TSS in HLA-DR3 transgenic mice. These experiments demonstrate that in vivo protection against lethal doses of SEB can be achieved by a statin of proven clinical safety and chimeric human-mouse antibodies, agents now widely used and known to be of low immunogenicity in human hosts.

Formulation and in vitro/in vivo evaluation of combining DNA repair and immune enhancing nutritional supplements.

Science.gov (United States)

Pero, R W; Amiri, A; Sheng, Y; Welther, M; Rich, M

2005-04-01

Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, untested and without regard to the principle of metabolic competition between the active components. Here, we report on the combination of a cat's claw water extract (C-Med-100, carboxy alkyl esters = active ingredients) + medicinal mushroom extracts (Cordyceps sinensis, Grifola blazei, Grifolafrondosa, Trametes versicolor and Ganoderma lucidum, polysaccharides = active ingredients) + nicotinamide + zinc into a formulation designed to optimize different modes of immunostimulatory action, and yet that would avoid metabolic antioxidant competition yielding less than expected efficacious effects. Isobole curve analyses of these two active classes of ingredients determined by growth inhibition of HL-60 human leukemic cells in vitro confirmed they were indeed synergistic when in combination, and not metabolically competitive. Furthermore, an in vivo study showed significant health benefit for 14 subjects treated for 4 weeks with the unique C-Med-100/mushroom extract formulation in that they had reduced pain, reduced fatigue, weight loss and a reduced presence of DNA damage in peripheral blood assessed by (8-OH) guanine DNA adducts and elevation in serum protein thiols. Because this broad-based panel of clinical parameters indicating clinical efficacy has never been demonstrated before for either of the active ingredients evaluated alone in humans, these data were taken as strong evidence that the combination of C-Med-100 + mushroom extracts + nicotinamide + zinc gave additive or synergistic effects to health benefit, and thus supported no efficacious limits from metabolic competition regarding this particular formulation.

Synergistic effect of aqueous extract of Telfaria occidentalis on the ...

African Journals Online (AJOL)

Synergistic effect of aqueous extract of Telfaria occidentalis on the biological activities of ... Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan. 2. ... development of resistance to most of the earlier drugs.

In vitro activity of flumequine in comparison with several other antimicrobial agents against five pathogens isolated in calves in The Netherlands.

Science.gov (United States)

Mevius, D J; Breukink, H J; van Miert, A S

1990-10-01

The in vitro activity of flumequine in comparison with several other drugs was tested against 17 P. multocida, 16 P. haemolytica, 21 S. dublin, 21 S. typhimurium and 21 E. coli strains, isolated in (veal) calves in the Netherlands. The MIC50 of flumequine for the respective pasteurellas was 0.25 and 1 microgram/ml, for the salmonellas and E. coli 0.5 micrograms/ml. In comparison with flumequine, enrofloxacin and ciprofloxacin showed higher in vitro activity, with MIC50 less than or equal to 0.008 micrograms/ml for ciprofloxacin. Decreased susceptibility of the pasteurellas was found for kanamycin, neomycin, streptomycin, gentamicin, oxytetracycline and doxycycline. The MIC50 of minocycline for P. multocida was 0.5 micrograms/ml and there was no cross resistance with the other tetracyclines. P. multocida was very susceptible to ampicillin (MIC50 less than or equal to 0.03 micrograms/ml), P. haemolytica, however, was 100% resistant to this drug. Both pasteurellas were susceptible to cephalothin and approximately 50% of the strains of both bacteria were resistant to chloramphenicol. The MIC50 of either spiramycin or tylosin was greater than or equal to their respective breakpoint-MIC values. Both pasteurellas were susceptible to the combination of trimethoprim and sulphamethoxazole. However, for P. multocida, the addition of sulphamethoxazole to trimethoprim had no synergistic effect on its MIC. In comparison with trimethorpim, aditoprim was less potent. Therefore only P. multocida was susceptible to aditoprim.

In vitro and in vivo therapeutic activity of ibuprofen against dermatophytes

International Nuclear Information System (INIS)

AlJanabi, Ali S

2009-01-01

To evaluate the in vitro and in vivo therapeutic activity of ibuprofen against dermatophytes. The period of study ranged from June to September 2008. For in vitro investigation of ibuprofen activity, measurement of colony diameter, and dry weight were employed against 4 isolated strains of dermatophytes from 46 patients (30-43 years) suffering from dermatophytoses at Morgan Hospital, Hilla City, Iraq in June 2008. For the in vivo evaluation of ibuprofen, rabbits as the main subjects, were infected with dermatophytes and treated with prepared ibuprofen cream (15mg/gm). In vitro application of ibuprofen showed cidal activity on 4 strains of dermatophytes at minimum inhibitory concentrations of 200 ug/ml. The infected rabbits were successfully cured of dermatophytoses after treatment with ibuprofen cream. Based on in vitro and in vivo application, Ibuprofen can be used as a short-term cure for dermatophytoses. (author)

Synergistic Radiation Protective Effect of Purified Auricularia auricular-judae Polysaccharide (AAP IV with Grape Seed Procyanidins

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Haina Bai

2014-12-01

Full Text Available The aim of this study was to investigate the synergistic antioxidant potential and protective effect of grape seed procyanidins (GSP in combination with Auricularia auricular-judae polysaccharides (AAP IV on radiation injury in splenocytes. Rat splenocyte irradiation resulted in significantly higher apoptosis rate, malondialdehyde (MDA (p < 0.005, reactive oxygen species (ROS (p < 0.01; cell viability, total superoxide dismutase (T-SOD (p < 0.01, catalase (CAT (p < 0.01, glutathione peroxidase (GSH-PX (p < 0.05, activity and glutathione (GSH (p < 0.01 levels were significantly reduced, compared with the control group. “GSP + AAP IV” treatment of rat splenocytes at doses of “GSP (0.3 μg/mL + AAP IV (50 μg/mL” displayed higher radioprotective and antioxidative effects than the administration of either GSP or AAP IV, as evident by lower levels of MDA (p < 0.001 concentration, as well as higher cell viability and T-SOD (p < 0.05, CAT (p < 0.005, GSH-PX (p < 0.01 and GSH content compared to the radiation group. In addition, in vivo studies have shown that “GSP + AAP IV” significantly ameliorated the decrease of spleen index (p < 0.005 and spleen GSH (p < 0.005 levels and significantly inhibited the increase of MDA (p < 0.005 levels of spleen with radiation-induced damage, compared with the non-treated group. The in vivo and in vitro results suggested that GSP and AAP IV have a synergistic protective effect against radiation-induced injury by improving the antioxidant and immunomodulation activities.

In Silico and In Vitro Study of the Bromelain-Phytochemical Complex Inhibition of Phospholipase A2 (Pla2

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Fatahiya Mohamed Tap

2018-01-01

Full Text Available Phospholipase A2 (Pla2 is an enzyme that induces inflammation, making Pla2 activity an effective approach to reduce inflammation. Therefore, investigating natural compounds for this Pla2 inhibitory activity has important therapeutic potential. The objective of this study was to investigate the potential in bromelain-phytochemical complex inhibitors via a combination of in silico and in vitro methods. Bromelain-amenthoflavone displays antagonistic effects on Pla2. Bromelian-asiaticoside and bromelain-diosgenin displayed synergistic effects at high concentrations of the combined compounds, with inhibition percentages of more than 70% and 90%, respectively, and antagonistic effects at low concentrations. The synergistic effect of the bromelain-asiaticoside and bromelain-diosgenin combinations represents a new application in treating inflammation. These findings not only provide significant quantitative data, but also provide an insight on valuable implications for the combined use of bromelain with asiaticoside and diosgenin in treating inflammation, and may help researchers develop more natural bioactive compounds in daily foods as anti-inflammatory agent.

Determining lower threshold concentrations for synergistic effects

DEFF Research Database (Denmark)

Bjergager, Maj-Britt Andersen; Dalhoff, Kristoffer; Kretschmann, Andreas

2017-01-01

which proven synergists cease to act as synergists towards the aquatic crustacean Daphnia magna. To do this, we compared several approaches and test-setups to evaluate which approach gives the most conservative estimate for the lower threshold for synergy for three known azole synergists. We focus...... on synergistic interactions between the pyrethroid insecticide, alpha-cypermethrin, and one of the three azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia magna immobilization. Three different experimental setups were applied: A standard 48h acute toxicity test, an adapted 48h test...... of immobile organisms increased more than two-fold above what was predicted by independent action (vertical assessment). All three tests confirmed the hypothesis of the existence of a lower azole threshold concentration below which no synergistic interaction was observed. The lower threshold concentration...

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine

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Wise Phyllis M

2001-03-01

Full Text Available Abstract Background Human immunodeficiency virus (HIV infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. Results Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. Conclusion Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.

Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

Science.gov (United States)

Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

2014-06-01

G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus

Science.gov (United States)

Li, Xue; Lu, Yun; Ren, Zhitao; Zhao, Longyin; Hu, Xinxin; Jiang, Jiandong; You, Xuefu

2013-01-01

Background Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA. Methodology A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays. Principal Findings SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log10 CFU/mL. Conclusions/Significance SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin

NF1, Sp1 and HSF1 are synergistically involved in sulfide-induced sqr activation in echiuran worm Urechis unicinctus

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaolong; Qin, Zhenkui; Li, Xueyu; Ma, Xiaoyu; Gao, Beibei; Zhang, Zhifeng, E-mail: zzfp107@ouc.edu.cn

2016-06-15

Highlights: • Sulfide activates sqr transcription against respiratory toxicity in Urechis unicinctus. • Sulfide increases expressions and activities of NF1, Sp1 and HSF1 in a time-dependent manner. • NF1 and Sp1 participate in both basal and early sulfide-induced sqr transcription. • HSF1 functions more significantly than NF1 and Sp1 in sulfide-induced sqr transcription. • Transcription factors NF1, Sp1 and HSF1 enhance sqr promoter activity synergistically. - Abstract: Background: Sulfide is a well-known environmental toxic substance. Mitochondrial sulfide oxidation is a main mechanism of sulfide detoxification in organisms, and sulfide: quinone oxidoreductase (SQR) is a key enzyme which is involved in transferring electrons from sulfide to ubiquinone and converting sulfide into thiosulfate. Previous studies have revealed the SQR-mediated mitochondrial sulfide oxidation exists in the echiuran worm Urechis unicinctus, and its sqr mRNA level increased significantly when the worm is exposed to sulfide. In this study, we attempt to reveal the synergistic regulation of transcription factors on sulfide-induced sqr transcription in U. unicinctus. Methods: ChIP and EMSA were used to identify the interactions between sqr proximal promoter (from −391 to +194 bp) and transcription factors NF1 (nuclear factor 1) and Sp1 (specificity protein 1). Site-directed mutation and transfection assays further revealed their binding sites and synergistic roles of HSF1, NF1 and Sp1 in the sqr transcription. When U. unicinctus were exposed to 150 μM sulfide, the expression levels and nuclear contents of NF1 and Sp1 were examined by Western blotting, and the binding contents between NF1 or Sp1 and the sqr promoter were also detected by ChIP. Results: Transcription factors NF1 and Sp1 were confirmed to interact with the sqr proximal promoter, and their binding sites were identified in −75 to −69 bp for NF1 and −210 to −201 bp for Sp1. Transfection assays showed mutation

In vitro antimetastatic activity of Agarwood (Aquilaria crassna essential oils against pancreatic cancer cells

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Saad Sabbar Dahham

2016-06-01

Conclusion: The present study elucidated for the first time the anti-pancreatic cancer properties of A. crassna essential oils, It can be concluded that the anticancer effects of the extract could be due to the synergistic effect of the biologically active phytoconstituents present in the essential oils.

Synergistic Effect of Auto-Activation and Small RNA Regulation on Gene Expression

Science.gov (United States)

Xiong, Li-Ping; Ma, Yu-Qiang; Tang, Lei-Han

2010-09-01

Auto-activation and small ribonucleic acid (RNA)-mediated regulation are two important mechanisms in controlling gene expression. We study the synergistic effect of these two regulations on gene expression. It is found that under this combinatorial regulation, gene expression exhibits bistable behaviors at the transition regime, while each of these two regulations, if working solely, only leads to monostability. Within the stochastic framework, the base pairing strength between sRNA and mRNA plays an important role in controlling the transition time between on and off states. The noise strength of protein number in the off state approaches 1 and is smaller than that in the on state. The noise strength also depends on which parameters, the feedback strength or the synthesis rate of small RNA, are tuned in switching the gene expression on and off. Our findings may provide a new insight into gene-regulation mechanism and can be applied in synthetic biology.

Synergistic Effect of Auto-Activation and Small RNA Regulation on Gene Expression

International Nuclear Information System (INIS)

Li-Ping, Xiong; Yu-Qiang, Ma; Lei-Han, Tang

2010-01-01

Auto-activation and small ribonucleic acid (RNA)-mediated regulation are two important mechanisms in controlling gene expression. We study the synergistic effect of these two regulations on gene expression. It is found that under this combinatorial regulation, gene expression exhibits bistable behaviors at the transition regime, while each of these two regulations, if working solely, only leads to monostability. Within the stochastic framework, the base pairing strength between sRNA and mRNA plays an important role in controlling the transition time between on and off states. The noise strength of protein number in the off state approaches 1 and is smaller than that in the on state. The noise strength also depends on which parameters, the feedback strength or the synthesis rate of small RNA, are tuned in switching the gene expression on and off. Our findings may provide a new insight into gene-regulation mechanism and can be applied in synthetic biology

Discovery of new A- and B-type laxaphycins with synergistic anticancer activity.

Science.gov (United States)

Cai, Weijing; Matthew, Susan; Chen, Qi-Yin; Paul, Valerie J; Luesch, Hendrik

2018-05-15

Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC 50 of 1.7 µM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemometrics Optimized Extraction Procedures, Phytosynergistic Blending and in vitro Screening of Natural Enzyme Inhibitors Amongst Leaves of Tulsi, Banyan and Jamun.

Science.gov (United States)

De, Baishakhi; Bhandari, Koushik; Singla, Rajeev K; Katakam, Prakash; Samanta, Tanmoy; Kushwaha, Dilip Kumar; Gundamaraju, Rohit; Mitra, Analava

2015-10-01

Tulsi, Banyan, and Jamun are popular Indian medicinal plants with notable hypoglycemic potentials. Now the work reports chemo-profiling of the three species with in-vitro screening approach for natural enzyme inhibitors (NEIs) against enzymes pathogenic for type 2 diabetes. Further along with the chemometrics optimized extraction process technology, phyto-synergistic studies of the composite polyherbal blends have also been reported. Chemometrically optimized extraction procedures, ratios of polyherbal composites to achieve phyto-synergistic actions, and in-vitro screening of NEIs amongst leaves of Tulsi, Banyan, and Jamun. The extraction process parameters of the leaves of three plant species (Ficus benghalensis, Syzigium cumini and Ocimum sanctum) were optimized by rotatable central composite design of chemometrics so as to get maximal yield of bio-actives. Phyto-blends of three species were prepared so as to achieve synergistic antidiabetic and antioxidant potentials and the ratios were optimized by chemometrics. Next, for in vitro screening of natural enzyme inhibitors the individual leaf extracts as well as composite blends were subjected to assay procedures to see their inhibitory potentials against the enzymes pathogenic in type 2 diabetes. The antioxidant potentials were also estimated by DPPH radical scavenging, ABTS, FRAP and Dot Blot assay. Considering response surface methodology studies and from the solutions obtained using desirability function, it was found that hydro-ethanolic or methanolic solvent ratio of 52.46 ± 1.6 and at a temperature of 20.17 ± 0.6 gave an optimum yield of polyphenols with minimal chlorophyll leaching. The species also showed the presence of glycosides, alkaloids, and saponins. Composites in the ratios of 1:1:1 and 1:1:2 gave synergistic effects in terms of polyphenol yield and anti-oxidant potentials. All composites (1:1:1, 1:2:1, 2:1:1, 1:1:2) showed synergistic anti-oxidant actions. Inhibitory activities against the

Abdominal and internal intercostal motoneurones are strong synergists for expiration but are not synergists for Group I monosynaptic afferent inputs

DEFF Research Database (Denmark)

Ford, Tim W; Meehan, Claire Francesca; Kirkwood, Peter

2014-01-01

, 9 being in Group B Dist motoneurones. The complete absence of heteronymous monosynaptic Group I reflex excitation between muscles that are synergistically activated in expiration leads us to conclude that such connections from muscle spindle afferents of the thoracic nerves have little role...... in controlling expiratory movements but, where present, support other motor acts....

In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus.

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Chang, Ping Chin; Li, Hua Yu; Tang, Hung Jen; Liu, Jien Wei; Wang, Jhi Joung; Chuang, Yin Ching

2007-02-01

Little is known about the possible synergism of baicalein, a bioactive flavone of Scutellariae radix (a Chinese herb), when used in conjunction with other antimicrobial agents against vancomycin-resistant Enterococcus (VRE). This in vitro study examined the possible synergism of the combination of baicalein and gentamicin against VRE. Minimal inhibitory concentrations (MICs) of baicalein as well as gentamicin were determined against 39 clinical isolates of VRE by the agar dilution method. Synergistic activities were determined using the checkerboard method based on the fractional inhibitory concentration indices and also the time-kill method. Further time-kill studies were conducted with these two agents against one randomly chosen clinical isolate, VRE-096. Minimal concentrations inhibiting 50% (MIC(50)) and 90% (MIC(90)) of isolates for baicalein and gentamicin were all >256 microg/mL. Synergism between baicalein and gentamicin was demonstrated against four clinical isolates of VRE (VRE-70, VRE-940, VRE-096 and VRE-721). When approximately 5 x 10(5) colony-forming units/mL of VRE-096 was incubated with both baicalein at a concentration of 32 microg/mL (1/8 x MIC) and gentamicin at a concentration of 128 microg/mL (1/2 x MIC), there was an inhibitory effect against VRE that persisted for 48 h. At 48 h, the combination of baicalein and gentamicin at these respective concentrations resulted in a reduction of growth by approximately 2 orders of magnitude compared to that for the starting inoculum and by 3 orders of magnitude compared to that for baicalein alone, the more active single agent. This study demonstrated that baicalein and gentamicin can act synergistically in inhibiting VRE in vitro.

In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii: a systematic review and meta-analysis.

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Ni, Wentao; Shao, Xiaodi; Di, Xiuzhen; Cui, Junchang; Wang, Rui; Liu, Youning

2015-01-01

In order to provide preliminary guidance for rational antibiotic combination therapy in the clinic, a systematic review and meta-analysis was performed to evaluate the in vitro synergistic activity of polymyxins combined with other antibiotics against Acinetobacter baumannii. An extensive literature search was undertaken without restriction according to region, publication type or language. All available in vitro synergy tests on antibiotic combinations consisting of polymyxins were included. The primary outcome assessed was the in vitro activity of combination therapy on bacterial kill or inhibition. In total, 70 published studies and 31 conference proceedings reporting testing of polymyxins in combination with 11 classes consisting of 28 antibiotic types against 1484 A. baumannii strains were included in the analysis. In time-kill studies, high in vitro synergy and bactericidal activity were found for polymyxins combined with several antibiotic classes such as carbapenems and glycopeptides. Carbapenems or rifampicin combination could efficiently suppress the development of colistin resistance and displayed a >50% synergy rate against colistin-resistant strains. Synergy rates of chequerboard microdilution and Etest methods in most antibiotic combinations were generally lower than those of time-kill assays. The benefits of these antibiotic combinations should be further demonstrated by well-designed clinical studies. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Revisiting the functional anatomy of the palmaris longus as a thenar synergist.

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Moore, Colin W; Fanous, Jacob; Rice, Charles L

2017-11-27

Surgical studies describe the palmaris longus (PL) as a synergist in thumb abduction, which may facilitate its use in restoring thumb function using opponensplasty. However, beyond morphological descriptions and isometric thenar abduction strength measures, the evidence supporting the PL as a thenar synergist in-vivo is limited. The purpose here was to determine whether the PL provides synergistic contributions to thenar musculature by: (1) recording PL muscle activity using indwelling electromyography (EMG) during thumb movements; and (2) quantifying changes in PL muscle architecture using ultrasonography. In 10 healthy males, PL muscle activity was recorded during maximal thenar muscle contractions (abduction, flexion, opposition, adduction, and extension) with the wrist secured in a neutral position. The PL EMG was normalized to its maximal EMG recorded during isometric wrist flexion. Dynamic changes in PL muscle thickness (M T ) were determined during abduction and adduction using ultrasound imaging. The results indicate that the PL is activated during thenar movements with greatest relative PL EMG recorded during thenar abduction (46%), flexion (35%) and opposition (37%). Compared to rest, PL M T significantly increased (21%) during maximal thenar abduction. With direct measures in vivo, this study supports morphological and surgical observations indicating the PL acts as an extrinsic hand muscle in enhancing thenar muscle actions. Knowledge of the synergistic relationship between the PL and thenar musculature may allow for further development of surgical opponensplasty approaches using the abductor pollicis brevis and PL as a functional digastric unit. Clin. Anat, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

Science.gov (United States)

Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

2016-11-16

The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

Characterization of fungal sulfated polysaccharides and their synergistic anticancer effects with doxorubicin.

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Cheng, Jing-Jy; Chang, Chia-Chuan; Chao, Chi-Hsein; Lu, Mei-Kuang

2012-09-01

Sulfated polysaccharides (SPSs) from two edible fungal species, including two strains of Antrodia cinnamomea and Poria cocos, were isolated. Fucose, glucosamine, galactose, glucose, and mannose were the major sugars in the SPSs, and these SPSs had a high sulfate content. The area percentage of low-molecular-weight SPSs (1-100 kDa) covered almost half of the SPS mixture of the A. cinnamomea strains. In contrast, high-molecular-weight SPSs (>1000 kDa) of P. cocos covered a large proportion of the area at 30.06%. SPSs from A. cinnamomea B86 showed stronger inhibition of endothelial cell (EC) tube formation in an in vitro assay of angiogenesis, than did A. cinnamomea 35396 or P. cocos. The degree of sulfation paralleled their antiangiogenic activity. When tumor cells were concurrently exposed to doxorubicin (DOX) and fungal SPSs, SPSs synergistically increased the cytotoxicity of DOX to different degree up to 50-fold. Fungal SPSs may offer new applications for combinational-therapy drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antimicrobial and synergistic studies of ranunculus muricatus l. against some indigenous bacteria

International Nuclear Information System (INIS)

Rasool, S.; Mughal, T.A.

2014-01-01

In the present study, antibacterial activity of the whole plant methanolic extract of Ranunculus muricatus L., was analyzed against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Bacillus pumilus, Salmonella typhimurium and Pseudomonas aeroginosa. Methanol was regarded as an excellent solvent for antimicrobial activity. It was observed as best bactericidal at a minimal inhibitory concentration (MIC) of 1-10 micro g/ml against all the bacterial cultures viz. B. pumilus, B. subtilis, S. aureus, E. coli, P. aeroginosa and S. typhimurium. Synergistic antibacterial activity of methanolic extracts was tested with respect to solvent extract of leaves of Ricinus communis, Nerium oleander, Withania somnifera, whole plant of Heliotropiaum curassavicum and fruits of Citrullus colocynthis. Synergistical study revealed the best antibacterial activity against B. subtilis and B. pumilus at a level of 1 micro g/ml except E. coli and S. aureus. (author)

Synergistic Antimicrobial Effect of Tribulus terrestris and Bitter Almond Extracts

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Hamid Abtahi

2014-12-01

Full Text Available Background: The antimicrobial effects of the extracts of different kinds of plants have been demonstrated in several studies. However, no study has been conducted so far on the synergistic effects of two herbal extracts on their germicidal effects. In this study, in addition to antibacterial effects of the aqueous, methanol or ethanol extracts of Tribulus terrestris and bitter almond on some bacteria, the synergistic effects of the extracts of these two plants were also evaluated. Materials and Methods: In this experimental study, water, methanol and ethanol extracts of seeds were screened against some bacterial strains. Seeds were extracted by percolation method. Aliquots of the extracts at variable concentrations were then incubated with different bacterial strains, and the antimicrobial activities of the extracts from seeds were determined by MIC. Three antibiotics were used as reference compounds for antibacterial activities. Seeds extract inhibited significantly the growth of the tested bacterial strains. Results: The greatest synergistic effect of T. terrestris and bitter almond extracts is detected in methanol and aqueous extracts. Among the bacterial strains tested, Staphylococcus aureus was most susceptibility. Conclusion: The results showed the highest antibacterial effect in the combination of methanol extract of T. terrestris and the aqueous extract of the bitter almond.

FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and cisplatin in oral squamous cell carcinoma cells

International Nuclear Information System (INIS)

Fang Liang; Wang Huiming; Zhou Lin; Yu Da

2011-01-01

FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of biological processes. The Phosphoinositide-3-kinase (PI3K)/Akt signaling pathway inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation. A loss or gain of FOXO3a activity has been correlated with efficiency of chemotherapies in various cancers including oral squamous cell carcinoma (OSCC). Therefore, in the current study, we have investigated the FOXO3a activity modulating and antitumor effects of rapamycin and cisplatin in OSCC cells. Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and apoptosis. Rapamycin downregulated the expression of S-phase kinase associated protein-2 (Skp2) and increased the FOXO3a protein stability but induced the upregulation of feedback Akt activation-mediated FOXO3a phosphorylation. Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin combined with cisplatin as its feedback Akt activation inhibitor revealed the most dramatic FOXO3a nuclear localization and reactivation with the prevention of its feedback loop and exposed significant synergistic effects of decreased cell proliferation and increased apoptosis in vitro and decreased tumor size in vivo. Furthermore, the downstream effects of FOXO3a reactivation were found to be accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination therapy boosts synergistic antitumor effects through the significant FOXO3a reactivation in OSCC cells. These results may represent a novel mechanism by which rapamycin/cisplatin combination therapy proves to be a potent molecular-targeted strategy for OSCC.

In-Vitro Antibacterial Activities And Preliminary Phytochemical ...

African Journals Online (AJOL)

Studies on the in-vitro antibacterial activities and phytochemical screening of the aqueous and ethanolic extracts of Zingiber officinale (ginger) against some clinical bacterial isolates (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) obtained from ear and urine samples were carried out using ...

Antimicrobial activity of nisin against the swine pathogen Streptococcus suis and its synergistic interaction with antibiotics.

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Lebel, Geneviève; Piché, Fanny; Frenette, Michel; Gottschalk, Marcelo; Grenier, Daniel

2013-12-01

Streptococcus suis serotype 2 is known to cause severe infections in pigs, including meningitis, endocarditis and pneumonia. Furthermore, this bacterium is considered an emerging zoonotic agent. Recently, increased antibiotic resistance in S. suis has been reported worldwide. The objective of this study was to evaluate the potential of nisin, a bacteriocin of the lantibiotic class, as an antibacterial agent against the pathogen S. suis serotype 2. In addition, the synergistic activity of nisin in combination with conventional antibiotics was assessed. Using a plate assay, the nisin-producing strain Lactococcus lactis ATCC 11454 proved to be capable of inhibiting the growth of S. suis (n=18) belonging to either sequence type (ST)1, ST25, or ST28. In a microdilution broth assay, the minimum inhibitory concentration (MIC) of purified nisin ranged between 1.25 and 5 μg/mL while the minimum bactericidal concentration (MBC) was between 5 and 10 μg/mL toward S. suis. The use of a capsule-deficient mutant of S. suis indicated that the presence of this polysaccharidic structure has no marked impact on susceptibility to nisin. Following treatment of S. suis with nisin, transmission electron microscopy observations revealed lysis of bacteria resulting from breakdown of the cell membrane. A time-killing curve showed a rapid bactericidal activity of nisin. Lastly, synergistic effects of nisin were observed in combination with several antibiotics, including penicillin, amoxicillin, tetracycline, streptomycin and ceftiofur. This study brought clear evidence supporting the potential of nisin for the prevention and treatment of S. suis infections in pigs. Copyright © 2013 Elsevier Inc. All rights reserved.

Synergistic antimicrobial activity between pentacyclic triterpenoids and antibiotics against Staphylococcus aureus strains

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Navaratnam Parasakthi

2011-06-01

Full Text Available Abstract Background There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin against reference strains of Staphylococcus aureus. Methods and Results The activity of the standard antibiotics and compounds on reference methicillin-sensitive and resistant strains of S. aureus were determined using the macrodilution broth method. The minimum inhibitory concentration (MIC of the compounds was compared with that of the standard antibiotics. The interaction between any two antimicrobial agents was estimated by calculating the fractional inhibitory concentration (FIC index of the combination. The various combinations of antibiotics and compounds reduced the MIC to a range of 0.05 to 50%. Conclusion Pentacyclic triterpenoids have shown anti-staphylococcal activities and although individually weaker than common antibiotics produced from bacteria and fungi, synergistically these compounds may use different mechanism of action or pathways to exert their antimicrobial effects, as implicated in the lowered MICs. Therefore, the use of current antibiotics could be maintained in their combination with plant-derived antibacterial agents as a therapeutic option in the treatment of S. aureus infections.

Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53

International Nuclear Information System (INIS)

Niemantsverdriet, Maarten; Jong, Edwin de; Langendijk, Johannes A.; Kampinga, Harm H.; Coppes, Robert P.

