WorldWideScience

Sample records for synergism

  1. Synergism

    International Nuclear Information System (INIS)

    Bekkum, D.W. van

    1988-12-01

    This report makes part of a series of eight reports which have been drawn up in behalf of the dutch Policy Notition Radiation Standards (BNS). In this report a survey is given of the actual scientific assumptions concerning the origine of tumours caused by exposure to ionizing radiation and other carcinogentia. It appears that the process of carcinogenesis is extended over a long period and proceeds probably via a large number of steps (subprocesses). Some of these steps take place under influence of materials or agentia which themselves cannot cause cancer. In this report the term synergisme means all those combinations of carcinogentia and other influences which together have more effect than may be expected on the base of a simple addition. A survey is given of the actually known factors which influence the induction of tumours and of their supposed way of operation. Two examples of tumours which can be induced by radiation and in which synergistic influences can play an important role are elucidated: breast cancer and hormones, and lung cancer and smoking. It is concluded that the influence of synergistic factors upon radiation carcinogenesis has to be evaluated for each tumour type separately. It is recommended, in the assession of the radiation limits, to take into account the specific sensitivity of subpopulations which have been exposed to synergistic factors and in particular for those tumours in which synergistic factors have a large influence. The elaboration of the quantitative meaning of these synergisms for the radiation hazard will require much more research. (author). 32 refs.; 3 figs.; 1 tab

  2. Synergism in anticorrosive paints

    Indian Academy of Sciences (India)

    Abstract. The present work depicts synergism anticorrosive behaviour between zinc hypophosphite and zinc phos- phate in a commercial pigment mixture. Also, the performance of anticorrosive paints was evaluated. Synergism anticorrosive behaviour was evaluated by corrosion potential and linear polarization ...

  3. Toxin synergism in snake venoms

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard

    2016-01-01

    Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components, and can be the result of toxins targeting the same protein, biochemical pathway or physiological process. Few...... simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel...

  4. Synergism of cockroach ( Periplaneta americana )

    African Journals Online (AJOL)

    Cockroach Periplaneta Americana α-amylase hydrolysed starch to maltose and maltodextrin. However, this enzyme was not active against maltose and maltotriose (2 h of reaction). α-Glucosidase of the same organism exhibited activities toward maltose and maltodextrin to glucose. Synergism was observed especially ...

  5. Dose-stress synergism in cancer risk assessment

    International Nuclear Information System (INIS)

    Pop-Jordanova, N.; Pop-Jordanov, J.

    2001-01-01

    Our hypothesis is that the relatively low risk of cancer or leukaemia from depleted uranium, as predicted by the World Health Organization and the International Atomic Energy Agency, is a result of neglecting the synergism between physico-chemical agents and psychological stress agents (here shortly denoted as dose-stress synergism). We use the modified risk assessment model that comprises a psycho-somatic extension, originally developed by us for assessing the risks of energy sources. Our preliminary meta-analysis of animal and human studies on cancers confirmed the existence of stress effects, including the amplifying synergism. Consequently, the psychological stress can increase the probability of even small toxic chemical or ionizing radiation exposure to produce malignancy. Such dose-stress synergism might influence the health risks among military personnel and the residents in the highly stressful environment in the Balkans. Further investigation is needed to estimate the order of magnitude of these combined effects in particular circumstances. (Original)

  6. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    Analgesic synergism of gabapentin and carbamazepine in rat model of diabetic neuropathic pain. Sinan Mohammed Abdullah AL-Mahmood, Shahrin Tarmizi Bin Che Abdullah, Nik Nur Fatnoon Nik Ahmad, Abdul Hadi Bin Mohamed, Tariq Abdul Razak ...

  7. Bacteriophage-antibiotic synergism to control planktonic and biofilm ...

    African Journals Online (AJOL)

    Bacteriophage-antibiotic synergism to control planktonic and biofilm producing clinical isolates of Pseudomonas aeruginosa. Amina Amal Mahmoud Nouraldin, Manal Mohammad Baddour, Reem Abdel Hameed Harfoush, Sara AbdelAziz Mohamed Essa ...

  8. The Scroll and the Sword: Synergizing Civil-Military Power

    Science.gov (United States)

    2006-03-14

    scroll is indeed mightier than the sword , both are mightiest in unison. This synergy, more than anything else, will help ensure that America and its...USAWC STRATEGY RESEARCH PROJECT THE SCROLL AND THE SWORD : SYNERGIZING CIVIL-MILITARY POWER by Colonel Christopher J. Holshek United States Army... Sword Synergizing Civil-Military Power 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Christopher Holshek 5d. PROJECT

  9. Synergizing vaccinations with therapeutics for measles eradication.

    Science.gov (United States)

    Plemper, Richard K; Hammond, Anthea L

    2014-02-01

    The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas. This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles. Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.

  10. Computational analyses of synergism in small molecular network motifs.

    Directory of Open Access Journals (Sweden)

    Yili Zhang

    2014-03-01

    Full Text Available Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically to alter the responses of the motifs to stimuli. Synergism (or antagonism was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.

  11. Synergism between soluble and dietary fiber bound antioxidants.

    Science.gov (United States)

    Çelik, Ecem Evrim; Gökmen, Vural; Skibsted, Leif H

    2015-03-04

    This study investigates the synergism between antioxidants bound to dietary fibers (DF) of grains and soluble antioxidants of highly consumed beverages or their pure antioxidants. The interaction between insoluble fractions of grains containing bound antioxidants and soluble antioxidants was investigated using (i) a liposome-based system by measuring the lag phase before the onset of oxidation and (ii) an ESR-based system by measuring the reduction percentage of Fremy's salt radical. In both procedures, antioxidant capacities of DF-bound and soluble antioxidants were measured as well as their combinations, which were prepared at different ratios. The simple addition effects of DF-bound and soluble antioxidants were compared with measured values. The results revealed a clear synergism for almost all combinations in both liposome- and ESR-based systems. The synergism observed in DF-bound-soluble antioxidant system paints a promising picture considering the role of fiber in human gastrointestinal (GI) tract health.

  12. Tests of pesticidal synergism with young pheasants and Japanese quail

    Science.gov (United States)

    Kreitzer, J.F.; Spann, J.W.

    1973-01-01

    Thirteen pairs of chemicals involving 18 pesticides and two polychlorinated biphenyl preparations were each fed for 5 days to Japanese quail or ring-necked pheasant chicks 7 to 16 days of age. Malathion + EPN, and malathion + trichlorofon were moderately synergistic in tests with both species, whereas joint toxicities of the other chemicals tended to be additive. Comparisons with other studies of joint action of pesticides against mammals and insects suggest that the two species of birds tested are less susceptible to synergism than are mammals or insects. The results also suggest that the likelihood of a factor of synergism greater than three in birds is not great.

  13. 78 FR 43889 - Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine...

    Science.gov (United States)

    2013-07-22

    ...] Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine Products; Public... entitled ``Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative Medicine... discuss current and future standards development activities involving cellular therapies and regenerative...

  14. Antimicrobial Synergic Effect of Allicin and Silver Nanoparticles on ...

    African Journals Online (AJOL)

    Antimicrobial Synergic Effect of Allicin and. Silver Nanoparticles on Skin Infection Caused by. Methicillin‑Resistant Staphylococcus aureus spp. Sharifi‑Rad J1,2, Hoseini‑Alfatemi SM3, Sharifi‑Rad M4, Iriti M5. 1Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran, 2Department of ...

  15. SYNERGIC EXTRACTION OF PANTOTHENIC ACID WITH TWO DIFFERENT EXTRACTANTS

    Directory of Open Access Journals (Sweden)

    A.-I. Galaction

    Full Text Available Abstract The influences of extractants concentrations and solvent polarity on the efficiency of pantothenic acid separation by synergic extraction with tri-n-octylamine (TOA and di(2-ethylhexyl phosphoric acid (D2EHPA mixture have been analyzed. The results indicated the formation of an interfacial compound which includes one molecule of pantothenic acid and one of D2EHPA, its hydrophobicity being increased by solvation with additional TOA molecules. For solvents with lower dielectric constants, n-heptane and n-butyl acetate, the number of amine molecules participating in the interfacial complex formation was controlled by solvent polarity and D2EHPA concentration, decreasing with the increase of these two parameters. For dichloromethane, the chemical structure of the extracted compound remained the same regardless of D2EHPA concentration. The most important synergic effect corresponded to the extractant mixture dissolved in n-heptane, at low D2EHPA concentration in the organic phase (5 g/l.

  16. Endo-exo Synergism in Cellulose Hydrolysis Revisited*

    Science.gov (United States)

    Jalak, Jürgen; Kurašin, Mihhail; Teugjas, Hele; Väljamäe, Priit

    2012-01-01

    Synergistic cooperation of different enzymes is a prerequisite for efficient degradation of cellulose. The conventional mechanistic interpretation of the synergism between randomly acting endoglucanases (EGs) and chain end-specific processive cellobiohydrolases (CBHs) is that EG-generated new chain ends on cellulose surface serve as starting points for CBHs. Here we studied the hydrolysis of bacterial cellulose (BC) by CBH TrCel7A and EG TrCel5A from Trichoderma reesei under both single-turnover and “steady state” conditions. Unaccountable by conventional interpretation, the presence of EG increased the rate constant of TrCel7A-catalyzed hydrolysis of BC in steady state. At optimal enzyme/substrate ratios, the “steady state” rate of synergistic hydrolysis became limited by the velocity of processive movement of TrCel7A on BC. A processivity value of 66 ± 7 cellobiose units measured for TrCel7A on 14C-labeled BC was close to the leveling off degree of polymerization of BC, suggesting that TrCel7A cannot pass through the amorphous regions on BC and stalls. We propose a mechanism of endo-exo synergism whereby the degradation of amorphous regions by EG avoids the stalling of TrCel7A and leads to its accelerated recruitment. Hydrolysis of pretreated wheat straw suggested that this mechanism of synergism is operative also in the degradation of lignocellulose. Although both mechanisms of synergism are used in parallel, the contribution of conventional mechanism is significant only at high enzyme/substrate ratios. PMID:22733813

  17. Investigations of ion-size-selective synergism in solvent extraction

    International Nuclear Information System (INIS)

    McDowell, W.J.; Case, G.N.; Aldrup, D.W.

    1983-01-01

    Organophilic crown ethers and other similar macrocyclic compounds produce a synergistic enhancement of the extraction of several metal ions by organic-phase-soluble carboxylic, phosphoric, and sulfonic acids. Ions examined include the alkali metals, the alkaline earths, and some first-row transition elements. In many cases, the synergistic effects are clearly related to the correspondence of the ion size to the macrocycle cavity diameter. In other cases this is less true, and occasionally, complete lack of synergism or even antagonism is observed. These phenomena have been investigated by systematic studies of the systems involved, by equilibrium studies of selected extraction systems, and by vapor-pressure osmometric studies of the intermolecular bonding between the organic-phase macrocycles and acids. Lack of synergism (when it is expected from size correspondence) does not appear to be due to bonding interactions between the macrocycle and the extractant acid. Other considerations suggest that synergism may depend on the degree to which the macrocycle can surround the ion. Possibilities for metal ion separations are noted, and the directions for further, needed investigations are indicated. 18 references, 14 figures, 2 tables

  18. Detsius effect on the skin trophism in synergism with radiation

    International Nuclear Information System (INIS)

    Dovgusha, V.V.; Zuevich, F.I.; Lobanova, I.Ya.; Ramzaev, V.P.; Rumyantsev, A.P.

    1993-01-01

    Detsins effect on the skin trophism in synergism with radiation (external X irradiation, radon-222 inhalation) and in case of the repeated administration in combination with sodium nitrate was investigated. Rats was used as experimental animals. It was shown that the preliminary X-irradiation at the dose 100R or radon inhalation (8.1x10 7 Bq/m 3 ) did not intensity the toxic effect of detsius and sodium nitrate at the dose 0.5 LD 50 . In case of repeated administration the detsius effect is lower than that in case of single administration at large dose. Conclusion is made that the detsius is hazardous material for children and it is necessary to ban the application of this pesticide in agriculture

  19. Ocean warming-acidification synergism undermines dissolved organic matter assembly.

    Directory of Open Access Journals (Sweden)

    Chi-Shuo Chen

    Full Text Available Understanding the influence of synergisms on natural processes is a critical step toward determining the full-extent of anthropogenic stressors. As carbon emissions continue unabated, two major stressors--warming and acidification--threaten marine systems on several scales. Here, we report that a moderate temperature increase (from 30°C to 32°C is sufficient to slow--even hinder--the ability of dissolved organic matter, a major carbon pool, to self-assemble to form marine microgels, which contribute to the particulate organic matter pool. Moreover, acidification lowers the temperature threshold at which we observe our results. These findings carry implications for the marine carbon cycle, as self-assembled marine microgels generate an estimated global seawater budget of ~1016 g C. We used laser scattering spectroscopy to test the influence of temperature and pH on spontaneous marine gel assembly. The results of independent experiments revealed that at a particular point, both pH and temperature block microgel formation (32°C, pH 8.2, and disperse existing gels (35°C. We then tested the hypothesis that temperature and pH have a synergistic influence on marine gel dispersion. We found that the dispersion temperature decreases concurrently with pH: from 32°C at pH 8.2, to 28°C at pH 7.5. If our laboratory observations can be extrapolated to complex marine environments, our results suggest that a warming-acidification synergism can decrease carbon and nutrient fluxes, disturbing marine trophic and trace element cycles, at rates faster than projected.

  20. Effect of pretreatment methods on the synergism of cellulase and xylanase during the hydrolysis of bagasse.

    Science.gov (United States)

    Jia, Lili; Gonçalves, Geisa A L; Takasugi, Yusaku; Mori, Yutaro; Noda, Shuhei; Tanaka, Tsutomu; Ichinose, Hirofumi; Kamiya, Noriho

    2015-06-01

    The effect of pretreatment with peracetic acid (PAA) or an ionic liquid (1-ethyl-3-methylimidazolium acetate, [Emim][OAc]) on the synergism between endoglucanase and endoxylanase in the hydrolysis of bagasse was investigated. An endoglucanase, Cel6A, with a carbohydrate-binding module (CBM) and two endoxylanases, XynZ-C without a CBM and Xyn11A with an intrinsic xylan/cellulose binding module (XBM), were selected. The hemicellulose content, especially arabinan, and the cellulose crystallinity of bagasse were found to affect the cellulase-xylanase synergism. More specifically, higher synergism (above 3.4) was observed for glucan conversion, at low levels of arabinan (0.9%), during the hydrolysis of PAA pretreated bagasse. In contrast, [Emim][OAc] pretreated bagasse, showed lower cellulose crystallinity and achieved higher synergism (over 1.9) for xylan conversion. Ultimately, the combination of Cel6A and Xyn11A resulted in higher synergism for glucan conversion than the combination of Cel6A with XynZ-C, indicating the importance of the molecular architecture of enzymes for metabolic synergism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Curcumin synergizes with resveratrol to inhibit colon cancer.

    Science.gov (United States)

    Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

    2009-01-01

    Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

  2. Synergic antibacterial activity of some essential oils from Lamiaceae

    Directory of Open Access Journals (Sweden)

    Sh. Fahimi

    2015-05-01

    Full Text Available Background and objectives: Despite the vast production of new antibiotics in the last three decades, resistance to these drugs by microorganisms has increased and essential oils (EOs have been recognized to possess antimicrobial properties. Methods:  In the present study, EOs obtained from aerial parts of Thymus vulgaris L., Lavandula angustifolia Mill., Rosmarinus officinalis L. and Mentha piperita L., were evaluated for their single and binary combined antibacterial activities against four Gram-positive and Gram-negative pathogenic bacteria: Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. Results: The results exhibited that some of the tested essential oils revealed antibacterial activities against the examined pathogens using broth microdilution method. Maximum activity of the testedessential oils was obtained from the combination of T. vulgaris and M. piperita essential oils against Staphylococcus aureus (MIC= 0.625 mg/mL. Conclusion: Combinations of the essential oils in this study showed synergic action against some pathogenic microorganisms which could be considered in medical and food industries as preservatives.

  3. Evidence of cue synergism in termite corpse response behavior

    Science.gov (United States)

    Ulyshen, Michael D.; Shelton, Thomas G.

    2012-02-01

    Subterranean termites of the genus Reticulitermes are known to build walls and tubes and move considerable amounts of soil into wood but the causes of this behavior remain largely unexplored. In laboratory assays, we tested the hypothesis that Reticulitermes virginicus (Banks) would carry more sand into wooden blocks containing corpses compared to corpse-free controls. We further predicted that the corpses of predatory ants would elicit a stronger response than those of a benign beetle species or nestmates. As hypothesized, significantly more sand was carried into blocks containing corpses and this material was typically used to build partitions separating the dead from the rest of the colony. Contrary to expectations, however, this behavior did not vary among corpse types. We then tested the hypothesis that oleic acid, an unsaturated fatty acid released during arthropod decay and used by ants and other arthropod taxa in corpse recognition, would induce a similar building response in R. virginicus. To additionally determine the role of foreign objects in giving rise to this behavior, the experiment was carried out with and without imitation corpses (i.e., small glass beads). As predicted, oleic acid induced building (a tenfold increase) but only when applied to beads, suggesting strong synergism between tactile and chemical cues. Oleic acid also significantly reduced the amount of wood consumed by R. virginicus and may possess useful repellent properties.

  4. SYNERGIC EFFECT OF THE ACTION OF OPERATIONAL AND FINANCIAL RISK

    Directory of Open Access Journals (Sweden)

    MELANIA ELENA MICULEAC

    2014-10-01

    Full Text Available This paper allows us to understand the complex action of total risk at microeconomic level, taking into account several factors: the area in which it acts: the operating activity, generating an economic risk, and the financing activity, generating a financial risk; the nature of the observed indicators: the nature of the profit and the nature of the cash; the synergic effect of the action of operational and financial risk, resulting the total risk. We consider that the innovative value of the article resides in the suggested model of correlation between the activity volume and the capital structure, because different approaches give different results, that is why we suggest a unitary approach, a more pragmatic one of the phenomenon. Also, we established the phases observed in order to establish the global profitability threshold of an international corporation which develops activities in several sectors, through several branches. In this article we have used the method of real leverage which measures the total risk of a company by mixing the operating leverage with the financial leverage.

  5. Synergism in materials erosion due to multispecies impact

    International Nuclear Information System (INIS)

    Auciello, O.; Haasz, A.A.; Stangeby, P.C.

    1985-01-01

    Microelectronic fabrication often involves the use of relatively low-pressure/low-temperature plasma discharges for etching micron-size features in integrated circuits: here erosion is a desired effect. Fusion plasmas, by contrast, cause erosion of the fusion device inner walls, which is generally not desirable. In both cases surfaces are bombarded simultaneously by plasma species which include ions, neutral atoms, electrons and photons, which might lead to enhanced erosion due to synergistic effects. Work performed to date suggests that similar chemistry may be involved in the erosion process associated with some semiconductor and fusion related materials: SiF 4 , SiCl 4 and CH 4 , are, for example,some of the principal species evolving from Si and C surfaces, when exposed to F, Cl and H atoms respectively, causing the observed erosion. Considerable effort has been expended on studies involving synergistic effects for semiconductor fabrication. Research on synergism related to the erosion of fusion materials (C and carbon compounds) commenced comparatively recently; however, its importance has been increasingly recognized and evidence of possible synergistic erosion of graphite has recently been obtained in the PLT fusion device. Experimental and theoretical work on synergistic effects in erosion of both semiconductors and fusion materials will be critically reviewed. (author)

  6. Synergism of Wild Grass and Hydrocarbonoclastic Bacteria in Petroleum Biodegradation

    Directory of Open Access Journals (Sweden)

    Nuni Gofar

    2013-05-01

    Full Text Available The concept of plants and microbes utilization for remediation measure of pollutant contaminated soil is the newest development in term of petroleum waste management technique. The research objective was to obtain wild grass types and hydrocarbonoclastic bacteria which are capable to synergize in decreasing petroleum concentration within petroleum contaminated soil. This research was conducted in a factorial by using a randomized completely block design. The first factor was wild grass type which were without plant, Tridax procumbens grass and Lepironia mucronata grass. The second factor was hydrocarbonoclastic bacteria type which were without bacterium, single bacterium of Alcaligenes faecalis, single bacterium of Pseudomonas alcaligenes, and mixed bacteria of Alcaligenes faecalis with P. alcaligenes. The results showed that mixed bacteria (A. faecalis and P. alcaligenes were capable to increase the crown and roots dry weights of these two grasses and bacteria population, decreased percentage of TPH (total petroleum hydrocarbon and had better pH value than that of single bacterium. The highest TPH decrease with magnitude of 70.1% was obtained on the treatment of L. mucronata grass in combination with mixed bacteria.

  7. Opioid Mechanism Involvement in the Synergism Produced by the Combination of Diclofenac and Caffeine in the Formalin Model

    OpenAIRE

    Flores-Ramos, Jos? Mar?a; D?az-Reval, M. Irene

    2013-01-01

    Analgesics can be administered in combination with caffeine for improved analgesic effectiveness in a process known as synergism. The mechanisms by which these combinations produce synergism are not yet fully understood. The aim of this study was to analyze whether the administration of diclofenac combined with caffeine produced antinociceptive synergism and whether opioid mechanisms played a role in this event. The formalin model was used to evaluate the antinociception produced by the oral ...

  8. Review of synergisms in materials erosion due to multispecies impact

    International Nuclear Information System (INIS)

    Haasz, A.A.; Auciello, O.; Stangeby, P.C.

    1985-05-01

    Plasma-surface interaction phenomena have become a subject of major interest because of their relevance in two important technological developments of recent decades, viz, microelectronics and thermonuclear fusion. Microelectronic fabrication often involves the use of relatively low-pressure/low-temperature plasma discharges for etching micron-size features in integrated circuits; here erosion is a desired effect. Fusion plasmas, by contrast, cause erosion of the fusion device inner walls, which is generally not desirable. In both cases surfaces are bombarded simultaneously by plasma species which include ions, neutral atoms, electrons and photons, which might lead to enhanced erosion due to synergistic effects. Work performed to date suggests that similar chemistry may be involved in the erosion process associated with some semiconductor and fusion related materials: SiF 4 , SiCl 4 and CH 4 , are, for example, some of the principal species evolving from Si and C surfaces, when exposed to F, Cl and H atoms, respectively, causing the observed erosion. Considerable effort has been expended on studies involving synergistic effects for semiconductor fabrication. Research on synergism related to the erosion of fusion materials (C and carbon compounds) commenced comparatively recently; however, its importance has been increasingly recognized, and evidence of possible synergistic erosion of graphite has recently been obtained in the PLT fusion device. In light of the the interdisciplinary nature of the subject, experimental and theoretical work on synergistic effects in erosion of both semiconductors and fusion materials will be critically reviewed here in an attempt to unify concepts related to results and mechanisms proposed to explain the observed phenomena, and to explore possible new avenues of research. 128 refs

  9. Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

    Science.gov (United States)

    Plemper, Richard K; Hammond, Anthea L

    2014-01-01

    Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

  10. Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

    Directory of Open Access Journals (Sweden)

    Fares Al-Ejeh

    Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death

  11. A combinatorial study on catalytic synergism in supported metal catalysts for fuel cell technology

    Science.gov (United States)

    Kobayashi, Tetsuhiko; Ueda, Atsushi; Yamada, Yusuke; Shioyama, Hiroshi

    2004-02-01

    In order to accelerate the catalyst development for the increasing demand on the fuel cell technology, it has been attempted to adopt a combinatorial approach. The catalytic synergism, often observed on the supported metal catalysts for the fuel cell utilization, has been subjected to study. It is proposed herein that not only a comparison of catalysts in one reaction, but also the comparison of interrelated reactions by use of a common catalyst library brings about important information to elucidate the catalytic synergism. Preliminary results of the comparison between the water-gas shift reaction and the steam reforming of MeOH on a given set of catalyst library are presented. An important indicator to predict the serendipitous synergism is expected to be obtained from such information by use of artificial intelligence.

  12. Towards a synergic innovation management model: the interplay of market, technology, and management innovations

    Directory of Open Access Journals (Sweden)

    Leonard Tchuta

    2017-03-01

    Full Text Available This paper outlines a model of firm innovation management known as the synergic innovation management model. Building on the theory of dynamic capabilities and core competence, the paper suggest three capabilities of firms namely market, technology, management capabilities that drive firms’ innovations. The combination of these three capabilities creates a unique configuration for a firm known as the firm’s core competence that informs the firm's strategic decisions. The synergic innovation management model guides firm in the simultaneous exploration of market, technology, and management innovations required for sustainable business. The paper concludes with limitations of the model and suggestions for further research.

  13. Synergism between tobramycin and ceftazidime against a resistant Pseudomonas aeruginosa strain, tested in an in vitro pharmacokinetic model

    NARCIS (Netherlands)

    J.G. den Hollander (Jan); A.M. Horrevorts; M.L. van Goor; H.A. Verbrugh (Henri); J.W. Mouton (Johan)

    1997-01-01

    textabstractSynergism between two antibiotics is usually tested by a checkerboard titration technique, or by time-kill methods. Both methods have the disadvantage that synergism is determined at constant concentrations of the antibiotics, which do not reflect reality in

  14. 75 FR 42743 - Synergics Roth Rock North Wind Energy, LLC; Supplemental Notice That Initial Market-Based Rate...

    Science.gov (United States)

    2010-07-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER10-1673-000] Synergics Roth Rock North Wind Energy, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...-referenced proceeding of Synergics Roth Rock North Wind Energy, LLC's application for market- based rate...

  15. 75 FR 42744 - Synergics Roth Rock Wind Energy, LLC; Supplemental Notice That Initial Market-Based Rate Filing...

    Science.gov (United States)

    2010-07-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER10-1637-000] Synergics Roth Rock Wind Energy, LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request...-referenced proceeding of Synergics Roth Rock Wind Energy, LLC's application for market-based rate authority...

  16. Sweetness potency and sweetness synergism of sweeteners in milk and coffee systems.

    Science.gov (United States)

    Choi, Ji-Hye; Chung, Seo-Jin

    2015-08-01

    This study investigated the presence of sweetness synergism in milk and instant coffee systems. It consists of three parts: 1) modeling concentration-sweetness intensity curves of sweeteners (stevia, sucralose, xylose, tagatose and erythritol); 2) measuring the sweetness potencies of sweeteners compared to sucrose at wide concentration range; and 3) investigating the presence of sweetness synergisms in binary sweetener mixtures. The panelists evaluated sweetness and other sensory characteristics of sweeteners using descriptive analysis. Based on the modeled curve derived from step 1, the concentration of each sweetener with sweetness intensity equal to 2.5% or 2.8% sucrose was calculated for milk and coffee systems, respectively. For the sweetness synergism study, one type of intense sweetener was mixed with one type of bulk sweetener, each eliciting 2.5% or 2.8% equi-sweetness to sucrose, and compared with 5% sucrose added to a milk system or 5.6% sucrose added to a coffee system. The sweetness potencies of bulk sweeteners generally increased whereas the sweetness potencies of intense sweeteners decreased as the concentration increased. The binary sweetener mixtures mostly showed additivity in milk and suppression in coffee system rather than synergism when the concentration dependent nature of sweetness potency for each sweetener was taken into account. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Synergism in mutations induction in Tradescantia by plants protection agents acting jointly with ionizing radiation

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.; Smagala, J.

    1990-01-01

    Tradescantia was first treated by plants protection agents such as: Ambusz, Afalton, Ripcord, Decis, deltametryne and after that irradiated with X radiation. The synergism of both factors was observed. The mutation frequency dependence on radiation doses was studied. 7 figs., 4 refs. (A.S.)

  18. Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae).

    Science.gov (United States)

    Faraone, Nicoletta; Hillier, N Kirk; Cutler, G Christopher

    2015-01-01

    Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender) and Thymus vulgaris (thyme) and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur.

  19. Relationship between the level of acquired resistance to gentamicin and synergism with amoxicillin in Enterococcus faecalis.

    Science.gov (United States)

    Aslangul, Elisabeth; Ruimy, Raymond; Chau, Françoise; Garry, Louis; Andremont, Antoine; Fantin, Bruno

    2005-10-01

    In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 microg/ml (1/16th the MIC), 16 microg/ml (one-eighth the MIC), 64 microg/ml (one-quarter the MIC), and 256 microg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 microg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.

  20. Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae)

    Science.gov (United States)

    Faraone, Nicoletta; Hillier, N. Kirk; Cutler, G. Christopher

    2015-01-01

    Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender) and Thymus vulgaris (thyme) and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae). The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur. PMID:26010088

  1. Plant Essential Oils Synergize and Antagonize Toxicity of Different Conventional Insecticides against Myzus persicae (Hemiptera: Aphididae.

    Directory of Open Access Journals (Sweden)

    Nicoletta Faraone

    Full Text Available Plant-derived products can play an important role in pest management programs. Essential oils from Lavandula angustifolia (lavender and Thymus vulgaris (thyme and their main constituents, linalool and thymol, respectively, were evaluated for insecticidal activity and synergistic action in combination with insecticides against green peach aphid, Myzus persicae (Sulzer (Hemiptera: Aphididae. The essential oils and their main constituents exerted similar insecticidal activity when aphids were exposed by direct sprays, but were non-toxic by exposure to treated leaf discs. In synergism experiments, the toxicity of imidacloprid was synergized 16- to 20-fold by L. angustifolia and T. vulgaris essential oils, but far less synergism occurred with linalool and thymol, indicating that secondary constituents of the oils were probably responsible for the observed synergism. In contrast to results with imidacloprid, the insecticidal activity of spirotetramat was antagonized by L. angustifolia and T. vulgaris essential oils, and linalool and thymol. Our results demonstrate the potential of plant essential oils as synergists of insecticides, but show that antagonistic action against certain insecticides may occur.

  2. Investigation on antibacterial synergism of Origanum vulgare and Thymus vulgaris essential oils

    Directory of Open Access Journals (Sweden)

    Stojković D.

    2013-01-01

    Full Text Available Essential oils are well known as strong antimicrobial agents of plant origin. In spite of this, the antimicrobial synergism of essential oils isolated from different plant species is poorly investigated. The following study examines the synergism of the essential oils of Origanum vulgare L. and Thymus vulgaris L against pathogenic bacteria, Staphylococcus aureus and Salmonella typhimurium. First, the antibacterial effect of the oils was tested, and the minimal inhibitory concentrations (MIC of both oils were determined using the microdilution method. To test whether the oils act synergistically, every possible combination of essential oil concentrations was used in a dynamic checkerboard method. The results indicated that the oils indeed acted synergistically with fractional inhibitory concentration indexes of 0.45 and 0.50. [Projekat Ministarstva nauke Republike Srbije, br. 173032

  3. Synergism between plant extract and antimicrobial drugs used on Staphylococcus aureus diseases

    Directory of Open Access Journals (Sweden)

    Joyce Elaine Cristina Betoni

    2006-06-01

    Full Text Available Searches for substances with antimicrobial activity are frequent, and medicinal plants have been considered interesting by some researchers since they are frequently used in popular medicine as remedies for many infectious diseases. The aim of this study was to verify the synergism between 13 antimicrobial drugs and 8 plant extracts - "guaco" (Mikania glomerata, guava (Psidium guajava, clove (Syzygium aromaticum, garlic (Allium sativum, lemongrass (Cymbopogon citratus, ginger (Zingiber officinale, "carqueja" (Baccharis trimera, and mint (Mentha piperita - against Staphylococcus aureus strains, and for this purpose, the disk method was the antimicrobial susceptibility test performed. Petri dishes were prepared with or without dilution of plant extracts at sub-inhibitory concentrations in Mueller-Hinton Agar (MHA, and the inhibitory zones were recorded in millimeters. In vitro anti-Staphylococcus aureus activities of the extracts were confirmed, and synergism was verified for all the extracts; clove, guava, and lemongrass presented the highest synergism rate with antimicrobial drugs, while ginger and garlic showed limited synergistic capacity.

  4. Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Alberts, D.S. (Univ. of Arizona, Tucson); Peng, Y.M.; Chen, H.S.G.; Moon, T.E.; Cetas, T.C.; Hoeschele, J.D.

    1980-08-01

    A small-animal model was developed as a guide to whole-body hyperthermia in cancer patients. Anesthetized DBA/2 mice were secured to a platform, and their hindlimbs were immersed in a 42.3/sup 0/C water bath for 30 to 60 minutes. Hindlimb hyperthermia resulted in steady-state rectal and femoral bone marrow and muscle temperatures of 42/sup 0/C and upper extremity muscle and esophagus temperatures of 41/sup 0/C. With this hyperthermia technique, the mouse spleen colony assay could be used to quantitate the lethality of hyperthermia and/or cis-dichloro-diammineplatinum(II) (cis-platinum) on clonogenic bone marrow and leukemia cells. Hyperthermia prior to cis-platinum administration increased cis-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism was greatest when cis-platinum administration immediately preceded hyperthermia and no evidence existed of synergism against normal bone marrow colonies. Correlative in vivo drug uptake studies showed a marked increase in leukemia cell uptake of /sup 195m/Pt-cis-platinum at elevated temperatures, which suggested a potential mechanism for the apparent antileukemia synergism of cis-platinum and heat.

  5. Effects of Elevated CO₂and Temperature on Pathogenicity Determinants and Virulence of Potato virus X/Potyvirus-Associated Synergism.

    Science.gov (United States)

    Aguilar, Emmanuel; Allende, Lucía; Del Toro, Francisco J; Chung, Bong-Nam; Canto, Tomás; Tenllado, Francisco

    2015-12-01

    Infections of plants by multiple viruses are common in nature and may result in synergisms in pathologies. Several environmental factors influence plant-virus interactions and act on virulence and host defense responses. Mixed viral infections may be more frequent under environmental conditions associated with global warming. Here, we address how changes in the two main parameters behind global warming, carbon dioxide concentrations ([CO₂]) and temperature, may affect virulence of Potato virus X (PVX)/potyvirus-associated synergism compared with single infections in Nicotiana benthamiana. Elevated [CO₂] resulted in attenuated virulence of single infection by PVX, which correlated with a lower accumulation of virus. In contrast, virulence of PVX/potyvirus-associated synergism was maintained at elevated [CO₂]. On the other hand, elevated temperature decreased markedly both virulence and virus titers in the synergistic infection. We also show that the HR-like response elicited by transient coexpression of PVX P25 together with the potyviral helper component-proteinase protein was significantly enhanced by elevated temperature, whereas it was reduced by elevated [CO₂]. Both proteins are main pathogenicity determinants in PVX-associated synergisms. These findings indicate that, under environmental conditions associated with global warming, virulence of PVX/potyvirus-associated synergisms is expected to vary relative to single infections and, thus, may have pathological consequences in the future.

  6. Antimicrobial synergism against different lineages of methicillin-resistant Staphylococcus aureus carrying SCCmec IV.

    Science.gov (United States)

    de Matos, P D M; Sedaca, S; Ferreira, D C; Iorio, N L; Toledo, V C S; Freitas, A I C; Coelho, F L; Sousa, C; Dos Santos, K R N; Pereira, M O

    2014-06-01

    To evaluate the synergistic activity of antimicrobial drugs against lineages of methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec IV. The biofilm production and related genes were also detected. Forty two MRSA isolates were tested for biofilm production and related genes. Biofilm/biomass susceptibility to gentamicin (G), linezolid (L), rifampicin (R) and vancomycin (V) was determined for six isolates from three lineages prevalent in Rio de Janeiro hospitals in concentrations ranging from 0·25 to 64 μg ml(-1). Biomass was evaluated by microtitre plate test and number of viable cells (CFU cm(-2)) and inspected by epifluorescence microscopy. All isolates presented the icaA and sasG genes, but only 38% were biofilm producers. There were 50 and 45% biomass reductions when concentrations ≥4 μg ml(-1) of R or L and ≥16 μg ml(-1) of G or V, respectively, were used. Synergism tests produced a 55% biomass reduction with R(2μgml-1) + G(16μgml-1), R(2μgml-1) + L(2μgml-1), R(2μgml-1) + V(4μgml-1), and L(2μgml-1) + V(4μgml-1). Number of viable cells was reduced from 2 to 3 logs with R(2μgml-1) + L(2μgml-1) and R(2μgml-1) + V(4μgml-1). Synergisms involving R plus L and R plus V caused important reductions in biofilm/biomass and the number of viable cells. Drug combinations should be considered in the chemotherapies of MRSA-SCCmec IV infections. Biofilms in MRSA infections restrict the clinical choice of antimicrobials. Thus, knowledge of the best options for monotherapy and drug synergisms could improve clinical results. © 2014 The Society for Applied Microbiology.

  7. PSA-operations synergism for the advanced test reactor shutdown operations PSA

    International Nuclear Information System (INIS)

    Atkinson, S.A.

    1996-01-01

    The Advanced Test Reactor (ATR) Probabilistic Safety Assessment (PSA) for shutdown operations, cask handling, and canal draining is a successful example of the importance of good PSA-operations synergism for achieving a realistic and accepted assessment of the risks and for achieving desired risk reduction and safety improvement in a best and cost-effective manner. The implementation of the agreed-upon upgrades and improvements resulted in the reductions of the estimated mean frequency for core or canal irradiated fuel uncovery events, a total reduction in risk by a factor of nearly 1000 to a very low and acceptable risk level for potentially severe events

  8. Structure-activity relationship of condensed tannins and synergism with trans-cinnamaldehyde against Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Ropiak, Honorata M; Desrues, Olivier; Williams, Andrew Richard

    2016-01-01

    ). A nonsignificant correlation was evident between the ability of CT fractions to inhibit C. elegans motility and the molar proportion of prodelphinidin subunits in purified CT samples. Synergistic inhibition of motility was achieved by combinations of CT and CIN. Galloylation of procyanidins was also a key factor...... compounds possessing anthelmintic activity against GIN. We investigated the relationship between the chemical structure of contrasting, purified CT and nematocidal effects using Caenorhabditis elegans. We also explored whether the nematocidal activity of CT could synergize with trans-cinnamaldehyde (CIN...

  9. Photodegradation of phenol on Y2O3 surface: synergism by semiconductors.

    Science.gov (United States)

    Karunakaran, C; Dhanalakshmi, R; Anilkumar, P

    2009-08-15

    Under UV light, phenol degrades on the surface of Y(2)O(3), an insulator, and the degradation follows first-order kinetics, depends linearly on the light intensity and slows down with pH. The efficiency of degradation is higher with UV-C light than with UV-A light. While particulate anatase TiO(2), ZnO, ZnS, Fe(2)O(3), CuO, CdO, and Nb(2)O(5) individually photodegrade phenol, each semiconductor shows synergism when present along with Y(2)O(3), indicating electron-transfer from phenol adsorbed on Y(2)O(3) to the illuminated semiconductors.

  10. Synergization of silicone with developed crosslinking to soy-based polyurethane foam matrix

    Science.gov (United States)

    Elvistia Firdaus, Flora

    2014-06-01

    Flexible polyurethane foam obtained from reaction of soybased polyol with TDI:MDI (80:20), and surfactant. The goal of this research is to determine the synergization effect of silicone with low molecular alcohols; methanol and ethylene glycol (EG) in soy-polyurethane formula on holding moisture of foams to density, foam solutions capacity, and cellular morphology. The optimized of polyol was achieved by ratio of epoxide/methanol 1:6 (mol/mol), and epoxide/EG 1:3 (mol/mol). It was found silicone surfactant can minimize solution absorbency in polyurethane foam matrix.

  11. Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms.

    Science.gov (United States)

    Kim, Dae-Sun; Dastidar, Himika; Zhang, Chunfen; Zemp, Franz J; Lau, Keith; Ernst, Matthias; Rakic, Andrea; Sikdar, Saif; Rajwani, Jahanara; Naumenko, Victor; Balce, Dale R; Ewanchuk, Ben W; Taylor, Pankaj; Yates, Robin M; Jenne, Craig; Gafuik, Chris; Mahoney, Douglas J

    2017-08-24

    Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8 + T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8 + T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSV ΔM51 ) promotes CD8 + T-cell accumulation within tumors and CD8 + T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSV ΔM51 therapy engenders CD8 + T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity.Oncolytic viruses (OV) and second mitochondrial activator of caspase (Smac)-mimetic compounds (SMC) synergistically kill cancer cells directly. Here, the authors show that SMC and OV therapies combination also synergize in vivo by promoting anticancer immunity through an increase in CD8 + T-cell response.

  12. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2014-04-01

    Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Ebf1 or Pax5 haploinsufficiency synergizes with STAT5 activation to initiate acute lymphoblastic leukemia.

    Science.gov (United States)

    Heltemes-Harris, Lynn M; Willette, Mark J L; Ramsey, Laura B; Qiu, Yi Hua; Neeley, E Shannon; Zhang, Nianxiang; Thomas, Deborah A; Koeuth, Thearith; Baechler, Emily C; Kornblau, Steven M; Farrar, Michael A

    2011-06-06

    As STAT5 is critical for the differentiation, proliferation, and survival of progenitor B cells, this transcription factor may play a role in acute lymphoblastic leukemia (ALL). Here, we show increased expression of activated signal transducer and activator of transcription 5 (STAT5), which is correlated with poor prognosis, in ALL patient cells. Mutations in EBF1 and PAX5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL, we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1, but this had little effect on most EBF1 or PAX5 target genes. Only a subset of target genes was deregulated; this subset included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.

  14. Investigation on synergism of composite additives for zinc corrosion inhibition in alkaline solution

    International Nuclear Information System (INIS)

    Zhou Hebing; Huang Qiming; Liang Man; Lv Dongsheng; Xu Mengqing; Li Hong; Li Weishan

    2011-01-01

    Highlights: → An kind of environmentally benign organic composite additives is used firstly. → The corrosion of zinc is inhibited used the organic compound as additive. → The rate performance of the battery used the organic compound as additive is improved. → The synergism of composite additives for zinc corrosion inhibition is investigated. - Abstract: The synergism of imidazole (IMZ) and poly(ethylene glycol) 600 (PEG) for zinc corrosion inhibition in 3 mol L -1 KOH solution was investigated using a combination of electrochemical and gravimetric methods, and the surface morphology of the zinc was observed by scanning electron microscopy. It is found that there is a synergistic effect between IMZ and PEG for the zinc corrosion inhibition. The difference in molecular structure, ring for IMZ and chain for PEG, and in binding atoms with zinc, nitrogen in IMZ and oxygen in PEG, contributes to this synergistic effect. IMZ inhibits zinc corrosion by mainly depressing the anodic reaction, whereas PEG by depressing the cathodic reaction. The storage performance of the zinc-manganese dioxide batteries using IMZ and/or PEG as inhibitors was determined by discharge test, with a comparison of the battery using mercury as the inhibitor. The battery containing 0.05% IMZ + 0.05% PEG exhibits better performance than the mercury-containing battery, especially when discharged at high rate.

  15. Denitrification synergized with ANAMMOX for the anaerobic degradation of benzene: performance and microbial community structure.

    Science.gov (United States)

    Peng, Shuchan; Zhang, Lilan; Zhang, DaiJun; Lu, Peili; Zhang, Xiaoting; He, Qiang

    2017-05-01

    To evaluate the effect of anaerobic ammonium oxidation (ANAMMOX) on benzene degradation under denitrification, a sequencing batch reactor (SBR) under denitrification synergized with ANAMMOX (SBR-DenAna) for benzene degradation was established by inoculating anaerobic ammonium-oxidizing bacteria (AnAOB) into a SBR under denitrification reactor (SBR-Den) for benzene degradation. The average rate of benzene degradation and the maximum first-order kinetic constant in SBR-DenAna were 2.34- and 1.41-fold those in SBR-Den, respectively, indicating that ANAMMOX improved the degradation of benzene under denitrification synergized with ANAMMOX. However, the average rate of benzene degradation decreased by 35% in the denitrification-ANAMMOX synergistic reactor when 10 mg N L -1 NO 2 - was added; the rate recovered once NO 2 - was depleted, indicating that ANAMMOX might detoxify NO 2 - . Results from high-throughput sequencing analysis revealed that Azoarcus within the family Rhodocyclaceae might be associated with benzene degradation in the two SBRs. AnAOB affiliated with the family Candidatus Brocadiaceae were just detected in SBR-DenAna.

  16. Synergism studies with binary mixtures of pyrethroid, carbamate and organophosphate insecticides on Frankliniella occidentalis (Pergande).

    Science.gov (United States)

    Bielza, Pablo; Espinosa, Pedro J; Quinto, Vicente; Abellán, Jaime; Contreras, Josefina

    2007-01-01

    The major mechanism of resistance to most insecticides in Frankliniella occidentalis (Pergande) is metabolic, piperonyl butoxide (PBO) suppressible, mediated by cytochrome-P450 monooxygenases and conferring cross-resistance among insecticide classes. The efficacy of insecticide mixtures of acrinathrin, methiocarb, formetanate and chlorpyrifos was studied by topical exposure in strains of F. occidentalis selected for resistance to each insecticide. The method consisted in combining increasing concentrations of one insecticide with a constant low rate of the second one as synergist. Acrinathrin activity against F. occidentalis was enhanced by carbamate insecticides, methiocarb being a much better synergist than formetanate. Monooxygenase action on the carbamates would prevent degradation of the pyrethroid, hence providing a level of synergism by competitive substrate inhibition. However, the number of insecticides registered for control of F. occidentalis is very limited, and they are needed for antiresistance strategies such as mosaics and rotations. Therefore, a study was made of the synergist effect of other carbamates not used against thrips, such as carbofuran and carbosulfan, against a susceptible strain and a field strain. Neither carbamate showed synergism to acrinathrin in the susceptible strain, but both did in the field strain, carbosulfan being a better synergist than carbofuran. The data obtained indicate that low rates of carbamates could be used as synergists to restore some pyrethroid susceptibility in F. occidentalis. Copyright (c) 2006 Society of Chemical Industry.

  17. Synergism between the effects of dietary cholesterol and coconut oil on plasma, liver and lipoprotein composition of neonatal chick.

    Science.gov (United States)

    Castillo, M; Hortal, J H; Aguilera, J A; Linares, A; García-Peregrín, E

    1998-06-01

    The nature of the synergism between dietary factors and the development of atherosclerosis has not been fully defined. Our studies showed that simultaneous supplementation of 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil) plus 1% cholesterol to the diet produced a sharp increase of plasma cholesterol, indicating a synergic influence of both dietary constituents. This increase was especially patent in the VLDL fraction, modifying the distribution of other lipid components between the core and the surface of these particles. These changes are consistent with the atherogenic function of VLDL and its responsiveness to dietary manipulation.

  18. Inter-domain synergism is required for efficient feeding of cellulose chain into active site of cellobiohydrolase Cel7A

    DEFF Research Database (Denmark)

    Kont, Riin; Kari, Jeppe; Borch, Kim

    2016-01-01

    systems. TrCel7A consists of catalytic domain (CD) and a smaller carbohydrate binding module (CBM) connected through the glycosylated linker peptide. A tunnel shaped active site rests in the CD and contains 10 glucose unit binding sites. The active site of TrCel7A is lined with four Trp residues with two...... to Ala substitution on on-rates was strongly dependent on the presence of the CBM-linker. This compensation between CBM-linker and Trp-38 indicates synergism between CBM-linker and CD in feeding the cellulose chain into the active site. The inter-domain synergism was pre-requisite for the efficient...

  19. Synergic phototoxic effect of visible light or Gallium-Arsenide laser in the presence of different photo-sensitizers on Porphyromonas gingivalis and Fusobacterium nucleatum

    Directory of Open Access Journals (Sweden)

    Habibollah Ghanbari

    2015-01-01

    Conclusion: Within the limitations of this study, the synergic phototoxic effect of visible light in combination with each of the photosensitizers on P. gingivalis and F. nucleatum. However, the synergic phototoxic effect of laser exposure and hydrogen peroxide and curcumin as photosensitizers on F. nucleatum was not shown.

  20. Synergic principles as a base working out of curriculums for professional formation on foreign language in non-linguistic universities

    OpenAIRE

    Anzina T. I.; Rozhina E.Yu.; Selivanova I.V.

    2017-01-01

    the conception of synergic approach presented in the article concerns building curriculums for foreign language. The competency format of the Federal State Educational Standard is a ground for structuring curriculums on the following principles: interdisciplinary, homeostatic, hierarchical, open, complimentary, nonlinear and activity and communication unity. It enables the education system to prepare a perspective specialist for an efficient professional performance.

  1. SUMO-Dependent Synergism Involving Heat Shock Transcription Factors with Functions Linked to Seed Longevity and Desiccation Tolerance

    Directory of Open Access Journals (Sweden)

    Raúl Carranco

    2017-06-01

    Full Text Available A transcriptional synergism between HaHSFA9 (A9 and HaHSFA4a (A4a contributes to determining longevity and desiccation tolerance of sunflower (Helianthus annuus, L. seeds. Potential lysine SUMOylation sites were identified in A9 and A4a and mutated to arginine. We show that A9 is SUMOylated in planta at K38. Although we did not directly detect SUMOylated A4a in planta, we provide indirect evidence from transient expression experiments indicating that A4a is SUMOylated at K172. Different combinations of wild type and SUMOylation site mutants of A9 and A4a were analyzed by transient expression in sunflower embryos and leaves. Although most of the precedents in literature link SUMOylation with repression, the A9 and A4a synergism was fully abolished when the mutant forms for both factors were combined. However, the combination of mutant forms of A9 and A4a did not affect the nuclear retention of A4a by A9; therefore, the analyzed mutations would affect the synergism after the mutual interaction and nuclear co-localization of A9 and A4a. Our results suggest a role for HSF SUMOylation during late, zygotic, embryogenesis. The SUMOylation of A9 (or A4a would allow a crucial, synergic, transcriptional effect that occurs in maturing sunflower seeds.

  2. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    Science.gov (United States)

    Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

    2014-01-01

    Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

  3. Saccharomyces cerevisiae Mixed Culture of Blackberry (Rubus ulmifolius L. Juice: Synergism in the Aroma Compounds Production

    Directory of Open Access Journals (Sweden)

    Pedro Ulises Bautista-Rosales

    2014-01-01

    Full Text Available Blackberry (Rubus sp. juice was fermented using four different strains of Saccharomyces cerevisiae (Vitilevure-CM4457, Enoferm-T306, ICV-K1, and Greroche Rhona-L3574 recognized because of their use in the wine industry. A medium alcoholic graduation spirit (<6GL° with potential to be produced at an industrial scale was obtained. Alcoholic fermentations were performed at 28C°, 200 rpm, and noncontrolled pH. The synergistic effect on the aromatic compounds production during fermentation in mixed culture was compared with those obtained by monoculture and physic mixture of spirits produced in monoculture. The aromatic composition was determined by HS-SPME-GC. The differences in aromatic profile principally rely on the proportions in aromatic compounds and not on the number of those compounds. The multivariance analysis, principal component analysis (PCA, and factorial discriminant analysis (DFA permit to demonstrate the synergism between the strains.

  4. LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.

    Science.gov (United States)

    Zhu, Shizhen; Zhang, Xiaoling; Weichert-Leahey, Nina; Dong, Zhiwei; Zhang, Cheng; Lopez, Gonzalo; Tao, Ting; He, Shuning; Wood, Andrew C; Oldridge, Derek; Ung, Choong Yong; van Ree, Janine H; Khan, Amish; Salazar, Brittany M; Lummertz da Rocha, Edroaldo; Zimmerman, Mark W; Guo, Feng; Cao, Hong; Hou, Xiaonan; Weroha, S John; Perez-Atayde, Antonio R; Neuberg, Donna S; Meves, Alexander; McNiven, Mark A; van Deursen, Jan M; Li, Hu; Maris, John M; Look, A Thomas

    2017-09-11

    A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Synergism of ergonomics, safety, and quality--a behavioral cybernetic analysis.

    Science.gov (United States)

    Smith, T J

    1999-01-01

    This report extends a control systems or cybernetic model of behavior to the behavior of groups of many individuals--organizations and institutions--operating together with technology as complex sociotechnical (ST) systems. The premise is that the level of quality in performance of a complex ST system is predicated upon the degree to which its organizational design incorporates elements of a closed-loop behavioral control system: control goals and objectives, sensory receptors, sensory feedback, learning and memory, effectors, and sensory feedback control. From a control systems perspective, ergonomics is essential to effective organizational self-regulation. If working conditions are poorly designed, work performance and safety and quality outcomes cannot be closely controlled. Conversely, as shown by field evidence, good design promotes synergism between ergonomics, safety, and quality as a closed-loop consequence of effective employee and organizational self-control of system performance, safety, and quality.

  6. Synergic effect of tungstophosphoric acid and sonication for rapid synthesis of crystalline nanocellulose.

    Science.gov (United States)

    Hamid, Sharifah Bee Abd; Zain, Siti Khadijah; Das, Rasel; Centi, Gabriele

    2016-03-15

    The utilization of sonication in combination with tungstophosphoric acid (PWA) catalyst reduces dramatically the time of operations from 30h to 10min by using an optimum sonication power of 225W. The basic cellulosic structure is maintained, allowing preparing high-quality nanocellulose. The size of the nanocellulose obtained was in the range from 15 to 35nm in diameter and several hundred nanometers in length, with a high crystallinity of about 88%. The nanocellulose shows a surface charge of -38.2mV which allows to obtaina stable colloidal suspension. The surface tension of the stable, swollen aqueous nanocellulose was close to that of water. These characteristics, together with the fast procedure allowed from the synergic combination of PWA and sonication, evidence the high potential of the proposed method for the industrial production of nanocellulose having the properties required in many applications. Copyright © 2015. Published by Elsevier Ltd.

  7. Synergism of Lumbricus rubellus and Pseudomonas putida Pf-20 in Inducing Resistance to Cucumber Mosaic Virus

    Directory of Open Access Journals (Sweden)

    WIWIEK SRI WAHYUNI

    2006-09-01

    Full Text Available Both Lumbricus rubellus and Pseudomonas putida decompose soil organic matters. The population of P. putida Pf-20 increased if L. rubellus was introduced to the cucumber growth medium. The process of organic decomposition was much better if the medium was introduced with both L. rubellus and P. putida Pf-20, compared to the medium contained only either one of those organisms. The activity of L. rubellus may serve to provide nutrients for both the cucumber and P. putida. The role of P. putida to reduce disease severity was increased if L. rubellus was introduced to the growth medium. The synergism of these two organisms, reduced either the level of disease severity to CMV-48 and C/N ratio of medium, but increased the content of available phosphor and potassium.

  8. Astaxanthin protecting membrane integrity against photosensitized oxidation through synergism with other carotenoids

    DEFF Research Database (Denmark)

    Du, Hui-Hui; Liang, Ran; Han, Rui-Min

    2015-01-01

    using optical microscopy and digital image heterogeneity analysis. The lowest initial rate of GUV budding after the lag phase was seen for GUVs with astaxanthin as the least reducing carotenoid, while the lowest final level of entropy appeared for those with lycopene or β-carotene as a more reducing...... carotenoid. The combination of astaxanthin and lycopene gave optimal protection against budding with respect to both a longer lag phase and lower final level of entropy by combining good electron acceptance and good electron donation. Quenching of singlet oxygen by carotenoids close to chlorophyll...... a in the membrane interior in parallel with scavenging of superoxide radicals by astaxanthin anchored in the surface may explain the synergism between carotenoids involving both type I and type II photosensitization by chlorophyll a....

  9. Gold(I)-Mediated Thiourea Organocatalyst Activation: A Synergic Effect for Asymmetric Catalysis.

    Science.gov (United States)

    Izaga, Anabel; Herrera, Raquel P; Gimeno, M Concepción

    2017-04-07

    Several group 11 metal complexes with chiral thiourea organocatalysts have been prepared and tested as organocatalysts. The promising results on the influence of metal-assisted thiourea organocatalysts in the asymmetric Friedel-Crafts alkylation of indole with nitrostyrene are described. Better results with the metal complexes have been achieved because of the cooperative effects between the chiral thiourea and the metal. The synergic effect between both species is higher than the effect promoted by each one separately, especially for gold(I). These outcomes are attributed to a pioneering gold(I) activation of the thiourea catalysts, affording a more acidic and rigid catalytic complex than that provided by the thiourea alone. Furthermore, the use of the gold-thiourea organocatalyst allows reducing the catalyst loading to 1-3 mol %. This contribution could become an important starting point for further investigations opening a new line of research overlooked so far in the literature.

  10. Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

    Science.gov (United States)

    Machover, D; Zittoun, J; Broët, P; Metzger, G; Orrico, M; Goldschmidt, E; Schilf, A; Tonetti, C; Tan, Y; Delmas-Marsalet, B; Luccioni, C; Falissard, B; Hoffman, R M

    2001-04-01

    Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

  11. Combined effect of environmental radiation and other agents: Is there a synergism trap?

    International Nuclear Information System (INIS)

    Hornhardt, S.; Jung, T.; Burkart, W.

    2002-01-01

    Most assessments of possible deleterious outcomes from environmental and occupational exposures concentrate on single agents and neglect the potential for combined effects, i.e. synergisms or antagonisms. Biomechanistic considerations based on multistep processes such as carcinogenesis indicate the potential for highly detrimental interactions, if two or more consecutive rate limiting steps are specifically effected by different agents. However, low specificity towards molecular structure or DNA-sequence - and therefore exchangeability - of many genotoxic agents indicate little functional specificity and therefore little vulnerability towards synergism at most occupational and environmental exposure situations. The low potential for significant combined effects for those common low exposure situations where non-genotoxic agents with highly non-linear dose effect relationships and apparent thresholds are involved, is also evident. Nevertheless, a quantitative assessment of the contribution of synergistic interactions to the total detriment from natural and man-made toxicants based on experimental data is far away. The existing database on combined effects is rudimentary, mainly descriptive and rarely covers exposure ranges large enough to make direct inferences to present day low dose exposure situations. In view of the multitude of possible interactions between the large number of potentially harmful agents in the human environment, descriptive approaches will have to be supplemented by the use of mechanistic models for critical health endpoints such as cancer. Finally an important question considering the shape of dose effect relationships for ionizing radiation arises from the unresolved question whether real or apparent thresholds may be used for any genotoxic agent separately or only one time for an exposed genome. (author)

  12. Phene synergism between root hair length and basal root growth angle for phosphorus acquisition.

    Science.gov (United States)

    Miguel, Magalhaes Amade; Postma, Johannes Auke; Lynch, Jonathan Paul

    2015-04-01

    Shallow basal root growth angle (BRGA) increases phosphorus acquisition efficiency by enhancing topsoil foraging because in most soils, phosphorus is concentrated in the topsoil. Root hair length and density (RHL/D) increase phosphorus acquisition by expanding the soil volume subject to phosphorus depletion through diffusion. We hypothesized that shallow BRGA and large RHL/D are synergetic for phosphorus acquisition, meaning that their combined effect is greater than the sum of their individual effects. To evaluate this hypothesis, phosphorus acquisition in the field in Mozambique was compared among recombinant inbred lines of common bean (Phaseolus vulgaris) having four distinct root phenotypes: long root hairs and shallow basal roots, long root hairs and deep basal roots, short root hairs and shallow basal roots, and short root hairs and deep basal roots. The results revealed substantial synergism between BRGA and RHL/D. Compared with short-haired, deep-rooted phenotypes, long root hairs increased shoot biomass under phosphorus stress by 89%, while shallow roots increased shoot biomass by 58%. Genotypes with both long root hairs and shallow roots had 298% greater biomass accumulation than short-haired, deep-rooted phenotypes. Therefore, the utility of shallow basal roots and long root hairs for phosphorus acquisition in combination is twice as large as their additive effects. We conclude that the anatomical phene of long, dense root hairs and the architectural phene of shallower basal root growth are synergetic for phosphorus acquisition. Phene synergism may be common in plant biology and can have substantial importance for plant fitness, as shown here. © 2015 American Society of Plant Biologists. All Rights Reserved.

  13. Spinosad resistance, esterase isoenzymes and temporal synergism in Frankliniella occidentalis (Pergande) in Australia.

    Science.gov (United States)

    Herron, Grant A; Gunning, Robin V; Cottage, Emma L A; Borzatta, Valerio; Gobbi, Carlotta

    2014-09-01

    Spinosad has been widely used in Australia to control western flower thrips Frankliniella occidentalis (Pergande) but spinosad usefulness is now compromised by resistance. Here we studied a highly spinosad resistant strain of F. occidentalis to explore if esterases had a role in spinosad resistance. Enhanced esterase activity in pressured spinosad-resistant F. occidentalis was confirmed via PAGE electrophoresis and estimated to be approximately three times higher than that in a susceptible strain. Spinosad-esterase inhibition data in the resistant strain, showed a concentration effect with significant esterase-spinosad binding occurring at spinosad concentrations from 6.2× 10(-7) to 1.5× 10(-5) M. Similarly, a spinosad-piperonyl butoxide (PBO) inhibition curve showed a concentration effect, with significant esterase-PBO binding occurring in the resistant strain at PBO concentrations between 3.3× 10(-5) M and 8.4× 10(-4) M. No binding of esterase to spinosad or PBO occurred in the susceptible strain. Results of bioassays in which spinosad resistant F. occidentalis were sprayed with a 4h delayed release formulation of cyclodextrin-complexed spinosad with immediately available PBO demonstrated that spinosad resistance was significantly reduced from 577 to 72-fold. With further development the PBO synergism of spinosad using a delayed release formulation, similar to that used here, may provide effective control for spinosad resistant F. occidentalis. Temporal synergism of spinosad may prove to be effective tactic for the control of spinosad resistant F. occidentalis where the main resistance mechanism involved has been confirmed to be esterase based. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    Directory of Open Access Journals (Sweden)

    Goard Carolyn A

    2010-03-01

    Full Text Available Abstract Background Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. Methods The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. Results We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. Conclusions The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a

  15. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

  16. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Dragana D Bozic

    2014-01-01

    Interpretation & conclusions: o0 ur study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents.

  17. Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

    Directory of Open Access Journals (Sweden)

    Norma Carrillo-Munguía

    2015-01-01

    Full Text Available Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception.

  18. A toxin-binding alkaline phosphatase fragment synergizes Bt toxin Cry1Ac against susceptible and resistant Helicoverpa armigera.

    Directory of Open Access Journals (Sweden)

    Wenbo Chen

    Full Text Available Evolution of resistance by insects threatens the continued success of pest control using insecticidal crystal (Cry proteins from the bacterium Bacillus thuringiensis (Bt in sprays and transgenic plants. In this study, laboratory selection with Cry1Ac yielded five strains of cotton bollworm, Helicoverpa armigera, with resistance ratios at the median lethal concentration (LC50 of activated Cry1Ac ranging from 22 to 1700. Reduced activity and reduced transcription of an alkaline phosphatase protein that binds Cry1Ac was associated with resistance to Cry1Ac in the four most resistant strains. A Cry1Ac-binding fragment of alkaline phosphatase from H. armigera (HaALP1f was not toxic by itself, but it increased mortality caused by Cry1Ac in a susceptible strain and in all five resistant strains. Although synergism of Bt toxins against susceptible insects by toxin-binding fragments of cadherin and aminopeptidase N has been reported previously, the results here provide the first evidence of synergism of a Bt toxin by a toxin-binding fragment of alkaline phosphatase. The results here also provide the first evidence of synergism of a Bt toxin by any toxin-binding peptide against resistant insects.

  19. Microfluidic liquid-air dual-gradient chip for synergic effect bio-evaluation of air pollutant.

    Science.gov (United States)

    Liu, Xian-Jun; Hu, Shan-Wen; Xu, Bi-Yi; Zhao, Ge; Li, Xiang; Xie, Fu-Wei; Xu, Jing-Juan; Chen, Hong-Yuan

    2018-05-15

    In this paper, a novel prototype liquid-air dual gradient chip is introduced, which has paved the way for effective synergic effect bio-evaluation of air pollutant. The chip is composed of an array of the agarose liquid-air interfaces, top air gradient layer and bottom liquid gradient layer. The novel agarose liquid-air interface allows for non-biased exposure of cells to all the substances in the air and diffusive interactions with the liquid phase; while the dual liquid-air gradient provides powerful screening abilities, which well reduced errors, saved time and cost from repeated experiment. Coupling the two functions, the chip subsequently facilitates synergic effect evaluation of both liquid and air factors on cells. Here cigarette smoke was taken as the model air pollutant, and its strong synergic effects with inflammatory level of A549 lung cancer cells on their fate were successfully quantified for the first time. These results well testified that the proposed dual-gradient chip is powerful and indispensable for bio-evaluation of air pollutant. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Alkaline pretreatment and the synergic effect of water and tetralin enhances the liquefaction efficiency of bagasse.