2010-01-01

Radiation-induced fibrosis is a severe side effect of radiotherapy. TGF-β and radiation synergistically induce expression of the profibrotic PAI-1 gene and this cooperation potentially involves p53. Here, we demonstrate that p53 is both indispensable and sufficient for the radiation effect inducing synergistic activation of PAI-1 by radiation and TGF-β.

Synergistic antitumor activity of histamine plus melphalan in isolated limb perfusion: preclinical studies.

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Brunstein, Flavia; Hoving, Saske; Seynhaeve, Ann L B; van Tiel, Sandra T; Guetens, Gunther; de Bruijn, Ernst A; Eggermont, Alexander M M; ten Hagen, Timo L M

2004-11-03

We have previously shown how tumor response of isolated limb perfusion (ILP) with melphalan was improved when tumor necrosis factor alpha (TNF-alpha) was added. Taking into account that other vasoactive drugs could also improve tumor response to ILP, we evaluated histamine (Hi) as an alternative to TNF-alpha. We used a rat ILP model to assess the combined effects of Hi and melphalan (n = 6) on tumor regression, melphalan uptake (n = 6), and tissue histology (n = 2) compared with Hi or melphalan alone. We also evaluated the growth of BN-175 tumor cells as well as apoptosis, necrosis, cell morphology, and paracellular permeability of human umbilical vein endothelial cells (HUVECs) after Hi treatment alone and in combination with melphalan. The antitumor effect of the combination of Hi and melphalan in vivo was synergistic, and Hi-dependent reduction in tumor volume was blocked by H1 and H2 receptor inhibitors. Tumor regression was observed in 66% of the animals treated with Hi and melphalan, compared with 17% after treatment with Hi or melphalan alone. Tumor melphalan uptake increased and vascular integrity in the surrounding tissue was reduced after ILP treatment with Hi and melphalan compared with melphalan alone. In vitro results paralleled in vivo results. BN-175 tumor cells were more sensitive to the cytotoxicity of combined treatment than HUVECs, and Hi treatment increased the permeability of HUVECs. Hi in combination with melphalan in ILP improved response to that of melphalan alone through direct and indirect mechanisms. These results warrant further evaluation in the clinical ILP setting and, importantly, in organ perfusion.

Synergistic properties of graphitic carbon nitride/cerium molybdate nanocomposites for enhanced photocatalytic activity

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Bhargava, V. S.; Singh, Gajendar; Sharma, Manu

2018-05-01

A polymeric semiconductor (g-C3N4), based nanocomposites have been achieved much attention due to its excellent thermal, chemical stability and suitable band positions for water splitting. g-C3N4 based nanocomposites show good performance in the field of photocatalysis, sensors, Li-ion batteries, supercapacitors and water purification technology. In this work, a series of novel g-C3N4/CeM nano composites were synthesized using a facile one-step ultra-sonication method. X-ray diffraction (XRD) pattern confirms the formation of g-C3N4 and cerium molybdate. The photocatalytic activity of nanocomposites indicated the substantial degradation of Methylene Blue (MB) dye up to 97% over the surface of g-C3N4/CeM under visible light illumination. All the g-C3N4/CeM composites possess higher photocatalytic activity than pure cerium molybdate. The proposed mechanism demonstrated that the different weight ratios of photocatalyst were most likely attributed to a synergistic effect between g-C3N4 and CeM. This approach is very simple, cost effective, and free from any surfactant that makes it valuable catalyst for various future applications.

Synergistic effect of Murraya koenigii and Telfairia occidentalis ...

African Journals Online (AJOL)

Larger zones of inhibition were observed for M. Koenigii extract than T. occidentalis extract, and larger zones of inhibition were observed by their synergy than on their separate use. Synergistic antibacterial activity of the extract ranged from 0 mm to 20.0 ± 0.03 mm, zone of inhibition of M. koenigii extract ranged from 0 mm ...

Synergistic pretreatment of waste activated sludge using CaO_2 in combination with microwave irradiation to enhance methane production during anaerobic digestion

International Nuclear Information System (INIS)

Wang, Jie; Li, Yongmei

2016-01-01

Highlights: • CaO_2/MW pretreatment synergistically enhanced WAS solubilization and CH_4 production. • MW irradiation facilitated more "·OH generation from CaO_2. • The optimal pretreatment condition for methane production was determined. • The growths of both hydrogenotrophic and acetate-utilizing methanogens were promoted. • The dewaterability of WAS was improved considerably by CaO_2/MW treatment. - Abstract: To investigate the effects of combined calcium peroxide (CaO_2) and microwave pretreatment on anaerobic digestion of waste activated sludge, lab-scale experiments were conducted to measure the solubilization, biodegradation, and dewaterability of the waste activated sludge. Additionally, the synergistic effects between CaO_2 and microwave were studied, and the microbial activity and methanogenic archaea community structure were analyzed. Combined pretreatment considerably facilitated the solubilization and subsequent anaerobic digestion of the waste activated sludge. The optimal pretreatment condition was CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) for methane production during the subsequent anaerobic digestion process. Under this condition, 80.2% higher CH_4 accumulation yield was achieved after 16 d of anaerobic digestion when compared with the control. The synergistic effects of CaO_2/microwave pretreatment resulted from the different mechanisms of CaO_2 and microwave treatments. Further, microwave irradiation increased "·OH generation from CaO_2 and significantly alleviated the inhibitory effect of CaO_2 on methanogens. The activities of hydrolytic enzymes and acid-forming enzymes in the waste activated sludge were improved after CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) pretreatment. Methanogenesis enzyme activity was also higher after CaO_2 treatment (0.1 g/gVSS)/microwave (480 W, 2 min) following a lag period. Illumina MiSeq sequencing analysis indicated that acetate-utilizing methanogen (Methanosaeta sp.) and H_2/CO_2-utilizing

Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

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Benjamin A Nacev

Full Text Available Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA, an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50 dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

Synergistic inhibition of endothelial cell proliferation, tube formation, and sprouting by cyclosporin A and itraconazole.

Science.gov (United States)

Nacev, Benjamin A; Liu, Jun O

2011-01-01

Pathological angiogenesis contributes to a number of diseases including cancer and macular degeneration. Although angiogenesis inhibitors are available in the clinic, their efficacy against most cancers is modest due in part to the existence of alternative and compensatory signaling pathways. Given that angiogenesis is dependent on multiple growth factors and a broad signaling network in vivo, we sought to explore the potential of multidrug cocktails for angiogenesis inhibition. We have screened 741 clinical drug combinations for the synergistic inhibition of endothelial cell proliferation. We focused specifically on existing clinical drugs since the re-purposing of clinical drugs allows for a more rapid and cost effective transition to clinical studies when compared to new drug entities. Our screen identified cyclosporin A (CsA), an immunosuppressant, and itraconazole, an antifungal drug, as a synergistic pair of inhibitors of endothelial cell proliferation. In combination, the IC(50) dose of each drug is reduced by 3 to 9 fold. We also tested the ability of the combination to inhibit endothelial cell tube formation and sprouting, which are dependent on two essential processes in angiogenesis, endothelial cell migration and differentiation. We found that CsA and itraconazole synergistically inhibit tube network size and sprout formation. Lastly, we tested the combination on human foreskin fibroblast viability as well as Jurkat T cell and HeLa cell proliferation, and found that endothelial cells are selectively targeted. Thus, it is possible to combine existing clinical drugs to synergistically inhibit in vitro models of angiogenesis. This strategy may be useful in pursuing the next generation of antiangiogenesis therapy.

In vitro Antifungal, Antioxidant and Cytotoxic Activities of a Partially ...

African Journals Online (AJOL)

Purpose: To determine the in vitro antifungal and antioxidant activities of the aqueous extract and protein fraction of Atlantia monophylla Linn (Rutaceae) leaf. Methods: Ammonium sulphate (0 – 80 %) precipitation method was used to extract protein from the leaves of A. monophylla Linn (Rutaceae). In vitro antifungal ...

Synergistic Synthetic Biology: Units in Concert

Science.gov (United States)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

Synergistic Synthetic Biology: Units in Concert

International Nuclear Information System (INIS)

Trosset, Jean-Yves; Carbonell, Pablo

2013-01-01

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

Synergistic effects of sodium hypochlorite and ultraviolet radiation in reducing the levels of selected foodborne pathogenic bacteria.

Science.gov (United States)

Ha, Ji-Hyoung; Ha, Sang-Do

2011-05-01

The purpose of this study was to determine whether combined treatment would produce synergistic effects to facilitate the sterilization of food products during production relative to single treatment. To assess this hypothesis, we investigated the bactericidal effects of ultraviolet (UV) irradiation and a commercial chemical disinfectant, sodium hypochlorite (NaClO), on Bacillus cereus F4810/72, Cronobacter sakazakii KCTC 2949, Staphylococcus aureus ATCC 35556, Escherichia coli ATCC 10536, and Salmonella Typhimurium novobiocin/nalidixic acid in vitro. Various concentrations of NaClO (20, 60, 100, and 200 ppm NaClO) were tested along with exposure to UV radiation at various doses (6, 96, 216, 360, and 504 mW s/cm(2)). The combined NaClO/UV treatments resulted in greater reductions in bacterial counts than either treatment alone. The synergy values against B. cereus, C. sakazakii, S. aureus, Salmonella Typhimurium, and E. coli were 0.25-1.17, 0.33-1.97, 0.42-1.72, 0.02-1.44, and 0.01-0.85 log(10) CFU/mL, respectively. The results of this study suggest that a significant synergistic benefit results from combined NaClO/UV processing against food-borne pathogenic bacteria in vitro.

In vitro antimycobacterial activity of acetone extract of Glycyrrhiza glabra

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Swapna S. Nair

2015-08-01

Full Text Available Context: Glycyrrhiza glabra (licorice has been used since ages as expectorant, antitussive and demulcent. G. glabra has been indicated in Ayurveda as an antimicrobial agent for the treatment of respiratory infections and tuberculosis. Aims: To evaluate the antimycobacterial activity of acetone extract of G. glabra by in vitro techniques. Methods: The anti-tubercular activity of acetone extract of G. glabra, obtained by Soxhlet extraction, was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294. The in vitro anti-tubercular activity was determined by Resazurin Microtiter Plate Assay (REMA and colony count method. Further, the anti-tubercular activity of acetone extract of G. glabra was determined in human macrophage U937 cell lines and was compared against that of the standard drugs isoniazid, rifampicin and ethambutol. Results: G. glabra extract showed significant activity against Mycobacterium tuberculosis, when evaluated by REMA/colony count methods and in U937 human macrophage cell lines infected with Mycobacterium tuberculosis H37Rv. The activity of the extract was comparable to those of standard drugs. It was observed that the extract showed time and concentration dependent antimycobacterial activity. Conclusions: The present study reveals that G. glabra extract has promising anti-tubercular activity by preliminary in vitro techniques and in U937 macrophage cell line. Therefore, it has the definite potential to be developed as an affordable, cost-effective drug against tuberculosis.

Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity.

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Liu, Jie; Zhang, Cao; Wang, Huailing; Zhang, Lei; Jiang, Zhenlei; Zhang, Jianrun; Liu, Zhijun; Chen, Heru

2018-05-10

Fifty 1,3-dioxyxanthone nitrates (4a ∼ i-n, n = 1-6) were designed and synthesized based on molecular similarity strategy. Incorporation of nitrate into 1,3-dioxyxanthones with electron-donating groups at 6-8 position brought about synergistic anticancer effect. Among them, compound 4g-4 was confirmed the most active agent against HepG-2 cells growth with an IC 50 of 0.33 ± 0.06 μM. It dose-dependently increased intramolecular NO levels. This activity was attenuated by either NO scavenger PTIO or mitochondrial aldehyde dehydrogenase (mtADH) inhibitor PCDA. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for different dose of 4g-4. 4g-4 arrested more cells on S phase. Results from Western Blot implied that 4g-4 regulated p53/MDM2 to promote cancer cell apoptosis. All the evidences support that 4g-4 is a promising anti-cancer agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Synergistic effects on dislocation loops in reduced-activation martensitic steel investigated by single and sequential hydrogen/helium ion irradiation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Weiping [Hubei Nuclear Solid Physics Key Laboratory, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Luo, Fengfeng [Hubei Nuclear Solid Physics Key Laboratory, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Institute of Applied Physics, Jiangxi Academy of Sciences, Nanchang 330029 (China); Yu, Yanxia; Zheng, Zhongcheng; Shen, Zhenyu [Hubei Nuclear Solid Physics Key Laboratory, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Guo, Liping, E-mail: guolp@whu.edu.cn [Hubei Nuclear Solid Physics Key Laboratory, Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Ren, Yaoyao [Center for Electron Microscopy, Wuhan University, Wuhan 430072 (China); Suo, Jinping [State Key Laboratory of Mould Technology, Institute of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

2016-10-15

Single-beam and sequential-beam irradiations were performed to investigate the H/He synergistic effect on dislocation loops in reduced-activation ferritic/martensitic (RAFM) steels. The irradiations were carried out with 10 keV H{sup +}, 18 keV He{sup +} and 160 keV Ar{sup +}, alone and in combination at 723 K. He{sup +} single-beam irradiation induced much larger dislocation loops than that induced by both H{sup +} and Ar{sup +} single-beam irradiation. H{sup +} post-irradiation after He{sup +} irradiation further increased the size of dislocation loops, whilst He{sup +} post-irradiation or Ar{sup +} post-irradiation following H{sup +} irradiation only slightly increased the size of dislocation loops. The experiment results indicate that pre-implanted H{sup +} can drastically inhibit the growth while post-implanted H{sup +} can significantly enhance the growth of dislocation loops induced by He{sup +} irradiation. The mechanisms behind the complex synergistic phenomena between H and He and the different roles that H and He played in the growth of dislocation loops are discussed.

In vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin against carbapenem-resistant Acinetobacter baumannii clinical isolates.

Science.gov (United States)

Singkham-In, Uthaibhorn; Chatsuwan, Tanittha

2018-01-31

Carbapenem-resistant Acinetobacter baumannii clinical isolates (n=23) were investigated for carbapenem resistance mechanisms and in vitro activities of carbapenems in combination with amikacin, colistin, or fosfomycin. Major carbapenem resistance mechanism was OXA-23 production. The vast majority of these isolates were OXA-23-producing A. baumannii ST195 and ST542, followed by novel STs, ST1417, and ST1423. The interuption of carO by a novel insertion sequence, ISAba40, was found in two isolates. The combinations of imipenem and fosfomycin, meropenem and amikacin, imipenem and amikacin, and imipenem and colistin were synergistic against carbapenem-resistant A. baumannii by 65.2%, 46.2%, 30.8%, and 17.4%, respectively. Surprisingly, the combination of imipenem and fosfomycin was the most effective in this study against A. baumannii, which is intrinsically resistant to fosfomycin. Imipenem and fosfomycin inhibit cell wall synthesis; therefore, fosfomycin may be an adjuvant and enhance the inhibition of cell wall synthesis of carbapenem-resistant A. baumannii when combined with imipenem. Copyright © 2018. Published by Elsevier Inc.

ENRAIZAMENTO DE CRAVO (Dianthus caryophyllus L. IN VITRO E EX VITRO

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G.R.F CUZZUOL

1996-01-01

Full Text Available Plântulas de cravo (Dianthus caryophyllus micropropagadas durante várias gerações pelo período de um ano, foram enraizadas in vitro com AIA, ANA e AIB nas concentrações de 0,0; 0,25; 0,5 e 1,0 mg/l, em fatorial do tipo 3 x 4, com todos os tratamentos promovendo a formação de raízes, mas não diferindo do controle. Foi confrontado em condição autotrófica, o desempenho entre plântulas enraizadas in vitro na presença e ausência do regulador AIA 0,5 mg/l e plântulas enraizadas ex vitro, sem nenhuma diferença quanto ao comprimento da parte aérea. Para a variável produção de massa de matéria seca os melhores resultados foram proporcionados pelas plantas que passaram pela fase de enraizamento in vitro, tendo o sistema radicular efeito sinergístico no crescimento da parte aérea.Plantlets of carnation (Dianthus caryophyllus L. micropropagated through several generations during one year, were observed with respect to rooting in vitro, in the presence of IAA , NAA and IBA, at the following concentrations: 0,0; 0,25; 0,5 and 1,0 mg/l. All treatments promoted root formation, however no differences were detected in comparison to control. As far as the lenght of the aerial part is concerned no difference was observed between in vitro rooting. in the presence or absence of IAA 0,5 mg/l, and ex vitro rooting. Plantlets which were rooted in vitro conditions showed higher production of fresh matter then those rooted ex vitro. The root system had a synergistic effect on the growth of the aerial part.

Can toxicokinetic and toxicodynamic modeling be used to understand and predict synergistic interactions between chemicals?

DEFF Research Database (Denmark)

Cedergreen, Nina; Dalhoff, Kristoffer; Li, Dan

2017-01-01

including synergists. The aim of the present study is to develop a mechanistic toxicokinetic (TK) and toxicodynamic (TD) model for the synergistic mixture of the azole fungicide, propiconazole (the synergist), and the insecticide, α-cypermethrin, on the mortality of the crustacean Daphnia magna. The study...... by their effect on the biotransformation rate but that this effect could only partly be explained by the effect of the two azoles on cytochrome P450 activity, measured on D. magna in vivo. TKTD models of interacting mixtures seem to be a promising tool to test mechanisms of interactions between chemicals...

In vitro and in vivo antioxidant activities of inulin.

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Hong-Mei Shang

Full Text Available This study was designed to investigate the in vitro and in vivo antioxidant activities of inulin. The in vitro assays demonstrated that the antioxidant activities of inulin, including the DPPH radical scavenging activity, ABTS scavenging activity and ferric reducing power, were weak and significantly lower than those of Vitamin C (P < 0.05. The influence of dietary supplementation with inulin on the antioxidant status of laying hens was evaluated with in vivo antioxidant assays. The results indicated that inulin supplementation quadratically improved the egg production rate of the laying hens (P < 0.01. The antioxidant enzyme activities in the serum, including SOD, CAT, and GSH-Px, and the total antioxidant capacity increased quadratically as inulin levels increased (P < 0.001. The levels of MDA in the serum decreased quadratically as inulin levels increased (P < 0.001. These findings suggest that inulin has the potential to improve the antioxidant status of laying hens.

Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage.

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Sana, Santanu; Datta, Sriparna; Biswas, Dipa; Sengupta, Dipanjan

2018-02-01

Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future. Copyright © 2017 Elsevier B.V. All rights reserved.

Pentamidine is active in vitro against Fusarium species.

Science.gov (United States)

Lionakis, Michail S; Lewis, Russell E; Samonis, George; Kontoyiannis, Dimitrios P

2003-10-01

Fusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates of Fusarium species (five Fusarium solani isolates and five non-F. solani isolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye staining. PNT had significant activities against all 10 Fusarium isolates. Non-F. solani isolates were more susceptible than F. solani isolates (P Fusarium isolates was confirmed microscopically after staining of PNT-treated Fusarium oxysporum hyphae with the fluorescent viability dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC). The MICs at which 50% of the isolates were inhibited (2 micro g/ml for non-F. solani isolates and 4 micro g/ml for F. solani isolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 micro g/ml for non-F. solani isolates) were much lower than the PNT tissue concentrations previously reported in humans using conventional daily intravenous PNT dosing. Finally, PNT was more active against Fusarium isolates in a hypoxic environment of in vitro growth (P Fusarium, an angiotropic mold, causes tissue infarcts with resultant low tissue perfusion. Our findings suggest that PNT may have a role in the management of Fusarium infections. Future in vivo studies are needed to verify these in vitro findings.

Antimalarial activity of plumbagin in vitro and in animal models.

Science.gov (United States)

Sumsakul, Wiriyaporn; Plengsuriyakarn, Tullayakorn; Chaijaroenkul, Wanna; Viyanant, Vithoon; Karbwang, Juntra; Na-Bangchang, Kesara

2014-01-12

Plumbagin is the major active constituent in several plants including Plumbago indica Linn. (root). This compound has been shown to exhibit a wide spectrum of biological and pharmacological activities. The present study aimed to evaluate the in vitro and in vivo antimalarial activity of plumbagin including its acute and subacute toxicity in mice. In vitro antimalarial activity of plumbagin against K1 and 3D7 Plasmodium falciparum clones were assessed using SYBR Green I based assay. In vivo antimalarial activity was investigated in Plasmodium berghei-infected mouse model (a 4-day suppressive test). Plumbagin exhibited promising antimalarial activity with in vitro IC50 (concentration that inhibits parasite growth to 50%) against 3D7 chloroquine-sensitive P. falciparum and K1 chloroquine-resistant P. falciparum clones of 580 (270-640) and 370 (270-490) nM, respectively. Toxicity testing indicated relatively low toxicity at the dose levels up to 100 (single oral dose) and 25 (daily doses for 14 days) mg/kg body weight for acute and subacute toxicity, respectively. Chloroquine exhibited the most potent antimalarial activity in mice infected with P. berghei ANKA strain with respect to its activity on the reduction of parasitaemia on day 4 and the prolongation of survival time. Plumbagin at the dose of 25 mg/kg body weight given for 4 days was safe and produced weak antimalarial activity. Chemical derivatization of the parent compound or preparation of modified formulation is required to improve its systemic bioavailability.

In vitro antifungal activity of methanol extracts of some Indian ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... vitro antifungal activity against some yeasts including Candida albicans (1) ATCC2091, ... Key words: medicinal plants, antifungal activity, methanol extracts, yeast, mould, Saussurea lappa. ... Caesalpinia pulcherrima.

Control of anthracnose caused by Colletotrichum species in guava, mango and papaya using synergistic combinations of chitosan and Cymbopogon citratus (D.C. ex Nees) Stapf. essential oil.

Science.gov (United States)

Lima Oliveira, Priscila Dinah; de Oliveira, Kataryne Árabe Rimá; Vieira, Willie Anderson Dos Santos; Câmara, Marcos Paz Saraiva; de Souza, Evandro Leite

2018-02-02

This study assessed the efficacy of chitosan (Chi) and Cymbopogon citratus (D.C. ex Nees) Stapf. essential oil (CCEO) combinations to control the mycelial growth of five pathogenic Colletotrichum species (C. asianum, C. siamense, C. fructicola, C. tropicale and C. karstii) in vitro, as well as the anthracnose development in guava (Psidium guajava L.) cv. Paluma, mango (Mangifera indica L.) cv. Tommy Atkins and papaya (Carica papaya L.) cv. Papaya artificially inoculated with these species. Combinations of Chi (2.5, 5 or 7.5mg/mL) and CCEO (0.15, 0.3, 0.6 or 1.25μL/mL) inhibited the mycelial growth of all tested fungal species in vitro. Examined Chi-CCEO combinations showed additive or synergistic interactions to inhibit the target Colletotrichum species based on the Abbott index. Coatings formed by synergistic Chi (5mg/mL) and CCEO (0.15, 0.3 or 0.6μL/mL) combinations decreased anthracnose lesion development in guava, mango and papaya inoculated with any of the tested Colleotrichum species during storage. Overall, anthracnose lesion development inhibition in fruit coated with synergistic Chi-CCEO combinations was higher than that observed in fruit treated with synthetic fungicides. These results show that the application of coatings formed by Chi-CCEO synergistic combinations could be effective to control postharvest anthracnose development in fruit. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vitro Antibacterial Activity of Essential Oils against Streptococcus pyogenes

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Julien Sfeir

2013-01-01

Full Text Available Streptococcus pyogenes plays an important role in the pathogenesis of tonsillitis. The present study was conducted to evaluate the in vitro antibacterial activities of 18 essential oils chemotypes from aromatic medicinal plants against S. pyogenes. Antibacterial activity of essential oils was investigated using disc diffusion method. Minimum Inhibitory Concentration of essential oils showing an important antibacterial activity was measured using broth dilution method. Out of 18 essential oils tested, 14 showed antibacterial activity against S. pyogenes. Among them Cinnamomum verum, Cymbopogon citratus, Thymus vulgaris CT thymol, Origanum compactum, and Satureja montana essential oils exhibited significant antibacterial activity. The in vitro results reported here suggest that, for patients suffering from bacterial throat infections, if aromatherapy is used, these essential oils, considered as potential antimicrobial agents, should be preferred.

Synergistic Effect of Cu2O and Urea as Modifiers of TiO2 for Enhanced Visible Light Activity

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Marcin Janczarek

2018-06-01

Full Text Available Low cost compounds, i.e., Cu2O and urea, were used as TiO2 modifiers to introduce visible light activity. Simple and cheap methods were applied to synthesize an efficient and stable nanocomposite photocatalytic material. First, the core-shell structure TiO2–polytriazine derivatives were prepared. Thereafter, Cu2O was added as the second semiconductor to form a dual heterojunction system. Enhanced visible light activity was found for the above-mentioned nanocomposite, confirming a synergistic effect of Cu2O and urea (via polytriazine derivatives on titania surface. Two possible mechanisms of visible light activity of the considered material were proposed regarding the type II heterojunction and Z-scheme through the essential improvement of the charge separation effect.

Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

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Leblond Lorraine

2007-07-01

Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

International Nuclear Information System (INIS)

Damaraju, Vijaya L; Bouffard, David Y; Wong, Clarence KW; Clarke, Marilyn L; Mackey, John R; Leblond, Lorraine; Cass, Carol E; Grey, Mike; Gourdeau, Henriette

2007-01-01

Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug

Synergistic reduction of toluylene blue induced by acetaldehyde and menadione in yeast cell suspension: Application to determination of yeast cell activity

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Shiro Yamashoji

2017-03-01

Full Text Available Membrane permeant acetaldehyde and menadione induced the synergistic reduction of toluylene blue (TB acting as non-membrane permeant redox indicator in yeast cell suspension. NADH and acetaldehyde also induced the synergistic TB reduction in permeabilized yeast cells and phosphate buffer, but menadione had no ability to promote TB reduction. The pre-incubation of acetaldehyde inhibited the above synergistic reduction of TB in intact and permeabilized yeast cell suspension. The pre-incubation of acetaldehyde might promote NADH oxidation by alcohol dehydrogenase, because acetaldehyde decreased the intracellular NAD(PH concentration. The above facts indicate that the synergistic reduction of TB is controlled by the order of addition of menadione and acetaldehyde. The synergistic reduction of TB by menadione and acetaldehyde was proportional to viable yeast cell number from 104 to 2×106 cells/ml, and this assay was applicable to cytotoxicity test. The time required for the above assay was only 2 min.

Prediction of in vitro and in vivo oestrogen receptor activity using hierarchical clustering

Science.gov (United States)

In this study, hierarchical clustering classification models were developed to predict in vitro and in vivo oestrogen receptor (ER) activity. Classification models were developed for binding, agonist, and antagonist in vitro ER activity and for mouse in vivo uterotrophic ER bindi...

Acidosis activates complement system in vitro.

OpenAIRE

Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

1998-01-01

We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic result...

Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics

DEFF Research Database (Denmark)

Rathe, Mathias; Lise, Kristensen,; Ellermann-Eriksen, Svend

Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics......Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics...

Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds

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H. Hajimehdipoor

2014-04-01

Full Text Available Phenolic and flavonoid compounds are secondary metabolites of plants which possess various activities such as anti-inflammatory, analgesic, anti-diabetes and anticancer effects. It has been established that these compounds can scavenge free radicals produced in the body. Because of this ability, not only the plants containing phenolic and flavonoid compounds but also, the pure compounds are used in medicinal products for prevention and treatment of many disorders. Considering that the golden aim of the pharmaceutical industries is using the most effective compounds with lower concentrations, determination of the best combination of the compounds with synergistic effects is important. In the present study, synergistic antioxidant effects of four phenolic compounds including caffeic acid, gallic acid, rosmarinic acid, chlorogenic acid and two flavonoids,  rutin and quercetin, have been investigated by FRAP (Ferric Reducing Antioxidant Power method. The synergistic effect was assessed by comparing the experimental antioxidant activity of the mixtures with calculated theoretical values and the interactions of the compounds were determined. The results showed that combination of gallic acid and caffeic acid demonstrated considerable synergistic effects (137.8% while other combinations were less potent. Among examined substances, rutin was the only one which had no effect on the other compounds. The results of ternary combinations of compounds demonstrated antagonistic effects in some cases. This was more considerable in mixture of rutin, caffeic acid, rosmarinic acid (-21.8%, chlorogenic acid, caffeic acid, rosmarinic acid (-20%, rutin, rosmarinic acid, gallic acid (-18.5% and rutin, chlorogenic acid, caffeic acid (-15.8%, while, combination of quercetin, gallic acid, caffeic acid (59.4% and quercetin, gallic acid, rutin (55.2% showed the most synergistic effects. It was concluded that binary and ternary combination of quercetin, rutin, caffeic acid

In vitro activity of difloxacin against canine bacterial isolates

NARCIS (Netherlands)

Hoven, van den J.R.; Wagenaar, J.A.; Walker, R.D.

2000-01-01

The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

2012-12-15

Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

Generation of induced pluripotent stem cells (iPSCs) stably expressing CRISPR-based synergistic activation mediator (SAM).