    Science.gov (United States)

    Li, Zhixia; Cao, Jiangfei; Huang, Kai; Hong, Yaming; Li, Cunlong; Zhou, Xinxin; Xie, Ning; Lai, Fang; Shen, Fang; Chen, Congjin

    2015-02-01

    Bagasse liquefaction (BL) in water, tetralin, and water/tetralin mixed solvents (WTMS) was investigated, and effects of tetralin content in WTMS, temperature, and alkaline pretreatment of bagasse on liquefaction efficiency were studied. At 300°C, bagasse conversion in WTMS with tetralin content higher than 50 wt% was 86-87 wt%, whereas bagasse conversion in water or tetralin was 67 wt% or 84 wt%, respectively. Because the solid conversion from liquefaction in WTMS with tetralin content higher than 50 wt% was always higher than that in water or tetralin at temperatures between 250 and 300°C, a synergic effect between water and tetralin is suggested. Alkaline pretreatment of bagasse resulted in significantly higher conversion and heavy oil yield from BL in water or WTMS. The effect of deoxygenation by the present liquefaction method is demonstrated by lower oxygen contents (16.01-19.59 wt%) and higher heating values (31.9-34.8 MJ/kg) in the produced oils. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus.

    Science.gov (United States)

    Wei, C-F; Chang, S-K; Shien, J-H; Kuo, H-C; Chen, W-Y; Chou, C-C

    2016-03-26

    Synergistic effects between the same class of antibiotics are rarely reported. In the current study, two amphenicols, namely florfenicol and thiamphenicol, exhibited both in vitro and in vivo synergism against clinical isolates ofStaphylococcus aureusfrom chickens, cattle and pigs. Checkerboard assays on 21S. aureusisolates showed that in 80 per cent of methicillin-susceptibleS. aureus(MSSA) and 82 per cent of methicillin-resistantS. aureus(MRSA) isolates tested, the minimal inhibitory concentration (MIC) of florfenicol could be reduced by 75 per cent (1/4 MIC) or more (up to 1/16 MIC) when combined with 1/2 MIC of thiamphenicol to exhibit antimicrobial activity comparable to the respective drugs at original strength (1×MIC). A synergistic effect (fractional inhibitory concentration index ≤0.5 or ≥2-log10decrease in colony-forming unit/ml in time-kill study) was evident against 30 per cent of MSSA and 45 per cent of MRSA strains tested. A study in mice revealed that the florfenicol/thiamphenicol combination at reduced dosages provided sufficient protection againstS. aureuschallenge. The possible mechanism warrants further study but likely includes the facilitated uptake of thiamphenicol via florfenicol action, and this facilitation was not limited to amphenicol class. The present study may offer new strategy for combination therapy and provide potential alternatives for effective treatment againstS. aureusinfections. British Veterinary Association.

  2. In vitro synergism of combinations of colistin with selected antibiotics against colistin-resistant Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Percin, Duygu

    2014-08-01

    Full Text Available [english] Aim: The in vitro activity of colistin in combination with sulbactam, netilmicin, and vancomycin against colistin-resistant strains was investigated. Furthermore, the clonal relationship of the strains was analyzed. Methods: Clonal relationship was investigated using rep-PCR. To screen for synergysm, the fractional inhibitory concentration index (FICI was calculated using checkerboard assay. The killing kinetics of the combination of colistin with vancomycin was assessed using time-kill assay. Results: Three different clones were found among 10 clinical isolates of colistin-resistant strains. Thereof, 8 strains were susceptible to netilmicin. Synergistic interaction was detected in 1 strain with the combination of colistin-netilmicin, in 5 strains with colistin-sulbactam, and in 9 strains with colistin-vancomycin. None of combinations had antagonistic activity. Colistin-vancomycin combination resulted in rapid bactericidal activity. Conclusion: These results show a distinct in vitro synergism between colistin and vancomycin, which might be useful to treat infection with multiple-resistant strains, prevent emergence of resistant strains, and to lower doses for both antibiotics to be used.

  3. Synergic effect of gamma radiation with thermal treatment for conserving natural apple juice from Gala variety

    International Nuclear Information System (INIS)

    Blumer, L.; Domarco, R.E.; Spoto, M.H.F.; Walder, J.M.M.; Matraia, C.

    1995-01-01

    This paper aims at the feasibility of a new method for conserving natural apple juice using no chemicals. The apple juice was extract from Gala apple variety and was bottled in sterile 100 ml amber vials. The samples were treated by: heat at 60 0 C for 20 minutes; heat at 80 0 C for 20 minutes; radiation; radiation plus heat (60 0 ); radiation plus heat 80 0 C. The radiation doses were 0,2,4 and 6 kGy at the dose rate of 1.6 kGy/h. The juice quality control was carried out by chemical analysis (total soluble solids, pH, acidity, ascorbic acid) following the AOAC methodology. The samples were stored under refrigeration conditions 5±3 0 C) up to 180 days. It was observed an alteration of the total soluble solids and the pH during the storage period for all treatments. The pH was also affected by the combined treatments (radiation plus heat). The acidity was affected by the interaction of storage period and heat temperature. The ascorbic acid was affected by the synergic effect of heat and radiation and by the interaction radiation and storage period. (author). 8 refs, 6 figs

  4. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

    Directory of Open Access Journals (Sweden)

    Ronald P. Haff

    2013-01-01

    Full Text Available Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA, a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2, tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

  5. DAMPs Synergize with Cytokines or Fibronectin Fragment on Inducing Chondrolysis but Lose Effect When Acting Alone

    Directory of Open Access Journals (Sweden)

    Lei Ding

    2017-01-01

    Full Text Available Objective and Design. To investigate whether endogenous damage-associated molecular patterns (DAMPs or alarmins originated from mitochondria or nucleus stimulates inflammatory response in articular chondrocytes to cause chondrolysis which leads to cartilage degradation featured in posttraumatic osteoarthritis (PTOA. Materials. Primary cultures of bovine or human chondrocytes isolated from cartilage of weight-bearing joints. Treatment. Chondrocytes were subjected to mitochondrial DAMPs (MTDs or HMGB1, a nuclear DAMP (NuD, with or without the presence of an N-terminal 29 kDa fibronectin fragment (Fn-f or proinflammatory cytokines (IL-1β and TNF-α. Injured cartilage-conditioned culturing medium containing a mixture of DAMPs was employed as a control. After 24 hrs, the protein expression of cartilage degrading metalloproteinases and iNOS in culture medium or cell lysates was examined with Western blotting, respectively. Results. HMGB1 was synergized with IL-1β in upregulating expression of MMP-3, MMP-13, ADAMTS-5, ADAM-8, and iNOS. Moreover, a moderate synergistic effect was detected between HMGB1 and Fn-f or between MTDs and TNF-α on MMP-3 expression. However, when acting alone, MTDs or HMGB1 did not upregulate cartilage degrading enzymes or iNOS. Conclusion. MTDs or HMGB1 could only stimulate inflammatory response in chondrocytes with the presence of cytokines or Fn-f.

  6. Radiation-thermal degradation of PE and PVC: Mechanism of synergism and dose rate effects

    Science.gov (United States)

    Clough, Roger L.; Gillen, Kenneth T.

    Polyethylene insulation and polyvinyl chloride jacketing materials that had been in use in a nuclear application were recently found to be substantially deteriorated. The damage had occurred under conditions where both the total estimated dose (about 2.5 Mrad) and the operating temperatures (about 43°C average) seemed relatively moderate. These results prompted us to initiate a program to study polyvinyl chloride and polyethylene degradation under conditions of combined γ-radiation and elevated temperature environments. A number of interesting aging effects were observed, including 1) a striking synergism between radiation and temperature and 2) strong dose-rate dependent effects which occur over a wide range of dose rates. The aging effects are explained in terms of a chain branching degradation mechanism involving thermally induced breakdown of peroxides which are formed in reactions initiated by the radiation. Evidence for this mechanism is derived from infrared spectra, from sequential radiation-elevated temperature experiments including experiments under inert atmosphere, from activation energy estimates and from a new technique involving treatment of intact samples with PH 3 for chemical reduction of peroxides. The results of our studies raise significant doubts about the utility of earlier compilations which purportedly serve as radiation life expectancy guides by indicating "tolerable radiation doses" for a variety of polymers.

  7. Chaperone-Targeting Cytotoxin and Endoplasmic Reticulum Stress-Inducing Drug Synergize to Kill Cancer Cells

    Directory of Open Access Journals (Sweden)

    Joseph M. Backer

    2009-11-01

    Full Text Available Diverse physiological and therapeutic insults that increase the amount of unfolded or misfolded proteins in the endoplasmic reticulum (ER induce the unfolded protein response, an evolutionarily conserved protective mechanism that manages ER stress. Glucose-regulated protein 78/immunoglobulin heavy-chain binding protein (GRP78/BiP is an ER-resident protein that plays a central role in the ER stress response and is the only known substrate of the proteolytic A subunit (SubA of a novel bacterial AB5 toxin. Here, we report that an engineered fusion protein, epidermal growth factor (EGF-SubA, combining EGF and SubA, is highly toxic to growing and confluent epidermal growth factor receptor-expressing cancer cells, and its cytotoxicity is mediated by a remarkably rapid cleavage of GRP78/BiP. Systemic delivery of EGF-SubA results in a significant inhibition of human breast and prostate tumor xenografts in mouse models. Furthermore, EGF-SubA dramatically increases the sensitivity of cancer cells to the ER stress-inducing drug thapsigargin, and vice versa, demonstrating the first example of mechanism-based synergism in the action of a cytotoxin and an ER-targeting drug.

  8. Synergic development of pharmacokinetics and bioanalytical methods as support of pharmaceutical research.

    Science.gov (United States)

    Marzo, M; Ciccarelli, R; Di Iorio, P; Giuliani, P; Caciagli, F; Marzo, A

    2016-06-01

    The development of pharmacokinetics led this science to achieve a relevant role in the investigation of new chemical entities for therapeutic application, and has allowed a series of new useful realizations of out of patent drugs like prolonged release and delayed release formulations, therapeutic delivery system (TDS) for drugs to be active in systemic circulation avoiding the first pass effect, orodispersible and effervescent formulations, intramuscular and subcutaneous depot formulations acting over a long period, oral inhalatory systems, and drug association at fixed dose. The above applications had pharmacokinetics as protagonist and have required the support from bioanalytical methods to assay drug concentrations, even in pg·mL(-1) of plasma, that really have paralleled the synergic development of pharmacokinetics.The complexity of the above realizations required specific guidelines from the regulatory authorities, mainly the US FDA and EU EMA, which have normalized and, in most cases, simplified the above applications admitting some waivers of in vivo bioequivalence.However, this review highlights some critical points, not yet focused on by operating guidelines, which need to be clarified by regulatory authorities. One of the most relevant issues is about the planning and conducting bioavailability and bioequivalence trials with endogenous substances, that possess own homeostatic equilibria with fluctuations, in some cases with specific rhythms, like melatonin and female sex hormones. The baseline subtraction required by guidelines to define the net contribute to the exogenous absorbed drug in most cases is a non-solvable problem. © The Author(s) 2015.

  9. Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation.

    Science.gov (United States)

    Reick, Christiane; Ellrichmann, Gisa; Thöne, Jan; Scannevin, Robert H; Saft, Carsten; Linker, Ralf A; Gold, Ralf

    2014-07-01

    Despite recent advances in development of treatments for multiple sclerosis, there is still an unmet need for more effective and also safe therapies. Based on the modes of action of interferon-beta (IFN-β) and dimethyl fumarate (DMF), we hypothesized that anti-inflammatory and neuroprotective effects may synergize in experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice by immunization with MOG35-55-peptide. Murine IFN-β was injected s.c. every other day at 10.000IU, and DMF was provided at 15mg/kg by oral gavage twice daily. Control mice received PBS injections and were treated by oral gavage with the vehicle methylcellulose. Mice were scored daily by blinded observers and histological, FACS and cytokine studies were performed to further elucidate the underlying mechanism of action. Combination therapy significantly ameliorated EAE disease course in comparison to controls and monotherapy with IFN-β. Histological analyses showed a significant effect on axon preservation with almost twice as much axons present in inflamed lesions as compared to control. Remarkably, the effect on axonal preservation was more pronounced under combination therapy than with both monotherapies. Neither monotherapy nor combination therapy demonstrated modulation of cytokines and frequency of antigen presenting cells. Combination of IFN-β and DMF resulted in greater beneficial effects with improved tissue protection as compared to the respective monotherapies. Further combination studies of these safe therapies in human disease are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Anti-mycobacterial activities of synthetic cationic α-helical peptides and their synergism with rifampicin.

    Science.gov (United States)

    Khara, Jasmeet S; Wang, Ying; Ke, Xi-Yu; Liu, Shaoqiong; Newton, Sandra M; Langford, Paul R; Yang, Yi Yan; Ee, Pui Lai Rachel

    2014-02-01

    The rapid emergence of multi-drug resistant tuberculosis (TB) and the lack of effective therapies have prompted the development of compounds with novel mechanisms of action to tackle this growing public health concern. In this study, a series of synthetic cationic α-helical antimicrobial peptides (AMPs) modified with different hydrophobic amino acids was investigated for their anti-mycobacterial activity, both alone and in synergistic combinations with the frontline anti-tuberculosis drug rifampicin. The addition of thiol groups by incorporating cysteine residues in the AMPs did not improve anti-mycobacterial activity against drug-susceptible and drug-resistant Mycobacterium tuberculosis, while the enhancement of peptide hydrophobicity by adding methionine residues increased the efficacy of the primary peptide against all strains tested, including clinically isolated multidrug-resistant mycobacteria. The peptide with the optimal composition M(LLKK)2M was bactericidal, and eradicated mycobacteria via a membrane-lytic mechanism as demonstrated by confocal microscopic studies. Mycobacteria did not develop resistance after multiple exposures to sub-lethal doses of the peptide. In addition, the peptide displayed synergism with rifampicin against both Mycobacterium smegmatis and Mycobacterium bovis BCG and additivity against M. tuberculosis. Moreover, such combination therapy is effective in delaying the emergence of rifampicin resistance. The ability to potentiate anti-TB drug activity, kill drug-resistant bacteria and prevent drug resistance highlights the potential utility of the peptide in combating multidrug-resistant TB. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Synergic lung changes in rats receiving combined exposure to paraquat and ionizing radiation

    International Nuclear Information System (INIS)

    Salovsky, P.; Shopova, V.

    1993-01-01

    Experiment was carried out on a total of 160 male Wistar rats. Paraquat was instilled per os intragastrically by a metal probe, in aqueous solution, at a daily dose of 0.46 mg/kg body wt given five times a week for 4 months. Directly upon termination of paraquat intake the animals received a single external whole-body exposure to 4 Gy of ionizing radiation. Changes in the parameters studied were recorded on Post-treatment Days 1, 5, 10, and 30. In bronchoalveolar lavage fluid (BALF), paraquat treatment alone was found to elevate lactate dehydrogenase (LDH) activity and content of thiobarbituric acid (TBA) reactants; lung homogenate from this treatment group showed diminution in superoxide dismutase (SOD) and catalase (CAT) activities and in content of nonprotein sulfhydryl groups (NPSH) on Days 1 and 5. Irradiation alone produced less substantial changes. With combined exposure to paraquat and radiation, there was more marked and more prolonged depression of the three parameters (SOD, CAT, and NPSH) of lung antioxidant defense and synergic increase in BALF content of TBA reactants and LDH activity. 29 refs., 5 figs., 2 tabs

  12. Deferoxamine synergizes with transforming growth factor-β signaling in chondrogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Huang

    2017-08-01

    Full Text Available Abstract Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, is an epidemic disease that affects millions of people worldwide. Despite extensive recent work on the cellular biology of osteoarthritis, the precise mechanisms involved are still poorly understood and there is no effective treatment for this disease. The role of transforming growth factor-beta (TGF-β in promoting chondrogenesis and inducing the expression of cartilage-specific extracellular matrix molecules to form cartilage is well-established. Historically, TGF-β has been considered to prevent osteoarthritis, but recent work suggests that TGF-β overexpression accelerates the progression of osteoarthritis in vivo. Clinically, it is therefore important to limit TGF-β expression while still providing effective treatment of osteoarthritis. One possible approach to achieve this effect would be to use a combination of TGF-β with other small molecular chemical compounds. Hypoxia promotes chondrogenesis and the usefulness of deferoxamine, a chelating agent that mimics hypoxia, in stimulating chondrogenesis has been investigated in clinical trials. In this study, we investigated the role of deferoxamine in TGF-β-induced chondrogenesis in pre-chondrogenic cells and examined whether deferoxamine synergizes with the TGF-β signaling pathway to promote chondrocyte differentiation.

  13. Synergism between dexketoprofen and meloxicam in an orofacial formalin test was not modified by opioid antagonists.

    Science.gov (United States)

    Gonzalez, Claudia; Zegpi, Carlos; Noriega, Viviana; Prieto, Juan C; Miranda, Hugo F

    2011-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the management of acute and chronic pain. The role of the opioid system in the synergism between NSAIDs is not well characterized. Mice were injected with a 5% formalin solution (20 μl) into the upper right lip to perform an orofacial formalin test. The isobolographic method was used to determine the interaction between dexketoprofen, which is the (S)-(+) enantiomer of ketoprofen, and meloxicam co-administration. Additionally, the non-selective, opioid antagonist naltrexone, the selective δ opioid receptor (DOP) antagonist naltrindole and the selective κ opioid receptor (KOP) antagonist norbinaltorphimine were used to assess the opioid effects on this interaction. Intraperitoneal administration of dexketoprofen or meloxicam induced dose-dependent antinociception with different phase I and phase II potencies in the orofacial formalin test. Meloxicam displayed similar potencies (ED(50)) in phase I (7.20 mg/kg) and phase II (8.60 mg/kg). Dexketoprofen was more potent in phase I (19.96 mg/kg) than in phase II (50.90 mg/kg). The interactions between dexketoprofen and meloxicam were synergistic in both phases. This was determined based on the fixed ratios (1:1) of their ED(50) values, which were determined by isobolographic analysis. Furthermore, this antinociceptive activity does not seem to be modulated by opioid receptor blockers because they did not induce changes in the nature of this interaction. This finding may be relevant with regards to NSAID multi-modal analgesia where an opioid antagonist must be used.

  14. Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Llop, Sabrina, E-mail: llop_sab@gva.es [FISABIO–Universitat de València–Universitat Jaume I Joint Research Unit of Epidemiology and Environmental Health, Av. Catalunya 21, 46020 Valencia (Spain); Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid (Spain); Lopez-Espinosa, Maria-Jose; Murcia, Mario [FISABIO–Universitat de València–Universitat Jaume I Joint Research Unit of Epidemiology and Environmental Health, Av. Catalunya 21, 46020 Valencia (Spain); Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid (Spain); Alvarez-Pedrerol, Mar [Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid (Spain); Centre for Research in Environmental Epidemiology (CREAL), Doctor Aiguader 88, 08003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 08003 Barcelona (Spain); Vioque, Jesús [Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid (Spain); Universidad Miguel Hernandez, Avenida de Alicante KM 87, 03550 Sant Joan d´Alacant (Spain); Aguinagalde, Xabier [Laboratorio de Salud Pública de Alava, Santiago 11, 01002 Vitoria Gasteiz (Spain); Julvez, Jordi [Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid (Spain); Centre for Research in Environmental Epidemiology (CREAL), Doctor Aiguader 88, 08003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 08003 Barcelona (Spain); and others

    2015-04-15

    Objective: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. Methods: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. Results: The geometric means of TSH, TT3, FT4 and mercury were 1.1 μU/L, 2.4 nmol/L, 10.5 pmol/L and 7.7 μg/L, respectively. Mercury levels were marginally significantly associated with TT3 (β: −0.05; 95%CI: −0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (−0.08; 95%CI: −0.15, −0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. Conclusion: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed. - Highlights: • We studied the relationship between mercury and thyroid hormones among pregnant. • Mercury was marginally significantly associated with TT3, but not with TSH or FT4. • This association was stronger among the iodine supplement. • These results could be of public health concern, but further research is needed.

  15. Cyclic AMP synergizes with butyrate in promoting β-defensin 9 expression in chickens.

    Science.gov (United States)

    Sunkara, Lakshmi T; Zeng, Xiangfang; Curtis, Amanda R; Zhang, Guolong

    2014-02-01

    Host defense peptides (HDP) have both microbicidal and immunomodulatory properties. Specific induction of endogenous HDP synthesis has emerged as a novel approach to antimicrobial therapy. Cyclic adenosine monophosphate (cAMP) and butyrate have been implicated in HDP induction in humans. However, the role of cAMP signaling and the possible interactions between cAMP and butyrate in regulating HDP expression in other species remain unknown. Here we report that activation of cAMP signaling induces HDP gene expression in chickens as exemplified by β-defensin 9 (AvBD9). We further showed that, albeit being weak inducers, cAMP agonists synergize strongly with butyrate or butyrate analogs in AvBD9 induction in macrophages and primary jejunal explants. Additionally, oral supplementation of forskolin, an adenylyl cyclase agonist in the form of a Coleus forskohlii extract, was found to induce AvBD9 expression in the crop of chickens. Furthermore, feeding with both forskolin and butyrate showed an obvious synergy in triggering AvBD9 expression in the crop and jejunum of chickens. Surprisingly, inhibition of the MEK-ERK mitogen-activated protein kinase (MAPK) pathway augmented the butyrate-FSK synergy, whereas blocking JNK or p38 MAPK pathway significantly diminished AvBD9 induction in chicken macrophages and jejunal explants in response to butyrate and FSK individually or in combination. Collectively, these results suggest the potential for concomitant use of butyrate and cAMP signaling activators in enhancing HDP expression, innate immunity, and disease resistance in both animals and humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Toxoplasmosis Complications and Novel Therapeutic Synergism Combination of Diclazuril plus Atovaquone

    Directory of Open Access Journals (Sweden)

    Helieh S Oz

    2014-09-01

    synergism

  17. Changes of the Microbial Community in Corn Soil Due to the Synergism Zeolite-Mineral Fertilizers

    Directory of Open Access Journals (Sweden)

    Roxana Vidican

    2016-11-01

    Full Text Available Microbial communities in agricultural ecosystems are characterized by a strong dynamic and radical change due to technological inputs applied. Corn is cultivated on large areas with high requirements for nutrients and an increased potential for activation of specific microbial groups. The aim of this study was to assess the unilateral and synergic effect of zeolite and mineral fertilizers on the development and transformation of microbial functional groups in the rhizosphere of corn. Physiological profile assessment of microbial communities has been carried out on the basis of substrate induced respiration, monitored over a period of 6 hours of incubation. The amount of CO2 registered in Microresp plates represents the activity of functional groups in decomposition of each type of substrate applied. Characteristic groups of microorganisms in maize rhizosphere are capable of decomposing acids: citric, L-malic, oxalic and α-Ketoglutaric. These substrates indicate the presence of high concentrations of organic matter in soil and the existence of a biological crust on the surface (citric acid, respectively the existence of powerful processes for the decomposition of organic material by actinomycetes (α-Ketoglutaric acid. The highest microbial activities were observed in groups of bacteria involved in processes of plant growth promotion and microbial groups with an important role in the processes of denitrification (oxalic acid. For the application of urea a triple value of activity of this type of microflora is observed. Functional groups codominant in soils cultivated with corn are specialized in efficient degradation of organic matter and biological crust, zeolite providing the complex substrate necessary for the development of these microorganisms.

  18. Analysis of Balance Scorecards Model Performance and Perspective Strategy Synergized by SEM

    Directory of Open Access Journals (Sweden)

    Waluyo Minto

    2016-01-01

    Full Text Available The performance assessment analysis after the economic crisis by using Balanced Scorecard (BSC method becomes a powerful and effective tool and can provide an integrated view of the performance of an organization. This strategy led to the Indonesian economy being stretched positively after the economic crisis. Taking effective decisions is not spared from combining four BSC perspectives and strategies that focus on a system with different behavior or steps. This paper combines two methods of BSC with structural equation modeling (SEM because they have the same concept, which is a causal relationship, where the research model concept SEM variables use BSC variable. The purpose of this paper is to investigate the influence of variables that synergized between balanced scorecard with SEM as a means of strategic planning in the future. This study used primary data with a large enough sample to meet the maximum likelihood estimation by assessment scale of seven semantic points. This research model is a combination of one and two step models. The next step is to test the measurement model, structural equation modeling, and modification models. The test results indicated that the model has multi colinearities. Therefore, the model is converted into one step model. The test results after being modified into a model of the goodness of fit indices showed a good score. All BSC variables have direct significant influence, including the perspective of strategic goals and sustainable competitive advantage. The implication of the simulation model of goodness of fit-modification results are DF = 227, Chi-square =276.550, P =0.058, CMIN/DF = 1.150, GFI = 0.831, AGFI = 0.791, CFI = 0.972, TLI = 0.965 and RMSEA = 0.039.

  19. 21st Century Extravehicular Activities: Synergizing Past and Present Training Methods for Future Spacewalking Success

    Science.gov (United States)

    Moore, Sandra K.; Gast, Matthew A.

    2009-01-01

    Neil Armstrong's understated words, "That's one small step for man, one giant leap for mankind." were spoken from Tranquility Base forty years ago. Even today, those words resonate in the ears of millions, including many who had yet to be born when man first landed on the surface of the moon. By their very nature, and in the the spirit of exploration, extravehicular activities (EVAs) have generated much excitement throughout the history of manned spaceflight. From Ed White's first space walk in June of 1965, to the first steps on the moon in 1969, to the expected completion of the International Space Station (ISS), the ability to exist, live and work in the vacuum of space has stood as a beacon of what is possible. It was NASA's first spacewalk that taught engineers on the ground the valuable lesson that successful spacewalking requires a unique set of learned skills. That lesson sparked extensive efforts to develop and define the training requirements necessary to ensure success. As focus shifted from orbital activities to lunar surface activities, the required skill-set and subsequently the training methods, changed. The requirements duly changed again when NASA left the moon for the last time in 1972 and have continued to evolve through the Skylab, Space Shuttle; and ISS eras. Yet because the visits to the moon were so long ago, NASA's expertise in the realm of extra-terrestrial EVAs has diminished. As manned spaceflight again shifts its focus beyond low earth orbit, EVA success will depend on the ability to synergize the knowledge gained over 40+ years of spacewalking to create a training method that allows a single crewmember to perform equally well, whether performing an EVA on the surface of the Moon, while in the vacuum of space, or heading for a rendezvous with Mars. This paper reviews NASA's past and present EVA training methods and extrapolates techniques from both to construct the basis for future EVA astronaut training.

  20. Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol

    Directory of Open Access Journals (Sweden)

    Mishra Paras K

    2010-09-01

    Full Text Available Abstract Background Hyperhomocysteinemia (HHcy and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR gamma. However, their synergistic contribution is not clear. Methods Diabetic Akita (Ins2+/- and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/- were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/- of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator. High performance liquid chromatography (HPLC was performed for determining plasma homocysteine (Hcy level in the above groups. Akita was treated with ciglitazone (CZ - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed. Results At twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD. In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4 and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP-9, TIMP-3 and NADPH oxidase 4 (NOX4 were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9. Conclusions Endogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.

  1. 21st Century extravehicular activities: Synergizing past and present training methods for future spacewalking success

    Science.gov (United States)

    Moore, Sandra K.; Gast, Matthew A.

    2010-10-01

    Neil Armstrong's understated words, "That's one small step for man, one giant leap for mankind" were spoken from Tranquility Base forty years ago. Even today, those words resonate in the ears of millions, including many who had yet to be born when man first landed on the surface of the moon. By their very nature, and in the true spirit of exploration, extravehicular activities (EVAs) have generated much excitement throughout the history of manned spaceflight. From Ed White's first spacewalk in the June of 1965, to the first steps on the moon in 1969, to the expected completion of the International Space Station (ISS), the ability to exist, live and work in the vacuum of space has stood as a beacon of what is possible. It was NASA's first spacewalk that taught engineers on the ground the valuable lesson that successful spacewalking requires a unique set of learned skills. That lesson sparked extensive efforts to develop and define the training requirements necessary to ensure success. As focus shifted from orbital activities to lunar surface activities, the required skill set and subsequently the training methods changed. The requirements duly changed again when NASA left the moon for the last time in 1972 and have continued to evolve through the SkyLab, Space Shuttle, and ISS eras. Yet because the visits to the moon were so long ago, NASA's expertise in the realm of extra-terrestrial EVAs has diminished. As manned spaceflight again shifts its focus beyond low earth orbit, EVA's success will depend on the ability to synergize the knowledge gained over 40+ years of spacewalking to create a training method that allows a single crewmember to perform equally well, whether performing an EVA on the surface of the Moon, while in the vacuum of space, or heading for a rendezvous with Mars. This paper reviews NASA's past and present EVA training methods and extrapolates techniques from both to construct the basis for future EVA astronaut training.

  2. Comparative toxicities and synergism of apple orchard pesticides to Apis mellifera (L. and Osmia cornifrons (Radoszkowski.

    Directory of Open Access Journals (Sweden)

    David J Biddinger

    Full Text Available The topical toxicities of five commercial grade pesticides commonly sprayed in apple orchards were estimated on adult worker honey bees, Apis mellifera (L. (Hymenoptera: Apidae and Japanese orchard bees, Osmia cornifrons (Radoszkowski (Hymenoptera: Megachilidae. The pesticides were acetamiprid (Assail 30SG, λ-cyhalothrin (Warrior II, dimethoate (Dimethoate 4EC, phosmet (Imidan 70W, and imidacloprid (Provado 1.6F. At least 5 doses of each chemical, diluted in distilled water, were applied to freshly-eclosed adult bees. Mortality was assessed after 48 hr. Dose-mortality regressions were analyzed by probit analysis to test the hypotheses of parallelism and equality by likelihood ratio tests. For A. mellifera, the decreasing order of toxicity at LD₅₀ was imidacloprid, λ-cyhalothrin, dimethoate, phosmet, and acetamiprid. For O. cornifrons, the decreasing order of toxicity at LD₅₀ was dimethoate, λ-cyhalothrin, imidacloprid, acetamiprid, and phosmet. Interaction of imidacloprid or acetamiprid with the fungicide fenbuconazole (Indar 2F was also tested in a 1∶1 proportion for each species. Estimates of response parameters for each mixture component applied to each species were compared with dose-response data for each mixture in statistical tests of the hypothesis of independent joint action. For each mixture, the interaction of fenbuconazole (a material non-toxic to both species was significant and positive along the entire line for the pesticide. Our results clearly show that responses of A. mellifera cannot be extrapolated to responses of O.cornifrons, and that synergism of neonicotinoid insecticides and fungicides occurs using formulated product in mixtures as they are commonly applied in apple orchards.

  3. Synergism between thrombin and adrenaline (epinephrine) in human platelets. Marked potentiation of inositol phospholipid metabolism.

    Science.gov (United States)

    Steen, V M; Tysnes, O B; Holmsen, H

    1988-01-01

    We have studied synergism between adrenaline (epinephrine) and low concentrations of thrombin in gel-filtered human platelets prelabelled with [32P]Pi. Suspensions of platelets, which did not contain added fibrinogen, were incubated at 37 degrees C to measure changes in the levels of 32P-labelled phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP) and phosphatidate (PA), aggregation and dense-granule secretion after stimulation. Adrenaline alone (3.5-4.0 microM) did not cause a change in any parameter (phosphoinositide metabolism, aggregation and dense-granule secretion), but markedly enhanced the thrombin-induced responses over a narrow range of thrombin concentrations (0.03-0.08 units/ml). The thrombin-induced hydrolysis of inositol phospholipids by phospholipase C, which was measured as the formation of [32P]PA, was potentiated by adrenaline, as was the increase in the levels of [32P]PIP2 and [32P]PIP. The presence of adrenaline caused a shift to the left for the thrombin-induced changes in the phosphoinositide metabolism, without affecting the maximal levels of 32P-labelled compounds obtained. A similar shift by adrenaline in the dose-response relationship was previously demonstrated for thrombin-induced aggregation and dense-granule secretion. Also, the narrow range of concentrations of thrombin over which adrenaline potentiates thrombin-induced platelet responses is the same for changes in phosphoinositide metabolism and physiological responses (aggregation and dense-granule secretion). Our observations clearly indicate that adrenaline directly or indirectly influences thrombin-induced changes in phosphoinositide metabolism. PMID:2845924

  4. Synergized antimicrobial activity of eugenol incorporated polyhydroxybutyrate films against food spoilage microorganisms in conjunction with pediocin.

    Science.gov (United States)

    Narayanan, Aarthi; Neera; Mallesha; Ramana, Karna Venkata

    2013-07-01

    Biopolymers and biopreservatives produced by microorganisms play an essential role in food technology. Polyhydroxyalkanoates and bacteriocins produced by bacteria are promising components to safeguard the environment and for food preservation applications. Polyhydroxybutyrate (PHB)-based antimicrobial films were prepared incorporating eugenol, from 10 to 200 μg/g of PHB. The films were evaluated for antimicrobial activity against foodborne pathogens, spoilage bacteria, and fungi such as Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Bacillus cereus, Aspergillus flavus, Aspergillus niger, Penicillium sp., and Rhizopus sp. The synergistic antimicrobial activity of the films in the presence of crude pediocin was also investigated. The broth system containing pediocin (soluble form) as well as antimicrobial PHB film demonstrated an extended lag phase and a significant growth reduction at the end of 24 h against the bacteria. Crude pediocin alone could not elicit antifungal activity, while inhibition of growth and sporulation were observed in the presence of antimicrobial PHB film containing eugenol (80 μg/g) until 7 days in the case of molds, i.e., A. niger, A. flavus, Penicillium sp., and Rhizopus sp. in potato dextrose broth. In the present study, we identified that use of pediocin containing broth in conjunction with eugenol incorporated PHB film could function in synergized form, providing effective hurdle toward food contaminating microorganisms. Furthermore, tensile strength, percent crystallinity, melting point, percent elongation to break, glass transition temperature, and seal strength of the PHB film with and without eugenol incorporation were investigated. The migration of eugenol on exposure to different liquid food simulants was also analyzed using Fourier transform infrared spectroscopy. The study is expected to provide applications for pediocin in conjunction with eugenol containing PHB film to enhance the shelf life of foods in the

  5. Vorinostat synergizes with ridaforolimus and abrogates the ridaforolimus-induced activation of AKT in synovial sarcoma cells.

    Science.gov (United States)

    Morgan, Sherif S; Cranmer, Lee D

    2014-11-18

    Curative treatments for patients with metastatic synovial sarcoma (SS) do not exist, and such patients have a poor prognosis. We explored combinations of molecularly-targeted and cytotoxic agents to identify synergistic treatment combinations in SS cells. Two SS cell lines (HS-SY-II and SYO-I) were treated with single agents or combinations of molecularly targeted therapies (HDAC inhibitor, vorinostat; mTOR inhibitor, ridaforolimus) and cytotoxic agents. After 72 hours, cell viability was measured using the MTS cell proliferation assay. Combination Indices (CI) were calculated to determine whether each combination was synergistic, additive, or antagonistic. Western Blot analysis assessed alterations in total and phospho-AKT protein levels in response to drug treatment. We determined the single-agent IC50 for ridaforolimus, vorinostat, doxorubicin, and melphalan in HS-SY-II and SYO-I. Synergism was apparent in cells co-treated with ridaforolimus and vorinostat: CI was 0.28 and 0.63 in HS-SY-II and SYO-I, respectively. Ridaforolimus/doxorubicin and ridaforolimus/melphalan exhibited synergism in both cell lines. An additive effect was observed with combination of vorinostat/doxorubicin in both cell lines. Vorinostat/melphalan was synergistic in HS-SY-II and additive in SYO-I. Western blot analysis demonstrated that ridaforolimus increased pAKT-ser473 levels; this effect was abrogated by vorinostat co-treatment. The combination of ridaforolimus and vorinostat demonstrates in vitro synergism in SS. Addition of vorinostat abrogated ridaforolimus-induced AKT activation. Since AKT activation is a possible mechanism of resistance to mTOR inhibitors, adding vorinostat (or another HDAC inhibitor) may be a route to circumvent AKT-mediated resistance to mTOR inhibitors.

  6. Synergic effects of 9,10-phenanthrenequinone and cadmium on pro-inflammatory responses in airway epithelial cells.

    Science.gov (United States)

    Honda, Akiko; Chowdhury, Pratiti Home; Ito, Sho; Okano, Hitoshi; Onishi, Toshinori; Kawaryu, Yusuke; Ueda, Kayo; Takano, Hirohisa

    2017-06-01

    We investigated the synergic effects of components of particulate matter with aerodynamic diameters ≤2.5μm (PM2.5) on airway inflammation. Co-exposure to cadmium (Cd) and 9,10-phenanthrenequinone (9,10-PQ) additively/synergistically increased pro-inflammatory responses in airway epithelial cells, whereas co-exposure to Cd and phenanthrene resulted in no acceleration. These results suggest that the combination of metal and a quinone derivative can contribute to the exacerbation of respiratory diseases by PM2.5. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

    Science.gov (United States)

    Gupta, Kajal; Singh, Sameer; van Hoek, Monique L

    2015-08-24

    Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism

  8. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2015-08-01

    Full Text Available Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP. Two synthetic 11-residue peptides (ATRA-1A and ATRA-2 containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4. We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost, making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP (EC50 = 0.05 μg/mL. High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed

  9. Synergized resmethrin and corticosterone alter the chicken's response to west nile virus

    Energy Technology Data Exchange (ETDEWEB)

    Jankowski, Mark David [Los Alamos National Laboratory; Franson, J Christian [US GEOLOGICAL SURVEY; Mostl, Erich [UNIV OF VIENNA; Porter, Warren P [UNIV OF WISCONSIN; Hofmeister, Erik K [US GEOLOGICAL SURVEY

    2009-01-01

    Debate concerning arbovirus control strategies remains contentious because concern regarding the relative risk of viral infection and environmental toxicant exposure is high but inadequately characterized. Taking this into account, mosquito control agencies employ aerial insecticides only after arbovirus surveillance data indicate high local mosquito-infection-rates. Successfully mitigating the risk of adult-mosquito-control insecticides ('adulticides') to non-target species such as humans, domestic animals, fish, beneficial insects and wildlife, while increasing their efficacy to reduce arbovirus outbreak intensity requires targeted scientific data from animal toxicity studies and environmental monitoring activities. Wild birds are an important reservoir host for WNv and are potentially exposed to insecticides used for mosquito control. However, no risk assessments have evaluated whether insecticides augment or extend the potential transmissibility of West Nile virus (WNv) in birds. In order to augment existing resmethrin risk assessments, we aimed to determine whether synergized resmethrin (SR) may cause chickens to develop an elevated or extended WN viremia and if subacute stress may affect its immunotoxicity. We distributed 40 chickens into four groups then exposed them prior to and during WNv infection with SR (50 {mu}g/l resmethrin + 150 {mu}g/l piperonyl butoxide) and/or 20 mg/I corticosterone (CORT) in their drinking-water. Corticosterone was given for 10 continuous days and SR was given for 3 alternate days starting the 3rd day of CORT exposure, then chickens were subcutaneously inoculated with WNv on the 5th day of CORT treatment. Compared to controls, CORT treatment extended and elevated viremia, enhanced WNv-specific antibody and increased the percentage of birds that shed oral virus, whereas SR treatment extended viremia, depressed WNv-specific IgG, and increased the percentage of CORT-treated birds that shed oral virus. Corticosterone and SR

  10. Ethanol and cocaine: environmental place conditioning, stereotypy, and synergism in planarians.

    Science.gov (United States)

    Tallarida, Christopher S; Bires, Kristopher; Avershal, Jacob; Tallarida, Ronald J; Seo, Stephanie; Rawls, Scott M

    2014-09-01

    More than 90% of individuals who use cocaine also report concurrent ethanol use, but only a few studies, all conducted with vertebrates, have investigated pharmacodynamic interactions between ethanol and cocaine. Planaria, a type of flatworm often considered to have the simplest 'brain,' is an invertebrate species especially amenable to the quantification of drug-induced behavioral responses and identification of conserved responses. Here, we investigated stereotypical and environmental place conditioning (EPC) effects of ethanol administered alone and in combination with cocaine. Planarians displayed concentration-related increases in C-shaped movements following exposure to ethanol (0.01-1%) (maximal effect: 9.9±1.1 C-shapes/5 min at 0.5%) or cocaine (0.1-5 mM) (maximal effect: 42.8±4.1 C-shapes/5 min at 5 mM). For combined administration, cocaine (0.1-5 mM) was tested with submaximal ethanol concentrations (0.01, 0.1%); the observed effect for the combination was enhanced compared to its predicted effect, indicating synergism for the interaction. The synergy with ethanol was specific for cocaine, as related experiments revealed that combinations of ethanol and nicotine did not result in synergy. For EPC experiments, ethanol (0.0001-1%) concentration-dependently increased EPC, with significant environmental shifts detected at 0.01 and 1%. Cocaine (0.001-1 μM) produced an inverted U-shaped concentration-effect curve, with a significant environmental shift observed at 0.01 μM. For combined exposure, variable cocaine concentrations (0.001-1 μM) were administered with a statistically ineffective concentration of ethanol (0.0001%). For each concentration of cocaine, the environmental shift was enhanced by ethanol, with significance detected at 1 μM. Cocaethylene, a metabolite of cocaine and ethanol, also produced C-shapes and EPC. Lidocaine (0.001-10 μM), an anesthetic and analog of cocaine, did not produce EPC or C-shaped movements. Evidence from planarians

  11. Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats.

    Science.gov (United States)

    Zhou, Hong-min; Zhong, Ming-li; Wang, Ru-huan; Long, Chao-liang; Zhang, Yan-fang; Cui, Wen-yu; Wang, Hai

    2015-11-01

    from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.

  12. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress

    Directory of Open Access Journals (Sweden)

    Mohammad Shokrzadeh

    2017-05-01

    Full Text Available Objective(s: Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN. In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO on the prevention of DN in streptozotocin induced-diabetic mice. Materials and Methods: Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent, diabetic group and four treatment groups which received U. dioica, pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ (200 mg/kg body wt, IP diluted in citrate buffer (pH= 4.6. After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Results: Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO, protein carbonyl in renal supernatant of diabetic mice was inhibited by U. dioica treatment.  Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Conclusion: Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

  13. Synergism effects of pioglitazone and Urtica dioica extract in streptozotocin-induced nephropathy via attenuation of oxidative stress.

    Science.gov (United States)

    Shokrzadeh, Mohammad; Sadat-Hosseini, Sara; Fallah, Marjan; Shaki, Fatemeh

    2017-05-01

    Hyperglycemia promotes oxidative stress that plays a crucial role in the pathogenesis of Diabetic nephropathy (DN). In this study, we investigated the synergism effects of hydroalcoholic extract of Urtica dioica and pioglitazone (PIO) on the prevention of DN in streptozotocin induced-diabetic mice. Forty-two mice were divided into six groups as follows: non-diabetic control group, DMSO group (as solvent), diabetic group and four treatment groups which received U. dioica , pioglitazone, U. dioica plus pioglitazone and vitE. Diabetes was induced by a single dose of streptozotocin (STZ) (200 mg/kg body wt, IP) diluted in citrate buffer (pH= 4.6). After 4 weeks treatment, all animals were anaesthetized and blood was collected for serum urea and creatinine levels assessment in plasma and kidney tissue were excised for evaluation of oxidative stress markers. Treatment with U. dioica significantly inhibited increase in serum urea and creatinine in plasma that were observed in diabetic mice. Furthermore, the elevated level of oxidative stress markers (glutathione oxidation, lipid peroxidation (LPO), protein carbonyl) in renal supernatant of diabetic mice was inhibited by U. dioica treatment. Interestingly, U. dioica promoted beneficial effects of PIO in reducing STZ-induced hyperglycemia, renal damage and oxidative stress markers. Our findings showed that PIO plus U. dioica have synergism protective effects against STZ-induced nephropathy that can be a candidate as a therapeutic approach in order to treatment of DN.

  14. Does Synergism in Microscopic Polarity Correlate with Extrema in Macroscopic Properties for Aqueous Mixtures of Dipolar Aprotic Solvents?

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    Duereh, Alif; Sato, Yoshiyuki; Smith, Richard Lee; Inomata, Hiroshi; Pichierri, Fabio

    2017-06-22

    Aqueous mixtures of dipolar aprotic solvents (acetonitrile, γ-valerolactone, γ-butyrolactone, tetrahydrofuran, 1,4-dioxane, acetone, pyridine, N-methyl-2-pyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethyl sulfoxide) show synergism in microscopic polarity and extrema in macroscopic viscosity (η) and molar excess enthalpy (H E ) in water-rich compositions that correlate with solvent functional group electrostatic basicity (β 2 H ). Microscopic polarities of aqueous solvent mixtures were estimated by measuring the spectral shift (λ max ) of 4-nitroaniline with UV-vis spectroscopy at 25 °C. Dynamic viscosities (η) and densities were measured for eight aqueous dipolar aprotic mixtures over the full range of compositions at (25 to 45) °C. The λ max , η, and H E values of the aqueous mixtures showed a linear trend with increasing electrostatic basicity of the solvent functional groups that is attributed to the size and strength of the hydration shell of water. Density functional theory (DFT) calculations were performed for 1:3 complexes (solvent: (H 2 O) 3 ) and it was found that aqueous mixtures with high basicity have high binding energies and short hydrogen bonding distances implying that the size and strength of the hydration shell of water is proportional to functional group basicity. Consideration of functional group basicity of dipolar aprotic solvents allows one to relate synergism in microscopic polarity to extrema in macroscopic properties for a wide range of aqueous dipolar aprotic solvent mixtures.

  15. A high efficient micro-proton exchange membrane fuel cell by integrating micro-nano synergical structures

    Science.gov (United States)

    Peng, Hsien-Chih; Wang, Chung-Nan; Yeh, Tsung-Kuang; Su, Yu-Chuan; Pan, Chin; Tseng, Fan-Gang

    2013-03-01

    A silicon-based micro-proton exchange membrane fuel cell (μ-PEMFC) which carries out an outstanding cell performance and high efficient catalyst utilization ratio is proposed in this paper by the employment of three micro-nano synergical techniques. Firstly, a novel design incorporating multi-walled carbon nano-tubes (MWCNTs) on radial shaped micro-channel walls to form micro/nano reaction chambers which significantly enhance the reaction surface areas for the performance improvement. In the second, the dispensing of ionomer onto the three-phase zones in the reaction chambers is controlled by different rotation speed and the optimized distribution can therefore be achieved for the improvement of catalyst utilization. In the third, the cell interfacial strength is greatly enhanced by the employment of micro-interlocks for maintaining excellent interface between Nafion membrane and reaction chambers while minimizing the system size. A μ-PEMFC is successfully fabricated by integrating aforementioned synergical micro/nano structures altogether. The best cell efficiency is 26 mW cm-2 which corresponds to a catalyst utilization ratio of 38.2 W g-pt-1, and can be considered among the best performed micro-fuel cells.

  16. Synergism between rare earth cerium(IV) ion and vanillin on the corrosion of cold rolled steel in 1.0 M HCl solution

    International Nuclear Information System (INIS)

    Li Xianghong; Deng Shuduan; Fu Hui; Mu Guannan

    2008-01-01

    The synergism between rare earth cerium(IV) ion and vanillin on the corrosion of cold rolled steel (CRS) in 1.0 M HCl solution was first investigated by weight loss, potentiodynamic polarization, ultraviolet and visible spectrophotometer (UV-vis), X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). The results revealed that vanillin had a moderate inhibitive effect, and the adsorption of vanillin obeyed the Temkin adsorption isotherm. For rare earth Ce 4+ , it had a negligible effect. However, incorporation of Ce 4+ with vanillin significantly improved the inhibition performance, and produced strong synergistic inhibition effect. Depending on the results, the synergism mechanism was proposed

  17. Synergism between rare earth cerium(IV) ion and vanillin on the corrosion of cold rolled steel in 1.0 M HCl solution

    Energy Technology Data Exchange (ETDEWEB)

    Li Xianghong [Department of Fundamental Courses, Southwest Forestry University, Kunming 650224 (China)], E-mail: xianghong-li@163.com; Deng Shuduan [Department of Wood Science and Technology, Southwest Forestry University, Kunming 650224 (China); Fu Hui [Department of Fundamental Courses, Southwest Forestry University, Kunming 650224 (China); Mu Guannan [Department of Chemistry, Yunnan University, Kunming 650091 (China)

    2008-12-15

    The synergism between rare earth cerium(IV) ion and vanillin on the corrosion of cold rolled steel (CRS) in 1.0 M HCl solution was first investigated by weight loss, potentiodynamic polarization, ultraviolet and visible spectrophotometer (UV-vis), X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). The results revealed that vanillin had a moderate inhibitive effect, and the adsorption of vanillin obeyed the Temkin adsorption isotherm. For rare earth Ce{sup 4+}, it had a negligible effect. However, incorporation of Ce{sup 4+} with vanillin significantly improved the inhibition performance, and produced strong synergistic inhibition effect. Depending on the results, the synergism mechanism was proposed.

  18. Autoradiographic studies with the 14C-IAA in relation to synergism between auxin and non-auxin chemicals in the rooting of bean (Phaseolus vulgaris L.) cuttings

    International Nuclear Information System (INIS)

    Chaudhury, K.G.; Basu, R.N.

    1980-01-01

    Indole and α-naphthol significantly synergized the IAA-induced rooting of P. vulqaris cuttings. The pattern of incorporation of radiocarbon of IAA-I- 14 C and IAA-2- 14 C supplied to the base of the cuttings was, however, not altered by the synergists and the same radioactive metabolites were located on the radioautograms of ethanolic extracts of the hypocotyls of cuttings under the different treatments. The results thereby discount the possibility of formation of bioactive complexes between auxins and synergists as the mechanism of synergism in rooting. The synergists, however, influenced the extent of incorporation of radiocarbon of the labelled auxin molecules into some of the radioactive metabolites. (auth.)

  19. Co-precipitation of ettringite of rapid and slow formation. Consequence: Expansive Synergic Effect. Its demonstration by mortars and concretes

    Directory of Open Access Journals (Sweden)

    Talero, R.

    2011-09-01

    Full Text Available Several prior papers have shown that enough pozzolans can bring about rapid formation ettringite (from its Al2O3r-. It has likewise been found that the formation rate of this ettringite is higher than the of slower forming ettringite originating from OPC (from its C3A. In this context: What type of effect will they ultimately produce? Addition? Synergism? Antagonism? or perhaps Inversion of final expansive action?. To reply to these questions, 4 PC and 12 blended cements containing 20%, 30% or 40% metakaolin, were tested using the ASTM C 452-68, EN 196-1 and RT-86:ΔL tests and also concrete specimens. The experimental results have shows that the joint precipitation in a common sulfate medium, of ettringite from pozzolan and from OPC, was always more synergic than additive, and the technical consequences of the Expansive Synergic Effect may be classified as beneficial, adverse or indifferent according to its sulfates content in excess is more or less adequate.En investigaciones anteriores se ha demostrado que bastantes puzolanas pueden originar ettringita de rápida formación (de su Al2O3r- cuya velocidad es mayor que la de la ettringita de lenta formación, o de origen CPO (de su C3A. En este contexto: ¿qué tipo de efecto será el que produzcan finalmente ambas ettringitas?, ¿adición?, ¿sinergismo?, ¿antagonismo? o ¿inversión de la acción expansiva?. Para responder a estas cuestiones, 4 CPO y 12 cementos con 20%, 30% y 40% de metakaolín fueron ensayados mediante los métodos ASTM C 452-68, EN 196-1 y RT-86:ΔL, y también mediante hormigones. Los resultados obtenidos han demostrado que la precipitación conjunta en un medio selenitoso común, de ettringita de origen puzolana y de origen CPO, es siempre cuantitativamente hablando, más que aditiva, sinérgica, pudiendo ser por ello las consecuencias técnicas del Efecto Sinérgico Expansivo, beneficiosas, adversas o indiferentes, según que el exceso de sulfatos presentes sea más o

  20. Enhanced activity of lysozyme-AgNP conjugate with synergic antibacterial effect without damaging the catalytic site of lysozyme.

    Science.gov (United States)

    Ernest, Vinita; Gajalakshmi, Sekar; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-10-01

    The conjugation of silver nanoparticles (AgNPs) with biomolecules such as oligosaccharides, DNA, proteins has attracted great attention of scientists recently. In this study, lysozyme-AgNP conjugates were evaluated for its synergic antimicrobial effect. AgNPs were synthesized and characterized using UV-Visible, X-ray diffraction analysis (XRD) and atomic force microscopy (AFM). AgNP (0-1 mM) was interacted with lysozyme for multi-spectrophotometric studies. Lysozyme was immobilized on AgNP at different ratios and the resulting nano-bio-conjugate was tested against Escherichia coli for potent synergic antibacterial effects. A surface plasmon peak at 420 nm confirmed the presence of AgNPs and spherical to oval-shaped AgNPs were observed by AFM. The particle size was calculated to be 25 nm by XRD analysis. The maximum immobilization efficiency (98%) was achieved at 0.01:1 ratio of enzyme:AgNP. UV-Visible and fluorescence spectral studies revealed the binding of AgNPs to lysozyme by the formation of ground-state complex and the binding parameters were calculated. Circular dichroism studies confirmed decrease by 11% in the α-helical and 29.32% in β-sheets of lysozyme upon AgNP interaction. FTIR spectra revealed the binding of AgNP through thiol (-SH) linkages of lysozyme. Our results showed that the antimicrobial activity of lysozyme-AgNP conjugate was enhanced up to 86% decrease in the cell growth. In summary, the immobilization of lysozyme on AgNP has yielded a nano-bio-conjugate with synergistic antibacterial properties.

  1. Release of piperonyl butoxide and permethrin from synergized ear tags on cattle and effects on horn fly mortality.

    Science.gov (United States)

    Li, Andrew Y; Miller, J Allen; Klavons, Jerome A

    2008-10-01

    A study was conducted to determine the release rates of piperonyl butoxide (PBO) and permethrin from synergized insecticidal cattle ear tags and their effects on mortality of the horn fly, Hematobia irritans irritans (L.) (Diptera: Muscidae). PBO was released from the ear tags at a higher rate than permethrin in both winter and summer trials. The cumulative release of PBO and permethrin from the ear tags at the end of 18 wk in the winter trial was 50.4 and 30.3%, respectively. The cumulative release of PBO and permethrin from the ear tags at the end of 18 wk in the summer trial was 66.7 and 44.7%, respectively. There was a significant correlation between the cumulative daily high ambient temperature (degrees C) and the cumulative release of both PBO and permethrin. Compared with the susceptible horn fly strain, the permethrin-resistant strain demonstrated 7.9- and 12.8-fold resistance to permethrin at the levels of LC50 and LC90, respectively. When exposed to filter paper wipes taken from the shoulders of cattle treated with the PBO-synergized permethrin tags from the summer trial, the resistant strain demonstrated reduced mortality compared with the susceptible strain. The mortality of the resistant strain at 2- and 3-h exposure exhibited a pattern of declining fly mortalities as a result of the decreased release of PBO and permethrin, as well as the decline in the ratio of PBO:permethrin released from the tags after 8 wk. A similar decline in horn fly mortalities was observed in the susceptible strain at 30-min exposure time that coincided with the pattern of reduced release of PBO and permethrin from the ear tags over the course of summer trial.

  2. Insecticide toxicity and synergism by enzyme inhibitors in 18 species of pest insect and natural enemies in crucifer vegetable crops.

    Science.gov (United States)

    Wu, Gang; Miyata, Tadashi; Kang, Chun Yu; Xie, Lian Hui

    2007-05-01

    The toxicities of three enzyme inhibitors and their synergistic effects on four insecticides were studied by using the dry film method on field populations of 18 species of insects collected in Jianxin and Shanjie, China, from 2003 to 2005. Meanwhile, the inhibitory effects of these enzyme inhibitors on the activities of acetylcholinesterases (AChE), carboxyesterases (CarE) and glutathione-S-transferases (GST), in vivo, were also studied. In general, triphenyl phosphate (TPP) and diethyl maleate (DEM) showed low toxicities to six herbivorous pest insects, four ladybirds and eight parasitoids. Piperonyl butoxide (PB) exhibited low toxicities to the herbivorous pest insects and ladybirds, but high toxicities to the eight parasitoids. The tolerance to the insecticides in 11 pest insects and natural enemies was mainly associated with the tolerance to PB. PB showed the highest synergism on methamidophos, fenvalerate, fipronil and avermectin in nine species of pest insects and natural enemies. In general, TPP and DEM showed significant synergisms to these four insecticides in four parasitoid species. However, in contrast to their effects on the parasitoids, the synergistic effects of TPP and DEM on the four insecticides by TPP and DEM against four pest insects and one ladybird varied depending on the insect species and enzyme inhibitor. Activity of AChE, CarE or GST could be strongly inhibited, in vivo, by PB, TPP or DEM, depending on the insect species and enzyme inhibitors. From the results obtained in this study, mixed-function oxidase (MFO) was thought to play the most critical role in insect tolerances to the tested insecticides in the field. Low competition existed in the evolution of insecticide resistance in the field populations of parasitoids, as compared with herbivorous pest insects and ladybirds. Possible causes of the high synergistic effects of PB on the four classes of insecticides, based on multiattack on the activity of CarE, GST or AChE in the insect

  3. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer's mice.

    Science.gov (United States)

    Cao, Chuanhai; Wang, Li; Lin, Xiaoyang; Mamcarz, Malgorzata; Zhang, Chi; Bai, Ge; Nong, Jasson; Sussman, Sam; Arendash, Gary

    2011-01-01

    Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.

  4. Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

    Energy Technology Data Exchange (ETDEWEB)

    Lombardo, Tomás [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina); Cavaliere, Victoria; Costantino, Susana N. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Kornblihtt, Laura [Servicio de Hematología, Hospital de Clínicas, José de San Martín (UBA), Buenos Aires (Argentina); Alvarez, Elida M. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Blanco, Guillermo A., E-mail: gblanco@ffyb.uba.ar [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina)

    2012-02-01

    Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou–Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O{sub 2}{sup −}) levels. Our results showed that combined arsenite + MG132 produced low levels of O{sub 2}{sup −} at 6 h and 24 h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80 μM hydrogen peroxide together with arsenite + MG132 changed synergism on cell death to antagonism at all effect levels while increasing O{sub 2}{sup −} levels. Arsenite + hydrogen peroxide also resulted in antagonism with increased O{sub 2}{sup −} levels in U937 cells. In Raji cells, arsenite + MG132 also produced low levels of O{sub 2}{sup −} at 6 h and 24 h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite + CAPE showed high levels of O{sub 2}{sup −} production at 6 h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O{sub 2}{sup −} levels at early time points after exposure. -- Highlights: ► Arsenic combined cytotoxic and anti-proliferative effects by Chou–Talalay method. ► Cytotoxic effect

  5. Observing lowermost tropospheric ozone pollution with a new multispectral synergic approach of IASI infrared and GOME-2 ultraviolet satellite measurements

    Science.gov (United States)

    Cuesta, Juan; Foret, Gilles; Dufour, Gaëlle; Eremenko, Maxim; Coman, Adriana; Gaubert, Benjamin; Beekmann, Matthias; Liu, Xiong; Cai, Zhaonan; Von Clarmann, Thomas; Spurr, Robert; Flaud, Jean-Marie

    2014-05-01

    Tropospheric ozone is currently one of the air pollutants posing greatest threats to human health and ecosystems. Monitoring ozone pollution at the regional, continental and global scale is a crucial societal issue. Only spaceborne remote sensing is capable of observing tropospheric ozone at such scales. The spatio-temporal coverage of new satellite-based instruments, such as IASI or GOME-2, offer a great potential for monitoring air quality by synergism with regional chemistry-transport models, for both inter-validation and full data assimilation. However, current spaceborne observations using single-band either UV or IR measurements show limited sensitivity to ozone in the atmospheric boundary layer, which is the major concern for air quality. Very recently, we have developed an innovative multispectral approach, so-called IASI+GOME-2, which combines IASI and GOME-2 observations, respectively in the IR and UV. This unique multispectral approach has allowed the observation of ozone plumes in the lowermost troposphere (LMT, below 3 km of altitude) over Europe, for the first time from space. Our first analyses are focused on typical ozone pollution events during the summer of 2009 over Europe. During these events, LMT ozone plumes at different regions are produced photo-chemically in the boundary layer, transported upwards to the free troposphere and also downwards from the stratosphere. We have analysed them using IASI+GOME-2 observations, in comparison with single-band methods (IASI, GOME-2 and OMI). Only IASI+GOME-2 depicts ozone plumes located below 3 km of altitude (both over land and ocean). Indeed, the multispectral sensitivity in the LMT is greater by 40% and it peaks at 2 to 2.5 km of altitude over land, thus at least 0.8 to 1 km below that for all single-band methods. Over Europe during the summer of 2009, IASI+GOME-2 shows 1% mean bias and 21% precision for direct comparisons with ozonesondes and also good agreement with CHIMERE model simulations

  6. HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities.

    Science.gov (United States)

    Pollara, Justin; Bonsignori, Mattia; Moody, M Anthony; Liu, Pinghuang; Alam, S Munir; Hwang, Kwan-Ki; Gurley, Thaddeus C; Kozink, Daniel M; Armand, Lawrence C; Marshall, Dawn J; Whitesides, John F; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L; O'Connell, Robert J; Kim, Jerome H; Michael, Nelson L; Montefiori, David C; Tomaras, Georgia D; Liao, Hua-Xin; Haynes, Barton F; Ferrari, Guido

    2014-07-01

    The RV144 ALVAC/AIDSVax HIV-1 vaccine clinical trial showed an estimated vaccine efficacy of 31.2%. Viral genetic analysis identified a vaccine-induced site of immune pressure in the HIV-1 envelope (Env) variable region 2 (V2) focused on residue 169, which is included in the epitope recognized by vaccinee-derived V2 monoclonal antibodies. The ALVAC/AIDSVax vaccine induced antibody-dependent cellular cytotoxicity (ADCC) against the Env V2 and constant 1 (C1) regions. In the presence of low IgA Env antibody levels, plasma levels of ADCC activity correlated with lower risk of infection. In this study, we demonstrate that C1 and V2 monoclonal antibodies isolated from RV144 vaccinees synergized for neutralization, infectious virus capture, and ADCC. Importantly, synergy increased the HIV-1 ADCC activity of V2 monoclonal antibody CH58 at concentrations similar to that observed in plasma of RV144 vaccinees. These findings raise the hypothesis that synergy among vaccine-induced antibodies with different epitope specificities contributes to HIV-1 antiviral antibody responses and is important to induce for reduction in the risk of HIV-1 transmission. Importance: The Thai RV144 ALVAC/AIDSVax prime-boost vaccine efficacy trial represents the only example of HIV-1 vaccine efficacy in humans to date. Studies aimed at identifying immune correlates involved in the modest vaccine-mediated protection identified HIV-1 envelope (Env) variable region 2-binding antibodies as inversely correlated with infection risk, and genetic analysis identified a site of immune pressure within the region recognized by these antibodies. Despite this evidence, the antiviral mechanisms by which variable region 2-specific antibodies may have contributed to lower rates of infection remain unclear. In this study, we demonstrate that vaccine-induced HIV-1 envelope variable region 2 and constant region 1 antibodies synergize for recognition of virus-infected cells, infectious virion capture, virus

  7. Synergism between basic Asp49 and Lys49 phospholipase A2 myotoxins of viperid snake venom in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Diana Mora-Obando

    Full Text Available Two subtypes of phospholipases A2 (PLA2s with the ability to induce myonecrosis, 'Asp49' and 'Lys49' myotoxins, often coexist in viperid snake venoms. Since the latter lack catalytic activity, two different mechanisms are involved in their myotoxicity. A synergism between Asp49 and Lys49 myotoxins from Bothrops asper was previously observed in vitro, enhancing Ca2+ entry and cell death when acting together upon C2C12 myotubes. These observations are extended for the first time in vivo, by demonstrating a clear enhancement of myonecrosis by the combined action of these two toxins in mice. In addition, novel aspects of their synergism were revealed using myotubes. Proportions of Asp49 myotoxin as low as 0.1% of the Lys49 myotoxin are sufficient to enhance cytotoxicity of the latter, but not the opposite. Sublytic amounts of Asp49 myotoxin also enhanced cytotoxicity of a synthetic peptide encompassing the toxic region of Lys49 myotoxin. Asp49 myotoxin rendered myotubes more susceptible to osmotic lysis, whereas Lys49 myotoxin did not. In contrast to myotoxic Asp49 PLA2, an acidic non-toxic PLA2 from the same venom did not markedly synergize with Lys49 myotoxin, revealing a functional difference between basic and acidic PLA2 enzymes. It is suggested that Asp49 myotoxins synergize with Lys49 myotoxins by virtue of their PLA2 activity. In addition to the membrane-destabilizing effect of this activity, Asp49 myotoxins may generate anionic patches of hydrolytic reaction products, facilitating electrostatic interactions with Lys49 myotoxins. These data provide new evidence for the evolutionary adaptive value of the two subtypes of PLA2 myotoxins acting synergistically in viperid venoms.

  8. Physicochemical characterization of pectinase activity from Bacillus spp. and their accessory role in synergism with crude xylanase and commercial cellulase in enzyme cocktail mediated saccharification of agrowaste biomass.

    Science.gov (United States)

    Thite, V S; Nerurkar, A S

    2018-02-07

    The aim of this study was to evaluate the physicochemical properties of the crude pectinase activity from three Bacillus isolates of ruminant dung origin and study their synergism with crude xylanases from the same Bacillus spp. and a commercial cellulase to evaluate their accessory role in improved biomass saccharification. Pectinolytic crude culture filtrate obtained from three ruminant dung isolates, Bacillus safensis M35, Bacillus altitudinis R31 and Bacillus altitudinis J208, on crude pectin containing medium possessed polygalacturonate hydrolase, pectate lyase and pectin lyase activities. Studies regarding their stability under various temperature and pH conditions revealed their mild acidic to alkaline and mesophilic nature with enzyme activity falling within the pH range 6·0-9·0 and temperature range 30-60°C. The pectinase activity was categorized as endolytic as it brought about ~50% reduction in relative viscosity of pectic polymer within initial 10 min of incubation. Synergism of pectinase activity with crude xylanase activities and/or commercial cellulase was clearly demonstrated as ~1·6 to ~1·9-fold increase in agrowaste biomass saccharification was obtained confirming the role of pectinases as accessory enzymes. Synergism of the broad-spectrum endopectinase activity obtained from three Bacillus isolates with accessory crude xylanases from the same isolates and commercial cellulase enhanced the agrowaste saccharification and confirmed the accessory role of crude pectinase as they formed an efficient enzyme cocktail functioning in a contributive manner for improvement of agrowaste biomass saccharification. Mesophilic crude endopectinases obtained from Bacillus spp. isolated from ruminant dung possessed activity in broad pH and temperature ranges as well as broad substrate specificity. Moreover, their synergism with crude xylanase and Primfast ® 200 cellulase demonstrated the potential to form efficient enzyme cocktail for application in plant

  9. Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

    2017-01-15

    Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of 2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat

  10. Synergism between Basic Asp49 and Lys49 Phospholipase A2 Myotoxins of Viperid Snake Venom In Vitro and In Vivo

    Science.gov (United States)

    Mora-Obando, Diana; Fernández, Julián; Montecucco, Cesare; Gutiérrez, José María; Lomonte, Bruno

    2014-01-01

    Two subtypes of phospholipases A2 (PLA2s) with the ability to induce myonecrosis, ‘Asp49’ and ‘Lys49’ myotoxins, often coexist in viperid snake venoms. Since the latter lack catalytic activity, two different mechanisms are involved in their myotoxicity. A synergism between Asp49 and Lys49 myotoxins from Bothrops asper was previously observed in vitro, enhancing Ca2+ entry and cell death when acting together upon C2C12 myotubes. These observations are extended for the first time in vivo, by demonstrating a clear enhancement of myonecrosis by the combined action of these two toxins in mice. In addition, novel aspects of their synergism were revealed using myotubes. Proportions of Asp49 myotoxin as low as 0.1% of the Lys49 myotoxin are sufficient to enhance cytotoxicity of the latter, but not the opposite. Sublytic amounts of Asp49 myotoxin also enhanced cytotoxicity of a synthetic peptide encompassing the toxic region of Lys49 myotoxin. Asp49 myotoxin rendered myotubes more susceptible to osmotic lysis, whereas Lys49 myotoxin did not. In contrast to myotoxic Asp49 PLA2, an acidic non-toxic PLA2 from the same venom did not markedly synergize with Lys49 myotoxin, revealing a functional difference between basic and acidic PLA2 enzymes. It is suggested that Asp49 myotoxins synergize with Lys49 myotoxins by virtue of their PLA2 activity. In addition to the membrane-destabilizing effect of this activity, Asp49 myotoxins may generate anionic patches of hydrolytic reaction products, facilitating electrostatic interactions with Lys49 myotoxins. These data provide new evidence for the evolutionary adaptive value of the two subtypes of PLA2 myotoxins acting synergistically in viperid venoms. PMID:25290688

  11. Separation and determination of a trace amount of lithium as its thenoyltrifluoroacetone complex with 12-crown-4 by means of synergic extraction and flame photometry

    OpenAIRE

    Itoh, Tatsuo; Billah, Mokarram; Honjo, Takaharu; Terada, Kikuo

    1991-01-01

    A new method for the separation and determination of a trace amount of lithium in ppb∼ppm level in water as its thenoyltrifluoroacetone (TTA) complex with 12-crown-4 (12C4) has been established by means of synergic extraction and back extraction combined with flame photometry. The effect of various factors (pH, solvent, reagent concentration, shaking time, preconcentration factor, and foreign ions etc.) on the extraction and back extraction of lithium has been investigated. Here the lithium T...

  12. Synergic Effect between Adsorption and Photocatalysis of Metal-Free g-C3N4 Derived from Different Precursors.

    Directory of Open Access Journals (Sweden)

    Huan-Yan Xu

    Full Text Available Graphitic carbon nitride (g-C3N4 used in this work was obtained by heating dicyandiamide and melamine, respectively, at different temperatures. The differences of g-C3N4 derived from different precursors in phase composition, functional group, surface morphology, microstructure, surface property, band gap and specific surface area were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, UV-visible diffuse reflection spectroscopy and BET surface area analyzer, respectively. The photocatalytic discoloration of an active cationic dye, Methylene Blue (MB under visible-light irradiation indicated that g-C3N4 derived from melamine at 500°C (CN-M500 had higher adsorption capacity and better photocatalytic activity than that from dicyandiamide at 500°C (CN-D500, which was attributed to the larger surface area of CN-M500. MB discoloration ratio over CN-M500 was affected by initial MB concentration and photocatalyst dosage. After 120 min reaction time, the blue color of MB solution disappeared completely. Subsequently, based on the measurement of the surface Zeta potentials of CN-M500 at different pHs, an active anionic dye, Methyl Orange (MO was selected as the contrastive target pollutant with MB to reveal the synergic effect between adsorption and photocatalysis. Finally, the photocatalytic mechanism was discussed.

  13. Synergic Effect between Adsorption and Photocatalysis of Metal-Free g-C3N4 Derived from Different Precursors

    Science.gov (United States)

    Xu, Huan-Yan; Wu, Li-Cheng; Zhao, Hang; Jin, Li-Guo; Qi, Shu-Yan

    2015-01-01

    Graphitic carbon nitride (g-C3N4) used in this work was obtained by heating dicyandiamide and melamine, respectively, at different temperatures. The differences of g-C3N4 derived from different precursors in phase composition, functional group, surface morphology, microstructure, surface property, band gap and specific surface area were investigated by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, UV-visible diffuse reflection spectroscopy and BET surface area analyzer, respectively. The photocatalytic discoloration of an active cationic dye, Methylene Blue (MB) under visible-light irradiation indicated that g-C3N4 derived from melamine at 500°C (CN-M500) had higher adsorption capacity and better photocatalytic activity than that from dicyandiamide at 500°C (CN-D500), which was attributed to the larger surface area of CN-M500. MB discoloration ratio over CN-M500 was affected by initial MB concentration and photocatalyst dosage. After 120 min reaction time, the blue color of MB solution disappeared completely. Subsequently, based on the measurement of the surface Zeta potentials of CN-M500 at different pHs, an active anionic dye, Methyl Orange (MO) was selected as the contrastive target pollutant with MB to reveal the synergic effect between adsorption and photocatalysis. Finally, the photocatalytic mechanism was discussed. PMID:26565712

  14. Antioxidant activity of amino acids in soybean oil at frying temperature: Structural effects and synergism with tocopherols.

    Science.gov (United States)

    Hwang, Hong-Sik; Winkler-Moser, Jill K

    2017-04-15

    The purpose of this study was to evaluate amino acids as natural antioxidants for frying. Twenty amino acids were added to soybean oil heated to 180°C, and the effects of amino acid structure on the antioxidant activity were investigated. Amino acids containing a thiol, a thioether, or an extra amine group such as arginine, cysteine, lysine, methionine, and tryptophan had the strongest antioxidant activities. At 5.5mM, these amino acids had stronger antioxidant activities than 0.02% (1.1mM) tert-butylhydroquinone (TBHQ). A functional group such as an amide, carboxylic acid, imidazole, or phenol appeared to negatively affect amino acid antioxidant activity. Synergism between amino acids and tocopherols was demonstrated, and we found that this synergistic interaction may be mostly responsible for the antioxidant activity that was observed. In a frying study with potato cubes, 5.5mM l-methionine had significantly stronger antioxidant activity than 0.02% TBHQ. Published by Elsevier Ltd.

  15. Mutagenic synergism detected between 1,2-dibromoethane and X rays in the stamen hairs of Tradescantia clone BNL 4430

    International Nuclear Information System (INIS)

    Xiao, Ling Zhi; Ichikawa, Sadao

    1998-01-01

    Mutagenic interaction between 1,2-dibromoethane (EDB) and X rays was studied in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink heterozygote. The young inflorescence-bearing shoots with roots of this clone cultivated in a nutrient solution circulating growth chamber were used as the tester plants. EDB is a promutagen and also a bifunctional alkylating agent with a high Swain-Scott substrate constant, but is thought to react probably via SN 1 mechanism. After confirming the dose-dependent mutagenicities of aqueous solutions of EDB for the first time in Tradescantia stamen hairs, a combined treatment with EDB and X rays was conducted, exposing acutely to 578 mGy X rays at the midpoint of 66.5 mM EDB treatment for 4 h. The induced somatic mutation frequency determined after the combined treatment was significantly higher (at 0.1% level) than that expected from the additive effects of EDB and X rays, showing that EDB and X rays acted obviously synergistically. The confirmation of the mutagenic synergism between EDB and X rays is reported here for the first time, although a likelihood of synergistic effects of EDB with 3 H beta rays has been suggested earlier. (author)

  16. Antifungal activity of Coriandrum sativum essential oil, its mode of action against Candida species and potential synergism with amphotericin B.

    Science.gov (United States)

    Silva, Filomena; Ferreira, Susana; Duarte, Andreia; Mendonça, Dina I; Domingues, Fernanda C

    2011-12-15

    The increasing incidence of drug-resistant pathogens and toxicity of existing antifungal compounds has drawn attention towards the antimicrobial activity of natural products. The aim of the present study was to evaluate the antifungal activity of coriander essential oil according to classical bacteriological techniques, as well as with flow cytometry. The effect of the essential oil upon germ tube formation, seen as an important virulence factor, and potential synergism with amphotericin B were also studied. Coriander essential oil has a fungicidal activity against the Candida strains tested with MLC values equal to the MIC value and ranging from 0.05 to 0.4% (v/v). Flow cytometric evaluation of BOX, PI and DRAQ5 staining indicates that the fungicidal effect is a result of cytoplasmic membrane damage and subsequent leakage of intracellular components such as DNA. Also, concentrations bellow the MIC value caused a marked reduction in the percentage of germ tube formation for C. albicans strains. A synergetic effect between coriander oil and amphotericin B was also obtained for C. albicans strains, while for C. tropicalis strain only an additive effect was observed. This study describes the antifungal activity of coriander essential oil on Candida spp., which could be useful in designing new formulations for candidosis treatment. Copyright © 2011 Elsevier GmbH. All rights reserved.

  17. The Synergic Characteristics of Surface Water Pollution and Sediment Pollution with Heavy Metals in the Haihe River Basin, Northern China

    Directory of Open Access Journals (Sweden)

    Peiru Kong

    2018-01-01

    Full Text Available Aquatic environmental deterioration is becoming a serious problem due to rapid urbanization and economic development, particularly in developing countries. As two important components of the aquatic environment, water quality and sediment pollution are widely considered to be concerns; however, they are considered separately in most cases. The relationship between water quality and sediment pollution with heavy metals has been little addressed. In this study, the Haihe River Basin (HRB, one of the most polluted areas in China, was used as a case study, and the eutrophication index (EI and the potential ecological risk index (RI were employed to evaluate water quality and sediment pollution of heavy metals, respectively. The results showed that generally in the HRB, the water quality was poor, while the risk of heavy metal pollution was relatively low. Surface water quality was mainly influenced by sewage discharges from human daily life, and heavy metal pollution was affected by industry structure, in that the areas with resource/energy consumption industries and high-pollution industries often have high risks of heavy metal pollution Synergic pollution from water eutrophication and sediment pollution with heavy metals was found, especially in the central areas of the HRB, and it was largely dependent on the type of human activities. In the places with intensive human activities, such as secondary industry, eutrophication occurred simultaneously with heavy metal pollution, other than in less human-affected areas. These findings are useful for planning aquatic environment protections and river ecosystem management.

  18. Triclosan demonstrates synergic effect with amphotericin B and fluconazole and induces apoptosis-like cell death in Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Elaheh eMovahed

    2016-03-01

    Full Text Available Objectives: Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans.Methods: Minimal inhibitory concentration (MIC of triclosan in different C. neoformans strains was first examined. The in vitro interactions between triclosan and two standard anti-fungal drugs (amphotericin B and fluconazole were further evaluated by microdilution checkerboard assay. Mechanism of triclosan fungicidal activity was then investigated by viewing the cell morphology under transmission electron microscope.Results: We reported that triclosan potently inhibited the growth of C. neoformans. A combination of triclosan with amphotericin B or with fluconazole enhanced their fungicidal effects. Triclosan-treated C. neoformans displayed characteristics such as nuclear chromatin condensation, extensive intracellular vacuolation and mitochondrial swelling, indicating that triclosan triggered apoptosis-like cell death.Conclusion: In summary, our report suggests triclosan as an independent drug or synergent for C. neoformans treatment.

  19. Synergism in the sorption of europium on chromatographic supports impregnated with dicarbollide acid and bidentate phosphororganic extractant

    International Nuclear Information System (INIS)

    Svoboda, K.; Kyrs, M.; Vanura, P.

    1997-01-01

    Extraction chromatographic supports (XAD-7) impregnated with binary mixtures of cobalt dicarbollide and one of the two phosphororganic extractants (dibutyl-N,N-diethylcarbamoylmethyl phosphonate, DBDECMP, or octyl(phenyl)-N,N-diisobutylcarbamoylmethyl phosphine oxide, (CMPO) were prepared using methanolic solutions of the extractants and subsequent evaporation of methanol at room temperature. The molar ratios (x) in isomolar series of the two extractants were 0.025, 0.5, 0.75, and 1. The sorbents were used for investigating Eu capture from 0.1 and 1M HNO 3 solutions under static conditions (24 hours shaking, 2 cm 3 aqueous phase with 0.2 g sorbent, Eu initial concentrations 3 * 10 -9 , 0.0001, 0.001, 0.01 and 0.1M). The sorbents containing mixtures of extractants corresponding to the interpolated value x=0.45 (phosphororg./dicarb.) exhibited the highest values of the distribution ratios of Eu. A synergic effect of three orders of magnitude for low concentrations of Eu was observed. A tentative determination is given of the nature and the equilibrium constants of the chemical reactions assumed. (author)

  20. Knockdown of REV3 synergizes with ATR inhibition to promote apoptosis induced by cisplatin in lung cancer cells.

    Science.gov (United States)

    Jiang, He-Guo; Chen, Ping; Su, Jin-Yu; Wu, Ming; Qian, Hai; Wang, Yi; Li, Jian

    2017-12-01

    It has been demonstrated that REV3, the catalytic subunit of the translesion synthesis (TLS) polymerase ζ, play an important role in DNA damage response (DDR) induced by cisplatin, and Ataxia-telangietasia mutated and Rad-3-related (ATR) knase is a central player in activating cell cycle checkpoint, stabilizing replication forks, regulating DDR, and promoting repair of DNA damage caused by cisplatin. Cancer cells deficient in either one of REV3 and ATR are more sensitive to cisplatin. However, whether co-inhibition of REV3 and ATR can further increase sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin is not clear. In this study, we show that REV3 knockdown combined with ATR inhibition further enhance cytotoxicity of cisplatin in NSCLC cells, including cisplatin-sensitive and -resistant cell lines, compared to individual knockdown of REV3 or ATR, which are accompanied by markedly caspase-dependent apoptosis response, pronounced DNA damage accumulation and severe impediment of interstrand crosslink (ICL), and double strand break (DSB) repair. Our results suggest that REV3 knockdown synergize strongly with ATR inhibition to significantly increase sensitivity of cisplatin in NSCLC cells by inhibiting ICL and DSB repair. Thus simultaneously targeting REV3 and ATR may represent one approach to overcome cisplatin resistance and improve chemotherapeutic efficacy in NSCLC treatment. © 2017 Wiley Periodicals, Inc.

  1. Pressure-dependent electron attachment and breakdown strengths of unitary gases, and synergism of binary gas mixtures: a relationship

    International Nuclear Information System (INIS)

    Hunter, S.R.; Christophorou, L.G.

    1984-04-01

    The relationship between the pressure-dependent electron attachment rate constants (k/sub a/) which have been observed in 1-C 3 F 6 and in several perfluoroalkanes, and the uniform field breakdown strengths (E/N)/sub lim/ in these gases is discussed. Measurements of the pressure dependence of k/sub a/ of OCS in a buffer gas of Ar are presented and the possible pressure dependence of (E/N)/sub lim/ in OCS is discussed. Uniform field breakdown measurements have been performed in C 3 F 8 , n-C 4 F 10 , and SO 2 over a range of gas pressures (3 less than or equal to P/sub T/ less than or equal to 290 kPa) and are reported. All three molecules have been found to possess pressure-dependent (E/N)/sub lim/ values. The various types of synergistic behavior which have been observed in binary gas dielectric mixtures are summarized and discussed. A new mechanism is outlined which can explain the synergism observed in several gas mixtures where the (E/N)/sub lim/ values of the mixutres are greater than those of the individual gas constituents. Model calculations are presented which support this mechanism, and can be used to explain the pressure-dependent synergistic effects which have been reported in 1-C 3 F 6 /SF 6 gas mixture

  2. Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks.

    Science.gov (United States)

    González-Domínguez, Raúl; Mateos, Rosa María; Lechuga-Sancho, Alfonso María; González-Cortés, José Joaquín; Corrales-Cuevas, Manuel; Rojas-Cots, Juan Alberto; Segundo, Carmen; Schwarz, Mónica

    2017-09-01

    High sugar consumption elicits numerous deleterious effects on health by inducing insulin resistance, which is closely associated with the development of metabolic disorders such as obesity or type-2 diabetes. Furthermore, there is also growing evidence that caffeine may play an important role in the regulation of insulin release and the appearance of related metabolic impairments. Thus, the aim of this work was to investigate the impact of acute sugar and caffeine intake on the metabolic health status by using a metabolomic multi-platform based on the combination of flow injection mass spectrometry and ultra-high performance liquid chromatography mass spectrometry. To this end, we performed a randomized, crossover and double-blind intervention study with different soft drinks from the same brand. Numerous metabolomic changes were detected in serum samples over time after the intake of sugar-sweetened beverages, including energy-related metabolites, amino acids and lipids, thus demonstrating the intense effects provoked by acute sugar consumption on the organism during 3 h of follow-up. However, the most significant findings were observed after the co-ingestion of caffeine, which could be indicative of a synergic effect of this psychostimulant on insulin-mediated perturbations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Bactericide, Immunomodulating, and Wound Healing Properties of Transgenic Kalanchoe pinnata Synergize with Antimicrobial Peptide Cecropin P1 In Vivo

    Directory of Open Access Journals (Sweden)

    A. A. Lebedeva

    2017-01-01

    Full Text Available Procedure of manufacturing K. pinnata water extracts containing cecropin P1 (CecP1 from the formerly described transgenic plants is established. It included incubation of leaves at +4°C for 7 days, mechanical homogenization of leaves using water as extraction solvent, and heating at +70°C for inactivating plant enzymes. Yield of CecP1 (after heating and sterilizing filtration was 0.3% of total protein in the extract. The water extract of K. pinnata + CecP1 exhibits favorable effect on healing of wounds infected with S. aureus (equal to Cefazolin and with a combination of S. aureus with P. aeruginosa (better than Cefazolin. Wild-type K. pinnata extract exhibited evident microbicide activity against S. aureus with P. aeruginosa but it was substantially strengthened in K. pinnata + CecP1 extract. K. pinnata extracts (both wild-type and transgenic did not exhibit general toxicity and accelerated wound recovery. Due to immunomodulating activity, wild-type K. pinnata extract accelerated granulation of the wound bed and marginal epithelialization even better than K. pinnata + CecP1 extract. Immunomodulating and microbicide activity of K. pinnata synergizes with microbicide activity of CecP1 accelerating elimination of bacteria.

  4. Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with Fungicide Activity of Biogenic Peptide Cecropin P1

    Directory of Open Access Journals (Sweden)

    N. S. Zakharchenko

    2017-01-01

    Full Text Available Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide cecropin P1 (CecP1 have been reported. Now we report biological testing K. pinnata extracts containing CecP1 as a candidate drug for treatment of wounds infected with Candida albicans. The drug constitutes the whole juice from K. pinnata leaves (not ethanol extract sterilized with nanofiltration. A microbicide activity of CecP1 against an animal fungal pathogen in vivo was demonstrated for the first time. However, a favorable therapeutic effect of the transgenic K. pinnata extract was attributed to a synergism between the fungicide activity of CecP1 and wound healing (antiscar, revascularizing, and immunomodulating effect of natural biologically active components of K. pinnata. A commercial fungicide preparation clotrimazole eliminated C. albicans cells within infected wounds in rats with efficiency comparable to CecP1-enriched K. pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not exhibit neither wound healing activity nor remodeling of the scar matrix. Taken together, our results allow assumption that CecP1-enriched K. pinnata extracts should be considered as a candidate drug for treatment of dermatomycoses, wounds infected with fungi, and bedsores.

  5. Bactericide, Immunomodulating, and Wound Healing Properties of Transgenic Kalanchoe pinnata Synergize with Antimicrobial Peptide Cecropin P1 In Vivo.

    Science.gov (United States)

    Lebedeva, A A; Zakharchenko, N S; Trubnikova, E V; Medvedeva, O A; Kuznetsova, T V; Masgutova, G A; Zylkova, M V; Buryanov, Y I; Belous, A S

    2017-01-01

    Procedure of manufacturing K. pinnata water extracts containing cecropin P1 (CecP1) from the formerly described transgenic plants is established. It included incubation of leaves at +4°C for 7 days, mechanical homogenization of leaves using water as extraction solvent, and heating at +70°C for inactivating plant enzymes. Yield of CecP1 (after heating and sterilizing filtration) was 0.3% of total protein in the extract. The water extract of K. pinnata + CecP1 exhibits favorable effect on healing of wounds infected with S. aureus (equal to Cefazolin) and with a combination of S. aureus with P. aeruginosa (better than Cefazolin). Wild-type K. pinnata extract exhibited evident microbicide activity against S. aureus with P. aeruginosa but it was substantially strengthened in K. pinnata + CecP1 extract. K. pinnata extracts (both wild-type and transgenic) did not exhibit general toxicity and accelerated wound recovery. Due to immunomodulating activity, wild-type K. pinnata extract accelerated granulation of the wound bed and marginal epithelialization even better than K. pinnata + CecP1 extract. Immunomodulating and microbicide activity of K. pinnata synergizes with microbicide activity of CecP1 accelerating elimination of bacteria.

  6. Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with Fungicide Activity of Biogenic Peptide Cecropin P1.

    Science.gov (United States)

    Zakharchenko, N S; Belous, A S; Biryukova, Y K; Medvedeva, O A; Belyakova, A V; Masgutova, G A; Trubnikova, E V; Buryanov, Y I; Lebedeva, A A

    2017-01-01

    Previously transgenic Kalanchoe pinnata plants producing an antimicrobial peptide cecropin P1 (CecP1) have been reported. Now we report biological testing K. pinnata extracts containing CecP1 as a candidate drug for treatment of wounds infected with Candida albicans. The drug constitutes the whole juice from K. pinnata leaves (not ethanol extract) sterilized with nanofiltration. A microbicide activity of CecP1 against an animal fungal pathogen in vivo was demonstrated for the first time. However, a favorable therapeutic effect of the transgenic K. pinnata extract was attributed to a synergism between the fungicide activity of CecP1 and wound healing (antiscar), revascularizing, and immunomodulating effect of natural biologically active components of K. pinnata . A commercial fungicide preparation clotrimazole eliminated C. albicans cells within infected wounds in rats with efficiency comparable to CecP1-enriched K. pinnata extract. But in contrast to K. pinnata extract, clotrimazole did not exhibit neither wound healing activity nor remodeling of the scar matrix. Taken together, our results allow assumption that CecP1-enriched K. pinnata extracts should be considered as a candidate drug for treatment of dermatomycoses, wounds infected with fungi, and bedsores.

  7. Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

    Science.gov (United States)

    Chagas, B S; Gurgel, A P A D; Paiva Júnior, S S L; Lima, R C P; Cordeiro, M N; Moura, R R; Coelho, A V C; Nascimento, K C G; Silva Neto, J C; Crovella, S; Freitas, A C

    2017-08-17

    Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control. Our data did not show a significant association between the GSTP1 polymorphism A/G (rs1695) and any HPV-related cervical abnormalities. However, considering the use of oral contraceptives, the GSTP1 rs1695 polymorphism was associated with higher susceptibility to the development of cervical lesions in HR-HPV-infected women. Our study suggests a synergic effect of oral contraceptive use, GSTP1 polymorphisms, and HR-HPV infection in the development of cervical lesions. Together, these risk factors may induce neoplastic transformation of the cervical squamous epithelium, setting conditions for secondary genetic events leading to cervical cancer.

  8. Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity.

    Directory of Open Access Journals (Sweden)

    Sophiya Karki

    Full Text Available The zinc finger antiviral protein (ZAP is a host factor that mediates inhibition of viruses in the Filoviridae, Retroviridae and Togaviridae families. We previously demonstrated that ZAP blocks replication of Sindbis virus (SINV, the prototype Alphavirus in the Togaviridae family at an early step prior to translation of the incoming genome and that synergy between ZAP and one or more interferon stimulated genes (ISGs resulted in maximal inhibitory activity. The present study aimed to identify those ISGs that synergize with ZAP to mediate Alphavirus inhibition. Using a library of lentiviruses individually expressing more than 350 ISGs, we screened for inhibitory activity in interferon defective cells with or without ZAP overexpression. Confirmatory tests of the 23 ISGs demonstrating the largest infection reduction in combination with ZAP revealed that 16 were synergistic. Confirmatory tests of all potentially synergistic ISGs revealed 15 additional ISGs with a statistically significant synergistic effect in combination with ZAP. These 31 ISGs are candidates for further mechanistic studies. The number and diversity of the identified ZAP-synergistic ISGs lead us to speculate that ZAP may play an important role in priming the cell for optimal ISG function.

  9. The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells

    International Nuclear Information System (INIS)

    Kerl, Kornelius; Eveslage, Maria; Jung, Manfred; Meisterernst, Michael; Frühwald, Michael; Ries, David; Unland, Rebecca; Borchert, Christiane; Moreno, Natalia; Hasselblatt, Martin; Jürgens, Heribert; Kool, Marcel; Görlich, Dennis

    2013-01-01

    Rhabdoid tumors are highly aggressive malignancies affecting infants and very young children. In many instances these tumors are resistant to conventional type chemotherapy necessitating alternative approaches. Proliferation assays (MTT), apoptosis (propidium iodide/annexin V) and cell cycle analysis (DAPI), RNA expression microarrays and western blots were used to identify synergism of the HDAC (histone deacetylase) inhibitor SAHA with fenretinide, tamoxifen and doxorubicin in rhabdoidtumor cell lines. HDAC1 and HDAC2 are overexpressed in primary rhabdoid tumors and rhabdoid tumor cell lines. Targeting HDACs in rhabdoid tumors induces cell cycle arrest and apoptosis. On the other hand HDAC inhibition induces deregulated gene programs (MYCC-, RB program and the stem cell program) in rhabdoid tumors. These programs are in general associated with cell cycle progression. Targeting these activated pro-proliferative genes by combined approaches of HDAC-inhibitors plus fenretinide, which inhibits cyclinD1, exhibit strong synergistic effects on induction of apoptosis. Furthermore, HDAC inhibition sensitizes rhabdoid tumor cell lines to cell death induced by chemotherapy. Our data demonstrate that HDAC inhibitor treatment in combination with fenretinide or conventional chemotherapy is a promising tool for the treatment of chemoresistant rhabdoid tumors

  10. Gingerol Synergizes the Cytotoxic Effects of Doxorubicin against Liver Cancer Cells and Protects from Its Vascular Toxicity

    Directory of Open Access Journals (Sweden)

    Fahad A. Al-Abbasi

    2016-07-01

    Full Text Available Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic value in different pathophysiological conditions, such as malignancy. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for potential chemo-modulatory effects in addition to potential vascular protective roles with doxorubicin. Diarylheptanoids showed stronger antioxidant effects, in comparison to hydroxyphenylalkanes, as demonstrated by DPPH assay and amelioration of CCl4-induced disturbed intracellular GSH/GSSG balance. Shogaol and 4′-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells, with IC50 values ranging from 3.1 to 19.4 µM. Gingerol significantly enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7, cells decreasing its IC50s by 10- and 4-fold, respectively. Cell cycle distribution was studied using DNA cytometry. Doxorubicin alone induced cell accumulation at S-phase and G2/M-phase, while in combination with gingerol it significantly induced cell cycle arrest at the G2/M-phase. Additionally, the vascular protective effect of gingerol against doxorubicin (10 µM was examined on isolated aortic rings. Co-incubation with 6-gingerol (30 µM completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin. In conclusion, despite its relatively weak antioxidant properties, gingerol protected from DOX-induced vascular damage, apparently not through a ROS scavenging mechanism. Besides, gingerol synergized the cytotoxic effects of DOX against liver cancer cells without influencing the cellular pharmacokinetics.

  11. Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer

    Directory of Open Access Journals (Sweden)

    Jorge F.S. Ferreira

    2010-04-01

    Full Text Available Artemisia annua is currently the only commercial source of the sesquiterpene lactone artemisinin.Since artemisinin was discovered as the active component of A. annua in early 1970s, hundreds of papers have focused on the anti-parasitic effects of artemisinin and its semi-synthetic analogs dihydroartemisinin, artemether, arteether, and artesunate. Artemisinin per se has not been used in mainstream clinical practice due to its poor bioavailability when compared to its analogs. In the past decade, the work with artemisinin-based compounds has expanded to their anti-cancer properties. Although artemisinin is a major bioactive component present in the traditional Chinese herbal preparations (tea, leaf flavonoids, also present in the tea, have shown a variety of biological activities and may synergize the effects of artemisinin against malaria and cancer. However, only a few studies have focused on the potential synergistic effects between flavonoids and artemisinin. The resurgent idea that multi-component drug therapy might be better than monotherapy is illustrated by the recent resolution of the World Health Organization to support artemisinin-based combination therapies (ACT, instead of the previously used monotherapy with artemisinins. In this critical review we will discuss the possibility that artemisinin and its semi-synthetic analogs might become more effective to treat parasitic diseases (such as malaria and cancer if simultaneously delivered with flavonoids. The flavonoids present in A. annua leaves have been linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body, but also have been linked to a beneficial immunomodulatory activity in subjects afflicted with parasitic and chronic diseases.

  12. Synergizing green and gray infrastructures to increase water supply resilience in the Brazos River basin in Texas

    Science.gov (United States)

    Gao, H.; Yamazaki, D.; Finley, T.; Bohn, T. J.; Low, G.; Sabo, J. L.

    2017-12-01

    Water infrastructure lies at the heart of the challenges and opportunities of Integrated Water Resource Management (IWRM). Green infrastructure (e.g., wetlands restoration) presents an alternative to its hard-path counterpart - gray infrastructure, which often has external, economic and unmeasured ecological costs. But the science framework to prioritize green infrastructure buildout is nascent. In this study, we addressed this gap in Brazos River basin in Texas, in the context of corporate decisions to secure water supplies for various water stewardship objectives. We developed a physically-based tool to quantify the potential for wetland restoration to restore desired flows (hydrology), and a financial framework for comparing its cost-benefit with heightening an existing dam (conservation finance). Our framework has three components. First, we harnessed a topographic index (HAND) to identify the potential wetlands sites. Second, we coupled a land surface model (VIC) with a hydrodynamic model (CaMa-Flood) to investigate the effects of wetland size, location, and vegetation on hydrology. Finally, we estimated the net present value, indirect rate of return and payback period for green (wetlands) vs. gray (reservoir expansion) infrastructure. We found wetlands have more substantial impact on peak flow than baseflow. Interestingly, wetlands can improve baseflow reliability but not directly except with the largest (>400 km2) projects. Peak flow reduction volumes of wetlands if used as credits towards reservoir flood-control storage provide adequate conservation storage to deliver guaranteed reliability of baseflow. Hence, the synergy of existing dams with newly created wetlands offers a promising natural solution to increase water supply resilience, while green projects also generate revenue compared to their gray counterparts. This study demonstrates the possibility of using innovative engineering design to synergize green and gray infrastructures to convert water

  13. Synergic Adsorption–Biodegradation by an Advanced Carrier for Enhanced Removal of High-Strength Nitrogen and Refractory Organics

    KAUST Repository

    Ahmad, Muhammad

    2017-03-29

    Coking wastewater contains not only high-strength nitrogen but also toxic biorefractory organics. This study presents simultaneous removal of high-strength quinoline, carbon, and ammonium in coking wastewater by immobilized bacterial communities composed of a heterotrophic strain Pseudomonas sp. QG6 (hereafter referred as QG6), ammonia-oxidizing bacteria (AOB), and anaerobic ammonium oxidation bacteria (anammox). The bacterial immobilization was implemented with the help of a self-designed porous cubic carrier that created structured microenvironments including an inner layer adapted for anaerobic bacteria, a middle layer suitable for coaggregation of certain aerobic and anaerobic bacteria, and an outer layer for heterotrophic bacteria. By coating functional polyurethane foam (FPUF) with iron oxide nanoparticles (IONPs), the biocarrier (IONPs-FPUF) could provide a good outer-layer barrier for absorption and selective treatment of aromatic compounds by QG6, offer a conducive environment for anammox in the inner layer, and provide a mutualistic environment for AOB in the middle layer. Consequently, simultaneous nitrification and denitrification were reached with the significant removal of up to 322 mg L (98%) NH, 311 mg L (99%) NO, and 633 mg L (97%) total nitrogen (8 mg L averaged NO concentration was recorded in the effluent), accompanied by an efficient removal of chemical oxygen demand by 3286 mg L (98%) and 350 mg L (100%) quinoline. This study provides an alternative way to promote synergic adsorption and biodegradation with the help of a modified biocarrier that has great potential for treatment of wastewater containing high-strength carbon, toxic organic pollutants, and nitrogen.

  14. Surface Modification of Polyester by Nano Titanium Dioxide in Alkaline Media and Their Synergism Effect on the Fabric

    Directory of Open Access Journals (Sweden)

    V. Allahyarzadeh

    2014-01-01

    Full Text Available The effect of alkaline hydrolysis with sodium hydroxide on nano titanium dioxide (nano TiO2 adsorption was studied on polyester fabric surface as well as the influence of nano TiO2 on the alkaline hydrolysis of polyester. To do this, the polyester fabrics were treated with different concentrations of nano TiO2 and boiling sodium hydroxide solution for 1 h. The results revealed that alkaline hydrolysis reduced the weight of the fabric, which was more prominent in presence of nano TiO2. Field emission scanning electronic microscope and energy dispersive X-ray confirmed the presence of nano TiO2 on the polyester fabric surface. Increasing sodium hydroxide and nanoTiO2 concentrations led to higher loading of nano particles on the polyester fabric surface. Also, the photocatalytic activity of nano TiO2 particles on the polyester fabric was confirmed by the degradation of methylene blue as a model stain under daylight irradiation. The results indicated that increasing sodium hydroxide and nano TiO2 concentrations led to higher photocatalytic activities of the alkali-treated polyester fabrics. Further, the bending rigidity of the treated polyester fabrics decreased while the water absorption of the fabric improved. Unexpectedly, the tensile strength of the nano TiO2 treated polyester fabrics improved even with the action of alkali and surface hydrolysis that usually produce fabric with lower tensile strength. The synergism influence of nano TiO2 particles in alkali hydrolysis of polyester fabric indicated to lower weight fabrics. Overall, this treatment was considered as another useful property such as higher self-cleaning, hydrophilicity and tensile strength.

  15. Synergic catalytic effect of Ti hydride and Nb nanoparticles for improving hydrogenation and dehydrogenation kinetics of Mg-based nanocomposite

    Directory of Open Access Journals (Sweden)

    Xiujuan Ma

    2017-02-01

    Full Text Available The Mg-9.3 wt% (TiH1.971-TiH−0.7 wt% Nb nanocomposite has been synthesized by hydrogen plasma-metal reaction (HPMR approach to enhance the hydrogen sorption kinetics of Mg at moderate temperatures by providing nanosizing effect of increasing H “diffusion channels” and adding transition metallic catalysts. The Mg nanoparticles (NPs were in hexagonal shape range from 50 to 350 nm and the average size of the NPs was 177 nm. The small spherical TiH1.971, TiH and Nb NPs of about 25 nm uniformly decorated on the surface of the big Mg NPs. The Mg-TiH1.971-TiH-Nb nanocomposite could quickly absorb 5.6 wt% H2 within 5 min at 573 K and 4.5 wt% H2 within 5 min at 523 K, whereas the pure Mg prepared by HPMR could only absorb 4 and 1.5 wt% H2 at the same temperatures. TiH1.971, TiH and Nb NPs transformed into TiH2 and NbH during hydrogenation and recovered after dehydrogenation process. The apparent activation energies of the nanocomposite for hydrogenation and dehydrogenation were 45.0 and 50.7 kJ mol−1, which are much smaller than those of pure Mg NPs, 123.8 and 127.7 kJ mol−1. The improved sorption kinetics of the Mg-based nanocomposite at moderate temperatures and the small activation energy can be interpreted by the nanostructure of Mg and the synergic catalytic effects of Ti hydrides and Nb NPs.

  16. Enhanced synergism of antibiotics with zinc oxide nanoparticles against extended spectrum β-lactamase producers implicated in urinary tract infections

    International Nuclear Information System (INIS)

    Bhande, Rashmi M.; Khobragade, C. N.; Mane, R. S.; Bhande, S.

    2013-01-01

    In this study, enhanced synergistic bioactivity of zinc oxide nanoparticles (ZnO NPs) with β-lactam antibiotics were evaluated against a panel of clinically isolated extended spectrum β-lactamase producers implicated in urinary tract infections. Chemically synthesized zinc oxide nanoparticles (15 nm) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high resolution transmittance electron microscopy (HR-TEM), selective area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and UV–Visible spectrophotometry techniques. The antimicrobial potency (10 ± 0.66, 12, 11.33 ± 1.10, and 0.7 ± 0.66 mm inhibiting zone) and minimum inhibitory concentrations (80, 60, 30, 50 μg/ml) of ZnO NPs were tested separately whereas time–kill and membrane leakage assays were evaluated in combination with ZnO NPs+ cefotaxime, ampicillin, ceftriaxone, cefepime against the β-lactamase producer strains of E. coli, K. pneumoniae, S. paucimobilis, and P. aeruginosa, respectively. Time–kill curve dynamics of ZnO NPs with β-lactam antibiotics revealed enhanced bactericidal activity (50, 85, 58, 50 % fold inhibition) by delaying the exponential and stationary phases of all isolates when tested separately. Posttime–kill effect was studied on cell membrane by assaying leakage of reducing sugars (130.2, 124.7, 137, and 115.8 μg/bacterial dry weight of 1 mg (μg/mg) and proteins (15, 10, 16, 18 μg/mg). These assays revealed that membrane leakage was due to synergism of ZnO NPs+ β-lactam antibiotics which successfully damage cell membrane thereby leading to death of all ESBL producers. The results demonstrate the utilization of ZnO NPs as a potentiator of β-lactam antibiotics and suggest the possibility to use nanoparticles in a combination therapy to treat UTI.

  17. Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

    Science.gov (United States)

    Liu, Hua; Talalay, Paul

    2013-01-01

    , particularly in view of the synergism with other phytochemicals. PMID:24191056

  18. Drinking water quality and chronic kidney disease of unknown etiology (CKDu): synergic effects of fluoride, cadmium and hardness of water.

    Science.gov (United States)

    Wasana, Hewa M S; Aluthpatabendi, Dharshani; Kularatne, W M T D; Wijekoon, Pushpa; Weerasooriya, Rohan; Bandara, Jayasundera

    2016-02-01

    High prevalence of chronic kidney disease of unknown etiology (CKDu) in some regions of the world is suspected mainly due to a toxin-mediated renal failure. We examined the incidence of CKDu and potable chemical water quality in a CKDu-affected region. This region has been identified as a high-risk zone for CKDu (location: latitude: 8.3500°-9.0000°, longitude: 80.3833°-81.3000°, North Central Province, NCP, Sri Lanka) by the World Health Organization (WHO). However, within this macro-region, small pockets of CKDu non-prevalence zones do exist; notably, the residents in those pockets consume spring water. Therefore, the drinking water quality of four areas, namely high-CKDu-prevalence areas (zone I), low-CKDu-prevalence area (zone II), the CKDu-free isolated pockets (zone III) and control areas (controls) were examined for F, Al, Cd, and As, and hardness and the statistical analysis were carried out to probe possible correlations among these parameters. The fluoride and hardness concentrations of water in zone III and control areas are much lower compared to zones I and II, and the water hardness is ~61 mg/L CaCO3. In zones I and II, the harness of drinking water is ~121-180 mg/L CaCO3; however, Al, Cd and As concentrations are almost comparable and below WHO recommendations. In most of the locations in zones I and II, the F concentration in drinking water is higher than the WHO recommendations. The peculiar distribution patterns of CKDu point to a synergic effect of trace elements in water for etiology of the disease.

  19. Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

    Directory of Open Access Journals (Sweden)

    Madácsi Ramóna

    2010-06-01

    Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

  20. Folate-Hapten-Mediated Immunotherapy Synergizes with Vascular Endothelial Growth Factor Receptor Inhibitors in Treating Murine Models of Cancer.

    Science.gov (United States)

    Bandara, N Achini; Bates, Cody D; Lu, Yingjuan; Hoylman, Emily K; Low, Philip S

    2017-03-01

    The overexpression of folate receptors (FR) on many human cancers has led to the development of folate-linked drugs for the imaging and therapy of FR-expressing cancers. In a recent phase I clinical trial of late-stage renal cell carcinoma patients, folate was exploited to deliver an immunogenic hapten, fluorescein, to FR + tumor cells in an effort to render the cancer cells more immunogenic. Although >50% of the patients showed prolonged stable disease, all patients eventually progressed, suggesting that the folate-hapten immunotherapy was insufficient by itself to treat the cancer. In an effort to identify a companion therapy that might augment the folate-hapten immunotherapy, we explored coadministration of two approved cancer drugs that had been previously shown to also stimulate the immune system. We report that sunitinib and axitinib (VEGF receptor inhibitors that simultaneously mitigate immune suppression) synergize with the folate-hapten-targeted immunotherapy to reduce tumor growth in three different syngeneic murine tumor models. We further demonstrate that the combination therapy not only enhances tumor infiltration of CD4 + and CD8 + effector cells, but surprisingly reduces tumor neovasculogenesis more than predicted. Subsequent investigation of the mechanism for this unexpected suppression of neovasculogenesis revealed that it is independent of elimination of any tumor cells, but instead likely derives from a reduction in the numbers of FR + tumor-associated macrophages and myeloid-derived suppressor cells, that is, immunosuppressive cells that release significant quantities of VEGF. These data suggest that a reduction in stromal cells of myeloid origin can inhibit tumor growth by suppressing neovasculogenesis. Mol Cancer Ther; 16(3); 461-8. ©2016 AACR . ©2016 American Association for Cancer Research.

  1. Enhanced synergism of antibiotics with zinc oxide nanoparticles against extended spectrum {beta}-lactamase producers implicated in urinary tract infections

    Energy Technology Data Exchange (ETDEWEB)

    Bhande, Rashmi M., E-mail: bhanderashmi@gmail.com; Khobragade, C. N., E-mail: profcnkbt@rediffmail.com [Swami Ramanand Teerth Marathwada University, School of Life Sciences (India); Mane, R. S., E-mail: rsmane@rediffmail.com; Bhande, S., E-mail: sambhajibhande@gmail.com [Swami Ramanand Teerth Marathwada University, School of Physical Sciences (India)

    2013-01-15

    In this study, enhanced synergistic bioactivity of zinc oxide nanoparticles (ZnO NPs) with {beta}-lactam antibiotics were evaluated against a panel of clinically isolated extended spectrum {beta}-lactamase producers implicated in urinary tract infections. Chemically synthesized zinc oxide nanoparticles (15 nm) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high resolution transmittance electron microscopy (HR-TEM), selective area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and UV-Visible spectrophotometry techniques. The antimicrobial potency (10 {+-} 0.66, 12, 11.33 {+-} 1.10, and 0.7 {+-} 0.66 mm inhibiting zone) and minimum inhibitory concentrations (80, 60, 30, 50 {mu}g/ml) of ZnO NPs were tested separately whereas time-kill and membrane leakage assays were evaluated in combination with ZnO NPs+ cefotaxime, ampicillin, ceftriaxone, cefepime against the {beta}-lactamase producer strains of E. coli, K. pneumoniae, S. paucimobilis, and P. aeruginosa, respectively. Time-kill curve dynamics of ZnO NPs with {beta}-lactam antibiotics revealed enhanced bactericidal activity (50, 85, 58, 50 % fold inhibition) by delaying the exponential and stationary phases of all isolates when tested separately. Posttime-kill effect was studied on cell membrane by assaying leakage of reducing sugars (130.2, 124.7, 137, and 115.8 {mu}g/bacterial dry weight of 1 mg ({mu}g/mg) and proteins (15, 10, 16, 18 {mu}g/mg). These assays revealed that membrane leakage was due to synergism of ZnO NPs+ {beta}-lactam antibiotics which successfully damage cell membrane thereby leading to death of all ESBL producers. The results demonstrate the utilization of ZnO NPs as a potentiator of {beta}-lactam antibiotics and suggest the possibility to use nanoparticles in a combination therapy to treat UTI.

  2. A naturally occurring plant cysteine protease possesses remarkable toxicity against insect pests and synergizes Bacillus thuringiensis toxin.

    Directory of Open Access Journals (Sweden)

    Srinidi Mohan

    Full Text Available When caterpillars feed on maize (Zea maize L. lines with native resistance to several Lepidopteran pests, a defensive cysteine protease, Mir1-CP, rapidly accumulates at the wound site. Mir1-CP has been shown to inhibit caterpillar growth in vivo by attacking and permeabilizing the insect's peritrophic matrix (PM, a structure that surrounds the food bolus, assists in digestion and protects the midgut from microbes and toxins. PM permeabilization weakens the caterpillar defenses by facilitating the movement of other insecticidal proteins in the diet to the midgut microvilli and thereby enhancing their toxicity. To directly determine the toxicity of Mir1-CP, the purified recombinant enzyme was directly tested against four economically significant Lepidopteran pests in bioassays. Mir1-CP LC(50 values were 1.8, 3.6, 0.6, and 8.0 ppm for corn earworm, tobacco budworm, fall armyworm and southwestern corn borer, respectively. These values were the same order of magnitude as those determined for the Bacillus thuringiensis toxin Bt-CryIIA. In addition to being directly toxic to the larvae, 60 ppb Mir1-CP synergized sublethal concentrations of Bt-CryIIA in all four species. Permeabilization of the PM by Mir1-CP probably provides ready access to Bt-binding sites on the midgut microvilli and increases its activity. Consequently, Mir1-CP could be used for controlling caterpillar pests in maize using non-transgenic approaches and potentially could be used in other crops either singly or in combination with Bt-toxins.

  3. Synergic hypocholesterolaemic effect of n-3 PUFA and oestrogen by modulation of hepatic cholesterol metabolism in female rats.

    Science.gov (United States)

    Oh, Yuna; Jin, Youri; Park, Yongsoon

    2015-12-14

    n-3 PUFA such as EPA and DHA as well as oestrogen have been reported to decrease blood levels of cholesterol, but their underlying mechanism is unclear. The purpose of this study was to determine the effects of the combination of n-3 PUFA supplementation and oestrogen injection on hepatic cholesterol metabolism. Rats were fed a modified AIN-93G diet with 0, 1 or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and, after 1-week recovery, rats were injected with 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Supplementation with n-3 PUFA and E2 injection significantly increased the ratio of the hepatic expression of phosphorylated AMP activated protein kinase (p-AMPK):AMP activated protein kinase (AMPK) and decreased sterol regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase and proprotein convertase subtilisin/kexin type 9. Supplementation with n-3 PUFA increased hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), sterol 12α-hydroxylase (CYP8B1) and sterol 27-hydroxylase (CYP27A1); however, E2 injection decreased CYP7A1 and CYP8B1 but not CYP27A1. Additionally, E2 injection increased hepatic expression of oestrogen receptor-α and β. In conclusion, n-3 PUFA supplementation and E2 injection had synergic hypocholesterolaemic effects by down-regulating hepatic cholesterol synthesis (n-3 PUFA and oestrogen) and up-regulating bile acid synthesis (n-3 PUFA) in ovariectomised rats.

  4. Synergism of the method of characteristic, R-functions and diffusion solution for accurate representation of 3D neutron interactions in research reactors using the AGENT code system

    International Nuclear Information System (INIS)

    Hursin, Mathieu; Xiao Shanjie; Jevremovic, Tatjana

    2006-01-01

    This paper summarizes the theoretical and numerical aspects of the AGENT code methodology accurately applied for detailed three-dimensional (3D) multigroup steady-state modeling of neutron interactions in complex heterogeneous reactor domains. For the first time we show the fine-mesh neutron scalar flux distribution in Purdue research reactor (that was built over forty years ago). The AGENT methodology is based on the unique combination of the three theories: the method of characteristics (MOC) used to simulate the neutron transport in two-dimensional (2D) whole core heterogeneous calculation, the theory of R-functions used as a mathematical tool to describe the true geometry and fuse with the MOC equations, and one-dimensional (1D) higher-order diffusion correction of 2D transport model to account for full 3D heterogeneous whole core representation. The synergism between the radial 2D transport and the 1D axial transport (to take into account the axial neutron interactions and leakage), called the 2D/1D method (used in DeCART and CHAPLET codes), provides a 3D computational solution. The unique synergism between the AGENT geometrical algorithm capable of modeling any current or future reactor core geometry and 3D neutron transport methodology is described in details. The 3D AGENT accuracy and its efficiency are demonstrated showing the eigenvalues, point-wise flux and reaction rate distributions in representative reactor geometries. The AGENT code, comprising this synergism, represents a building block of the computational system, called the virtual reactor. Its main purpose is to perform 'virtual' experiments and demonstrations of various mainly university research reactor experiments

  5. Synergic phototoxic effect of visible light or Gallium-Arsenide laser in the presence of different photo-sensitizers on Porphyromonas gingivalis and Fusobacterium nucleatum.

    Science.gov (United States)

    Ghanbari, Habibollah; Mousavi, Seyed Amir; Forouzanfar, Ali; Zakeri, Mahdi; Shafaee, Hooman; Shahnaseri, Shirin

    2015-01-01

    According to the development of resistant strains of pathogenic bacteria following treatment with antimicrobial chemotherapeutic agents, alternative approaches such as lethal photosensitization are being used. The aim of this study was to evaluate the effect of visible light and laser beam radiation in conjugation with three different photosensitizers on the survival of two main periodontopathogenic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum in different exposure periods. In this in vitro prospective study, strains of P. gingivalis and F. nucleatum. were exposed to visible light at wavelengths of 440 nm and diode laser light, Gallium-Arsenide, at wavelength of 830 nm in the presence of a photosensitizer (erythrosine, curcuma, or hydrogen peroxide). They were exposed 1-5 min to each light. Each experiment was repeated 3 times for each strain of bacteria. Data were analyzed by two-ways ANOVA and least significant difference post-hoc tests. P < 0.05 was considered as significant. After 4 days the colonies were counted. Viability of P. gingivalis was reduced 10% and 20% subsequent to exposure to visible light and diode laser, respectively. The values were 65% and 75% for F. nucleatum in a period of 5-min, respectively. Exposure to visible light or laser beam in conjugation with the photosensitizers suspension caused significant reduction in the number of P. gingivalis in duration of 5-min, suggesting a synergic phototoxic effect. However, the survival rate of F. nucleatum following the exposure to laser with hydrogen peroxide, erythrosine and rhizome of Curcuma longa (curcumin) after 5-min was 10%, 20% and 90% respectively. Within the limitations of this study, the synergic phototoxic effect of visible light in combination with each of the photosensitizers on P. gingivalis and F. nucleatum. However, the synergic phototoxic effect of laser exposure and hydrogen peroxide and curcumin as photosensitizers on F. nucleatum was not shown.

  6. Liquid-liquid extraction and separation of VIII group elements, especially ruthenium, by synergic combinations or aromatic polyimines and micellar cationic exchangers

    International Nuclear Information System (INIS)

    Vitart, X.

    1991-01-01

    This thesis aims to characterize and to quantify the chemical equilibria involved in d-elements liquid-liquid extraction systems, especially elements belonging to the VIII group (Fe, Ni, Co, Ru, Rh, Pd, Pt). These systems are composed of synergic combination of aromatic polyimines and micellar cationic exchangers. Substitutions are first performed in aqueous acidic media by aromatic polyimines; then extractions are operated using micellic canionic exchangers. Chemical equilibria, selectivity effects, especially those due to ion-pair formations, kinetics, extractant behaviour are analysed and quantified [fr

  7. Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1.

    Science.gov (United States)

    Lee, Jong Doo; Choi, Min-Ah; Ro, Simon Weonsang; Yang, Woo Ick; Cho, Arthur E H; Ju, Hye-Lim; Baek, Sinhwa; Chung, Sook In; Kang, Won Jun; Yun, Mijin; Park, Jeon Han

    2016-01-01

    Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a

  8. Stable Pseudohyphal Growth in Budding Yeast Induced by Synergism between Septin Defects and Altered MAP-kinase Signaling.

    Science.gov (United States)

    Kim, Junwon; Rose, Mark D

    2015-12-01

    Upon nutrient limitation, budding yeasts like Saccharomyces cerevisiae can be induced to adopt alternate filament-like growth patterns called diploid pseudohyphal or invasive haploid growth. Here, we report a novel constitutive pseudohyphal growth state, sharing some characteristics with classic forms of filamentous growth, but differing in crucial aspects of morphology, growth conditions and genetic regulation. The constitutive pseudohyphal state is observed in fus3 mutants containing various septin assembly defects, which we refer to as sadF growth (septin assembly defect induced filamentation) to distinguish it from classic filamentation pathways. Similar to other filamentous states, sadF cultures comprise aggregated chains of highly elongated cells. Unlike the classic pathways, sadF growth occurs in liquid rich media, requiring neither starvation nor the key pseudohyphal proteins, Flo8p and Flo11p. Moreover sadF growth occurs in haploid strains of S288C genetic background, which normally cannot undergo pseudohyphal growth. The sadF cells undergo highly polarized bud growth during prolonged G2 delays dependent on Swe1p. They contain septin structures distinct from classical pseudo-hyphae and FM4-64 labeling at actively growing tips similar to the Spitzenkörper observed in true hyphal growth. The sadF growth state is induced by synergism between Kss1p-dependent signaling and septin assembly defects; mild disruption of mitotic septins activates Kss1p-dependent gene expression, which exacerbates the septin defects, leading to hyper-activation of Kss1p. Unlike classical pseudo-hyphal growth, sadF signaling requires Ste5, Ste4 and Ste18, the scaffold protein and G-protein β and γ subunits from the pheromone response pathway, respectively. A swe1 mutation largely abolished signaling, breaking the positive feedback that leads to amplification of sadF signaling. Taken together, our findings show that budding yeast can access a stable constitutive pseudohyphal growth

  9. Interactive effect of light colours and temporal synergism of circadian neural oscillations in reproductive regulation of Japanese quail.

    Science.gov (United States)

    Yadav, Suneeta; Chaturvedi, Chandra Mohini

    2016-09-01

    Avian literature reports the modulation of 'photoperiodic gonadal responses' by the temporal phase relation of serotonergic and dopaminergic oscillations in Japanese quail. But, the modulation of 'light colour responses' by the temporal synergism of neural oscillations is not yet known. Hence the present study was designed to investigate the interaction of the light colour (blue, red) and the phase relation of neural oscillations in the reproductive regulation of Japanese quail. Three week old male Japanese quail were divided into two groups and maintained under a long day length condition (16L:8D) and were exposed to a 30 lux intensity of blue LED (light emitting diode) (B LED) and a red LED light (R LED). At the age of 15.5weeks, quail of one subgroup of B LED were injected with serotonin precursor (5-HTP) and dopamine precursor (l-DOPA) 12hrs apart (B LED+12-hr) and those of the R LED group were injected with the same drugs (5mg/100g body weight over a period of thirteen days) but 8hrs apart (R LED+8-hr). The remaining subgroups of both the light colour groups (B LED & R LED) received normal saline twice daily and served as controls. Cloacal gland volume was recorded weekly until 35.5weeks of age when the study was terminated and reproductive parameters (testicular volume, GSI, seminiferous tubule diameter and plasma testosterone) were assessed. Results indicate that the 8-hr temporal phase relation of neural oscillations suppresses reproductive activity even during the photosensitive phase of the red light exposed quail (R LED+8-hr) compare to the R LED controls. On the other hand, the 12-hr temporal phase relation stimulates the gonadal development of the B LED+12-hr quail compared to the B LED controls which after completing one cycle entered into a regressive phase and remained sexually quiescent. These experiments suggest that the temporal phase relations of circadian neural oscillations, in addition to modulating the classical photoperiodic responses, may

  10. Pharmacological synergism of bee venom and melittin with antibiotics and plant secondary metabolites against multi-drug resistant microbial pathogens.

    Science.gov (United States)

    Al-Ani, Issam; Zimmermann, Stefan; Reichling, Jürgen; Wink, Michael

    2015-02-15

    The goal of this study was to investigate the antimicrobial activity of bee venom and its main component, melittin, alone or in two-drug and three-drug combinations with antibiotics (vancomycin, oxacillin, and amikacin) or antimicrobial plant secondary metabolites (carvacrol, benzyl isothiocyanate, the alkaloids sanguinarine and berberine) against drug-sensitive and antibiotic-resistant microbial pathogens. The secondary metabolites were selected corresponding to the molecular targets to which they are directed, being different from those of melittin and the antibiotics. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were evaluated by the standard broth microdilution method, while synergistic or additive interactions were assessed by checkerboard dilution and time-kill curve assays. Bee venom and melittin exhibited a broad spectrum of antibacterial activity against 51 strains of both Gram-positive and Gram-negative bacteria with strong anti-MRSA and anti-VRE activity (MIC values between 6 and 800 µg/ml). Moreover, bee venom and melittin showed significant antifungal activity (MIC values between 30 and 100 µg/ml). Carvacrol displayed bactericidal activity, while BITC exhibited bacteriostatic activity against all MRSA and VRE strains tested (reference strains and clinical isolates), both compounds showed a remarkable fungicidal activity with minimum fungicidal concentration (MFC) values between 30 and 200 µg/ml. The DNA intercalating alkaloid sanguinarine showed bactericidal activity against MRSA NCTC 10442 (MBC 20 µg/ml), while berberine exhibited bacteriostatic activity against MRSA NCTC 10442 (MIC 40 µg/ml). Checkerboard dilution tests mostly revealed synergism of two-drug combinations against all the tested microorganisms with FIC indexes between 0.24 and 0.50, except for rapidly growing mycobacteria in which combinations exerted an additive effect (FICI = 0.75-1). In time-kill assays all three

  11. From additivity to synergism

    DEFF Research Database (Denmark)

    Ritz, Christian; Streibig, Jens Carl

    2014-01-01

    Interest in synergistic or antagonistic effects through mixture experiments has grown immensely over the past two decades, not the least within in pharmacology and toxicology. Several definitions of reference models exist; one commonly used reference model is concentration or dose addition, which...... assumes compounds, when administrated simultaneously, do not interfere with each other at the site of action. We focus on statistical modelling that allows evaluation of dose addition. We will describe several statistical approaches that are suitable for analysis mixture data where synergistic...... or antagonistic effects may be present. The statistical models are defined and explained and some of the approaches exemplified. Code in open-source software is provided....

  12. Synergism and radiological protection

    International Nuclear Information System (INIS)

    1978-01-01

    The German original of this English translation was published by the German Federal Minsitry of the Interior in the Bundesanzeiger No.212 of November 11, 1977. If there are any differences between the German original and this English translation the version as published in the German original should be consulted. (orig.) [de

  13. Synergism in anticorrosive paints

    Indian Academy of Sciences (India)

    CONICET–CICPBA): Centro de Investigación y Desarrollo en Tecnología de Pinturas, Calle 52e/121 y 122, (B1900AYB), La Plata 1900, Argentina; Universidad Nacional de La Plata, La Plata 1900, Argentina ...

  14. Synergism in anticorrosive paints

    Indian Academy of Sciences (India)

    very good results. Nowadays, together with zinc phosphate, zinc molybdophosphate is one of the non-lead, non-chrome anticorrosive pigments in the market. The objective of this research was to study the syner- gistic behaviour between a first-generation phosphate pig- ment, a 'complementary' pigment (zinc oxide) and ...

  15. Synergic and conflicting issues in planning underground use to produce energy in densely populated countries, as Italy

    International Nuclear Information System (INIS)

    Quattrocchi, Fedora; Boschi, Enzo; Spena, Angelo; Buttinelli, Mauro; Cantucci, Barbara; Procesi, Monia

    2013-01-01

    Highlights: ► In densely populated countries, the public need a synergic approach to produce low-carbon energy. ► The paper is mapping coexistent and different underground technologies to produce low-GHG energy. ► The paper calculate Energy Density Potential in Land – EDPL in terms of [GW h/ha/year]. ► Draw-plate technologies platforms (EU-ZEP, etc.) should merge using underground together. ► Synergies among the different uses of deep underground (up to 5000 m) jointing the energy lobbies. -- Abstract: In densely populated countries there is a growing and compelling need to use underground for different and possibly coexisting technologies to produce “low carbon” energy. These technologies include (i) clean coal combustion merged with CO 2 Capture and Storage (CCS); (ii) last-generation nuclear power or, in any case, safe nuclear wastes disposal, both “temporary” and “geological” somewhere in Europe (at least in one site): Nuclear wastes are not necessarily associated to nuclear power plants; (iii) safe natural gas (CH 4 ) reserves to allow consumption also when the foreign pipelines are less available or not available for geopolitical reasons and (iv) “low-space-consuming” renewables in terms of Energy Density Potential in Land (EDPL measured in [GW h/ha/year]) as geothermics. When geothermics is exploited as low enthalpy technology, the heat/cool production could be associated, where possible, to increased measures of “building efficiency”, low seismic risks building reworking and low-enthalpy heat managing. This is undispensable to build up “smart cities”. In any case the underground geological knowledge is prerequisite. All these technologies have been already proposed and defined by the International Energy Agency (IEA) Road Map 2009 as priorities for worldwide security: all need to use underground in a rational and safe manner. The underground is not renewable in most of case histories [10,11]. IEA recently matched and

  16. Synthesis, characterization, microbiological evaluation, genotoxicity and synergism tests of new nano silver complexes with sulfamoxole: X-ray diffraction of [Ag2(SMX)2]·DMSO.

    Science.gov (United States)

    Velluti, Francesca; Mosconi, Natalia; Acevedo, Ana; Borthagaray, Graciela; Castiglioni, Jorge; Faccio, Ricardo; Back, Davi Fernando; Moyna, Guillermo; Rizzotto, Marcela; Torre, María H

    2014-12-01

    The synthesis and microbiological evaluation of two new Ag(I) complexes with sulfamoxole (SMX), [Ag2(SMX)2]·H2O and [Ag4(SCN)3(SMX)]·H2O are described. Both were characterized by elemental analysis, thermogravimetry, powder and single crystal X-ray diffraction, NMR, Raman and experimental and theoretical IR spectroscopies. Their antibacterial and antifungal properties were evaluated by agar and broth dilution assays, respectively. In addition, synergism tests for Pseudomonas aeruginosa were performed, and genotoxicity studies were carried out employing the Allium cepa test. Both complexes displayed good activity against Escherichia coli, Staphylococcus aureus, P. aeruginosa, and 10 fungi strains, with lower minimum inhibitory concentrations (MICs) than that of free SMX in all cases. The nanometrical crystallite particle size determined from XRPD, DLS and TEM might explain the good microbiological activity in spite of the low solubility of both complexes. The fractional inhibitory concentration (FIC) calculated from the P. aeruginosa test data indicated that the activity of the complexes is not due to synergism of the free components in the concentration ratios studied. Moreover, none of the complexes displayed cytotoxic effects on onions in the concentration range tested, and chromosome aberrations were not observed. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Synergic effect of the TiO2-CeO2 nanoconjugate system on the band-gap for visible light photocatalysis

    International Nuclear Information System (INIS)

    Contreras-García, M.E.; García-Benjume, M. Lorena; Macías-Andrés, Víctor I.; Barajas-Ledesma, E.; Medina-Flores, A.; Espitia-Cabrera, M.I.