Science.gov (United States)

Xiong, Kai; Zhou, Yan; Hyttel, Poul; Bolund, Lars; Freude, Kristine Karla; Luo, Yonglun

2016-11-01

Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated. These SAM-iPSCs provide a novel, useful tool to investigate genetic regulation of stem cell proliferation and differentiation through CRISPR-mediated activation of endogenous genes. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase.

Science.gov (United States)

Chan, Ben C L; Ip, Margaret; Lau, Clara B S; Lui, S L; Jolivalt, Claude; Ganem-Elbaz, Carine; Litaudon, Marc; Reiner, Neil E; Gong, Huansheng; See, Raymond H; Fung, K P; Leung, P C

2011-09-01

Baicalein, the active constituent derived from Scutellaria baicalensis Georgi., has previously been shown to significantly restore the effectiveness of β-lactam antibiotics and tetracycline against methicillin-resistant Staphylococcus aureus (MRSA). With multiple therapeutic benefits, the antibacterial actions of baicalein may also be involved in overcoming other bacterial resistance mechanisms. The aim of the present study was to further investigate antibacterial activities of baicalein in association with various antibiotics against selected Staphylococcus aureus strains with known specific drug resistance mechanisms. A panel of clinical MRSA strains was used for further confirmation of the antibacterial activities of baicalein. The effect of baicalein on inhibiting the enzymatic activity of a newly discovered MRSA-specific pyruvate kinase (PK), which is essential for Staphylococcus aureus growth and survival was also examined. In the checkerboard dilution test and time-kill assay, baicalein at 16 μg/ml could synergistically restore the antibacterial actions of ciprofloxacin against the NorA efflux pump overexpressed SA-1199B, but not with the poor NorA substrate, pefloxacin. Moreover, synergistic effects were observed when baicalein was combined with ciprofloxacin against 12 out of 20 clinical ciprofloxacin resistant strains. For MRSA PK studies, baicalein alone could inhibit the enzymatic activity of MRSA PK in a dose-dependent manner. Our results demonstrated that baicalein could significantly reverse the ciprofloxacin resistance of MRSA possibly by inhibiting the NorA efflux pump in vitro. The inhibition of MRSA PK by baicalein could lead to a deficiency of ATP which might further contribute to the antibacterial actions of baicalein against MRSA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In vitro antimetastatic activity of Agarwood ( Aquilaria crassna ...

African Journals Online (AJOL)

In vitro antimetastatic activity of Agarwood (Aquilaria crassna) essential oils against pancreatic cancer cells. Saad Sabbar Dahham, Yasser M Tabana, Loiy E Ahmed Hassan, Mohamed B Khadeer Ahamed, Aman Shah Abdul Majid, Amin Malik Shah Abdul Majid ...

Comparative in-vitro activity of Imipenem and Doripenem against ...

African Journals Online (AJOL)

Background: Doripenem is a recent carbapenem not commercially available in Nigeria with broad spectrum antibacterial activity against various clinical infections. Carbapenems have been shown to be the last line of agents against ESBL producing organisms. Objective: To determine the in-vitro activity of Imipenem and ...

Anethole, a potential antimicrobial synergist, converts a fungistatic dodecanol to a fungicidal agent.

Science.gov (United States)

Fujita, Ken-Ichi; Fujita, Tomoko; Kubo, Isao

2007-01-01

Anethole shows synergistic effects on the antifungal activities of phytochemicals including polygodial and (2E)-undecenal against Saccharomyces cerevisiae and Candida albicans. It was found that a fungistatic dodecanol combined with a sublethal amount of anethole showed a fungicidal activity against S. cerevisiae. The MIC of dodecanol quickly reduced cell viability, but the cell viability recovered shortly after and then finally became no longer different from the control, indicating that the effect of dodecanol on this yeast was classified as sublethal damage. On the other hand, anethole completely restricted the recovery of cell viability. Therefore the expression of the synergistic effect was probably due to a blockade of the recovery process from dodecanol-induced stress.

[Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

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Ueki, H

1987-11-01

We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.

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Jennifer Keiser

Full Text Available BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI = 2.53. Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively. A highly synergistic effect (CI = 0.15 was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSION/SIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be

Synergistic effect of eugenol with Colistin against clinical isolated Colistin-resistant Escherichia coli strains

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Yi-ming Wang

2018-01-01

Full Text Available Abstract Background Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli strains, and to evaluate potential interaction. Methods Antimicrobial susceptibility, minimum inhibitory concentration (MIC and fractional inhibitory concentration index (FICI of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625. Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains. Graphical abstract Synergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.

Proto-oncogene FBI-1 (Pokemon) and SREBP-1 Synergistically Activate Transcription of Fatty-acid Synthase Gene (FASN)*S⃞

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Choi, Won-Il; Jeon, Bu-Nam; Park, Hyejin; Yoo, Jung-Yoon; Kim, Yeon-Sook; Koh, Dong-In; Kim, Myung-Hwa; Kim, Yu-Ri; Lee, Choong-Eun; Kim, Kyung-Sup; Osborne, Timothy F.; Hur, Man-Wook

2008-01-01

FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-à-brac, tramtrack, and broad complex and pox virus zinc finger) domain family. Recent evidence suggested that FBI-1 might be involved in adipogenic gene expression. Coincidentally, expression of FBI-1 and fatty-acid synthase (FASN) genes are often increased in cancer and immortalized cells. Both FBI-1 and FASN are important in cancer cell proliferation. SREBP-1 is a major regulator of many adipogenic genes, and FBI-1 and SREBP-1 (sterol-responsive element (SRE)-binding protein 1) interact with each other directly via their DNA binding domains. FBI-1 enhanced the transcriptional activation of SREBP-1 on responsive promoters, pGL2-6x(SRE)-Luc and FASN gene. FBI-1 and SREBP-1 synergistically activate transcription of the FASN gene by acting on the proximal GC-box and SRE/E-box. FBI-1, Sp1, and SREBP-1 can bind to all three SRE, GC-box, and SRE/E-box. Binding competition among the three transcription factors on the GC-box and SRE/E-box appears important in the transcription regulation. FBI-1 is apparently changing the binding pattern of Sp1 and SREBP-1 on the two elements in the presence of induced SREBP-1 and drives more Sp1 binding to the proximal promoter with less of an effect on SREBP-1 binding. The changes induced by FBI-1 appear critical in the synergistic transcription activation. The molecular mechanism revealed provides insight into how proto-oncogene FBI-1 may attack the cellular regulatory mechanism of FASN gene expression to provide more phospholipid membrane components needed for rapid cancer cell proliferation. PMID:18682402

Synergistic action of fatty acids, sulphides and stilbene against acaricide-resistant Rhipicephalus microplus ticks.

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Arceo-Medina, G N; Rosado-Aguilar, J A; Rodríguez-Vivas, R I; Borges-Argaez, R

2016-09-15

Six compounds in a methanolic extract of Petiveria alliacea stem (cis-stilbene; benzyl disulphide; benzyl trisulphide; and methyl esters of hexadecanoic acid, octadecadienoic acid and octadecenoic acid) are known to exercise acaricide activity against cattle tick Rhipicephalus microplus larvae and adults. The synergistic effect of 57 combinations of these six compounds on acaricide activity against R. microplus was evaluated. Larvae immersion tests produced the lethal concentrations needed to kill 50% (LC 50 ) and 99% (LC 99 ) of the population. Adult immersion tests produced rates (%) for mortality, oviposition inhibition and eclosion inhibition. Individually, none of the compounds (1% concentration) exhibited acaricide activity (mortality ≤2.3%). When combined, however, nine mixtures exhibited a synergistic increase in activity, with high mortality rates (≥92%) in larvae. Values for LC 50 ranged from 0.07 to 0.51% and those for LC 99 from 0.66 to 5.16%. Thirty six compound mixtures had no significant activity (mortality ≤30%) against larvae. Two mixtures exhibited synergism against adults, with high rates (≥92%) of oviposition inhibition. The mixtures based on the benzyl disulphide+benzyl trisulphide pairing produced a synergistic effect against acaricide-resistant R. microplus larva and adults, and are therefore the most promising combination for controlling this ubiquitous ectoparasite. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

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Johanna Poecheim

2015-12-01

Full Text Available Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA. The formulations included (1 trimethyl chitosan (TMC nanoparticles, (2 a squalene-in-water nanoemulsion, and (3 a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9. In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2 was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.

Human harvest, climate change and their synergistic effects drove the Chinese Crested Tern to the brink of extinction

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Shuihua Chen

2015-07-01

Full Text Available Synergistic effect refers to simultaneous actions of separate factors which have a greater total effect than the sum of the individual factor effects. However, there has been a limited knowledge on how synergistic effects occur and individual roles of different drivers are not often considered. Therefore, it becomes quite challenging to manage multiple threatening processes simultaneously in order to mitigate biodiversity loss. In this regard, our hypothesis is, if the traits actually play different roles in the synergistic interaction, conservation efforts could be made more effectively. To understand the synergistic effect and test our hypothesis, we examined the processes associated with the endangerment of critically endangered Chinese Crested Tern (Thalasseus bernsteini, whose total population number was estimated no more than 50. Through monitoring of breeding colonies and investigations into causative factors, combined with other data on human activities, we found that widespread human harvest of seabird eggs and increasing frequency of typhoons are the major factors that threatened the Chinese Crested Tern. Furthermore, 28 percent of breeding failures were due to the synergistic effects in which egg harvest-induced renestings suffered the higher frequent typhoons. In such combined interactions, the egg harvest has clearly served as a proximal factor for the population decline, and the superimposition of enhanced typhoon activity further accelerated the species toward imminent extinction. Our findings suggest that species endangerment, on one hand, should be treated as a synergistic process, while conservation efforts, on the other hand, should focus principally on combatting the threat that triggers synergistic effects.

Effects of immune synergist of Chinese medicinal herbs on the ...

African Journals Online (AJOL)

AJL

2012-01-19

Jan 19, 2012 ... 1Institute of Animal Husbandry and Veterinary Sciences, Shanxi Academy of Agricultural Sciences, Taiyuan 030032, China. 2Modern ... Two-month-old piglets were fed with 1, 1.5 and 2% immune synergist of Chinese medicinal herbs together with ..... saponins that are capable of activating immune system.

A Hybrid Approach to Composite Damage and Failure Analysis Combining Synergistic Damage Mechanics and Peridynamics

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2017-12-31

Composite Damage and Failure Analysis Combinin Synergistic Damage Mechanics and Peridynamics 6. AUTHOR(S) 5b. GRANT NUMBER N00014-16-1-2173 5c...NUMBER 8. PERFORMING ORGANIZATION REPORT NUMBER Texas A&M Engineering Experiment Station (TEES) 400 Harvey Mitchell Parkway, Suite 300 College...1.3 related to Synergistic Damage Mechanics and Tasks 2.2 and 2.4 related to Peridynamics, as described in the project proposal. The activities

Application of a lipid-coated hollow calcium phosphate nanoparticle in synergistic co-delivery of doxorubicin and paclitaxel for the treatment of human lung cancer A549 cells

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Wu C

2017-10-01

Full Text Available Chao Wu, Jie Xu, Yanna Hao, Ying Zhao, Yang Qiu, Jie Jiang, Tong Yu, Peng Ji, Ying Liu Pharmacy School, Jinzhou Medical University, Jinzhou, China Abstract: In this study, we developed a lipid-coated hollow calcium phosphate (LCP nanoparticle for the combined application of two chemotherapeutic drugs to human lung cancer A549 cells. Hydrophilic doxorubicin (DOX was incorporated into the hollow structure of hollow calcium phosphate (HCP, and a lipid bilayer containing hydrophobic paclitaxel (PTX was subsequently coated on the surface of HCP. The study on combinational effects demonstrated that the combination of DOX and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells. The particle size, zeta potential, and encapsulation efficiency were measured to obtain optimal values: particle size was 335.0 3.2 nm, zeta potential -41.1 mV, and encapsulation efficiency 80.40%±2.24%. An in vitro release study indicated that LCP produced a sustained drug release. A549 cells had a better uptake of LCP with good biocompatibility. Furthermore, in vitro cytotoxicity experiment, apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on LCP had significant synergistic anti-tumor activity. All conclusions suggested that LCP is a promising platform for co-delivery of multiple anti-tumor drugs. Keywords: doxorubicin, paclitaxel, co-delivery, lipid, hollow calcium phosphate, lung cancer cell

Activity-based in vitro selection of T4 DNA ligase

International Nuclear Information System (INIS)

Takahashi, Fumio; Funabashi, Hisakage; Mie, Masayasu; Endo, Yaeta; Sawasaki, Tatsuya; Aizawa, Masuo; Kobatake, Eiry

2005-01-01

Recent in vitro methodologies for selection and directed evolution of proteins have concentrated not only on proteins with affinity such as single-chain antibody but also on enzymes. We developed a display technology for selection of T4 DNA ligase on ribosome because an in vitro selection method for DNA ligase had never been developed. The 3' end of mRNA encoding the gene of active or inactive T4 DNA ligase-spacer peptide fusion protein was hybridized to dsDNA fragments with cohesive ends, the substrate of T4 DNA ligase. After in vitro translation of the mRNA-dsDNA complex in a rabbit reticulocyte system, a mRNA-dsDNA-ribosome-ligase complex was produced. T4 DNA ligase enzyme displayed on a ribosome, through addition of a spacer peptide, is able to react with dsDNA in the complex. The complex expressing active ligase was biotinylated by ligation with another biotinylated dsDNA probe and selected with streptavidin-coated magnetic beads. We effectively selected active T4 DNA ligase from a small amount of protein. The gene of the active T4 DNA ligase was enriched 40 times from a mixture of active and inactive genes using this selection strategy. This ribosomal display strategy may have high potential to be useful for selection of other enzymes associated with DNA

Phytochemical characteristics and in vitro antibacterial activity of ...

African Journals Online (AJOL)

The aqueous and ethanol stem bark-extracts of Caesalpinia pulcherrima (Pride of Barbados) were screened for phyto-constituents and in vitro antimicrobial activity on clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhi and Klebsiella pneumoniae using ...

In Vitro Activities of New Antimicrobials against Nocardia brasiliensis

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Vera-Cabrera, Lucio; Gonzalez, Eva; Choi, Sung H.; Welsh, Oliverio

2004-01-01

The in vitro sensitivities of 30 strains of Nocardia brasiliensis to DA-7867, gatifloxacin, moxifloxacin, and BMS-284756 (garenoxacin) were determined using the broth microdilution method. All N. brasiliensis strains were sensitive to these antimicrobials. The most active drug in vitro was DA-7867, with a MIC at which 90% of the isolates tested were inhibited of 0.03 μg/ml and a MIC at which 50% of the isolates tested were inhibited of 0.06 μg/ml. PMID:14742215

Synergistic effect of high pressure processing and Lactobacillus casei antimicrobial activity against pressure resistant Listeria monocytogenes.

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Chung, Hyun-Jung; Yousef, Ahmed E

2010-09-30

The purpose of this study was to evaluate combinations of high pressure processing (HPP) and Lactobacillus casei antimicrobial activity against Listeria monocytogenes strains with variation in pressure resistance in culture and in a food model. In culture, combination of HPP (350 MPa, for 1-20 min) and Lb. casei cell extract (CE, 32 CEAU/ml) showed a significant synergistic bactericidal effect (P5 log(10)CFU/ml. Synergy between CE and HPP was most evident in the pressure-resistant strain, OSY-8578. Similar result was observed in meat products where high pressure (500 MPa for 1 min), and high-activity CE (100 CEAU/g) caused >5 log reduction in the viability of L. monocytogenes Scott A. The combination treatment resulted in the absence of peaks associated with cellular components in DSC thermogram suggesting that the presence of CE may have caused a considerable damage to cellular components during the high pressure treatment. Copyright 2010 Elsevier B.V. All rights reserved.

Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors.

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Margaret Pain

Full Text Available Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel's structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing.

Synergistic Adsorption and Flotation of New Mixed Cationic/Nonionic Collectors on Muscovite

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Hao Jiang

2017-05-01

Full Text Available The mixed cationic collector cetyltrimethylammonium chloride (CTAC and nonionic collector octanol (OCT was found to exhibit a synergistic effect on the flotation and adsorption of muscovite. To understand the underlying synergistic mechanism, flotation, contact angle, surface tension, and adsorption measurements were carried out. The results obtained from flotation measurements indicated that the mixed CTAC/OCT exhibits a better collecting ability than CTAC or OCT. The recovery of muscovite with CTAC only rapidly decreased from 97.25% at pH 2.64 to 75.26% at pH 5.82, followed by a flat horizontal at a pH is higher than 6. In contrast, a high recovery of greater than 85% muscovite was observed using mixed CTAC/OCT at α CTAC = 0.67 (the mole ratio of CTAC:OCT = 2:1 over the investigated pH range. From the surface activity parameters (CMC, γ CMC, Γmax, Amin estimated from surface measurements and interaction parameters (βm, βσ, in addition to the micellar and interfacial compositions ( x 1 m , x 1 σ obtained from the theory of regular solutions, a synergistic effect is evident in the mixed micelle and at the water/air interface. Moreover, the mixed CTAC/OCT at α CTAC = 0.67 exhibited the maximum synergistic interaction. The results obtained from surface tension measurements indicated that the mixed CTAC/OCT exhibits considerably higher surface activities compared to single CTAC or OCT. The contact angle results confirmed that the mixed CTAC/OCT is a better collector than the individual CTAC or OCT for the flotation of muscovite. According to the results obtained from adsorption experiments, compared with that of individual CTAC or OCT, the amounts of CTAC and OCT adsorbed on the muscovite surface are considerably increase in the mixed systems because of co-adsorption. Based on these results, the mixed CTAC/OCT exhibits a remarkable synergistic effect during the flotation and adsorption of muscovite.

Synergistic Effects of PPARγ Ligands and Retinoids in Cancer Treatment

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Masahito Shimizu

2008-01-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the nuclear receptor superfamily. The activation of PPARs by their specific ligands is regarded as one of the promising strategies to inhibit cancer cell growth. However, recent clinical trials targeting several common cancers showed no beneficial effect when PPAR ligands are used as a monotherapy. Retinoid X receptors (RXRs, which play a critical role in normal cell proliferation as a master regulator for nuclear receptors, preferentially form heterodimers with PPARs. A malfunction of RXRα due to phosphorylation by the Ras/MAPK signaling pathway is associated with the development of certain types of human malignancies. The activation of PPARγ/RXR heterodimer by their respective ligands synergistically inhibits cell growth, while inducing apoptosis in human colon cancer cells when the phosphorylation of RXRα was inhibited. We herein review the synergistic antitumor effects produced by the combination of the PPAR, especially PPARγ, ligands plus other agents, especially retinoids, in a variety of human cancers. We also focus on the phosphorylation of RXRα because the inhibition of RXRα phosphorylation and the restoration of its physiological function may activate PPAR/RXR heterodimer and, therefore, be a potentially effective and critical strategy for the inhibition of cancer cell growth.

Statistical metamodeling for revealing synergistic antimicrobial interactions.

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Hsiang Chia Chen

2010-11-01

Full Text Available Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future.

Synergistic activation of the CMV promoter by NF-κB P50 and PKG

International Nuclear Information System (INIS)

He Bin; Weber, Georg F.

2004-01-01

Several DNA binding NF-κB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-κB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-κB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-κB sites. These interactions may be relevant for the activation of viral gene expression

Sequential Exposure of Bortezomib and Vorinostat is Synergistic in Multiple Myeloma Cells

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Nanavati, Charvi; Mager, Donald E.

2018-01-01

Purpose To examine the combination of bortezomib and vorinostat in multiple myeloma cells (U266) and xenografts, and to assess the nature of their potential interactions with semi-mechanistic pharmacodynamic models and biomarkers. Methods U266 proliferation was examined for a range of bortezomib and vorinostat exposure times and concentrations (alone and in combination). A non-competitive interaction model was used with interaction parameters that reflect the nature of drug interactions after simultaneous and sequential exposures. p21 and cleaved PARP were measured using immunoblotting to assess critical biomarker dynamics. For xenografts, data were extracted from literature and modeled with a PK/PD model with an interaction parameter. Results Estimated model parameters for simultaneous in vitro and xenograft treatments suggested additive drug effects. The sequence of bortezomib preincubation for 24 hours, followed by vorinostat for 24 hours, resulted in an estimated interaction term significantly less than 1, suggesting synergistic effects. p21 and cleaved PARP were also up-regulated the most in this sequence. Conclusions Semi-mechanistic pharmacodynamic modeling suggests synergistic pharmacodynamic interactions for the sequential administration of bortezomib followed by vorinostat. Increased p21 and cleaved PARP expression can potentially explain mechanisms of their enhanced effects, which require further PK/PD systems analysis to suggest an optimal dosing regimen. PMID:28101809

Evaluation of in-vitro antibacterial activity and anti-inflammatory activity for different extracts of Rauvolfia tetraphylla L. root bark

OpenAIRE

B. Ganga Rao; P. Umamaheswara Rao; E. Sambasiva Rao; T. Mallikarjuna Rao; V.S. Praneeth. D

2012-01-01

Objective: To assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats. Methods: In-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 20...

Pentamidine Is Active In Vitro against Fusarium Species

OpenAIRE

Lionakis, Michail S.; Lewis, Russell E.; Samonis, George; Kontoyiannis, Dimitrios P.

2003-01-01

Fusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates of Fusarium species (five Fusarium solani isolates and five non-F. solani isolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye s...

White piedra: further evidence of a synergistic infection.

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Youker, Summer R; Andreozzi, Robert J; Appelbaum, Peter C; Credito, Kim; Miller, Jeffrey J

2003-10-01

White piedra is a fungal infection of the hair shaft caused by Trichosporon beigelii. A synergistic coryneform bacterial infection is often present with T beigelii. White piedra, although not commonly reported to infect scalp hair in North America, is an important consideration in the differential diagnosis of scalp hair concretions. We report a case of white piedra of scalp hair with synergistic coryneform bacterial infection in two sisters, both US natives. Culture and light and electronmicroscopic evidence of the synergistic infection are presented.

In vitro and in vivo antitrypanosomal activity of Xanthium strumarium leaves.

Science.gov (United States)

Talakal, T S; Dwivedi, S K; Sharma, S R

1995-12-15

Antitrypanosomal activity of crude 50% ethanolic extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity at all four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml, in vitro. In vivo trial revealed that the extract exerted antitrypanosomal effect at dosage of 100, 300 and 1000 mg/kg, intraperitoneally. At 100 and 300 mg/kg doses the survival period of the Trypanosoma evansi infected mice was significantly prolonged. However, the extract was found to be toxic to the animals at 1000 mg/kg dose.

Antibacterial Activity of Protocatechuic Acid Ethyl Ester on Staphylococcus aureus Clinical Strains Alone and in Combination with Antistaphylococcal Drugs

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Maria Miklasińska

2015-07-01

Full Text Available The aim of the presented study was to examine in vitro the antibacterial activity of protocatechuic acid ethyl ester (ethyl 3,4-dihydroxybenzoate, EDHB against Staphylococcus aureus clinical isolates alone and in the combination with four selected antibiotics. The EDHB antimicrobial activity was tested against twenty S. aureus strains isolated from the clinical samples, and three reference strains. The phenotypes and genotypes of resistance to methicillin for the tested strains were defined as well as the phenotypic resistance to macrolides, lincosamides and streptogramin B (MLSB. EDHB displayed diverse activity against examined S. aureus strains with the minimal inhibitory concentration (MIC within the range from 64 to 1024 µg/mL. Addition of ¼ MIC of EDHB into the Mueller-Hinton Agar (MHA resulted in augmented antibacterial effect in the presence of clindamycin. In the case of cefoxitin no synergistic effect with EDHB was noted. For erythromycin and vancomycin the decrease of mean MICs in the presence of EDHB was observed but did not reach statistical significance. The results of the present study showed that in vitro EDHB possesses antibacterial activity against S. aureus clinical strains and triggers a synergistic antimicrobial effect with clindamycin and to the lesser extent with erythromycin and vancomycin.

Synergistic effects of irradiation of waste water

International Nuclear Information System (INIS)

Woodbridge, D.D.; Cooper, P.C.; Vandenburg, A.J.; Musselman, H.D.; Lowe, H.N.; Florida Inst. of Tech., Melbourne; Army Facilities Engineering Support Agency, Fort Belvoir, Va.

1975-01-01

Theoretical considerations of the use of high level radiation in the treatment of waste water have failed to consider the effects of the hydrated electron and the potential of possible synergistic effects of combining chlorine, oxygen, and irradiation. An extensive testing program at the University Center for Pollution Research of Florida Institute of Technology over the past four years has shown that irradiation of waste water samples immersed in an aqueous environment provide bacterial kill and reduction in organic pollution far greater than that obtained from theoretical considerations of G values and earlier experiments where the waste samples were not immersed in an aqueous environment. These testing programs have investigated the synergistic effects of combining oxygen and irradiation. Each of these combined treatments resulted in an increased bacterial kill factor. Tests on Staphylococcus aureus bacteria and fecal streptococcus bacteria indicate that the synergistic effects observed for fecal coliform bacteria also apply to the pathogenic bacteria. A statistical analysis of the data obtained shows the interrelationships between the various effects on the bacteria. A definite shielding factor due to the turbidity of the waste water has been shown to exist. Synergistic effects have been shown to significantly offset the shielding effects. Optimization of these synergistic effects can greatly increase the effectiveness of irradiation in the treatment of waste water. (orig.) [de

ASSESSMENT OF IN VITRO ANDROGENIC ACTIVITY IN KRAFT MILL EFFLUENT

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Detection of In Vitro Androgenic Activity in Feedlot Effluent. Lambright, CS 1 , Guillette, LJ, Jr.2, Gray, LE, Jr.1 , 1USEPA, NHEERL, RTP, NC, 2 University of Florida, Dept. of Zoology, Gainesville FLRecent studies have shown the presence of androgenic activity in water...

Hydrodeoxygenation of prairie cordgrass bio-oil over Ni based activated carbon synergistic catalysts combined with different metals.

Science.gov (United States)

Cheng, Shouyun; Wei, Lin; Zhao, Xianhui; Kadis, Ethan; Cao, Yuhe; Julson, James; Gu, Zhengrong

2016-06-25

Bio-oil can be upgraded through hydrodeoxygenation (HDO). Low-cost and effective catalysts are crucial for the HDO process. In this study, four inexpensive combinations of Ni based activated carbon synergistic catalysts including Ni/AC, Ni-Fe/AC, Ni-Mo/AC and Ni-Cu/AC were evaluated for HDO of prairie cordgrass (PCG) bio-oil. The tests were carried out in the autoclave under mild operating conditions with 500psig of H2 pressure and 350°C temperature. The catalysts were characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) and transmission electron microscope (TEM). The results show that all synergistic catalysts had significant improvements on the physicochemical properties (water content, pH, oxygen content, higher heating value and chemical compositions) of the upgraded PCG bio-oil. The higher heating value of the upgraded bio-oil (ranging from 29.65MJ/kg to 31.61MJ/kg) improved significantly in comparison with the raw bio-oil (11.33MJ/kg), while the oxygen content reduced to only 21.70-25.88% from 68.81% of the raw bio-oil. Compared to raw bio-oil (8.78% hydrocarbons and no alkyl-phenols), the Ni/AC catalysts produced the highest content of gasoline range hydrocarbons (C6-C12) at 32.63% in the upgraded bio-oil, while Ni-Mo/AC generated the upgraded bio-oil with the highest content of gasoline blending alkyl-phenols at 38.41%. Copyright © 2016 Elsevier B.V. All rights reserved.

Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids▿

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Li, Xing-Cong; Jacob, Melissa R.; Khan, Shabana I.; Ashfaq, M. Khalid; Babu, K. Suresh; Agarwal, Ameeta K.; ElSohly, Hala N.; Manly, Susan P.; Clark, Alice M.

2008-01-01

Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C16 to C20: 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. PMID:18458131

Potent in vitro antifungal activities of naturally occurring acetylenic acids.

Science.gov (United States)

Li, Xing-Cong; Jacob, Melissa R; Khan, Shabana I; Ashfaq, M Khalid; Babu, K Suresh; Agarwal, Ameeta K; Elsohly, Hala N; Manly, Susan P; Clark, Alice M

2008-07-01

Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C(16) to C(20): 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides. Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes, and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus, with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 muM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 mumol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies.