    2014-01-01

    Graphical abstract: - Highlights: • Nanostructured TiO 2 -CeO 2 films are successfully synthesized by combining of sputtering and electrophoresis methods. • Synergic effect of CeO 2 on TiO 2 band gap was demonstrated, CeO 2 diminishes it from 3.125 to 2.74. • Morphologic characterization of the nanoconjugate TiO 2 -CeO 2 films by different microscopy techniques. - Abstract: The TiO 2 -CeO 2 photocatalytic system in films is proposed here, in order to obtain photocatalytic systems that can be excited by solar light. The films were obtained through the electrophoretic deposition (EPD) of TiO 2 -CeO 2 gel on sputtered Ti Corning glass substrates. The synergic effect of CeO 2 in TiO 2 films was analyzed as a function of the optical band gap reduction at different concentrations (1, 5, 10, and 15 mol%). The effect of two thermal treatments was also evaluated. The lowest band gap value was obtained for the sample with 5 mol% ceria that was thermally treated at 700 °C. The nanostructured films were characterized by Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high angle annular dark field (HAADF), high resolution transmission electron microscopy (HRTEM), and atomic force microscopy (AFM). The nanocomposites were formed by TiO 2 and CeO 2 nanoparticles in the anatase and fluorite type phases, respectively

  18. Investigation of the synergic effect of some neutral organophosphoric compounds on the extraction of uranium from phosphoric acid solutions by D1-(2-Ethyl Hexyl) phosphoric acid

    International Nuclear Information System (INIS)

    Stas, J.; Khorfan, S.; Koudsi, Y.

    1998-05-01

    The extraction of uranium (VI) from pure phosphoric acid media by D2EHPA/Kerosene has been studied. The mechanism of the extraction was found as follows: The logarithm of the equilibrium constant of the extraction (LogKex) was found (3.06), (3.32), (3.24), (3.3) for the following phosphoric acid concentrations respectively (1), (2), (3), (4) Mol/1, and the enthalpy change DELTA H was found (-100.68 kj/mol). (-76 kj/mol) for (1), (2) mol/1 phosphoric acid concentrations. The synergic effect of TOPO, TBP, and TBPI with DEHPA have been studied during the extraction of uranium from pure phosphoric acid and Syrian commercial phosphoric acid. The synergic effect increases as follows: TBP< TBPI<< TOPO (In pure phosphoric acid), TBPI approx TBP<< TOPO (In Syrian commercial phosphoric acid). The difficulty of extracting uranium (VI) from Syrian commercial phosphoric acid in comparison with pure phosphoric acid is due to the presence of several impurities capable of complexing uranium, and a small amounts of solid and organic matters, all these are factors which reduce the distribution coefficient of uranium. (Author)

  19. Synergism of coumarins from the Chinese drug Zanthoxylum nitidum with antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, Guo-Ying; Wang, Chun-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

    2016-12-15

    Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious therapeutic challenge in current clinic and new drug development. Natural coumarins have diverse bioactivities and the potential of resistance modifying effects. This study is to present in-depth evaluations of in vitro antimicrobial activities of four natural coumarins 5-geranyloxy-7-methoxycoumarin (Gm, 1), (5,7-dimethoxy-8-prenyloxycoumarin (artanin, Ar, 2)), isopimpinellin (Is, 3) and phellopterin (Ph, 4) from Zanthoxylum nitidum (Roxb.) DC. (Rutaceae) extracts, focusing on their potential restoration the activity of conventional antibacterial agents against clinical MRSA strains. Bioactivity-guided fractionation and spectral analyses were used to isolate the coumarins and identify the structures, respectively. The double broth microdilution method was used to assay the coumarins' alone activity. The classic checkerboard microdilution and dynamic time-killing methods were used to evaluate combinatory effects. The four plant coumarins Gm (1), Ar (2), Is (3) and Ph (4) were isolated and identified from Z. nitidum extracts. Coumarins 1-4 displayed promising inhibition against both MSSA and MRSA with minimal inhibitory concentrations (MICs) of 8-64µg/ml, but very weak against Gram-negative pathogen and yeast with MICs of 256 to ≥1024µg/ml. The geranyloxy and prenyloxy substitutions showed to be more active than the methoxy substitution on the coumarin skeletons. 1-4 also showing different extent of synergism with a total of eight conventional antibacterial agents, i.e. chloramphenicol (CL), gentamicin (CN), fosfomycin (FF), levofloxacin (LE), minocycline (MI), piperacillin/tazobactam (P/T), teicoplanin (TE) and vancomycin (VA) against ten clinical MRSA strains. Four to ten of the tested MRSA strains showed bacteriostatic synergy in the eleven combinations. The anti-MRSA modifying effects were related to different arrangement in the combinations with fractional inhibitory concentration indices

  20. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

    Science.gov (United States)

    Nonogaki, Katsunori; Kaji, Takao

    2015-12-01

    Pharmacologic stimulation of serotonin 5-HT4 receptors increased plasma active glucagon-like-peptide-1 (GLP-1) levels independent of feeding, and that pharmacologic stimulation of 5-HT4 receptors and pharmacologic inhibition of dipeptidyl peptidase-4 exerted synergic effects on plasma active GLP-1 levels and glucose tolerance in mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Enhanced vitamin B12 production in an innovative lupin tempeh is due to synergic effects of Rhizopus and Propionibacterium in cofermentation.

    Science.gov (United States)

    Signorini, Camilla; Carpen, Aristodemo; Coletto, Luigi; Borgonovo, Gigliola; Galanti, Elisabetta; Capraro, Jessica; Magni, Chiara; Abate, Ambra; Johnson, Stuart K; Duranti, Marcello; Scarafoni, Alessio

    2017-10-18

    Fermentation represents a valuable and cost-effective approach for food stabilisation and nutritional improvement. Tempeh is an example of soybean solid-state fermentation. In this work, we investigated the possibility of producing a tempeh analogue containing high amounts of vitamin B12 using seeds of three different species of the legume lupin, namely Lupinus albus, L. angustifolius and L. mutabilis, with Rhizopus oligosporus and Propionibacterium freudenreichii cofermentation. Synergic effects of Rhizopus and Propionibacterium in increasing vitamin B12 up to 1230 ng/g dw was observed. These findings indicate that this cofermentation can improve lupin nutritional quality and safety to provide a tempeh analogue with added value for vegan and vegetarian communities and low-income populations. The level of potentially toxic lupin alkaloids was also monitored during the tempeh preparation.

  2. Reinforced plaster by means of the synergic action between concrete additives (superfluidifiers, fluidiflers and airing-plasticizers and E glass fibres

    Directory of Open Access Journals (Sweden)

    del Río Merino, M.

    2000-12-01

    Full Text Available Through the analysis of the different compounds (plaster + additives + E glass fibres we pretend to demostrate that a synergic action is present between certain concrete additives (superfluidifiers, fluidiflers, and airingplasticizers and E glass fibre, on the basis of the flection resistance of plaster matrix based compound materials.

    Mediante el análisis de diferentes compuestos (escayola + aditivos + fibras de vidrio E se pretende demostrar que existe una acción sinérgica entre ciertos aditivos del hormigón (superfluidificantes, fluidificantes y aireantes-plastificantes y los refuerzos a base de fibras de vidrio E, sobre la resistencia a flexión de los materiales compuestos de matriz principal escayola.

  3. Factors influencing the synergism between cobalt-60 gamma radiation and 13kHz ultrasound of the bacterium Escherichia coli B

    International Nuclear Information System (INIS)

    Crundell, M.J.

    1982-04-01

    A detailed description is given of the level of synergism observed using the bacterium Escherichia coli B when the dose and dose rate of both ultrasound and gamma radiation were varied. As an essential pre-requisite, techniques for the measurement of these parameters were developed. Prior to the main investigation, a systematic study of the dose rate effects of the separate irradiations was made so that any anomalous behaviour could be investigated as regards the synergistic effect. The study led to a model for the synergistic effect being proposed in order to explain the observed behaviour. This model was tested further by a series of experiments in which recovery after sonication or gamma irradiation was compared. (author)

  4. A physical mechanism to explain the delivery of chemical penetration enhancers into skin during transdermal sonophoresis - Insight into the observed synergism.

    Science.gov (United States)

    Polat, Baris E; Deen, William M; Langer, Robert; Blankschtein, Daniel

    2012-03-10

    The synergism between low-frequency sonophoresis (LFS) and chemical penetration enhancers (CPEs), especially surfactants, in transdermal enhancement has been investigated extensively since this phenomenon was first observed over a decade ago. In spite of the identifying that the origin of this synergism is the increased penetration and subsequent dispersion of CPEs in the skin in response to LFS treatment, to date, no mechanism has been directly proposed to explain how LFS induces the observed increased transport of CPEs. In this study, we propose a plausible physical mechanism by which the transport of all CPEs is expected to have significantly increased flux into the localized-transport regions (LTRs) of LFS-treated skin. Specifically, the collapse of acoustic cavitation microjets within LTRs induces a convective flux. In addition, because amphiphilic molecules preferentially adsorb onto the gas/water interface of cavitation bubbles, amphiphiles have an additional adsorptive flux. In this sense, the cavitation bubbles effectively act as carriers for amphiphilic molecules, delivering surfactants directly into the skin when they collapse at the skin surface as cavitation microjets. The flux equations derived for CPE delivery into the LTRs and non-LTRs during LFS treatment, compared to that for untreated skin, explain why the transport of all CPEs, and to an even greater extent amphiphilic CPEs, is increased during LFS treatment. The flux model is tested with a non-amphiphilic CPE (propylene glycol) and both nonionic and ionic amphiphilic CPEs (octyl glucoside and sodium lauryl sulfate, respectively), by measuring the flux of each CPE into untreated skin and the LTRs and non-LTRs of LFS-treated skin. The resulting data shows very good agreement with the proposed flux model. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Synergic effect of the TiO{sub 2}-CeO{sub 2} nanoconjugate system on the band-gap for visible light photocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Contreras-García, M.E. [Instituto de Investigaciones Metalúrgicas, edificio “U”, Ciudad Universitaria, Universidad Michoacana de San Nicolás de Hidalgo, C.P. 58060, Morelia, Michoacán (Mexico); García-Benjume, M. Lorena, E-mail: lbenjume@yahoo.com [Instituto de Investigaciones Metalúrgicas, edificio “U”, Ciudad Universitaria, Universidad Michoacana de San Nicolás de Hidalgo, C.P. 58060, Morelia, Michoacán (Mexico); Macías-Andrés, Víctor I. [Instituto de Investigaciones Metalúrgicas, edificio “U”, Ciudad Universitaria, Universidad Michoacana de San Nicolás de Hidalgo, C.P. 58060, Morelia, Michoacán (Mexico); Barajas-Ledesma, E. [Universidad de La Ciénega del Estado de Michoacán de Ocampo, Avenida Universidad 3000, C.P. 59000, Sahuayo, Michoacán (Mexico); Medina-Flores, A. [Instituto de Investigaciones Metalúrgicas, edificio “U”, Ciudad Universitaria, Universidad Michoacana de San Nicolás de Hidalgo, C.P. 58060, Morelia, Michoacán (Mexico); Espitia-Cabrera, M.I. [Facultad de Ingeniería Química, edificio “M”, Ciudad Universitaria, Universidad Michoacana de San Nicolás de Hidalgo, C.P. 58060, Morelia, Michoacán (Mexico)

    2014-04-01

    Graphical abstract: - Highlights: • Nanostructured TiO{sub 2}-CeO{sub 2} films are successfully synthesized by combining of sputtering and electrophoresis methods. • Synergic effect of CeO{sub 2} on TiO{sub 2} band gap was demonstrated, CeO{sub 2} diminishes it from 3.125 to 2.74. • Morphologic characterization of the nanoconjugate TiO{sub 2}-CeO{sub 2} films by different microscopy techniques. - Abstract: The TiO{sub 2}-CeO{sub 2} photocatalytic system in films is proposed here, in order to obtain photocatalytic systems that can be excited by solar light. The films were obtained through the electrophoretic deposition (EPD) of TiO{sub 2}-CeO{sub 2} gel on sputtered Ti Corning glass substrates. The synergic effect of CeO{sub 2} in TiO{sub 2} films was analyzed as a function of the optical band gap reduction at different concentrations (1, 5, 10, and 15 mol%). The effect of two thermal treatments was also evaluated. The lowest band gap value was obtained for the sample with 5 mol% ceria that was thermally treated at 700 °C. The nanostructured films were characterized by Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), high angle annular dark field (HAADF), high resolution transmission electron microscopy (HRTEM), and atomic force microscopy (AFM). The nanocomposites were formed by TiO{sub 2} and CeO{sub 2} nanoparticles in the anatase and fluorite type phases, respectively.

  6. mTOR inhibitors suppress homologous recombination repair and synergize with PARP inhibitors via regulating SUV39H1 in BRCA-proficient triple-negative breast cancer

    Science.gov (United States)

    Mo, Wei; Liu, Qingxin; Lin, Curtis Chun-Jen; Dai, Hui; Peng, Yang; Liang, Yulong; Peng, Guang; Meric-Bernstam, Funda; Mills, Gordon B.; Li, Kaiyi; Lin, Shiaw-Yih

    2016-01-01

    Purpose Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and has the worst outcome among all subtypes of breast cancers. Although PARP inhibitors represent a promising treatment in TNBC with BRCA1/BRCA2 mutations, there is great interest in identifying drug combinations that can extend the utility of PARP inhibitors to a majority of TNBC patients with wild-type BRCA1/BRCA2. Here we explored whether mTOR inhibitors, through modulating homologous recombination (HR) repair, would provide therapeutic benefit in combination with PARP inhibitors in preclinical models of BRCA-proficient TNBC. Experimental Design We have studies the effects of mTOR inhibitors on HR repair following DNA double-strand breaks (DSBs). We further demonstrated the in vitro and in vivo activities of combined treatment of mTOR inhibitors with PARP inhibitors in BRCA-proficient TNBC. Moreover, microarray analysis and rescue experiments were employed to investigate the molecular mechanisms of action. Results We found that mTOR inhibitors significantly suppressed HR repair in two BRCA-proficient TNBC cell lines. mTOR inhibitors and PARP inhibitors in combination exhibited strong synergism against these TNBC cell lines. In TNBC xenografts, we observed enhanced efficacy of everolimus in combination with talazoparib (BMN673) compared with either drug alone. We further identified through microarray analysis and by rescue assays that mTOR inhibitors suppressed HR repair and synergized with PARP inhibitors through regulating the expression of SUV39H1 in BRCA-proficient TNBCs. Conclusions Collectively, these findings strongly suggest that combining mTOR inhibitors and PARP inhibitors would be an effective therapeutic approach to treat BRCA-proficient TNBC patients. PMID:26546619

  7. Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models

    Directory of Open Access Journals (Sweden)

    María Virtudes Céspedes

    2016-12-01

    Full Text Available We explored whether the combination of lurbinectedin (PM01183 with the antimetabolite gemcitabine could result in a synergistic antitumor effect in pancreatic ductal adenocarcinoma (PDA mouse models. We also studied the contribution of lurbinectedin to this synergism. This drug presents a dual pharmacological effect that contributes to its in vivo antitumor activity: (i specific binding to DNA minor grooves, inhibiting active transcription and DNA repair; and (ii specific depletion of tumor-associated macrophages (TAMs. We evaluated the in vivo antitumor activity of lurbinectedin and gemcitabine as single agents and in combination in SW-1990 and MIA PaCa-2 cell-line xenografts and in patient-derived PDA models (AVATAR. Lurbinectedin-gemcitabine combination induced a synergistic effect on both MIA PaCa-2 [combination index (CI=0.66] and SW-1990 (CI=0.80 tumor xenografts. It also induced complete tumor remissions in four out of six patient-derived PDA xenografts. This synergism was associated with enhanced DNA damage (anti-γ-H2AX, cell cycle blockage, caspase-3 activation and apoptosis. In addition to the enhanced DNA damage, which is a consequence of the interaction of the two drugs with the DNA, lurbinectedin induced TAM depletion leading to cytidine deaminase (CDA downregulation in PDA tumors. This effect could, in turn, induce an increase of gemcitabine-mediated DNA damage that was especially relevant in high-density TAM tumors. These results show that lurbinectedin can be used to develop ‘molecularly targeted’ combination strategies.

  8. Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models

    Science.gov (United States)

    Céspedes, María Virtudes; Guillén, María José; López-Casas, Pedro Pablo; Sarno, Francesca; Gallardo, Alberto; Álamo, Patricia; Cuevas, Carmen; Hidalgo, Manuel; Galmarini, Carlos María; Allavena, Paola; Avilés, Pablo; Mangues, Ramón

    2016-01-01

    ABSTRACT We explored whether the combination of lurbinectedin (PM01183) with the antimetabolite gemcitabine could result in a synergistic antitumor effect in pancreatic ductal adenocarcinoma (PDA) mouse models. We also studied the contribution of lurbinectedin to this synergism. This drug presents a dual pharmacological effect that contributes to its in vivo antitumor activity: (i) specific binding to DNA minor grooves, inhibiting active transcription and DNA repair; and (ii) specific depletion of tumor-associated macrophages (TAMs). We evaluated the in vivo antitumor activity of lurbinectedin and gemcitabine as single agents and in combination in SW-1990 and MIA PaCa-2 cell-line xenografts and in patient-derived PDA models (AVATAR). Lurbinectedin-gemcitabine combination induced a synergistic effect on both MIA PaCa-2 [combination index (CI)=0.66] and SW-1990 (CI=0.80) tumor xenografts. It also induced complete tumor remissions in four out of six patient-derived PDA xenografts. This synergism was associated with enhanced DNA damage (anti-γ-H2AX), cell cycle blockage, caspase-3 activation and apoptosis. In addition to the enhanced DNA damage, which is a consequence of the interaction of the two drugs with the DNA, lurbinectedin induced TAM depletion leading to cytidine deaminase (CDA) downregulation in PDA tumors. This effect could, in turn, induce an increase of gemcitabine-mediated DNA damage that was especially relevant in high-density TAM tumors. These results show that lurbinectedin can be used to develop ‘molecularly targeted’ combination strategies. PMID:27780828

  9. Protease-Sensitive Inhibitory Activity of Cell-free Supernatant of Lactobacillus crispatus 156 Synergizes with Ciprofloxacin, Moxifloxacin and Streptomycin Against Pseudomonas aeruginosa: An In Vitro Study.

    Science.gov (United States)

    Kaur, Sukhraj; Sharma, Preeti

    2015-06-01

    Ciprofloxacin and streptomycin are frequently prescribed for the treatment of medical conditions originating due to infection by Pseudomonas aeruginosa. However, fluoroquinolone administration has been linked to the outgrowth of Clostridium difficile pathogen, especially in immunocompromised patients. Secondly, frequent administration of antibiotics may lead to development of resistance in the pathogens. Thus, there is a need to explore innovative adjunct therapies to lower the therapeutic doses of the antibiotics. Herein, we evaluated the synergism, if any, between conventional antibiotics and the cell-free supernatant (CFS) of vaginal Lactobacillus crispatus 156 against P. aeruginosa MTCC 741. L. crispatus 156 was isolated from the human vaginal tract, and its CFS had broad-spectrum antimicrobial activity against various Gram-positive and Gram-negative pathogens, including P. aeruginosa. The inhibitory substance present in the CFS completely lost its activity after treatment with proteinases and was resistant to temperatures up to 80 °C and pH ranging from 2 to 6. The cumulative production of the inhibitory substance in CFS was studied, and it showed that the secretion of the inhibitory substance was initiated in middle log phase of growth and peaked in late log phase. Further, CFS synergized the activities of ciprofloxacin, moxifloxacin, and streptomycin as evaluated in terms of checkerboard titrations. It lowered the minimum inhibitory concentration (MIC) of ciprofloxacin by almost 30 times and MIC of both moxifloxacin and streptomycin by 8 times. Interestingly, pepsin treatment of CFS caused the complete abrogation of its synergistic effect with all the three antibiotics. Thus, from the study, it can be concluded that probiotic-based alternative therapeutic regimen can be designed for the treatment of P. aeruginosa infections.

  10. Antagonism or synergism between papaya ringspot virus and papaya mosaic virus in Carica papaya is determined by their order of infection.

    Science.gov (United States)

    Chávez-Calvillo, Gabriela; Contreras-Paredes, Carlos A; Mora-Macias, Javier; Noa-Carrazana, Juan C; Serrano-Rubio, Angélica A; Dinkova, Tzvetanka D; Carrillo-Tripp, Mauricio; Silva-Rosales, Laura

    2016-02-01

    Antagonism between unrelated plant viruses has not been thoroughly described. Our studies show that two unrelated viruses, papaya ringspot virus (PRSV) and papaya mosaic virus (PapMV) produce different symptomatic outcomes during mixed infection depending on the inoculation order. Synergism occurs in plants infected first with PRSV or in plants infected simultaneously with PRSV and PapMV, and antagonism occurs in plants infected first with PapMV and later inoculated with PRSV. During antagonism, elevated pathogenesis-related (PR-1) gene expression and increased reactive oxygen species production indicated the establishment of a host defense resulting in the reduction in PRSV titers. Polyribosomal fractioning showed that PRSV affects translation of cellular eEF1α, PR-1, β-tubulin, and PapMV RNAs in planta, suggesting that its infection could be related to an imbalance in the translation machinery. Our data suggest that primary PapMV infection activates a defense response against PRSV and establishes a protective relationship with the papaya host. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Antioxidative and prooxidative effects in food lipids and synergism with α-tocopherol of açaí seed extracts and grape rachis extracts

    DEFF Research Database (Denmark)

    Melo, Priscilla Siqueira; Arrivetti, Leandro de Oliveira Rodrigues; de Alencar, Severino Matias

    2016-01-01

    Extracts of açaí seed and of grape rachis alone or in combination with α-tocopherol were evaluated as antioxidants in (i) bulk soybean oil, (ii) soybean oil liposomes and (iii) soybean-oil/water emulsions. The extracts made with 57% aqueous ethanol showed an antioxidant activity not dependent......-tocopherol, effects explained by the solubility of extract components in the water-phase and of α-tocopherol in the lipid-phase. Phenolic profiling of the extracts by U-HPLC-ESI-LTQ-MS was used to identify active antioxidants. Açaí seed and grape rachis extracts served as good sources of procyanidins and flavan-3-ols...... on concentration for grape rachis extracts and a concentration-dependent prooxidative activity for açaí seed extracts in bulk soybean oil. Both the extracts, however, protected liposome suspensions and oil/water emulsions against lipid oxidation. Synergism was demonstrated when extracts were combined with α...

  12. Synergic Interaction of Rifaximin and Mutaflor (Escherichia coli Nissle 1917 in the Treatment of Acetic Acid-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Artur Dembiński

    2016-01-01

    Full Text Available Background. Inflammatory bowel disease results from the dysregulation of immune response to environmental and microbial agents in genetically susceptible individuals. The aim of the present study was to examine the effect of rifaximin and/or Mutaflor (Escherichia coli Nissle 1917, EcN administration on the healing of acetic acid-induced colitis. Methods. Colitis was induced in male Wistar rats by rectal enema with 3.5% acetic acid solution. Rifaximin (50 mg/kg/dose and/or Mutaflor (109 CFU/dose were given intragastrically once a day. The severity of colitis was assessed at the 8th day after induction of inflammation. Results. Treatment with rifaximin significantly accelerated the healing of colonic damage. This effect was associated with significant reversion of the acetic acid-evoked decrease in mucosal blood flow and DNA synthesis. Moreover, administration of rifaximin significantly reduced concentration of proinflammatory TNF-α and activity of myeloperoxidase in colonic mucosa. Mutaflor given alone was without significant effect on activity of colitis. In contrast, Mutaflor given in combination with rifaximin significantly enhanced therapeutic effect of rifaximin. Moreover, Mutaflor led to settle of the colon by EcN and this effect was augmented by pretreatment with rifaximin. Conclusion. Rifaximin and Mutaflor exhibit synergic anti-inflammatory and therapeutic effect in acetic acid-induced colitis in rats.

  13. Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity

    Science.gov (United States)

    Erkes, Dan A; Xu, Guangwu; Daskalakis, Constantine; Zurbach, Katherine A; Wilski, Nicole A; Moghbeli, Toktam; Hill, Ann B; Snyder, Christopher M

    2016-01-01

    Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8+ T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8+ T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8+ T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8+ T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection. PMID:27434584

  14. Antimicrobial synergism and cytotoxic properties of Citrus limon L., Piper nigrum L. and Melaleuca alternifolia (Maiden and Betche) Cheel essential oils.

    Science.gov (United States)

    Nikolić, Miloš M; Jovanović, Katarina K; Marković, Tatjana Lj; Marković, Dejan Lj; Gligorijević, Nevenka N; Radulović, Siniša S; Kostić, Marina; Glamočlija, Jasmina M; Soković, Marina D

    2017-11-01

    The chemical composition, antimicrobial and synergistic effect, and cytotoxic activity of Citrus limon (lemon), Piper nigrum (green pepper) and Melaleuca alternifoila (tea tree) essential oils (EOs) were investigated. Chemical analyses of essential oils were tested by GC-FID and GC-MS spectroscopy. The antimicrobial activity assay was conducted using microdilution method against several oral bacteria and Candida spp. originating from the humans with oral disorders. The synergistic antimicrobial activity was evaluated using checkerboard method. The cytotoxicity evaluation of EOs was assessed using MTT test. Limonene (37.5%) and β-pinene (17.9%) were the major compounds in C. limon oil, β-pinene (34.4%), δ-3-carene (19.7%), limonene (18.7%) and α-pinene (10.4%) in P. nigrum oil and terpinen-4-ol (38.6%) and γ-terpinene (21.7%) in M. alternifolia oil. The broad-spectrum antimicrobial activity was achieved by tested three EOs, with C. limon oil being the strongest against bacteria and M. alternifolia oil strongest against fungi. The EOs demonstrated synergism; their combined application revealed an increase in antimicrobial activity. All tested essential oils showed lower cytotoxic activity in comparison with the positive control, and the obtained results confirmed a dose-dependent activity. The results of this study encourage use of tested EOs in development of a novel agent intended for prevention or therapy of corresponding oral disorders. © 2017 Royal Pharmaceutical Society.

  15. Degradation of Bisphenol A by Peroxymonosulfate Catalytically Activated with Mn1.8Fe1.2O4Nanospheres: Synergism between Mn and Fe.

    Science.gov (United States)

    Huang, Gui-Xiang; Wang, Chu-Ya; Yang, Chuan-Wang; Guo, Pu-Can; Yu, Han-Qing

    2017-11-07

    A high-efficient, low-cost, and eco-friendly catalyst is highly desired to activate peroxides for environmental remediation. Due to the potential synergistic effect between bimetallic oxides' two different metal cations, these oxides exhibit superior performance in the catalytic activation of peroxymonosulfate (PMS). In this work, novel Mn 1.8 Fe 1.2 O 4 nanospheres were synthesized and used to activate PMS for the degradation of bisphenol A (BPA), a typical refractory pollutant. The catalytic performance of the Mn 1.8 Fe 1.2 O 4 nanospheres was substantially greater than that of the Mn/Fe monometallic oxides and remained efficient in a wide pH range from 4 to 10. More importantly, a synergistic effect between solid-state Mn and Fe was identified in control experiments with Mn 3 O 4 and Fe 3 O 4 . Mn was inferred to be the primary active site in the surface of the Mn 1.8 Fe 1.2 O 4 nanospheres, while Fe(III) was found to play a key role in the synergism with Mn by acting as the main adsorption site for the reaction substrates. Both sulfate and hydroxyl radicals were generated in the PMS activation process. The intermediates of BPA degradation were identified and the degradation pathways were proposed. This work is expected to help to elucidate the rational design and efficient synthesis of bimetallic materials for PMS activation.

  16. Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells.

    Science.gov (United States)

    Hamunyela, Roswita H; Serafin, Antonio M; Akudugu, John M

    2017-02-01

    Targeting pro-survival cell signaling components has been promising in cancer therapy, but the benefit of targeting with single agents is limited. For malignancies such as triple-negative breast cancer, there is a paucity of targets that are amenable to existing interventions as they are devoid of the human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER). Concurrent targeting of cell signaling entities other than HER2, PR and ER with multiple agents may be more effective. Evaluating modes of interaction between agents can inform efficient selection of agents when used in cocktails. Using clonogenic cell survival, interaction between inhibitors of HER2 (TAK-165), phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) (NVP-BEZ235), and the pro-survival gene (Bcl-2) (ABT-263) in three human breast cell lines (MDA-MB-231, MCF-7 and MCF-12A) ranged from strong to very strong synergism. The strongest synergy was demonstrated in PR and ER negative cells. Inhibition of PI3K, mTOR and Bcl-2 could potentially be effective in the treatment of triple-negative cancers. The very strong synergy observed even at lowest concentrations of inhibitors indicates that these cocktails might be able to be used at a minimised risk of systemic toxicity. Concurrent use of multiple inhibitors can potentiate conventional interventions like radiotherapy and chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Toxic Synergism Between Quinolinic Acid and Glutaric Acid in Neuronal Cells Is Mediated by Oxidative Stress: Insights to a New Toxic Model.

    Science.gov (United States)

    Pierozan, Paula; Colín-González, Ana Laura; Biasibetti, Helena; da Silva, Janaina Camacho; Wyse, Angela; Wajner, Moacir; Santamaria, Abel

    2017-09-21

    It has been shown that synergistic toxic effects of quinolinic acid (QUIN) and glutaric acid (GA), both in isolated nerve endings and in vivo conditions, suggest the contribution of these metabolites to neurodegeneration. However, this synergism still requires a detailed characterization of the mechanisms involved in cell damage during its occurrence. In this study, the effects of subtoxic concentrations of QUIN and/or GA were tested in neuronal cultures, co-cultures (neuronal cells + astrocytes), and mixed cultures (neuronal cells + astrocytes + microglia) from rat cortex and striatum. The exposure of different cortical and striatal cell cultures to QUIN + GA resulted in cell death and stimulated different markers of oxidative stress, including reactive oxygen species (ROS) formation; changes in the activity of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase; and depletion of endogenous antioxidants such as -SH groups and glutathione. The co-incubation of neuronal cultures with QUIN + GA plus the N-methyl-D-aspartate antagonist MK-801 prevented cell death but not ROS formation, whereas the antioxidant melatonin reduced both parameters. Our results demonstrated that QUIN and GA can create synergistic scenarios, inducing toxic effects on some parameters of cell viability via the stimulation of oxidative damage. Therefore, it is likely that oxidative stress may play a major causative role in the synergistic actions exerted by QUIN + GA in a variety of cell culture conditions involving the interaction of different neural types.

  18. 3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

    Science.gov (United States)

    Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

    2017-07-17

    Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

  19. Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection.

    Science.gov (United States)

    Wren, John T; Blevins, Lance K; Pang, Bing; Basu Roy, Ankita; Oliver, Melissa B; Reimche, Jennifer L; Wozniak, Jessie E; Alexander-Miller, Martha A; Swords, W Edward

    2017-04-01

    Even in the vaccine era, Streptococcus pneumoniae (the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by S. pneumoniae , in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and S. pneumoniae potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using in vitro models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens. Copyright © 2017 American Society for Microbiology.

  20. Dasatinib synergizes with ATRA to trigger granulocytic differentiation in ATRA resistant acute promyelocytic leukemia cell lines via Lyn inhibition-mediated activation of RAF-1/MEK/ERK.

    Science.gov (United States)

    Ding, Ming; Weng, Xiang-Qin; Sheng, Yan; Wu, Jing; Liang, Cui; Cai, Xun

    2017-10-31

    All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In this study, dasatinib synergized with ATRA to trigger differentiation in ATRA-resistant APL cell lines. The combined treatment activated RAF-1, MEK and ERK as well as enhanced ATRA-promoted up-regulation of the protein level of PU.1, C/EBPβ and C/EBPε. U0126 (MEK specific inhibitor) and sorafenib tosylate (RAF-1 specific inhibitor) suppressed the combined treatment-induced differentiation, ERK phosphorylation and the up-regulation of C/EBPs and PU.1. Sorafenib tosylate also attenuated the MEK activity. However, the combined treatment did not enhance Ras activity and Ras inhibitor neither blocked MEK activation nor inhibited differentiation. Therefore, the combined treatment induced differentiation via Ras independent RAF-1/MEK/ERK. Earlier than RAF-1 activation, dasatinib suppressed Lyn activity, the predominant activated Src family kinase (SFK) and dephosphorylated RAF-1 at S259. Furthermore, SFK inhibitor, PP2 did suppress Lyn activity and mimicked the effect of dasatinib on ATRA-induced differentiation as well as decreased phosphorylation of RAF-1 at S259. Thus, it was suggested that Lyn inhibition might activate RAF-1 by the dephosphorylation of RAF at S259 and lead to differentiation. In conclusion, the combination of dasatinib and ATRA could overcome ATRA resistance through Lyn inhibition-mediated activation of RAF-1/MEK/ERK. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Study of synergism of cobalt II and '4f' elements in liquid-liquid extraction from melt alkaline nitrates

    International Nuclear Information System (INIS)

    Targhetta, Jocelyne

    1972-01-01

    This research study addresses the synergetic effect which can be obtained by adding some elements in the solvent-based extraction technique in melt salt medium. More specifically, it reports the study of the synergism of a pair of neutral organophosphorous agents (the hexamethylphosphorotriamide or HMPT and the 1,2 bis-phosphino-ethane dioxide or 2-DPO) and a chelating-neutral organophosphorous agent (HTTA et 2-DPO) pair during the extraction of bivalent cobalt and of some '4f' elements (Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Tm, Yb) from the (Li-R)NO 3 eutectic at 160 C. After a presentation of the experimental techniques and a report of the measurement of concentrations, the author reports the extraction of various nitrates (Co II, Nd III, Tm III, Yb III) by each of the agents (2-DPO, HMPT, HTTA). For each element, the author tries to identify the extracted forms in the organic phase and to assess extraction constants. The next part addresses synergetic effects of the two pairs (HTTA-2-DPO and HMPT-2-DPO) during the extraction of Co II. The author finally reports and discusses the results obtained for the extraction of lanthanides with the above-mentioned pairs

  2. Antioxidative and prooxidative effects in food lipids and synergism with α-tocopherol of açaí seed extracts and grape rachis extracts.

    Science.gov (United States)

    Melo, Priscilla Siqueira; Arrivetti, Leandro de Oliveira Rodrigues; Alencar, Severino Matias de; Skibsted, Leif H

    2016-12-15

    Extracts of açaí seed and of grape rachis alone or in combination with α-tocopherol were evaluated as antioxidants in (i) bulk soybean oil, (ii) soybean oil liposomes and (iii) soybean-oil/water emulsions. The extracts made with 57% aqueous ethanol showed an antioxidant activity not dependent on concentration for grape rachis extracts and a concentration-dependent prooxidative activity for açaí seed extracts in bulk soybean oil. Both the extracts, however, protected liposome suspensions and oil/water emulsions against lipid oxidation. Synergism was demonstrated when extracts were combined with α-tocopherol, effects explained by the solubility of extract components in the water-phase and of α-tocopherol in the lipid-phase. Phenolic profiling of the extracts by U-HPLC-ESI-LTQ-MS was used to identify active antioxidants. Açaí seed and grape rachis extracts served as good sources of procyanidins and flavan-3-ols, imparted high antioxidant activity especially when combined with α-tocopherol and are suggested for protection of food oil/water emulsions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Intratumoral Infection with Murine Cytomegalovirus Synergizes with PD-L1 Blockade to Clear Melanoma Lesions and Induce Long-term Immunity.

    Science.gov (United States)

    Erkes, Dan A; Xu, Guangwu; Daskalakis, Constantine; Zurbach, Katherine A; Wilski, Nicole A; Moghbeli, Toktam; Hill, Ann B; Snyder, Christopher M

    2016-08-01

    Cytomegalovirus is an attractive cancer vaccine platform because it induces strong, functional CD8(+) T-cell responses that accumulate over time and migrate into most tissues. To explore this, we used murine cytomegalovirus expressing a modified gp100 melanoma antigen. Therapeutic vaccination by the intraperitoneal and intradermal routes induced tumor infiltrating gp100-specific CD8(+) T-cells, but provided minimal benefit for subcutaneous lesions. In contrast, intratumoral infection of established tumor nodules greatly inhibited tumor growth and improved overall survival in a CD8(+) T-cell-dependent manner, even in mice previously infected with murine cytomegalovirus. Although murine cytomegalovirus could infect and kill B16F0s in vitro, infection was restricted to tumor-associated macrophages in vivo. Surprisingly, the presence of a tumor antigen in the virus only slightly increased the efficacy of intratumoral infection and tumor-specific CD8(+) T-cells in the tumor remained dysfunctional. Importantly, combining intratumoral murine cytomegalovirus infection with anti-PD-L1 therapy was synergistic, resulting in tumor clearance from over half of the mice and subsequent protection against tumor challenge. Thus, while a murine cytomegalovirus-based vaccine was poorly effective against established subcutaneous tumors, direct infection of tumor nodules unexpectedly delayed tumor growth and synergized with immune checkpoint blockade to promote tumor clearance and long-term protection.

  4. The synergic effects of CTLA-4/Foxp3-related genotypes and chromosomal aberrations on the risk of recurrent spontaneous abortion among a Chinese Han population.

    Science.gov (United States)

    Fan, Qin'e; Zhang, Juanjuan; Cui, Yu; Wang, Chaoyun; Xie, Yongjun; Wang, Qiurong; Wu, Libing

    2018-02-23

    The current study was aimed to investigate the association of CLTA-4/Foxp3 polymorphisms and chromosomal abnormalities with recurrent spontaneous abortion (RSA) risk in a Chinese Han population. Altogether, 1284 RSA women and 1046 women with normal pregnancy were incorporated in this study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was implemented to genotype the single-nucleotide polymorphisms (SNPs) located within CTLA4 and Foxp3. Moreover, the cytogenetic diagnosis was performed in line with the standards of G banding karyotype. As a consequence, rs231775 and rs3087243 of CTLA4, as well as rs2232365 and rs2232368 of Foxp3, all appeared to modify the risk of RSA. Besides, significant differences were found between the ratio of structural abnormality and that of numerical abnormality (P 3) than normal karyotypes. Of note, the synergic effects of the genotypes and chromosomal abnormality all tallied with the sub-multiplication model (OR chromosome  × OR SNP  > OR chromosome+SNP ), while rs2232365 GG and chromosomal aberration impacted the RSA risk in a super-multiplicative way that OR chromosome  × OR SNP  < OR chromosome+SNP . In conclusion, susceptibility to RSA was subject to the synthetic regulation of chromosomal aberrations and genetic mutations within CLTA-4 and Foxp3, suggesting that the conduction of karyotype analysis and genetic detection for RSA patients could effectively guide effective RSA counseling and sound child rearing.

  5. A Mutation in the Intracellular Loop III/IV of Mosquito Sodium Channel Synergizes the Effect of Mutations in Helix IIS6 on Pyrethroid Resistance

    Science.gov (United States)

    Wang, Lingxin; Nomura, Yoshiko; Du, Yuzhe; Liu, Nannan; Zhorov, Boris S.

    2015-01-01

    Activation and inactivation of voltage-gated sodium channels are critical for proper electrical signaling in excitable cells. Pyrethroid insecticides promote activation and inhibit inactivation of sodium channels, resulting in prolonged opening of sodium channels. They preferably bind to the open state of the sodium channel by interacting with two distinct receptor sites, pyrethroid receptor sites PyR1 and PyR2, formed by the interfaces of domains II/III and I/II, respectively. Specific mutations in PyR1 or PyR2 confer pyrethroid resistance in various arthropod pests and disease vectors. Recently, a unique mutation, N1575Y, in the cytoplasmic loop linking domains III and IV (LIII/IV) was found to coexist with a PyR2 mutation, L1014F in IIS6, in pyrethroid-resistant populations of Anopheles gambiae. To examine the role of this mutation in pyrethroid resistance, N1575Y alone or N1575Y + L1014F were introduced into an Aedes aegypti sodium channel, AaNav1-1, and the mutants were functionally examined in Xenopus oocytes. N1575Y did not alter AaNav1-1 sensitivity to pyrethroids. However, the N1575Y + L1014F double mutant was more resistant to pyrethroids than the L1014F mutant channel. Further mutational analysis showed that N1575Y could also synergize the effect of L1014S/W, but not L1014G or other pyrethroid-resistant mutations in IS6 or IIS6. Computer modeling predicts that N1575Y allosterically alters PyR2 via a small shift of IIS6. Our findings provide the molecular basis for the coexistence of N1575Y with L1014F in pyrethroid resistance, and suggest an allosteric interaction between IIS6 and LIII/IV in the sodium channel. PMID:25523031

  6. Critical Role of the Neonatal Fc Receptor (FcRn) in the Pathogenic Action of Antimitochondrial Autoantibodies Synergizing with Anti-desmoglein Autoantibodies in Pemphigus Vulgaris.

    Science.gov (United States)

    Chen, Yumay; Chernyavsky, Alex; Webber, Robert J; Grando, Sergei A; Wang, Ping H

    2015-09-25

    Pemphigus vulgaris (PV) is a life-long, potentially fatal IgG autoantibody-mediated blistering disease targeting mucocutaneous keratinocytes (KCs). PV patients develop pathogenic anti-desmoglein (Dsg) 3 ± 1 and antimitochondrial antibodies (AMA), but it remained unknown whether and how AMA enter KCs and why other cell types are not affected in PV. Therefore, we sought to elucidate mechanisms of cell entry, trafficking, and pathogenic action of AMA in PV. We found that PVIgGs associated with neonatal Fc receptor (FcRn) on the cell membrane, and the PVIgG-FcRn complexes entered KCs and reached mitochondria where they dissociated. The liberated AMA altered mitochondrial membrane potential, respiration, and ATP production and induced cytochrome c release, although the lack or inactivation of FcRn abolished the ability of PVIgG to reach and damage mitochondria and to cause detachment of KCs. The assays of mitochondrial functions and keratinocyte adhesion demonstrated that although the pathobiological effects of AMA on KCs are reversible, they become irreversible, leading to epidermal blistering (acantholysis), when AMA synergize with anti-Dsg antibodies. Thus, it appears that AMA enter a keratinocyte in a complex with FcRn, become liberated from the endosome in the cytosol, and are trafficked to the mitochondria, wherein they trigger pro-apoptotic events leading to shrinkage of basal KCs uniquely expressing FcRn in epidermis. During recovery, KCs extend their cytoplasmic aprons toward neighboring cells, but anti-Dsg antibodies prevent assembly of nascent desmosomes due to steric hindrance, thus rendering acantholysis irreversible. In conclusion, FcRn is a common acceptor protein for internalization of AMA and, perhaps, for PV autoantibodies to other intracellular antigens, and PV is a novel disease paradigm for investigating and elucidating the role of FcRn in this autoimmune disease and possibly other autoimmune diseases. © 2015 by The American Society for

  7. Synergism studies on some radionuclides of nuclear and environmental importance using phosphonate compounds mixed with oxygen and phosphorous containing neutral compounds

    International Nuclear Information System (INIS)

    EL-Zahhar, A.Abd El Wahed M.

    1998-01-01

    As solvent extraction is a technique which has been highly developed within various national energy programs because of its suitability as selective separation process for fission products, actinides and other radioactive substances. It is very important to look for to be used as extractants and to study the optimum condition under which these compounds can be used as such. This work aims at studying the use of the carbamoyl phosphonate as an extractant in the extraction of certain elements. Also studying the effect of mixed extraction (possibility of enhancing extraction or synergism) as will as temperature effect on the extraction process and calculating the thermodynamic parameters of the proposed extraction reactions. To compare the extraction behavior of the phosphonate compound with other chelating agents as HTTA and HDEHP , studying the extraction of the same elements with these cheating agents under the same conditions is also one of the objectives of this work. This work also aims at studying the extraction of certain elements in comparable oxidation states. The selected elements; uranium which represents the main pert in the nuclear fuel, cobalt which is produced in the nuclear fission products, europium which is also produced as a fission product and is analog of the trivalent actinides series and chromium which is a corrosion product in the nuclear fuel cycle and is an analogue of transition elements. The work also aims at studying the extraction of the selected elements from different aqueous media of low acidic nature to classify the effect of the aqueous phase on the extraction systems handled

  8. Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CpG of the rat spinal cord in vitro.

    Directory of Open Access Journals (Sweden)

    Francesco Dose

    Full Text Available Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 μM generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in

  9. The novel Akt inhibitor API-1 induces c-FLIP degradation and synergizes with TRAIL to augment apoptosis independent of Akt inhibition.

    Science.gov (United States)

    Li, Bo; Ren, Hui; Yue, Ping; Chen, Mingwei; Khuri, Fadlo R; Sun, Shi-Yong

    2012-04-01

    API-1 (pyrido[2,3-d]pyrimidines) is a novel small-molecule inhibitor of Akt, which acts by binding to Akt and preventing its membrane translocation and has promising preclinical antitumor activity. In this study, we reveal a novel function of API-1 in regulation of cellular FLICE-inhibitory protein (c-FLIP) levels and TRAIL-induced apoptosis, independent of Akt inhibition. API-1 effectively induced apoptosis in tested cancer cell lines including activation of caspase-8 and caspase-9. It reduced the levels of c-FLIP without increasing the expression of death receptor 4 (DR4) or DR5. Accordingly, it synergized with TRAIL to induce apoptosis. Enforced expression of ectopic c-FLIP did not attenuate API-1-induced apoptosis but inhibited its ability to enhance TRAIL-induced apoptosis. These data indicate that downregulation of c-FLIP mediates enhancement of TRAIL-induced apoptosis by API-1 but is not sufficient for API-1-induced apoptosis. API-1-induced reduction of c-FLIP could be blocked by the proteasome inhibitor MG132. Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability. These data together suggest that API-1 downregulates c-FLIP by facilitating its ubiquitination and proteasome-mediated degradation. Because other Akt inhibitors including API-2 and MK2206 had minimal effects on reducing c-FLIP and enhancement of TRAIL-induced apoptosis, it is likely that API-1 reduces c-FLIP and enhances TRAIL-induced apoptosis independent of its Akt-inhibitory activity. 2012 AACR

  10. Synergism and rules from combination of Baicalin, Jasminoidin and Desoxycholic acid in refined Qing Kai Ling for treat ischemic stroke mice model.

    Directory of Open Access Journals (Sweden)

    Jian Li

    Full Text Available Refined Qing-Kai-Ling (QKL, a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid, plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA and principal component analysis (PCA to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5 could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4 were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM, emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.

  11. High mobility group box 1 protein synergizes with lipopolysaccharide and peptidoglycan for nitric oxide production in mouse peritoneal macrophages in vitro.

    Science.gov (United States)

    Chakraborty, Rituparna; Bhatt, Kunal H; Sodhi, Ajit

    2013-05-01

    Extracellular high mobility group box 1 (HMGB1) protein and nitric oxide (NO) has been credited with multiple inflammatory functions using in vivo and in vitro systems. Therefore, delineating their regulation may be an important therapeutic strategy for the treatment of sepsis. In the present study, it is demonstrated that recombinant HMGB1 (rHMGB1) synergizes with sub threshold concentration of TLR2 agonist (PGN; 1 μg/ml) as well as with TLR4 agonist (LPS; 1 ng/ml) to induce NO release in mouse peritoneal macrophages. The enhanced iNOS expression was also observed at the transcription and translational level. Co-incubation of macrophages with rHMGB1 with either PGN or LPS showed enhanced expression of TLR2, TLR4 and RAGE. TLR2, TLR4 or RAGE knockdown macrophages effectively inhibited the rHMGB1+PGN or LPS induced NO synergy. It was further observed that the JNK MAPK inhibitor SP600125 attenuated the PGN+rHMGB1 induced iNOS/NO synergy whereas p38 MAPK inhibitor SB908912 inhibited iNOS/NO synergy induced by LPS+rHMGB1. It was also observed that the activation of NF-κB is essential for the synergy as the pharmacological inhibition or siRNA knockdown of NF-κB (cRel) significantly reduced the rHMGB1+PGN or rHMGB1+LPS induced enhanced iNOS/NO expression. Altogether, the data suggests that the co-incubation of macrophages with rHMGB1 with either LPS or PGN induces the synergistic effect on iNOS expression and NO release by the upregulation of surface receptors (TLR2, TLR4 and RAGE) which in turn amplifies the MAPKs (p38 and JNK) and NF-κB activation and results in enhanced iNOS expression and NO production. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats

    International Nuclear Information System (INIS)

    Tikoo, Kulbhushan; Kumar, Parveen; Gupta, Jeena

    2009-01-01

    Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats. Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-γ expression were examined by western blotting. Our data shows involvement of TNF-α in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-γ in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-γ directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications. To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer

  13. Co-inhibition of pol θ and HR genes efficiently synergize with cisplatin to suppress cisplatin-resistant lung cancer cells survival

    Science.gov (United States)

    Dai, Chun-Hua; Chen, Ping; Li, Jian; Lan, Tin; Chen, Yong-Chang; Qian, Hai; Chen, Kang; Li, Mei-Yu

    2016-01-01

    Cisplatin exert its anticancer effect by creating intrastrand and interstrand DNA cross-links which block DNA replication and is a major drug used to treat lung cancer. However, the main obstacle of the efficacy of treatment is drug resistance. Here, we show that expression of translesion synthesis (TLS) polymerase Q (POLQ) was significantly elevated by exposure of lung cancer cells A549/DR (a cisplatin-resistant A549 cell line) to cisplatin. POLQ expression correlated inversely with homologous recombination (HR) activity. Co-depletion of BRCA2 and POLQ by siRNA markedly increased sensitivity of A549/DR cells to cisplatin, which was accompanied with impairment of double strand breaks (DSBs) repair reflected by prominent cell cycle checkpoint response, increased chromosomal aberrations and persistent colocalization of p-ATM and 53BP1 foci induced by cisplatin. Thus, co-knockdown of POLQ and HR can efficiently synergize with cisplatin to inhibit A549/DR cell survival by inhibiting DNA DSBs repair. Similar results were observed in A549/DR cells co-depleted of BRCA2 and POLQ following BMN673 (a PARP inhibitor) treatment. Importantly, the sensitization effects to cisplatin and BMN673 in A549/DR cells by co-depleting BRCA2 and POLQ was stronger than those by co-depleting BRCA2 and other TLS factors including POLH, REV3, or REV1. Our results indicate that there is a synthetic lethal relationship between pol θ-mediated DNA repair and HR pathways. Pol θ may be considered as a novel target for lung cancer therapy. PMID:27533083

  14. Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

    2017-10-01

    A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were allcarbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless

  15. Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.

    Science.gov (United States)

    Cunningham, Kathryn A; Anastasio, Noelle C; Fox, Robert G; Stutz, Sonja J; Bubar, Marcy J; Swinford, Sarah E; Watson, Cheryl S; Gilbertson, Scott R; Rice, Kenner C; Rosenzweig-Lipson, Sharon; Moeller, F Gerard

    2013-01-16

    Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT(2A) receptor (5-HT(2A)R) and 5-HT(2C)R; either a selective 5-HT(2A)R antagonist or a 5-HT(2C)R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT(2A)R antagonist plus 5-HT(2C)R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT(2A)R antagonist M100907 plus the 5-HT(2C)R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT(2A)R antagonist plus a 5-HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules.

  16. Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance

    Directory of Open Access Journals (Sweden)

    Yee-Huang Ku

    2017-12-01

    Full Text Available Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL-producing Klebsiella pneumoniae (KP clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 105 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline

  17. Synergic Use of Sentinel-1 and Sentinel-2 Images for Operational Soil Moisture Mapping at High Spatial Resolution over Agricultural Areas

    Directory of Open Access Journals (Sweden)

    Mohammad El Hajj

    2017-12-01

    Full Text Available Soil moisture mapping at a high spatial resolution is very important for several applications in hydrology, agriculture and risk assessment. With the arrival of the free Sentinel data at high spatial and temporal resolutions, the development of soil moisture products that can better meet the needs of users is now possible. In this context, the main objective of the present paper is to develop an operational approach for soil moisture mapping in agricultural areas at a high spatial resolution over bare soils, as well as soils with vegetation cover. The developed approach is based on the synergic use of radar and optical data. A neural network technique was used to develop an operational method for soil moisture estimates. Three inversion SAR (Synthetic Aperture Radar configurations were tested: (1 VV polarization; (2 VH polarization; and (3 both VV and VH polarization, all in addition to the NDVI information extracted from optical images. Neural networks were developed and validated using synthetic and real databases. The results showed that the use of a priori information on the soil moisture condition increases the precision of the soil moisture estimates. The results showed that VV alone provides better accuracy on the soil moisture estimates than VH alone. In addition, the use of both VV and VH provides similar results, compared to VV alone. In conclusion, the soil moisture could be estimated in agricultural areas with an accuracy of approximately 5 vol % (volumetric unit expressed in percent. Better results were obtained for soil with a moderate surface roughness (for root mean surface height between 1 and 3 cm. The developed approach could be applied for agricultural plots with an NDVI lower than 0.75.

  18. Curcuminoids extract, hydrolyzed collagen and green tea extract synergically inhibit inflammatory and catabolic mediator's synthesis by normal bovine and osteoarthritic human chondrocytes in monolayer.

    Directory of Open Access Journals (Sweden)

    Fanny Comblain

    Full Text Available The main objective of this study was to assess the in vitro effects of curcuminoids extract, hydrolyzed collagen and green tea extract in normal bovine chondrocytes and osteoarthritic human chondrocytes cultured in monolayer. This study also investigated the synergic or additive effects of these compounds. Enzymatically isolated primary bovine or human chondrocytes were cultured in monolayer until confluence and then incubated for 24 hours or 48 hours in the absence or in the presence of interleukin-1β and with or without curcuminoids extract, hydrolyzed collagen or green tea extract, added alone or in combination, at different concentrations. Cell viability was neither affected by these compounds, nor by interleukin 1β. In the absence of interleukin-1β, compounds did not significantly affect bovine chondrocytes metabolism. In human chondrocytes and in the absence of interleukin 1β, curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract significantly inhibited matrix metalloproteinase-3 production. In interleukin-1β-stimulated bovine chondrocytes, interleukin-6, inducible nitric oxide synthase, cyclooxygenase2, matrix metalloproteinase 3, a disintegrin and metalloproteinase with thrombospondin type I motifs 4 and a disintegrin and metalloproteinase with thrombospondin type I motifs 5 expressions were decreased by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. The combination of the three compounds was significantly more efficient to inhibit interleukin-1β stimulated matrix metalloproteinase-3 expression than curcuminoids extract alone. In interleukin-1β-stimulated human chondrocytes, nitric oxide, interleukin-6 and matrix metalloproteinase 3 productions were significantly reduced by curcuminoids extract alone or in combination with hydrolyzed collagen and green tea extract. These findings indicate that a mixture of curcuminoids extract, hydrolyzed collagen

  19. Synergism between rare earth cerium(IV) ion and vanillin on the corrosion of steel in H2SO4 solution: Weight loss, electrochemical, UV-vis, FTIR, XPS, and AFM approaches

    International Nuclear Information System (INIS)

    Li Xianghong; Deng Shuduan; Fu Hui; Mu Guannan; Zhao Ning

    2008-01-01

    The synergism between rare earth cerium(IV) ion and vanillin (4-hydroxy-3-methoxy-benzaldehyde) on the corrosion of cold rolled steel (CRS) in 1.0 M H 2 SO 4 solution at five temperatures ranging from 20 to 60 deg. C was first studied by weight loss and potentiodynamic polarization methods. The inhibited solutions were analyzed by ultraviolet and visible spectrophotometer (UV-vis). The adsorbed film of CRS surface containing optimum doses of the blends Ce 4+ -vanillin was investigated by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). The results revealed that vanillin had a moderate inhibitive effect, and the inhibition efficiency (IE) increased with the vanillin concentration. The adsorption of vanillin obeyed Temkin adsorption isotherm. Polarization curves showed that vanillin was a mixed-type inhibitor in sulfuric acid, while prominently inhibited the cathodic reaction. For the cerium(IV) ion, it had a negligible effect, and the maximum IE was only about 20%. However, incorporation of Ce 4+ with vanillin improved significantly the inhibition performance. The IE for Ce 4+ in combination with vanillin was higher than the summation of IE for single Ce 4+ and single vanillin, which was synergism in nature. A high inhibition efficiency, 98% was obtained by a mixture of 25-200 mg l -1 vanillin and 300-475 mg l -1 Ce 4+ . UV-vis showed that the new complex of Ce 4+ -vanillin was formed in 1.0 M H 2 SO 4 for Ce 4+ combination with vanillin. Polarization studies showed that the complex of Ce 4+ -vanillin acted as a mixed-type inhibitor, which drastically inhibits both anodic and cathodic reactions. FTIR and XPS revealed that a protective film formed in the presence of both vanillin and Ce 4+ was composed of cerium oxide and the complex of Ce 4+ -vanillin. The synergism between Ce 4+ and vanillin could also be evidenced by AFM images. Depending on the results, the synergism mechanism was discussed

  20. Synergism between rare earth cerium(IV) ion and vanillin on the corrosion of steel in H{sub 2}SO{sub 4} solution: Weight loss, electrochemical, UV-vis, FTIR, XPS, and AFM approaches

    Energy Technology Data Exchange (ETDEWEB)

    Li Xianghong [Department of Fundamental Courses, Southwest Forestry University, Kunming 650224 (China)], E-mail: xianghong-li@163.com; Deng Shuduan [Department of Wood Science and Technology, Southwest Forestry University, Kunming 650224 (China); Fu Hui [Department of Fundamental Courses, Southwest Forestry University, Kunming 650224 (China); Mu Guannan [Department of Chemistry, Yunnan University, Kunming 650091 (China); Zhao Ning [Department of Fundamental Courses, Southwest Forestry University, Kunming 650224 (China)

    2008-06-30

    The synergism between rare earth cerium(IV) ion and vanillin (4-hydroxy-3-methoxy-benzaldehyde) on the corrosion of cold rolled steel (CRS) in 1.0 M H{sub 2}SO{sub 4} solution at five temperatures ranging from 20 to 60 deg. C was first studied by weight loss and potentiodynamic polarization methods. The inhibited solutions were analyzed by ultraviolet and visible spectrophotometer (UV-vis). The adsorbed film of CRS surface containing optimum doses of the blends Ce{sup 4+}-vanillin was investigated by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and atomic force microscope (AFM). The results revealed that vanillin had a moderate inhibitive effect, and the inhibition efficiency (IE) increased with the vanillin concentration. The adsorption of vanillin obeyed Temkin adsorption isotherm. Polarization curves showed that vanillin was a mixed-type inhibitor in sulfuric acid, while prominently inhibited the cathodic reaction. For the cerium(IV) ion, it had a negligible effect, and the maximum IE was only about 20%. However, incorporation of Ce{sup 4+} with vanillin improved significantly the inhibition performance. The IE for Ce{sup 4+} in combination with vanillin was higher than the summation of IE for single Ce{sup 4+} and single vanillin, which was synergism in nature. A high inhibition efficiency, 98% was obtained by a mixture of 25-200 mg l{sup -1} vanillin and 300-475 mg l{sup -1} Ce{sup 4+}. UV-vis showed that the new complex of Ce{sup 4+}-vanillin was formed in 1.0 M H{sub 2}SO{sub 4} for Ce{sup 4+} combination with vanillin. Polarization studies showed that the complex of Ce{sup 4+}-vanillin acted as a mixed-type inhibitor, which drastically inhibits both anodic and cathodic reactions. FTIR and XPS revealed that a protective film formed in the presence of both vanillin and Ce{sup 4+} was composed of cerium oxide and the complex of Ce{sup 4+}-vanillin. The synergism between Ce{sup 4+} and vanillin could also be evidenced

  1. Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells.

    Science.gov (United States)

    Joiakim, Aby; Mathieu, Patricia A; Shelp, Catherine; Boerner, Julie; Reiners, John J

    2016-05-01

    CYP1A1 and CYP1A2 are transcriptionally activated in the human normal breast epithelial cell line MCF10A following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Shifting MCF10A cultures to medium deficient in serum and epidermal growth factor (EGF) caused rapid reductions in the activated (i.e., phosphorylated) forms of extracellular regulated kinases (ERKs) and the epidermal growth factor receptor (EGFR). Shifting to serum/EGF-deficient medium also enhanced TCDD-mediated induction of cytochrome P450 (CYP)1A1 Treatment of cells cultured in complete medium with the EGFR inhibitors gefitinib (Iressa), AG1478, and CI-1033 resulted in concentration-dependent reductions of active EGFR and ERKs, and increased CYP1A1 mRNA content ∼3- to 18-fold above basal level. EGFR inhibitors synergized with TCDD and resulted in transient CYP1A1 and CYP1A2 mRNA accumulations ∼8-fold greater (maximum at 5 hours) than that achieved with only TCDD. AG1478, gefitinib, and TCDD individually induced small increases (∼1.2- to 2.5-fold) in CYP1A1 protein content but did not cause additive or synergistic accumulations of CYP1A1 protein when used in combination. The mitogen-activated protein kinase kinase inhibitor PD184352 inhibited ERK and EGFR activation in a concentration-dependent fashion without causing CYP1A1 mRNA accumulation. However, cotreatment with PD184352 potentiated TCDD-mediated CYP1A1 induction. TCDD-mediated induction of CYP1A1 in MCF7-TET on-EGFR cells, a MCF7 variant in which EGFR expression can be controlled, was not affected by the activity status of EGFR or ERKs. Hence, EGFR signaling mutes both basal and ligand-induced expression of two aryl hydrocarbon receptor-responsive P450s in MCF10A cultures. However, these effects are cell context-dependent. Furthermore, CYP1A1 mRNA and protein abundance are not closely coupled in MCF10A cultures. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  2. On the “possible” synergism of the different phases of TiO 2 in photo-catalysis for hydrogen production

    KAUST Repository

    Wahab, A.K.

    2017-05-19

    The effect of TiO2 phase composition on the photocatalytic hydrogen production of water/ethanol (95/5 volume ratio) has been studied in order to understand the structural effect (and associated electronic properties) on the reaction within the so called “synergistic effect” concept. Within the investigated series of 1wt.% Pt/TiO2 with initial particle dimension of ca. 15nm the highest hydrogen production rate per unit area was observed for catalysts composed of 80% anatase, 18% rutile and 2% brookite. The associated particle sizes for this catalyst were 44, 82 and 33nm for the three phases, respectively. XRD patterns analyzed by the Rietveld method as well as X-ray absorption near-edge spectra (XANES) of the Ti K-edge mapped the phase transformation from anatase/brookite to rutile where it appears that the brookite phase is initially transformed to anatase phase. XRD patterns and Raman shift were found to be more sensitive to subtle changes in phase composition when compared to UV-vis absorbance or XANES of the Ti K-edge. The photocatalytic reaction for the complete series was conducted in identical condition and with excess photon flux in order to extract accurate reaction rates. In addition to the observed multi-phase effects on the reaction rate, other parameters extracted from the Rietveld refinement of the X-ray diffraction patterns were found to be useful. In particular, at the narrow window where the reaction rate was found to be maximum, the c-dimension of the anatase phase had values in the range 9.510–9.515Å. These c-dimension values are between those observed for nanoparticles with less than 20nm in size and those for larger particles with a size above 50nm. Results from this work indicate that the synergism between anatase and rutile on the photocatalytic reaction for hydrogen production, often attributed to increase the charge carrier life time, may be linked to the lattice expansion of the anatase phase which in turn would affect its electronic

  3. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    Energy Technology Data Exchange (ETDEWEB)

    An, Caiyan [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia (China); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Wu, Taoya; Bao, Muqiri; Bao, Liang [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Damirin, Alatangaole, E-mail: bigaole@imu.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China)

    2015-05-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  4. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    International Nuclear Information System (INIS)

    An, Caiyan; Sato, Koichi; Wu, Taoya; Bao, Muqiri; Bao, Liang; Tobo, Masayuki; Damirin, Alatangaole

    2015-01-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  5. Material synergism fusion-fission

    International Nuclear Information System (INIS)

    Sankara Rao, K.B.; Raj, B.; Cook, I.; Kohyama, A.; Dudarev, S.