A new extract of the plant calendula officinalis produces a dual in vitro effect: cytotoxic anti-tumor activity and lymphocyte activation

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Collado Antonia

2006-05-01

Full Text Available Abstract Background Phytopharmacological studies of different Calendula extracts have shown anti-inflamatory, anti-viral and anti-genotoxic properties of therapeutic interest. In this study, we evaluated the in vitro cytotoxic anti-tumor and immunomodulatory activities and in vivo anti-tumor effect of Laser Activated Calendula Extract (LACE, a novel extract of the plant Calendula Officinalis (Asteraceae. Methods An aqueous extract of Calendula Officinalis was obtained by a novel extraction method in order to measure its anti-tumor and immunomodulatory activities in vitro. Tumor cell lines derived from leukemias, melanomas, fibrosarcomas and cancers of breast, prostate, cervix, lung, pancreas and colorectal were used and tumor cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of LACE on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in LACE-treated cells. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously human Ando-2 melanoma cells. Results The LACE extract showed a potent in vitro inhibition of tumor cell proliferation when tested on a wide variety of human and murine tumor cell lines. The inhibition ranged from 70 to 100%. Mechanisms of inhibition were identified as cell cycle arrest in G0/G1 phase and Caspase-3-induced apoptosis. Interestingly, the same extract showed an opposite effect when tested on PBLs and NKL cell line, in which in vitro induction of proliferation and activation of these cells was observed. The intraperitoneal injection or oral administration of LACE extract in nude mice inhibits in vivo tumor growth of Ando-2 melanoma cells and prolongs the survival day of the mice. Conclusion These results indicate that LACE aqueous extract has two complementary activities in vitro with potential anti-tumor therapeutic effect: cytotoxic tumor cell activity and lymphocyte activation

A new extract of the plant calendula officinalis produces a dual in vitro effect: cytotoxic anti-tumor activity and lymphocyte activation

International Nuclear Information System (INIS)

Jiménez-Medina, Eva; Garcia-Lora, Angel; Paco, Laura; Algarra, Ignacio; Collado, Antonia; Garrido, Federico

2006-01-01

Phytopharmacological studies of different Calendula extracts have shown anti-inflamatory, anti-viral and anti-genotoxic properties of therapeutic interest. In this study, we evaluated the in vitro cytotoxic anti-tumor and immunomodulatory activities and in vivo anti-tumor effect of Laser Activated Calendula Extract (LACE), a novel extract of the plant Calendula Officinalis (Asteraceae). An aqueous extract of Calendula Officinalis was obtained by a novel extraction method in order to measure its anti-tumor and immunomodulatory activities in vitro. Tumor cell lines derived from leukemias, melanomas, fibrosarcomas and cancers of breast, prostate, cervix, lung, pancreas and colorectal were used and tumor cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of LACE on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in LACE-treated cells. In vivo anti-tumor activity was evaluated in nude mice bearing subcutaneously human Ando-2 melanoma cells. The LACE extract showed a potent in vitro inhibition of tumor cell proliferation when tested on a wide variety of human and murine tumor cell lines. The inhibition ranged from 70 to 100%. Mechanisms of inhibition were identified as cell cycle arrest in G0/G1 phase and Caspase-3-induced apoptosis. Interestingly, the same extract showed an opposite effect when tested on PBLs and NKL cell line, in which in vitro induction of proliferation and activation of these cells was observed. The intraperitoneal injection or oral administration of LACE extract in nude mice inhibits in vivo tumor growth of Ando-2 melanoma cells and prolongs the survival day of the mice. These results indicate that LACE aqueous extract has two complementary activities in vitro with potential anti-tumor therapeutic effect: cytotoxic tumor cell activity and lymphocyte activation. The LACE extract presented in vivo anti-tumoral activity in nude

Phytochemical Screening and In Vitro Antitrypanosomal Activity of ...

African Journals Online (AJOL)

Phytochemical Screening and In Vitro Antitrypanosomal Activity of the Aerial Parts of Artemisia abyssinica Against Trypanosoma congolense Field Isolate. ... of infected blood and extracts at concentrations of 4, 2 and 0.4 mg/ml coupled with infectivity test in which a mixture of infected blood was inoculated to healthy mice.

Antibacterial and Synergistic Activity Against β-Lactamase-Producing Nosocomial Bacteria by Bacteriocin of LAB Isolated From Lesser Known Traditionally Fermented Products of India

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Koel Biswas

2017-04-01

Full Text Available There is an ever-growing need to control antibiotic-resistance owing to alarming resistance to commonly available antimicrobial agents for which contemporary and alternative approaches are being explored. The present study assessed the antibacterial activity of bacteriocins from lactic acid bacteria (LAB from lesser known traditionally fermented products of India for their synergistic potential with common antibiotics against clinical β-lactamases producing pathogens. A total of 84 isolates of LAB were screened for their antibacterial efficacy against Streptococcus pyogenes, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae and Bacillus cereus as well as against clinical pathogens harbouring β-lactamase genes such as blaCTX-M, blaVIM, blaIMP, blaSHV and blaNDM. Synergistic activity of bacteriocins were determined in combination with antibiotics namely, cefotaxime, polymyxin B, imipenem and tigecycline. Purified bacteriocins from Lactobacillus, Pediococcus and Enterococcus inhibited the growth of β-lactamase harbouring clinical pathogens which significantly higher inhibitions when compared with antibiotics alone. Minimum inhibitory concentration of the extracts ranged from 6.66 to 26.66 mg/ml and 10 to 33.33 mg/ml for Pediococcus pentosaceus LU11 and Lactobacillus plantarum LS6. The bacteriocinogenic activity of LAB opens scope for bioprospection of antibacterial components in the current struggle against increasing pandrug resistance and slowing down the expansion of multi-drug resistance.

Synergistic effect of (+)-pinitol from Saraca asoca with β-lactam antibiotics and studies on the in silico possible mechanism.

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Ahmad, Furkan; Misra, Laxminarain; Gupta, Vivek Kumar; Darokar, Mahendra Pandurang; Prakash, Om; Khan, Feroz; Shukla, Rakesh

2016-01-01

Saraca asoca bark has been used in the Ayurvedic system of medicine for female urino-genital disorders. We have recently reported the isolation and characterization of several compounds as markers to develop HPLC profiling of its methanol and aqueous methanol extracts. Now, a HPLC-PDA inactive compound, (+)-pinitol has been isolated and characterized from the bark of this medicinally important tree. Pinitol is a well known bioactive compound for a variety of biological activities, including hypoglycemic and anti-inflammatory activities. A process for the isolation of relatively good concentration of (+)-pinitol from S. asoca bark has been developed and its in vitro anti TNF-α and anti-inflammatory activities against carragenan-induced edema confirmed. While conducting experiments on the possible agonistic activity, it was found that (+)-pinitol showed up to eight fold reduction in the doses of β-lactam antibiotics. The mechanism of its agonistic activity was studied by docking experiments which showed that different conformations of (+)-pinitol and antibiotics were actually in the same binding site with no significant change in the binding energy. These docking simulations, thus predict the possible binding mode of studied compounds and probable reason behind the synergistic effect of (+)-pinitol along with β-lactam antibiotics.

In Vitro Synergy of Telavancin and Rifampin Against Enterococcus faecium Resistant to Both Linezolid and Vancomycin.

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Pankey, George A; Ashcraft, Deborah S

2013-01-01

An emerging pathogen is Enterococcus faecium resistant to both linezolid and vancomycin (LRVRE). Antimicrobial combinations may be required for therapy and need to be evaluated. The combination of daptomycin and rifampin has demonstrated good in vitro activity against gram-positive bacteria, including E faecium. Telavancin, a newer lipoglycopeptide, has shown in vitro activity against E faecium. We evaluated the combination of telavancin and rifampin and compared the results to the combination of daptomycin and rifampin used previously on the same isolates. Twenty-four genetically unique (by pulsed-field gel electrophoresis), clinical LRVRE isolates were collected in the United States from 2001-2004. Etest minimal inhibitory concentrations (MICs) (μg/mL) were 0.064-8 for telavancin, 1-4 for daptomycin, and 0.012 to >32 for rifampin. In vitro synergy testing was performed in triplicate by an Etest MIC:MIC ratio method, and summation fractional inhibitory concentration (ΣFIC) was calculated: synergy ≤0.5; indifference >0.5-4; and antagonism >4. The Etest method showed synergy (ΣFICs of 0.1-0.5) with telavancin + rifampin in 20/24 (83%) isolates and indifference (ΣFICs of 0.6-0.8) in 4/24 (17%) isolates. Similarly, the daptomycin + rifampin combination showed synergy (ΣFICs of 0.1-0.5) in 21/24 (88%) isolates and indifference (ΣFICs of 0.6-1.0) in 3/24 (12%) isolates by the Etest method. No antagonism was found. In vitro synergy with both combinations (rifampin + telavancin or daptomycin) was 83% and 88%, respectively, by Etest against these LRVRE isolates. Although both daptomycin and telavancin in combination with rifampin showed a high incidence of synergistic activity, further in vitro synergy testing with this combination should be performed against additional E faecium isolates. In vitro synergy may or may not translate into in vivo effectiveness.

Antibiotic activity and synergistic effect of antimicrobial peptide against pathogens from a patient with gallstones

International Nuclear Information System (INIS)

Park, Yoonkyung; Park, Soon Nang; Park, Seong-Cheol; Park, Joon Yong; Park, Yong Ha; Hahm, Joon Soo; Hahm, Kyung-Soo

2004-01-01

HP (2-20) is a peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1 that has been shown to have antimicrobial activity against various species of bacteria. When we tested the effects of HP (2-20), we found that this peptide displayed strong activity against pathogens from a patient with gallstones, but it did not have hemolytic activity against human erythrocytes. We also found that HP (2-20) had potent activity against cefazolin sodium-resistant bacterial cell lines, and that HP (2-20) and cefazolin sodium had synergistic effects against cell lines resistant to the latter. To investigate the mechanism of action of HP (2-20), we performed fluorescence activated flow cytometry using pathogens from the patient with gallstones. As determined by propidium iodide (PI) staining, pathogenic bacteria treated with HP (2-20) showed higher fluorescence intensity than untreated cells, similar to melittin-treated cells, and that HP (2-20) acted in an energy- and salt-dependent manner. Scanning electron microscopy showed that HP (2-20) caused significant morphological alterations in the cell surface of pathogens from the patient with gallstones. By determining their 16S rDNA sequences, we found that both the pathogens from the patient with gallstones and the cefazolin sodium-resistant cell lines showed 100% homology with sequences from Pseudomonas aeruginosa. Taken together, these results suggest that HP (2-20) has antibiotic activity and that it may be used as a lead drug for the treatment of acquired pathogens from patients with gallstones and antibiotic-resistant cell lines

Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

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V. Tamara Perchyonok

2014-11-01

Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

Assessment of in vitro antitumoral and antimicrobial activities of ...

African Journals Online (AJOL)

Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the eastern Mediterranean sea. ... African Journal of Biotechnology ... algal extracts obtained from the marine algae Scytosiphon lomentaria, Padina pavonica, Cystoseira mediterranea (Phaeophyceae), Hypnea musciformis and ...

In vitro biological activity of tannins from Acacia and other tree fruits ...

African Journals Online (AJOL)

This study was designed to investigate impact of tannins on in vitro ruminal fermentation parameters as well as relationships between concentration and in vitro biological activity of tannins present in tree fruits. Dry and mature fruits of known phenolic content harvested from Acacia nilotica, A. erubescens, A. erioloba, ...

In Vitro Analysis of Antioxidant Activities of Oxalis Corniculata Linn ...

African Journals Online (AJOL)

In Vitro Analysis of Antioxidant Activities of Oxalis Corniculata Linn. Fractions in Various Solvents. D Ahmed, S Zara, H Baig. Abstract. As part of our search for natural antioxidants, this work presents an evaluation of antioxidant activities of methanolic extract of Oxalis corniculata and its sub-fractions in hexane, chloroform, ...

Bromelain enzyme from pineapple: in vitro activity study under different micropropagation conditions.

Science.gov (United States)

Vilanova Neta, Jaci Lima; da Silva Lédo, Ana; Lima, Aloisio André Bonfim; Santana, José Carlos Curvelo; Leite, Nadjma Souza; Ruzene, Denise Santos; Silva, Daniel Pereira; de Souza, Roberto Rodrigues

2012-09-01

The aim of this work was to evaluate the activity of bromelain in pineapple plants (Ananas comosus var. Comosus), Pérola cultivar, produced in vitro in different culture conditions. This enzyme, besides its pharmacological effects, is also employed in food industries, such as breweries and meat processing. In this work, the enzymatic activity was evaluated in the tissues of leaves and stems of plants grown in culture medium without plant growth regulator. The most significant levels of bromelain were observed in leaf tissue after 4 months of culture in vitro in medium with a filter paper bridge, followed by medium gelled by the agar. The results of this study, regarding the different structures of the pineapple (leaves and stems) in vitro showed that the activity of bromelain varied depending on the culture conditions, the time and structure of which was quantified, ensuring a viable strategy in the production of seedlings with high levels of bromelain in subsequent phases of micropropagation.

In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors.

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Brun, R; Bühler, Y; Sandmeier, U; Kaminsky, R; Bacchi, C J; Rattendi, D; Lane, S; Croft, S L; Snowdon, D; Yardley, V; Caravatti, G; Frei, J; Stanek, J; Mett, H

1996-01-01

A series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (MGBG) was examined for in vitro antitrypanosomal activities and cytotoxicities for human cells. One-third of the compounds tested showed trypanocidal activity at concentrations below 0.5 microM after an incubation period of 72 h. Structure-activity analysis revealed that bicyclic compounds with homocyclic rings and unmodified termini were the most active compounds. Results obtained in three laboratories employing different methods and trypanosome populations consistently ranked compound CGP 40215A highest. This compound had a 50% inhibitory concentration of 0.0045 microM for Trypanosoma brucei rhodesiense, was also active against other trypanosome species, including a multidrug-resistant Trypanosoma brucei brucei, and was significantly less toxic than other compounds tested for a human adenocarcinoma cell line, with a 50% inhibitory concentration of 1.14 mM. The effect of CGP 40215A was time and dose dependent, and low concentrations of the compound required exposure times of > 2 days to exert trypanocidal activity. Compounds were inactive against Leishmania donovani and Trypanosoma cruzi amastigotes in murine macrophages in vitro. PMID:8726017

Biological activity of some novel synthesized 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives: In vitro and in vivo antineoplastic activity

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Satyajit Dutta

2014-12-01

Full Text Available In the present work few novel 2-(4-methylbenzenesulphonamidopentanedioic acid bis amide derivatives and the basic compound 2-(4-methylphenylsulfonamidopentanedioic acid have been synthesized, characterized and screened for their possible antineoplastic activity both in vitro and in vivo. The in vitro activity was performed against five human cell lines like human breast cancer (MCF-7, leukemia (K-562, ovarian cancer (OVACAR-3, human colon adenocarcinoma (HT-29 and Human kidney carcinoma (A-498. The in vivo activity was performed in female swiss albino mice against Ehrlich ascites carcinoma (EAC. Among the synthesized compounds, ureide, anilide, p-nitoanilide and o-bromoanilide derivatives of 2-(4-methyl benzene sulphonyl-pentanedioic acid bis amides showed encouraging activity in both the in vitro and in vivo compared to other compounds.

A rhizosphere-associated symbiont, Photobacterium spp. strain MELD1, and its targeted synergistic activity for phytoprotection against mercury.

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Dony Chacko Mathew

Full Text Available Though heavy metal such as mercury is toxic to plants and microorganisms, the synergistic activity between them may offer benefit for surviving. In this study, a mercury-reducing bacterium, Photobacterium spp. strain MELD1, with an MIC of 33 mg x kg(-1 mercury was isolated from a severely mercury and dioxin contaminated rhizosphere soil of reed (Phragmites australis. While the whole genome sequencing of MELD1 confirmed the presence of a mer operon, the mercury reductase MerA gene showed 99% sequence identity to Vibrio shilloni AK1 and implicates its route resulted from the event of horizontal gene transfer. The efficiency of MELD1 to vaporize mercury (25 mg x kg(-1, 24 h and its tolerance to toxic metals and xenobiotics such as lead, cadmium, pentachlorophenol, pentachloroethylene, 3-chlorobenzoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin is promising. Combination of a long yard bean (Vigna unguiculata ssp. Sesquipedalis and strain MELD1 proved beneficial in the phytoprotection of mercury in vivo. The effect of mercury (Hg on growth, distribution and tolerance was examined in root, shoot, leaves and pod of yard long bean with and without the inoculation of strain MELD1. The model plant inoculated with MELD1 had significant increases in biomass, root length, seed number, and increased mercury uptake limited to roots. Biolog plate assay were used to assess the sole-carbon source utilization pattern of the isolate and Indole-3-acetic acid (IAA productivity was analyzed to examine if the strain could contribute to plant growth. The results of this study suggest that, as a rhizosphere-associated symbiont, the synergistic activity between the plant and MELD1 can improve the efficiency for phytoprotection, phytostabilization and phytoremediation of mercury.

A rhizosphere-associated symbiont, Photobacterium spp. strain MELD1, and its targeted synergistic activity for phytoprotection against mercury.

Science.gov (United States)

Mathew, Dony Chacko; Ho, Ying-Ning; Gicana, Ronnie Gicaraya; Mathew, Gincy Marina; Chien, Mei-Chieh; Huang, Chieh-Chen

2015-01-01

Though heavy metal such as mercury is toxic to plants and microorganisms, the synergistic activity between them may offer benefit for surviving. In this study, a mercury-reducing bacterium, Photobacterium spp. strain MELD1, with an MIC of 33 mg x kg(-1) mercury was isolated from a severely mercury and dioxin contaminated rhizosphere soil of reed (Phragmites australis). While the whole genome sequencing of MELD1 confirmed the presence of a mer operon, the mercury reductase MerA gene showed 99% sequence identity to Vibrio shilloni AK1 and implicates its route resulted from the event of horizontal gene transfer. The efficiency of MELD1 to vaporize mercury (25 mg x kg(-1), 24 h) and its tolerance to toxic metals and xenobiotics such as lead, cadmium, pentachlorophenol, pentachloroethylene, 3-chlorobenzoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin is promising. Combination of a long yard bean (Vigna unguiculata ssp. Sesquipedalis) and strain MELD1 proved beneficial in the phytoprotection of mercury in vivo. The effect of mercury (Hg) on growth, distribution and tolerance was examined in root, shoot, leaves and pod of yard long bean with and without the inoculation of strain MELD1. The model plant inoculated with MELD1 had significant increases in biomass, root length, seed number, and increased mercury uptake limited to roots. Biolog plate assay were used to assess the sole-carbon source utilization pattern of the isolate and Indole-3-acetic acid (IAA) productivity was analyzed to examine if the strain could contribute to plant growth. The results of this study suggest that, as a rhizosphere-associated symbiont, the synergistic activity between the plant and MELD1 can improve the efficiency for phytoprotection, phytostabilization and phytoremediation of mercury.

A Rhizosphere-Associated Symbiont, Photobacterium spp. Strain MELD1, and Its Targeted Synergistic Activity for Phytoprotection against Mercury

Science.gov (United States)

Mathew, Dony Chacko; Ho, Ying-Ning; Gicana, Ronnie Gicaraya; Mathew, Gincy Marina; Chien, Mei-Chieh; Huang, Chieh-Chen

2015-01-01

Though heavy metal such as mercury is toxic to plants and microorganisms, the synergistic activity between them may offer benefit for surviving. In this study, a mercury-reducing bacterium, Photobacterium spp. strain MELD1, with an MIC of 33 mg . kg-1 mercury was isolated from a severely mercury and dioxin contaminated rhizosphere soil of reed (Phragmites australis). While the whole genome sequencing of MELD1 confirmed the presence of a mer operon, the mercury reductase MerA gene showed 99% sequence identity to Vibrio shilloni AK1 and implicates its route resulted from the event of horizontal gene transfer. The efficiency of MELD1 to vaporize mercury (25 mg . kg-1, 24 h) and its tolerance to toxic metals and xenobiotics such as lead, cadmium, pentachlorophenol, pentachloroethylene, 3-chlorobenzoic acid, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin is promising. Combination of a long yard bean (Vigna unguiculata ssp. Sesquipedalis) and strain MELD1 proved beneficial in the phytoprotection of mercury in vivo. The effect of mercury (Hg) on growth, distribution and tolerance was examined in root, shoot, leaves and pod of yard long bean with and without the inoculation of strain MELD1. The model plant inoculated with MELD1 had significant increases in biomass, root length, seed number, and increased mercury uptake limited to roots. Biolog plate assay were used to assess the sole-carbon source utilization pattern of the isolate and Indole-3-acetic acid (IAA) productivity was analyzed to examine if the strain could contribute to plant growth. The results of this study suggest that, as a rhizosphere-associated symbiont, the synergistic activity between the plant and MELD1 can improve the efficiency for phytoprotection, phytostabilization and phytoremediation of mercury. PMID:25816328

In-vitro antimicrobial activity of crude extracts of Diospyros ...

African Journals Online (AJOL)

Diospyros species in folklore medicine are used as anti-inflammatory, antibacterial, antioxidant, anticancer and antiviral agents. The in vitro antimicrobial activity of crude extracts of the leaves of Diospyros monbuttensis were evaluated against three bacterial species (Staphylococcus aureus, Escherichia coli and ...

Antimicrobial activity of extracts from in vivo and in vitro propagated ...

African Journals Online (AJOL)

The antimicrobial activity of 18 different extracts from in vivo and in vitro grown L. album L. plants was evaluated against clinical bacteria and yeasts using the well diffusion method. All the used extracts demonstrated antibacterial activity, whereas only the water extracts from leaves (in vivo) possessed antifungal activity ...

In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

Science.gov (United States)

Rochon-Edouard, Stéphanie; Pestel-Caron, Martine; Lemeland, Jean-François; Caron, François

2000-01-01

Several studies have previously reported synergistic effects between vancomycin and a given β-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a β-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different β-lactam–vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the β-lactam–vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and

FASTSAT-HSV01 Synergistic Observations of the Magnetospheric Response During Active Periods: MINI-ME, PISA and TTI

Science.gov (United States)

Casas, Joseph C.; Collier, Michael R.; Rowland, Douglas E.; Sigwarth, John B.; Boudreaux, Mark E.

2010-01-01

Understanding the complex processes within the inner magnetosphere of Earth particularly during storm periods requires coordinated observations of the particle and field environment using both in-situ and remote sensing techniques. In fact in order to gain a better understanding of our Heliophysics and potentially improve our space weather forecasting capabilities, new observation mission approaches and new instrument technologies which can provide both cost effective and robust regular observations of magnetospheric activity and other space weather related phenomenon are necessary. As part of the effort to demonstrate new instrument techniques and achieve necessary coordinated observation missions, NASA's Fast Affordable Science and Technology Satellite Huntsville 01 mission (FASTSAT-HSVOI) scheduled for launch in 2010 will afford a highly synergistic solution which satisfies payload mission opportunities and launch requirements as well as contributing iri the near term to our improved understanding of Heliophysics. NASA's FASTSAT-HSV01 spacecraft on the DoD Space Test Program-S26 (STP-S26) Mission is a multi-payload mission executed by the DoD Space Test Program (STP) at the Space Development and Test Wing (SDTW), Kirtland AFB, NM. and is an example of a responsive and economical breakthrough in providing new possibilities for small space technology-driven and research missions. FASTSAT-HSV is a unique spacecraft platform that can carry multiple small instruments or experiments to low-Earth orbit on a wide range of expendable launch vehicles for a fraction of the cost traditionally required for such missions. The FASTSAT-HSV01 mission allows NASA to mature and transition a technical capability to industry while increasing low-cost access to space for small science and technology (ST) payloads. The FASTSAT-HSV01 payload includes three NASA Goddard Space Flight Center (GSFC) new technology built instruments that will study the terrestrial space environment and

Synergistic and Dose-Controlled Regulation of Cellulase Gene Expression in Penicillium oxalicum.

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Li, Zhonghai; Yao, Guangshan; Wu, Ruimei; Gao, Liwei; Kan, Qinbiao; Liu, Meng; Yang, Piao; Liu, Guodong; Qin, Yuqi; Song, Xin; Zhong, Yaohua; Fang, Xu; Qu, Yinbo

2015-09-01

Filamentous fungus Penicillium oxalicum produces diverse lignocellulolytic enzymes, which are regulated by the combinations of many transcription factors. Here, a single-gene disruptant library for 470 transcription factors was constructed and systematically screened for cellulase production. Twenty transcription factors (including ClrB, CreA, XlnR, Ace1, AmyR, and 15 unknown proteins) were identified to play putative roles in the activation or repression of cellulase synthesis. Most of these regulators have not been characterized in any fungi before. We identified the ClrB, CreA, XlnR, and AmyR transcription factors as critical dose-dependent regulators of cellulase expression, the core regulons of which were identified by analyzing several transcriptomes and/or secretomes. Synergistic and additive modes of combinatorial control of each cellulase gene by these regulatory factors were achieved, and cellulase expression was fine-tuned in a proper and controlled manner. With one of these targets, the expression of the major intracellular β-glucosidase Bgl2 was found to be dependent on ClrB. The Bgl2-deficient background resulted in a substantial gene activation by ClrB and proved to be closely correlated with the relief of repression mediated by CreA and AmyR during cellulase induction. Our results also signify that probing the synergistic and dose-controlled regulation mechanisms of cellulolytic regulators and using it for reconstruction of expression regulation network (RERN) may be a promising strategy for cellulolytic fungi to develop enzyme hyper-producers. Based on our data, ClrB was identified as focal point for the synergistic activation regulation of cellulase expression by integrating cellulolytic regulators and their target genes, which refined our understanding of transcriptional-regulatory network as a "seesaw model" in which the coordinated regulation of cellulolytic genes is established by counteracting activators and repressors.

Antitumor and antimicrobial activities and inhibition of in-vitro lipid ...

African Journals Online (AJOL)

The antitumor activity was measured in DLA cell line induced mice. Inhibition of in vitro lipid peroxidation activity of the D. nobile in both liver homogenate and RBC ghosts was also carried out. The aqueous extracts of stem and flower of D. nobile showed better zone of bacterial inhibition than that of ethanol and chloroform

XMAP215 is a microtubule nucleation factor that functions synergistically with the γ-tubulin ring complex.

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Thawani, Akanksha; Kadzik, Rachel S; Petry, Sabine

2018-05-01

How microtubules (MTs) are generated in the cell is a major question in understanding how the cytoskeleton is assembled. For several decades, γ-tubulin has been accepted as the universal MT nucleator of the cell. Although there is evidence that γ-tubulin complexes are not the sole MT nucleators, identification of other nucleation factors has proven difficult. Here, we report that the well-characterized MT polymerase XMAP215 (chTOG/Msps/Stu2p/Alp14/Dis1 homologue) is essential for MT nucleation in Xenopus egg extracts. The concentration of XMAP215 determines the extent of MT nucleation. Even though XMAP215 and the γ-tubulin ring complex (γ-TuRC) possess minimal nucleation activity individually, together, these factors synergistically stimulate MT nucleation in vitro. The amino-terminal TOG domains 1-5 of XMAP215 bind to αβ-tubulin and promote MT polymerization, whereas the conserved carboxy terminus is required for efficient MT nucleation and directly binds to γ-tubulin. In summary, XMAP215 and γ-TuRC together function as the principal nucleation module that generates MTs in cells.

Evaluation of In Vitro Anti-inflammatory Activity of Azomethines of Aryl Oxazoles

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V. Niraimathi

2011-01-01

Full Text Available Ability to inhibit erythrocyte hemolysis is often used as a characteristic of the membrane stabilising action of chemical compounds. Azomethines of aryl oxazoles were evaluated for anti-inflammatory by in vitro hemolytic membrane stabilising study. The effect of inflammation condition was studied on erythrocyte exposed to hypotonic solution. In this in vitro method the membrane stabilising action leads to anti-inflammatory activity and was compared with that produced by diclofenac sodium as the reference standard. Results of the evaluation indicate that the synthesised compounds found to exhibit membrane stabilising activity.

Parasite-Mediated Degradation of Synthetic Ozonide Antimalarials Impacts In Vitro Antimalarial Activity.

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Giannangelo, Carlo; Stingelin, Lukas; Yang, Tuo; Tilley, Leann; Charman, Susan A; Creek, Darren J

2018-03-01

The peroxide bond of the artemisinins inspired the development of a class of fully synthetic 1,2,4-trioxolane-based antimalarials, collectively known as the ozonides. Similar to the artemisinins, heme-mediated degradation of the ozonides generates highly reactive radical species that are thought to mediate parasite killing by damaging critical parasite biomolecules. We examined the relationship between parasite dependent degradation and antimalarial activity for two ozonides, OZ277 (arterolane) and OZ439 (artefenomel), using a combination of in vitro drug stability and pulsed-exposure activity assays. Our results showed that drug degradation is parasite stage dependent and positively correlates with parasite load. Increasing trophozoite-stage parasitemia leads to substantially higher rates of degradation for both OZ277 and OZ439, and this is associated with a reduction in in vitro antimalarial activity. Under conditions of very high parasitemia (∼90%), OZ277 and OZ439 were rapidly degraded and completely devoid of activity in trophozoite-stage parasite cultures exposed to a 3-h drug pulse. This study highlights the impact of increasing parasite load on ozonide stability and in vitro antimalarial activity and should be considered when investigating the antimalarial mode of action of the ozonide antimalarials under conditions of high parasitemia. Copyright © 2018 American Society for Microbiology.

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

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Wu X

2017-03-01

Full Text Available Xiaozhe Wu,1 Zhan Li,1 Xiaolu Li,2,3 Yaomei Tian,1 Yingzi Fan,1 Chaoheng Yu,1 Bailing Zhou,1 Yi Liu,4 Rong Xiang,5 Li Yang1 1State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, 2International Center for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 3Department of Plastic and Burn Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 4Department of Microbial Examination, Sichuan Center for Disease Control and Prevention, Chengdu, 5Nankai University School of Medicine, Tianjin, People’s Republic of China Abstract: Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001 and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin on clinical bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. The AZT-resistance genes (ermA, ermB, ermC, mefA, and msrA were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L. When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7–AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus

In vitro antioxidant activity and phytochemical screening of methanol ...