    2007-01-01

    In fission and fusion reactors the common features such as operating temperatures and neutron exposures will have the greatest impact on materials performance and component lifetimes. Developing fast neutron irradiation resisting materials is a common issue for both fission and fusion reactors. The high neutron flux levels in both these systems lead to unique materials problems like void swelling, irradiation creep and helium embitterment. Both fission and fusion rely on ferritic-martensitic steels based on 9%Cr compositions for achieving the highest swelling resistance but their creep strength sharply decreases above ∝ 823K. The use of oxide dispersion strengthened (ODS) alloys is envisaged to increase the operating temperature of blanket systems in the fusion reactors and fuel clad tubes in fast breeder reactors. In view of high operating temperatures, cyclic and steady load conditions and the long service life, properties like creep, low cycle fatigue,fracture toughness and creepfatigue interaction are major considerations in the selection of structural materials and design of components for fission and fusion reactors. Currently, materials selection for fusion systems has to be based upon incomplete experimental database on mechanical properties. The usage of fairly well developed databases, in fission programmes on similar materials, is of great help in the initial design of fusion reactor components. Significant opportunities exist for sharing information on technology of irradiation testing, specimen miniaturization, advanced methods of property measurement, safe windows for metal forming, and development of common materials property data base system. Both fusion and fission programs are being directed to development of clean steels with very low trace and tramp elements, characterization of microstructure and phase stability under irradiation, assessment of irradiation creep and swelling behaviour, studies on compatibility with helium and developing fabrication and joining technologies for ferritic steels. There is also synergy in codifying mechanical design rules for high temperature structural materials. The rapid development of fusion requires a fundamental understanding and a robust predictive capability of radiation damage in materials located in high flux regions. A joint approach for solving material problems would bring significant benefits, including the acceleration of development of both areas. (orig.)

  6. The VE/CAD synergism

    International Nuclear Information System (INIS)

    Sperling, R.B.

    1993-01-01

    Value Engineering (VE) and Computer-Aided Design (CAD) can be used synergistically to reduce costs and improve facilities designs. The cost and schedule impacts of implementing alternative design ideas developed by VE teams can be greatly reduced when the drawings have been produced with interactive CAD systems. To better understand the interrelationship between VE and CAD, the fundamentals of the VE process are explained; and example of a VE proposal is described and the way CAD drawings facilitated its implementation is illustrated

  7. Potential of multispectral synergism for observing tropospheric ozone by combining IR and UV measurements from incoming LEO (EPS-SG) and GEO (MTG) satellite sensors

    Science.gov (United States)

    Costantino, Lorenzo; Cuesta, Juan; Emili, Emanuele; Coman, Adriana; Foret, Gilles; Dufour, Gaëlle; Eremenko, Maxim; Chailleux, Yohann; Beekmann, Matthias; Flaud, Jean-Marie

    2017-04-01

    Satellite observations offer a great potential for monitoring air quality on daily and global basis. However, measurements from currently in orbit sensors do not allow to probe surface concentrations of gaseous pollutants such as tropospheric ozone (Liu et al., 2010). Using single-band approaches based on spaceborne measurements of either thermal infrared radiance (TIR, Eremenko et al., 2008) or ultraviolet reflectance (UV, Liu et al., 2010) only ozone down to the lower troposphere (3 km) may be observed. A recent multispectral method (referred to as IASI+GOME-2) combining the information of IASI and GOME-2 (both onboard MetOp satellites) spectra, respectively from the TIR and UV, has shown enhanced sensitivity for probing ozone at the lowermost troposphere (LMT, below 3 km of altitude) with maximum sensitivity down to 2.20 km a.s.l. over land, while sensitivity for IASI or GOME-2 only peaks at 3 to 4 km at lowest (Cuesta et al., 2013). Future spatial missions will be launched in the upcoming years on both low and geostationary orbits, such as EPS-SG (EUMETSAT Polar System Second Generation) and MTG (Meteosat Third Generation), carrying respectively IASI-NG (for IR) and UVNS (for UV), and IRS (for IR) and UVN (Sentinel 4, for UV). This new-generation sensors will enhance the capacity to observe ozone pollution and particularly by synergism of multispectral measurements. In this work we develop a pseudo-observation simulator and evaluate the potential of future EPS-SG and MTG satellite observations, through IASI-NG+UVNS and IRS+UVN multispectral methods to observe near-surface O3. The pseudo-real state of atmosphere (nature run) is provided by MOCAGE (MOdèle de Chimie Atmosphérique à Grande Échelle) chemical transport model. Simulations are calibrated by careful comparisons with real data, to ensure the best coherence between pseudo-reality and reality, as well as between the pseudo-observation simulator and existing satellite products. We perform full and

  8. Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients

    DEFF Research Database (Denmark)

    Tarnow, L; Kjeld, T; Knudsen, E

    2000-01-01

    AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three...... polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A1c (HbA1c). METHODS: We...... studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 +/- 10.0 years, diabetes...

  9. Synergic chemical analysis - the coupling of TG with FTIR, MS and GC-MS; 1. The determination of the gases released during the thermal oxidation of a printed circuit board

    International Nuclear Information System (INIS)

    Webb, M.; Last, P.M.; Breen, C.

    1999-01-01

    This contribution reports the coupling of TG with FTIR, MS and GC-MS (Synergic chemical analysis). During thermogravimetric analysis the gases evolved are analysed using 'real-time' FTIR and MS. Simultaneously the gases are collected on an absorbent trap (organic trap module, OTM) for subsequent analysis using GC-MS. As an example the technique has been used to identify the products evolved from a printed circuit board during thermal oxidation. The use of TG-FTIR-MS-OTM-GC-MS provided information that could not be available through single techniques alone. For example, it was possible to ascertain the temperature range over which bromophenol was released. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  10. Proposta metodológica para análise da ocorrência de sinergismo e efeitos potencializadores entre aleloquímicos Methodological proposal for analysis of synergism and potentializing effects among allelochemicals

    Directory of Open Access Journals (Sweden)

    A.P.S. Souza Filho

    2006-09-01

    Full Text Available Os procedimentos envolvendo a análise de sinergismo entre aleloquímicos têm envolvido, basicamente, a utilização de concentrações fixas. Neste trabalho, propõe-se um modelo teórico envolvendo quatro possibilidades de respostas: uma que demonstra a existência de sinergismo (possibilidade A do modelo; outra que revela a inexistência de sinergismo (possibilidade B do modelo; e duas que revelam que uma substância potencializa o efeito de outra (possibilidades C e D do modelo. Para efeito de teste do modelo, utilizaram-se duas substâncias químicas (ácido 3,4,5-trimetoxibenzóico [S1] e ácido verátrico [S2] isoladas das folhas de Parkia pendula, com atividade alelopática já comprovada, nas seguintes proporções: S1 pura, S2 pura e combinações de S1 e S2, nas seguintes proporções: 3:1, 1:1 e 1:3. Como plantas indicadoras foram utilizadas as plantas daninhas malícia (Mimosa pudica e mata-pasto (Senna obtusifolia. Os resultados, analisados em relação às quatro possibilidades estabelecidas no modelo teórico, permitiram inferir a inexistência de efeitos sinérgicos entre as duas substâncias testadas. As variações entre os resultados obtidos e a possibilidade B do modelo podem ser atribuídas ao potencial inibitório da substância e à sensibilidade das espécies receptoras às substâncias testadas.The procedures involving the analysis of synergism between allelochemicals have basically involved the use of fixed concentrations. This work deals with theoretical model involving four possibilities of response: one demonstraing the existence of synergism (possibility A of the model; one demonstraing the absence of synergism (possibility B of the model and two showing that a substance potentializes the effect of another (possibilities C and D of the model. Two isolated chemical substances (3,4,5-trimetoxybenzoic acid [S1] and 3,4-dimetoxybenzoic acid [S2] were used to test the model, isolated from Parkia pendula leaves with

  11. From Chaos to Order: “Synergetic Society, Synergic Administration and Synergistic Planning” Case Study: The Building Process of a Primary School in the Process of Self-Organization after the 1999 Marmara Earthquakes

    Directory of Open Access Journals (Sweden)

    Nazire DİKER

    2009-01-01

    Full Text Available In contemporary societies, through the advances in the technologies of informatics and communication, global interactions are increased, and developments, variations, changes, and transformations in any field are shared more rapidly than at any previous time in human history. Existing systems have been unable to show the necessary flexibility regarding the new requirements and the problems of new relations due to unpredictable circumstances. This can lead to the perception of chaotic societies and cause ontological problems in planning, which is based on future predictions. The main goal of this paper is to summarize the “synergetic society model”, “synergic administration” and “synergistic planning approaches” (developed for the dissertation. These concepts will help us to understand uncertain and unpredictable social changes. According to our model, “social synergy”, which is spontaneously emerging and organizing via communication channels, is thoroughly examined in the processes of chaos and self-organization as experienced following the eastern Marmara earthquake in 1999. The building process of a primary school with the help of social synergy in Kılıçköy / Yalova after the earthquake is explained on the basis of communication channels between different levels and with varying dynamics.

  12. Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1.

    Directory of Open Access Journals (Sweden)

    Frank Götschel

    Full Text Available Aberrant activation of Hedgehog (HH signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. Our experimental data demonstrated that the Daoy human medulloblastoma cell line possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic HH or Smoothened agonist induced expression of GLI1 protein and simultaneously prevented the processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed at the transcriptomic and proteomic levels. The Daoy cells responded to the HH/EGF co-treatment by downregulating GLI1, PTCH, and HHIP at the transcript level; this was also observed when Amphiregulin (AREG was used instead of EGF. We identified a novel crosstalk mechanism whereby EGFR signaling silences proteins acting as negative regulators of HH signaling, as AKT- and ERK-signaling independent process. EGFR/HH signaling maintained high GLI1 protein levels which contrasted the GLI1 downregulation on the transcript level. Conversely, a high-level synergism was also observed, due to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile. This suggests that there are more wide-spread, yet context-dependent interactions, between HH/GLI and growth factor receptor signaling in human malignancies.

  13. The HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) synergizes with cisplatin and induces apoptosis in cisplatin-resistant esophageal squamous cell carcinoma cell lines via the Akt/XIAP pathway.

    Science.gov (United States)

    Ui, Takashi; Morishima, Kazue; Saito, Shin; Sakuma, Yuji; Fujii, Hirofumi; Hosoya, Yoshinori; Ishikawa, Shumpei; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro; Yasuda, Yoshikazu

    2014-02-01

    Although cisplatin (CDDP) is a key drug in the treatment of esophageal squamous cell carcinoma (ESCC), acquired chemoresistance remains a major problem. Combination therapy may represent one strategy to overcome this resistance. Heat shock protein 90 (HSP90) is known to be overexpressed in several types of cancer cells, and its inhibition by small molecules, either alone or in combination, has shown promise in the treatment of solid malignancies. In the present study, we evaluated the synergistic effects of combining CDDP with the HSP90 inhibitor 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) on two CDDP-resistant human esophageal squamous cancer cell lines, KYSE30 and KYSE150. The results obtained demonstrated the synergistic inhibitory effects of CDDP and 17-AAG on the growth of KYSE30 and KYSE150 cells. Cell growth and cell number were more effectively reduced by the combined treatment with CDDP and 17-AAG than by the treatment with either CDDP or 17-AAG alone. Western blotting revealed that the combined action of CDDP and 17-AAG cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3, which demonstrated that the reduction in both cell growth and cell number was mediated by apoptosis. Time-course experiments showed that reduction in X-linked inhibitor of apoptosis protein (XIAP) and phosphorylated Akt were concomitant with apoptosis. The results of the present study demonstrate that 17-AAG synergizes with CDDP and induces apoptosis in CDDP-resistant ESCC cell lines, and also that modulation of the Akt/XIAP pathway may underlie this synergistic effect. Combination therapy with CDDP and an HSP90 inhibitor may represent a promising strategy to overcome CDDP resistance in ESCC.

  14. Epitope-dependent synergism and antagonism between CD40 antibodies and soluble CD40 ligand for the regulation of CD23 expression and IgE synthesis in human B cells.

    Science.gov (United States)

    Challa, A; Pound, J D; Armitage, R J; Gordon, J

    1999-06-01

    The induction of IgE synthesis in naive B cells requires two T-cell-derived signals: one delivered through CD40 and the other via interleukin-4 (IL-4). The natural counterstructure to CD40 is the CD40 ligand (CD40L). We have asked about the interplay between CD40L and CD40 mAb that recognize distinct epitopes in delivering signals for regulating IL-4-dependent IgE synthesis and the expression of CD23, the low-affinity IgE receptor, in resting B cells. After culture of purified human tonsillar B cells with CD40 agonists and IL-4, surface CD23 was determined by flow cytometric analysis. CD23 levels in cell lysates and supernatants were quantified by ELISA, as were those of secreted IgE. With regard to both induction of CD23 and IgE production, soluble CD40L trimer (sCD40LT) showed synergistic interaction with two mAb to CD40 which bind to epitopes located outside the ligand binding site (EA5 and 5C3), but not with a mAb (G28-5) which effectively competes for CD40L binding to CD40. Each of the two noncompeting mAb to CD40 was able to cooperate strongly with sCD40LT in promoting high-level induction of CD23 even in the absence of IL-4, an effect mirrored in the promotion of strong homotypic clustering and high-rate DNA synthesis. G28-5, uniquely, induced a down-regulation in IL-4-induced CD23 expression with time, a change that was accompanied by an increase in the amount of soluble CD23 detected. While the two noncompeting mAb consistently synergized with sCD40LT for the promotion of IL-4-dependent IgE synthesis, sCD40LT and G28-5 (which, by itself, was the most potent of the CD40 mAb at inducing IL-4-dependent IgE production) exhibited mutual antagonism in this regard, the level of which could be quite profound. This study demonstrates that appropriate targeting of CD40 can modulate IgE synthesis either positively or negatively.

  15. Synergism in extraction of beryllium(II)

    International Nuclear Information System (INIS)

    El-Yamani, I.S.; Farah, M.Y.; Abd El-Messieh, E.N.

    1978-01-01

    The extraction of Be(II) from sulphuric acid solutions by binary mixtures particularly that of the sodium salt of di-(2-ethyl hexyl)-phosphoric acid (NaDEHP) and tributyl phosphate (TBP) has been described. The organic phase was prepared by adding the calculated amount of the extractant mixture to the required diluent. The aqueous phase was prepared by dissolving a high grade BeSO 4 x4H 2 O in H 2 SO 4 solution of the required concentration. Equal volumes of both the tracer-labelled aqueous phase and the organic phase mixture were shaken mechanically in separatory funnels. After centrifugation, aliquots of both phases were counted in a γ-scintillation counter. The dependence of extraction on acidity, diluent type and solvents concentration was thoroughly examined. A possible extraction mechanism is suggested. (T.G.)

  16. Siamese crocodile plasma synergizes with ceftazidime against ...

    African Journals Online (AJOL)

    The effects of the antibacterial agents were analyzed using a bacterial suspension standard curve, minimum inhibitory concentration (MIC), Checkerboard assays, viability curves, membrane permeability assays, enzyme assays, and transmission electron microscopy. Results: CREnC strains expressed ESBL-AmpC gene ...

  17. Siamese crocodile plasma synergizes with ceftazidime against ...

    African Journals Online (AJOL)

    Methods: Protein fractions were from crocodile plasma and tested them on CREnC strains. Multiplex polymerase chain reaction ... nervous, musculoskeletal, and integumentary system [1]. From 2011 to 2013, the ... 2018 The authors. This work is licensed under the Creative Commons Attribution 4.0 International License ...

  18. Campaign Synergism: Operational Level Combat Power

    Science.gov (United States)

    1990-04-30

    34 See Jominis Te Art of Wa , trans. H.H. Mendell --aid W.P. Craighill (Philade hia, a..: J.B. Li1)pncop and Co., 171.; reprint edition, Westport, C...D:trine," LjfiL 33 (Aug 33): 264-. Epy, Colonel (Ret) Trevor N. "Let’ Get SeriouAbtMliper, Aj 33 (May 83): 18-25. Ellison, Major Gregor W. "Operational Art

  19. Nuclear synergism of the light elements

    International Nuclear Information System (INIS)

    Harms, A.A.

    1983-05-01

    Some basic issues concerning accelerator initiated and fusion sustained nuclear energy systems are examined. For this purpose we identify selected nuclear fusion reactions characterized by a variable ion-to-neutron content and explore their intrinsic couplings and regenerative features. These are then related to particular systems concepts which emphasize fusion physics and accelerator technology. It is concluded that several light-element reaction systems possess appealing and interesting properties and can further be associated with selected advanced nuclear technologies. Their eventual implementation as nuclear energy systems requires further research in fusion physics, accelerator technology and mathematical physics. Because of the substantial potential benefits of such nuclear energy systems, it is concluded that research in this area should be pursued with much vigour. (orig.)

  20. Synergism in Pharmacokinetics of Retagliptin and Metformin ...

    African Journals Online (AJOL)

    Methods: In open-label, randomized, three-period, three-treatment crossover studies, 15 subjects received 100 mg retagliptin, 1500 mg ... counter medication or vitamins within 2 weeks prior to enrollment. Volunteers with evidence of ..... Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes. Diabet.

  1. New Co–Pd–Zn γ-Brasses with Dilute Ferrimagnetism and Co2Zn11 Revisited: Establishing the Synergism between Theory and Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Weiwei; Miller, Gordon J

    2014-04-22

    A synergism between electronic structure theory and the targeted synthesis of new ternary γ-brass compounds is demonstrated in the Co–Zn system. Co2Zn11, which adopts a cubic γ-brass structure, is shown to be at the Zn-rich end of a homogeneity range that varies from 15.4 to 22.1 atom % Co. Four samples were examined by single-crystal diffraction, all of which crystallize in space group I43¯m with the lattice parameter ranging from 8.9851(1) to 8.8809(1) Å as the Co content increases. In the 26-atom γ-brass clusters, Co atoms preferentially occupy the outer tetrahedron (OT) sites and then replace Zn atoms at the octahedron (OH) sites at higher Co concentrations. In addition, a small fraction of vacancies occurs on the inner tetrahedron (IT) sites. The electronic structure of Co2Zn11 shows two distinct pseudogaps near the Fermi level: one at 292 valence electrons per primitive unit cell and the other at 302–304 valence electrons per primitive unit cell. Using molecular orbital arguments applied to the body-centered cubic packing of the 26-atom Co4Zn22 γ-brass cluster, these pseudogaps arise from (i) splitting among the valence s and p orbitals, which gives rise to the Hume–Rothery electron counting rule, and (ii) splitting within the manifold of Co 3d orbitals via Co–Zn orbital interactions. Co2Zn11 is Pauli paramagnetic, although the density of states at the Fermi level is large, whereas Curie–Weiss behavior emerges for higher Co concentrations. Because Pd has a size and an electronegativity similar to those of Zn, and inspired by the pseudogaps in the electronic density of states curve of Co2Zn11, Pd-doped γ-brass compounds were designed and two new γ-brass compounds were obtained: Co0.92(2)Pd1.08Zn11 and Co2.50(1)Pd2.50Zn8. In these, the site preferences for Co and Pd can

  2. Bacteriophage-antibiotic synergism to control planktonic and biofilm ...

    African Journals Online (AJOL)

    Amina Amal Mahmoud Nouraldin

    2015-07-11

    Jul 11, 2015 ... Abstract Introduction: Pseudomonas aeruginosa (P. aeruginosa) is a highly resistant opportunistic pathogen and is capable of forming biofilms on medical devices. Bacterial biofilms, which are micro-colonies encased in extracellular polysaccharide material are so difficult to be treated by con- ventional ...

  3. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    Science.gov (United States)

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Naturally occurring antifungal agents against Zygosaccharomyces bailii and their synergism.

    Science.gov (United States)

    Fujita, Ken-Ichi; Kubo, Isao

    2005-06-29

    Polygodial was found to exhibit a fungicidal activity against a food spoilage yeast, Zygosaccharomyces bailii, with the minimum fungicidal concentration (MFC) of 50 microg/mL (0.17 mM). The time-kill curve study showed that polygodial was fungicidal at any growth stage. The primary action of polygodial comes from its ability to disrupt the native membrane-associated function of integral proteins as nonionic surface active agents (surfactants) followed by a decrease in plasma membrane fluidity. The fungicidal activity of polygodial was increased 128-fold in combination with a sublethal amount (equivalent of 1/2 MFC) of anethole and vice versa relative to the fungicidal activity of anethole. The fungicidal activity of sorbic acid was enhanced 512-fold in combination with 1/2 MFC of polygodial. Conversely, the fungicidal activity of polygodial was enhanced 128-fold in combination with 1/2 MFC of sorbic acid.

  5. Science synergism study for EOS on evolution of desert surfaces

    Science.gov (United States)

    Farr, Tom G.

    1987-01-01

    The effectiveness of EOS data as a basis for the study of desert surfaces' evolution is presently evaluated for both long and short term geomorphic evolution. Attention is given to the usefulness of such sensor systems planned for EOS as MODIS for regional vegetation distribution/variability monitoring, HIRIS for visible-near IR observations, TIMS for lithological identification, HMMR and SSMI for soil characteristics, LASA for atmospheric profiles, SAR for surface roughness, ALT for two-dimensional topography, ACR for the calibration of imaging sensors, and ERBE for climate modeling and regional surface albedo variation determinations.

  6. Synergism and antagonism of Baygon with some additives against ...

    African Journals Online (AJOL)

    Larvae of the mosquito Culex pipiens were subjected to continuous laboratory selection with Baygon for 15 successive generations. This resistant strain was tested with some additives, piperonyl–butoxide, sesame oil and clove oil, to investigate their synergistic or antagonistic effect. The use of sesame oil and ...

  7. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    REFERENCES. 1. Deli G, Bosnyak E, Pusch G, Komoly S, Feher G. Diabetic neuropathies: diagnosis and management. Neuroendocrinology 2014; 98(4): 267-280. 2. Franklin GM, Kahn LB, Baxter J, Marshall JA, HAMMAN. RF. Sensory neuropathy in non-insulin-dependent diabetes mellitus The San Luis Valley Diabetes ...

  8. Synergism of Selective Tumor Vascular Thrombosis and Protease Activated Prodrug

    National Research Council Canada - National Science Library

    Liu, Cheng

    2008-01-01

    ... by administration of protease-activated prodrug. The activation of coagulation cascade and tumor vascular thrombosis as well as the following activation of the thrombolytic pathways led to explosive amplification of serine protease cascades...

  9. Synergism of UV Radiation and Heat for Cell Inactivation

    International Nuclear Information System (INIS)

    Kim, Jin-Kyu; Lee, Yun-Jong; Lee, Ju-Woon; Kim, Su-Hyoun; Petin, Vladislav G.

    2006-01-01

    Organisms including human beings are constantly exposed to UV radiation. The potential hazards of UV radiation have risen due to a depletion of the protective ozone layer in the stratosphere and the formation of ozone holes. Moreover, the effect of UV radiation may greatly increase due to synergistic interaction of UV radiation with other environmental factors. Fluence rate is known to constitute a very important parameter in photobiology. While it is generally accepted that lowering the UV radiation fluence rate results in a decrease of the cell killing or mutagenesis efficiency per unit dose, the matter is still unclear with regards to the synergistic interaction of UV radiation and another environmental agent. It is of great interest to investigate whether or not the synergistic interaction can take place at low intensities of such environmental factors. Heat is known to be an important modifier of UV radiation sensitivity. Exposure of skin to UV radiation is often encountered at hot ambient temperatures. Therefore, the elucidation of new fundamental aspects of the simultaneous action of UV radiation and heat is an actual task. Thus, the purpose of the present work was to establish whether the UV fluence rate alters the synergistic interaction between heat and UV radiation for cell inactivation

  10. Synergic motives and economic success of mergers of Czech companies

    Directory of Open Access Journals (Sweden)

    Jaroslav Sedláček

    2013-01-01

    Full Text Available One of the motives for mergers and acquisitions is the synergy effect, which can take several forms. This paper tries to find out whether mergers implemented at the Czech market bring positive or negative synergies. The basis of our investigation is the database of the companies that implemented a merger within 2001–2009; out of these, the companies that published their financial statements in a digitalized form were selected. We monitored the development of six indicators characterizing the economic status of a company. The values of these indicators were compared for all participating companies before the merger and for the successor company three years after the merger. The hypotheses were formulated so that they expressed an expectation of a positive synergy brought about by mergers. However, hypothesis testing has not provided a clear result. A positive effect of a merger on the key indicator of net assets, whose growth means an increase in the accounting value of the company after the merger, has been proved for small and medium-sized companies only. The effect of mergers on the increase in indicators has been confirmed for retained earnings from past years and personal costs. Further research will concentrate on the relations between the indicators with the aim to create an integral indicator for the economic success of mergers.

  11. Efficacy of Lycium barbarum polysaccharide and synergism with ...

    African Journals Online (AJOL)

    cisplatin in ovarian cancer in mice. ... in the chemotherapy and combination therapy groups, while organ index increased significantly in co-CH group. Morphological structure of tumor, liver and kidney became normal after combination therapy.

  12. Efficacy of Lycium barbarum polysaccharide and synergism with ...

    African Journals Online (AJOL)

    in the control of the growth of cancer cells [7]. The side effects of the drug include bone marrow suppression, peripheral neuropathy and arthralgia [8]. DDP inhibits DNA synthesis and is a cell cycle non-specific agent for tumors. The main side effects associated with DDP are liver and kidney toxicity, and bone marrow.

  13. Antimicrobial synergic effect of Allicin and silver nanoparticles on ...

    African Journals Online (AJOL)

    Aim: The aim of this study is to investigate antimicrobial properties of allicin, silver nanoparticles (Ag NPs) and their combination again skin infection caused by methicillin‑resistant Staphylococcus aureus (MRSA) strains in an animal model. Materials and Methods: In vivo, the effects of allicin, Ag NPs and their combination ...

  14. Light and gravity signals synergize in modulating plant development

    Science.gov (United States)

    Vandenbrink, Joshua P.; Kiss, John Z.; Herranz, Raul; Medina, F. Javier

    2014-01-01

    Tropisms are growth-mediated plant movements that help plants to respond to changes in environmental stimuli. The availability of water and light, as well as the presence of a constant gravity vector, are all environmental stimuli that plants sense and respond to via directed growth movements (tropisms). The plant response to gravity (gravitropism) and the response to unidirectional light (phototropism) have long been shown to be interconnected growth phenomena. Here, we discuss the similarities in these two processes, as well as the known molecular mechanisms behind the tropistic responses. We also highlight research done in a microgravity environment in order to decouple two tropisms through experiments carried out in the absence of a significant unilateral gravity vector. In addition, alteration of gravity, especially the microgravity environment, and light irradiation produce important effects on meristematic cells, the undifferentiated, highly proliferating, totipotent cells which sustain plant development. Microgravity produces the disruption of meristematic competence, i.e., the decoupling of cell proliferation and cell growth, affecting the regulation of the cell cycle and ribosome biogenesis. Light irradiation, especially red light, mediated by phytochromes, has an activating effect on these processes. Phytohormones, particularly auxin, also are key mediators in these alterations. Upcoming experiments on the International Space Station will clarify some of the mechanisms and molecular players of the plant responses to these environmental signals involved in tropisms and the cell cycle. PMID:25389428

  15. SYNER-G buildings, lifelines, transportation networks and critical facilities

    CERN Document Server

    Pitilakis, K; Kaynia, AM

    2014-01-01

    This volume collates serviceable fragility functions from an international selection of seismic risk probability research, developing and adapting them to a European context to improve damage forecasts for buildings, infrastructure, and critical facilities.

  16. Light and gravity signals synergize in modulating plant development

    Directory of Open Access Journals (Sweden)

    Joshua P. Vandenbrink

    2014-10-01

    Full Text Available Tropisms are growth-mediated plant movements that help plants to respond to changes in environmental stimuli. The availability of water and light, as well as the presence of a constant gravity vector, are all environmental stimuli that plants sense and respond to via directed growth movements (tropisms. The plant response to gravity (gravitropism and the response to unidirectional light (phototropism have long been shown to be interconnected growth phenomena. Here, we discuss the similarities in these two processes, as well as the known molecular mechanisms behind the tropistic responses. We also highlight experiments done in a microgravity environment in order to decouple two tropisms through experiments carried out in the absence of a significant unilateral gravity vector. In addition, alteration of gravity, especially the microgravity environment, and light irradiation produce important effects on meristematic cells, the undifferentiated, highly proliferating, totipotent cells which sustain plant development. Microgravity produces the disruption of meristematic competence, i.e. the decoupling of cell proliferation and cell growth, affecting the regulation of cell cycle and ribosome biogenesis. Light irradiation, especially red light, mediated by phytochromes, has an activating effect on these processes. Phytohormones, particularly auxin, are key mediators in these alterations. Upcoming experiments on the International Space Station will clarify some of the unknown mechanisms and molecular players of the plant responses to these environmental signals involved in tropisms and the cell cycle.

  17. Effects of nutrients antagonism and synergism on fertilizer use efficiency

    NARCIS (Netherlands)

    Rietra, R.P.J.J.; Heinen, M.; Dimpla, C.; Bindraban, P.S.

    2015-01-01

    Soil-borne pathogens cause major crop losses in global agriculture, adding up to billions of dollars of lost productivity each year. Alternative strategies applying nanotechnology in agriculture have focused on smart delivery systems and nanosensors to increase efficiency. However, low micronutrient

  18. Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation

    NARCIS (Netherlands)

    Groenendijk, Floris H; Mellema, Wouter W; van der Burg, Eline; Schut, Eva; Hauptmann, Michael; Horlings, Hugo M; Willems, Stefan M|info:eu-repo/dai/nl/33189582X; van den Heuvel, Michel M; Jonkers, Jos; Smit, Egbert F; Bernards, René|info:eu-repo/dai/nl/070416990

    2015-01-01

    The multikinase inhibitor sorafenib is under clinical investigation for the treatment of many solid tumors, but in most cases, the molecular target responsible for the clinical effect is unknown. Furthermore, enhancing the effectiveness of sorafenib using combination strategies is a major clinical

  19. Free fatty acids profiling in response to carnitine synergize with ...

    African Journals Online (AJOL)

    Background: The objective of this study was to investigate the fatty acids profiling in diabetic rats induced by sterptozocine (STZ) and their response to administration of lutein and carnitine. Materials and methods: Ninety male albino rats were divided into 6 groups as follows: Normal control. The remaining rats were injected ...

  20. Endo/exo-synergism of cellulases increases with substrate conversion

    DEFF Research Database (Denmark)

    Olsen, Johan Pelck; Borch, Kim; Westh, Peter

    2017-01-01

    Synergy between cellulolytic enzymes is important for their industrial utilization, and numerous studies have addressed the problem of how to optimize the composition of enzyme cocktails with respect to this. The degree of synergy (DS) may change with substrate conversion, and some studies have s...

  1. Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical cancer.

    Science.gov (United States)

    Byun, Jung Mi; Jeong, Dae Hoon; Lee, Dae Sim; Kim, Joo Ran; Park, Sae Gwang; Kang, Mi Seon; Kim, Young Nam; Lee, Kyung Bok; Sung, Moon Su; Kim, Ki Tae

    2013-04-01

    Tetraarsenic oxide (As4O6, TAO) is a new arsenic compound that inhibits cell growth and induces apoptosis in human cervical cancer cell lines. In the present study, we report that the growth of tumor cells (CaSki) was inhibited by treatment with TAO alone or in combination with cisplatin or paclitaxel in vitro and in vivo. Proliferation was assessed by WST-1 assay, and apoptosis was assessed by Annexin-V/PI FACS analysis in the CaSki cell line treated with a single agent or with the combinations of two agents. Expression of apoptosis-related proteins was analyzed by western blot analysis. A mouse xenograft model using CaSki cells was used to determine the in vivo activity of tetraarsenic oxide alone and in combination with cisplatin or paclitaxel by estimation of tumor size. At the end of the experiment, tumor tissue from each mouse was removed and processed for TUNEL analysis for confirmation of apoptotic cells. TAO was able to inhibit cell proliferation in a time- and dose-dependent manner. A combination of TAO and cisplatin effectively induced apoptosis by activating caspase-3. Using a mouse xenograft model, the sizes of tumors which were treated with a single agent and with a combination of agents decreased in a time-dependent manner. A combination of TAO and cisplatin resulted in a significantly reduced tumor size (Pcisplatin. Thus, TAO is a good candidate for use in a combined regimen with cisplatin for patients with cervical cancer.

  2. Photodynamic action of methylene blue: mutagenesis and synergism

    International Nuclear Information System (INIS)

    Capella, M.A.M.

    1988-01-01

    The associated mutagenesis and the interactions with physical agents in order to potencialize its biological effects are studied. The induction of mutation in bacterias due to photodynamic action of methylene blue is presented as well as the induction of single breaks in bacterial DNA and the relationship between the repair systems, especially the SOS one. The interaction of the photodynamic therapy with low intensity electric current is discussed. (M.A.C.) [pt

  3. Synergizing expectation and execution for stroke communities of practice innovations

    Directory of Open Access Journals (Sweden)

    Riopelle Richard J

    2010-06-01

    Full Text Available Abstract Background Regional networks have been recognized as an interesting model to support interdisciplinary and inter-organizational interactions that lead to meaningful care improvements. Existing communities of practice within the a regional network, the Montreal Stroke Network (MSN offers a compelling structure to better manage the exponential growth of knowledge and to support care providers to better manage the complex cases they must deal with in their practices. This research project proposes to examine internal and external factors that influence individual and organisational readiness to adopt national stroke best practices and to assess the impact of an e-collaborative platform in facilitating knowledge translation activities. Methods We will develop an e-collaborative platform that will include various social networking and collaborative tools. We propose to create online brainstorming sessions ('jams' around each best practice recommendation. Jam postings will be analysed to identify emergent themes. Syntheses of these analyses will be provided to members to help them identify priority areas for practice change. Discussions will be moderated by clinical leaders, whose role will be to accelerate crystallizing of ideas around 'how to' implement selected best practices. All clinicians (~200 involved in stroke care among the MSN will be asked to participate. Activities during face-to-face meetings and on the e-collaborative platform will be documented. Content analysis of all activities will be performed using an observation grid that will use as outcome indicators key elements of communities of practice and of the knowledge creation cycle developed by Nonaka. Semi-structured interviews will be conducted among users of the e-collaborative platform to collect information on variables of the knowledge-to-action framework. All participants will be asked to complete three questionnaires: the typology questionnaire, which classifies individuals into one of four mutually exclusive categories of information seeking; the e-health state of readiness, which covers ten domains of the readiness to change; and a community of practice evaluation survey. Summary This project is expected to enhance our understanding of collaborative work across disciplines and organisations in accelerating implementation of best practices along the continuum of care, and how e-technologies influence access, sharing, creation, and application of knowledge.

  4. Synergizing Crosswell Seismic and Electromagnetic Techniques for Enhancing Reservoir Characterization

    KAUST Repository

    Katterbauer, Klemens

    2015-11-18

    Increasing complexity of hydrocarbon projects and the request for higher recovery rates have driven the oil-and-gas industry to look for a more-detailed understanding of the subsurface formation to optimize recovery of oil and profitability. Despite the significant successes of geophysical techniques in determining changes within the reservoir, the benefits from individually mapping the information are limited. Although seismic techniques have been the main approach for imaging the subsurface, the weak density contrast between water and oil has made electromagnetic (EM) technology an attractive complement to improve fluid distinction, especially for high-saline water. This crosswell technology assumes greater importance for obtaining higher-resolution images of the interwell regions to more accurately characterize the reservoir and track fluid-front developments. In this study, an ensemble-Kalman-based history-matching framework is proposed for directly incorporating crosswell time-lapse seismic and EM data into the history-matching process. The direct incorporation of the time-lapse seismic and EM data into the history-matching process exploits the complementarity of these data to enhance subsurface characterization, to incorporate interwell information, and to avoid biases that may be incurred from separate inversions of the geophysical data for attributes. An extensive analysis with 2D and realistic 3D reservoirs illustrates the robustness and enhanced forecastability of critical reservoir variables. The 2D reservoir provides a better understanding of the connection between fluid discrimination and enhanced history matches, and the 3D reservoir demonstrates its applicability to a realistic reservoir. History-matching enhancements (in terms of reduction in the history-matching error) when incorporating both seismic and EM data averaged approximately 50% for the 2D case, and approximately 30% for the 3D case, and permeability estimates were approximately 25% better compared with a standard history matching with only production data.

  5. How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

    Science.gov (United States)

    Yuan, Haidan; Ma, Qianqian; Cui, Heying; Liu, Guancheng; Zhao, Xiaoyan; Li, Wei; Piao, Guangchun

    2017-07-07

    Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.

  6. Space Resource Utilization: Technologies and Potential Synergism with Terrestrial Mining

    Science.gov (United States)

    Sanders, Gerald B.

    2015-01-01

    Space Resources and Their Uses: The idea of using resources in space to support human exploration and settlement or for economic development and profit beyond the surface of Earth has been proposed and discussed for decades. Work on developing a method to extract oxygen from lunar regolith started even before humans set foot on the Moon for the first time. The use of space resources, commonly referred to as In Situ Resource Utilization (ISRU), involves the processes and operations to harness and utilize resources in space (both natural and discarded) to create products for subsequent use. Potential space resources include water, solar wind implanted volatiles (hydrogen, helium, carbon, nitrogen, etc.), vast quantities of metals and minerals in extraterrestrial soils, atmospheric constituents, unlimited solar energy, regions of permanent light and darkness, the vacuum and zero-gravity of space itself, trash and waste from human crew activities, and discarded hardware that has completed its primary purpose. ISRU covers a wide variety of concepts, technical disciplines, technologies, and processes. When considering all aspects of ISRU, there are 5 main areas that are relevant to human space exploration and the commercialization of space: 1. Resource Characterization and Mapping, 2. In Situ Consumables Production, 3. Civil Engineering and Construction, 4. In Situ Energy Production and Storage, and 5. In Situ Manufacturing.

  7. Interaction and Synergism of Microbial Fuel Cell Bacteria within Methanogenesis

    Science.gov (United States)

    Klaus, David

    2004-01-01

    Biological hydrogen production from waste biomass has both terrestrial and Martian advanced life support applications. On earth, biological hydrogen production is being explored as a greenhouse neutral form of clean and efficient energy. In a permanently enclosed space habitat, carbon loop closure is required to reduce mission costs. Plants are grown to revitalize oxygen supply and are consumed by habitat inhabitants. Unharvested portions must then be recycled for reuse in the habitat. Several biological degradation techniques exist, but one process, biophotolysis, can be used to produce hydrogen from inedible plant biomass. This process is two-stage, with one stage using dark fermentation to convert plant wastes into organic acids. The second stage, photofermentation, uses photoheterotrophic purple non-sulfur bacteria with the addition of light to turn the organic acids into hydrogen and carbon dioxide. Such a system can prove useful as a co-generation scheme, providing some of the energy needed to power a larger primary carbon recovery system, such as composting. Since butyrate is expected as one of the major inputs into photofermentation, a characterization study was conducted with the bacterium Rhodobacter sphaeroides SCJ, a novel photoheterotrophic non-sulfur purple bacteria, to examine hydrogen production performance at 10 mM-100 mM butyrate concentrations. As butyrate levels increased, hydrogen production increased up to 25 mM, and then decreased and ceased by 100 mM. Additionally, lag phase increased with butyrate concentration, possibly indicating some product inhibition. Maximal substrate conversion efficiency was 8.0%; maximal light efficiency was 0.89%; and maximal hydrogen production rate was 7.7 Umol/mg/cdw/hr (173 ul/mg cdw/hr). These values were either consistent or lower than expected from literature.

  8. Cytokines Synergize to Combat Metastatic Neuroblastoma | Center for Cancer Research

    Science.gov (United States)

    Neuroblastoma is the most common extracranial solid tumor in children, and clinical outcomes of patients with this disease are quite variable. Prognosis is particularly poor for patients with high-risk tumors (classification based on patients’ age, extent of disease spread, and other biological features).

  9. Synergizing expectation and execution for stroke communities of practice innovations

    Science.gov (United States)

    2010-01-01

    Background Regional networks have been recognized as an interesting model to support interdisciplinary and inter-organizational interactions that lead to meaningful care improvements. Existing communities of practice within the a regional network, the Montreal Stroke Network (MSN) offers a compelling structure to better manage the exponential growth of knowledge and to support care providers to better manage the complex cases they must deal with in their practices. This research project proposes to examine internal and external factors that influence individual and organisational readiness to adopt national stroke best practices and to assess the impact of an e-collaborative platform in facilitating knowledge translation activities. Methods We will develop an e-collaborative platform that will include various social networking and collaborative tools. We propose to create online brainstorming sessions ('jams') around each best practice recommendation. Jam postings will be analysed to identify emergent themes. Syntheses of these analyses will be provided to members to help them identify priority areas for practice change. Discussions will be moderated by clinical leaders, whose role will be to accelerate crystallizing of ideas around 'how to' implement selected best practices. All clinicians (~200) involved in stroke care among the MSN will be asked to participate. Activities during face-to-face meetings and on the e-collaborative platform will be documented. Content analysis of all activities will be performed using an observation grid that will use as outcome indicators key elements of communities of practice and of the knowledge creation cycle developed by Nonaka. Semi-structured interviews will be conducted among users of the e-collaborative platform to collect information on variables of the knowledge-to-action framework. All participants will be asked to complete three questionnaires: the typology questionnaire, which classifies individuals into one of four mutually exclusive categories of information seeking; the e-health state of readiness, which covers ten domains of the readiness to change; and a community of practice evaluation survey. Summary This project is expected to enhance our understanding of collaborative work across disciplines and organisations in accelerating implementation of best practices along the continuum of care, and how e-technologies influence access, sharing, creation, and application of knowledge. PMID:20529305

  10. Atividade antimicrobiana e sinérgica das frações das folhas de Schinopsis brasiliensis Engl. frente a clones multirresistentes de Staphylococcus aureus Antimicrobial and synergic activity of fractions from the leaves of Schinopsis brasiliensis Engl. against Staphylococcus aureus multiresistant clones

    Directory of Open Access Journals (Sweden)

    A.M. Saraiva

    2013-01-01

    Full Text Available No presente estudo objetivou-se avaliar a atividade antimicrobiana e sinérgica de 4 frações das folhas de Schinopsis brasiliensis Engl (F1', F2', F1" e F2" frente às cepas Staphylococcus aureus MRSA multirresistentes. Os métodos utilizados foram poços de difusão em ágar, concentração mínima inibitória (CMI - diluição em ágar, e bioautografia. Nos resultados bioautográficos observou-se três halos de inibição relacionados, no mínimo, à quatro constituintes ativos; sendo dois deles isolados das folhas (galato de metila e ácido gálico. A F2" (200∝g/mL apresentou halos de inibição de 16 e 19mm frente as cepas de S. aureus multirresistente e Klebsiella pneumoniae, e CMI 100∝g/mL, respectivamente. Quanto as análises das associações das frações F1" ou F2" (25 e 50∝g/mL com a tetraciclina e oxacilina, mostraram ações aditiva e sinérgica para a F2" (50∝g/mL, embora não suficiente para que a CMI atingisse valores inferiores a 2 e 4∝g/mL, necessário para serem classificadas como cepas sensíveis a oxacilina e tetraciclina, respectivamente. "Assim, conclui-se que a F2" das folhas de S. brasiliensis apresentou potencial antimicrobiano frente às cepas de S. aureus MRSA multirresistentes e que as associações das frações com os antibióticos testados não apresentaram benefícios não justificando o uso concomitante.The aim of this study was to evaluate the antimicrobial and synergic activity of 4 leaf fractions of Schinopsis brasiliensis Engl (F1', F2', F1" and F2" against multidrug-resistant Staphylococcus aureus strains. The used methods were agar well diffusion, minimum inhibitory concentration (MIC - agar dilution, and bioautography. The bioautographic results showed three inhibition zones that corresponded to at least four active compounds, two of which (methyl gallate and gallic acid have already been isolated from leaves. The F2" (200∝g/mL fraction showed inhibition zones of 16 mm and 19 mm against S

  11. The effect of opioid antagonists on synergism between dexketoprofen and tramadol.

    Science.gov (United States)

    Zegpi, C; Gonzalez, C; Pinardi, G; Miranda, H F

    2009-10-01

    The antinociceptive activity of dexketoprofen was studied in mice using the formalin assay for orofacial pain. The interaction between dexketoprofen and co-administered tramadol was studied using isobolographic analysis. The intraperitoneal administration of dexketoprofen or tramadol, showed dose-dependent antinociceptive activity in both phases of the assay. When administered together, the interaction was mildly synergistic during the first phase, and antagonistic in the second phase. Selective opioid receptor antagonists where used in order to measure the analgesic activity of tramadol in other regions of the CNS. The co-administration of dexketoprofen and tramadol, with previous administration of naltrexone, showed high synergistic activity during the first phase, and less but still synergistic during the second. When using naltrindole, the interaction was mildly more synergistic than the mixture dexketoprofen+tramadol during both phases. Using norbinaltorphimine, the interaction was synergistic in both phases, more marked in the second. These results suggest that the opioid activity of tramadol has an inhibiting effect in antinociceptive activity of the interaction between dexketoprofen and tramadol during the inflammatory (late) stages of pain.

  12. Synergic effect of combination of glycyrol and fluconazole against experimental cutaneous candidiasis due to Candida albicans.

    Science.gov (United States)

    Rhew, Zheong-Imm; Han, Yongmoon

    2016-10-01

    In this study, we investigated the anti-fungal activity of glycyrol, a coumarine isolated from licorice (Glycyrrhizae Radix), in a murine model of cutaneous candidiasis caused by Candida albicans. Compared to the infected sites, located on the mice's back, of the untreated control mice, the infected sites treated with glycyrol had reduced CFU (colony forming unit) values up to 60 and 85.5 % at 20 and 40 μg/mouse of glycyrol, respectively (P < 0.01). The antifungal activity of glycyrol was synergistically increased when glycyrol (10 μg/mouse) was combined with fluconazole (10 μg/mouse), demonstrating that the combination therapy is approximately 4 times more effective than fluconazole alone at 20 μg/mouse (P < 0.01). Additionally, the combination activity was 1.65 times greater than the antifungal activity of fluconazole alone at 40 μg/mouse (P < 0.05). In seeking glycyrol's antifungal mechanism, we determined that glycyrol inhibited hyphal induction and cell wall adherence of C. albicans. Thus, it is very likely that, by damaging the cell wall, glycyrol helps fluconazole invade C. albicans more readily and attack fluconazole's target in the fungus membrane. In summary, our data indicate that glycyrol may contribute to the development of a novel agent that possesses antifungal activity against cutaneous candidiasis.

  13. FREE FATTY ACIDS PROFILING IN RESPONSE TO CARNITINE SYNERGIZE WITH LUTEIN IN DIABETIC RATS.

    Science.gov (United States)

    Al-Malki, Abdulrahman L; Moselhy, Said S

    2016-01-01

    The objective of this study was to investigate the fatty acids profiling in diabetic rats induced by sterptozocine (STZ) and their response to administration of lutein and carnitine. Ninety male albino rats were divided into 6 groups as follows: Normal control. The remaining rats were injected i.p a single dose of STZ (65 mg /kg bw) for induction of diabetes. Diabetic rats were grouped as: GP II: (Untreated): GP III: Rats were given orally with L-lutein (100 mg/kg bw).GP IV: Rats were given carnitine (30 μg/kg) i.p . GP V: Rats were given carnitine and lutein GP VI were given metformin (100mg/kg bw/d) for 6 weeks. Treatment of diabetic rats with lutein, L-carnitine, combined decreased the levels of glucose, HA1C compared with untreated diabetic (plutein, carnitine, combined to normal rats significantly decreased the levels of myristic, palmitice, palmitoleic, stearic, linoleic, α-linolenic, arachidic and eicosadienoic when compared with control normal rats (plutein and carnitine could ameliorate deleterious effect induced by STZ and attenuate the changed fatty acid composition.

  14. Novel inhibitors of Staphylococcus aureus RnpA that synergize with mupirocin.

    Science.gov (United States)

    Lounsbury, Nicole; Eidem, Tess; Colquhoun, Jennifer; Mateo, George; Abou-Gharbia, Magid; Dunman, Paul M; Childers, Wayne E

    2018-01-31

    We recently discovered RnpA as a promising new drug discovery target for methicillin-resistant S. aureus (MRSA). RnpA is an essential protein that is thought to perform two required cellular processes. As part of the RNA degrasome Rnpa mediates RNA degradation. In combination with rnpB it forms RNase P haloenzymes which are required for tRNA maturation. A high throughput screen identified RNPA2000 as an inhibitor of both RnpA-associated activities that displayed antibacterial activity against clinically relevant strains of S. aureus, including MRSA. Structure-activity studies aimed at improving potency and replacing the potentially metabotoxic furan moiety led to the identification of a number of more potent analogs. Many of these new analogs possessed overt cellular toxicity that precluded their use as antibiotics but two derivatives, including compound 5o, displayed an impressive synergy with mupirocin, an antibiotic used for decolonizing MSRA whose effectiveness has recently been jeopardized by bacterial resistance. Based on our results, compounds like 5o may ultimately find use in resensitizing mupirocin-resistant bacteria to mupirocin. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Pump selection and Synergic Retrofit trademark; Pumpenauswahl und Synergetic Retrofit trademark

    Energy Technology Data Exchange (ETDEWEB)

    Hirschberger, M.; Kuhlmann, J.; Hofaecker, G. [Ruhrpumpen GmbH, Witten (Germany)

    2000-12-01

    Selection of the right pump for a given application is the crucial factor that determines its efficient and reliable operation. Of the performance data, the NPSHa value is the most important. The suction specific speed (SSS) may be an important decision aid. The achievable pump efficiency depends on the specific pump speed n. The pump should also run near optimum for optimum energy use and minimum vibrations. This will increase reliability and prolong the pump life. [German] Die Auswahl der richtigen Pumpe fuer den jewelligen Anwendungsfall ist entscheidend fuer den effizienten und zuverlaessigen Einsatz. Die Festlegung der Betriebsdaten ist dabei der erste wichtige Schritt, wobei der vorhandene NPSHa-Wert der Anlage von entscheidender Bedeutung ist. Die suction specific speed SSS kann dabei eine wichtige Entscheidungshilfe sein. Der erreichbare Wirkungsgrad ist von der spezifischen Drehzahl nq der Pumpe abhaengig. Des Weiteren ist es wichtig, dass die Pumpe im Bereich des Optimums arbeiten sollte. Sie nutzt dann die eingesetzte Energie optimal aus. In diesem Arbeitsbereich sind die Schwingungswerte und damit die Belastung der Pumpe am geringsten. Zuverlaessigkeit und Lebensdauer werden somit erhoeht. (orig.)

  16. Heterotrophic microalgae cultivation to synergize biodiesel production with waste remediation: progress and perspectives.

    Science.gov (United States)

    Venkata Mohan, S; Rohit, M V; Chiranjeevi, P; Chandra, Rashmi; Navaneeth, B

    2015-05-01

    Microalgae are inexhaustible feedstock for synthesis of biodiesel rich in polyunsaturated fatty acids (PUFA) and valuable bioactive compounds. Their cultivation is critical in sustaining the global economy in terms of human consumption of food and fuel. When compared to autotrophic cultivation, heterotrophic systems are more suitable for producing high cell densities of microalgae for accumulation of large quantities of lipids (triacylglycerols) which can be converted into biodiesel. Consorted efforts are made in this communication to converge recent literature on heterotrophic cultivation systems with simultaneous wastewater treatment and algal oil production. Challenges faced during large scale production and limiting factors which hinder the microalgae growth are enumerated. A strategic deployment of integrated closed loop biorefinery concept with multi-product recovery is proposed to exploit the full potential of algal systems. Sustainable algae cultivation is essential to produce biofuels leading to green future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque Biofilms In Vivo

    Science.gov (United States)

    Falsetta, Megan L.; Klein, Marlise I.; Colonne, Punsiri M.; Scott-Anne, Kathleen; Gregoire, Stacy; Pai, Chia-Hua; Gonzalez-Begne, Mireya; Watson, Gene; Krysan, Damian J.; Bowen, William H.

    2014-01-01

    Streptococcus mutans is often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC). S. mutans may not act alone; Candida albicans cells are frequently detected along with heavy infection by S. mutans in plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viable S. mutans cells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeable S. mutans microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Our in vitro data also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence with C. albicans induces the expression of virulence genes in S. mutans (e.g., gtfB, fabM). We also found that Candida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease. PMID:24566629

  18. Synergism between soluble guanylate cyclase signaling and neuropeptides extends lifespan in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Abergel, Rachel; Livshits, Leonid; Shaked, Maayan; Chatterjee, Arijit Kumar; Gross, Einav

    2017-04-01

    Oxygen (O 2 ) homeostasis is important for all aerobic animals. However, the manner by which O 2 sensing and homeostasis contribute to lifespan regulation is poorly understood. Here, we use the nematode Caenorhabditis elegans to address this question. We demonstrate that a loss-of-function mutation in the neuropeptide receptor gene npr-1 and a deletion mutation in the atypical soluble guanylate cyclase gcy-35 O 2 sensor interact synergistically to extend worm lifespan. The function of npr-1 and gcy-35 in the O 2 -sensing neurons AQR, PQR, and URX shortens the lifespan of the worm. By contrast, the activity of the atypical soluble guanylate cyclase O 2 sensor gcy-33 in these neurons is crucial for lifespan extension. In addition to AQR, PQR, and URX, we show that the O 2 -sensing neuron BAG and the interneuron RIA are also important for the lifespan lengthening. Neuropeptide processing by the proprotein convertase EGL-3 is essential for lifespan extension, suggesting that the synergistic effect of joint loss of function of gcy-35 and npr-1 is mediated through neuropeptide signal transduction. The extended lifespan is regulated by hypoxia and insulin signaling pathways, mediated by the transcription factors HIF-1 and DAF-16. Moreover, reactive oxygen species (ROS) appear to play an important function in lifespan lengthening. As HIF-1 and DAF-16 activities are modulated by ROS, we speculate that joint loss of function of gcy-35 and npr-1 extends lifespan through ROS signaling. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  19. Infusions and decoctions of mixed herbs used in folk medicine: synergism in antioxidant potential.

    Science.gov (United States)

    Guimarães, Rafaela; Barros, Lillian; Carvalho, Ana Maria; Ferreira, Isabel C F R

    2011-08-01

    Infusions (herbal teas) and decoctions are used frequently to administer oral doses of herbs. Although some herbs are used as single ingredients, they are often prepared as mixtures, as reported by numerous ethnobotanical surveys. The present work was carried out to identify the different types of interaction (synergistic, additive and antagonistic effects) which may be found in the antioxidant activity of preparations from mixtures of the popular herbs Aloysia citrodora (lemon verbena), Foeniculum vulgare (fennel) and Mentha spicata (spearmint). Herbs were prepared using traditional methods, and the effects after different periods of storage, up to 120 days, were also evaluated. Antioxidant activity was evaluated using DPPH radical scavenging activity, reducing power and inhibition of lipid peroxidation by the β-carotene - linoleate system and the TBARS assay. Known antioxidant compounds such as total phenolics, flavonoids, ascorbic acid and reducing sugars were also determined. Spearmint was found to be present in the herb mixtures with the greatest antioxidant activity and these also had the highest flavonoid content. The most potent antioxidant activity was found in combinations of different herbs, suggesting synergistic effects. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Wax co-cracking synergism of high density polyethylene to alternative fuels

    Directory of Open Access Journals (Sweden)

    Magdy Motawie

    2015-09-01

    Full Text Available Attempts have been made to understand the thermal degradation of high density polyethylene (HDPE and their combined co-cracking using different ratios of HDPE and petroleum wax under nitrogen atmosphere. We have conducted the experiments using HDPE as the raw material and petroleum wax as co-feed by at 400 and 450 °C reaction temperatures. The product distribution was noted along with reaction time of 0.5–3 h for the degradation. Thermal gravimetric analysis (TGA technique was used to measure the weight change of the feedstock as a function of temperature and time. Differential scanning calorimetry (DSC was used to determine the degradation temperature. Products were characterized using gas chromatography (GC and infrared spectroscopy (FTIR, some other standard physical methods were used to determine the main properties of the liquid products. Results show that the mixed plastic-wax samples could be converted into gases, gasoline, and middle distillate depending upon the composition of feed polymer/wax ratio. It was found that the products mostly consisted of paraffin and olefin compounds, with carbon numbers of C1–C4, C5–C9 and C10–C19 in the case of gases, gasoline and middle distillate respectively.

  1. Beyond tradition: synergizing intellectual and material capital to forge the new academic-service partnership.

    Science.gov (United States)

    Bleich, Michael R; Hewlett, Peggy O; Miller, Karen L; Bender, Kaye

    2004-01-01

    Academic-service partnerships are being touted as a solution to workforce problems. "Traditional" approaches to these partnerships have been directed primarily at academic and hospital institutions for mutual benefit. An expanded model of partnership possibilities is presented through three detailed exemplars that include population health (with descriptors from an Institute of Medicine study addressing the public's health in the 21st century), public-private ventures (public institution with faith-based and community agencies), and nursing-corporate opportunities (academia and a proprietary information technology corporate supplier). The benefits of these expanded partnerships and the criteria for selecting a partnership sensitive to the scholarship of practice and the mission/purpose/goals of each partnering organization is highlighted.

  2. Synergic application of spectroscopic and theoretical methods to the chlorogenic acid structure elucidation

    Science.gov (United States)

    Marković, Svetlana; Tošović, Jelena; Dimitrić Marković, Jasmina M.

    2016-07-01

    Although chlorogenic acid (5-O-caffeoylquinic acid, 5CQA) is a dietary polyphenol known for its pharmacological and nutritional properties, its structural features have not been completely elucidated. This is the first study whose aim is to contribute to clarification of the 5CQA structure by comparing the experimental and simulated IR, Raman, 1H NMR, 13C NMR, and UV spectra. For this purpose, a comprehensive conformational analysis of 5CQA was performed to reveal its most stable conformations in the gas-state and solution (DMSO and methanol). The lowest-energy conformers were used to predict the spectra at two levels of theory: B3LYP-D3/and M06-2X/6-311+G(d,p) in combination with the CPCM solvation model. Both methods provide very good agreement between all experimental and simulated spectra, thus indicating correct arrangement of the atoms in the 5CQA molecule. The quinic moiety is characterized with directed hydrogen bonds, where the carboxylic hydrogen is not oriented towards the carbonyl oxygen of the carboxylic group, but towards the oxygen of the proximate hydroxyl group. In the gas-state the lowest-energy conformers are characterized with the O4sbnd H4 ⋯ O9‧ hydrogen bond, whereas in the solvated state the structures with the O4sbnd H4 ⋯ O10‧ hydrogen bond prevail. Knowing the fine structural details, i.e. the proper conformation of 5CQA, provides a solid base for all further investigations related to this compound.

  3. S Synerg with istic ac thiam ction o ethoxa of Azos am on maize ...

    African Journals Online (AJOL)

    sunny

    The work was developed in the Laboratory of Plant Physiology and. Laboratory of Phytopathology, State University of ... Treatments were added to seeds by hand shaking in polyethylene bags until visual homogeneity. The ..... induction involving high metabolic costs, it is necessary to complement the fertilization with higher ...

  4. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  5. Compositional Analysis of Martian Soil: Synergism of APEX and MECA Experiments on MPS 2001

    Science.gov (United States)

    Arvidson, R.; Marshall, J.

    1999-01-01

    The APEX (ATHENA Precursor Experiment) payload for the Mars 2001 mission will analyze soil and dust with a multispectral panoramic imager and an emission spectrometer on a mast on the lander, a Moessbauer spectrometer on the lander robotic arm (RA), and APXS measurements on the Marie Curie rover. These analytical methods will provide data on elemental abundances and mineralogy. The MECA payload on the lander will apply microscopy, AFM, wet chemistry, adhesive substrates, and electrometry to determine the shape and size of particles in the soil and dust, the presence of toxic substances, and electrostatic, magnetic, and hardness qualities of particles. The two experiments will complement one another through several interactions: (1) The panoramic imager provides the geological setting in which both APEX and MECA samples are acquired, (2) The RA provides samples to MECA from the surface and subsurface and will permit APEX analytical tools access to materials below the immediate surface, (3) Comparisons can be made between elemental analyses of the Moessbauer, IR, APXS on APEX and the wet chemistry of MECA which will define trace elements (ionic species in solution) and soil redox potential and conductivity. (4) APEX bulk compositional measurements will place MECA trace measurements in context, and similarly, MECA microscopy will provide particle size data that may correlate with compositional differences determined by the APEX instruments. Additionally, lithic fragments viewed by the MECA microscope station should correlate with mineral/rock species inferred by APEX data, (5) If APEX instruments detect quartz for example, the scratch plates of the MECA microscope stage will define if a mineral of this hardness is registered during abrasion tests. This is by no means an exhaustive list of potential interactions, but it is clear that both the sheer number of analytical techniques and their complementarity should provide an analytically powerful capability for both planetary and HEDS communities.

  6. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette

    Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular...... dysfunction and local vascular inflammation has been suggested. Aim: This study addresses the involvement of vascular risk factors of MS and T2DM such as elevated glucose, increased insulin levels, as well as selected cytokines on vascular contractile function. Methods: Small mesenteric resistance arteries...... isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined...

  7. Synergism of diabetic and inflammatory culture conditions on reactivity of isolated small arteries

    DEFF Research Database (Denmark)

    Blædel, Martin Mads; Boonen, Harrie C.M.; Sams Nielsen, Anette

    Background: Cardiovascular disease (CVD) is the manifestation of atherosclerosis, which has been linked to obesity, the metabolic syndrome (MS) and overt type 2 diabetes (T2DM). Vascular dysfunction has been proposed to precede atherosclerosis, and in addition, a correlation between vascular...... isolated from 8 week old male SD rats were cultured for 21 hours in Endothelial Basal Medium (EBM-2) in petri dishes and in the absence or presence of either 30 mM D-glucose, 100 nM insulin, 100 ng/mL TNFa or any combination of these. Contractile reactivity of normalised arteries was then determined...... by wire myography as a response to cumulatively increasing concentrations of noradrenaline (NA). Results: 21 hour culture of isolated mesenteric arteries significantly reduced the arteries maximal high potassium-induced contractile reactivity and increased the contractility to noradrenaline slightly...

  8. Synergism between ultraviolet radiation and reductone in Escherichia coli UVR: quantitative analysis of produced injuries

    International Nuclear Information System (INIS)

    Mota, H.C.

    1980-01-01

    The relationship between cell viability and DNA-single and double-strand breaks induced by UV-reductone treatment of E.coli AB1157 and AB1886 cells was studied. A molecular and quantitative analysis was done by sedimentation in sucrose gradients. Bacteriophage T4-DNA was submitted to similar conditions. The two bacterial strains showed the same kinetics of single strand-breaks induction by reductone, in agreement with the hypothesis that the repair of these lesion is independent of uvr A uvr B genes product. This paper suggests that the 'UV-sensibilization' to reductone action is linked to a synergistic process between reductone induced single breaks and the enzymatic incisions accumulated by modification in the excision repair, during the treatment. (author)

  9. Radiation embrittlement of PWR reactor vessel weld metals: nickel and copper synergism effects

    International Nuclear Information System (INIS)

    Guionnet, C.; Houssin, B.; Brasseur, D.; Lefort, A.; Gros, D.; Perdreau, R.

    1982-01-01

    In general, PWR reactor vessels are made of low alloy nickel manganese molybdenum steel. The behavior of this material under neutron irradiation is now relatively well known. On the other hand, the weld metals used for these vessels, which are also irradiated, exhibit a wide range of metallurgical structures and trace element contents, and further studies are necessary to gain a better understanding of their behavior under irradiation. Fourteen weld deposits were irradiated with a fluence of 5 x 10 19 n/cm 2 (E > 1 MeV) at 288 0 C. The results of the corresponding Charpy V-notch impact tests are presented. Emphasis is given to the roles of copper and nickel. The effects of the different welding processes (shielded metal arc and submerged arc welding) are also studied. The consumable products used were either of commercial origin or made specially in order to obtain copper contents between 0.02 and 0.18% and nickel contents between 0.07 and 1.85%. The results indicate that nickel strongly enhances irradiation damage in the same way as copper, but the effects of the nickel contents seem to be very dependent on the copper contents. The roles of these two elements (and also that of phosphorus) in the brittle-ductile transition temperature shift is quantitatively expressed in a formula which takes the irradiation damage of these 14 welds into account, together with that of 16 further base metal samples irradiated under identical conditions in the same laboratory. Meanwhile irradiation damage did not appear to be related to the particular welding process used

  10. Synergism between methods for inhibiting the spoilage of damp maize during storage

    International Nuclear Information System (INIS)

    Paster, N.; Menasherov, M.; Lacey, J.; Fanelli, C.

    1992-01-01

    Combinations of physical and chemical treatments were used in attempts to control mould development in maize grain containing 18% moisture. The treatments involved the use of propionic acid (0.1 or 0.2% v/w), γ-irradiation (1.0 or 2.0 kGy) and modified atmospheres (40% or 60% CO 2 in the presence of 20% oxygen) either separately or in combination. Mould colonisation during storage was assessed by dilution plating and measurements of respiratory CO 2 produced by grain samples. Spoilage was most effectively counteracted using a combination of 0.2% propionic acid with 2 kGy irradiation and 40% or 60% CO 2 , and this was more successful than any single component used separately, even after 45 days of treatment. Synergistic interaction between treatments thus allows the prospect of more efficient maize storage rather than employing single techniques. This concept could be important in practice because each component is employed only at a relatively low level of intensity. (author)

  11. Role of Surface Interactions in the Synergizing Polymer/Clay Flame Retardant Properties

    Energy Technology Data Exchange (ETDEWEB)

    Pack, S.; Kashiwagi, T; Cao, C; Korach, C; Lewin, M; Rafailovich, M

    2010-01-01

    The absorption of resorcinol di(phenyl phosphate) (RDP) oligomers on clay surfaces has been studied in detail and is being proposed as an alternative method for producing functionalized clays for nanocomposite polymers. The ability of these clays to be exfoliated or intercalated in different homopolymers was investigated using both transmission electron microscopy and small-angle X-ray scattering results, compared with contact angle measurements on Langmuir-Blodgett clay monolayers, where the interfacial energies were used as predictors of the polymer/clay interactions. We found that the contact angle between PS/RDP clay monolayer substrates was {approx}2.5{sup o}, whereas the angle for polystyrene (PS)/Cloisite 20A clays substrates was {approx}32{sup o}, consistent with the large degree of exfoliation observed in PS for the RDP-coated clays. The interfacial activity of these clays was also measured, and we found that the RDP-coated clays segregated to the interfaces of PC/poly(styrene-co-acrylonitrile) blends, while they segregated into the poly(methyl methacrylate) (PMMA) domain of PS/PMMA blends. This morphology was explained in terms of the relative energy advantage in placing the RDP versus the Cloisite clays at the interfaces. Finally, we demonstrated the effects of the relative surface energies of the clays in segregating to the blend air interface when heated to high temperatures. The segregation was shown to affect the composition and mechanical properties of the resulting chars, which in turn could determine their flame retardant response.

  12. Synergism between hydrogen peroxide and seventeen acids against six bacterial strains.

    Science.gov (United States)

    Martin, H; Maris, P

    2012-09-01

    The objective of this study was to evaluate the bactericidal efficacy of hydrogen peroxide administered in combination with 17 mineral and organic acids authorized for use in the food industry. The assays were performed on a 96-well microplate using a microdilution technique based on the checkerboard titration method. The six selected strains were reference strains and strains representative of contaminating bacteria in the food industry. Each synergistic hydrogen peroxide/acid combination found after 5-min contact time at 20°C in distilled water was then tested in conditions simulating four different use conditions. Thirty-two combinations were synergistic in distilled water; twenty-five of these remained synergistic with one or more of the four mineral and organic interfering substances selected. Hydrogen peroxide/formic acid combination was synergistic for all six bacterial strains in distilled water and remained synergistic with interfering substances. Six other combinations maintained their synergistic effect in the presence of an organic load but only for one or two bacterial strains. Synergistic combinations of disinfectants were revealed, among them the promising hydrogen peroxide/formic acid combination. A rapid screening method was proposed and used to reveal the synergistic potential of disinfectant and/or sanitizer combinations. © 2012 ANSES Fougères Laboratory Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  13. Synergic effect of Citric Acid and Red Onion skin extract on the ...

    African Journals Online (AJOL)

    Michael Horsfall

    ABSTRACT The antioxidant potentials of citric acid and onion skin extract on the oxidative stability of vegetable oil were examined. Results from the peroxide values showed that citric acid had the best antioxidative potentials at a concentration of 0.2g/100g of vegetable oil. This was followed by the antioxidative potentials of ...

  14. Extinction of fear is facilitated by social presence: Synergism with prefrontal oxytocin.

    Science.gov (United States)

    Brill-Maoz, Naama; Maroun, Mouna

    2016-04-01

    This study addressed the question of whether extinction in pairs would have a beneficial effect on extinction of fear conditioning. To that end, we established an experimental setting for extinction in which we trained animals to extinguish contextual fear memory in pairs. Taking advantage of the role of oxytocin (OT) in the medial prefrontal cortex (mPFC) in the mediation of memory extinction and social interaction, we also sought to study its role in social interaction-induced effects on extinction. Our results clearly show that the social presence of another animal in the extinction context facilitates extinction, and that this facilitation is mediated through mPFC-OT. Our results suggest that social interaction may be a positive regulator of fear inhibition, implying that social interaction may be an easy, accessible therapeutic tool for the treatment of fear-associated disorders. Copyright © 2016. Published by Elsevier Ltd.

  15. Data on the positive synergic action of dimethylacetamide and trehalose on quality of cryopreserved chicken sperm

    Directory of Open Access Journals (Sweden)

    Fabio Mosca

    2016-12-01

    Full Text Available This data article contains supporting information regarding the research article entitled “Combined effect of permeant and non-permeant cryoprotectants on the quality of frozen/thawed chicken sperm”(Mosca et. al., 2016 [1]. The combined effect of the permeant cryoprotectants agent dimethylacetamide and the non-permeant cryoprotectants agent trehalose on the quality of frozen-thawed chicken semen was assessed. In particular, the quantitative dimethylacetamide/trehalose ratio was investigated freezing semen samples according to the following treatments: trehalose 0.1 M+0% dimethylacetamide (DMA-0, trehalose 0.1 M+3% dimethylacetamide (DMA-3, trehalose 0.1 M+6% dimethylacetamide (DMA-6.

  16. Analgesia Synergism of Essential Oil from Pericarp of Zanthoxylum schinifolium and Verapamil

    Science.gov (United States)

    Wu, Gao; Wu, Hanbin

    2014-01-01

    Objective. To evaluate the synergistic analgesic effect of essential oil of Zanthoxylum schinifolium Sieb. et Zucc. (EOZ) and verapamil (Ver). Method. The qualitative and quantitative composition of EOZ were determined with gas chromatography/Mass spectrometer. The interaction between EOZ and Ver in antinociceptive activity was evaluated by using acetic acid-induced writhing, hot plate, and tail flick tests in mice and in isolated toad sciatic nerve test. Results. Linalool, limonene, and sabinene are the major components of EOZ. EOZ (middle-dose: 40 mg·kg−1, high-dose: 80 mg·kg−1) and EOZ + Ver (Each dose group) have remarkable analgesic effects on pain in mice induced by acetic acid-induced writhing, hot plate, and tail flick tests. Low-dose EOZ (20 mg·kg−1) had no analgesic action, but when it is combined with Ver it has shown significant antinociception. Verapamil has a faint analgesic effect but was not able to inhibit action potential transmission in toad sciatic nerve. EOZ (0.2%) and EOZ + Ver (0.2% + 0.05%) also inhibited action potential transmission in toad sciatic nerve. Combination of EOZ with Ver had a greater analgesic effect and inhibition of nerve action potential transmission compared to its components EOZ and Ver. Conclusion. The combination of EOZ with Ver produces a synergistic analgesic effect. PMID:25114705

  17. Synergism between two helper cell subpopulations characterized by different radiosensitivity and nylon adherence

    International Nuclear Information System (INIS)

    Agarossi, G.; Mancini, C.; Doria, G.

    1981-01-01

    The present work extends our previous results on the radiosensitivity of the helper cell function. Two helper cell subpopulations, 1 radiosensitive and the other radioresistant, have been demonstrated in the spleen of mice at different times after priming with HRBC. The radiosensitive subpopulation increases with the increasing time interval between carrier-priming and irradiation. The 2 cell subpopulations have been further characterized by different nylon adherence properties: radioresistant helper cells adhere to nylon wool, whereas radiosensitive cells pass through. The 2 cell subpopulations were separated by x-irradiation and nylon wool filtration, and their helper activity was assessed separately or after recombination. The results favor the notion that 2 functionally independent helper T cells, as characterized by different radiosensitivity and nylon adherence, participate synergistically in the helper activity of primed spleen cells

  18. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  19. Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.

    Science.gov (United States)

    Min, Chengyin; Moore, Nathan; Shearstone, Jeffrey R; Quayle, Steven N; Huang, Pengyu; van Duzer, John H; Jarpe, Matthew B; Jones, Simon S; Yang, Min

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and inhibitors of DNA methyltransferase or histone deacetylase (HDAC) enzymes have exhibited activity in preclinical AML models. Combination studies with HDAC inhibitors plus DNA methyltransferase inhibitors have potential beneficial clinical activity in AML, however the toxicity profiles of non-selective HDAC inhibitors in the combination setting limit their clinical utility. In this work, we describe the preclinical development of selective inhibitors of HDAC1 and HDAC2, which are hypothesized to have improved safety profiles, for combination therapy in AML. We demonstrate that selective inhibition of HDAC1 and HDAC2 is sufficient to achieve efficacy both as a single agent and in combination with azacitidine in preclinical models of AML, including established AML cell lines, primary leukemia cells from AML patient bone marrow samples and in vivo xenograft models of human AML. Gene expression profiling of AML cells treated with either an HDAC1/2 inhibitor, azacitidine, or the combination of both have identified a list of genes involved in transcription and cell cycle regulation as potential mediators of the combinatorial effects of HDAC1/2 inhibition with azacitidine. Together, these findings support the clinical evaluation of selective HDAC1/2 inhibitors in combination with azacitidine in AML patients.

  20. Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Chengyin Min

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and inhibitors of DNA methyltransferase or histone deacetylase (HDAC enzymes have exhibited activity in preclinical AML models. Combination studies with HDAC inhibitors plus DNA methyltransferase inhibitors have potential beneficial clinical activity in AML, however the toxicity profiles of non-selective HDAC inhibitors in the combination setting limit their clinical utility. In this work, we describe the preclinical development of selective inhibitors of HDAC1 and HDAC2, which are hypothesized to have improved safety profiles, for combination therapy in AML. We demonstrate that selective inhibition of HDAC1 and HDAC2 is sufficient to achieve efficacy both as a single agent and in combination with azacitidine in preclinical models of AML, including established AML cell lines, primary leukemia cells from AML patient bone marrow samples and in vivo xenograft models of human AML. Gene expression profiling of AML cells treated with either an HDAC1/2 inhibitor, azacitidine, or the combination of both have identified a list of genes involved in transcription and cell cycle regulation as potential mediators of the combinatorial effects of HDAC1/2 inhibition with azacitidine. Together, these findings support the clinical evaluation of selective HDAC1/2 inhibitors in combination with azacitidine in AML patients.

  1. Glucocorticoids and Polyamine Inhibitors Synergize to Kill Human Leukemic CEM Cells

    Directory of Open Access Journals (Sweden)

    Aaron L. Miller

    2002-01-01

    Full Text Available Glucocorticoids are well-known apoptotic agents in certain classes of lymphoid cell malignancies. Reduction of intracellular polyamine levels by use of inhibitors that block polyamine synthesis slows or inhibits growth of many cells in vitro. Several such inhibitors have shown efficacy in clinical trials, though the toxicity of some compounds has limited their usefulness. We have tested the effects of combinations of the glucocorticoid dexamethasone. (20Dex and two polyamine inhibitors, difluoromethylornithine. (20DFMO and methyl glyoxal bis guanylhydrazone. (20MGBG, on the clonal line of human acute lymphoblastic leukemia cells, CEM-C7-14. Dex alone kills these cells, though only after a delay of at least 24 hours. We also evaluated a partially glucocorticoid-resistant c-Myc-expressing CEM-C7-14 clone. We show that Dex downregulates ornithine decarboxylase. (20ODC, the rate-limiting enzyme in polyamine synthesis. Pretreatment with the ODC inhibitor DFMO, followed by addition of Dex, enhances steroid-evoked kill slightly. The combination of pretreatment with sublethal concentrations of both DFMO and the inhibitor of S-adenosylmethionine decarboxylase, MGBG, followed by addition of Dex, results in strong synergistic cell kill. Both the rapidity and extent of cell kill are enhanced compared to the effects of Dex alone. These results suggest that use of such combinations in vivo may result in apoptosis of malignant cells with lower overall toxicity.

  2. Glucocorticoids and Polyamine Inhibitors Synergize to Kill Human Leukemic CEM Cells1

    Science.gov (United States)

    Miller, Aaron L; Johnson, Betty H; Medh, Rheem D; Townsend, Courtney M; Thompson, E Brad

    2002-01-01

    Abstract Glucocorticoids are well-known apoptotic agents in certain classes of lymphoid cell malignancies. Reduction of intracellular polyamine levels by use of inhibitors that block polyamine synthesis slows or inhibits growth of many cells in vitro. Several such inhibitors have shown efficacy in clinical trials, though the toxicity of some compounds has limited their usefulness. We have tested the effects of combinations of the glucocorticoid dexamethasone (Dex) and two polyamine inhibitors, difluoromethylornithine (DFMO) and methyl glyoxal bis guanylhydrazone (MGBG), on the clonal line of human acute lymphoblastic leukemia cells, CEM-C7-14. Dex alone kills these cells, though only after a delay of at least 24 hours. We also evaluated a partially glucocorticoid-resistant c-Myc-expressing CEM-C7-14 clone. We show that Dex downregulates ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis. Pretreatment with the ODC inhibitor DFMO, followed by addition of Dex, enhances steroid-evoked kill slightly. The combination of pretreatment with sublethal concentrations of both DFMO and the inhibitor of S-adenosylmethionine decarboxylase, MGBG, followed by addition of Dex, results in strong synergistic cell kill. Both the rapidity and extent of cell kill are enhanced compared to the effects of Dex alone. These results suggest that use of such combinations in vivo may result in apoptosis of malignant cells with lower overall toxicity. PMID:11922393

  3. Synergic activity, for anaerobes, of trovafloxacin with clindamycin or metronidazole: chequerboard and time-kill methods.

    Science.gov (United States)

    Ednie, L M; Credito, K L; Khantipong, M; Jacobs, M R; Appelbaum, P C

    2000-05-01

    Chequerboard titrations were used to test the activity of trovafloxacin, alone and in combination with clindamycin or metronidazole, against 156 Gram-positive or Gram-negative anaerobes, including 47 Bacteroides fragilis group, 36 Prevotella spp., 26 fusobacteria, 21 peptostreptococci and 26 clostridia. MIC50/MIC90 values (mg/L) of each drug alone against all 156 strains were: trovafloxacin, 0.5/1; clindamycin, 0.25/2; metronidazole, 1/2. Synergy (FIC indices 0. 5-2.0); no antagonism (FIC indices >4.0) was seen. In addition, synergy was tested by time-kill methodology for each of the above combinations against 12 Gram-positive or Gram-negative strains. Results indicated that synergy (defined as a >/= 2 log(10) decrease in cfu/mL at 48 h compared with the more active drug alone) was found between trovafloxacin at or below the MIC and both clindamycin and metronidazole at or below the MIC in one strain each of Bacteroides fragilis, Bacteroides thetaiotaomicron, Prevotella intermedia, Fusobacterium varium, Peptostreptococcus asaccharolyticus and Clostridium bifermentans. Synergy between trovafloxacin (

  4. pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

    Science.gov (United States)

    Altunkaya, Arzu; Gökmen, Vural; Skibsted, Leif H

    2016-01-01

    Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Synergism among volatile organic compounds resulting in increased antibiosis in Oidium sp.

    Science.gov (United States)

    Strobel, Gary A; Spang, Shanney; Kluck, Katreena; Hess, W M; Sears, Joe; Livinghouse, Tom

    2008-06-01

    Oidium sp. has been recovered as an endophyte in Terminalia catappa (tropical chestnut) in Costa Rica. The volatile organic compounds (VOCs) of this organism uniquely and primarily consist of esters of propanoic acid, 2-methyl-, butanoic acid, 2-methyl-, and butanoic acid, 3-methyl-. The VOCs of Oidium sp. are slightly inhibitory to many plant pathogenic fungi. Previous work on the VOCs of Muscodor albus demonstrated that besides esters of small organic acids, a small organic acid and a naphthalene derivative were needed to obtain maximum antibiotic activity. Thus, the addition of exogenous volatile compounds such as isobutyric acid and naphthalene, 1,1'-oxybis caused a dramatic synergistic increase in the antibiotic activity of the VOCs of Oidium sp. against Pythium ultimum. In fact, at elevated concentrations, there was not only 100% inhibition of P. ultimum but killing as well. In addition, a coculture of Muscodor vitigenus (making only naphthalene) and Oidium sp. plus isobutyric acid produced an additive antibiosis effect against P. ultimum. The biological implications of multiple volatile compounds acting to bring about antibiosis in nature are discussed.

  6. Climate change, insurance and the building sector: technological synergisms between adaptation and mitigation

    International Nuclear Information System (INIS)

    Mills, E.

    2003-01-01

    Examining the intersection of risk analysis and sustainable energy strategies reveals numerous examples of energy-efficient and renewable energy technologies that offer insurance loss-prevention benefits. The growing threat of climate change provides an added motivation for the risk community to understand better this area of opportunity. While analyses of climate change mitigation typically focus on the emissions-reduction characteristics of sustainable energy technologies, less often recognised are a host of synergistic ways in which these technologies also offer adaptation benefits, e.g. making buildings more resilient to natural disasters. While there is already some relevant activity, there remain various barriers to expanding these efforts significantly. Achieving successful integration of sustainable energy considerations with risk-management objectives requires a more proactive orientation, and coordination among diverse actors and industry groups. (author)

  7. Synergism between clindamycin and colloidal bismuth subcitrate against Helicobacter (Campylobacter) pylori in vitro.

    Science.gov (United States)

    Vogt, K; Hahn, H

    1990-11-01

    A combination of clindamycin and colloidal bismuth subcitrate was evaluated for synergistic inhibition of Helicobacter pylori employing the agar dilution method. A total of 47 clinical isolates of Helicobacter pylori were examined. Synergistic interaction was observed in 36%, additive behaviour in 64% of the strains. No antagonism could be detected.

  8. Synergism Analysis of Bedding Slope with Piles and Anchor Cable Support under Sine Wave Vehicle Load

    Directory of Open Access Journals (Sweden)

    Li Dan-Feng

    2016-01-01

    Full Text Available Slope instability under dynamic load is the technical difficulty in the engineering; the evaluation of slope stability under dynamic load and the control of dynamic load is particularly important. In this paper, taking the right side slope of K27+140 m~380 m typical section (K27 slope for short in Chongqing Fuling-Fengdu-Shizhu expresses highway as an example to calculate and analyze. The K27 slope is under sinusoidal vehicle load and supported by anchor cable and antislide pile to resist downslide strength; at the same time, the combined effect of them is studied. Three-dimensional finite element methodology (FEM is used to simulate the bedding slope with piles and anchor cable support; furthermore, the eigenvalue can be obtained. In order to reduce error of the elastic boundary conditions caused by the reflection effect of wavelengths, the combination of Lysmer surface viscous boundary and traditional ground support boundaries is utilized to analyze and calculate the time-histories during bedding slope under dynamic load. The dynamic response of pile anchor support to resist sliding force is obtained. The concept of the pile anchor supporting coordinate interval is put forward. Furthermore, it is verified that the pile anchor supporting coordinate interval can be used to evaluate the stability of the slope under dynamic load and provide a new method for the control of the dynamic load.

  9. Public health education at the University of Florida: synergism and educational innovation.

    Science.gov (United States)

    Perri, Michael G; Peoples-Sheps, Mary; Blue, Amy; Lednicky, John A; Prins, Cindy

    2015-03-01

    The College of Public Health and Health Professions at the University of Florida is composed of five public health departments and four clinical health professions departments, and the college is one of six that make up the university's Health Science Center. These organizational resources, along with the university's explicit emphasis on collaboration across professions, colleges, institutes, and centers and the strong leadership and full support of deans and other academic leaders, provide a strong foundation for educational innovations. Three key areas in which the college has built upon these opportunities are interprofessional education, development of One Health instructional programs, and application of cutting-edge technology to students' educational experiences. These innovations represent the types of creative approaches to preparing the 21st-century workforce that can be developed through collaboration among multiple disciplines in a major university.

  10. Visualization of network target crosstalk optimizes drug synergism in myocardial ischemia.

    Directory of Open Access Journals (Sweden)

    Xiaojing Wan

    Full Text Available Numerous drugs and compounds have been validated as protecting against myocardial ischemia (MI, a leading cause of heart failure; however, synergistic possibilities among them have not been systematically explored. Thus, there appears to be significant room for optimization in the field of drug combination therapy for MI. Here, we propose an easy approach for the identification and optimization of MI-related synergistic drug combinations via visualization of the crosstalk between networks of drug targets corresponding to different drugs (each drug has a unique network of targets. As an example, in the present study, 28 target crosstalk networks (TCNs of random pairwise combinations of 8 MI-related drugs (curcumin, capsaicin, celecoxib, raloxifene, silibinin, sulforaphane, tacrolimus, and tamoxifen were established to illustrate the proposed method. The TCNs revealed a high likelihood of synergy between curcumin and the other drugs, which was confirmed by in vitro experiments. Further drug combination optimization showed a synergistic protective effect of curcumin, celecoxib, and sililinin in combination against H₂O₂-induced ischemic injury of cardiomyocytes at a relatively low concentration of 500 nM. This result is in agreement with the earlier finding of a denser and modular functional crosstalk between their networks of targets in the regulation of cell apoptosis. Our study offers a simple approach to rapidly search for and optimize potent synergistic drug combinations, which can be used for identifying better MI therapeutic strategies. Some new light was also shed on the characteristic features of drug synergy, suggesting that it is possible to apply this method to other complex human diseases.

  11. Visualization of network target crosstalk optimizes drug synergism in myocardial ischemia.

    Science.gov (United States)

    Wan, Xiaojing; Meng, Jia; Dai, Yingnan; Zhang, Yina; Yan, Shuang

    2014-01-01

    Numerous drugs and compounds have been validated as protecting against myocardial ischemia (MI), a leading cause of heart failure; however, synergistic possibilities among them have not been systematically explored. Thus, there appears to be significant room for optimization in the field of drug combination therapy for MI. Here, we propose an easy approach for the identification and optimization of MI-related synergistic drug combinations via visualization of the crosstalk between networks of drug targets corresponding to different drugs (each drug has a unique network of targets). As an example, in the present study, 28 target crosstalk networks (TCNs) of random pairwise combinations of 8 MI-related drugs (curcumin, capsaicin, celecoxib, raloxifene, silibinin, sulforaphane, tacrolimus, and tamoxifen) were established to illustrate the proposed method. The TCNs revealed a high likelihood of synergy between curcumin and the other drugs, which was confirmed by in vitro experiments. Further drug combination optimization showed a synergistic protective effect of curcumin, celecoxib, and sililinin in combination against H₂O₂-induced ischemic injury of cardiomyocytes at a relatively low concentration of 500 nM. This result is in agreement with the earlier finding of a denser and modular functional crosstalk between their networks of targets in the regulation of cell apoptosis. Our study offers a simple approach to rapidly search for and optimize potent synergistic drug combinations, which can be used for identifying better MI therapeutic strategies. Some new light was also shed on the characteristic features of drug synergy, suggesting that it is possible to apply this method to other complex human diseases.

  12. A Role for Thiopurine Metabolites in the Synergism Between Thiopurines and Infliximab in Inflammatory Bowel Disease.

    Science.gov (United States)

    Mogensen, Ditte V; Brynskov, Jørn; Ainsworth, Mark A; Nersting, Jacob; Schmiegelow, Kjeld; Steenholdt, Casper

    2018-02-28

    Interactions between principal cytotoxic thiopurine metabolites, that is 6-thioguanine nucleotides [6-TGN], and infliximab [IFX] and anti-IFX antibodies [Abs] may contribute to higher effectiveness of IFX-thiopurine combination therapy than monotherapies in inflammatory bowel disease. To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, eight patients who had responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included. In the first cohort, IFX-thiopurine combination therapy reduced anti-IFX Ab detection [8/40; 20%] as compared with IFX monotherapy [22/49; 45%], odds ratio [OR] 0.31 [0.12-0.80], p 0.05]. Methylated mercaptopurine metabolite associations were consistently negative. Superior effect of IFX-thiopurine combination therapy over monotherapies partly relates to decrease in anti-IFX Abs, which associates with 6-TGN levels and has a lower therapeutic threshold than during thiopurine monotherapy. Additional benefit likely ascribes to synergy between different anti-inflammatory modes of action rather than direct drug interactions. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  13. A role for thiopurine metabolites in the synergism between thiopurines and infliximab in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Mogensen, Ditte V; Brynskov, Jørn; Ainsworth, Mark A

    2018-01-01

    : Superior effect of IFX-thiopurine-combination therapy over monotherapies partly relates to decreased anti-IFX Abs, which associates with 6-TGN levels and has a lower therapeutic thresholds than during thiopurine monotherapy. Additional benefit likely ascribes to synergy between different anti...

  14. A synergism between adaptive effects and evolvability drives whole genome duplication to fixation

    NARCIS (Netherlands)

    Cuypers, Thomas D; Hogeweg, Paulien; Hogeweg, P.

    Whole genome duplication has shaped eukaryotic evolutionary history and has been associated with drastic environmental change and species radiation. While the most common fate of WGD duplicates is a return to single copy, retained duplicates have been found enriched for highly interacting genes.

  15. Synergism between 9-deazainosine and DL-alpha-difluoromethylornithine in treatment of experimental African trypanosomiasis.

    Science.gov (United States)

    Bacchi, C J; Berens, R L; Nathan, H C; Klein, R S; Elegbe, I A; Rao, K V; McCann, P P; Marr, J J

    1987-09-01

    Kinetoplastid hemoflagellates are sensitive to growth inhibition by various purine analogs. In this study the activities of 9-deazainosine (9-DINO), formycin B, and sinefungin were compared in experimental murine Trypanosoma brucei subsp. brucei infections, both singly and in combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine). Used singly, all of the purine analogs were able to suppress an acute T. brucei subsp. brucei infection. 9-DINO and formycin B were the most active. None of the purine analogs was curative when used singly against a strain causing chronic central nervous system infection. 9-DINO was highly effective when used in combination with DFMO in curing this central nervous system infection and another more stringent experimental infection. Neither sinefungin nor formycin B was active in combination with DFMO in curing the central nervous system experimental infection. 9-DINO was metabolized to phosphorylated derivatives of 9-deazaadenosine and 9-deazaguanosine by bloodstream trypomastigotes, but not by murine erythrocyte suspensions or kidney or liver homogenates--a potential rationale for the selectivity of the analog. These studies indicate that 9-DINO is a potent, nontoxic purine analog which, in combination with DFMO, is capable of late-stage cures of African trypanosomiasis.

  16. Synergism between 9-deazainosine and DL-alpha-difluoromethylornithine in treatment of experimental African trypanosomiasis.

    OpenAIRE

    Bacchi, C J; Berens, R L; Nathan, H C; Klein, R S; Elegbe, I A; Rao, K V; McCann, P P; Marr, J J

    1987-01-01

    Kinetoplastid hemoflagellates are sensitive to growth inhibition by various purine analogs. In this study the activities of 9-deazainosine (9-DINO), formycin B, and sinefungin were compared in experimental murine Trypanosoma brucei subsp. brucei infections, both singly and in combination with the ornithine decarboxylase inhibitor DL-alpha-difluoromethylornithine (DFMO, eflornithine). Used singly, all of the purine analogs were able to suppress an acute T. brucei subsp. brucei infection. 9-DIN...

  17. Synergism of ochratoxin B and calcium-channel antagonist verapamil caused mitochondrial dysfunction.

    Science.gov (United States)

    Chatopadhyay, Pronobesh; Tariang, Banlumlang; Agnihotri, Amit; Veer, Vijay

    2014-09-01

    We examined the mechanism by which the ochratoxin B induced interaction with calcium-channel antagonist verapamil and mitochondrial dysfunction of the rat trachea in vitro experiment. The tracheas were cut into 2-3 mm wide rings and suspended in a tissue bath. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Verapamil (1 × 10(-6) M) produced a concentration-dependent contraction response in rat's tracheal rings pre-contracted by acetylcholine. Incubation of rat's tracheal rings with the ochratoxin B significantly potentiated the contraction responses of verapamil. Verapamil and OTB accelerate the overloading of Ca(2+) in tracheal smooth muscle contributes the tissue toxicity as shown in electron microscopy and mitochondrial enzymes, through a mechanism that could involve perturbations of Ca(2+) homeostasis. These results proved that ochratoxin B is a potential vasoconstrictor mycotoxin with the presence of calcium-channel antagonist. In conclusion, disturbance of Ca(2+) homeostasis caused by OTA and plays a significant role in produces toxicity through mitochondrial enzyme inhibition.

  18. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Mira A. Patel

    2014-09-01

    Full Text Available The current standard of care for glioblastoma (GBM is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ. As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  19. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Mira A.; Kim, Jennifer E.; Ruzevick, Jacob [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States); Li, Gordon [Department of Neurosurgery, Stanford University Medical Center, 1201 Welch Rd., P309 MSLS, Stanford, CA 94305 (United States); Lim, Michael, E-mail: mlim3@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States)

    2014-09-29

    The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.

  20. Apple volatiles synergize the response of codling moth to pear ester

    Science.gov (United States)

    This work was undertaken to identify host volatiles from apples and investigate whether these can be used to enhance the efficacy of pear ester, ethyl (2E,4Z)-2,4-decadienoate, for monitoring female and male codling moth, Cydia pomonella L. Volatiles from immature apple trees were collected in the f...

  1. Development of the Human Placenta and Fetal Heart: Synergic or Independent?

    Directory of Open Access Journals (Sweden)

    Graham J. Burton

    2018-04-01

    Full Text Available The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c. give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12–14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces smooth muscle cells surrounding the placental arteries to dedifferentiate and adopt a proliferative phenotype. This change is associated with increased umbilical resistance measured by Doppler ultrasound, and is likely to exert a major effect on the developing heart through the afterload. Thus, both the umbilical and maternal placental circulations may impact on development of the heart.

  2. Effects of spinosad on Helicoverpa armigera (Lepidoptera: Noctuidae) from China: tolerance status, synergism and enzymatic responses.

    Science.gov (United States)

    Wang, Dong; Qiu, Xinghui; Ren, Xuexiang; Zhang, Wencheng; Wang, Kaiyun

    2009-09-01

    Spinosad is increasingly used in pest management programmes, and resistance to it has been detected in recent years. However, there is no report on the susceptibilities of field populations of Helicoverpa armigera (Hübner) from China. Furthermore, the impact of spinosad on metabolic enzymes in this pest remains unknown. Four populations of H. armigera from different locations in China displayed less than 6.5-fold difference in LC(50) to spinosad, the highest being in the Xinjiang population, followed by Xiajin, Taian and Hubei populations, while there was no significant difference at LC(99) level among the four populations. The toxicity of spinosad could be synergised by piperonyl butoxide (PBO) and triphenylphosphate (TPP), but not by diethyl maleate (DEM). Spinosad exposure for 48 h significantly increased the activities of p-nitroanisole O-demethylase (ODM), while no significant changes in glutathione-S-transferase (GST) and carboxyl esterase (CarE) were observed. Field populations of H. armigera from China displayed marginally different susceptibilities to spinosad and had a relatively low LC(50). Cytochrome P450 monooxygenase might be involved in the metabolism of, and hence resistance to, spinosad in this pest in China. Copyright 2009 Society of Chemical Industry.

  3. Analgesia Synergism of Essential Oil from Pericarp of Zanthoxylum schinifolium and Verapamil

    Directory of Open Access Journals (Sweden)

    Gao Wu

    2014-01-01

    Full Text Available Objective. To evaluate the synergistic analgesic effect of essential oil of Zanthoxylum schinifolium Sieb. et Zucc. (EOZ and verapamil (Ver. Method. The qualitative and quantitative composition of EOZ were determined with gas chromatography/Mass spectrometer. The interaction between EOZ and Ver in antinociceptive activity was evaluated by using acetic acid-induced writhing, hot plate, and tail flick tests in mice and in isolated toad sciatic nerve test. Results. Linalool, limonene, and sabinene are the major components of EOZ. EOZ (middle-dose: 40 mg·kg−1, high-dose: 80 mg·kg−1 and EOZ + Ver (Each dose group have remarkable analgesic effects on pain in mice induced by acetic acid-induced writhing, hot plate, and tail flick tests. Low-dose EOZ (20 mg·kg−1 had no analgesic action, but when it is combined with Ver it has shown significant antinociception. Verapamil has a faint analgesic effect but was not able to inhibit action potential transmission in toad sciatic nerve. EOZ (0.2% and EOZ + Ver (0.2% + 0.05% also inhibited action potential transmission in toad sciatic nerve. Combination of EOZ with Ver had a greater analgesic effect and inhibition of nerve action potential transmission compared to its components EOZ and Ver. Conclusion. The combination of EOZ with Ver produces a synergistic analgesic effect.

  4. Climate change, insurance, and the buildings sector: Technological synergisms between adaptation and mitigation

    Energy Technology Data Exchange (ETDEWEB)

    Mills, Evan

    2002-11-01

    Examining the intersection of risk analysis and sustainable energy strategies reveals numerous examples of energy efficient and renewable energy technologies that offer insurance loss-prevention benefits. The growing threat of climate change provides an added motivation for the risk community to better understand this area of opportunity. While analyses of climate change mitigation typically focus on the emissions-reduction characteristics of sustainable energy technologies, less often recognized are a host of synergistic ways in which these technologies also offer adaptation benefits, e.g. making buildings more resilient to natural disasters. While there is already some relevant activity, there remain various barriers to significantly expanding these efforts. Achieving successful integration of sustainable energy considerations with risk-management objectives requires a more proactive orientation, and coordination among diverse actors and industry groups.

  5. An Inert Pesticide Adjuvant Synergizes Viral Pathogenicity and Mortality in Honey Bee Larvae.

    Science.gov (United States)

    Fine, Julia D; Cox-Foster, Diana L; Mullin, Christopher A

    2017-01-16

    Honey bees are highly valued for their pollination services in agricultural settings, and recent declines in managed populations have caused concern. Colony losses following a major pollination event in the United States, almond pollination, have been characterized by brood mortality with specific symptoms, followed by eventual colony loss weeks later. In this study, we demonstrate that these symptoms can be produced by chronically exposing brood to both an organosilicone surfactant adjuvant (OSS) commonly used on many agricultural crops including wine grapes, tree nuts and tree fruits and exogenous viral pathogens by simulating a horizontal transmission event. Observed synergistic mortality occurred during the larval-pupal molt. Using q-PCR techniques to measure gene expression and viral levels in larvae taken prior to observed mortality at metamorphosis, we found that exposure to OSS and exogenous virus resulted in significantly heightened Black Queen Cell Virus (BQCV) titers and lower expression of a Toll 7-like-receptor associated with autophagic viral defense (Am18w). These results demonstrate that organosilicone spray adjuvants that are considered biologically inert potentiate viral pathogenicity in honey bee larvae, and guidelines for OSS use may be warranted.

  6. An Inert Pesticide Adjuvant Synergizes Viral Pathogenicity and Mortality in Honey Bee Larvae

    OpenAIRE

    Fine, Julia D.; Cox-Foster, Diana L.; Mullin, Christopher A.

    2017-01-01

    Honey bees are highly valued for their pollination services in agricultural settings, and recent declines in managed populations have caused concern. Colony losses following a major pollination event in the United States, almond pollination, have been characterized by brood mortality with specific symptoms, followed by eventual colony loss weeks later. In this study, we demonstrate that these symptoms can be produced by chronically exposing brood to both an organosilicone surfactant adjuvant ...

  7. RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

    Directory of Open Access Journals (Sweden)

    Simona Lamba

    2014-09-01

    Full Text Available KRAS is the most frequently mutated oncogene in human cancer, yet no therapies are available to treat KRAS mutant cancers. We used two independent reverse genetic approaches to identify components of the RAS-signaling pathways required for growth of KRAS mutant tumors. Small interfering RNA (siRNA screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition. An unbiased kinome short hairpin RNA (shRNA-based screen confirmed this synthetic lethal interaction in colorectal as well as in lung cancer cells bearing KRAS mutations. Compounds targeting RAF kinases can reverse resistance to the MEK inhibitor selumetinib. MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. Prolonged dual blockade of RAF and MEK leads to persistent ERK suppression and efficiently induces apoptosis. Our data underlie the relevance of developing combinatorial regimens of drugs targeting the RAF-MEK pathway in KRAS mutant tumors.

  8. Synergic Effect of α-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model

    OpenAIRE

    Pérez-Rojas, Jazmin M.; González-Macías, Raquel; González-Cortes, Jaime; Jurado, Rafael; Pedraza-Chaverri, José; García-López, Patricia

    2016-01-01

    Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II) (CDDP) has some serious side effects. Alpha-mangostin (α-M), has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-M and/or CDDP wa...

  9. Synergic Effect ofα-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model.

    Science.gov (United States)

    Pérez-Rojas, Jazmin M; González-Macías, Raquel; González-Cortes, Jaime; Jurado, Rafael; Pedraza-Chaverri, José; García-López, Patricia

    2016-01-01

    Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II) (CDDP) has some serious side effects. Alpha -mangostin ( α -M), has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α -M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α -M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS) production, and the cell cycle were determined with flow cytometry. For α -M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu) mice, and then tumor volume and body weight were measured weekly, whereas α -M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α -M+CDDP showing significantly greater cytotoxicity than CDDP or α -M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest that α -M may be useful as a neoadjuvant agent in cervical cancer therapy.

  10. Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed electromagnetic field and biochemical stimuli

    OpenAIRE

    Wang, Qian; Wu, Wenchao; Han, Xiaoyu; Zheng, Ai; Lei, Song; Wu, Jiang; Chen, Huaiqing; He, Chengqi; Luo, Fengming; Liu, Xiaojing

    2014-01-01

    Background Pulsed electromagnetic field (PEMF) is a non-invasive physical therapy used in the treatment of fracture nonunion or delayed healing. PEMF can facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential source of stem cells for cell therapy. However, whether PEMF could modulate the osteogenic differentiation of AECs is unknown. In the present study, the effects of PEMF on the osteogenic...

  11. Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed electromagnetic field and biochemical stimuli.

    Science.gov (United States)

    Wang, Qian; Wu, Wenchao; Han, Xiaoyu; Zheng, Ai; Lei, Song; Wu, Jiang; Chen, Huaiqing; He, Chengqi; Luo, Fengming; Liu, Xiaojing

    2014-08-11

    Pulsed electromagnetic field (PEMF) is a non-invasive physical therapy used in the treatment of fracture nonunion or delayed healing. PEMF can facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential source of stem cells for cell therapy. However, whether PEMF could modulate the osteogenic differentiation of AECs is unknown. In the present study, the effects of PEMF on the osteogenic differentiation of AECs were investigated. AECs were isolated from amniotic membrane of human placenta by trypsin digestion and were induced by PEMF and/or osteo-induction medium. After 21 days we used real time RT-PCR and immunocytochemistry to study the expression of osteoblast markers. The signal transduction of osteogenesis was further investigated. The PEMF stimulation, or osteo-induction medium alone could induce osteogenic differentiation of AECs, as shown by expression of osteoblast specific genes and proteins including alkaline phosphatase and osteocalcin. Furthermore, a combination of PEMF and osteo-induction medium had synergy effects on osteogenic differentiation. In our study, the gene expression of BMP-2, Runx2, β-catenin, Nrf2, Keap1 and integrinβ1 were up-regulated in the osteogenic differentiation of AECs induced by PEMF and/or osteo-induction medium. Combined application of PEMF and osteo-induction medium is synergistic for the osteogenic differentiation of AECs. It might be a novel approach in the bone regenerative medicine.

  12. Synergism of Saturn, Enceladus and Titan and Formation of HCNO Exobiological Molecules

    Science.gov (United States)

    Sittler, Edward C., Jr.; Cooper, John F.

    2010-01-01

    Saturn as a system has two very exotic moons Titan and Enceladus. Titan with energy input from Saturn's magnetosphere, solar UV irradiation, and cosmic rays can make HCN based molecules as discussed in earlier paper by [1]. Space radiation effects at both moons, and as coupled by the Saturn magnetosphere could cause an unexpected series of events leading to the evolution of biological models at Titan composed of HCNO with oxygen as the new ingredient. The "Old Faithful" model by [2] suggests that Enceladus, highly irradiated by Saturn magnetospheric electrons, has episodic ejections of water vapor driven by radiolytic oxidation gas products into Saturn's magnetosphere. At Titan Cassini discovered 1) that keV oxygen ions, evidently from Enceladus, are bombarding Titan's upper atmosphere [3] and 2) the discovery of heavy positive and negative ions within Titan's upper atmosphere [4]. Initial models of heavy ion formation in Titan's upper atmosphere invoked polymerization of aromatics such as Benzenes and their radicals to make PAHs [5], while a more recent model by [6] has raised the possibility of carbon chains forming from the polymerization of acetylene and its radicals to eventually make fullerenes. Laboratory measurements indicate that fullerenes, which are hollow carbon shells, can trap the keV oxygen and with the clustering of fullerenes and possible mixture with PAHs, some with nitrogen molecules, can make the larger aerosols with oxygen within them. Then with further ionizing irradiation from cosmic rays deep in the atmosphere "tholin" molecules are produced with all the molecular components present from which organic molecules can form. Among the molecular components are amino acids, the fundamental building blocks of life as we know it. This process maybe a common chemical pathway, both at the system level and at the molecular level, to form prebiotic and perhaps even biotic molecules. Such processes can be occurring throughout our universe, such as molecular clouds in the ISM.

  13. Synergism of Saturn, Enceladus and Titan and Formation of HCNO Prebiotic Molecules

    Science.gov (United States)

    Sittler, Edward C.; Cooper, John F.

    2011-01-01

    Saturn as a system has two very exotic moons Titan and Enceladus. Titan, taking in energy from Saturn's magnetosphere, solar UV irradiation, and cosmic rays, can make HCN based molecules as discussed in earlier paper by Raulin and Owen. Space radiation effects at both moons, and as coupled by the Saturn magnetosphere, could cause an unexpected series of events potentially leading to prebiotic chemical evolution at Titan with HCNO from magnetospheric oxygen as the new ingredient. The "Old Faithful" model suggests that Enceladus, highly irradiated by Saturn magnetospheric electrons and thus having a source of chemical energy from radiolytic gas production, has episodic ejections of water vapor, carbon dioxide, and various hydrocarbons into Saturn's magnetosphere. The hydrocarbons do not survive transport through the plasma environment, but oxygen ions from Enceladus water molecules become the dominant ion species in the outer magnetosphere. At Titan, Cassini discovered that 1) keV oxygen ions, evidently from Enceladus, are bombarding Titan's upper atmosphere and 2) heavy positive and negative ions exist in significant abundances within Titan's upper atmosphere. Initial models of heavy ion formation in Titan's upper atmosphere invoked polymerization of aromatics such as benzenes and their radicals to make polycyclic aromatic hydrocarbons (PAH) , while a more recent model by Sittler et al., has raised the possibility of carbon chains forming from the polymerization of acetylene and its radicals to make fullerenes. Laboratory measurements indicate that fullerenes, which are hollow carbon shells, can trap keV oxygen ions. Clustering of the fullerenes with aerosol mixtures from PAHs and the dominant nitrogen molecules could form larger aerosols enriched in trapped oxygen. Aerosol precipitation could then convey these chemically complex structures deeper into the atmosphere and to the moon surface. Ionizing solar UV, magnetospheric electron, and galactic cosmic ray irradiation would provide further energy for processing into more complex organic forms. Further ionizing irradiation from cosmic rays deep in the atmosphere "tho lin" molecules are produced with all the molecular components present from which prebiotic organic molecules can form. This synergy of Saturn system, exogenic irradiation, and molecular processes provides a potential pathway for accumulation of prebiotic chemistry on the surface of Titan. Since fullerenes are also thought to exist in interstellar space, similar processes may also occur there to seed molecular clouds with prebiotic chemical species. We will also discuss possible future laboratory experiments that could be done to investigate fullerene formation at Titan and the trapping of oxygen in fullerenes.

  14. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia.

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C; Moura, Ivan C; Hermine, Olivier

    2010-04-12

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.

  15. Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia

    Science.gov (United States)

    Callens, Celine; Coulon, Séverine; Naudin, Jerome; Radford-Weiss, Isabelle; Boissel, Nicolas; Raffoux, Emmanuel; Wang, Pamella Huey Mei; Agarwal, Saurabh; Tamouza, Houda; Paubelle, Etienne; Asnafi, Vahid; Ribeil, Jean-Antoine; Dessen, Philippe; Canioni, Danielle; Chandesris, Olivia; Rubio, Marie Therese; Beaumont, Carole; Benhamou, Marc; Dombret, Hervé; Macintyre, Elizabeth; Monteiro, Renato C.

    2010-01-01

    Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML. PMID:20368581

  16. Synergism between profile and cross section shape optimization for negative central shear advanced tokamaks

    International Nuclear Information System (INIS)

    Turnbull, A.D.; Taylor, T.S.; Lao, L.L.

    1996-01-01

    The Advanced Tokamak (AT) concept is aimed at achieving high beta, high confinement, and a well aligned high bootstrap current fraction in a tokamak configuration consistent with steady state operation. The required improvements over the simple O-D scaling laws, normally used to predict standard, pulsed tokamak performance, axe obtained by taking into account the dependence of the stability and confinement on the 2-D equilibrium; the planned TPX experiment was designed to take full advantage of both advanced profiles and advanced cross-section shaping. Systematic stability studies of the promising Negative Central Shear (NCS) configuration have been performed for a wide variety of cross-section shapes and profile variations. The ideal MHD beta limit is found to be strongly dependent on both and, in fact, there is a clear synergistic relationship between the gains in beta from optimizing the profiles and optimizing the shape. Specifically, for a circular cross-section with highly peaked profiles, β is limited to normalized β values of β N = β/(I/aB) ∼ 2% (mT/MA). A small gain in beta can be achieved by broadening the pressure; however, the root-mean-square beta (β*) is slightly reduced. With peaked pressure profiles, a small increase in β N over that in a circular cross-section is also obtained by strong shaping. At fixed q, this translates to a much larger gain in β and β*. With both optimal profiles and strong shaping, however, the gain in all the relevant fusion performance parameters is dramatic; β and β* can be increased a factor 5 for example. Moreover, the bootstrap alignment is improved. For an optimized strongly shaped configuration, confinement, beta values, and bootstrap alignment adequate for a practical AT power plant appear to be realizable. Data from DIII-D supports these predictions and analysis of the DIII-D data will be presented

  17. OK-432 synergizes with IFN-γ to confer dendritic cells with enhanced antitumor immunity.

    Science.gov (United States)

    Pan, Ke; Lv, Lin; Zheng, Hai-xia; Zhao, Jing-jing; Pan, Qiu-zhong; Li, Jian-jun; Weng, De-sheng; Wang, Dan-dan; Jiang, Shan-shan; Chang, Alfred E; Li, Qiao; Xia, Jian-chuan

    2014-03-01

    Generation of functional dendritic cells (DCs) with boosted immunity after the withdrawal of initial activation/maturation conditions remains a significant challenge. In this study, we investigated the impact of a newly developed maturation cocktail consisting of OK-432 and interferon-gamma (IFN-γ) on the function of human monocyte-derived DCs (MoDCs). We found that OK-432 plus IFN-γ stimulation could induce significantly stronger expression of surface molecules, production of cytokines, as well as migration of DCs compared with OK-432 stimulation alone. Most importantly, DCs matured with OK-432 plus IFN-γ-induced maintained secretion of interleukin-12 (IL-12)p70 in secondary culture after stimulus withdrawal. Functionally, OK-432 plus IFN-γ-conditioned DCs induce remarkable Th1 and Tc1 responses more effectively than OK-432 alone, even more than the use of α-type-1 cytokine cocktail. As a result, DCs matured with OK-432 plus IFN-γ can prime stronger cytotoxic lymphocyte (CTL) and natural killer (NK) cell response against tumor cells in vitro. Peripheral blood mononuclear cells activated by DCs matured with OK-432 plus IFN-γ also showed greater tumor growth inhibition in vivo in null mice. Molecular mechanistic analysis showed that DC maturation using IFN-γ in concert with OK-432 involves the activation of p38 and nuclear factor-kappa B (NF-κB) pathways. This study provided a novel strategy to generate more potent immune segments in DC vaccine.

  18. Hypomethylating agents synergize with irinotecan to improve response to chemotherapy in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Anup Sharma

    Full Text Available Colorectal cancer (CRC is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment. For irinotecan (IRI, growth diminished by 16-62 fold as assessed, by both proliferation (IC50 and anchorage independent cell growth soft agar assays. Treatment of resistant HCT116 cell line along with in-vivo, for CRC line xenografts, AZA plus IRI again exhibits this synergistic response with significant improvement in survival and tumor regression in the mice. Genome-wide expression correlates changes in pathways for cell adhesion and DNA repair with the above responses. A Phase 1/2 clinical trial testing this concept is already underway testing the clinical efficacy of this concept in IRI resistant, metastatic CRC (NCT01896856.

  19. Combined inhibition of MEK and mTOR has a synergic effect on angiosarcoma tumorgrafts.

    Science.gov (United States)

    Andersen, Nicholas J; Boguslawski, Elissa B; Kuk, Cynthia Y; Chambers, Christopher M; Duesbery, Nicholas S

    2015-07-01

    Angiosarcoma (AS) is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. Using tumorgraft models, we previously showed that AS is sensitive to small-molecule inhibitors that target mitogen-activated/extracellular-signal-regulated protein kinase kinases 1 and 2 (MEK). The objective of this study was to identify drugs that combine with MEK inhibitors to more effectively inhibit AS growth. We examined the in vitro synergy between the MEK inhibitor PD0325901 and inhibitors of eleven common cancer pathways in melanoma cell lines and canine angiosarcoma cell isolates. Combination indices were calculated using the Chou-Talalay method. Optimized combination therapies were evaluated in vivo for toxicity and efficacy using canine angiosarcoma tumorgrafts. Among the drugs we tested, rapamycin stood out because it showed strong synergy with PD0325901 at nanomolar concentrations. We observed that angiosarcomas are insensitive to mTOR inhibition. However, treatment with nanomolar levels of mTOR inhibitor renders these cells as sensitive to MEK inhibition as a melanoma cell line with mutant BRAF. Similar results were observed in B-Raf wild-type melanoma cells as well as in vivo, where treatment of canine AS tumorgrafts with MEK and mTOR inhibitors was more effective than monotherapy. Our data show that a low dose of an mTOR inhibitor can dramatically enhance angiosarcoma and melanoma response to MEK inhibition, potentially widening the field of applications for MEK-targeted therapy.

  20. Synergic Effect of α-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model

    Science.gov (United States)

    González-Macías, Raquel; González-Cortes, Jaime; Jurado, Rafael; García-López, Patricia

    2016-01-01

    Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II) (CDDP) has some serious side effects. Alpha-mangostin (α-M), has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS) production, and the cell cycle were determined with flow cytometry. For α-M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu) mice, and then tumor volume and body weight were measured weekly, whereas α-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α-M+CDDP showing significantly greater cytotoxicity than CDDP or α-M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest that α-M may be useful as a neoadjuvant agent in cervical cancer therapy. PMID:28053694

  1. Synergic Effect of α-Mangostin on the Cytotoxicity of Cisplatin in a Cervical Cancer Model

    Directory of Open Access Journals (Sweden)

    Jazmin M. Pérez-Rojas

    2016-01-01

    Full Text Available Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II (CDDP has some serious side effects. Alpha-mangostin (α-M, has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS production, and the cell cycle were determined with flow cytometry. For α-M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu mice, and then tumor volume and body weight were measured weekly, whereas α-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α-M+CDDP showing significantly greater cytotoxicity than CDDP or α-M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest that α-M may be useful as a neoadjuvant agent in cervical cancer therapy.

  2. Synergic use of TOMS and AERONET observations for characterization of aerosol absorption

    Science.gov (United States)

    Torres, O.; Sinyuk, A.; Bhartia, P. K.; Dubovik, O.; Holben, B.

    2003-04-01

    The role of aerosol absorption on the radiative transfer balance of the earth-atmosphere system is one of the largest sources of uncertainty in the analysis of global climate change. Global measurements of aerosol single scattering albedo are, therefore, necessary to properly assess the radiative forcing effect of aerosols. Remote sensing of aerosol absorption is currently carried out using both ground (Aerosol Robotic Network) and space (Total Ozone Mapping Spectrometer) based observations. The satellite technique uses measurements of backscattered near ultraviolet radiation. Carbonaceous aerosols, resulting from the combustion of biomass, are one of the most predominant absorbing aerosol types in the atmosphere. In this presentation, TOMS and AERONET retrievals of single scattering albedo of carbonaceous aerosols, are compared for different environmental conditions: agriculture related biomass burning in South America and Africa and peat fires in Eastern Europe. The AERONET and TOMS derived aerosol absorption information are in good quantitative agreement. The most absorbing smoke is detected over the African Savanna. Aerosol absorption over the Brazilian rain forest is less absorbing. Absorption by aerosol particles resulting from peat fires in Eastern Europe is weaker than the absorption measured in Africa and South America. This analysis shows that the near UV satellite method of aerosol absorption characterization has the sensitivity to distinguish different levels of aerosol absorption. The analysis of the combined AERONET-TOMS observations shows a high degree of synergy between satellite and ground based observations.

  3. Synergism between abdominal and pelvic floor muscles in healthy women: a systematic review of observational studies

    Directory of Open Access Journals (Sweden)

    Lia Ferla

    Full Text Available Abstract Introduction: The training of the pelvic floor muscles is widely used for treating pelvic floor dysfunctions, like urinary incontinence. During the training, abdominal contractions are avoided; however several studies support the use of the synergy between these muscle groups. Objective: Carrying out a systematic review of studies that seek to identify the presence of synergy between the muscles of the abdomen and the pelvic floor and its functionality in women without pelvic floor dysfunction. Methodology: To conduct the review, we have followed the recommendations proposed by the Cochrane Collaboration for systematic reviews. The literature search included the databases SCIELO, PEDro, MEDLINE, Cochrane CENTRAL and EMBASE, and manual research, the starting date of the databases until August 2013. We included cross observational studies with healthy women who were assessed to find the presence of synergy between the abdominal muscles and the pelvic floor. Results: We included 10 articles and they all showed the existence of synergy between the abdominal and pelvic floor muscles in healthy women in the supine, sitting and standing positions. Conclusion: Thus, we can conclude that there is synergy between the muscles of the abdomen and the pelvic floor in healthy women. Better understanding the behavior of these muscles and synergy may favor the development of strategies for the prevention and treatment of disorders of the female pelvic floor muscles.

  4. Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer

    Science.gov (United States)

    Rabinowicz, Noa; Mangala, Lingegowda S.; Brown, Kevin R.; Checa-Rodriguez, Cintia; Castiel, Asher; Moskovich, Oren; Zarfati, Giulia; Trakhtenbrot, Luba; Levy-Barda, Adva; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Pradeep, Sunila; van Praag, Yael; Lopez-Berestein, Gabriel; David, Ahuvit; Novikov, Ilya; Huertas, Pablo; Rottapel, Robert; Sood, Anil K.; Izraeli, Shai

    2017-01-01

    Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing DNA damage was not associated with reduced DNA repair. Indeed, we observed that depletion of STIL enhanced canonical homologous recombination repair and increased BRCA1 and RAD51 foci in response to DNA double strand breaks. Thus, inhibition of STIL significantly enhances the efficacy of DNA damaging chemotherapeutic drugs in treatment of ovarian cancer. PMID:28423708

  5. The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing

    NARCIS (Netherlands)

    Tesori, V.; Piscaglia, A.C.; Samengo, D.; Barba, M.; Bernardini, C.; Scatena, R.; Pontoglio, A.; Castellini, L.; Spelbrink, H.; Maulucci, G.; Puglisi, M.A.; Pani, G.; Gasbarrini, A.

    2015-01-01

    Although the only effective drug against primary hepatocarcinoma, the multikinase inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor resistance. To characterize cancer cell metabolic response to

  6. Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis.

    Science.gov (United States)

    van der Weyden, Louise; Papaspyropoulos, Angelos; Poulogiannis, George; Rust, Alistair G; Rashid, Mamunur; Adams, David J; Arends, Mark J; O'Neill, Eric

    2012-08-01

    The tumor suppressor gene RASSF1A is inactivated through point mutation or promoter hypermethylation in many human cancers. In this study, we conducted a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Rassf1a-null mice to identify candidate genes that collaborate with loss of Rassf1a in tumorigenesis. We identified 10 genes, including the transcription factor Runx2, a transcriptional partner of Yes-associated protein (YAP1) that displays tumor suppressive activity through competing with the oncogenic TEA domain family of transcription factors (TEAD) for YAP1 association. While loss of RASSF1A promoted the formation of oncogenic YAP1-TEAD complexes, the combined loss of both RASSF1A and RUNX2 further increased YAP1-TEAD levels, showing that loss of RASSF1A, together with RUNX2, is consistent with the multistep model of tumorigenesis. Clinically, RUNX2 expression was frequently downregulated in various cancers, and reduced RUNX2 expression was associated with poor survival in patients with diffuse large B-cell or atypical Burkitt/Burkitt-like lymphomas. Interestingly, decreased expression levels of RASSF1 and RUNX2 were observed in both precursor T-cell acute lymphoblastic leukemia and colorectal cancer, further supporting the hypothesis that dual regulation of YAP1-TEAD promotes oncogenic activity. Together, our findings provide evidence that loss of RASSF1A expression switches YAP1 from a tumor suppressor to an oncogene through regulating its association with transcription factors, thereby suggesting a novel mechanism for RASSF1A-mediated tumor suppression. ©2012 AACR.

  7. An inert pesticide adjuvant synergizes viral pathogenicity and mortality in honey bee larvae

    Science.gov (United States)

    Honey bees are highly valued for their pollination services in agricultural settings, and recent declines in managed populations have caused concern. Colony losses following a major pollination event in the United States, almond pollination, have been characterized by brood mortality with specific s...

  8. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    Fotin-Mleczek, Mariola; Zanzinger, Kai; Heidenreich, Regina; Lorenz, Christina; Kowalczyk, Aleksandra; Kallen, Karl-Josef; Huber, Stephan M

    2014-01-01

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4 + , CD8 + and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  9. Synergic effects of the partnership networks formation at the industrial market

    OpenAIRE

    Butenko, Natalia; Paschuk, Lidiia

    2013-01-01

    В статье определена сущность партнерских сетей, раскрыты первопричины и особенности возникновения синергического эффекта в рамках партнерских сетей на промышленном рынке.

  10. Synergic extraction of europium (III) by TTA and selected carbinols or ketons in carbontetrachloride

    International Nuclear Information System (INIS)

    El-Naggar, H.A.; El-Madany, S.

    1988-01-01

    The extraction of Eu(III) by HTTA dissolved in CCl 4 has been carried from acid-perchlorate and acid-acetate solutions. Some oxygen containing solvents have been added to the chelate in extraction of the acetate complex of Eu(III). The reaction mechanisms and the equilibrium constants are calculated for the different extracted species. The data obtained are discussed in the light of the structure of carbinols and ketones used as adducts

  11. Synergisms between yellow mustard mucilage and galactomannans and applications in food products--a mini review.

    Science.gov (United States)

    Cui, Steve W; Eskin, Michael A N; Wu, Ying; Ding, Shaodong

    2006-12-21

    Yellow or white mustard (Sinapis alba L.) is unique in the mustard family by containing large amounts of mucilaginous material in the seed coat. This material was shown to exhibit similar rheological properties to xanthan gum such as shear thinning flow behavior and weak gel structure. This review will discuss the synergistic interactions between yellow mustard mucilage (YMM) and galactomannans, particularly locust bean gum (LBG), and its potential food applications. In addition, synergistic interactions between YMM, with or without LBG, on starch paste viscosity and syneresis will also be reviewed. The thickening, texturizing and stabilizing properties of YMM, and its ability to form gels at very low concentration in the presence of LBG, could lead to many food and industrial applications.

  12. Antimicrobial Peptide Novicidin Synergizes with Rifampin, Ceftriaxone, and Ceftazidime against Antibiotic-Resistant Enterobacteriaceae In Vitro.

    Science.gov (United States)

    Soren, Odel; Brinch, Karoline Sidelmann; Patel, Dipesh; Liu, Yingjun; Liu, Alexander; Coates, Anthony; Hu, Yanmin

    2015-10-01

    The spread of antibiotic resistance among Gram-negative bacteria is a serious clinical threat, and infections with these organisms are a leading cause of mortality worldwide. Traditional novel drug development inevitably leads to the emergence of new resistant strains, rendering the new drugs ineffective. Therefore, reviving the therapeutic potentials of existing antibiotics represents an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide, is effective against Gram-negative bacteria. Here, we investigated novicidin as a possible antibiotic enhancer. The actions of novicidin in combination with rifampin, ceftriaxone, or ceftazidime were investigated against 94 antibiotic-resistant clinical Gram-negative isolates and 7 strains expressing New Delhi metallo-β-lactamase-1. Using the checkerboard method, novicidin combined with rifampin showed synergy with >70% of the strains, reducing the MICs significantly. The combination of novicidin with ceftriaxone or ceftazidime was synergistic against 89.7% of the ceftriaxone-resistant strains and 94.1% of the ceftazidime-resistant strains. Synergistic interactions were confirmed using time-kill studies with multiple strains. Furthermore, novicidin increased the postantibiotic effect when combined with rifampin or ceftriaxone. Membrane depolarization assays revealed that novicidin alters the cytoplasmic membrane potential of Gram-negative bacteria. In vitro toxicology tests showed novicidin to have low hemolytic activity and no detrimental effect on cell cultures. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against resistant Gram-negative bacteria in vitro. In addition, novicidin boosted the activity of rifampin. This strategy can have major clinical implications in our fight against antibiotic-resistant bacterial infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Synergism of clinical evaluation and penile sonographic imaging in diagnosis of penile fracture: a case report

    Directory of Open Access Journals (Sweden)

    Bello Jibril

    2012-09-01

    Full Text Available Abstract Introduction Penile fracture is an uncommon urologic emergency, and is the traumatic rupture of the tunica albuginea covering the corpus cavernosa. This usually occurs following blunt trauma sustained during coitus, masturbation or self-manipulations to hide or suppress an erection. Clinical diagnosis can often be easily made with typical history and examination findings. However, the patient may present atypically and/or with a suspicion of associated urethral injury. The roles of various diagnostic investigations are being evaluated in these situations. Case presentation We report the case of a 31-year-old African man with penile fracture and suspected associated urethral injury that occurred after self-manipulations to hide an erection. Conclusions Penile ultrasound and sonourethrography provide useful additional diagnostic information to supplement clinical history and physical examination findings and can be performed easily, at low cost and with no delays to surgery.

  14. Synergism of turpentine and ethanol as attractants for certain pine-infesting beetles (Coleoptera)

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, T.W.; Wilkening, A.J.; Atkinson, T.H.; Nation, J.L.; Wilkinson, R.C.; Foltz, J.L.

    1988-06-01

    Responses of seven species of pine-infesting beetles to traps baited with either turpentine, ethanol, turpentine and ethanol released from separate dispensers, or a 1:1 solution of turpentine and ethanol released from one dispenser were assessed in three field experiments. The weevil species, Pachylobius picivorus (Germar), and the cerambycid pine sawyer, Monochamus carolinenis (Olivier), were attracted to turpentine and were unaffected by the addition of ethanol. The ambrosia beetle, Xyleborus affinis Eichhoff, responded to ethanol alone but was not attracted to turpentine, nor did the presence of turpentine significantly affects its response to ethanol. The remaining four species) hylobius pales, M. titillator, Dendroctonus terebrans and x. pubescens) displayed responses to turpentine that were enhanced by the addition of ethanol, but in different ways according to the method of deployment. Reasons for increased responses by some species to a solution of turpentine and ethanol over the two released separately are not clear; they may lie in different dosages of evaporation rates of volatiles in the field. Laboratory analyses of trapped headspace volatiles from dispensers containing only turpentine and those containing a solution of turpentine and ethanol revealed no differences in the amounts of four principal monoterpene hydrocarbons (..cap alpha..-pinene, camphene, ..beta..-pinene, and limonene) released over time.

  15. Owl monkey CCR5 reveals synergism between CD4 and CCR5 in HIV-1 entry.

    Science.gov (United States)

    Nahabedian, John; Sharma, Amit; Kaczmarek, Maryska E; Wilkerson, Greg K; Sawyer, Sara L; Overbaugh, Julie

    2017-12-01

    Studying HIV-1 replication in the presence of functionally related proteins from different species has helped define host determinants of HIV-1 infection. Humans and owl monkeys, but not macaques, encode a CD4 receptor that permits entry of transmissible HIV-1 variants due to a single residue difference. However, little is known about whether divergent CCR5 receptor proteins act as determinants of host-range. Here we show that both owl monkey (Aotus vociferans) CD4 and CCR5 receptors are functional for the entry of transmitted HIV-1 when paired with human versions of the other receptor. By contrast, the owl monkey CD4/CCR5 pair is generally a suboptimal receptor combination, although there is virus-specific variation in infection with owl monkey receptors. Introduction of the human residues 15Y and 16T within a sulfation motif into owl monkey CCR5 resulted in a gain of function. These findings suggest there is cross-talk between CD4 and CCR5 involving the sulfation motif. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma

    NARCIS (Netherlands)

    Kroesen, M.; Bull, C.; Gielen, P.R.; Brok, I.C.; Armandari, I.; Wassink, M.; Looman, M.W.G.; Boon, L.; Brok, M.H.M.G.M. den; Hoogerbrugge, P.M.; Adema, G.J.