African Journals Online (AJOL)

In this study, phytochemical screening and in vitro antioxidant activity of methanol extracts of D. edulis and F. capensis leaves were evaluated. Each plant leaves were extracted in methanol using standard procedures. The phytochemical screening of the resulting extracts showed the presence of cardiac glycosides, ...

Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

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Zou Zhengyun

2012-04-01

Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

Fatty acid, carotenoid and tocopherol compositions of 20 Canadian lentil cultivars and synergistic contribution to antioxidant activities.

Science.gov (United States)

Zhang, Bing; Deng, Zeyuan; Tang, Yao; Chen, Peter; Liu, Ronghua; Ramdath, D Dan; Liu, Qiang; Hernandez, Marta; Tsao, Rong

2014-10-15

Understanding the profile of lipophilic phytochemicals in lentils is necessary to better understand the health benefits of lentils. The fatty acid, carotenoid and tocopherol compositions and antioxidant activities of the lipophilic extracts of 20 lentil cultivars (10 red and 10 green) were therefore examined. Lentils contained 1.52-2.95% lipids, of which 77.5-81.7% were unsaturated essential fatty acids. Total tocopherols ranged from 37 to 64μg/g DW, predominantly γ-tocopherol (96-98% of the tocopherol content), followed by δ- and α-tocopherol. trans-Lutein was the primary and major carotenoid (64-78%) followed by trans-zeaxanthin (5-13%). Carotenoids and tocopherols showed weak correlation with 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity (r=0.4893 and 0.3259, respectively), but good correlation when combined (r=0.6688), suggesting they may act synergistically. Carotenoids were found to contribute the most to the strong antioxidant activity measured by photochemiluminescence (PCL) assay. Results from this study contribute to the development of lentil cultivars and related functional foods with increased health benefits. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Evaluation of in-vitro antibacterial activity and anti-inflammatory activity for different extracts of Rauvolfia tetraphylla L. root bark.

Science.gov (United States)

Ganga Rao, B; Umamaheswara Rao, P; Sambasiva Rao, E; Mallikarjuna Rao, T; Praneeth D, V S

2012-10-01

To assess the in-vitro antibacterial activity and anti-inflammatory activity of orally administered different extracts (Hydro-alcoholic, methanolic, ethyl acetate and hexane) of Rauvolfia tetraphylla (R. tetraphylla) root bark in Carrageenan induced acute inflammation in rats. In-vitro antibacterial activity was evaluated for extracts against four Gram positive and four Gram negative bacteria by using cylinder plate assay. Hydro-alcoholic extract (70% v/v ethanol) at 200, 400 and 800 mg/kg doses and methanolic, ethyl acetate and hexane extracts at doses 100, 200 and 400 mg/kg were tested for anti-inflammatory activity in Carrageenan induced rat paw oedema model and paw thickness was measured every one hour up to 6 hrs. All extracts of R. tetraphylla root bark showed good zone of inhibition against tested bacterial strains. In Carrageenan induced inflammation model, hydro-alcoholic and methanolic extract of R. tetraphylla root bark at three different doses produced significant (P<0.001) reduction when compared to vehicle treated control group and hexane, ethyl acetate extracts. In the present study extracts of R. tetraphylla root bark shows good in-vitro antibacterial activity and in-vivo anti-inflammatory activity in rats.

The Vitamin E Analog Gamma-Tocotrienol (GT3 and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM

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Rupak Pathak

2016-11-01

Full Text Available Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR and strongly induce endothelial thrombomodulin (TM; which is known to have anti-inflammatory; anti-coagulation; anti-oxidant; and radioprotective properties. However; high-dose toxicity limits the clinical use of statins. The vitamin E family member gamma-tocotrienol (GT3 also suppresses HMGCR activity and induces TM expression without causing significant adverse side effects; even at high concentrations. To investigate the synergistic effect of statins and GT3 on TM; a low dose of atorvastatin and GT3 was used to treat human primary endothelial cells. Protein-level TM expression was measured by flow cytometry. TM functional activity was determined by activated protein C (APC generation assay. Expression of Kruppel-like factor 2 (KLF2, one of the key transcription factors of TM, was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. TM expression increased in a dose-dependent manner after both atorvastatin and GT3 treatment. A combined treatment of a low-dose of atorvastatin and GT3 synergistically up-regulated TM expression and functional activity. Finally; atorvastatin and GT3 synergistically increased KLF2 expression. These findings suggest that combined treatment of statins with GT3 may provide significant health benefits in treating a number of pathophysiological conditions; including inflammatory and cardiovascular diseases.

Synergistic function of four novel thermostable glycoside hydrolases from a long-term enriched thermophilic methanogenic digester

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Meng eWang

2015-05-01

Full Text Available In biofuel production from lignocellulose, low thermostability and product inhibition strongly restrict the enzyme activities and production process. Application of multiple thermostable glycoside hydrolases, forming an enzyme cocktail, can result in a synergistic action and therefore improve production efficiency and reduce operational costs. Therefore, increasing enzyme thermostabilities and compatibility are important for the biofuel industry. In this study, we reported the screening, cloning and biochemical characterization of four novel thermostable lignocellulose hydrolases from a metagenomic library of a long-term dry thermophilic methanogenic digester community, which were highly compatible with optimal conditions and specific activities. The optimal temperatures of the four enzymes, β-xylosidase, xylanase, β-glucosidase, and cellulase ranged from 60°C to 75°C, and over 80% residual activities were observed after 2 h incubation at 50°C. Mixtures of these hydrolases retained high residual synergistic activities after incubation with cellulose, xylan, and steam-exploded corncob at 50°C for 72 h. In addition, about 55% dry weight of steam-exploded corncob was hydrolyzed to glucose and xylose by the synergistic action of the four enzymes at 50°C for 48 h. This work suggested that since different enzymes from a same ecosystem could be more compatible, screening enzymes from a long-term enriching community could be a favorable strategy.

Synergistic Effects of Natural Medicinal Plant Extracts on Growth Inhibition of Carcinoma (KB) Cells under Oxidative Stress

International Nuclear Information System (INIS)

Kim, Jeong Hee; Ju, Eun Mi; Kim, Jin Kyu

2000-01-01

Medicinal plants with synergistic effects on growth inhibition of cancer cells under oxidative stress were screened in this study. Methanol extracts from 51 natural medicinal plants, which were reported to have anticancer effect on hepatoma, stomach cancer or colon cancers which are frequently found in Korean, were prepared and screened for their synergistic activity on growth inhibition of cancer cells under chemically-induced oxidative stress by using MTT assay. Twenty seven samples showed synergistic activity on the growth inhibition in various extent under chemically-induced oxidative stress. Among those samples, eleven samples, such as Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum, Pulsatilla koreana, Oldenlandia diffiusa, Anthriscus sylvestris, Schizandra chinensis, Gleditsia sinensis, Cridium officinale, showed decrease in IC 50 values more than 50%, other 16 samples showed decrease in IC 50 values between 50-25%, compared with the value acquired when medicinal plant sample was used alone. Among those 11 samples, extract of Catalpa ovata showed the highest activity. IC 50 values were decrease to 61% and 28% when carcinoma cells were treated with Catalpa ovata extract in combination of 75 and 100 μM of hydrogen peroxide, respectively

Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

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Zhen Hua Wu

Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

MAPK/ERK and Wnt/β-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

International Nuclear Information System (INIS)

Jin, Caixia; Samuelson, Lisa; Cui, Cai-Bin; Sun, Yangzhong; Gerber, David A.

2011-01-01

Highlights: → Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1 + HPC proliferation and colony formation. → Activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. → Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1 + HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1 + HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/β-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/β-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

MAPK/ERK and Wnt/{beta}-Catenin pathways are synergistically involved in proliferation of Sca-1 positive hepatic progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Jin, Caixia [Department of Surgery, University of North Carolina at Chapel Hill (United States); Department of Medical Genetics and Cell Biology, Ningxia Medical University, Yinchuan 750004 (China); Samuelson, Lisa; Cui, Cai-Bin; Sun, Yangzhong [Department of Surgery, University of North Carolina at Chapel Hill (United States); Gerber, David A., E-mail: david_gerber@med.unc.edu [Department of Surgery, University of North Carolina at Chapel Hill (United States); Lineberger Cancer Center, University of North Carolina at Chapel Hill (United States)

2011-06-17

Highlights: {yields} Activation of MAPK/ERK pathway with epidermal growth factor (EGF) significantly increased Sca-1{sup +} HPC proliferation and colony formation. {yields} Activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. {yields} Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation and maintain long-term HPCs in vitro. -- Abstract: Hepatic progenitor cells (HPCs) persist in adulthood and have the potential to play a major role in regenerating diseased liver. However, the signaling pathways that both directly and indirectly regulate HPCs' self-renewal and differentiation remain elusive. Previously, we identified a bipotent, stem cell antigen-1 (Sca-1) positive HPC population from naive adult liver tissue. In the present study, we aimed to investigate the involvement of various signaling pathways in Sca-1{sup +} HPC proliferation. Epidermal growth factor (EGF) supplementation shows a significant increase in Sca-1{sup +} HPC proliferation and colony formation while stimulating phosphorylation of ERK1/2 and activating the induction of Cyclin D1. There were no demonstrable effects of EGF on Akt. The MEK inhibitor, PD0325901, inhibits proliferation and ERK1/2 phosphorylation while also suppressing the expression of Cyclin D1. In addition, activation of either IL-6/STAT3 or Wnt/{beta}-Catenin pathway did not independently support cell proliferation and colony formation of HPCs. The Wnt/{beta}-Catenin pathway can cooperate with EGF to significantly promote HPC colony formation ratio and maintain long-term HPC in vitro. The data indicates that the MAPK/ERK pathway is both essential and critical for HPC proliferation, and the Wnt signaling pathway is not sufficient, while it works synergistically with the MAPK/ERK signaling pathway to promote HPC proliferation.

Synergistic rate boosting of collagen fibrillogenesis in heterogeneous mixtures of crowding agents.

Science.gov (United States)

Dewavrin, Jean-Yves; Abdurrahiem, Muhammed; Blocki, Anna; Musib, Mrinal; Piazza, Francesco; Raghunath, Michael

2015-03-26

The competition for access to space that arises between macromolecules is the basis of the macromolecular crowding phenomenon, known to modulate biochemical reactions in subtle ways. Crowding is a highly conserved physiological condition in and around cells in metazoans, and originates from a mixture of heterogeneous biomolecules. Here, using collagen fibrillogenesis as an experimental test platform and ideas from the theory of nonideal solutions, we show that an entropy-based synergy is created by a mixture of two different populations of artificial crowders, providing small crowders with extra volume occupancy when in the vicinity of bigger crowders. We present the physiological mechanism by which synergistic effects maximize volume exclusion with the minimum amount of heterogeneous crowders, demonstrating how the evolutionarily optimized crowded conditions found in vivo can be reproduced effectively in vitro.

Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

Science.gov (United States)

Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

2018-04-01

Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

Science.gov (United States)

Kobayashi, S; Arai, S; Hayashi, S; Sakaguchi, T

1989-01-01

The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors. PMID:2786369

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction.

Science.gov (United States)

Goyal, Akash; Yu, Francois T H; Tenwalde, Mathea G; Chen, Xucai; Althouse, Andrew; Villanueva, Flordeliza S; Pacella, John J

2017-07-01

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi. Venous- and arterial-type microthrombi were infused onto a mesh with 40-μm pores to simulate MVO. Pulsed US (1 MHz) was delivered with inertial cavitation (IC) (1.0 MPa, 1000 cycles, 0.33 Hz) and stable cavitation (SC) US (0.23 MPa, 20% duty cycle, 0.33 Hz) regimes while MB suspension (2 × 10 6  MBs/mL) was infused. The efficacy of sonoreperfusion with these parameters was tested with and without tPA. Sonoreperfusion efficacy was significantly greater for IC + tPA compared with tPA alone, IC, SC and SC + tPA, suggesting lytic synergism between tPA and US for both venous- and arterial-type microthrombi. In contrast to our previous in vitro studies using 1.5 MPa at 5000 US cycles without tPA, the IC regime employed herein used 90% less US energy. These findings suggest an IC regime can be used with tPA synergistically to achieve a high degree of fibrinolysis for both thrombus types. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Anti-candidal activity of homoeopathic drugs: An in-vitro evaluation

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Girish Gupta

2015-01-01

Conclusion: The results of these experiments support the concept of "evidence based medicine" depicting that homoeopathic medicines not only work in in-vivo but are equally effective in in-vitro conditions having definite inhibitory activity against Candida albicans.

In vitro evaluation of antioxidant activity of Cordia dichotoma (Forst f.) bark.

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Nariya, Pankaj B; Bhalodia, Nayan R; Shukla, Vinay J; Acharya, Rabinarayan; Nariya, Mukesh B

2013-01-01

Cordia dichotoma Forst. f. bark, identified as botanical source of Shleshmataka in Ayurvedic pharmacopoeia. Present investigation was undertaken to evaluate possible antioxidant potential of methanolic and butanol extract of C. dichotoma bark. In vitro antioxidant activity of methanolic and butanol extract was determined by 1,1, diphenyl-2, picrylhydrazyl (DPPH) free radical scavenging assay. The extracts were also evaluated for their phenolic contents and antioxidant activity. Phenolic content was measured using Folin-Ciocalteu reagent and was calculated as Gallic acid equivalents. Antiradical activity of methanolic extract was measured by DPPH assay and was compared to ascorbic acid and ferric reducing power of the extract was evaluated by Oyaizu method. In the present study three in vitro models were used to evaluate antioxidant activity. The first two methods were for direct measurement of radical scavenging activity and remaining one method evaluated the reducing power. The present study revealed that the C. dichotoma bark has significant radical scavenging activity.

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

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Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

2013-02-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

The synergistic effect between vanillin and doxorubicin in ehrlich ascites carcinoma solid tumor and MCF-7 human breast cancer cell line.

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Elsherbiny, Nehal M; Younis, Nahla N; Shaheen, Mohamed A; Elseweidy, Mohamed M

2016-09-01

Despite the remarkable anti-tumor activity of doxorubicin (DOX), its clinical application is limited due to multiple organ toxicities. Products with less side effects are therefore highly requested. The current study investigated the anti-cancer activities of vanillin against breast cancer and possible synergistic potentiation of DOX chemotherapeutic effects by vanillin. Vanillin (100mg/kg), DOX (2mg/kg) and their combination were administered i.p. to solid Ehrlich tumor-bearing mice for 21days. MCF-7 human breast cancer cell line was treated with vanillin (1 and 2mM), DOX (100μM) or their combination. Protection against DOX-induced nephrotoxicity was studied in rats that received vanillin (100mg/kg, ip) for 10days with a single dose of DOX (15mg/kg) on day 6. Vanillin exerted anticancer effects comparable to DOX and synergesticlly potentiated DOX anticancer effects both in-vivo and in-vitro. The anticancer potency of vanillin in-vivo was mediated via apoptosis and antioxidant capacity. It also offered an in-vitro growth inhibitory effect and cytotoxicity mediated by apoptosis (increased caspase-9 and Bax:Bcl-2 ratio) along with anti-metasasis effect. Vanillin protected against DOX-induced nephrotoxicity in rats. In conclusion, vanillin can be a potential lead molecule for the development of non-toxic agents for the treatment of breast cancer either alone or combined with DOX. Copyright © 2016. Published by Elsevier GmbH.

Overview of synergistic aging effects

International Nuclear Information System (INIS)

Steigelmann, W.; Farber, M.

1982-01-01

Proper, technically defensible qualification of materials and equipment for nuclear power facilities requires that the effects of combined environment exposures be addressed. The full significance of synergistic effects resulting from combined stresses still remains largely an unknown to be provided for by use of conservatisms, allowing a sizeable margin in test programs and analyses to account for possible combined effects. However, these margins, when applied to sequential aging tests, may under- or over-estimate the qualified life of the material or equipment. Experimentation with radiation dose-rate effects, simultaneous vs. sequential ordered exposures, and other combined environment testing are highlighted in this paper to provide an overview of the current state-of-knowledge concerning synergistic effects and their significance to qualification programs

Identification of a novel acetate-utilizing bacterium belonging to Synergistes group 4 in anaerobic digester sludge.

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Ito, Tsukasa; Yoshiguchi, Kazumi; Ariesyady, Herto Dwi; Okabe, Satoshi

2011-12-01

Major acetate-utilizing bacterial and archaeal populations in methanogenic anaerobic digester sludge were identified and quantified by radioisotope- and stable-isotope-based functional analyses, microautoradiography-fluorescence in situ hybridization (MAR-FISH) and stable-isotope probing of 16S rRNA (RNA-SIP) that can directly link 16S rRNA phylogeny with in situ metabolic function. First, MAR-FISH with (14)C-acetate indicated the significant utilization of acetate by only two major groups, unidentified bacterial cells and Methanosaeta-like filamentous archaeal cells, in the digester sludge. To identify the acetate-utilizing unidentified bacteria, RNA-SIP was conducted with (13)C(6)-glucose and (13)C(3)-propionate as sole carbon source, which were followed by phylogenetic analysis of 16S rRNA. We found that bacteria belonging to Synergistes group 4 were commonly detected in both 16S rRNA clone libraries derived from the sludge incubated with (13)C-glucose and (13)C-propionate. To confirm that this bacterial group can utilize acetate, specific FISH probe targeting for Synergistes group 4 was newly designed and applied to the sludge incubated with (14)C-acetate for MAR-FISH. The MAR-FISH result showed that bacteria belonging to Synergistes group 4 significantly took up acetate and their active population size was comparable to that of Methanosaeta in this sludge. In addition, as bacteria belonging to Synergistes group 4 had high K(m) for acetate and maximum utilization rate, they are more competitive for acetate over Methanosaeta at high acetate concentrations (2.5-10  mM). To our knowledge, it is the first time to report the acetate-utilizing activity of uncultured bacteria belonging to Synergistes group 4 and its competitive significance to acetoclastic methanogen, Methanosaeta.

Synergistic effects of irradiation of waste-water

International Nuclear Information System (INIS)

Woodbridge, D.D.

1975-01-01

Water is an absolute necessity for all forms of animal and plant life. As man's requirements for water increase, the need for better methods of purification also increase. Technology has been slow to develop new methods of water treatment for the direct utilization of waste-water. Many new construction projects are at a standstill because waste-water treatment methods have not been developed to handle adequately the ever-increasing flow of sewage. Theoretical considerations of the use of high-level radiation in the treatment of waste-water have failed to consider the effects of the hydrated electron, and the potential of the possible synergistic effects of combining chlorine, oxygen and irradiation. An extensive testing programme at the University Center for Pollution Research of the Florida Institute of Technology over the past four years has shown that irradiation of waste-water samples immersed in an aqueous environment provide bacterial kill and reduction in organic pollution far greater than that obtained from theoretical considerations of G values and earlier experiments where the waste samples were not immersed in an aqueous environment. These testing programmes have investigated the synergistic effects of combining oxygen and irradiation. Each of these combined treatments resulted in an increased bacterial kill factor. Tests on Staphylococcus aureus bacteria and faecal streptococcus bacteria indicate that the synergistic effects observed for faecal coliform bacteria also apply to the pathogenic bacteria. A statistical analysis of the data obtained shows the relationships between the various effects on the bacteria. A definite shielding factor from the turbidity of the waste-water has been shown to exist. Synergistic effects have been shown to offset significantly the shielding effects. Optimization of these synergistic effects can greatly increase the effectiveness of irradiation in the treatment of waste-water. (author)

Ionic Liquids: The Synergistic Catalytic Effect in the Synthesis of Cyclic Carbonates

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Flora T.T. Ng

2013-10-01

Full Text Available This review presents the synergistic effect in the catalytic system of ionic liquids (ILs for the synthesis of cyclic carbonate from carbon dioxide and epoxide. The emphasis of this review is on three aspects: the catalytic system of metal-based ionic liquids, the catalytic system of hydrogen bond-promoted ionic liquids and supported ionic liquids. Metal and ionic liquids show a synergistic effect on the cycloaddition reactions of epoxides. The cations and anions of ionic liquids show a synergistic effect on the cycloaddition reactions. The functional groups in cations or supports combined with the anions have a synergistic effect on the cycloaddition reactions. Synergistic catalytic effects of ILs play an important role of promoting the cycloaddition reactions of epoxides. The design of catalytic system of ionic liquids will be possible if the synergistic effect on a molecular level is understood.

In vitro Antifungal Activity of Baccharis trimera Less (DC) Essential ...

African Journals Online (AJOL)

investigate their in vitro antifungal activity against seven fungal strains that cause onychomycosis. Methods: The ... 220 °C and detector at 220 °C. The carrier gas used was ... wavelength of 530 nm [31]. ..... (HTSS) followed by 3D graphs.

Co-delivery of cisplatin and CJM-126 via photothermal conversion nanoparticles for enhanced synergistic antitumor efficacy

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You, Chaoqun; Wu, Hongshuai; Wang, Mingxin; Gao, Zhiguo; Zhang, Xiangyang; Sun, Baiwang

2018-01-01

Polymeric biomaterials that can be smartly disassembled through the cleavage of the covalent bonds in a controllable way upon an environmental stimulus such as pH change, redox, special enzymes, temperature, or ultrasound, as well as light irradiation, but are otherwise stable under normal physiological conditions have attracted great attention in recent decades. The 2-(4-aminophenyl) benzothiazole molecule (CJM-126), as one of the benzothiazole derivatives, has exhibited a synergistic effect with cisplatin (CDDP) and restrains the bioactivities of a series of human breast cancer cell lines. In our study, novel NIR-responsive targeted binary-drug-loaded nanoparticles encapsulating indocyanine green (ICG) dye were prepared as a new co-delivery and combined therapeutic vehicle. The prepared drug-loaded polymeric nanoparticles (TNPs/CDDP-ICG) are stable under normal physiological conditions, while burst drugs release upon NIR laser irradiation in a mild acidic environment. The results further confirmed that the designed co-delivery platform showed higher cytotoxicity than the single free CDDP due to the synergistic treatment of CJM-126 and CDDP in vitro. Taken together, the work might provide a promising approach for effective site-specific antitumor therapy.

Antimicrobial activity of the imipenem/rifampicin combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures.

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Wang, Yang; Bao, Wanguo; Guo, Na; Chen, Haiying; Cheng, Wei; Jin, Kunqi; Shen, Fengge; Xu, Jiancheng; Zhang, Qiaoli; Wang, Chao; An, Yanan; Zhang, Kaiyu; Wang, Feng; Yu, Lu

2014-12-01

To investigate the antimicrobial activity of imipenem and rifampicin alone and in combination against clinical isolates of Acinetobacter baumannii grown in planktonic and biofilm cultures. Minimum inhibitory concentrations were determined for each isolate grown in suspension and in biofilm using a microbroth dilution method. Chequerboard assays and the agar disk diffusion assay were used to determine synergistic, indifferent or antagonistic interactions between imipenem and rifampicin. We used the tissue culture plate method for A. baumannii biofilm formation to measure the percentage of biofilm inhibition and the amount of extracellular DNA after the treatment. To understand the synergistic mechanisms, we conducted hydroxyl radical formation assays. The results were verified by confocal laser scanning microscopy. Imipenem and rifampicin showed effective antimicrobial activity against suspensions and biofilm cultures of A. baumannii, respectively. Synergistic antimicrobial effects between imipenem and rifampicin were observed in 13 and 17 of the 20 clinical isolates when in suspension and in biofilms, respectively. Imipenem and rifampicin alone and in combination generated hydroxyl radicals, which are highly reactive oxygen forms and the major components of bactericidal agents. Furthermore, treatment with imipenem and rifampicin individually or in combination has obvious antibiofilm effects. The synergistic activity of imipenem and rifampicin against clinical isolates of A. baumannii (in suspension and in biofilms) was observed in vitro. Therefore, we conclude that imipenem combined with rifampicin has the potential to be used as a combinatorial therapy for the treatment of infectious diseases caused by A. baumannii.

Combination of Antioxidants from Different Sources Could Offer Synergistic Benefits: A Case Study of Tea and Ginger Blend.

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Makanjuola, Solomon A; Enujiugha, Victor N; Omoba, Olufunmilayo S; Sanni, David M

2015-11-01

Tea and ginger are plants with high antioxidant potential. Combinations of antioxidants from different sources could also produce synergistic antioxidant effects. This study investigated the influence of solvent on antioxidant content of tea, ginger, and tea + ginger blends. Under the investigated extraction conditions, water was the most effective extraction solvent to maximise peroxide scavenging and iron chelating activity of tea, ginger, and their blends. Aqueous ethanol was the most effective solvent to maximise ABTS radical scavenging activity and ethanol was the best solvent to maximise DPPH radical scavenging activity. A good multivariate regression model that explains the relationship between the total flavonoid content of the extracts and their antioxidant activities was obtained (R2 and Q2 of 0.93 and 0.83, respectively). Extracts of tea-ginger blends exhibited synergistic effects in their ABTS and DPPH radical scavenging activity.

An in vitro model for screening estrogen activity of environmental samples after metabolism

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Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

2004-09-15

For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

Synergistic Use of Geniposide and Ginsenoside Rg1 Balance Microglial TNF-α and TGF-β1 following Oxygen-Glucose Deprivation In Vitro: A Genome-Wide Survey

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Jun Wang

2015-01-01

Full Text Available Ischemia-activated microglia are like a double-edged sword, characterized by both neurotoxic and neuroprotective effects. The aim of this study was to reveal the synergistic effect of geniposide and ginsenoside Rg1 based on tumor necrosis factor- (TNF- α and transforming growth factor- (TGF- β1 balance of microglia. BV2 microglial cells were divided into 5 groups: control, model (oxygen-glucose deprivation (OGD, geniposide-treated, ginsenoside-Rg1-treated, and combination-treated. A series of assays were used to detect on (i cell viability; (ii NO content; (iii expression (content of TNF-α and TGF-β1; and (iv gene expression profiles. The results showed that integrated use of geniposide and ginsenoside Rg1 significantly inhibited NO level and protected cell viability, improved the content and expression of TGF-β1, and reduced the content and expression of TNF-α. Separated use of geniposide or ginsenoside Rg1 showed different effects at different emphases. Next-generation sequencing showed that Fcγ-receptor-mediated phagocytosis pathway played a key regulatory role in the balance of TNF-α and TGF-β1 when cotreated with geniposide and ginsenoside Rg1. These findings suggest that synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible avenue for the application.

Regulation of Xenopus laevis DNA topoisomerase I activity by phosphorylation in vitro

International Nuclear Information System (INIS)

Kaiserman, H.B.; Ingebritsen, T.S.; Benbow, R.M.

1988-01-01

DNA topoisomerase I has been purified to electrophoretic homogeneity from ovaries of the frog Xenopus laevis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the most purified fraction revealed a single major band at 110 kDa and less abundant minor bands centered at 62 kDa. Incubation of the most purified fraction with immobilized calf intestinal alkaline phosphatase abolished all DNA topoisomerase enzymatic activity in a time-dependent reaction. Treatment of the dephosphorylated X. laevis DNA topoisomerase I with a X. laevis casein kinase type II activity and ATP restored DNA topoisomerase activity to a level higher than that observed in the most purified fraction. In vitro labeling experiments which employed the most purified DNA topoisomerase I fraction, [γ- 32 P]ATP, and the casein kinase type II enzyme showed that both the 110- and 62-kDa bands became phosphorylated in approximately molar proportions. Phosphoamino acid analysis showed that only serine residues became phosphorylated. Phosphorylation was accompanied by an increase in DNA topoisomerase activity in vitro. Dephosphorylation of DNA topoisomerase I appears to block formation of the initial enzyme-substrate complex on the basis of the failure of the dephosphorylated enzyme to nick DNA in the presence of camptothecin. The authors conclude that X. laevis DNA topoisomerase I is partially phosphorylated as isolated and that this phosphorylation is essential for expression of enzymatic activity in vitro. On the basis of the ability of the casein kinase type II activity to reactivate dephosphorylated DNA topoisomerase I, they speculate that this kinase may contribute to the physiological regulation of DNA topoisomerase I activity

Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo

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Keiser Jennifer

2012-12-01

Full Text Available Abstract Background Soil-transmitted helminth (STH infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI=0.16, mebendazole-levamisole (CI=0.17 and albendazole-mebendazole (CI=0.23. For albendazole-ivermectin, moderate synergism was observed (CI=0.81 and for albendazole-levamisole a nearly additive effect was documented (CI=0.93 in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.

Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

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Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

2014-01-01

Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

Directory of Open Access Journals (Sweden)

Hye Yeon Choi

Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

Reversal of fluconazole resistance induced by a synergistic effect with Acca sellowiana in Candida glabrata strains.