    2016-01-01

    Neuroblastoma (NBL) is a childhood malignancy of the sympathetic nervous system. For high-risk NBL patients, the mortality rate is still over 50%, despite intensive multimodal treatment. Anti-GD2 monoclonal antibody (mAB) in combination with systemic cytokine immunotherapy has shown clinical

  17. EMSE: Synergizing EM and seismic data attributes for enhanced forecasts of reservoirs

    KAUST Repository

    Katterbauer, Klemens

    2014-10-01

    New developments of electromagnetic and seismic techniques have recently revolutionized the oil and gas industry. Time-lapse seismic data is providing engineers with tools to more accurately track the dynamics of multi-phase reservoir fluid flows. With the challenges faced in distinguishing between hydrocarbons and water via seismic methods, the industry has been looking at electromagnetic techniques in order to exploit the strong contrast in conductivity between hydrocarbons and water. Incorporating this information into reservoir simulation is expected to considerably enhance the forecasting of the reservoir, hence optimizing production and reducing costs. Conventional approaches typically invert the seismic and electromagnetic data in order to transform them into production parameters, before incorporating them as constraints in the history matching process and reservoir simulations. This makes automatization difficult and computationally expensive due to the necessity of manual processing, besides the potential artifacts. Here we introduce a new approach to incorporate seismic and electromagnetic data attributes directly into the history matching process. To avoid solving inverse problems and exploit information in the dynamics of the flow, we exploit petrophysical transformations to simultaneously incorporate time lapse seismic and electromagnetic data attributes using different ensemble Kalman-based history matching techniques. Our simulation results show enhanced predictability of the critical reservoir parameters and reduce uncertainties in model simulations, outperforming with only production data or the inclusion of either seismic or electromagnetic data. A statistical test is performed to confirm the significance of the results. © 2014 Elsevier B.V. All rights reserved.

  18. Synergism of Short-Term Air Pollution Exposures and Neighborhood Disadvantage on Initial Stroke Severity.

    Science.gov (United States)

    Wing, Jeffrey J; Sánchez, Brisa N; Adar, Sara D; Meurer, William J; Morgenstern, Lewis B; Smith, Melinda A; Lisabeth, Lynda D

    2017-11-01

    Little is known about the relation between environment and stroke severity. We investigated associations between environmental exposures, including neighborhood socioeconomic disadvantage and short-term exposure to airborne particulate matter stroke severity. First-ever ischemic stroke cases were identified from the Brain Attack Surveillance in Corpus Christi project (2000-2012). Associations between pollutants, disadvantage, and National Institutes of Health Stroke Scale were modeled using linear and logistic regression with adjustment for demographics and risk factors. Pollutants and disadvantage were modeled individually, jointly, and with interactions. Higher disadvantage scores and previous-day ozone concentrations were associated with higher odds of severe stroke. Higher levels of particulate matter stroke among those in higher disadvantage areas (odds ratio, 1.24; 95% confidence interval, 1.00-1.55) but not in lower disadvantage areas (odds ratio, 0.82; 95% confidence interval, 0.56-1.22; P interaction =0.097). Air pollution exposures and neighborhood socioeconomic status may be important in understanding stroke severity. Future work should consider the multiple levels of influence on this important stroke outcome. © 2017 American Heart Association, Inc.

  19. Additivity vs Synergism: Investigation of the Additive Interaction of Cinnamon Bark Oil and Meropenem in Combinatory Therapy.

    Science.gov (United States)

    Yang, Shun-Kai; Yusoff, Khatijah; Mai, Chun-Wai; Lim, Wei-Meng; Yap, Wai-Sum; Lim, Swee-Hua Erin; Lai, Kok-Song

    2017-11-04

    Combinatory therapies have been commonly applied in the clinical setting to tackle multi-drug resistant bacterial infections and these have frequently proven to be effective. Specifically, combinatory therapies resulting in synergistic interactions between antibiotics and adjuvant have been the main focus due to their effectiveness, sidelining the effects of additivity, which also lowers the minimal effective dosage of either antimicrobial agent. Thus, this study was undertaken to look at the effects of additivity between essential oils and antibiotic, via the use of cinnamon bark essential oil (CBO) and meropenem as a model for additivity. Comparisons between synergistic and additive interaction of CBO were performed in terms of the ability of CBO to disrupt bacterial membrane, via zeta potential measurement, outer membrane permeability assay and scanning electron microscopy. It has been found that the additivity interaction between CBO and meropenem showed similar membrane disruption ability when compared to those synergistic combinations which was previously reported. Hence, results based on our studies strongly suggest that additive interaction acts on a par with synergistic interaction. Therefore, further investigation in additive interaction between antibiotics and adjuvant should be performed for a more in depth understanding of the mechanism and the impacts of such interaction.

  20. Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts.

    Science.gov (United States)

    Micucci, Matteo; Malaguti, Marco; Toschi, Tullia Gallina; Di Lecce, Giuseppe; Aldini, Rita; Angeletti, Andrea; Chiarini, Alberto; Budriesi, Roberta; Hrelia, Silvana

    2015-01-01

    This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE), of a Hibiscus sabdariffa L. flower extract (HSE), and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs) to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

  1. Calcium/calcineurin synergizes with prostratin to promote NF-κB dependent activation of latent HIV.

    Directory of Open Access Journals (Sweden)

    Jonathan K Chan

    Full Text Available Attempts to eradicate HIV have been thwarted by the persistence of a small pool of quiescent memory CD4 T cells that harbor a transcriptionally silent, integrated form of the virus that can produce infectious virions following an anamnestic immune response. Transcription factors downstream of T-cell receptor activation, such as NF-κB/Rel and nuclear factor of activated T cells (NFAT transcription members, are considered important regulators of HIV transcription during acute HIV infection. We now report studies exploring their precise role as antagonists of HIV latency using cell and primary CD4 T cell models of HIV-1 latency. Surprisingly, RNA interference studies performed in J-Lat CD4 T cells suggested that none of the NFATs, including NFATc1, NFATc2, NFATc3, and NFAT5, played a key role in the reactivation of latent HIV. However, cyclosporin A markedly inhibited the reactivation response. These results were reconciled when calcium signaling through calcineurin was shown to potentiate prostratin induced activation of NF-κB that in turn stimulated the latent HIV long terminal repeat (LTR. Similar effects of calcineurin were confirmed in a primary CD4 T cell model of HIV latency. These findings highlight an important role for calcineurin in NF-κB-dependent induction of latent HIV transcription. Innovative approaches exploiting the synergistic actions of calcineurin and prostratin in the absence of generalized T-cell activation merit exploration as a means to attack the latent viral reservoir.

  2. Phytosterols synergize with endotoxin to augment inflammation in Kupffer cells but alone have limited direct effect on hepatocytes

    Science.gov (United States)

    Phytosterols are implicated in the development of parenteral nutrition–associated liver disease. A newly proposed mechanism for phytosterol-mediated parenteral nutrition–associated liver disease is through phytosterol-facilitated hepatic proinflammatory cytokine release following exposure to intesti...

  3. Phytosterols have limited direct effect on hepatocyte transporter expression but synergize with endotoxin to enhance Kupffer cell inflammatory response

    Science.gov (United States)

    Phytosterols, non-nutritive components of soybean oil-based lipid emulsions (SO), have been implicated in the development of parenteral nutrition associated liver disease (PNALD). Phytosterols may drive the pathogenesis of PNALD through a two-hit mechanism: suppression of hepatic bile clearance thro...

  4. Biological effects of Ocimum gratissimum L. are due to synergic action among multiple compounds present in essential oil.

    Science.gov (United States)

    Galindo, Luciane Almeida; Pultrini, Aline de Moraes; Costa, Mirtes

    2010-10-01

    Species of genus Ocimum (Lamiaceae) are economically important due to their essential oils and utilization as medicine for many disorders, including the central nervous system. A previous study showed seasonal variations in chemical profile and in central nervous system activities of essential oil from Ocimum gratissimum L. The preparation obtained in spring was able to protect the animals against tonic episodes induced by electroshock while those obtained in other seasons were effective in increasing barbiturate-induced sleeping time. The chemical analysis of essential oils showed eugenol and 1,8-cineole as principal compounds and trans-caryophyllene as a sesquiterpene in higher proportion. In the present study these three compounds were evaluated, separately or mixed in the same proportion detected in spring, in the open-field and rota-rod tests, against convulsions induced by pentylenetetrazole (PTZ; 60 mg/kg, subcutaneously, s.c.) or maximal electroshock (MES; 50 mA, 0.11 s) and in sodium pentobarbital (45 mg/kg, intraperitoneally, i.p.)-induced sleeping time. The compounds, isolated or in association, did not show efficaciousness in altering convulsive episodes, and only when in association were able to increase sleeping time duration. The absence of similar essential oil activity in the isolated compounds contributes to the idea that the major compounds are not always responsible for a biological effect observed in medicinal plant preparations. This view reinforces the concept of a multitargeted approach as a therapeutic strategy, contributing to an integrated understanding of the phenomena related to experimental activity of a complex herbal mixture.

  5. Synergic mechanism of adsorption and metal-free catalysis for phenol degradation by N-doped graphene aerogel.

    Science.gov (United States)

    Ren, Xiaohua; Guo, Huanhuan; Feng, Jinkui; Si, Pengchao; Zhang, Lin; Ci, Lijie

    2018-01-01

    3D porous N-doped reduced graphene oxide (N-rGO) aerogels were synthesized by a hydrothermal reduction of graphene oxide (GO) with urea and following freeze-drying process. N-rGO aerogels have a high BET surface of 499.70 m 2 /g and a high N doping content (5.93-7.46 at%) including three kinds of N (graphitic, pyridinic and pyrrolic). Their high catalytic performance for phenol oxidation in aqueous solution was investigated by catalytic activation of persulfate (PS). We have demonstrated that N-rGO aerogels are promising metal-free catalysts for phenol removal. Kinetics studies indicate that phenol degradation follows first-order reaction kinetics with the reaction rate constant of 0.16799 min -1 for N-rGO-A(1:30). Interestingly, the comparison of direct catalytic oxidation with adsorption-catalytic oxidation experiments indicates that adsorption plays an important role in the catalytic oxidation of phenol by decreasing the phenol degradation time. Spin density and adsorption modeling demonstrates that graphitic N in N-rGO plays the most important role for the catalytic performance by inducing high positive charge densities to adjacent carbon atoms and facilitating phenol adsorption on these carbon sites. Furthermore, the activation mechanism of persulfate (PS) on N-rGO was first investigated by DFT method and PS can be activated to generate strongly oxidative radical (SO 4 · - ) by transferring electrons to N-rGO. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. No synergism between bis(propyl)-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice.

    Science.gov (United States)

    Zheng, Cheng-You; Guo, Bao-Jian; Cai, Wei; Cui, Wei; Mak, Shing-Hung; Wang, Yu-Qiang; Lee, Simon Ming-Yuen; Han, Yi-Fan; Zhang, Zai-Jun

    2016-08-01

    Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl)-cognitin (B3C), a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects.

  7. No synergism between bis(propyl-cognitin and rasagiline on protecting dopaminergic neurons in Parkinson's disease mice

    Directory of Open Access Journals (Sweden)

    Cheng-you Zheng

    2016-01-01

    Full Text Available Rasagiline, a monoamine oxidase-B inhibitor, and bis(propyl-cognitin (B3C, a novel dimer are reported to be neuroprotective. Herein, the synergistical neuroprotection produced by rasagiline and B3C was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced mice of Parkinsonism. By using neurobehavioural tests, high-performance liquid chromatography and western blot assay, we showed that B3C at 0.3 mg/kg, rasagiline at 0.02 mg/kg, as well as co-treatment with B3C and rasagiline prevented MPTP-induced behavioural abnormities, increased the concentrations of dopamine and its metabolites in the striatum, and up-regulated the expression of tyrosine hydroxylase in the substantia nigra. However, the neuroprotective effects of co-treatment were not significantly improved when compared with those of B3C or rasagiline alone. Collectively, we have demonstrated that B3C at 0.3 mg/kg and rasagline at 0.02 mg/kg could not produce synergistic neuroprotective effects

  8. Hybrid MoS2/h-BN Nanofillers As Synergic Heat Dissipation and Reinforcement Additives in Epoxy Nanocomposites.

    Science.gov (United States)

    Ribeiro, Hélio; Trigueiro, João Paulo C; Silva, Wellington M; Woellner, Cristiano F; Owuor, Peter S; Cristian Chipara, Alin; Lopes, Magnovaldo C; Tiwary, Chandra S; Pedrotti, Jairo J; Villegas Salvatierra, Rodrigo; Tour, James M; Chopra, Nitin; Odeh, Ihab N; Silva, Glaura G; Ajayan, Pulickel M

    2017-09-26

    Two-dimensional (2D) nanomaterials as molybdenum disulfide (MoS 2 ), hexagonal boron nitride (h-BN), and their hybrid (MoS 2 /h-BN) were employed as fillers to improve the physical properties of epoxy composites. Nanocomposites were produced in different concentrations and studied in their microstructure, mechanical and thermal properties. The hybrid 2D mixture imparted efficient reinforcement to the epoxy leading to increases of up to 95% in tensile strength, 60% in ultimate strain, and 58% in Young's modulus. Moreover, an enhancement of 203% in thermal conductivity was achieved for the hybrid composite as compared to the pure polymer. The incorporation of MoS 2 /h-BN mixture nanofillers in epoxy resulted in nanocomposites with multifunctional characteristics for applications that require high mechanical and thermal performance.

  9. Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Benjamin L Duell

    Full Text Available Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10 in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

  10. Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts

    Directory of Open Access Journals (Sweden)

    Deharo Eric

    2011-03-01

    Full Text Available Abstract In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the “drugs beside the drug”, looking for those products (otherwise discarded along the fractionation process able to boost the activity of isolated active compounds.

  11. Correlation between melanogenic and catalase activity in in vitro human melanocytes: a synergic strategy against oxidative stress.

    Science.gov (United States)

    Maresca, Vittoria; Flori, Enrica; Briganti, Stefania; Mastrofrancesco, Arianna; Fabbri, Claudia; Mileo, Anna M; Paggi, Marco G; Picardo, Mauro

    2008-04-01

    UV-induced DNA damage can lead to melanoma, the most dangerous form of skin cancer. Understanding the mechanisms employed by melanocytes to protect against UV is therefore a key issue. In melanocytes, catalase is the main enzyme responsible for degrading hydrogen peroxide and we have previously shown that that low basal levels of catalase activity are associated with the light phototype in in vitro and ex vivo models. Here we investigate the possible correlation between its activity and melanogenesis in primary cultures of human melanocytes. We show that while the total melanin concentration is directly correlated to the level of pigmentation, the more the degree of pigmentation increased, the lower the proportion of pheomelanin present. Moreover, in human melanocytes in vitro, catalase-specific mRNA, protein and enzymatic activity were all directly correlated with total cellular melanin content. We also observed that immediately after a peroxidative treatment, the increase in reactive oxygen species was inversely associated with pigmentation level. Darkly pigmented melanocytes therefore possess two protective strategies represented by melanins and catalase activity that are likely to act synergistically to counteract the deleterious effects of UV radiation. By contrast, lightly pigmented melanocytes possess lower levels of melanogenic and catalase activity and are therefore more susceptible to accumulate damage after UV exposition.

  12. Novel synergism by complex ligands in solvent extraction of rare earth metals(III) with β-diketones

    International Nuclear Information System (INIS)

    Imura, H.; Ebisawa, M.; Kato, M.; Ohashi, K.

    2006-01-01

    The extraction of rare earth metals(III) (RE) with hexafluoroacetylacetone (Hhfa) and 2-thenoyltrifluoroacetone (Htta) was studied in the presence of some cobalt(III) chelates such as tris(acetylacetonato)cobalt(III), tris(4-isopropyltropolonato)cobalt(III), tris(8-quinolinolato)cobalt(III), tris(8-quinolinethiolato)cobalt(III), and tris(diethyldithiocarbamato)cobalt(III) in benzene or toluene. The synergistic enhancement of the extraction of RE, especially of lanthanum(III) was found in all the systems. Therefore, those cobalt(III) chelates act as synergists or complex ligands. The equilibrium analysis and IR spectroscopic study were performed to evaluate the present synergistic mechanism. It was found that the RE-β-diketone chelates form 1:1 adducts, i.e., binuclear complexes, with the cobalt(III) chelates in the organic phase. The formation constants (β s,1 ) were determined and compared with those reported previously. The spectroscopic studies demonstrated that adducts have two different structures with inner- and outer-sphere coordination. In the former the cobalt(III) chelate directly coordinated to the RE ion and displaced the coordinated water molecules. In the latter the hydrogen-bonding was formed between the coordinating oxygen or sulfur atoms of cobalt(III) chelate and hydrogen atoms of the coordinated water molecules in the RE-β-diketone chelate. The types of the adducts are mainly due to the steric factors of the RE-β-diketone chelates and the cobalt(III) chelates

  13. Mtx toxins synergize Bacillus sphaericus and Cry11Aa against susceptible and insecticide-resistant Culex quinquefasciatus larvae.

    Science.gov (United States)

    Wirth, Margaret C; Yang, Yangkun; Walton, William E; Federici, Brian A; Berry, Colin

    2007-10-01

    Two mosquitocidal toxins (Mtx) of Bacillus sphaericus, which are produced during vegetative growth, were investigated for their potential to increase toxicity and reduce the expression of insecticide resistance through their interactions with other mosquitocidal proteins. Mtx-1 and Mtx-2 were fused with glutathione S-transferase and produced in Escherichia coli, after which lyophilized powders of these fusions were assayed against Culex quinquefasciatus larvae. Both Mtx proteins showed a high level of activity against susceptible C. quinquefasciatus mosquitoes, with 50% lethal concentrations (LC(50)) of Mtx-1 and Mtx-2 of 0.246 and 4.13 microg/ml, respectively. The LC(50)s were 0.406 to 0.430 microg/ml when Mtx-1 or Mtx-2 was mixed with B. sphaericus, and synergy improved activity and reduced resistance levels. When the proteins were combined with a recombinant Bacillus thuringiensis strain that produces Cry11Aa, the mixtures were highly active against Cry11A-resistant larvae and resistance was also reduced. The mixture of two Mtx toxins and B. sphaericus was 10 times more active against susceptible mosquitoes than B. sphaericus alone, demonstrating the influence of relatively low concentrations of these toxins. These results show that, similar to Cyt toxins from B. thuringiensis subsp. israelensis, Mtx toxins can increase the toxicity of other mosquitocidal proteins and may be useful for both increasing the activity of commercial bacterial larvicides and managing potential resistance to these substances among mosquito populations.

  14. Impact of synergism of calcium phosphomycin/tylosin tartarate supplements on the performance of broilers in the Lebanon

    Directory of Open Access Journals (Sweden)

    Zahi El-Hajj

    2010-03-01

    Full Text Available The authors evaluate the impact of a synergistic preparation (SP of supplements (a combination of calcium phosphomycin and tylosine tartarate on the performance of broilers with a history of carcass condemnation at slaughter. The experiment included 120-day old broilers (Ross 308, divided equally into two treatment groups, with three replicates per treatment and 20 birds per replicate. The two groups included controls that did not receive SP and those that were treated with SP. The SP group received treatment at three intervals (at 1-5 days of age: 160 mg/kg body weight; at 21-25 days of age: 80 mg/kg; and at 29-33 days of age: 80 mg/kg body weight. The administration of SP at a low level improved performance in SP birds compared to controls and also resulted in the lowest cumulative mortality (1.67% vs 6.67%, respectively, the lowest feed conversion of 1.91 between 1 and 43 days of age and the highest live body weight (2 544.75 g vs 2 390.18 g. The administration of SP at a low level improved performance and reduced the frequency of specific gross lesions at market age (tracheitis, lung congestion, breast blisters and bursal congestion.

  15. Impact of synergism of calcium phosphomycin/tylosin tartarate supplements on the performance of broilers in the Lebanon.

    Science.gov (United States)

    Barbour, Elie K; El-Hajj, Zahi; Shaib, Houssam; Itani, Houssam; Saadeh, Maya; Haidar, Wiam; Jaber, Lina; Demloj, Rania; Harakeh, Steve

    2010-01-01

    The authors evaluate the impact of a synergistic preparation (SP) of supplements (a combination of calcium phosphomycin and tylosine tartarate) on the performance of broilers with a history of carcass condemnation at slaughter. The experiment included 120-day old broilers (Ross 308), divided equally into two treatment groups, with three replicates per treatment and 20 birds per replicate. The two groups included controls that did not receive SP and those that were treated with SP. The SP group received treatment at three intervals (at 1-5 days of age: 160 mg/kg body weight; at 21-25 days of age: 80 mg/kg; and at 29-33 days of age: 80 mg/kg body weight). The administration of SP at a low level improved performance in SP birds compared to controls and also resulted in the lowest cumulative mortality (1.67% vs 6.67%, respectively), the lowest feed conversion of 1.91 between 1 and 43 days of age and the highest live body weight (2,544.75 g vs 2,390.18 g). The administration of SP at a low level improved performance and reduced the frequency of specific gross lesions at market age (tracheitis, lung congestion, breast blisters and bursal congestion).

  16. Synergism of Electrospinning and Nano-alumina Trihydrate on the Polymorphism, Crystallinity and Piezoelectric Performance of PVDF Nanofibers

    Science.gov (United States)

    Khalifa, Mohammed; Deeksha, B.; Mahendran, Arunjunairaj; Anandhan, S.

    2018-03-01

    Poly(vinlylidene fluoride) (PVDF) is known for its electroactive phases, which can be nucleated by incorporating nanoparticles into PVDF to enhance its piezoelectric performance. In this study, the synergistic effect of electrospinning and nano alumina trihydrate (ATH) filler was used to enhance the electroactive β phase of PVDF. Electrospun nanofibers of PVDF/ATH nanocomposite (PANCF) were synthesized with different loadings of ATH. The presence of ATH enhances the surface charges of the electrospun droplets, leading to thinner fibers. The highest β-phase content was found to be 70.1% for PANCF with 10% ATH. The piezoelectric performance of the nanofiber mats was studied using an indigenous setup. The highest voltage output of 840 mV was produced by PANCF with 10% ATH. These nanofibers could be a promising material in the field of sensors, actuators and energy-harvesting applications.

  17. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

    Directory of Open Access Journals (Sweden)

    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  18. EGFR-targeted TRAIL and a Smac mimetic synergize to overcome apoptosis resistance in KRAS mutant colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Yvonne Möller

    Full Text Available TRAIL is a death receptor ligand that induces cell death preferentially in tumor cells. Recombinant soluble TRAIL, however, performs poorly as an anti-cancer therapeutic because oligomerization is required for potent biological activity. We previously generated a diabody format of tumor-targeted TRAIL termed Db(αEGFR-scTRAIL, comprising single-stranded TRAIL molecules (scTRAIL and the variable domains of a humanized variant of the EGFR blocking antibody Cetuximab. Here we define the bioactivity of Db(αEGFR-scTRAIL with regard to both EGFR inhibition and TRAIL receptor activation in 3D cultures of Caco-2 colorectal cancer cells, which express wild-type K-Ras. Compared with conventional 2D cultures, Caco-2 cells displayed strongly enhanced sensitivity toward Db(αEGFR-scTRAIL in these 3D cultures. We show that the antibody moiety of Db(αEGFR-scTRAIL not only efficiently competed with ligand-induced EGFR function, but also determined the apoptotic response by specifically directing Db(αEGFR-scTRAIL to EGFR-positive cells. To address how aberrantly activated K-Ras, which leads to Cetuximab resistance, affects Db(αEGFR-scTRAIL sensitivity, we generated stable Caco-2tet cells inducibly expressing oncogenic K-Ras(G12V. In the presence of doxycycline, these cells showed increased resistance to Db(αEGFR-scTRAIL, associated with the elevated expression of the anti-apoptotic proteins cIAP2, Bcl-xL and FlipS. Co-treatment of cells with the Smac mimetic SM83 restored the Db(αEGFR-scTRAIL-induced apoptotic response. Importantly, this synergy between Db(αEGFR-scTRAIL and SM83 also translated to 3D cultures of oncogenic K-Ras expressing HCT-116 and LoVo colorectal cancer cells. Our findings thus support the notion that Db(αEGFR-scTRAIL therapy in combination with apoptosis-sensitizing agents may be promising for the treatment of EGFR-positive colorectal cancers, independently of their KRAS status.

  19. SMAC-armed vaccinia virus induces both apoptosis and necroptosis and synergizes the efficiency of vinblastine in HCC.

    Science.gov (United States)

    Pan, Qiang; Huang, Yuanyong; Chen, Lieyang; Gu, JinFa; Zhou, Xiumei

    2014-10-01

    Hepatocellular carcinoma (HCC) has particularly high incidence rate in Asia and its resistance to the chemotherapeutic drugs and cell death make it intractable. Vaccinia virus (VV) is a potential vehicle and has been widely used in cancer therapy. SMAC/DIABLO is a critical factor in activating caspases and eliminating inhibition of IAPs when the programmed cell death is promoted. In this study, we constructed a tumor-targeted vaccinia virus carrying SMAC/DIABLO gene that was knocked in the region of viral thymidine kinase gene (VV-SMAC). Our results showed that VV-SMAC efficiently infected and destroyed HCC cells via triggering both caspase-dependent apoptosis and necroptosis with depletion of IAPs. Furthermore, ripoptosome, a prerequisite complex of necroptosis, was assembled and induced by VV-SMAC. In addition, the combination of VV-SMAC and vinblastine represented a synergistic effect on HCC cells. In summary, our data suggest that VV-SMAC is a potential candidate and combination of VV-SMAC and vinblastine may provide a new avenue in treatment of HCC.

  20. Development of Eco-friendly Soy Protein Isolate Films with High Mechanical Properties through HNTs, PVA, and PTGE Synergism Effect

    Science.gov (United States)

    Liu, Xiaorong; Song, Ruyuan; Zhang, Wei; Qi, Chusheng; Zhang, Shifeng; Li, Jianzhang

    2017-03-01

    This study was to develop novel soy protein isolate-based films for packaging using halloysite nanotubes (HNTs), poly-vinyl alcohol (PVA), and 1,2,3-propanetriol-diglycidyl-ether (PTGE). The structural, crystallinity, opacity, micromorphology, and thermal stability of the resultant SPI/HNTs/PVA/PTGE film were analyzed by the Attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), UV-Vis spectrophotometry, scanning electron microscopy (SEM), and thermo-gravimetric analysis (TGA). The SPI/HNTs/PVA/PTGE film illustrated that HNTs were uniformly dispersed in the SPI matrix and the thermal stability of the film was enhanced. Furthermore, the tensile strength (TS) of the SPI/HNTs/PVA/PTGE film was increased by 329.3% and the elongation at the break (EB) remained unchanged. The water absorption (WA) and the moisture content (MC) were decreased by 5.1% and 10.4%, respectively, compared to the unmodified film. The results highlighted the synergistic effects of SPI, HNTs, PVA, and PTGE on the mechanical properties, water resistance, and thermal stability of SPI films, which showed excellent strength and flexibility. In short, SPI films prepared from HNTs, PVA, and PTGE showed considerable potential as packaging materials.

  1. Synergism between essential oils and antimicrobial drugs against Staphylooccus aureus and Escherichia coli strains from human infections

    OpenAIRE

    Zago, Juliana A. A. [UNESP; Ushimaru, Priscila I. [UNESP; Barbosa, Lidiane N. [UNESP; Fernandes Junior, Ary [UNESP

    2009-01-01

    Estudos com plantas e utilização em terapias combinatórias têm sido estimulados. Verificou-se as possíveis interações entre óleos essenciais de plantas [canela (Cinnamomum zeylanicum Blume Lauraceae), capim-cidreira (Cymbopogon citratus (DC.) Stapf, Poaceae), hortelã-pimenta (Mentha piperita L. Lamiaceae), gengibre (Zingiber officinale Roscoe Zingiberaceae), cravo-da-índia (Caryophillus aromaticus L. Myrtaceae) e alecrim (Rosmarinus officinalis L. Lamiaceae)] combinados a oito drogas antimicr...

  2. Diclofenac inhibits tumor necrosis factor-a-induced nuclear factor-kB activation causing synergic hepatocyte apoptosis

    NARCIS (Netherlands)

    Frederiksson, L; Herpers, B; Benedetti, G; Matadin, Q; Puigvert, J.C.; de Bont, H; Dragovic, S.; Vermeulen, N.P.E.; Commandeur, J.N.M.; Danen, E; de Graauw, M; van de Water, B.

    2011-01-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by

  3. Synergism between anodic oxidation with diamond anodes and heterogeneous catalytic photolysis for the treatment of pharmaceutical pollutants

    Directory of Open Access Journals (Sweden)

    Juan M. Peralta-Hernández

    2016-03-01

    Full Text Available The mineralization of diclofenac and acetaminophen has been studied by single anodic oxidation with boron-doped diamond (AO-BDD using an undivided electrolysis cell, by single heterogeneous catalytic photolysis with titanium dioxide (HCP-TiO2 and by the combination of both advanced oxidation processes. The results show that mineralization can be obtained with either single technology. The type of functional groups of the pollutant does not influence the results of the single AO-BDD process, but it has a significant influence on the results obtained with HCP-TiO2. A clear synergistic effect appears when both processes are combined showing improvements in the oxidation rate of more than 50% for diclofenac and nearly 200% for acetaminophen at the highest current exerted. Results obtained are explained in terms of the production of oxidants on the surface of BDD (primarily peroxodisulfate and the later homogeneous catalytic light decomposition of these oxidants in the bulk. This mechanism is consistent with the larger improvement observed at higher current densities, for which the production of oxidants is promoted.

  4. Influence of the amine salt anion on the synergic solvent extraction of praseodymium with mixtures of chelating extractants and tridodecylamine

    Energy Technology Data Exchange (ETDEWEB)

    Dukov, I.L.; Jordanov, V.M. [Higher Inst. of Chemical Technology, Sofia (Bulgaria)

    1995-11-01

    The solvent extraction of Pr with thenoyltrifluoroacetone, (HTTA) or 1-phenyl-3-methyl-4-benzoyl-pyrazol-5-one(HP) and tridodecylammonium salt (TDAHA,A{sup -} = Cl{sup -},NO{sub 3}{sup -}, ClO{sub 4}{sup -}) in C{sub 6}H{sub 6} has been studied. The composition of the extracted species has been determined as Pr(TTA){sub 3} TDAHA and TDAH{sup +}[PrP{sub 4}]{sup -}. The values of the equilibrium constants, have been calculated. The extraction mechanism has been discussed on the basis of the experimental data. 34 refs., 6 figs., 2 tabs.

  5. Mixed Beam Murine Harderian Gland Tumorigenesis: Predicted Dose-Effect Relationships if neither Synergism nor Antagonism Occurs

    Energy Technology Data Exchange (ETDEWEB)

    Siranart, Nopphon; Blakely, Eleanor A.; Cheng, Alden; Handa, Naval; Sachs, Rainer K.

    2016-12-01

    Complex mixed radiation fields exist in interplanetary space, and not much is known about their latent effects on space travelers. In silico synergy analysis default predictions are useful when planning relevant mixed-ion-beam experiments and interpreting their results. These predictions are based on individual dose-effect relationships (IDER) for each component of the mixed-ion beam, assuming no synergy or antagonism. For example, a default hypothesis of simple effect additivity has often been used throughout the study of biology. However, for more than a century pharmacologists interested in mixtures of therapeutic drugs have analyzed conceptual, mathematical and practical questions similar to those that arise when analyzing mixed radiation fields, and have shown that simple effect additivity often gives unreasonable predictions when the IDER are curvilinear. Various alternatives to simple effect additivity proposed in radiobiology, pharmacometrics, toxicology and other fields are also known to have important limitations. In this work, we analyze upcoming murine Harderian gland (HG) tumor prevalence mixed-beam experiments, using customized open-source software and published IDER from past single-ion experiments. The upcoming experiments will use acute irradiation and the mixed beam will include components of high atomic number and energy (HZE). We introduce a new alternative to simple effect additivity, "incremental effect additivity", which is more suitable for the HG analysis and perhaps for other end points. We use incremental effect additivity to calculate default predictions for mixture dose-effect relationships, including 95% confidence intervals. We have drawn three main conclusions from this work. 1. It is important to supplement mixed-beam experiments with single-ion experiments, with matching end point(s), shielding and dose timing. 2. For HG tumorigenesis due to a mixed beam, simple effect additivity and incremental effect additivity sometimes give default predictions that are numerically close. However, if nontargeted effects are important and the mixed beam includes a number of different HZE components, simple effect additivity becomes unusable and another method is needed such as incremental effect additivity. 3. Eventually, synergy analysis default predictions of the effects of mixed radiation fields will be replaced by more mechanistic, biophysically-based predictions. However, optimizing synergy analyses is an important first step. If mixed-beam experiments indicate little synergy or antagonism, plans by NASA for further experiments and possible missions beyond low earth orbit will be substantially simplified.

  6. Calcium/calcineurin synergizes with prostratin to promote NF-κB dependent activation of latent HIV.

    Science.gov (United States)

    Chan, Jonathan K; Bhattacharyya, Darshana; Lassen, Kara G; Ruelas, Debbie; Greene, Warner C

    2013-01-01

    Attempts to eradicate HIV have been thwarted by the persistence of a small pool of quiescent memory CD4 T cells that harbor a transcriptionally silent, integrated form of the virus that can produce infectious virions following an anamnestic immune response. Transcription factors downstream of T-cell receptor activation, such as NF-κB/Rel and nuclear factor of activated T cells (NFAT) transcription members, are considered important regulators of HIV transcription during acute HIV infection. We now report studies exploring their precise role as antagonists of HIV latency using cell and primary CD4 T cell models of HIV-1 latency. Surprisingly, RNA interference studies performed in J-Lat CD4 T cells suggested that none of the NFATs, including NFATc1, NFATc2, NFATc3, and NFAT5, played a key role in the reactivation of latent HIV. However, cyclosporin A markedly inhibited the reactivation response. These results were reconciled when calcium signaling through calcineurin was shown to potentiate prostratin induced activation of NF-κB that in turn stimulated the latent HIV long terminal repeat (LTR). Similar effects of calcineurin were confirmed in a primary CD4 T cell model of HIV latency. These findings highlight an important role for calcineurin in NF-κB-dependent induction of latent HIV transcription. Innovative approaches exploiting the synergistic actions of calcineurin and prostratin in the absence of generalized T-cell activation merit exploration as a means to attack the latent viral reservoir.

  7. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    Science.gov (United States)

    Chang, Chih-Hsien; Liu, Shin-Yi; Chi, Chih-Wen; Yu, Hsiang-Lin; Chang, Tsui-Jung; Tsai, Tung-Hu; Lee, Te-Wei; Chen, Yu-Jen

    2015-01-01

    External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. PMID:26056445

  8. Toxicological and biochemical basis of synergism between the entomopathogenic fungus Lecanicillium muscarium and the insecticide matrine against Bemisia tabaci (Gennadius)

    Science.gov (United States)

    Ali, Shaukat; Zhang, Can; Wang, Zeqing; Wang, Xing-Min; Wu, Jian-Hui; Cuthbertson, Andrew G. S.; Shao, Zhenfang; Qiu, Bao-Li

    2017-04-01

    The sweetpotato whitefly Bemisia tabaci (Gennadius) was challenged with different combinations of matrine (insecticide) and Lecanicillium muscarium (entomopathogenic fungus). Our results revealed a synergistic relationship between matrine and L. muscarium on mortality and enzyme activities of B. tabaci. To illustrate the biochemical mechanisms involved in detoxification and immune responses of B. tabaci against both control agents, activities of different detoxifying and antioxidant enzymes were quantified. After combined application of matrine and L. muscarium, activities of carboxylestrease (CarE), glutathione-s-transferase (GSTs) and chitinase (CHI) decreased during the initial infection period. Acetylcholinestrase (AChE) activities increased during the entire experimental period, whereas those of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) decreased during the later infection period. The increased mortality and suppression of enzymatic response of B. tabaci following matrine and L. muscarium application suggests a strong synergistic effect between both agents. The strong synergistic effect is possibly related to the disturbance of acetylcholine balance and changes in AchE activities of the whitefly as both matrine and L. muscarium target insect acetylcholine (Ach) receptors which in turn effects AchE production. Therefore, our results have revealed the complex biochemical processes involved in the synergistic action of matrine and L. muscarium against B. tabaci.

  9. Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death.

    Science.gov (United States)

    Lv, Da-Lun; Chen, Lei; Ding, Wei; Zhang, Wei; Wang, He-Li; Wang, Shuai; Liu, Wen-Bei

    2018-01-01

    Melanoma is a leading cause of cancer death worldwide, and SMI-4a and G-Rh2 exert anti-tumor activity in multiple cancer. However, SMI-4a as well as a synergistic relationship between SMI-4a and G-Rh2 in anti-melanoma capacity are still unknown. Therefore, we investigated the effects of SMI-4a and combined SMI-4a with G-Rh2 on the viability, apoptosis and autophagy of melanoma, and to preliminarily explore the underlying mechanism of SMI-4a and combined SMI-4a with G-Rh2 in inhibiting tumor growth. Cell viability was examined with cell counting Kit 8 assay and colony formation assay; Apoptosis was evaluated by flow cytometry and Caspase 3/7 activity assay; Western blotting was used to test proteins related to autophagy and the AKT/mammalian target of rapamycin (mTOR) signaling pathway; Tumor xenograft model in BALB/c nude mice was performed to evaluate the effects of SMI-4a and combined SMI-4a with G-Rh2 in anti-melanoma in vivo. SMI-4a, a pharmacological inhibitor of PIM-1, could decrease cell viability, induce apoptosis, and promote Caspase 3/7 activity in both A375 and G361 melanoma cells, and SMI-4a inhibited tumor growth by inducing autophagy via down-regulating AKT/mTOR axis in melanoma cells. Furthermore, G-Rh2 amplified the anti-tumor activity of SMI-4a in melanoma cells via strengthening autophagy. Our results suggested that SMI-4a could enhance autophagy-inducing apoptosis by inhibiting AKT/mTOR signaling pathway in melanoma cells, and G-Rh2 could enhance the effects of SMI-4a against melanoma cancer via amplifying autophagy induction. This study demonstrates that combined SMI-4a and G-Rh2 might be a novel alternative strategy for melanoma treatment.

  10. An environment with strong gravitational and magnetic field alterations synergizes to promote variations in Arabidopsis thaliana callus global transcriptional state

    Data.gov (United States)

    National Aeronautics and Space Administration — Using diamagnetic levitation we have exposed A. thaliana in vitro callus cultures to five environments with different levels of effective gravity (from levitation...

  11. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  12. Synergism of thymol, carvacrol and eugenol in larvae of the cattle tick, Rhipicephalus microplus, and brown dog tick, Rhipicephalus sanguineus.

    Science.gov (United States)

    Araújo, L X; Novato, T P L; Zeringota, V; Maturano, R; Melo, D; DA Silva, B C; Daemon, E; DE Carvalho, M G; Monteiro, C M O

    2016-12-01

    The effects of combinations of the monoterpenes thymol and carvacrol and the phenylpropanoid eugenol in larvae of Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae) and Rhipicephalus sanguineus sensu lato (s.l.) (Acari: Ixodidae) were assessed by the larval packet test. The CompuSyn program was used to make qualitative assessments of the effects (synergistic, additive and antagonistic) of the associations. The effects of all combinations tested against R. microplus larvae were synergistic, with combination indices (CIs) eugenol and thymol + eugenol have synergistic effects in R. microplus and R. sanguineus s.l. larvae. © 2016 The Royal Entomological Society.

  13. Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Anne Waschbisch

    Full Text Available Immunoglobulin-like transcript (ILT 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue. We also studied the ability of interferon beta, alone or in combination with vitamin D, to induce upregulation of these receptors in vitro, and compared expression levels between interferon-treated and untreated multiple sclerosis patients. In vitro interferon beta treatment led to a robust upregulation of ILT3 and ILT4 on monocytes, and dihydroxyvitamin D3 increased expression of ILT3 but not ILT4. ILT3 was abundant in demyelinating lesions in postmortem brain, and expression on monocytes in the cerebrospinal fluid was higher than in peripheral blood, suggesting that the central nervous system milieu induces ILT3, or that ILT3 positive monocytes preferentially enter the brain. Our data are consistent with involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D.

  14. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and episilvestrol isolated from Aglaia stellatopilosa

    OpenAIRE

    DAKER, MAELINDA; YEO, JIUN-TZEN; BAKAR, NORHASIMAH; ABDUL RAHMAN, ASMA' SAIYIDATINA AISHAH ABDUL; AHMAD, MUNIRAH; YEO, TIONG-CHIA; KHOO, ALAN SOO-BENG

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation ...

  15. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  16. Auxin-cytokinin synergism in vitro for producing genetically stable plants of Ruta graveolens using shoot tip meristems

    OpenAIRE

    Mohammad Faisal; Naseem Ahmad; Mohammad Anis; Abdulrahman A. Alatar; Ahmad A. Qahtan

    2018-01-01

    An efficient micropropagation protocol was developed for Ruta graveolens Linn. using shoot tip meristems derived from a 4-month-old field grown plant. In vitro shoot regeneration and proliferation was accomplished on Murashige and Skoogs (MS) semi-solid medium in addition to different doses of cytokinins viz.6- benzyl adenine (BA), Kinetin (Kn) or 2-isopetynyl adenine (2iP), singly or in combination with auxins viz. indole-3-acetic acid (IAA), indole-3-butyric acid (IBA) or α-naphthalene acet...

  17. Spire and Formin 2 synergize and antagonize in regulating actin assembly in meiosis by a ping-pong mechanism.

    Directory of Open Access Journals (Sweden)

    Pierre Montaville

    2014-02-01

    Full Text Available In mammalian oocytes, three actin binding proteins, Formin 2 (Fmn2, Spire, and profilin, synergistically organize a dynamic cytoplasmic actin meshwork that mediates translocation of the spindle toward the cortex and is required for successful fertilization. Here we characterize Fmn2 and elucidate the molecular mechanism for this synergy, using bulk solution and individual filament kinetic measurements of actin assembly dynamics. We show that by capping filament barbed ends, Spire recruits Fmn2 and facilitates its association with barbed ends, followed by rapid processive assembly and release of Spire. In the presence of actin, profilin, Spire, and Fmn2, filaments display alternating phases of rapid processive assembly and arrested growth, driven by a "ping-pong" mechanism, in which Spire and Fmn2 alternately kick off each other from the barbed ends. The results are validated by the effects of injection of Spire, Fmn2, and their interacting moieties in mouse oocytes. This original mechanism of regulation of a Rho-GTPase-independent formin, recruited by Spire at Rab11a-positive vesicles, supports a model for modulation of a dynamic actin-vesicle meshwork in the oocyte at the origin of asymmetric positioning of the meiotic spindle.

  18. A transcriptomic analysis of turmeric: Curcumin represses the expression of cholesterol biosynthetic genes and synergizes with simvastatin.

    Science.gov (United States)

    Einbond, Linda Saxe; Manservisi, Fabiana; Wu, Hsan-Au; Balick, Michael; Antonetti, Victoria; Vornoli, Andrea; Menghetti, Ilaria; Belpoggi, Fiorella; Redenti, Stephen; Roter, Alan

    2018-02-03

    The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. The active component curcumin induces a variety of diverse biological effects and forms a series of degradation and metabolic products in vivo. Our hypothesis is that the field of toxicogenomics provides tools that can be used to characterize the mode of action and toxicity of turmeric components and to predict turmeric-drug interactions. Male Sprague-Dawley rats were treated for 4 days with turmeric root containing about 3% curcumin (comparable to what people consume in the fresh or dried root) or a fraction of turmeric enriched for curcumin (∼74%) and liver tissue collected for gene expression analysis. Two doses of each agent were added to the diet, corresponding to 540 and 2700 mg/kg body weight/day of turmeric. The transcriptomic effects of turmeric on rat liver tissue were examined using 3 programs, ToxFx Analysis Suite, in the context of a large drug database, Ingenuity Pathway and NextBio analyses. ToxFx analysis indicates that turmeric containing about 3% or 74% curcumin represses the expression of cholesterol biosynthetic genes. The dose of 400 mg/kg b.w./day curcumin induced the Drug Signature associated with hepatic inflammatory infiltrate. Ingenuity analysis confirmed that all 4 turmeric treatments had a significant effect on cholesterol biosynthesis, specifically the Cholesterol biosynthesis superpathway and Cholesterol biosynthesis 1 and 2. Among the top 10 up or downregulated genes, all 4 treatments downregulated PDK4; while 3 treatments downregulated ANGPTL4 or FASN. These findings suggest curcumin may enhance the anticancer effects of certain classes of statins, which we confirmed with biological assays. Given this enhancement, lower levels of statins may be required, and even be desirable. Our findings also warn of possible safety issues, such as potential inflammatory liver effects, for patients who ingest a combination of certain classes of statins and curcumin. Transcriptomic analysis suggests that turmeric is worthwhile to study to prevent and treat cancer and lipid disorders. Our approach lays new groundwork for studies of the mode of action and safety of herbal medicines and can also be used to develop a methodology to standardize herbal medicines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    International Nuclear Information System (INIS)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

    2012-01-01

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA A ) receptors. However, seizure activity itself causes the endocytosis of GABA A receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD 50 ; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ► PHY attenuated GD-induced seizure development, but not seizure duration.

  20. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  1. Synergism between Ni and W in the NiW/gama-Al2O3 Hydrotreating Catalysts

    Czech Academy of Sciences Publication Activity Database

    Spojakina, A.A.; Palcheva, R.; Jirátová, Květa; Tyuliev, G.; Petrov, L.

    2005-01-01

    Roč. 104, 1-2 (2005), s. 45-52 ISSN 1011-372X Institutional research plan: CEZ:AV0Z40720504 Keywords : NiW/gama-Al2O3 * Thiophene hydrodesulfurization * TPR, XPS Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 2.088, year: 2005

  2. Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Pei-Jie Shi

    2016-02-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK down-regulation in the treatment of ALL. Methods The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID mouse model. Results When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2 gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. Conclusions FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel and powerful strategy for treating ALL.

  3. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo

    DEFF Research Database (Denmark)

    Grüner, Sabine; Prostredna, Miroslava; Schulte, Valerie

    2003-01-01

    Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet beta1 integrins in these processes remains mostly undefined. Here, we demonstrate by intra...

  4. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

    Science.gov (United States)

    Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

    1998-03-01

    An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

  5. Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF-1α–mediated tumor apoptotic switch

    Science.gov (United States)

    Magnon, Claire; Opolon, Paule; Ricard, Marcel; Connault, Elisabeth; Ardouin, Patrice; Galaup, Ariane; Métivier, Didier; Bidart, Jean-Michel; Germain, Stéphane; Perricaudet, Michel; Schlumberger, Martin

    2007-01-01

    Tumor radioresponsiveness depends on endothelial cell death, which leads in turn to tumor hypoxia. Radiation-induced hypoxia was recently shown to trigger tumor radioresistance by activating angiogenesis through hypoxia-inducible factor 1–regulated (HIF-1–regulated) cytokines. We show here that combining targeted radioiodide therapy with angiogenic inhibitors, such as canstatin, enhances direct tumor cell apoptosis, thereby overcoming radio-induced HIF-1–dependent tumor survival pathways in vitro and in vivo. We found that following dual therapy, HIF-1α increases the activity of the canstatin-induced αvβ5 signaling tumor apoptotic pathway and concomitantly abrogates mitotic checkpoint and tetraploidy triggered by radiation. Apoptosis in conjunction with mitotic catastrophe leads to lethal tumor damage. We discovered that HIF-1 displays a radiosensitizing activity that is highly dependent on treatment modalities by regulating key apoptotic molecular pathways. Our findings therefore support a crucial role for angiogenesis inhibitors in shifting the fate of radiation-induced HIF-1α activity from hypoxia-induced tumor radioresistance to hypoxia-induced tumor apoptosis. This study provides a basis for developing new biology-based clinically relevant strategies to improve the efficacy of radiation oncology, using HIF-1 as an ally for cancer therapy. PMID:17557121

  6. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts

    Science.gov (United States)

    Vinholes, Juliana; Vizzotto, Márcia

    2017-01-01

    Background: Camellia sinensis, the most consumed and popular beverages worldwide, and Eugenia uniflora, a Brazilian native species, have been already confirmed to have beneficial effects in the treatment of diabetes mellitus. However, their potential acting together against an enzyme linked to this pathology has never been exploited. Objective: The aim of this study was to evaluate the inhibitory properties of individual and combined ethanolic extracts of the leaves of C. sinensis and E. uniflora over alpha-glucosidase, a key digestive enzyme used on the Type 2 diabetes mellitus (T2DM) control. In addition, their inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and peroxyl radicals was also assayed. Materials and Methods: Enzyme inhibition and antioxidant potential were assessed based on in vitro assays. Total phenolic compounds, carotenoids, and chlorophylls A and B were achieved using spectrophotometric methods. Results: E. uniflora was almost 40 times more active on alpha-glucosidase than C. sinensis and combined extracts showed a significant synergistic effect with an obtained IC50 value almost 5 times lower than the theoretical value. C. sinensis extract was twice more active than E. uniflora concerning DPPH•, in contrast, E. uniflora was almost 10 times more effective than C. sinensis on inhibition of peroxyl radicals with a significant synergistic effect for combined extracts. The extracts activities may be related with their phytochemicals, mainly phenolic compounds, and chlorophylls. Conclusion: Combined C. sinensis and E. uniflora ethanolic extracts showed synergistic effect against alpha-glucosidase and lipid peroxidation. These herbal combinations can be used to control postprandial hyperglycemia and can also provide antioxidant defenses to patients with T2DM. SUMMARY Alfa-glucosidase and antioxidant Interaction between Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts was investigated.Extracts showed synergistic effect over alpha-glucosidase and peroxyl radicals.Total phenolic, carotenoids and chlorophylls A and B can be responsible by the observed activities.Extracts could be used as alternative to control postprandial hyperglycemia.Extracts could increase antioxidant defenses to patients with T2DM. Abbreviations Used: T2DM: Type 2 diabetes mellitus; DPPH: 2,2-diphenyl-1-picrylhydrazyl radical; PNPG: 4-Nitrophenyl β-D-glucuronide; LOO: Lipid peroxidation; SEM: Standard error of the mean; CAE: Chlorogenic acid equivalent PMID:28250662

  7. Triclosan demonstrates synergic effect with amphotericin B and fluconazole and induces apoptosis-like cell death in Cryptococcus neoformans

    OpenAIRE

    Elaheh eMovahed; Grace Min Yi eTan; Komathy eMunusamy; Tee Cian eYeow; Sun Tee eTay; Won Fen eWong; Chung Yeng eLooi

    2016-01-01

    Objectives: Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans. Methods: Minimal inhibitory concentration (MIC) of triclosan in different C. neoformans strains was first examined. The in vitro interactions be...

  8. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  9. Blue light treatment of Pseudomonas aeruginosa: Strong bactericidal activity, synergism with antibiotics and inactivation of virulence factors.

    Science.gov (United States)

    Fila, Grzegorz; Kawiak, Anna; Grinholc, Mariusz Stanislaw

    2017-08-18

    Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies. Although blue light irradiation is a promising alternative approach, only limited and preliminary studies have described its effect on virulence factors. The current study aimed to investigate the effects of lethal and sub-lethal doses of blue light treatment (BLT) on P. aeruginosa virulence factors. We analyzed the inhibitory effects of blue light irradiation on the production/activity of several virulence factors. Lethal BLT inhibited the activity of pyocyanin, staphylolysin, pseudolysin and other proteases, but sub-lethal BLT did not affect the production/expression of proteases, phospholipases, and flagella- or type IV pili-associated motility. Moreover, a eukaryotic cytotoxicity test confirmed the decreased toxicity of blue light-treated extracellular P. aeruginosa fractions. Finally, the increased antimicrobial susceptibility of P. aeruginosa treated with sequential doses of sub-lethal BLT was demonstrated with a checkerboard test. Thus, this work provides evidence-based proof of the susceptibility of drug-resistant P. aeruginosa to BLT-mediated killing, accompanied by virulence factor reduction, and describes the synergy between antibiotics and sub-lethal BLT.

  10. Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma cells - synergism with autophagy inhibition.

    Science.gov (United States)

    Kubista, Bernd; Schoefl, Thomas; Mayr, Lisa; van Schoonhoven, Sushilla; Heffeter, Petra; Windhager, Reinhard; Keppler, Bernhard K; Berger, Walter

    2017-04-12

    Osteosarcoma is the most frequent primary malignant bone tumor. Although survival has distinctly increased due to neoadjuvant chemotherapy in the past, patients with metastatic disease and poor response to chemotherapy still have an adverse prognosis. Hence, development of new therapeutic strategies is still of utmost importance. Anticancer activity of KP46 against osteosarcoma cell models was evaluated as single agent and in combination approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay. Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays. KP46 exerted exceptional anticancer activity at the nanomolar to low micromolar range, depending on the assay format, against all osteosarcoma cell models with minor but significant differences in IC 50 values. KP46 treatment of osteosarcoma cells caused rapid loss of cell adhesion, weak cell cycle accumulation in S-phase and later signs of apoptotic cell death. Furthermore, already at sub-cytotoxic concentrations KP46 reduced the migratory potential of osteosarcoma cells and exerted synergistic effects with cisplatin, a standard osteosarcoma chemotherapeutic. Moreover, the gallium compound induced signs of autophagy in osteosarcoma cells. Accordingly, blockade of autophagy by chloroquine but also by the Bcl-2 inhibitor obatoclax increased the cytotoxic activity of KP46 treatment significantly, suggesting autophagy induction as a protective mechanism against KP46. Together, our results identify KP46 as a new promising agent to supplement standard chemotherapy and possible future targeted therapy in osteosarcoma.

  11. Antioxidant activity of amino acids in soybean oil at frying temperature: Structural effects and synergism with tocopherols

    Science.gov (United States)

    The purpose of this study was to evaluate amino acids as natural antioxidants for frying. Twenty amino acids were added to soybean oil heated to 180 ºC, and the effects of amino acid structure on the antioxidant activity were investigated. Amino acids containing a thiol, a thioether, or an extra ami...

  12. Synergic effect of chitosan and dicalcium phosphate on tricalcium silicate-based nanocomposite for root-end dental application.

    Science.gov (United States)

    Panahi, Fatemeh; Rabiee, Sayed Mahmood; Shidpour, Reza

    2017-11-01

    In recent years, cement composites based on calcium silicate have been more generally considered for medical applications. Calcium silicate Cement are among the categories that are used in dental root canal treatment. The aim of this study is to make new calcium silicate cement with dicalcium phosphate and chitosan additives to preserve and strengthen desirable properties of this type of cements. In this study, composite dental cement based on calcium silicate was prepared. Then effect of adding biodegradable and biocompatible polymer such as chitosan on setting properties and its structure were studied. In this study, a combination of calcium silicate, dicalcium phosphate (DCP) and bismuth oxide (Bi 2 O 3 ) as powder phase and 2% solution of the chitosan dissolved in 1% acetic acid solution as liquid phase, was used. As well as control sample was obtained by mixing the powder with distilled water as the liquid phase. Based on the obtained results, setting time of composite cement was changed from 51 to 67 minutes by adding chitosan polymer. Presence of chitosan also reduced the compressive strength a little. The bioactivity of the cement were studied in a solution of simulated body fluid (SBF) for 14 days. The samples were analyzed by SEM to identify the microstructure and by XRD to determine crystal structure. The composition of cement before incubation in SBF was included early phases (phase calcium silicate and calcium phosphate) that after 14 days of immersion in SBF, they were converted to layer-shaped hydroxy apatite and the presence of chitosan had not any influence on the final phase of hydroxy apatite. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. How Can 1+1=3? beta(2)-Adrenergic and Glucocorticoid Receptor Agonist Synergism in Obstructive Airway Diseases

    NARCIS (Netherlands)

    Schmidt, Martina; Michel, Martin C.

    2011-01-01

    For a long time it was believed that beta(2)-adrenergic receptor agonists used in the treatment of obstructive airway diseases worked primarily on airway smooth muscle cells, causing relaxation, whereas glucocorticoids primarily improved airway function via their anti-inflammatory action, indicating

  14. Ultrasound synergized with three-phase partitioning for extraction and separation of Corbicula fluminea polysaccharides and possible relevant mechanisms.

    Science.gov (United States)

    Yan, Jing-Kun; Wang, Yao-Yao; Qiu, Wen-Yi; Wang, Zhen-Bin; Ma, Haile

    2018-01-01

    Ultrasound and three-phase partitioning (USTPP) were combined to extract and separate polysaccharides (PS) efficiently from Corbicula fluminea crude extracts. The following optimum experimental conditions were established: 20% (w/v) ammonium sulfate concentration, 1:1 (v/v) t-butanol to crude extract ratio, 180W ultrasonic power, 40kHz frequency, 100% duty cycle, 10min irradiation time, and 35°C. The maximum extraction yield of PS obtained from USTPP was approximately 11.22%, which was higher than the maximum yields from conventional three-phase partitioning (TPP; 9.32%) and ultrasound extraction (USE; 6.05%). The extraction time for USTPP was significantly reduced to 10min from 30 and 60min for TPP and USE methods, respectively. The primary chemical structures of PS collected through the three extraction protocols were basically conserved. The synergistic effects of ultrasound and TPP on PS extraction were also determined. Results revealed that USTPP is an effective technique to extract and separate PS from C. fluminea potentially applied in food, cosmetics, and medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Adsorption-synergic biodegradation of diesel oil in synthetic seawater by acclimated strains immobilized on multifunctional materials.

    Science.gov (United States)

    Wang, Xin; Wang, Xuejiang; Liu, Mian; Bu, Yunjie; Zhang, Jing; Chen, Jie; Zhao, Jianfu

    2015-03-15

    Using enrichment culture technique, three isolates marked as ODB-1, ODB-2 and ODB-3, were selected from oil contaminated seawater. 16S rDNA gene sequencing indicated that ODB-1 affiliated with Pseudomonas sp. while ODB-2 and ODB-3 affiliated with Brevundimonas sp. Subsequently, the bacterial cells were immobilized on the surface of expanded graphite (EG), expanded perlite (EP) and bamboo charcoal (BC). Among the three isolates, ODB-1 showed a strong binding to the bio-carriers through extracellular polysaccharides, while ODB-2 and ODB-3 made the adhesion to bio-carrier through direct physical adsorption. The immobilized bacteria exhibited good salinity tolerance compared with the planktonic bacteria. Their total diesel oil removal rates were more than 85% after 6 days' incubation. Adsorption-biodegradation process played an important role in the oil-pollution remediation. EG-bacteria system was treated as a promising remediation method, which achieved nearly 100% removal of diesel oil. Thereinto, over 83% removal of diesel oil owed to biodegradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell entry to the central nervous system

    DEFF Research Database (Denmark)

    Millward, Jason M; Caruso, Maria; Campbell, Iain L

    2007-01-01

    for the chemokines CXCL10 and CCL5, to levels comparable to those seen during experimental autoimmune encephalomyelitis. Other chemokines (CXCL2, CCL2, CCL3) were not induced. Mice lacking the IFN-gammaR showed no response, and a control viral vector did not induce chemokine expression. Chemokine expression...... was predominantly localized to meningeal and ependymal cells, and was also seen in astrocytes and microglia. IFN-gamma-induced chemokine expression did not lead to inflammation. However, when pertussis toxin was given i.p. to mice infected with the IFN-gamma vector, there was a dramatic increase in the number of T...

  17. The Role of Template Structure and Synergism between Inorganic and Organic Structure Directing Agents in the Synthesis of UTL Zeolite

    Czech Academy of Sciences Publication Activity Database

    Shvets, O. V.; Kasian, N.; Zukal, Arnošt; Pinkas, Jiří; Čejka, Jiří

    2010-01-01

    Roč. 22, č. 11 (2010), s. 3482-3495 ISSN 0897-4756 R&D Projects: GA ČR GA203/08/0604; GA ČR GA104/07/0383 Institutional research plan: CEZ:AV0Z40400503 Keywords : UTL zeolite * synthesis * zeolite molecular sietes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 6.400, year: 2010

  18. Antibacterial Activity of Alkaloid Fractions from Berberis microphylla G. Forst and Study of Synergism with Ampicillin and Cephalothin.

    Science.gov (United States)

    Manosalva, Loreto; Mutis, Ana; Urzúa, Alejandro; Fajardo, Victor; Quiroz, Andrés

    2016-01-11

    Berberis microphylla is a native plant that grows in Patagonia and is commonly used by aboriginal ethnic groups in traditional medicine as an antiseptic for different diseases. The present study evaluated the antibacterial and synergistic activity of alkaloid extracts of B. microphylla leaves, stems and roots used either individually or in combination with antibiotics against Gram-positive and Gram-negative bacteria. The in vitro antibacterial activities of leaf, stem and root alkaloid extracts had significant activity only against Gram-positive bacteria. Disc diffusion tests demonstrated that the root extract showed similar activity against B. cereus and S. epidermidis compared to commercial antibiotics, namely ampicillin and cephalothin, and pure berberine, the principal component of the alkaloid extracts, was found to be active only against S. aureus and S. epidermidis with similar activity to that of the root extract. The minimum inhibitory concentrations (MICs) of the alkaloid extracts ranged from 333 to 83 μg/mL, whereas minimum bactericidal concentrations (MBCs) varied from 717 to 167 μg/mL. In addition, synergistic or indifferent effects between the alkaloid extracts and antibiotics against bacterial strains were confirmed.

  19. The anti-fibrotic agent pirfenidone synergizes with cisplatin in killing tumor cells and cancer-associated fibroblasts

    International Nuclear Information System (INIS)

    Mediavilla-Varela, Melanie; Boateng, Kingsley; Noyes, David; Antonia, Scott J.

    2016-01-01

    Anti-fibrotic drugs such as pirfenidone have been developed for the treatment of idiopathic pulmonary fibrosis. Because activated fibroblasts in inflammatory conditions have similar characteristics as cancer-associated fibroblasts (CAFs) and CAFs contribute actively to the malignant phenotype, we believe that anti-fibrotic drugs have the potential to be repurposed as anti-cancer drugs. The effects of pirfenidone alone and in combination with cisplatin on human patient-derived CAF cell lines and non-small cell lung cancer (NSCLC) cell lines were examined. The impact on cell death in vitro as well as tumor growth in a mouse model was determined. Annexin V/PI staining and Western blot analysis were used to characterize cell death. Synergy was assessed with the combination index method using Calcusyn software. Pirfenidone alone induced apoptotic cell death in lung CAFs at a high concentration (1.5 mg/mL). However, co-culture in vitro experiments and co-implantation in vivo experiments showed that the combination of low doses of cisplatin (10 μM) and low doses of pirfenidone (0.5 mg/mL), in both CAFs and tumors, lead to increased cell death and decreased tumor progression, respectively. Furthermore, the combination of cisplatin and pirfenidone in NSCLC cells (A549 and H157 cells) leads to increased apoptosis and synergistic cell death. Our studies reveal for the first time that the combination of cisplatin and pirfenidone is active in preclinical models of NSCLC and therefore may be a new therapeutic approach in this disease. The online version of this article (doi:10.1186/s12885-016-2162-z) contains supplementary material, which is available to authorized users

  20. The small molecule SI113 synergizes with mitotic spindle poisons in arresting the growth of human glioblastoma multiforme

    Science.gov (United States)

    Abbruzzese, Claudia; Catalogna, Giada; Gallo, Enzo; di Martino, Simona; Mileo, Anna M.; Carosi, Mariantonia; Dattilo, Vincenzo; Schenone, Silvia; Musumeci, Francesca; Lavia, Patrizia; Perrotti, Nicola; Amato, Rosario; Paggi, Marco G.

    2017-01-01

    Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we explored the outcome of the association between SI113 and selected spindle poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM cells, drastically reducing their viability and clonogenic capabilities in vitro, as well as inhibiting tumor growth in vivo. We also defined the molecular bases of such a synergistic effect. Because SI113 displays low systemic toxicity, yet strong activity in potentiating the effect of radiotherapy in GBM cells, we believe that this drug could be a strong candidate for clinical trials, with the aim to add it to the current GBM therapeutic approaches. PMID:29340013

  1. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats.

    Directory of Open Access Journals (Sweden)

    Samah G Abdel Baki

    Full Text Available BACKGROUND: There are no drugs presently available to treat traumatic brain injury (TBI. A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO, N-acetylcysteine (NAC, simvastatin, cyclosporine A, and progesterone had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. METHODOLOGY/PRINCIPAL FINDINGS: Drugs were dosed one hour after injury using the controlled cortical impact (CCI TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Co-administration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when the drugs were dosed one hour after injury. CONCLUSIONS/SIGNIFICANCE: These observations suggest a potentially valuable role for MINO plus NAC to treat TBI.

  2. Minocycline synergizes with N-acetylcysteine and improves cognition and memory following traumatic brain injury in rats.