Science.gov (United States)

R M Machado, Gabriella da; Pippi, Bruna; Dalla Lana, Daiane Flores; Amaral, Ana Paula S; Teixeira, Mário Lettieri; Souza, Kellen C B de; Fuentefria, Alexandre M

2016-11-01

The increased incidence of non-albicans Candida (NAC) resistant to fluconazole (FLZ) makes it necessary to use new therapeutic alternatives. Acca sellowiana (O.berg) Burret (Myrtaceae) is a guava with several proven biological activities. The interaction with fluconazole can be a feasible alternative to overcome this resistance. This study evaluates the in vitro antifungal activity of fractions obtained from the lyophilized aqueous extract of the leaves of A. sellowiana against resistant strains of NAC. The antifungal activity of the fractions was evaluated at 500 μg/mL by microdilution method. Checkerboard assay was performed to determine the effect of the combination of the F2 fraction and antifungal at concentrations: MIC/4, MIC/2, MIC, MIC × 2 and MIC × 4. Candida glabrata showed the lowest MIC values (500-3.90 μg/mL) and the F2 active fraction was the most effective. The association of F2 with FLZ showed a strong synergistic effect (FICI ≤ 0.5) against 100% of C. glabrata resistant isolates. Moreover, the F2 active fraction has demonstrated that probably acts in the cell wall of these yeasts. There was no observed acute dermal toxicity of lyophilized aqueous extract of leaves of A. sellowiana on pig ear skin cells. The interaction between substances present in the F2 active fraction is possibly responsible for the antifungal activity presented by this fraction. This study is unprecedented and suggests that the combination of F2 active fraction and FLZ might be used as an alternative treatment for mucocutaneus infections caused by C. glabrata resistant.

Synergistic interaction and mode of action of Citrus hystrix essential oil against bacteria causing periodontal diseases.

Science.gov (United States)

Wongsariya, Karn; Phanthong, Phanida; Bunyapraphatsara, Nuntavan; Srisukh, Vimol; Chomnawang, Mullika Traidej

2014-03-01

Citrus hystrix de Candolle (Rutaceae), an edible plant regularly used as a food ingredient, possesses antibacterial activity, but there is no current data on the activity against bacteria causing periodontal diseases. C. hystrix essential oil from leaves and peel were investigated for antibiofilm formation and mode of action against bacteria causing periodontal diseases. In vitro antibacterial and antibiofilm formation activities were determined by broth microdilution and time kill assay. Mode of action of essential oil was observed by SEM and the active component was identified by bioautography and GC/MS. C. hystrix leaves oil exhibited antibacterial activity at the MICs of 1.06 mg/mL for P. gingivalis and S. mutans and 2.12 mg/mL for S. sanguinis. Leaf oil at 4.25 mg/mL showed antibiofilm formation activity with 99% inhibition. The lethal effects on P. gingivalis were observed within 2 and 4 h after treated with 4 × MIC and 2 × MIC, respectively. S. sanguinis and S. mutans were completely killed within 4 and 8 h after exposed to 4 × MIC and 2 × MIC of oil. MICs of tested strains showed 4 times reduction suggesting synergistic interaction of oil and chlorhexidine. Bacterial outer membrane was disrupted after treatment with leaves oil. Additionally, citronellal was identified as the major active compound of C. hystrix oil. C. hystrix leaf oil could be used as a natural active compound or in combination with chlorhexidine in mouthwash preparations to prevent the growth of bacteria associated with periodontal diseases and biofilm formation.

Plant extracts of spices and coffee synergistically dampen nuclear factor-κB in U937 cells.

Science.gov (United States)

Kolberg, Marit; Paur, Ingvild; Balstad, Trude R; Pedersen, Sigrid; Jacobs, David R; Blomhoff, Rune

2013-10-01

A large array of bioactive plant compounds (phytochemicals) has been identified and synergy among these compounds might contribute to the beneficial effects of plant foods. The transcription factor nuclear factor-κB (NF-κB) has been suggested as a target for many phytochemicals. Due to the complexity of mechanisms involved in NF-κB regulation, including numerous feedback loops, and the large number of phytochemicals which regulate NF-κB activity, we hypothesize that synergistic or antagonistic effects are involved. The objectives of our study were to develop a statistical methodology to evaluate the concept of synergy and antagonism and to use this methodology in a monocytic cell line (U937 expressing an NF-κB-luciferase reporter) treated with lipopolysaccharide and phytochemical-rich plant extracts. Both synergistic and antagonistic effects were clearly observed. Observed synergy was most pronounced for the combinations of oregano and coffee, and thyme and oregano. For oregano and coffee the synergistic effect was highest at 5 mg/mL with 13.9% (P oregano the highest synergistic effects was at 3 mg/mL with 13.7% (P phytochemical-rich plants may exert synergistic and antagonistic effects on NF-κB regulation. Such complex mechanistic interactions between phytochemicals are likely to underlie the protective effects of a plant-based diet on life-style related diseases. © 2013 Elsevier Inc. All rights reserved.

Sensibilidad in vitro de micobacterias a dos péptidos sintéticos híbridos con actividad antimicrobiana In-vitro activity of two hybrid synthetic peptides having antimicrobial activity against mycobacteria

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E. Zerbini

2006-12-01

Full Text Available El aumento de aislamientos clínicos de Mycobacterium tuberculosis resistentes a las drogas esenciales y de casos de micobacteriosis diseminadas debidas al complejo Mycobacterium avium hacen necesario investigar nuevos agentes antimicobacterianos. Los péptidos antimicrobianos son un nuevo grupo de antibióticos que poseen un mecanismo de acción particular. Algunos de ellos, como la cecropina y la melitina, han sido aislados de insectos y han demostrado buena actividad in vitro contra bacterias gram positivas y gram negativas. Híbridos sintéticos de esos péptidos han presentado mayor actividad que los péptidos individuales. En este trabajo se evaluó la actividad in vitro de dos péptidos híbridos sintéticos de melitina y cecropina contra M. tuberculosis, complejo M. avium, Mycobacterium fortuitum y Mycobacterium smegmatis. Se determinó la concentración inhibitoria mínima empleando la técnica de macrodilución en caldo. Luego se estableció la concentración bactericida mínima en medio Lowenstein Jensen. Los péptidos evaluados mostraron ser activos in vitro contra M. smegmatis, mientras que no presentaron ninguna actividad contra las otras micobacterias estudiadas.The increase in both Mycobacterium tuberculosis human clinical isolates resistant to the essential drugs and cases of disseminated micobacteriosis due to Mycobacterium avium Complex, underlines the need to investigate new antimicobacterial agents. The antimicrobial peptides are a new group of active antibiotics with a particular mechanism of action. Some of them, like cecropin and melittin, isolated from insects, have demonstrated good in vitro activity against Gram-positive and Gram-negative bacteria. Synthetic hybrids of those peptides have been more active than individual peptides. In this study, the in vitro activity of two hybrid synthetic peptides from melittin and cecropin against M. tuberculosis, M. avium Complex, Mycobacterium fortuitum and Mycobacterium smegmatis

Linarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo

Science.gov (United States)

Feng, Xinchi; Wang, Xin; Liu, Youping; Di, Xin

2015-01-01

Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in-vitro and ex-vivo. Ellman’s colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In-vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 μM. Ex-vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/Kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/Kg). Molecular docking study revealed that both 4’-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer’s disease. PMID:26330885

In vitro activity of cefoxitin and imipenem against Mycobacterium abscessus complex.

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Lavollay, M; Dubée, V; Heym, B; Herrmann, J-L; Gaillard, J-L; Gutmann, L; Arthur, M; Mainardi, J-L

2014-05-01

The in vitro activity of cefoxitin and imipenem was compared for 43 strains of the Mycobacterium abscessus complex, mostly isolated from cystic fibrosis patients. The MICs of imipenem were lower than those of cefoxitin, although the number of imipenem-resistant strains was higher according to the CLSI breakpoints. Strain comparisons indicated that the MICs of cefoxitin were significantly higher for Mycobacterium bolletii than for M. abscessus. The MICs of both β-lactams were higher for the rough morphotype than for the smooth morphotype. The clinical impact of the in vitro difference between the activity of imipenem and that of cefoxitin remains to be determined. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

In vitro activity of mecillinam against anaerobic bacteria.

OpenAIRE

Steinkraus, G E; McCarthy, L R

1980-01-01

A microtiter broth dilution method was employed to determine the in vitro activity of mecillinam against 201 recent clinical isolates of anaerobic bacteria. Both the anerobic gram-positive and anaerobic gram-negative bacilli displayed a wide range of minimal inhibitory concentrations of mecillinam; most strains were resistant to the antibiotic. The anaerobic cocci exhibited a narrower range of minimal inhibitory concentrations than were observed with other anaerobes, but also exhibited mecill...

Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.

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Lin, Yu-Wei; Yu, Heidi H; Zhao, Jinxin; Han, Mei-Ling; Zhu, Yan; Akter, Jesmin; Wickremasinghe, Hasini; Walpola, Hasini; Wirth, Veronika; Rao, Gauri G; Forrest, Alan; Velkov, Tony; Li, Jian

2018-06-01

Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations. Copyright © 2018 American Society for Microbiology.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

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Butt AM

2015-02-01

Full Text Available Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin, Haliza Katas Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Doxorubicin (DOX, an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407 and vitamin E TPGS (d-α-tocopheryl polyethylene glycol succinate, TPGS are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA for folate-mediated receptor targeting to cancer cells. Methods: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer

Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

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Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis.

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Mario, Débora Nunes; Guarro, Josep; Santurio, Janio Morais; Alves, Sydney Hartz; Capilla, Javier

2015-08-01

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Synergistic effect on co-gasification reactivity of biomass-petroleum coke blended char.

Science.gov (United States)

Wei, Juntao; Guo, Qinghua; Gong, Yan; Ding, Lu; Yu, Guangsuo

2017-06-01

In this work, effects of gasification temperature (900°C-1100°C) and blended ratio (3:1, 1:1, 1:3) on reactivity of petroleum coke and biomass co-gasification were studied in TGA. Quantification analysis of active AAEM transformation and in situ investigation of morphological structure variations in gasification were conducted respectively using inductively coupled plasma optical emission spectrometer and heating stage microscope to explore synergistic effect on co-gasification reactivity. The results indicated that char gasification reactivity was enhanced with increasing biomass proportion and gasification temperature. Synergistic effect on co-gasification reactivity was presented after complete generation of biomass ash, and gradually weakened with increasing temperature from 1000°C to 1100°C after reaching the most significant value at 1000°C. This phenomenon was well related with the appearance of molten biomass ash rich in glassy state potassium and the weakest inhibition effect on active potassium transformation during co-gasification at the temperature higher than 1000°C. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

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Monica Lacerda Lopes Martins

2013-12-01

Full Text Available In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES, a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg, with acetylcholine (ACh as positive control (5 µg/kg, i.v.. The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.. Captopril (30 mg/kg was used as positive control. Bulbostylis capillaris (86.89 ± 15.20% and ERE (74.89 ± 11.95%, ERE were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%. ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

Synergistic effect of Ebselen and gamma radiation on breast cancer cells.

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Thabet, Noura M; Moustafa, Enas M

2017-08-01

To explore the synergistic effect of a seleno-organic compound Ebselen (Ebs) and/or γ-radiation to exert antitumor effects on human breast cancer (MCF-7) cell line in vitro. Ebs cytotoxicity at various concentrations (10, 25, 50 and 75 μg), cell proliferation and clonogenic assay of Ebs and/or γ-radiation (at 1, 3 and 6 Gy), expression of p-IκBα and NF-κB, inflammatory cytokines levels (TNF-α, IL-2, INF-γ, IL-10 and TGF-β), apoptotic factors (Caspase-3, Granzyme-B and TRAIL) and angiogenic factor (VEGF) were investigated. The results showed that the effective dosage of this combination was observed at 25 μg/ml of Ebs with γ-radiation at 6 Gy. Data displayed a significant reduction in NF-κB mRNA along with an elevation in granzyme-B mRNA and TRAIL mRNA expression. Furthermore, protein expression of caspase-3 was elevated, whereas p-IκBα and p-NF-κB(p65) protein expression was reduced significantly. Also, a significant decline in TNF-α, IL-2, INF-γ, TGF-β with a significant increase in IL-10 levels were revealed. Meanwhile, a significant decrease in VEGF level and proliferation capacity were observed. We conclude that a combination of Ebs with radiotherapy has a major antitumor efficiency in inducing apoptosis and inhibiting cancer cell progression, due to the synergistic effect in regulating gene and protein expression, and in a modulating response of pro-and anti-inflammatory cytokines.

Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity

Science.gov (United States)

Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

2015-10-01

Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.

Synergistic streptococcal phage λSA2 and B30 endolysins kill streptococci in cow milk and in a mouse model of mastitis.

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Schmelcher, Mathias; Powell, Anne M; Camp, Mary J; Pohl, Calvin S; Donovan, David M

2015-10-01

Bovine mastitis results in billion dollar losses annually in the USA alone. Streptococci are among the most relevant causative agents of this disease. Conventional antibiotic therapy is often unsuccessful and contributes to development of antibiotic resistance. Bacteriophage endolysins represent a new class of antimicrobials against these bacteria. In this work, we characterized the endolysins (lysins) of the streptococcal phages λSA2 and B30 and evaluated their potential as anti-mastitis agents. When tested in vitro against live streptococci, both enzymes exhibited near-optimum lytic activities at ionic strengths, pH, and Ca(2+) concentrations consistent with cow milk. When tested in combination in a checkerboard assay, the lysins were found to exhibit strong synergy. The λSA2 lysin displayed high activity in milk against Streptococcus dysgalactiae (reduction of CFU/ml by 3.5 log units at 100 μg/ml), Streptococcus agalactiae (2 log), and Streptococcus uberis (4 log), whereas the B30 lysin was less effective. In a mouse model of bovine mastitis, both enzymes significantly reduced intramammary concentrations of all three streptococcal species (except for B30 vs. S. dysgalactiae), and the effects on mammary gland wet weights and TNFα concentrations were consistent with these findings. Unexpectedly, the synergistic effect determined for the two enzymes in vitro was not observed in the mouse model. Overall, our results illustrate the potential of endolysins for treatment of Streptococcus-induced bovine mastitis.

Influence of In vitro Digestion on Antioxidative Activity of Coconut ...

African Journals Online (AJOL)

Purpose: To investigate the antioxidative stability of coconut meat protein hydrolysates (CMPHs) in the gastrointestinal tract, and evaluate the changes in antioxidant activity, amino acid composition and molecular weight distribution of CMPHs during gastrointestinal (GI )digestion. Methods: A two-stage in vitro digestion ...

In vitro antibacterial activity of Anogeissus leiocarpus leaf extracts on ...

African Journals Online (AJOL)

In vitro antibacterial activity of aqueous and ethanol extracts of the leaf of Anogeissus leiocarpus was tested on some bacteria associated with diarrhea which included Escherichia coli,Salmonella typhi,Salmonella typhimurium, Klebsiella aerogens and Yersinia enterocolitica using agar well diffusion method. There was ...

In vitro reconstitution of the active T. castaneum telomerase.

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Schuller, Anthony P; Harkisheimer, Michael J; Skordalakes, Emmanuel

2011-07-14

Efforts to isolate the catalytic subunit of telomerase, TERT, in sufficient quantities for structural studies, have been met with limited success for more than a decade. Here, we present methods for the isolation of the recombinant Tribolium castaneum TERT (TcTERT) and the reconstitution of the active T. castaneum telomerase ribonucleoprotein (RNP) complex in vitro. Telomerase is a specialized reverse transcriptase that adds short DNA repeats, called telomeres, to the 3' end of linear chromosomes that serve to protect them from end-to-end fusion and degradation. Following DNA replication, a short segment is lost at the end of the chromosome and without telomerase, cells continue dividing until eventually reaching their Hayflick Limit. Additionally, telomerase is dormant in most somatic cells in adults, but is active in cancer cells where it promotes cell immortality. The minimal telomerase enzyme consists of two core components: the protein subunit (TERT), which comprises the catalytic subunit of the enzyme and an integral RNA component (TER), which contains the template TERT uses to synthesize telomeres. Prior to 2008, only structures for individual telomerase domains had been solved. A major breakthrough in this field came from the determination of the crystal structure of the active, catalytic subunit of T. castaneum telomerase, TcTERT. Here, we present methods for producing large quantities of the active, soluble TcTERT for structural and biochemical studies, and the reconstitution of the telomerase RNP complex in vitro for telomerase activity assays. An overview of the experimental methods used is shown in Figure 1.

Phosphorus doped and defects engineered graphene for improved electrochemical sensing: synergistic effect of dopants and defects

International Nuclear Information System (INIS)

Chu, Ke; Wang, Fan; Tian, Ye; Wei, Zhen

2017-01-01

Heteroatom-doped graphene materials emerged as promising metal-free catalysts have recently attracted a growing interest in electrochemical sensing applications. However, their catalytic activity and sensing performances still need to be further improved. Herein, we reported the development of unique phosphorus (P)-doped and plasma-etched graphene (denoted as PG-E) as an efficient metal-free electrocatalyst for dopamine (DA) sensing. It was demonstrated that introducing both P-dopants and plasma-engineered defects in graphene could synergistically improve the activity toward electrocatalytic oxidation of DA by increasing the accessible active sites and promoting the electron transport capability. The resulting PG-E modified electrode showed exceptional DA sensing performances with low detection limit, high selectivity and good stability. These results suggested that the synergistic effect of dopants and defects might be an important factor for developing the advanced graphene-based metal-free catalysts for electrochemical sensing.

Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans.

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Ying-Lien Chen

Full Text Available The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.

Antioxidant activity of wine assessed by different in vitro methods

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Di Lorenzo Chiara

2017-01-01

Full Text Available Epidemiological studies have suggested that a diet rich in antioxidant compounds could help in counteracting the effects of reactive oxygen species, reducing the risk factors for chronic diseases. The moderate consumption of wine, especially red wine, has been associated with the reduction in mortalities from cardiovascular diseases. One of the possible reasons for the protective effect of wine can be identified in the high content of polyphenols (mainly flavonoids, which have significant antioxidant activity. Even though several in vitro tests have been developed for the measure of the antioxidant property, no method has showed a satisfactory correlation with the in vivo situation. On these bases, the aim of this study was the application and comparison of different in vitro methods to assess the antioxidant activity of red, rosé and white wines. The methods were: 1 Folin-Cocalteau's assay for the quantification of total polyphenol content; 2 the DPPH (1,1-diphenyl-2-picrylhydrazyl spectrophotometric assay and the Trolox Equivalent Antioxidant Capacity (TEAC spectrophotometric assay for measuring the antioxidant activity of samples; 3 High Performance Thin Layer Chromatography for separation of phenolic substances and assessment of the associated antioxidant activity; 4 electrochemical detection by using a biosensor. Although all the approaches show some limitations, this battery of tests offers a more reliable body of data on the antioxidant activity of vine derivatives.

Synergistic activation of G protein-gated inwardly rectifying potassium channels by cholesterol and PI(4,5)P2.

Science.gov (United States)

Bukiya, Anna N; Rosenhouse-Dantsker, Avia

2017-07-01

G-protein gated inwardly rectifying potassium (GIRK or Kir3) channels play a major role in the control of the heart rate, and require the membrane phospholipid phosphatidylinositol-bis-phosphate (PI(4,5)P 2 ) for activation. Recently, we have shown that the activity of the heterotetrameric Kir3.1/Kir3.4 channel that underlies atrial K ACh currents was enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) were also enhanced by cholesterol. Here we employ planar lipid bilayers to investigate the crosstalk between PI(4,5)P 2 and cholesterol, and demonstrate that these two lipids act synergistically to activate Kir3.4* currents. Further studies using the Xenopus oocytes heterologous expression system suggest that PI(4,5)P 2 and cholesterol act via distinct binding sites. Whereas PI(4,5)P 2 binds to the cytosolic domain of the channel, the putative binding region of cholesterol is located at the center of the transmembrane domain overlapping the central glycine hinge region of the channel. Together, our data suggest that changes in the levels of two key membrane lipids - cholesterol and PI(4,5)P 2 - could act in concert to provide fine-tuning of Kir3 channel function. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

International Nuclear Information System (INIS)

Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

2011-01-01

The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

In vitro antifungal activity of methanol extracts of some Indian ...

African Journals Online (AJOL)

The methanol extract of 9 Indian medicinal plants belonging to 9 different families were evaluated for in vitro antifungal activity against some yeasts including Candida albicans (1) ATCC2091, C. albicans (2) ATCC18804, Candida glabrata NCIM3448, Candida tropicalis ATCC4563, Cryptococcus luteolus ATCC32044, ...

In vitro Activity and Safety Assessment of New Synthesized Thiazolo ...

African Journals Online (AJOL)

Purpose: To synthesis a series of novel thiazolo pyrimidine derivatives and evaluate them in vitro for their safety and anthelmintic activity against E. multilocularis metacestodes using BALB/c mice. Methods: A new series of substituted amino thiazole, hydrazinothiazole and thiazolo pyrimidine derivatives (2-6) were ...

In vitro antioxidant, antibacterial and anti-tumor activities of total ...

African Journals Online (AJOL)

Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin ...

PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with β2 AR agonists by a natural agent arctigenin.

Science.gov (United States)

Fang, R; Cui, Q; Sun, J; Duan, X; Ma, X; Wang, W; Cheng, B; Liu, Y; Hou, Y; Bai, G

2015-12-01

Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, β2 adrenergic receptor (β2 AR) agonists bind to the β2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the β2 AR agonist, but the target for this remained elusive. Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PDE4D resulted in cAMP accumulation in human bronchial smooth muscle. The inhibition of PDK1 showed a synergistic function with β2 AR agonists and relaxed the constriction of segregated guinea pig tracheal muscle. The PDK1/Akt/PDE4D axis serves as a novel asthma target, which may benefit airflow obstruction. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vitro antitumour activity of orsellinates.

Science.gov (United States)

Bogo, Danielle; de Matos, Maria Fatima Cepa; Honda, Neli Kika; Pontes, Elenir Curi; Oguma, Patricia Midori; da Santos, Evelyn Cristina Silva; de Carvalho, João Ernesto; Nomizo, Auro

2010-01-01

Lichen phenolic compounds exhibit antioxidant, antimicrobial, antiproliferative, and cytotoxic activities. The purpose of this study was to evaluate the anticancer activity of lecanoric acid, a secondary metabolite of the lichen Parmotrema tinctorum, and its derivatives, orsellinates, obtained by structural modification. A cytotoxicity assay was carried out in vitro with sulforhodamine B (SRB) using HEp-2 larynx carcinoma, MCF7 breast carcinoma, 786-0 kidney carcinoma, and B16-F10 murine melanoma cell lines, in addition to a normal (Vero) cell line in order to calculate the selectivity index of the compounds. n-Butyl orsellinate was the most active compound, with IC50 values (the concentration that inhibits 50% of growth) ranging from 7.2 to 14.0 microg/mL, against all the cell lines tested. The compound was more active (IC50 = 11.4 microg/mL) against B16-F10 cells than was cisplatin (12.5 microg/mL). Conversely, lecanoric acid and methyl orsellinate were less active against all cell lines, having an IC50 value higher than 50 microg/mL. Ethyl orsellinate was more active against HEp-2 than against MCF7, 786-0, or B16-F10 cells. The same pattern was observed for n-propyl and n-butyl orsellinates. n-Pentyl orsellinate was less active than n-propyl or n-butyl orsellinates against HEp-2 cells. The orsellinate activity increased with chain elongation (from methyl to n-butyl), a likely consequence of an increase in lipophilicity. The results revealed that the structural modification of lecanoric acid increases the cytotoxic activity of the derivatives tested.

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

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Stanneck Dorothee

2012-04-01

Full Text Available Abstract Background The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies. Methods The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo. Results An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis demonstrated that the combination of these products was highly effective against these

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

Science.gov (United States)

2012-01-01

Background The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies. Methods The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo. Results An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of

Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic-Resistant Acne-Related Bacteria.

Science.gov (United States)

Kim, Ji-Hoon; Yu, Daeung; Eom, Sung-Hwan; Kim, Song-Hee; Oh, Junghwan; Jung, Won-Kyo; Kim, Young-Mog

2017-06-08

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, one of the most common skin diseases. Acne vulgaris is often associated with acne-related bacteria such as Propionibacterium acnes , Staphylococcus epidermidis , Staphylococcus aureus , and Pseudomonas aeruginosa . Some of these bacteria exhibit a resistance against commercial antibiotics that have been used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we tested in vitro antibacterial effect of chitosan-phytochemical conjugates on acne-related bacteria. Three chitosan-phytochemical conjugates used in this study exhibited stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) showed the highest antibacterial effect on acne-related bacteria along with minimum inhibitory concentration (MIC; 8 to 256 μg/mL). Additionally, the MIC values of antibiotics against antibiotic-resistant P. acnes and P. aeruginosa strains were dramatically reduced in combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration (FIC) indices clearly revealed a synergistic antibacterial effect of CCA with antibiotics. Thus, the median sum of FIC (∑FIC) values against the antibiotic-resistant bacterial strains ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics. The results of the present study suggested a potential possibility of chitosan-phytochemical conjugates in the control of infections related to acne vulgaris.

In vitro antimalarial activity of Calophyllum bicolor and hemozoin crystals observed by Transmission Electron Microscope (TEM)

OpenAIRE

Abbas Jamilah

2018-01-01

Objective : In continuation of our antimalarial candidate drug discovery program on Indonesia medicinal plants especially from stem bark of Calophyllum bicolor. Metode : We extracted of bioactive crude extract with hexane, acetone and methanol from stem bark of Calophyllum bicolor and evaluated their antimalarial activity by using parasite Plasmodium falciparum in vitro. Results: Methanol fraction showed most active and potent antimalarial activity dose dependent in in vitro experiments with ...

A Phytoanticipin Derivative, Sodium Houttuyfonate, Induces in Vitro Synergistic Effects with Levofloxacin against Biofilm Formation by Pseudomonas aeruginosa

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Jing Shao

2012-09-01

Full Text Available Antibiotic resistance has become the main deadly factor in infections, as bacteria can protect themselves by hiding in a self-constructed biofilm. Consequently, more attention is being paid to the search for “non-antibiotic drugs” to solve this problem. Phytoanticipins, the natural antibiotics from plants, could be a suitable alternative, but few works on this aspect have been reported. In this study, a preliminary study on the synergy between sodium houttuyfonate (SH and levofloxacin (LFX against the biofilm formation of Pseudomonas aeruginosa was performed. The minimal inhibitory concentrations (MIC of LFX and SH, anti-biofilm formation and synergistic effect on Pseudomonas aeruginosa, and quantification of alginate were determined by the microdilution method, crystal violet (CV assay, checkerboard method, and hydroxybiphenyl colorimetry. The biofilm morphology of Pseudomonas aeruginosa was observed by fluorescence microscope and scanning electric microscope (SEM. The results showed that: (i LFX and SH had an obvious synergistic effect against Pseudomonas aeruginosa with MIC values of 0.25 μg/mL and 128 μg/mL, respectively; (ii ½ × MIC SH combined with 2 × MIC LFX could suppress the biofilm formation of Pseudomonas aeruginosa effectively, with up to 73% inhibition; (iii the concentration of alginate decreased dramatically by a maximum of 92% after treatment with the combination of antibiotics; and (iv more dead cells by fluorescence microscope and more removal of extracellular polymeric structure (EPS by SEM were observed after the combined treatment of LFX and SH. Our experiments demonstrate the promising future of this potent antimicrobial agent against biofilm-associated infections.

OSU-2S/sorafenib synergistic antitumor combination against hepatocellular carcinoma: The role of PKCδ/p53

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Hany A Omar

2016-11-01

Full Text Available Background: Sorafenib (Nexavar® is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC. However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices < 1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusions: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity towards both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol.

Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition.

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Ling, Guixia; Zhang, Tianhong; Zhang, Peng; Sun, Jin; He, Zhonggui

Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA - BCRP inhibitor), and GcNa (Bcl-2 inhibitor). GcNa and dextran sulfate were incorporated as anionic compounds to enhance the encapsulation efficiency of MTO (up to 97.8%±1.9%) and sustain the release of cationic MTO by electrostatic interaction. The results of a series of in vitro and in vivo investigations indicated that the TMLGNs were taken up by the resistant cancer cells by an endocytosis pathway that escaped the efflux induced by BCRP, and the simultaneous release of CsA with MTO further efficiently inhibited the efflux of the released MTO by BCRP; meanwhile GcNa induced the apoptosis process, and an associated synergistic antitumor activity and reversion of MDR were achieved because the reversal index was almost 1.0.

Antibacterial activities of selected Cameroonian spices and their synergistic effects with antibiotics against multidrug-resistant phenotypes

Science.gov (United States)

2011-01-01

Background The emergence of multi-drug resistant (MDR) phenotypes is a major public health problem today in the treatment of bacterial infections. The present study was designed to evaluate the antibacterial activities of the methanol extracts of eleven Cameroonian spices on a panel of twenty nine Gram negative bacteria including MDR strains. Methods The phytochemical analysis of the extracts was carried out by standard tests meanwhile the liquid micro-broth dilution was used for all antimicrobial assays. Results Phytochemical analysis showed the presence of alkaloids, phenols and tannins in all plants extracts. The results of the antibacterial assays indicated that all tested extracts exert antibacterial activities, with the minimum inhibitory concentration (MIC) values varying from 32 to 1024 μg/ml. The extracts from Dichrostachys glomerata, Beilschmiedia cinnamomea, Aframomum citratum, Piper capense, Echinops giganteus, Fagara xanthoxyloïdes and Olax subscorpioïdea were the most active. In the presence of efflux pump inhibitor, PAßN, the activity of the extract from D. glomerata significantly increased on 69.2% of the tested MDR bacteria. At MIC/5, synergistic effects were noted with the extract of D. glomerata on 75% of the tested bacteria for chloramphenicol (CHL), tetracycline (TET) and norfloxacin (NOR). With B. cinnamomea synergy were observed on 62.5% of the studied MDR bacteria with CHL, cefepime (FEP), NOR and ciprofloxacin (CIP) and 75% with erythromycin (ERY). Conclusion The overall results provide information for the possible use of the studied extracts of the spices in the control of bacterial infections involving MDR phenotypes. PMID:22044718

In vitro antibacterial activity of crude methanol extracts of various ...

African Journals Online (AJOL)

Parthenium hysterophorus is an aggressive and exotic weed plant traditionally reported to be used as remedy for various diseases. In the present study in vitro antibacterial activities of P. hysterophorus leaf, flower, bark and root crude methanol extracts were evaluated against five reference strains of pathogenic bacterial ...

In vivo and in vitro Antimalarial Activity of Vernonia amygdalina ...

African Journals Online (AJOL)

omoregie

ABSTRACT. The in vitro antiplasmodial activity and cytotoxicity of extracts from Jatropha tanjorensis leaves ... an important role in the traditional methods of malaria treatment ... system consisted of TLC plates 10 × 10 cm silica gel. 60F254 .... Based on this classification, the three ... cost intervention during malaria infection.

In vitro anti-inflammatory and free radical scavenging activities of ...

African Journals Online (AJOL)

Methods: In vitro antioxidant activity was determined using free radical scavenging assays such as DPPH, ABTS and NO2. The antiinflammatory potential was carried out using inhibition of protein denaturation of egg albumin as a model of anti-inflammatory capacity. Results: Both the crude methanolic extract and saponins ...

Anti-glycated and antiradical activities in vitro of polysaccharides from Ganoderma capense.

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Yan, Chunyan; Kong, Fansheng; Zhang, Dezhi; Cui, Jiangxia

2013-01-01

Ganoderma capense is a Ganoderma species and is widely used, especially in Asia, as a well-known medicinal mushroom for health-promoting effect and for treatment of chronic diseases, such as diabetes, aging, etc. G. capense is rich of polysaccharide. To isolate the polysaccharides from G. capense and evaluate their anti-glycated and antiradical activities in vitro. The dried powder of submerged fermentation culturing mycelium of G. capense was defatted, extracted with water/alkaline water followed by ethanol precipitation and deproteinated. And four crude polysaccharides, named as GC50, GC70, GC90 and GCB, were obtained. For the first time, the in vitro anti-glycated activities of the four samples were studied by non-enzymatic glycation reaction. Then, the DPPH radical and hydroxyl radical assays were established to estimate the antiradical capacity of the four samples. Meanwhile the contents of polysaccharides were determined by phenol-sulphuric acid colorimetry. Preliminary antiradical in vitro studies indicated that the four crude polysaccharides showed concentration-dependent scavenging abilities on DPPH and hydroxyl radicals. The evaluation of anti-glycation activity suggested that GC70 had good potential for inhibiting the formation of advanced glycation end products. Time- and dose-dependent effects were also observed for all GC70 samples.

Additional information to the in vitro antioxidant activity of Ginkgo biloba L

NARCIS (Netherlands)

Lugasi, A; Horvahovich, P; Dworschák, E

The in vitro antioxidant and free radical scavenging activity of the ethanol extract from Ginkgo biloba L. was examined in different systems. The extract showed hydrogen-donating ability, reducing power, copper-binding property, free radical scavenging activity in a H2O2/.OH-luminol system and it

In vitro antioxidant activities of the fractions of Coccinia grandis l. leaf ...

African Journals Online (AJOL)

The present study was aimed at investigating the antioxidant activities of the various fractions of the hydromethanolic extract of the leaves of Coccinia grandis L. Voigt. (Cucurbitaceae). The antioxidant activities of the fractions have been evaluated by using nine in vitro assays and were compared to standard antioxidants ...

Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts

Science.gov (United States)

2011-01-01

Background Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Methods Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Results Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. Conclusions The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines. PMID:21429215

Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts.

Science.gov (United States)

Predes, Fabricia S; Ruiz, Ana L T G; Carvalho, João E; Foglio, Mary A; Dolder, Heidi

2011-03-23

Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines. © 2011 Predes et al; licensee BioMed Central Ltd.

Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts

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Carvalho João E

2011-03-01

Full Text Available Abstract Background Arctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts. Methods Hot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy. Results Higher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines. Conclusions The hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines.

Mathematical description of synergistic interaction between radon and smoking

International Nuclear Information System (INIS)

Jin Kyu Kim; Petin, V.G.; Belkina, S.V.

2007-01-01

Complete text of publication follows. Background: A certain level of background exposure to ionizing radiation and natural or man-made chemicals is always present in the environment. Radon and its short-lived decay products are considered as important sources of public exposure to the natural radioactivity. It is well known from epidemiological and toxicological studies that synergistic interaction between smoking and radon occurs, which is especially important for high natural background areas. Objective: This study has been done to suggest a mathematical model to describe the synergistic interaction of radon with tobacco smoking, and to demonstrate the ability of the model to describe carcinogenic effects of the combined action. Methods: A simple mathematical model was formulated to describe and predict the synergistic interaction of radon with smoking. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arisen from the interaction of sublesions induced by the two factors under consideration. Results: The predictions of the model were verified by comparison with experimental data published by other researchers. The model appears to be appropriate and the predictions are valid. Conclusions: : The suggested mathematical model predicts the greatest level of synergistic effect and condition under which the maximum synergy is attained. The synergistic effect appeared to decline with any deviation from the optimal value of the ratio of carcinogenic effective damages produced by each agent alone.

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

Science.gov (United States)

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro activity of DMG-Mino and DMG-DM Dot, two new glycylcyclines, against anaerobic bacteria.

Science.gov (United States)

Nord, C E; Lindmark, A; Persson, I

1993-10-01

The in vitro activity of DMG-Mino and DMG-DM Dot against 350 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides species and fusobacteria was determined by the agar dilution method. Their activity was compared with that of minocycline, doxycycline, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. DMG-Mino and DMG-DM Dot and imipenem were the most active agents tested. DMG-Mino and DMG-DM Dot had in vitro activity superior to that of minocycline and doxycycline.

In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn.

Science.gov (United States)

Paarakh, Padmaa M; Sreeram, Dileep Chandra; D, Shruthi S; Ganapathy, Sujan P S

2015-12-01

Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally. To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method. Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, (1)H-NMR, (13)C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting. In vitro cytotoxic activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20 to 100 μg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase. Fingerprinting of isolated piperine were done by HPTLC method. The IC50 value was found to be 61.94 ± 0.054 μg/ml in in vitro cytotoxic activity in HeLa Cell lines. Piperine was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.6 kJ mol(-1) binding and 7.06 kJ mol(-1) docking energy with two hydrogen bonds. piperine has shown to possess in vitro cytotoxic activity and in silico studies.

Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity

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Bruckbauer A

2013-02-01

Full Text Available Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB, acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet, low (0.75 g/kg diet, or very low (0.25 g/kg diet doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR, plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidation

Synergistic effect of baicalein, wogonin and oroxylin A mixture: multistep inhibition of the NF-κB signalling pathway contributes to an anti-inflammatory effect of Scutellaria root flavonoids.

Science.gov (United States)

Shimizu, Tomofumi; Shibuya, Nobuhiko; Narukawa, Yuji; Oshima, Naohiro; Hada, Noriyasu; Kiuchi, Fumiyuki

2018-01-01

Scutellaria root, the root of Scutellaria baicalensis Georgi, is a crude drug used for inflammatory diseases. In our previous report, the combination of flavonoids contained in Scutellaria root have been found to inhibit PGE 2 production more strongly than individual flavonoids. Here, to investigate the mechanism of the synergistic effect, we examined the effects of an equimolar mixture (F-mix) of baicalein (1), wogonin (2) and oroxylin A (3) on the production of PGE 2 in LPS-treated J774.1 cells. Although 1 and 3 inhibited COX-2 activity, the F-mix showed no synergistic effect on COX-2 inhibition. Therefore, we investigated the steps leading to the activation of COX-2 protein. Compounds 1-3 and F-mix inhibited the expression of COX-2 protein. However, only 2 inhibited the expression of COX-2 mRNA among the flavonoids, and the F-mix showed no synergistic effect. Only 1 inhibited NF-κB translocation into the nucleus, and the F-mix showed no synergistic effect. Although 2 did not affect NF-κB translocation, it strongly inhibited NF-κB-dependent transcriptional activity, and the F-mix inhibited the activity slightly more than 2. Compounds 1-3 also inhibited NO production, and the F-mix showed a synergistic effect. However, the effects of each flavonoid on the expression of iNOS mRNA were not consistent with those on COX-2 mRNA. Because the flavonoids inhibit different steps in the production of PGE 2 and NO, and their mixture did not show apparent synergistic effects in each step, we conclude that the synergistic effect of the flavonoid mixture reflects the total effect of the flavonoids inhibiting different steps in the NF-κB signalling pathway.

Simultaneous, But Not Consecutive, Combination With Folinate Salts Potentiates 5-Fluorouracil Antitumor Activity In Vitro and In Vivo.

Science.gov (United States)

Di Paolo, Antonello; Orlandi, Paola; Di Desidero, Teresa; Danesi, Romano; Bocci, Guido

2017-08-07

The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV), or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72 h. TYMS and SLC19A1 gene expression was performed with real-time PCR. In vivo experiments were performed in xenografted nude mice, which were treated with 5-FU escalating doses and CaLV or NaLV alone or in simultaneous and sequential combination. The simultaneous combination of folinate salts and 5-FU was synergistic (NaLV) or additive (CaLV) in a 24-h treatment in both cell lines. In contrast, the sequential combination of both folinate salts and 5-FU was antagonistic at 24 and 72 h. The simultaneous combination of 5-FU and NaLV or CaLV inhibited TYMS gene expression at 24 h, whereas the sequential combination reduced SLC19A1 gene expression. In vivo experiments confirmed the enhanced antitumor activity of the 5-FU + NaLV simultaneous combination with a good toxicity profile, whereas the sequential combination with CaLV failed to potentiate 5-FU activity. In conclusion, only the simultaneous, but not the consecutive, in vitro and in vivo combination of 5-FU and both folinate salt formulations potentiated the antiproliferative effects of the drugs.

In vitro activity of colistin in antimicrobial combination against carbapenem-resistant Acinetobacter baumannii isolated from patients with ventilator-associated pneumonia in Vietnam.

Science.gov (United States)

Le Minh, Vien; Thi Khanh Nhu, Nguyen; Vinh Phat, Voong; Thompson, Corinne; Huong Lan, Nguyen Phu; Thieu Nga, Tran Vu; Thanh Tam, Pham Thi; Tuyen, Ha Thanh; Hoang Nhu, Tran Do; Van Hao, Nguyen; Thi Loan, Huynh; Minh Yen, Lam; Parry, Christopher M; Trung Nghia, Ho Dang; Campbell, James I; Hien, Tran Tinh; Thwaites, Louise; Thwaites, Guy; Van Vinh Chau, Nguyen; Baker, Stephen

2015-10-01

Acinetobacter baumannii has become one of the major infection threats in intensive care units (ICUs) globally. Since 2008, A. baumannii has been the leading cause of ventilator-associated pneumonia (VAP) in our ICU at an infectious disease hospital in southern Vietnam. The emergence of this pathogen in our setting is consistent with the persistence of a specific clone exhibiting resistance to carbapenems. Antimicrobial combinations may be a strategy to treat infections caused by these carbapenem-resistant A. baumannii. Therefore, we assessed potential antimicrobial combinations against local carbapenem-resistant A. baumannii by measuring in vitro interactions of colistin with four antimicrobials that are locally certified for treating VAP. We first performed antimicrobial susceptibility testing and multilocus variable number tandem repeat analysis (MLVA) genotyping on 74 A. baumannii isolated from quantitative tracheal aspirates from patients with VAP over an 18-month period. These 74 isolates could be subdivided into 21 main clusters by MLVA and >80 % were resistant to carbapenems. We selected 56 representative isolates for in vitro combination synergy testing. Synergy was observed in four (7 %), seven (13 %), 20 (36 %) and 38 (68 %) isolates with combinations of colistin with ceftazidime, ceftriaxone, imipenem and meropenem, respectively. Notably, more carbapenem-resistant A. baumannii isolates (36/43; 84 %) exhibited synergistic activity with a combination of colistin and meropenem than carbapenem-susceptible A. baumannii isolates (2/13; 15 %) (P = 0.023; Fisher's exact test). Our findings suggest that combinations of colistin and meropenem should be considered when treating carbapenem-resistant A. baumannii infections in Vietnam, and we advocate clinical trials investigating combination therapy for VAP.

Antihypertensive activity of peptides identified in the in vitro gastrointestinal digest of pork meat.

Science.gov (United States)

Escudero, Elizabeth; Toldrá, Fidel; Sentandreu, Miguel Angel; Nishimura, Hitoshi; Arihara, Keizo

2012-07-01

This study investigated the in vivo antihypertensive activity of three novel peptides identified in the in vitro digest of pork meat. These peptides were RPR, KAPVA and PTPVP and all of them showed significant antihypertensive activity after oral administration to spontaneously hypertensive rats, RPR being the peptide with the greatest in vivo activity. To our knowledge, this is the first report showing the in vivo antihypertensive action of the three peptides from nebulin (RPR) and titin (KAPVA and PTPVP), thus confirming their reported in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. These findings suggest that pork meat could constitute a source of bioactive constituents that could be utilized in functional foods or nutraceuticals. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vitro activity of selected medicinal plants in Kenya on ...

African Journals Online (AJOL)

Although chemotherapy has been used to control the disease, cases of drug resistance by trypanosomes are a major problem and prospects of vaccine development are remote. Herbal medicines have been claimed to be effective in the control of the disease in endemic areas. This study evaluated the in vitro activity of ...

In vitro investigation on antifungal activity of some plant extracts ...

African Journals Online (AJOL)

Prof. Ogunji

In vitro investigation on antifungal activity of some plant extracts against Pyricularia oryzae. Olufolaji, D. B.1, Adeosun, B.O.1 and Onasanya, R. O.2. 1. Department of Crop, Soil and Pest Management, The Federal University of Technology, PMB 704. Akure, Ondo state, Nigeria. 2. Department of Agriculture, Federal College ...

Functional analysis of HPV-like particle-activated Langerhans cells in vitro.

Science.gov (United States)

Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin

2015-01-01

Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.

Study of the in vitro antiplasmodial, antileishmanial and antitrypanosomal activities of medicinal plants from Saudi Arabia.

Science.gov (United States)

Al-Musayeib, Nawal M; Mothana, Ramzi A; Al-Massarani, Shaza; Matheeussen, An; Cos, Paul; Maes, Louis

2012-09-25

The present study investigated the in vitro antiprotozoal activity of sixteen selected medicinal plants. Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC₅₀ Albizia lebbeck pericarp, Caralluma sinaica, Periploca aphylla and Prosopius juliflora. Activity against T. brucei was obtained in Prosopis juliflora. Cytotoxicity (MRC-5 IC₅₀ < 10 μg/mL) and hence non-specific activities were observed for Conocarpus lancifolius.

Berberine Enhances the Antibacterial Activity of Selected Antibiotics against Coagulase-Negative Staphylococcus Strains in Vitro

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Robert D. Wojtyczka

2014-05-01

Full Text Available Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

Berberine enhances the antibacterial activity of selected antibiotics against coagulase-negative Staphylococcus strains in vitro.

Science.gov (United States)

Wojtyczka, Robert D; Dziedzic, Arkadiusz; Kępa, Małgorzata; Kubina, Robert; Kabała-Dzik, Agata; Mularz, Tomasz; Idzik, Danuta

2014-05-22

Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis.

Science.gov (United States)

Jorge, A T S; Arroteia, K F; Santos, I A; Andres, E; Medina, S P H; Ferrari, C R; Lourenço, C B; Biaggio, R M T T; Moreira, P L

2012-10-01

Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Acetylcholinesterase inhibition and antibacterial activity of Mondia whitei adventitious roots and ex vitro-grown somatic embryogenic-biomass

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Ponnusamy Baskaran

2016-10-01

Full Text Available Mondia whitei (Hook.f. Skeels is an important endangered medicinal and commercial plant in South Africa. In vitro propagation systems are required for biomass production and bioactivity analysis to supplement wild resources/stocks. Adventitious roots from somatic embryogenic explants using suspension culture and ex vitro-grown plants produced via somatic embryogenesis were established using different plant growth regulator treatments. The adventitious root biomass and different parts of ex vitro-grown and mother plants were used to investigate the potential for acetylcholinesterase (AChE and antibacterial activities. Adventitious roots derived from 2.5 µM indole-3-acetic acid (IAA treatments and ex vitro-grown plants derived from meta-topolin riboside (mTR and IAA treatments gave the best AChE and antibacterial activities. The in vitro-established M. whitei and ex vitro biomass have comparable ability to function as inhibitors of acetylcholinesterase and antibacterial agents, and can be used as potent bioresources in traditional medicine

In vitro and in vivo antimicrobial activities of seeds of Caesalpinia bonduc (Lin.) Roxb.

Science.gov (United States)

Arif, Tasleem; Mandal, T K; Kumar, Naresh; Bhosale, J D; Hole, Archana; Sharma, G L; Padhi, M M; Lavekar, G S; Dabur, Rajesh

2009-05-04

Caesalpinia bonduc (Lin.) Roxb. is a known drug in Ayurveda to treat various diseases specifically tumors, cysts and cystic fibrosis (CF). The aim of this study was to assess in vitro as well as in vivo antimicrobial activity of Caesalpinia bonduc seeds. The in vitro antimicrobial activities of seed coat and seed kernel extracts were investigated by microbroth dilution assay. In vivo activities of hydro-alcoholic extracts were investigated in rat models of chronic Pseudomonas aeruginosa pneumonia mimicking that in patients with cystic fibrosis. Various extracts of plant seeds exhibited in vitro antimicrobial activities in a range of 22-350 microg/ml. The extracts also showed activity against methicillin resistant (MR) Staphylococcus aureus and ampicillin resistant (AR) Pseudomonas aeruginosa as in the sensitive strains. In rat model of chronic Pseudomonas aeruginosa pneumonia, hydro-alcoholic extracts of Caesalpinia bonduc seed kernel (CBSK) and Caesalpinia bonduc seed coat (CBSC) were injected subcutaneously in the test groups of animals. The control groups were treated with cortisone and saline. Two weeks after challenge with Pseudomonas aeruginosa, the CBSK treated animals showed a significant bacterial clearance from the lungs (PCaesalpinia bonduc may have the potential to be promising natural medicine, with other forms of treatments, for CF patients with chronic Pseudomonas aeruginosa lung infections.

Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In Vitro Study.

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Butt, Aroosa Ishtiaq; Khan, Bushra Tayyaba; Khan, Asma; Khan, Qamar-Uz-Zaman

2017-01-01

Gastroparesis and GERD occur concomitantly in 40 percent of the cases. Prokinetic drugs and acid blockers are employed as the main treatment modality. Ranitidine is an acid blocker with additional prokinetic activity and Itopride is a known prokinetic drug. This study was designed to observe the synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated duodenum of rabbits. Ranitidine (10-5-10-3) and itopride (10-6-10-5) were added in increasing concentrations to isolated duodenum of rabbits and contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative dose response curves were constructed. The potentiating prokinetic effect of Ranitidine on itopride was seen by using a fixed dose of ranitidine and cumulatively enhancing doses of itopride on iWorx. Ranitidine and itopride produced a dose dependent reversible contraction of the isolated tissue of rabbits with ranitidine showing a max response of 0.124mV and itopride showing a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic effect of itopride at low doses but at high dose the effect began to wane off. Ranitidine and itopride produce a statistically significant synergistic potentiating prokinetic effect at low doses in vitro.

A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria

Science.gov (United States)

Yin, Meili; Li, Zhenhua; Zhou, Li; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

2016-03-01

Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF4:Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin-resistant S. aureus (DR-S. aureus) and gram-negative kanamyclin-resistant E. coli (DR-E. coli) bacteria upon near-infrared (NIR) laser irradiation. In this system, the cationic macroporous nature of the hydrogel acts as a molecular ‘anion sponge’, which sucks the outer part of the anionic microbe membrane into the gel interior voids and causes microbe membrane disruption. By incorporating UCNPs/MB-doped silica into the hydrogel, we have combined photodynamic therapy (PDT) with quaternized chitosan to obtain a high therapeutic index via a synergistic effect. In vitro experiments have demonstrated that our system had excellent antibacterial efficiency to both DR-S. aureus and DR-E. coli bacteria. More importantly, our new synergistic treatment modality provided an excellent therapy platform for drug-resistant bacteria, which could improve antimicrobial efficiency.

A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria

International Nuclear Information System (INIS)

Yin, Meili; Li, Zhenhua; Zhou, Li; Dong, Kai; Ren, Jinsong; Qu, Xiaogang

2016-01-01

Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF 4 :Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin-resistant S. aureus (DR-S. aureus) and gram-negative kanamyclin-resistant E. coli (DR-E. coli) bacteria upon near-infrared (NIR) laser irradiation. In this system, the cationic macroporous nature of the hydrogel acts as a molecular ‘anion sponge’, which sucks the outer part of the anionic microbe membrane into the gel interior voids and causes microbe membrane disruption. By incorporating UCNPs/MB-doped silica into the hydrogel, we have combined photodynamic therapy (PDT) with quaternized chitosan to obtain a high therapeutic index via a synergistic effect. In vitro experiments have demonstrated that our system had excellent antibacterial efficiency to both DR-S. aureus and DR-E. coli bacteria. More importantly, our new synergistic treatment modality provided an excellent therapy platform for drug-resistant bacteria, which could improve antimicrobial efficiency. (paper)

Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells.

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Michele Cea

Full Text Available Aberrant histone deacetylase (HDAC activity is frequent in human leukemias. However, while classical, NAD(+-independent HDACs are an established therapeutic target, the relevance of NAD(+-dependent HDACs (sirtuins in leukemia treatment remains unclear. Here, we assessed the antileukemic activity of sirtuin inhibitors and of the NAD(+-lowering drug FK866, alone and in combination with traditional HDAC inhibitors. Primary leukemia cells, leukemia cell lines, healthy leukocytes and hematopoietic progenitors were treated with sirtuin inhibitors (sirtinol, cambinol, EX527 and with FK866, with or without addition of the HDAC inhibitors valproic acid, sodium butyrate, and vorinostat. Cell death was quantified by propidium iodide cell staining and subsequent flow-cytometry. Apoptosis induction was monitored by cell staining with FITC-Annexin-V/propidium iodide or with TMRE followed by flow-cytometric analysis, and by measuring caspase3/7 activity. Intracellular Bax was detected by flow-cytometry and western blotting. Cellular NAD(+ levels were measured by enzymatic cycling assays. Bax was overexpressed by retroviral transduction. Bax and SIRT1 were silenced by RNA-interference. Sirtuin inhibitors and FK866 synergistically enhanced HDAC inhibitor activity in leukemia cells, but not in healthy leukocytes and hematopoietic progenitors. In leukemia cells, HDAC inhibitors were found to induce upregulation of Bax, a pro-apoptotic Bcl2 family-member whose translocation to mitochondria is normally prevented by SIRT1. As a result, leukemia cells become sensitized to sirtuin inhibitor-induced apoptosis. In conclusion, NAD(+-independent HDACs and sirtuins cooperate in leukemia cells to avoid apoptosis. Combining sirtuin with HDAC inhibitors results in synergistic antileukemic activity that could be therapeutically exploited.

In vivo and in vitro antibacterial activity of conglutinin, a mammalian plasma lectin

DEFF Research Database (Denmark)

Friis-Christiansen, P; Thiel, S; Svehag, S E

1990-01-01

of BALB/c mice with Salmonella typhimurium is mediated by conglutinin. Conglutinin also demonstrated antibacterial activity against E. coli and S. typhimurium in vitro. The expression of this activity required the presence of heat-labile serum factors and peritoneal exudate or spleen cells...

In Vitro antioxidant activity of extracts from the leaves of Abies ...

African Journals Online (AJOL)

Traditionally, the leaves of Abies pindrow Royle are employed as an ayurvedic remedy for fever, hypoglycaemic, respiratory and inflammatory conditions. In this study, dichloromethane, methanol and acetone extracts of A. pindrow leaves were analysed for their phytochemical content and in vitro antioxidant activities.

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia ...

African Journals Online (AJOL)

In vitro and in vivo antiplasmodial activity of extracts from Polyalthia suaveolens, Uvaria angolensis and Monodora tenuifolia (Annonaceae). Alvine Ngoutane Mfopa, Cedric Derick Jiatsa Mbouna, Lauve Rachel Yamthe Tchokouaha, Marthe Aimée Tchuenmegne Tchuente, Rufin Marie Toghueo Kouipou, Patrick Valere ...

Ultrastrong Bioinspired Graphene-Based Fibers via Synergistic Toughening.

Science.gov (United States)

Zhang, Yuanyuan; Li, Yuchen; Ming, Peng; Zhang, Qi; Liu, Tianxi; Jiang, Lei; Cheng, Qunfeng

2016-04-13

Ultrastrong bioinspired graphene-based fibers are designed and prepared via synergistic toughening of ionic and covalent bonding. The tensile strength reaches up to 842.6 MPa and is superior to all other reported graphene-based fibers. In addition, its electrical conductivity is as high as 292.4 S cm(-1). This bioinspired synergistic toughening strategy supplies new insight toward the construction of integrated high-performance graphene-based fibers in the near future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro and in vivo activities of Peganum harmala extract against Leishmania major

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Parvaneh Rahimi-Moghaddam

2011-01-01

Conclusions: P harmala seeds extract showed significant in vitro and in vivo antileishmanial activities. Most biological activity of the extract could be attributed to its beta-carboline content. However, another alkaloid of P harmala seeds extract, peganine, has also been reported to have antileishmanial activity. These beneficial effects can be attributed to the cumulative effects of various biologically active components present in it.

Comparative in vitro activity of the new oxacephem antibiotic, flomoxef (6315-S).

Science.gov (United States)

Ruckdeschel, G; Eder, W

1988-10-01

The in vitro activity of flomoxef (6315-S) was determined and compared to that of different cephalosporins against 787 clinical isolates of staphylococci, Enterobacteriaceae and anaerobes. Flomoxef is similar in activity to latamoxef and cefotaxime against Enterobacteriaceae, slightly more active than cephalothin and cefamandole against oxacillin-sensitive strains of Staphylococcus aureus and minimally less active than cefamandole against oxacillin-resistant strains. Flomoxef showed similar or better activity than latamoxef and cefoxitin against most of the anaerobic species of medical importance.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

Science.gov (United States)

Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

2017-06-01

bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine) also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.

High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

Directory of Open Access Journals (Sweden)

Morgan A Wambaugh

2017-06-01

combinations that bypass drug resistance. Trimethoprim and sulfamethizole are both folate biosynthesis inhibitors. We find that this activity disrupts nucleotide homeostasis, which blocks DNA replication in the presence of AZT. Building on these data, we show that other small molecules that disrupt nucleotide homeostasis through other mechanisms (hydroxyurea and floxuridine also act synergistically with AZT. These novel combinations inhibit the growth and virulence of trimethoprim-resistant clinical Escherichia coli and Klebsiella pneumoniae isolates, suggesting that they may be able to be rapidly advanced into clinical use. In sum, we present a generalizable method to screen for novel synergistic combinations, to identify particular mechanisms resulting in synergy, and to use the mechanistic knowledge to rationally design new combinations that bypass drug resistance.

Mefloquine in combination with hemin causes severe damage to adult Schistosoma japonicum in vitro.

Science.gov (United States)

Xiao, Shu-hua; Qiao, Chunhua; Xue, Jian; Wang, Lili

2014-03-01

In order to explore the interaction of mefloquine with hemin against adult Schistosoma japonicum in vitro, the 50% and 95% lethal concentration (LC50 and LC95) of mefloquine and hemin against schistosomes, some factors, such as other iron providing agents, iron chelaters, zinc protoporphyrin-IX, and biological relevant reductants, that might impact on antischistosomal activity induced by interaction of mefloquine with hemin, and preliminary analysis of chemical interaction of both compounds were undertaken. The LC50 and LC95 of mefloquine and hemin alone against schistosomes were determined to be 6.5μg/ml and 7.8μg/ml as well as 232μg/ml and 355μg/ml, respectively. The LC50 and LC95 of mefloquine in the presence of hemin 100μg/ml was 0.24μg/ml and 0.59μg/ml, respectively. On the other hand the LC50 and LC95 of hemin in the presence of mefloquine 1μg/ml was 23.2μg/ml and 77.2μg/ml, respectively. Meanwhile, mefloquine/hemin combinations showed potential synergistic effects against adult S. japonicum, with combination index (CI) values vitamine C or cysteine showed no apparent worm protection effect from toxic mefloquine-hemin even at higher concentrations (242.3-614.6μg/ml, i.e., 6.4-17.8-fold higher than the concentration of hemin). Chemical interaction of mefloquine with hemin was studied in 40% DMSO-Tris buffer solution. Both UV-Vis spectrum and mass spectrum demonstrated the strong interaction of mefloquine with hemin, which resulted in a reduction of hemin color and emergence of an adduct formed by mefloquine and hemin. The results confirm that mefloquine combined with hemin exhibits potential synergistic effect against adult S. japonicum in vitro. Copyright © 2013 Elsevier B.V. All rights reserved.

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

Science.gov (United States)

Hahn, R. C.; Fontes, C. J. F.; Batista, R. D.; Hamdan, J. S.

2002-01-01

In vitro, terbinafine is highly active against a broad spectrum of pathogenic fungi. We evaluated the activities of terbinafine and itraconazole against 31 isolates of Paracoccidioides brasiliensis. The tests were conducted by using a broth macrodilution procedure. MICs, in micrograms per milliliter, were as follows: terbinafine, 0.015 to 1.0 (geometric mean, 0.1188); itraconazole, 0.007 to 0.5 (geometric mean, 0.03165). The usual therapy for paracoccidioidomycosis is sulfonamides, amphotericin B, and azole derivatives (ketoconazole, itraconazole, and fluconazole). In comparison to amphotericin B, azole derivatives allow shorter treatment courses, can be administered orally, and are equally effective. Itraconazole has as high efficacy as ketoconazole, but with superior tolerance. It is the current drug of choice for treatment of paracoccidioidomycosis. The data obtained in this study indicate that terbinafine is active against P. brasiliensis in vitro and suggest that this allylamine can be considered a new option as drug therapy for paracoccidioidomycosis. PMID:12149337

Phenomenological theory of synergistic effects in plasma-wall interaction

International Nuclear Information System (INIS)

Itoh, N.; Hasebe, Y.

1986-01-01

A phenomenological theory for synergistic effects under multi-species particle bombardement has been developed. The theory is based on a model in which two free-energy minima are assumed to be overcome under actions of radiation for a process to be completed. The synergistic factor, the ratio of the yield of the process under irradiation with two species of particles to the summation of the yields of the process under irradiation with each of two component species, is obtained as a function of the beam flux for several parameters relevant to thermodynamic and radiation-enhanced processes. The criterion for the synergistic effect is obtained. The theory has been shown to be able to explain the yield-flux relation obtained by Haasz et al. for hydrogen-induced methane formation from graphite. (orig.)

In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

Science.gov (United States)

Galgóczy, L; Tóth, Liliána; Virágh, M; Papp, T; Vágvölgyi, C S

2012-12-01

The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

In-vitro antimicrobial activity of selected honeys on clinical isolates of ...

African Journals Online (AJOL)

Background Helicobacter pylori is a gram-negative bacterium incriminated in gastroduodenal ulcers, and mucosa-associated lymphoid tissue lymphoma imposing a major burden on health care systems worldwide. Honeys have been shown to have in vitro activity against microaorganisms and suitable for use in ulcers, ...

Antioxidant activity influenced by in vivo and in vitro mutagenesis in ...

African Journals Online (AJOL)

The antioxidant potential (1,1-diphenyl-2-picrylhydrazyl (DPPHº)-scavenging activity) of in vitro regenerated and induced mutant sugarcane (Saccharum officinarum L.) was investigated. Efficient callus induction and shoot regeneration were induced in bud explants when incubated on Murashige and Skoog (MS) medium ...

In vitro systems: standardization of endpoints

International Nuclear Information System (INIS)

Dewey, W.C.

1979-01-01

Principles are discussed for utilizing cell culture systems to assay for interactions between drugs and radiation. Emphasis is based on the necessity of using synchronous cultures to determine whether the interaction is independent, additive, or synergistic, and to determine the effect of drugs on recovery from sublethal x-ray damage (SLD). Furthermore, in studies of drug effects on SLD, adequate controls must be included to distinguish between effects associated with the interaction of 2 x-ray doses and the effects associated with interaction of a second x-ray dose with prior drug exposure. Finally, different methods of expressing drug exposure are reviewed, and associated problems related to predicting in vivo effects from in vitro results are mentioned

Enhanced Biofilm Formation and Increased Resistance to Antimicrobial Agents and Bacterial Invasion Are Caused by Synergistic Interactions in Multispecies Biofilms

DEFF Research Database (Denmark)

Burmølle, Mette; Webb, J.S.; Rao, D.

2006-01-01

from the surface of the marine alga Ulva australis, were screened for synergistic interactions within biofilms when present together in different combinations. Four isolates, Microbacterium phyllosphaerae, Shewanella japonica, Dokdonia donghaensis, and Acinetobacter lwoffii, were found to interact......Most biofilms in their natural environments are likely to consist of consortia of species that influence each other in synergistic and antagonistic manners. However, few reports specifically address interactions within multispecies biofilms. In this study, 17 epiphytic bacterial strains, isolated...... synergistically in biofilms formed in 96-well microtiter plates: biofilm biomass was observed to increase by >167% in biofilms formed by the four strains compared to biofilms composed of single strains. When exposed to the antibacterial agent hydrogen peroxide or tetracycline, the relative activity (exposed...

Purification and synergistic antibacterial activity of arginine derived cyclic dipeptides, from Achromobacter sp. associated with a rhabditid entomopathogenic nematode against major clinically relevant biofilm forming wound bacteria

Directory of Open Access Journals (Sweden)

NISHANTH KUMAR S

2015-08-01

Full Text Available Skin and chronic wound infections caused by various pathogenic bacteria are an increasing and urgent health problem worldwide. In the present study ethyl acetate cell-free culture filtrate of an Achromobacter sp. associated with a Rhabditis entomopathogenic nematode (EPN, displayed promising antibacterial property and was further purified by silica gel column chromatography to get three different cyclic dipeptides (CDPs. Based on the spectral data and Marfey’s analyses, the CDPs were identified as cyclo(D-Leu-D-Arg (1, cyclo(L-Trp-L-Arg (2, and cyclo(D-Trp-D-Arg (3, respectively. Three CDPs were active against all the ten wound associated bacteria tested. The significant antibacterial activity was recorded by CDP 3, and highest activity of 0.5 µg/ml was recorded against Staphylococcus aureus and Pseudomonas aeruginosa. The synergistic antibacterial activities of CDPs and ampicillin were assessed using the checkerboard microdilution method. The results of the current study recorded that the combined effects of CDPs and ampicillin principally recorded synergistic activity. Interestingly, the combination of CDPs and ampicillin also recorded enhanced inhibited biofilm formation by bacteria. Moreover, CDPs significantly stimulate the production of the anti-inflammatory cytokines IL-10 and IL-4 by human peripheral blood mononuclear cells but are without significant effect on the production of TNF-α, a pro-inflammatory cytokines. The three CDPs have been examined for their activities against intracellular S. aureus in murine macrophages (J774 using 24 h exposure to 1X and 2X MIC concentrations. Significance decrease in intracellular S. aureus burden was recorded by CDPs. CDPs also recorded no cytotoxicity towards FS normal fibroblast, VERO and L231 normal lung epithelial cell lines. Antimicrobial activity of the arginine containing CDPs against the wound associated bacteria is reported here for the first. Moreover, this is also the report on the

The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns.

Science.gov (United States)

de Curtis, Marco; Librizzi, Laura; Uva, Laura

2016-02-15

Research on ictogenesis is based on the study of activity between seizures and during seizures in animal models of epilepsy (chronic condition) or in in vitro slices obtained from naïve non-epileptic brains after treatment with pro-convulsive drugs, manipulations of the extracellular medium and specific stimulation protocols. The in vitro isolated guinea pig brain retains the functional connectivity between brain structures and maintains interactions between neuronal, glial and vascular compartments. It is a close-to-in vivo preparation that offers experimental advantages not achieved with the use of other experimental models. Neurophysiological and imaging techniques can be utilized in this preparation to study brain activity during and between seizures induced by pharmacological or functional manipulations. Cellular and network determinants of interictal and ictal discharges that reproduce abnormal patterns observed in human focal epilepsies and the associated changes in extracellular ion and blood-brain permeability can be identified and analyzed in the isolated guinea pig brain. Ictal and interictal patterns recorded in in vitro slices may show substantial differences from seizure activity recorded in vivo due to slicing procedure itself. The isolated guinea pig brain maintained in vitro by arterial perfusion combines the typical facilitated access of in vitro preparations, that are difficult to approach during in vivo experiments, with the preservation of larger neuronal networks. The in vitro whole isolated guinea pig brain preparation offers an unique experimental model to study systemic and neurovascular changes during ictogenesis. Published by Elsevier B.V.

Synergistic Enhancement of Enzyme Performance and Resilience via Orthogonal Peptide-Protein Chemistry Enabled Multilayer Construction.

Science.gov (United States)

Zhang, Xue-Jian; Wang, Xiao-Wei; Sun, Jiaxing; Su, Chao; Yang, Shuguang; Zhang, Wen-Bin

2018-05-16

Protein immobilization is critical to utilize their unique functions in diverse applications. Herein, we report that orthogonal peptide-protein chemistry enabled multilayer construction can facilitate the incorporation of various folded structural domains, including calmodulin in different states, affibody and dihydrofolate reductase (DHFR). An extended conformation is found to be the most advantageous for steady film growth. The resulting protein thin films exhibit sensitive and selective responsive behaviors to bio-signals (Ca2+, TFP, NADPH, etc.) and fully maintain the catalytic activity of DHFR. The approach is applicable to different substrates such as hydrophobic gold and hydrophilic silica microparticles. The DHFR enzyme can be immobilized onto silica microparticles with tunable amounts. The multi-layer set-up exhibits a synergistic enhancement of DHFR activity with increasing number of bilayers and also makes the embedded DHFR more resilient to lyophilization. Therefore, this is a convenient and versatile method for protein immobilization with potential benefits of synergistic enhancement in enzyme performance and resilience.

Synergistic effect of graphene oxide on the methanol oxidation for fuel cell application

Science.gov (United States)

Siwal, Samarjeet; Ghosh, Sarit; Nandi, Debkumar; Devi, Nishu; Perla, Venkata K.; Barik, Rasmita; Mallick, Kaushik

2017-09-01

Aromatic polypyrene was synthesized by the oxidative polymerization of pyrene with potassium tetrachloropalladate (II), as oxidant. During the polymerization process the palladium salt was reduced to metallic palladium and forms the metal-polymer composite material. Polypyrene stabilized palladium nanoparticles showed electrocatalytic activity toward the oxidation of methanol. The performance of the electrocatalytic activity was substantially improved with the incorporation of graphene oxide to the palladium-polypyrene composite and the synergistic performance was attributed to the electronic and structural properties of the system.

Magnetocaloric Effect and Thermoelectric Cooling - A Synergistic Cooling Technology

Science.gov (United States)

2018-01-16

Thermoelectric Cooling - A Synergistic Cooling Technology Sb. GRANT NUMBER N00173-14-1-G016 Sc. PROGRAM ELEMENT NUMBER 82-2020-17 6. AUTHOR(S) 5d...Magnetocaloric Effect and Thermoelectric Cooling - A Synergistic Cooling Technology NRL Grant N00173-14-l-G016 CODE 8200: Spacecraft Engineering Department...82-11-0 1: Space and Space Systems Technology General Engineering & Research, L.L.C. Technical & Administrative point of contact: Dr. Robin

Antibacterial and Antioxidant Activity of Essential Oil Terpenes against Pathogenic and Spoilage-Forming Bacteria and Cell Structure-Activity Relationships Evaluated by SEM Microscopy

Directory of Open Access Journals (Sweden)

Hatice Zengin

2014-11-01

Full Text Available The antibacterial activity and antioxidant effect of the compounds α-terpineol, linalool, eucalyptol and α-pinene obtained from essential oils (EOs, against pathogenic and spoilage forming bacteria were determined. The antibacterial activities of these compounds were observed in vitro on four Gram-negative and three Gram-positive strains. S. putrefaciens was the most resistant bacteria to all tested components, with MIC values of 2% or higher, whereas E. coli O157:H7 was the most sensitive strain among the tested bacteria. Eucalyptol extended the lag phase of S. Typhimurium, E. coli O157:H7 and S. aureus at the concentrations of 0.7%, 0.6% and 1%, respectively. In vitro cell growth experiments showed the tested compounds had toxic effects on all bacterial species with different level of potency. Synergistic and additive effects were observed at least one dose pair of combination against S. Typhimurium, E. coli O157:H7 and S. aureus, however antagonistic effects were not found in these combinations. The results of this first study are encouraging for further investigations on mechanisms of antimicrobial activity of these EO components.

Potassium humate inhibits complement activation and the production of inflammatory cytokines in vitro

Energy Technology Data Exchange (ETDEWEB)

van Rensburg, C.E.J.; Naude, P.J. [University of Pretoria, Pretoria (South Africa)

2009-08-15

The effects of brown coal derived potassium humate on lymphocyte proliferation, cytokine production and complement activation were investigated in vitro. Potassium humate increased lymphocyte proliferation of phytohaemaglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 20 to 80 {mu} g/ml, in a dose dependant manner. On the other hand potassium humate, at 40 {mu} g/ml, significantly inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL. Regarding complement activation it was found that potassium humate inhibits the activation of both the alternative and classical pathways without affecting the stability of the red blood cell membranes. These results indicate that the anti-inflammatory potential of potassium humate could be partially due to the inhibition of pro-inflammatory cytokines responsible for the initiation of these reactions as well as inhibition of complement activation. The increased lymphocyte proliferation observed, might be due to increased IL-2 production as previously been documented.

Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

Directory of Open Access Journals (Sweden)

Xiao-Peng Mei

2012-09-01

Full Text Available Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

Optimisation of synergistic biomass-degrading enzyme systems for efficient rice straw hydrolysis using an experimental mixture design.

Science.gov (United States)

Suwannarangsee, Surisa; Bunterngsook, Benjarat; Arnthong, Jantima; Paemanee, Atchara; Thamchaipenet, Arinthip; Eurwilaichitr, Lily; Laosiripojana, Navadol; Champreda, Verawat

2012-09-01

Synergistic enzyme system for the hydrolysis of alkali-pretreated rice straw was optimised based on the synergy of crude fungal enzyme extracts with a commercial cellulase (Celluclast™). Among 13 enzyme extracts, the enzyme preparation from Aspergillus aculeatus BCC 199 exhibited the highest level of synergy with Celluclast™. This synergy was based on the complementary cellulolytic and hemicellulolytic activities of the BCC 199 enzyme extract. A mixture design was used to optimise the ternary enzyme complex based on the synergistic enzyme mixture with Bacillus subtilis expansin. Using the full cubic model, the optimal formulation of the enzyme mixture was predicted to the percentage of Celluclast™: BCC 199: expansin=41.4:37.0:21.6, which produced 769 mg reducing sugar/g biomass using 2.82 FPU/g enzymes. This work demonstrated the use of a systematic approach for the design and optimisation of a synergistic enzyme mixture of fungal enzymes and expansin for lignocellulosic degradation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Establishment of an efficient in vitro regeneration protocol for rapid and mass propagation of Dendrobium chrysotoxum Lindl. using seed culture.

Science.gov (United States)

Nongdam, Potshangbam; Tikendra, Leimapokpam

2014-01-01

An efficient in vitro regeneration protocol from seed culture has been established successfully for Dendrobium chrysotoxum, an epiphytic orchid having tremendous ornamental and medicinal values. Seed germination response was encouraging in Mitra (M) medium enriched with different combinations of auxins and cytokinins. Medium supplemented with 0.4% activated charcoal (AC), 2 mg/L 6-benzyl amino purine (BAP), and 2 mg/L indole-3-acetic acid (IAA) produced best seed germination percentage in 2 weeks of culture. Incorporation of higher concentration of kinetin (KN) or BAP in combination with low auxin in medium induced pronounced shooting and leaf formation. Reduction in leaf development was evident when cytokinins exist singly in medium indicating synergistic effect of auxin and cytokinin in leaf induction. Presence of elevated level of indole-3-butyric acid (IBA) or 1-naphthalene acetic acid (NAA) with low cytokinin content in medium generated more in vitro rooting, though IBA was found to be more effective in rooting induction as compared to NAA. The in vitro protocol for asymbiotic seed germination developed from the present investigation can be used for rapid mass propagation of this highly important Dendrobium orchid species.

Establishment of an Efficient In Vitro Regeneration Protocol for Rapid and Mass Propagation of Dendrobium chrysotoxum Lindl. Using Seed Culture

Science.gov (United States)

2014-01-01

An efficient in vitro regeneration protocol from seed culture has been established successfully for Dendrobium chrysotoxum, an epiphytic orchid having tremendous ornamental and medicinal values. Seed germination response was encouraging in Mitra (M) medium enriched with different combinations of auxins and cytokinins. Medium supplemented with 0.4% activated charcoal (AC), 2 mg/L 6-benzyl amino purine (BAP), and 2 mg/L indole-3-acetic acid (IAA) produced best seed germination percentage in 2 weeks of culture. Incorporation of higher concentration of kinetin (KN) or BAP in combination with low auxin in medium induced pronounced shooting and leaf formation. Reduction in leaf development was evident when cytokinins exist singly in medium indicating synergistic effect of auxin and cytokinin in leaf induction. Presence of elevated level of indole-3-butyric acid (IBA) or 1-naphthalene acetic acid (NAA) with low cytokinin content in medium generated more in vitro rooting, though IBA was found to be more effective in rooting induction as compared to NAA. The in vitro protocol for asymbiotic seed germination developed from the present investigation can be used for rapid mass propagation of this highly important Dendrobium orchid species. PMID:25401154

IN VITRO ANTIBACTERIAL ACTIVITIES STUDY OF POLYMERIC CIPROFLOXACIN SUSPENSIONS

OpenAIRE

Sahoo Subhashree; Chakraborti Chandra Kanti; Behera Pradipta Kumar

2012-01-01

To study the in vitro antibacterial activities of mucoadhesive suspensions containing Ciprofloxacin, three different formulations were prepared by using three polymers, such as Hydroxypropyl methylcellulose (HPMC) (S1), Carbapol934 (S2) and Carbapol940 (S3), along with some common ingredients (bases). For the investigation, agar well diffusion method was performed taking Staphylococcus aureus (ATCC 25923), Bacillus subtilis and Escherichia coli (ATCC 25922). Apart from S. aureus, S1 and Cipro...

Synergistic extraction of actinides : Part I. Hexa-and pentavalent actinides

International Nuclear Information System (INIS)

Patil, S.K.; Ramakrishna, V.V.

1980-01-01

A detailed discussion on the reported literature on the synergistic extraction of hexa- and pentavalent actinide ions, by different combinations of extractants and from different aqueous media, is presented. Structural aspects of the various complexes involved in synergism also are reviewed. A short account of the applications based on synergistic extraction is also given. (author)

In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn

Science.gov (United States)

Rajani, G.P.; Ashok, Purnima

2009-01-01

Objectives: To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity. Materials and Methods: Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels. Result: Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h. Conclusion: From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity. PMID:20177495

Synergistic and Antagonistic Interplay between Myostatin Gene Expression and Physical Activity Levels on Gene Expression Patterns in Triceps Brachii Muscles of C57/BL6 Mice

Science.gov (United States)

Caetano-Anollés, Kelsey; Mishra, Sanjibita; Rodriguez-Zas, Sandra L.

2015-01-01

Levels of myostatin expression and physical activity have both been associated with transcriptome dysregulation and skeletal muscle hypertrophy. The transcriptome of triceps brachii muscles from male C57/BL6 mice corresponding to two genotypes (wild-type and myostatin-reduced) under two conditions (high and low physical activity) was characterized using RNA-Seq. Synergistic and antagonistic interaction and ortholog modes of action of myostatin genotype and activity level on genes and gene pathways in this skeletal muscle were uncovered; 1,836, 238, and 399 genes exhibited significant (FDR-adjusted P-value myostatin-reduced relative to active and inactive wild-type, (ii) inactive myostatin-reduced and active wild-type, and (iii) inactive myostatin-reduced and inactive wild-type. Several remarkable genes and gene pathways were identified. The expression profile of nascent polypeptide-associated complex alpha subunit (Naca) supports a synergistic interaction between activity level and myostatin genotype, while Gremlin 2 (Grem2) displayed an antagonistic interaction. Comparison between activity levels revealed expression changes in genes encoding for structural proteins important for muscle function (including troponin, tropomyosin and myoglobin) and for fatty acid metabolism (some linked to diabetes and obesity, DNA-repair, stem cell renewal, and various forms of cancer). Conversely, comparison between genotype groups revealed changes in genes associated with G1-to-S-phase transition of the cell cycle of myoblasts and the expression of Grem2 proteins that modulate the cleavage of the myostatin propeptide. A number of myostatin-feedback regulated gene products that are primarily regulatory were uncovered, including microRNA impacting central functions and Piezo proteins that make cationic current-controlling mechanosensitive ion channels. These important findings extend hypotheses of myostatin and physical activity master regulation of genes and gene pathways

Tramadol and propentofylline coadministration exerted synergistic effects on rat spinal nerve ligation-induced neuropathic pain.

Science.gov (United States)

Zhang, Jin; Wu, Dan; Xie, Cheng; Wang, Huan; Wang, Wei; Zhang, Hui; Liu, Rui; Xu, Li-Xian; Mei, Xiao-Peng

2013-01-01

Neuropathic pain is an intractable clinical problem. Drug treatments such as tramadol have been reported to effectively decrease neuropathic pain by inhibiting the activity of nociceptive neurons. It has also been reported that modulating glial activation could also prevent or reverse neuropathic pain via the administration of a glial modulator or inhibitor, such as propentofylline. Thus far, there has been no clinical strategy incorporating both neuronal and glial participation for treating neuropathic pain. Therefore, the present research study was designed to assess whether coadministration of tramadol and propentofylline, as neuronal and glial activation inhibitors, respectively, would exert a synergistic effect on the reduction of rat spinal nerve ligation (SNL)-induced neuropathic pain. Rats underwent SNL surgery to induce neuropathic pain. Pain behavioral tests were conducted to ascertain the effect of drugs on SNL-induced mechanical allodynia with von-Frey hairs. Proinflammatory factor interleukin-1β (IL-1β) expression was also detected by Real-time RT-PCR. Intrathecal tramadol and propentofylline administered alone relieved SNL-induced mechanical allodynia in a dose-dependent manner. Tramadol and propentofylline coadministration exerted a more potent effect in a synergistic and dose dependent manner than the intrathecal administration of either drug alone. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration. Inhibiting proinflammatory factor IL-1β contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain. Thus, our study provided a rationale for utilizing a novel strategy for treating neuropathic pain by blocking the proinflammatory factor related pathways in the central nervous system.

In vitro and in vivo studies of the combination of IGF1R inhibitor figitumumab (CP-751,871) with HER2 inhibitors trastuzumab and neratinib.

Science.gov (United States)

Chakraborty, Ashok K; Zerillo, Cynthia; DiGiovanna, Michael P

2015-08-01

The insulin-like growth factor I receptor (IGF1R) has been linked to resistance to HER2-directed therapy with trastuzumab (Herceptin). We examined the anti-tumor activity of figitumumab (CP-751,871), a human monoclonal antibody that blocks IGF1R ligand binding, alone and in combination with the therapeutic anti-HER2 antibody trastuzumab and the pan-HER family tyrosine kinase inhibitor neratinib, using in vitro and in vivo breast cancer model systems. In vitro assays of proliferation, apoptosis, and signaling, and in vivo anti-tumor experiments were conducted in HER2-overexpressing (BT474) and HER2-normal (MCF7) models. We find single-agent activity of the HER2-targeting drugs but not figitumumab in the BT474 model, while the reverse is true in the MCF7 model. However, in both models, combining figitumumab with HER2-targeting drugs shows synergistic anti-proliferative and apoptosis-inducing effects, and optimum inhibition of downstream signaling. In murine xenograft models, synergistic anti-tumor effects were observed in the HER2-normal MCF7 model for the combination of figitumumab with trastuzumab, and, in the HER2-overexpressing BT474 model, enhanced anti-tumor effects were observed for the combination of figitumumab with either trastuzumab or neratinib. Analysis of tumor extracts from the in vivo experiments showed evidence of the most optimal inhibition of downstream signaling for the drug combinations over the single-agent therapies. These results suggest promise for such combinations in treating patients with breast cancer, and that, unlike the case for single-agent therapy, the therapeutic effects of such combinations may be independent of expression levels of the individual receptors or the single-agent activity profile.

Synergistic Man: Outcome Model for Counselors

Science.gov (United States)

Rousseve, Ronald J.

1973-01-01

Drawing on the insights of Ruth Benedict and Abraham Maslow in their search for an ethical gauge by which to rate personal-social health, this article proposes synergistic man'' as the desired outcome model for counselors. (Author)

In vitro antioxidant and α-amylase inhibition activities of spiced red ...

African Journals Online (AJOL)

Spiced chili paste (green or red), locally known as Datta, is a traditional popular spicy paste consumed in Ethiopia. This study investigated the total phenolic contents (TPC), total flavonoid contents (TFC), in vitro antioxidant, and α-amylase inhibition activities of water, acetone, petroleum ether, methanol, and 80% methanol ...

Antiseptic mouthwashes: in vitro antibacterial activity.

Science.gov (United States)

Watanabe, Evandro; Nascimento, Andresa P; Guerreiro-Tanomaru, Juliane M; Razaboni, Ana M; de Andrade, Denise; Tanomaru-Filho, Mário

2015-01-01

Mouthwashes are used as an adjunct to tooth brushing for improving breath and preventing oral diseases. The aim of this study was to compare the in vitro Maximum Inhibitory Dilution (MID) of 3 mouthwashes with different active ingredients against mutans streptococci (MS). The products analyzed were Periogard®, Cepacol® and Plax® Fresh Mint. Their antibacterial activity was assessed in duplicate in 96-well microtiter plates against 36 clinical isolates of MS. Each mouthwash was submitted to a serial two-fold dilution (1/2.5 to 1/5120) using double concentration of Tryptose Soy Broth with 1.0% yeast extract. The final volume in each well was 100 mL plus 5 mL of a bacterial suspension, equivalent to 107 CFU/mL. They were incubated microaerobically at 37 °C for 48 hours and the MIDs determined. MID was 1/320 for Periogard® and Cepacol®, and 1/20 for PlaxR® Statistical analysis revealed that the MID of Periogard® MID did not differ from that of Cepacol® (p>0.05), and was higher than that of Plax® (pantiseptic mouthwashes containing chlorhexidine (Periogard®) and cetylpyridinium chloride (Cepacol®) had higher in vitroantibacterial activity (MID) against MS than the antiseptic mouthwash containing triclosan (Plax®), according to microbiological method employed.

Pomegranate ellagitannins inhibit α-glucosidase activity in vitro and reduce starch digestibility under simulated gastro-intestinal conditions.

Science.gov (United States)

Bellesia, Andrea; Verzelloni, Elena; Tagliazucchi, Davide

2015-02-01

Pomegranate extract was tested for its ability to inhibit α-amylase and α-glucosidase activity. Pomegranate extract strongly inhibited rat intestinal α-glucosidase in vitro whereas it was a weak inhibitor of porcine α-amylase. The inhibitory activity was recovered in an ellagitannins-enriched fraction and punicalagin, punicalin, and ellagic acid were identified as α-glucosidase inhibitors (IC(50) of 140.2, 191.4, and 380.9 μmol/L, respectively). Kinetic analysis suggested that the pomegranate extract and ellagitannins inhibited α-glucosidase activity in a mixed mode. The inhibitory activity was demonstrated using an in vitro digestion system, mimicking the physiological gastro-intestinal condition, and potatoes as food rich in starch. Pre-incubation between ellagitannins and α-glucosidase increased the inhibitory activity, suggesting that they acted by binding to α-glucosidase. During digestion punicalin and punicalagin concentration decreased. Despite this loss, the pomegranate extract retained high inhibitory activity. This study suggests that pomegranate ellagitannins may inhibit α-glucosidase activity in vitro possibly affecting in vivo starch digestion.

Synergistic effects of atmospheric pressure plasma-emitted components on DNA oligomers: a Raman spectroscopic study.

Science.gov (United States)

Edengeiser, Eugen; Lackmann, Jan-Wilm; Bründermann, Erik; Schneider, Simon; Benedikt, Jan; Bandow, Julia E; Havenith, Martina

2015-11-01

Cold atmospheric-pressure plasmas have become of increasing importance in sterilization processes especially with the growing prevalence of multi-resistant bacteria. Albeit the potential for technological application is obvious, much less is known about the molecular mechanisms underlying bacterial inactivation. X-jet technology separates plasma-generated reactive particles and photons, thus allowing the investigation of their individual and joint effects on DNA. Raman spectroscopy shows that particles and photons cause different modifications in DNA single and double strands. The treatment with the combination of particles and photons does not only result in cumulative, but in synergistic effects. Profilometry confirms that etching is a minor contributor to the observed DNA damage in vitro. Schematics of DNA oligomer treatment with cold atmospheric-pressure plasma. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.