    Science.gov (United States)

    Abdel Baki, Samah G; Schwab, Ben; Haber, Margalit; Fenton, André A; Bergold, Peter J

    2010-08-31

    There are no drugs presently available to treat traumatic brain injury (TBI). A variety of single drugs have failed clinical trials suggesting a role for drug combinations. Drug combinations acting synergistically often provide the greatest combination of potency and safety. The drugs examined (minocycline (MINO), N-acetylcysteine (NAC), simvastatin, cyclosporine A, and progesterone) had FDA-approval for uses other than TBI and limited brain injury in experimental TBI models. Drugs were dosed one hour after injury using the controlled cortical impact (CCI) TBI model in adult rats. One week later, drugs were tested for efficacy and drug combinations tested for synergy on a hierarchy of behavioral tests that included active place avoidance testing. As monotherapy, only MINO improved acquisition of the massed version of active place avoidance that required memory lasting less than two hours. MINO-treated animals, however, were impaired during the spaced version of the same avoidance task that required 24-hour memory retention. Co-administration of NAC with MINO synergistically improved spaced learning. Examination of brain histology 2 weeks after injury suggested that MINO plus NAC preserved white, but not grey matter, since lesion volume was unaffected, yet myelin loss was attenuated. When dosed 3 hours before injury, MINO plus NAC as single drugs had no effect on interleukin-1 formation; together they synergistically lowered interleukin-1 levels. This effect on interleukin-1 was not observed when the drugs were dosed one hour after injury. These observations suggest a potentially valuable role for MINO plus NAC to treat TBI.

  3. Effects of low-carbohydrate diet therapy in overweight subject with autoimmune thyroiditis: possible synergism with ChREBP

    Directory of Open Access Journals (Sweden)

    Esposito T

    2016-09-01

    Full Text Available Teresa Esposito,1,2 Jean Marc Lobaccaro,3 Maria Grazia Esposito,4 Vincenzo Monda,1 Antonietta Messina,1 Giuseppe Paolisso,5 Bruno Varriale,2 Marcellino Monda,1 Giovanni Messina1,6 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, 2Laboratory of Molecular Biology and Genetics, Department of Experimental Medicine, Second University of Naples, Naples, Italy; 3UMR, Clermont Université, Centre de Recherche en Nutrition Humaine d’Auvergne, Aubière Cedex, France; 4Complex Surgery Unit, Evangelic Hospital Villa Betania, 5Department of Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell’Invecchiamento, Second University of Naples, Naples, 6Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy Abstract: The thyroid is one of the metabolism regulating glands. Its function is to determine the amount of calories that the body has to burn to maintain normal weight. Thyroiditides are inflammatory processes that mainly result in autoimmune diseases. We have conducted the present study in order to have a clear picture of both autoimmune status and the control of body weight. We have evaluated the amount of either thyroid hormones, or antithyroid, or anti-microsomal, or anti-peroxidase antibodies (Abs in patients with high amounts of Abs. In a diet devoid of carbohydrates (bread, pasta, fruit, and rice, free from goitrogenic food, and based on body mass index, the distribution of body mass and intracellular and extracellular water conducted for 3 weeks gives the following results: patients treated as above showed a significant reduction of antithyroid (-40%, P<0.013, anti-microsomal (-57%, P<0.003, and anti-peroxidase (-44%, P<0,029 Abs. Untreated patients had a significant increase in antithyroid (+9%, P<0.017 and anti-microsomal (+30%, P<0.028 Abs. Even the level of anti-peroxidase Abs increased without reaching statistical significance (+16%, P>0064. With regard to the body parameters measured in patients who followed this diet, reduction in body weight (-5%, P<0.000 and body mass index (-4%, P<0.000 were observed. Since 83% of patients with high levels of autoantibodies are breath test positive to lactase with a lactase deficit higher than 50%, this fact led us to hypothesize a correlation with carbohydrate-responsive element-binding protein and therefore a possible role of carbohydrate metabolism in the development and maintenance of autoimmune thyroiditis associated with body weight increase and slower basic metabolism. Keywords: thyroiditis, thyroid hormones, thyroid autoantibodies, low-carbohydrate diet, protein diet

  4. Synergism between erythropoietin and interleukin-3 in the induction of hematopoietic stem cell proliferation and erythroid burst colony formation

    NARCIS (Netherlands)

    Migliaccio, G.; Migliaccio, A.R.; Visser, J.W.M

    1988-01-01

    The influence of recombinant erythropoietin (Ep) and interleukin-3 (IL-3) on the proliferation and differentiation of murine hematopoietic stem and progenitor cells was investigated in serum-deprived cultures. The differentiation of progenitor cells, purified by collecting blast cell colonies from

  5. IDO1 inhibition synergizes with radiation and PD-1 blockade to durably increase survival against advanced glioblastoma.

    Science.gov (United States)

    Ladomersky, Erik; Zhai, Lijie; Lenzen, Alicia; Lauing, Kristen L; Qian, Jun; Scholtens, Denise M; Gritsina, Galina; Sun, Xuebing; Liu, Ye; Yu, Fenglong; Gong, Wenfeng; Liu, Yong; Jiang, Beibei; Tang, Zhiyu; Patel, Ricky; Platanias, Leonidas C; James, C David; Stupp, Roger; Lukas, Rimas V; Binder, David C; Wainwright, Derek A

    2018-03-02

    Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with a median survival of 15-20 months. Numerous approaches and novel therapeutics for treating GBM have been investigated in the setting of phase III clinical trials, including a recent analysis of the immune checkpoint inhibitor, Nivolumab (anti-PD-1), which failed to improve recurrent GBM patient survival. However, rather than abandoning immune checkpoint inhibitor treatment for GBM, which has shown promise in other types of cancer, ongoing studies are currently evaluating this therapeutic class when combined with other agents. Here, we investigated immunocompetent orthotopic mouse models of GBM treated with the potent CNS-penetrating IDO1 enzyme inhibitor, BGB-5777, combined with anti-PD1 mAb, as well as radiation therapy (RT), based on our recent observation that tumor-infiltrating T cells directly increase immunosuppressive IDO1 levels in human GBM, the previously-described enhancement of immune cell functions after PD-1 blockade, as well as the pro-inflammatory effects of radiation. Our results demonstrate a durable survival benefit from this novel three-agent treatment, but not for any single- or dual-agent combination. Unexpectedly, treatment efficacy required IDO1 enzyme inhibition in non-GBM cells, rather than tumor cells. Timing of effector T cell infiltration, animal subject age and usage of systemic chemotherapy, all directly impacted therapy-mediated survival benefit.  These data highlight a novel and clinically-relevant immunotherapeutic approach with associated mechanistic considerations that have formed the basis of a newly-initiated phase I/II trial for GBM patients. Copyright ©2018, American Association for Cancer Research.

  6. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A., E-mail: lucille.a.lange@us.army.mil

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 μg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ► Soman (GD) produced seizure activity resulting in neuropathology in rats. ► Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ► CED/DZP showed superior anticonvulsant and neuroprotective capacity. ► Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ► PHY attenuated GD-induced seizure development, but not seizure duration.

  7. Low-Salt Diet and Circadian Dysfunction Synergize to Induce Angiotensin II-Dependent Hypertension in Mice.

    Science.gov (United States)

    Pati, Paramita; Fulton, David J R; Bagi, Zsolt; Chen, Feng; Wang, Yusi; Kitchens, Julia; Cassis, Lisa A; Stepp, David W; Rudic, R Daniel

    2016-03-01

    Blood pressure exhibits a robust circadian rhythm in health. In hypertension, sleep apnea, and even shift work, this balanced rhythm is perturbed via elevations in night-time blood pressure, inflicting silent damage to the vasculature and body organs. Herein, we examined the influence of circadian dysfunction during experimental hypertension in mice. Using radiotelemetry to measure ambulatory blood pressure and activity, the effects of angiotensin II administration were studied in wild-type (WT) and period isoform knockout (KO) mice (Per2-KO, Per2, 3-KO, and Per1, 2, 3-KO/Per triple KO [TKO] mice). On a normal diet, administration of angiotensin II caused nondipping blood pressure and exacerbated vascular hypertrophy in the Period isoform KO mice relative to WT mice. To study the endogenous effects of angiotensin II stimulation, we then administered a low-salt diet to the mice, which does stimulate endogenous angiotensin II in addition to lowering blood pressure. A low-salt diet decreased blood pressure in wild-type mice. In contrast, Period isoform KO mice lost their circadian rhythm in blood pressure on a low-salt diet, because of an increase in resting blood pressure, which was restorable to rhythmicity by the angiotensin receptor blocker losartan. Chronic administration of low salt caused vascular hypertrophy in Period isoform KO mice, which also exhibited increased renin levels and altered angiotensin 1 receptor expression. These data suggest that circadian clock genes may act to inhibit or control renin/angiotensin signaling. Moreover, circadian disorders such as sleep apnea and shift work may alter the homeostatic responses to sodium restriction to potentially influence nocturnal hypertension. © 2016 American Heart Association, Inc.

  8. In vitro assessment of the synergism between extracts of Cocos nucifera husk and some standard antibiotics

    Directory of Open Access Journals (Sweden)

    Taiwo Adesola Akinyele

    2017-04-01

    Conclusions: This investigation suggests the crude extracts of C. nucifera to be a potential broad spectrum antimicrobial compound. Therefore, further study is needed to isolate the pure compounds from these crude extracts.

  9. Evodiamine synergizes with doxorubicin in the treatment of chemoresistant human breast cancer without inhibiting P-glycoprotein.

    Directory of Open Access Journals (Sweden)

    Shengpeng Wang

    Full Text Available Drug resistance is one of the main hurdles for the successful treatment of breast cancer. The synchronous targeting of apoptosis resistance and survival signal transduction pathways may be a promising approach to overcome drug resistance. In this study, we determined that evodiamine (EVO, a major constituent of the Chinese herbal medicine Evodiae Fructus, could induce apoptosis of doxorubicin (DOX-sensitive MCF-7 and DOX-resistant MCF-7/ADR cells in a caspase-dependent manner, as confirmed by significant increases of cleaved poly(ADP-ribose polymerase (PARP, caspase-7/9, and caspase activities. Notably, the reversed phenomenon of apoptosis resistance by EVO might be attributed to its ability to inhibit the Ras/MEK/ERK pathway and the expression of inhibitors of apoptosis (IAPs. Furthermore, our results indicated that EVO enhanced the apoptotic action of DOX by inhibiting the Ras/MEK/ERK cascade and the expression of IAPs without inhibiting the expression and activity of P-glycoprotein (P-gp. Taken together, our data indicate that EVO, a natural product, may be useful applied alone or in combination with DOX for the treatment of resistant breast cancer.

  10. Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy

    NARCIS (Netherlands)

    Giorgetti, Elise; Rusmini, Paola; Crippa, Valeria; Cristofani, Riccardo; Boncoraglio, Alessandra; Cicardi, Maria E.; Galbiati, Mariarita; Poletti, Angelo

    2015-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone

  11. Auxin-cytokinin synergism in vitro for producing genetically stable plants of Ruta graveolens using shoot tip meristems

    Directory of Open Access Journals (Sweden)

    Mohammad Faisal

    2018-02-01

    Full Text Available An efficient micropropagation protocol was developed for Ruta graveolens Linn. using shoot tip meristems derived from a 4-month-old field grown plant. In vitro shoot regeneration and proliferation was accomplished on Murashige and Skoogs (MS semi-solid medium in addition to different doses of cytokinins viz.6- benzyl adenine (BA, Kinetin (Kn or 2-isopetynyl adenine (2iP, singly or in combination with auxins viz. indole-3-acetic acid (IAA, indole-3-butyric acid (IBA or α-naphthalene acetic acid (NAA. Highest regeneration frequency (27.6% was obtained on (MS medium composed of BA (10 µM with maximum number (9.4 of shoots and 4.3 cm shoot length after 4 weeks of incubation. Among various combinations tried best regeneration frequency (71% of multiple shoot formation with highest number (12.6 of shoots per shoot tip explants were achieved in MS medium augmented with a combination BA (10.0 µM and NAA (2.5 µM after 4 weeks of incubation. The optimum frequency (97% of rhizogenesis was achieved on half-strength MS medium having 0.5 µM IBA after 4 weeks of incubation. Tissue culture raised plantlets with 5–7 fully opened leaves with healthy root system were successfully acclimatized off in Soilrite™ with 80% survival rate followed by transportation to normal soil under natural light. Genetic stability among in vitro raised progeny was evaluated by ISSR and RAPD markers. The entire banding pattern revealed from in vitro regenerated plants was monomorphic to the donor. The present protocol provides an alternative option for commercial propagation and fruitful setting up of genetically uniform progeny for sustainable utilization and germplasm preservation.

  12. Development of Eco-friendly Soy Protein Isolate Films with High Mechanical Properties through HNTs, PVA, and PTGE Synergism Effect.

    Science.gov (United States)

    Liu, Xiaorong; Song, Ruyuan; Zhang, Wei; Qi, Chusheng; Zhang, Shifeng; Li, Jianzhang

    2017-03-10

    This study was to develop novel soy protein isolate-based films for packaging using halloysite nanotubes (HNTs), poly-vinyl alcohol (PVA), and 1,2,3-propanetriol-diglycidyl-ether (PTGE). The structural, crystallinity, opacity, micromorphology, and thermal stability of the resultant SPI/HNTs/PVA/PTGE film were analyzed by the Attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) spectroscopy, X-ray diffraction (XRD), UV-Vis spectrophotometry, scanning electron microscopy (SEM), and thermo-gravimetric analysis (TGA). The SPI/HNTs/PVA/PTGE film illustrated that HNTs were uniformly dispersed in the SPI matrix and the thermal stability of the film was enhanced. Furthermore, the tensile strength (TS) of the SPI/HNTs/PVA/PTGE film was increased by 329.3% and the elongation at the break (EB) remained unchanged. The water absorption (WA) and the moisture content (MC) were decreased by 5.1% and 10.4%, respectively, compared to the unmodified film. The results highlighted the synergistic effects of SPI, HNTs, PVA, and PTGE on the mechanical properties, water resistance, and thermal stability of SPI films, which showed excellent strength and flexibility. In short, SPI films prepared from HNTs, PVA, and PTGE showed considerable potential as packaging materials.

  13. Pore-Forming and Enzymatic Activities of Bordetella pertussis Adenylate Cyclase Toxin Synergize in Promoting Lysis of Monocytes

    Czech Academy of Sciences Publication Activity Database

    Basler, Marek; Mašín, Jiří; Osička, Radim; Šebo, Peter

    2006-01-01

    Roč. 74, č. 5 (2006), s. 2207-2214 ISSN 0019-9567 R&D Projects: GA AV ČR IAA5020406; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50200510 Keywords : bordetella pertussis * cyaa * cytotoxicity Subject RIV: EE - Microbiology, Virology Impact factor: 4.004, year: 2006

  14. IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell entry to the central nervous system

    DEFF Research Database (Denmark)

    Millward, Jason M; Caruso, Maria; Campbell, Iain L

    2007-01-01

    was predominantly localized to meningeal and ependymal cells, and was also seen in astrocytes and microglia. IFN-gamma-induced chemokine expression did not lead to inflammation. However, when pertussis toxin was given i.p. to mice infected with the IFN-gamma vector, there was a dramatic increase in the number of T...... lymphocytes detected in the CNS by flow cytometry. This increase in blood-derived immune cells in the CNS did not occur with pertussis toxin alone, and did not manifest as histologically detectable inflammatory pathology. These results show that IFN-gamma induces a characteristic glial chemokine response...

  15. Cardiac and Vascular Synergic Protective Effect of Olea europea L. Leaves and Hibiscus sabdariffa L. Flower Extracts

    Directory of Open Access Journals (Sweden)

    Matteo Micucci

    2015-01-01

    Full Text Available This study was aimed at investigating the cardiovascular effects of an Olea europea L. leaf extract (OEE, of a Hibiscus sabdariffa L. flower extract (HSE, and of their 13 : 2 w/w mixture in order to assess their cardiac and vascular activity. Both extracts were fully characterized in their bioactive compounds by HPLC-MS/MS analysis. The study was performed using primary vascular endothelial cells (HUVECs to investigate the antioxidant and cytoprotective effect of the extracts and their mixture and isolated guinea-pig left and right atria and aorta to evaluate the inotropic and chronotropic activities and vasorelaxant properties. In cultured HUVECs, OEE and HSE reduced intracellular reactive oxygen species formation and improved cell viability, following oxidative stress in dose-dependent manner. OEE and HSE exerted negative inotropic and vasorelaxant effects without any chronotropic property. Interestingly, the mixture exerted higher cytoprotective effects and antioxidant activities. Moreover, the mixture exerted an inotropic effect similar to each single extract, while it revealed an intrinsic negative chronotropic activity different from the single extract; its relaxant activity was higher than that of each single extract. In conclusion OEE and HSE mixture has a good potential for pharmaceutical and nutraceutical application, thanks to the synergistic effects of the single phytochemicals.

  16. Combining etoposide and dexrazoxane synergizes with radiotherapy and improves survival in mice with central nervous system tumors

    DEFF Research Database (Denmark)

    Hofland, Kenneth Francis; Thougaard, Annemette Vinding; Dejligbjerg, Marielle

    2005-01-01

    quantification of phosphorylated histone H2AX (gammaH2AX). RESULTS: Escalated etoposide dosing (90 mg/kg) combined with dexrazoxane (125 mg/kg) and cerebral radiotherapy (10 Gy x 1) increased the median survival by 60% (P = 0.001) without increased toxicity, suggesting that escalated etoposide levels may indeed...

  17. The Anticholinergic and Antiglutamatergic Drug Caramiphen Reduces Seizure Duration in Soman-Exposed Rats: Synergism with the Benzodiazepine Diazepam

    Science.gov (United States)

    2012-01-01

    oArticle history : Received 9 December 2011 Revised 20 January 2012 Accepted 22 January 2012 Available online 30 January 2012 Keywords: Soman Caramiphen...purchased as follows: 1) diaze- pam (DZP; United States Pharmacopeia, USP) from Hospira Inc. (Lake Forrest, IL, USA), 2) buprenorphine hydrochloride from...administered buprenorphine (buprenex solution; 1:1 dilution in sterile water; 0.07 ml, sc) immediately after removal from anesthesia. The rats were given

  18. Chemical Equilibrium and Synergism for Solvent Extraction of Trace Lithium with Thenoyltrifluoroacetone in the Presence of Trioctylphosphine Oxide

    International Nuclear Information System (INIS)

    Kim, Young Sang; In, Gyo; Choi, Jong Moon

    2003-01-01

    Equilibria and applications of a synergistic extraction were studied for the determination of a trace lithium by using thenoyltrifluoroacetone (TTA) and trioctylphosphine oxide (TOPO) as ligands. Several equations were derived for the extraction of lithium into m-xylene as a phase of Li-TTA·mTOPO adduct. Distribution coefficients and extraction constant were determined together with a stability constant of the adduct. The adduct was quantitatively extracted from the basic solution of higher than pH 9 by shaking for 30 minutes. m- Xylene was selected as an optimum solvent by comparing the extraction efficiency among several kinds of organic solvents. The stability constant (β 2 ) for Li-TTA/2TOPO was 150 times higher than Li-TTA/TOPO. The distribution coefficient of Li-TTA/2TOPO into m-xylene was 9.12 and the logarithmic extraction constant (log Kex) was 6.76. Trace lithium of sub-ppm level in seawater samples could be determined under modified conditions and a detection limit equivalent to 3 times standard deviation for background absorption was 0.42 ng/mL

  19. The small molecule SI113 synergizes with mitotic spindle poisons in arresting the growth of human glioblastoma multiforme.

    Science.gov (United States)

    Abbruzzese, Claudia; Catalogna, Giada; Gallo, Enzo; di Martino, Simona; Mileo, Anna M; Carosi, Mariantonia; Dattilo, Vincenzo; Schenone, Silvia; Musumeci, Francesca; Lavia, Patrizia; Perrotti, Nicola; Amato, Rosario; Paggi, Marco G

    2017-12-19

    Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we explored the outcome of the association between SI113 and selected spindle poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM cells, drastically reducing their viability and clonogenic capabilities in vitro , as well as inhibiting tumor growth in vivo . We also defined the molecular bases of such a synergistic effect. Because SI113 displays low systemic toxicity, yet strong activity in potentiating the effect of radiotherapy in GBM cells, we believe that this drug could be a strong candidate for clinical trials, with the aim to add it to the current GBM therapeutic approaches.

  20. Synergic effect of n-3 polyunsaturated fatty acids and rosiglitazone in the amelioration of insulin resistance and adipose tissue inflammatinon

    Czech Academy of Sciences Publication Activity Database

    Kuda, Ondřej; Jílková, Zuzana; Rossmeisl, Martin; Flachs, Pavel; Ogston, N. C.; Mohamed-Ali, V.; Cinti, S.; Kopecký, Jan

    2007-01-01

    Roč. 50, Suppl.1 (2007), S260-S260 ISSN 0012-186X. [Annual Meeting of the European Association for the Study of Diabetes /43./. 18.09.2007-21.09.2007, Amsterdam] R&D Projects: GA ČR(CZ) GD303/03/H065 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * insulin * rosiglitazone * PUFA Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  1. Antibacterial synergic effect of honey from two stingless bees: Scaptotrigona bipunctata Lepeletier, 1836, and S. postica Latreille, 1807

    Science.gov (United States)

    Nishio, E. K.; Ribeiro, J. M.; Oliveira, A. G.; Andrade, C. G. T. J.; Proni, E. A.; Kobayashi, R. K. T.; Nakazato, G.

    2016-02-01

    Several studies have tested antimicrobial activity of combinations of honey and various substances. In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM). The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v-1) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined. This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains.

  2. Synergic and antagonistic relationship between MMP-2 and MMP-9 with fibrosis and inflammation in Chagas' cardiomyopathy.

    Science.gov (United States)

    Medeiros, N I; Gomes, J A S; Correa-Oliveira, R

    2017-08-01

    Cardiomyopathy is the most important clinical manifestation in the chronic phase of Chagas' disease because of its frequency, severity and impact on morbidity and mortality. The extracellular matrix degradation during cardiac remodeling in Trypanosoma cruzi infection is driven by matrix metalloproteinases (MMPs), primarily the MMP-2 and MMP-9 gelatinases. MMPs also regulate some molecules related to inflammation, such as growth factors, cytokines and chemokines. The involvement of MMP-2 and MMP-9 is not yet fully understood in Chagas' disease. It has been proposed that the gelatinases may have opposite effect on inflammation/regulation and cardiac remodeling. MMP-2 would participate in regulation, offering a protective role for cardiac damage in asymptomatic patients and would be a good marker for the initiation of changes in the heart. On the other hand, MMP-9 can be used as a marker for serious changes on the heart and would be associated with inflammation and fibrosis. Here, we consolidate all characteristics involving MMP-2 and MMP-9 in Chagas' disease based on current studies to clarify their participation on the inflammation/regulation and fibrosis, and the synergistic or antagonistic role between them. © 2017 John Wiley & Sons Ltd.

  3. Sodium-potassium synergism in Theobroma cacao: stimulation of photosynthesis, water-use efficiency and mineral nutrition.

    Science.gov (United States)

    Gattward, James N; Almeida, Alex-Alan F; Souza, José O; Gomes, Fábio P; Kronzucker, Herbert J

    2012-11-01

    In ecological setting, sodium (Na(+)) can be beneficial or toxic, depending on plant species and the Na(+) level in the soil. While its effects are more frequently studied at high saline levels, Na(+) has also been shown to be of potential benefit to some species at lower levels of supply, especially in C4 species. Here, clonal plants of the major tropical C3 crop Theobroma cacao (cacao) were grown in soil where potassium (K(+)) was partially replaced (at six levels, up to 50% replacement) by Na(+), at two concentrations (2.5 and 4.0 mmol(c) dm(-3)). At both concentrations, net photosynthesis per unit leaf area (A) increased more than twofold with increasing substitution of K(+) by Na(+). Concomitantly, instantaneous (A/E) and intrinsic (A/g(s)) water-use efficiency (WUE) more than doubled. Stomatal conductance (g(s)) and transpiration rate (E) exhibited a decline at 2.5 mmol dm(-3), but remained unchanged at 4 mmol dm(-3). Leaf nitrogen content was not impacted by Na(+) supplementation, whereas sulfur (S), calcium (Ca(2+)), magnesium (Mg(2+)) and zinc (Zn(2+)) contents were maximized at 2.5 mmol dm(-3) and intermediate (30-40%) replacement levels. Leaf K(+) did not decline significantly. In contrast, leaf Na(+) content increased steadily. The resultant elevated Na(+)/K(+) ratios in tissue correlated with increased, not decreased, plant performance. The results show that Na(+) can partially replace K(+) in the nutrition of clonal cacao, with significant beneficial effects on photosynthesis, WUE and mineral nutrition in this major perennial C3 crop. Copyright © Physiologia Plantarum 2012.

  4. Improving oxidative stability of olive oil: Incorporation of Spirulina and evaluation of its synergism with citric acid

    International Nuclear Information System (INIS)

    Alavi, N.; Golmakani, M.T.

    2017-01-01

    The effects of different Spirulina concentrations used alone and in combination with citric acid on the oxidative stability of olive oil were assessed. The amounts of primary and secondary oxidation products produced in Spirulina samples were lower than that of the control. The improved oxidative stability indices of Spirulina samples with and without citric acid were in the range of 85.20–94.47% and 258.10–260.21%, respectively. In comparison with the control, Spirulina samples manifested significantly higher carotenoid and chlorophyll contents at the beginning and end of the storage period. The presence of these bioactive compounds results from the presence of Spirulina in the medium and can thus retard the oxidation of olive oil. A higher oxidative stability was reached using BHT in comparison with Spirulina samples. Furthermore, no synergistic action was observed in possible connections between citric acid and Spirulina. In conclusion, Spirulina can enhance oxidative stability and improve the shelf life of olive oil. [es

  5. Alpha1 and D2 receptors in a place avoidance task in rats: evidence for a synergism

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Petrásek, Tomáš; Valeš, Karel

    2008-01-01

    Roč. 104, Suppl.2 (2008), s. 1135-1135 ISSN 1212-0383. [World congress of psychiatry /14./. 20.09.2008-25.09.2008, Prague] R&D Projects: GA ČR(CZ) GA309/07/0341; GA MZd(CZ) NR9178; GA MŠk(CZ) LC554; GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * avoidance * memory * rat Subject RIV: FH - Neurology

  6. ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

    Directory of Open Access Journals (Sweden)

    Power Deborah M

    2006-12-01

    Full Text Available Abstract Background ICI 182,780 (ICI belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus. Methods Three independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus or sea bream received intra-peritoneal implants containing estradiol-17 beta (E2, ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream. Results E2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2. Conclusion These results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but its actions are tissue-specific. The mechanisms for the ICI agonistic activity are still unknown; although the ICI induced up-regulation of ER alpha mRNA could be one of the factors contributing to the cellular response.

  7. ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

    OpenAIRE

    Pinto, Patricia; Singh, Pratap B.; Condeça, João B.; Teodósio, H. R.; Power, Deborah; Canario, Adelino V. M.

    2006-01-01

    Abstract Background ICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus). Methods Three independent in vivo experiments were performed in which mature male tilapia (Oreochrom...

  8. Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant staphylococci

    Science.gov (United States)

    Mohammad, Haroon; Mayhoub, Abdelrahman S.; Cushman, Mark; Seleem, Mohamed N.

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates. Additionally, the anti-biofilm activity of the novel thiazoles was investigated against Staphylococcus epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to re-sensitize VRSA to vancomycin, reducing its minimum inhibitory concentration (MIC) by 512-fold in two strains. Additionally, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively the results obtained demonstrate compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm. PMID:25315757

  9. Synergism between inositol polyphosphates and TOR kinase signaling in nutrient sensing, growth control, and lipid metabolism in Chlamydomonas

    Science.gov (United States)

    The networks that govern carbon metabolism and control intracellular carbon partitioning in photosynthetic cells are poorly understood. Target of rapamycin (TOR) kinase is a conserved growth regulator that integrates nutrient signals and modulates cell growth in eukaryotes, though the TOR signaling ...

  10. Original research paper. Hydrazinyldiene-chroman-2,4-diones in inducing growth arrest and apoptosis in breast cancer cells: Synergism with doxorubicin and correlation with physicochemical properties.

    Science.gov (United States)

    Ballazhi, Lulzime; Imeri, Faik; Jashari, Ahmed; Popovski, Emil; Stojković, Goran; Dimovski, Aleksandar J; Mikhova, Bozhana; Mladenovska, Kristina

    2017-03-01

    This study evaluates the effects of previously synthesized hydrazinyldiene-chroman-2,4-diones on cell proliferation and apoptosis, cell cycle distribution and migration capacity of MCF-7 breast cancer cells in synergy with doxorubicin. Physicochemical properties of the synthesized compounds were correlated with their structure and activity. Significant cell viability decrease in comparison with the effect of doxorubicin alone and the reference 4-hydroxycoumarin was observed when combination treatment comprising doxorubicin and the title compounds was applied. Synergistic effect with doxorubicin was also observed in down-regulation of phospho-Thr308Akt levels, confirming reduced proliferation and increased apoptosis. Combined treatment increased the percentage of cells arrested at the G2/M stage. Additive inhibition of cell migration was also observed, pointing to the possibility of reducing the risk of metastases. With their solubility profile and log D7.4, all the synthesized compounds follow Lipinski's rule of five for good permeability (absorption) potential.

  11. Synergism between demethylation inhibitor fungicides or gibberellin inhibitor plant growth regulators and bifenthrin in a pyrethroid-resistant population of Listronotus maculicollis (Coleoptera: Curculionidae).

    Science.gov (United States)

    Ramoutar, D; Cowles, R S; Requintina, E; Alm, S R

    2010-10-01

    In 2007-2008, the "annual bluegrass weevil," Listronotus maculicollis Kirby (Coleoptera: Curculionidae), a serious pest of Poa annua L. (Poales: Poaceae) on U.S. golf courses, was shown to be resistant to two pyrethroids, bifenthrin and lambda-cyhalothrin. In 2008, we showed that bifenthrin resistance was principally mediated by oxidase detoxification (cytochrome P450 [P450]). P450s can be inhibited by demethylation inhibitor fungicides and gibberellin inhibitor plant growth regulators, both of which are commonly used on golf courses. We tested these compounds for synergistic activity with bifenthin against a pyrethroid-resistant population of L. maculicollis. The LD50 value for bifenthrin was significantly reduced from 87 ng per insect (without synergists) to 9.6-40 ng per insect after exposure to the fungicides fenarimol, fenpropimorph, prochloraz, propiconazole, and pyrifenox and the plant growth regulators flurprimidol, paclobutrazol, and trinexapac-ethyl. Simulated field exposure with formulated products registered for use on turf revealed enhanced mortality when adult weevils were exposed to bifenthrin (25% mortality, presented alone) combined with field dosages of propiconizole, fenarimol, flurprimidol, or trinexapac-ethyl (range, 49-70% mortality).

  12. Neurotensin-Conjugated Reduced Graphene Oxide with Multi-Stage Near-Infrared-Triggered Synergic Targeted Neuron Gene Transfection In Vitro and In Vivo for Neurodegenerative Disease Therapy.

    Science.gov (United States)

    Hsieh, Tsung-Ying; Huang, Wei-Chen; Kang, Yi-Da; Chu, Chao-Yi; Liao, Wen-Lin; Chen, You-Yin; Chen, San-Yuan

    2016-12-01

    Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro-specific peptide)-conjugated polyethylenimine (PEI)-modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two-stage near-infrared (NIR)-laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First-stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second-stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO-PEI-NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC-12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi-stage stimuli-responsive NIR laser treatment. The combination of neuro-specific targeting peptide and external NIR-laser-triggered aid provides a nanoplatform for gene therapy in CNS diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis.

    Science.gov (United States)

    O'Brien, Andrew J; Villani, Linda A; Broadfield, Lindsay A; Houde, Vanessa P; Galic, Sandra; Blandino, Giovanni; Kemp, Bruce E; Tsakiridis, Theodoros; Muti, Paola; Steinberg, Gregory R

    2015-07-15

    Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 μM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted. © 2015 Authors; published by Portland Press Limited.

  14. Flavopiridol Synergizes with Sorafenib to Induce Cytotoxicity and Potentiate Antitumorigenic Activity in EGFR/HER-2 and Mutant RAS/RAF Breast Cancer Model Systems

    Directory of Open Access Journals (Sweden)

    Teddy S Nagaria

    2013-08-01

    Full Text Available Oncogenic receptor tyrosine kinase (RTK signaling through the Ras-Raf-Mek-Erk (Ras-MAPK pathway is implicated in a wide array of carcinomas, including those of the breast. The cyclin-dependent kinases (CDKs are implicated in regulating proliferative and survival signaling downstream of this pathway. Here, we show that CDK inhibitors exhibit an order of magnitude greater cytotoxic potency than a suite of inhibitors targeting RTK and Ras-MAPK signaling in cell lines representative of clinically recognized breast cancer (BC subtypes. Drug combination studies show that the pan-CDK inhibitor, flavopiridol (FPD, synergistically potentiated cytotoxicity induced by the Raf inhibitor, sorafenib (SFN. This synergy was most pronounced at sub-EC50 SFN concentrations in MDA-MB-231 (KRAS-G13D and BRAF-G464V mutations, MDA-MB-468 [epidermal growth factor receptor (EGFR overexpression], and SKBR3 [ErbB2/EGFR2 (HER-2 overexpression] cells but not in hormone-dependent MCF-7 and T47D cells. Potentiation of SFN cytotoxicity by FPD correlated with enhanced apoptosis, suppression of retinoblastoma (Rb signaling, and reduced Mcl-1 expression. SFN and FPD were also tested in an MDA-MB-231 mammary fat pad engraftment model of tumorigenesis. Mice treated with both drugs exhibited reduced primary tumor growth rates and metastatic tumor load in the lungs compared to treatment with either drug alone, and this correlated with greater reductions in Rb signaling and Mcl-1 expression in resected tumors. These findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant BCs.

  15. Systematic analysis of secreted proteins reveals synergism between IL6 and other proteins in soft agar growth of MCF10A cells.

    Science.gov (United States)

    Van Huffel, Sofie C; Tham, Jill M; Zhang, Xiaoqian; Lim, Kohpang; Yang, Chunxuan; Tan, Yikloo; Ong, Felicia; Lee, Ian; Hong, Wanjin

    2011-03-25

    Breast cancer, the most common malignancy in women, still holds many secrets. The causes for non-hereditary breast cancer are still unknown. To elucidate any role for circulating naturally secreted proteins, a screen of secreted proteins' influence of MCF10A cell anchorage independent growth was set up. To systematically screen secreted proteins for their capacity to transform mammalian breast epithelial cells, a soft agar screen of MCF10A cells was performed using a library of ~ 470 secreted proteins. A high concentration of infecting viral particles was used to obtain multiple infections in individual cells to specifically study the combined effect of multiple secreted proteins. Several known breast cancer factors, such as Wnt, FGF and IL were retained, as well as factors that were previously unknown to have a role in breast cancer, such as paraoxonase 1 and fibroblast growth factor binding protein 2. Additionally, a combinatory role of Interleukin 6 with other factors in MCF10A anchorage-independent growth is demonstrated. The transforming effect of combinations of IL6 with other secreted proteins allows studying the transformation of mammary epithelial cells in vitro, and may also have implications in in vivo studies where secreted proteins are upregulated or overexpressed.

  16. Therapeutic synergism in the treatment of post-stroke arm paresis utilizing botulinum toxin, robotic therapy, and constraint-induced movement therapy.

    Science.gov (United States)

    Takebayashi, Takashi; Amano, Satoru; Hanada, Keisuke; Umeji, Atsushi; Takahashi, Kayoko; Koyama, Tetsuo; Domen, Kazuhisa

    2014-11-01

    Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy (CIMT), and robotic therapy (RT) each represent promising approaches to enhance arm motor recovery after stroke. To provide more effective treatment for a 50-year-old man with severe left spastic hemiparesis, we attempted to facilitate CIMT with adaptive approaches to extend the wrist and fingers using RT for 10 consecutive weeks after BtxA injection. This combined treatment resulted in substantial improvements in arm function and the amount of arm use in activities of daily living, and may be effective for stroke patients with severe arm paresis. However, we were unable to sufficiently prove the efficacy of combined treatment based only on a single case. To fully elucidate the efficacy of the combined approach for patients with severe hemiparesis after stroke, future studies of a larger number of patients are needed. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  17. Introducing new physical synergism effect arise together presence of multi wall carbon nanotube and Vulcan in the micro porous layer of gas diffusion electrode

    Energy Technology Data Exchange (ETDEWEB)

    Abdullah Mirzaie, R. [Shahid Rajaee Univ., Tehran (Iran, Islamic Republic of). Dept. of Chemistry; Gharibi, H. [Tarbiat Modarres Univ., Tehran (Iran, Islamic Republic of); Javaheri, M. [Tarbiat Modarres Univ., Tehran (Iran, Islamic Republic of). Dept. of Chemistry; Asfa, A. [Shahid Rajaee Univ., Tehran (Iran, Islamic Republic of)

    2009-07-01

    This study investigated the influence of multi-wall carbon nanotube (MWCNT) in fuel cell components. In particular, it examined how vulcanization in the microporous layer affects the performance of the gas-diffusion electrode (GDE) for the cathodic oxygen reduction reaction. Different percentages of MWCNT and Vulcan were used in the microporous layer of the GDE. A porosimeter, scanning electron microscope (SEM) and four probe conductometer was used to study the morphological and physical structure of the fabricated microporous layer. Linear sweep voltametry (LSV), electrochemical impedance spectroscopy (EIS), chronoamperometry and SEM techniques were used to study the electrochemical performance of prepared gas diffusion electrodes for oxygen reduction reaction. The results showed that the combination of MWCNT and Vulcan perturb the morphological structure in the microporous layer. The optimized value of MWCNT in the microporous layer varies with different platinum loading in the reaction layer. The optimized values were found to be 60 wt per cent, 80 wt per cent and 40 wt per cent MWCNT at 0.115 mg per cm{sup 2}, 0.5 mg per cm{sup 2} and 1 mg per cm{sup 2} Pt loading respectively.

  18. Synergism Effect of the Essential Oil from Ocimum basilicum var. Maria Bonita and Its Major Components with Fluconazole and Its Influence on Ergosterol Biosynthesis

    Science.gov (United States)

    Cardoso, Nathalia N. R.; Alviano, Celuta S.; Blank, Arie F.; Romanos, Maria Teresa V.; Fonseca, Beatriz B.; Rozental, Sonia; Rodrigues, Igor A.; Alviano, Daniela S.

    2016-01-01

    The aim of this study was to evaluate the activity of the EO and its major components of Ocimum basilicum var. Maria Bonita, a genetically improved cultivar, against the fluconazole sensitive and resistant strains of Candida albicans and Cryptococcus neoformans. Geraniol presented better results than the EO, with a low MIC (76 μg/mL against C. neoformans and 152 μg/mL against both Candida strains). The combination of EO, linalool, or geraniol with fluconazole enhanced their antifungal activity, especially against the resistant strain (MIC reduced to 156, 197, and 38 μg/mL, resp.). The ergosterol assay showed that subinhibitory concentrations of the substances were able to reduce the amount of sterol extracted. The substances tested were able to reduce the capsule size which suggests they have an important mechanism of action. Transmission electron microscopy demonstrated cell wall destruction of C. neoformans after treatment with subinhibitory concentrations. In C. albicans ultrastructure alterations such as irregularities in the membrane, presence of vesicles, and cell wall thickening were observed. The biofilm formation was inhibited in both C. albicans strains at MIC and twice MIC. These results provide further support for the use of O. basilicum EO and its major components as a potential source of antifungal agents. PMID:27274752

  19. The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage-independent growth and synergizes with ras for invasive growth.

    NARCIS (Netherlands)

    Spanos, W.C.; Hoover, A.; Harris, G.F.; Wu, S.; Strand, G.L.; Anderson, M.E.; Klingelhutz, A.J.; Hendriks, W.J.A.J.; Bossler, A.D.; Lee, J.H.

    2008-01-01

    The human papillomavirus (HPV) oncogene E6 has been shown to perform multiple functions (p53 degradation, telomerase activation, etc.) that play a role in oncogenic transformation. Beyond known E6 functions, an undefined mechanism that allows cellular invasion requires the E6 PDZ binding motif

  20. Flt3 ligand synergizes with granulocyte-colony-stimulating factor in bone marrow mobilization to improve functional outcome after spinal cord injury in the rat.

    Science.gov (United States)

    Urdziková, Lucia; Likavčanová-Mašínová, Katarína; Vaněček, Václav; Růžička, Jiří; Sedý, Jiří; Syková, Eva; Jendelová, Pavla

    2011-10-01

    The effect of granulocyte-colony-stimulating factor (G-CSF) and/or the cytokine fms-like thyrosin kinase 3 (Flt3) ligand on functional outcome and tissue regeneration was studied in a rat model of spinal cord injury (SCI). Rats with a balloon-induced compression lesion were injected with G-CSF and/or Flt3 ligand to mobilize bone marrow cells. Behavioral tests (Basso-Beattie-Bresnahan and plantar test), blood counts, morphometric evaluation of the white and gray matter, and histology were performed 5 weeks after SCI. The mobilization of bone marrow cells by G-CSF, Flt3 ligand and their combination improved the motor and sensory performance of rats with SCI, reduced glial scarring, increased axonal sprouting and spared white and gray matter in the lesion. The best results were obtained with a combination of G-CSF and Flt3. G-CSF alone or in combination with Flt3 ligand significantly increased the number of white blood cells, but not red blood cells or hemoglobin content, during and after the time-course of bone marrow stimulation. The combination of factors led to infiltration of the lesion by CD11b(+) cells. The observed improvement in behavioral and morphologic parameters and tissue regeneration in animals with SCI treated with a combination of both factors could be associated with a prolonged time-course of mobilization of bone marrow cells. The intravenous administration of G-CSF and/or Flt3 ligand represents a safe and effective treatment modality for SCI.

  1. Anti-inflammatory effect of targeted delivery of SOD to endothelium: mechanism, synergism with NO donors and protective effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Vladimir V Shuvaev

    Full Text Available Pro-inflammatory activation of vascular endothelium is implicated in pathogenesis of severe conditions including stroke, infarction and sepsis. We have recently reported that superoxide dismutase (SOD conjugated with antibodies (Ab/SOD that provide targeted delivery into endothelial endosomes mitigates inflammatory endothelial activation by cytokines and agonists of Toll-like receptors (TLR. The goal of this study was to appraise potential utility and define the mechanism of this effect. Ab/SOD, but not non-targeted SOD injected in mice alleviated endotoxin-induced leukocyte adhesion in the cerebral vasculature and protected brain from ischemia-reperfusion injury. Transfection of endothelial cells with SOD, but not catalase inhibited NFκB signaling and expression of Vascular Cell Adhesion Molecule-1 induced by both cytokines and TLR agonists. These results affirmed that Ab/SOD-quenched superoxide anion produced by endothelial cells in response to proinflammatory agents mediates NFκB activation. Furthermore, Ab/SOD potentiates anti-inflammatory effect of NO donors in endothelial cells in vitro, as well as in the endotoxin-challenged mice. These results demonstrate the central role of intracellular superoxide as a mediator of pro-inflammatory activation of endothelium and support the notion of utility of targeted interception of this signaling pathway for management of acute vascular inflammation.

  2. Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Jacobsen, S.; Hansen, Harald S.; Jensen, B.

    1987-01-01

    ]arachidonic acid was converted to [C]prostaglandin D. A potentiated effect was found between thapsigargin and 12--tetradecanoylphorbol 13-acetate, as well as between A23187 and the phorbol ester with respect to release of [C]arachidonic acid and histamine. It is suggested that the synergistic effect is due......Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C...

  3. Cannabis-dependence risk relates to synergism between neuroticism and proenkephalin SNPs associated with amygdala gene expression: case-control study.

    Directory of Open Access Journals (Sweden)

    Didier Jutras-Aswad

    Full Text Available Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2 and proenkephalin (PENK genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown.Healthy young adults (18-27 years with cannabis dependence and without a dependence diagnosis were studied (N = 50/group in relation to a priori-determined single nucleotide polymorphisms (SNPs of the DRD2 and PENK genes. Negative affect, Impulsive Risk Taking and Neuroticism-Anxiety temperamental traits, positive and negative reward-learning performance and stop-signal reaction times were examined. The findings replicated the known association between the rs6277 DRD2 SNP and decisions associated with negative reinforcement outcomes. Moreover, PENK variants (rs2576573 and rs2609997 significantly related to Neuroticism and cannabis dependence. Cigarette smoking is common in cannabis users, but it was not associated to PENK SNPs as also validated in another cohort (N = 247 smokers, N = 312 non-smokers. Neuroticism mediated (15.3%-19.5% the genetic risk to cannabis dependence and interacted with risk SNPs, resulting in a 9-fold increase risk for cannabis dependence. Molecular characterization of the postmortem human brain in a different population revealed an association between PENK SNPs and PENK mRNA expression in the central amygdala nucleus emphasizing the functional relevance of the SNPs in a brain region strongly linked to negative affect.Overall, the findings suggest an important role for Neuroticism as an endophenotype linking PENK polymorphisms to cannabis-dependence vulnerability synergistically amplifying the apparent genetic risk.

  4. Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region.

    Science.gov (United States)

    Taneja, Neelam; Mishra, Arti; Kumar, Ajay; Verma, Garima; Sharma, Meera

    2015-01-01

    There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥ 0.25 µg/ml), SFM2 (≥ 4 µg/ml) and SFM3 (≥ 32 µg/ml) were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥ 0.25 µg/ml) and SDM2 (≥ 4 µg/ml) were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

  5. Interleukin-21, B cell activating factor and unmethylated CPG oligodeoxynucleotides synergize in promoting anti-proteinase 3 autoantibody production in vitro

    NARCIS (Netherlands)

    Lepse, Nikola; Land, Judith; Rutgers, Abraham; Kallenberg, Cornelis; Stegeman, Coen A.; Heeringa, Peter; Abdulahad, Wayel H.

    2012-01-01

    Background/Purpose: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are characterized by the presence of circulating autoantibodies that are often directed against proteinase 3 (PR3). Although the mechanisms that lead to ANCA production in AAV are not clear, bacterial

  6. Synergism of co-mutation of two amino acid residues in NS1 protein increases the pathogenicity of influenza virus in mice.

    Science.gov (United States)

    Pu, Juan; Wang, Jingjing; Zhang, Yi; Fu, Guanghua; Bi, Yuhai; Sun, Yipeng; Liu, Jinhua

    2010-08-01

    The NS1 influenza virus gene is thought to play an important role in replication and pathogenicity during infection. Previous studies have shown that mutations in the highly pathogenic avian NS1 influenza virus gene can influence virulence. However, little is known regarding the pathogenic mechanism of the NS1 gene in low pathogenic avian influenza virus. We found that NS1 genes originating from two H3 avian influenza viruses, A/duck/Beijing/40/04 (Dk/BJ/40/04) and A/duck/Beijing/61/05 (Dk/BJ/61/05), possessing three amino acid residue differences at positions 127, 205 and 209 contributed to an altered virulence in rescued NS1 recombinant viruses on a A/WSN/33 (WSN) virus background (WSN:40NS1 and WSN:61NS1) in mice. To further determine the effect on pathogenicity, we generated a series of recombinant viruses with mutations at positions 127, 205 and 209 in the NS1 gene of WSN:61NS1. Experiments in mice indicated that when compared with WSN:61NS1, viruses with only single mutations enhanced incidence of infection in mice but were not lethal. Viruses bearing substitution of two amino acid residues in the NS1 protein replicated well in lung tissue and caused 20-100% mortality in mice. Our findings demonstrate that co-mutation of amino acid residues at multiple positions in the NS1 protein can increase the pathogenicity of influenza virus in mice. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Antimicrobial Susceptibility among Colistin, Sulbactam, and Fosfomycin and a Synergism Study of Colistin in Combination with Sulbactam or Fosfomycin against Clinical Isolates of Carbapenem-Resistant Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Sombat Leelasupasri

    2018-01-01

    Full Text Available This in vitro study aimed to determine the activity of colistin plus sulbactam and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB. Fifteen clinical isolates were obtained from patients admitted to Phyathai II International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were evaluated using the E-test or broth microdilution and the synergistic activity of the antibacterial combinations (colistin plus sulbactam or fosfomycin was determined using the chequerboard method. Clonal relationships were explored using repetitive element palindromic- (REP- PCR. The CRAB isolates were categorized by REP-PCR in 8 groups [A-H]. All CRAB isolates were universally susceptible to colistin but only 20.0% were susceptible to sulbactam. The MIC ranges for colistin, sulbactam, and fosfomycin were 0.75–2 mg/L, 2–96 mg/L, and 64–256 mg/L, respectively. A chequerboard assay revealed that the rates of synergistic and additive effect rates of colistin plus sulbactam and colistin plus fosfomycin were 53.3% and 73.3% of isolates, respectively. No antagonistic effect in any colistin-based combination was observed. However, almost CRAB strains in clone A showed the synergy or additive effects of colistin-sulbactam combination, whereas the other clone (B-H mostly showed indifferent effects. In conclusion, colistin plus sulbactam and colistin plus fosfomycin against CRAB seem to be interesting option but the efficacy in clinical use has to be evaluated.

  8. [Catalytic Degradation of Diclofenac Sodium over the Catalyst of 3D Flower-like alpha-FeOOH Synergized with H2O2 Under Visible Light Irradiation].

    Science.gov (United States)

    Xu, Jun-ge; Li, Yun-qin; Huang, Hua-shan; Yuan, Bao-ling; Cui, Hao-jie; Fu, Ming-lai

    2015-06-01

    Three dimensional (3D) flower-like alpha-FeOOH nanomaterials were prepared by oil bath reflux method using FeSO4, urea, ethanol and water, and the products which were characterized by XRD, FT-IR and SEM techniques. The SEM images showed that the 3D flower-like samples consisted of nanorods with a length of 400-500 nm and a diameter of 40-60 nm. The catalytic performance of the samples was evaluated by catalytic degradation of diclofenac sodium using H2O2 as the oxidant under simulated visible light. The results showed that the as-prepared samples presented high efficient catalytic performances, and more than 99% of the initial diclofenac sodium (30 mg x L(-1)) was degraded in 90 min. A radical mechanism can be proposed for the catalytic degradation of diclofenac sodium solution.

  9. The Natural Antimicrobial Subtilosin A Synergizes with Lauramide Arginine Ethyl Ester (LAE), ε-Poly-L-lysine (Polylysine), Clindamycin Phosphate and Metronidazole, Against the Vaginal Pathogen Gardnerella vaginalis.

    Science.gov (United States)

    Cavera, Veronica L; Volski, Anna; Chikindas, Michael L

    2015-06-01

    Bacterial vaginosis (BV) is a common, recurrent vaginal infection linked to increased chances of preterm delivery, incidence of sexually transmitted infections and fertility problems. BV is caused by a shift of the vaginal ecosystem from predominately Lactobacillus to a multispecies Actinomyces biofilm with the most common representatives identified as Gardnerella vaginalis and Prevotella spp. Current treatments have been associated with increased resistance as well as negative effects on healthy microbiota. The objective of this study was to evaluate the synergistic potential of ten two-antimicrobial combinations against G. vaginalis and four representative lactobacilli. The four tested antimicrobials were lauramide arginine ethyl ester, ε-poly-L-lysine, clindamycin phosphate, metronidazole and the bacteriocin subtilosin A. The use of bacteriocins as either synergist or alternative treatment positions bacteriocins as an excellent alternative to current antibiotics. The microdilution method was used to determine the minimum inhibitory concentration (MIC) of each of the antimicrobials individually, and the checkerboard assay was used to evaluate these MICs in combination. Clindamycin and subtilosin (CS), and metronidazole and subtilosin were synergistic against G. vaginalis in terms of fractional inhibitory concentration index (FICI). All tested combinations were found to have Bliss synergy. The combination of clindamycin and polylysine (CP) was identified as antagonistic against L. acidophilus in terms of both FICI and Bliss synergy. The combination of clindamycin and metronidazole (CM) was antagonistic against L. vaginalis for both FICI and Bliss synergy. The combinations of CP, clindamycin and LAE, CS, and LAE and polylysine were identified as Bliss antagonistic against L. vaginalis but did not indicate FICI antagonism.

  10. Synergic activation of toll-like receptor (TLR 2/6 and 9 in response to Ureaplasma parvum & urealyticum in human amniotic epithelial cells.

    Directory of Open Access Journals (Sweden)

    Martha Triantafilou

    Full Text Available Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM, preterm labour (PL pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs in order to "sense" pathogens. One such family of PRRs are the Toll like receptor family (TLR. In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA, trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.

  11. Synergism of mixtures of dicamba and 2,4-dichlorophenoxyacetic acid herbicide formulations on the neotropical fish Cnesterodon decemmaculatus (Pisces, Poeciliidae).

    Science.gov (United States)

    Ruiz de Arcaute, C; Soloneski, S; Larramendy, M L

    2018-05-01

    Dicamba (DIC) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two of the most applied auxinic herbicides worldwide, both individually and as part of a mixture. However, the toxicity and interactions achieved when applied as a mixture have not yet been characterised. The equitoxic and non-equitoxic acute toxicity exerted by binary mixtures of Banvel ® (57.71% DIC) and DMA ® (58.4% 2,4-D) on the Neotropical fish Cnesterodon decemmaculatus were evaluated. Results revealed mean values of 1.02 (range, 0.96-1.08) for the toxic unit (TU) that induced 50% mortality (TU 50 96 h ) to the fish exposed to binary equitoxic mixtures of the commercial formulations Banvel ® -DMA ® . These results suggest that the mixture is nearly concentration additive. Furthermore, results demonstrated the occurrence of synergistic interaction when non-equitoxic combinations of Banvel ® -or DMA ® -formulated herbicides were assayed. In this context and regardless of their concentrations, either Banvel ® - or DMA ® -induced toxicity were synergised by the presence of the counterpart within mixtures. The present study represents the first evidence of the lethality exerted by mixtures of two auxinic herbicides-namely, DIC and 2,4-D-reported to date for fish and other biotic matrices. When C. decemmaculatus is used as the target organism, a synergistic pattern is observed following exposure to a mixture of both herbicides. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Synergism between low-energy neutral particles and energetic ions in the pulsed glow discharge deposition of diamond-like carbon films

    International Nuclear Information System (INIS)

    Afanasyev-Charkin, I.V.; Nastasi, M.

    2004-01-01

    Diamond-like carbon films were deposited using pulsed glow discharge deposition at 4 kV. The duty factor was varied and all other parameters were kept constant. It was shown that the contribution of neutral particles to the total number of deposition atoms is much larger than that of energetic ions. At the same time, there is a relationship between the deposition of neutral particles and ion bombardment. The sticking coefficient of the neutral particles in proportional to the flux of energetic ions and does not exceed 5x10 -4 for the deposition parameters used in our experiment

  13. Synergism of optical and radar data for forest structure and biomass / Sinergismo entre dados ópticos e de radar da estrutura da floresta e biomassa

    Directory of Open Access Journals (Sweden)

    Sassan S. Saatchi

    2010-10-01

    Full Text Available AbstractThe structure of forests, the three-dimensional arrangement of individual trees, has a profound effect on how ecosystems function and carbon cycle, water and nutrients. Repeated optical satellite observations of vegetation patterns in two-dimensions have made significant contributions to our understanding of the state and dynamics of the global biosphere. Recent advances in Remote Sensing technology allow us to view the biosphere in three-dimensions and provide us with refined measurements of horizontal as well as vertical structure of forests. This paper provides an overview of the recent advances in fusion of optical and radar imagery in assessing terrestrial ecosystem structure and aboveground biomass. In particular, the paper will focus on radar and LIDAR sensors from recent and planned spaceborne missions and provide theoretical and practical applications of the measurements. Finally, the relevance of these measurements for reducing the uncertainties of terrestrial carbon cycle and the response of ecosystems to future climate will be discussed in details. ResumoA estrutura de florestas, o arranjo tridimensional de árvores individuais, tem um efeito profundo sobre o funcionamento dos ecossistemas e do ciclo do carbono, água e nutrientes. Repetidas observações de satélite óptico de padrões de vegetação em duas dimensões trouxeram contribuições significativas para a nossa compreensão do estado e da dinâmica da biosfera global. Recentes avanços na tecnologia de Sensoriamento Remoto nos permitem ver a biosfera em três dimensões e nos fornecer medições apuradas da estrutura horizontal, bem como a vertical das florestas. Esse artigo fornece uma visão geral dos recentes avanços na fusão de imagens ópticas e de radar para avaliar a estrutura do ecossistema terrestre e biomassa. Em particular, o trabalho concentra-se em sensores radar e LIDAR de recentes missões espaciais planejadas e fornece aplicações teóricas e praticas das medições. Por fim, a relevância dessas medidas para reduzir as incertezas do ciclo de carbono terrestre e de resposta dos ecossistemas ao clima no futuro será discutida em detalhes.

  14. CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology

    Directory of Open Access Journals (Sweden)

    Parisa Kalantari

    2018-01-01

    Full Text Available The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5, a C-type lectin receptor (CLR related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs.

  15. Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, Simone; Moser, Lydia

    2007-01-01

    Objective: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent...

  16. In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, Guo-Ying; Zhang, Xin-Juan; Han, Jun; Li, Yu-Qing; Wang, Gen-Chun

    2015-12-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a problematic pathogen posing a serious therapeutic challenge in the clinic. It is often multidrug-resistant (MDR) to conventional classes of antibacterial agents and there is an urgent need to develop new agents or strategies for treatment. Magnolol (ML) and honokiol (HL) are two naturally occurring diallylbiphenols which have been reported to show inhibition of MRSA. In this study their synergistic effects with antibacterial agents were further evaluated via checkerboard and time-kill assays. The susceptibility spectrum of clinical MRSA strains was tested by the disk diffusion method. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of ML and HL were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and time-killing experiments. ML and HL showed similar activity against both MSSA and MRSA with MIC/MBC at 16 ~ 64 mg/L, with potency similar to amikacin (AMK) and gentamicin (GEN). When they were used in combination with conventional antibacterial agents, they showed bacteriostatic synergy with FICIs between 0.25 ~ 0.5, leading to the combined MICs decreasing to as low as 1 ~ 2 and 1 ~ 16 mg/L for ML (HL) and the agents, respectively. MIC50 of the combinations decreased from 16 mg/L to 1 ~ 4 mg/L for ML (HL) and 8 ~ 128 mg/L to 2 ~ 64 mg/L for the antibacterial agents, which exhibited a broad spectrum of synergistic action with aminoglycosides (AMK, etilmicin (ETM) and GEN), floroquinolones (levofloxacin (LEV), ciprofloxacin and norfloxacin), fosfomycin (FOS) and piperacillin. The times of dilution (TOD, the extent of decreasing in MIC value) were determined up to 16 for the combined MIC. A more significant synergy after combining was determined as ML (HL) with AMK, ETM, GEN and FOS. ML (HL) combined with antibacterial agents did not show antagonistic effects on any of the ten MRSA strains. Reversal effects of MRSA resistance to AMK and GEN by ML and HL were also observed, respectively. All the combinations also showed better dynamic bactericidal activity against MRSA than any of single ML (HL) or the agents at 24 h incubation. The more significant synergy of combinations were determined as HL (ML) + ETM, HL + LEV and HL + AMK (GEN or FOS), with △LC24 of 2.02 ~ 2.25. ML and HL showed synergistic potentiation of antibacterial agents against clinical isolates of MRSA and warrant further pharmacological investigation.

  17. Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Mazen Alzaharna

    Full Text Available Andrographolide (Andro has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death.

  18. Inhibition of CCl formation during the combustion of MSW gasification syngas: An experimental study on the synergism and competition between oxidation and chlorination.

    Science.gov (United States)

    Zhang, Rui-Zhi; Yin, Ren-Hao; Luo, Yong-Hao

    2018-03-17

    For the safe disposal of MSW, a four-step gasification-combustion conversion process is proposed in this work, consisting of material gasification, ash melting, syngas conversion and combustion. Based on the control method of dioxin in gasification process which has been studied previously, experiments of tar chlorination process under oxidative atmospheres were carried out in a homogeneous flow reaction system, using benzene as the tar model compound, to find a way for the inhibition of CCl formation during the syngas combustion process. Results indicated that Cl 2 reacts with benzene more easily than O 2 under low temperatures, and has a positive effect on both oxidative cracking and polymerization. For chlorination reactions, high temperature enhances the chlorination degree and leads to the formation of perchlorinated hydrocarbons, but also promotes the rupture of the weak CCl bonds. With the rise of temperature, hexachlorobenzene became the major product, the amounts of all chlorinated hydrocarbons decreased rapidly, and the conversion direction depended on the amount of O 2 . O 2 generally promotes the formation of hydrogen chloride, and inhibits the chlorination of hydrocarbons. At a temperature above 900 °C, the total amount of chlorinated hydrocarbons was very low under oxidative atmospheres, even only with a equivalence ratio of 0.2. However, during the oxidation process under low temperatures, CCl can also be formed on cyclopentadienyl and 1,3-butadienyl radicals, whose chlorination products were observed. The synergistic and competitive effects between oxidation and chlorination are concluded and the major benzene conversion pathways are summarized according to the products detected. Copyright © 2018. Published by Elsevier Ltd.

  19. A novel polymyxin derivative that lacks the fatty acid tail and carries only three positive charges has strong synergism with agents excluded by the intact outer membrane.

    Science.gov (United States)

    Vaara, Martti; Siikanen, Osmo; Apajalahti, Juha; Fox, John; Frimodt-Møller, Niels; He, Hui; Poudyal, Anima; Li, Jian; Nation, Roger L; Vaara, Timo

    2010-08-01

    Polymyxins are cationic lipopeptides (five cationic charges) and the last resort for the treatment of serious Gram-negative infections caused by multiresistant strains. NAB741 has a cyclic peptide portion identical to that of polymyxin B but carries in the linear peptide portion a threonyl-D-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). At the N terminus of the peptide, NAB741 carries an acetyl group instead of a mixture of methyl octanoyl and methyl heptanoyl residues. NAB741 sensitized Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii to antibiotics against which the intact outer membrane is an effective permeability barrier. When tested by using Etest strips on plates containing increasing concentrations of NAB741, the fractional inhibition concentration index (FICI) of the combination of NAB741 with rifampin ranged from

  20. A Novel Polymyxin Derivative That Lacks the Fatty Acid Tail and Carries Only Three Positive Charges Has Strong Synergism with Agents Excluded by the Intact Outer Membrane▿

    OpenAIRE

    Vaara, Martti; Siikanen, Osmo; Apajalahti, Juha; Fox, John; Frimodt-Møller, Niels; He, Hui; Poudyal, Anima; Li, Jian; Nation, Roger L.; Vaara, Timo

    2010-01-01

    Polymyxins are cationic lipopeptides (five cationic charges) and the last resort for the treatment of serious Gram-negative infections caused by multiresistant strains. NAB741 has a cyclic peptide portion identical to that of polymyxin B but carries in the linear peptide portion a threonyl-d-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). At the N terminus of the peptide, NAB741 carries an acetyl group instead of a mi...

  1. Synergism between ammonia, lactic acid and carboxylic acids as kairomones in the host-seeking behaviour of the malaria mosquito Anopheles gambiae sensu stricto (Diptera: Culicidae)

    NARCIS (Netherlands)

    Smallegange, R.C.; Qiu, Y.T.; Loon, van J.J.A.; Takken, W.

    2005-01-01

    Host odours play a major role in the orientation and host location of blood-feeding mosquitoes. Anopheles gambiae Giles sensu stricto, which is the most important malaria vector in Africa, is a highly anthropophilic mosquito species, and the host-seeking behaviour of the females of this mosquito is

  2. Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes

    Science.gov (United States)

    Lee, Darwin V.; Li, Dongmei; Yan, Qingyun; Zhu, Yimin; Goodwin, Bryan; Calle, Roberto; Brenner, Martin B.; Talukdar, Saswata

    2014-01-01

    Fibroblast growth factor 21 (FGF21) has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC) adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway. PMID:25365322

  3. Synergic Investigation Of The Self-Assembly Structure And Mechanism Of Retroviral Capsid Proteins By Solid State NMR, Transmission Electron Microscopy And Multiscale simulation

    Science.gov (United States)

    2017-03-29

    manifestation of structural rearrangements, are likely a consequence of the localized large change of torsion angles of the loops between helices, interdomain...structures of native HIV-1 capsid protein reveal conformational variability, Science, 349 (2015) 99-103. [32] T.R. Gamble , S.H. Yoo, F.F. Vajdos, U.K

  4. Mesenchymal stem cell expression of SDF-1β synergizes with BMP-2 to augment cell-mediated healing of critical-sized mouse calvarial defects.

    Science.gov (United States)

    Herberg, Samuel; Aguilar-Perez, Alexandra; Howie, R Nicole; Kondrikova, Galina; Periyasamy-Thandavan, Sudharsan; Elsalanty, Mohammed E; Shi, Xingming; Hill, William D; Cray, James J

    2017-06-01

    Bone has the potential for spontaneous healing. This process, however, often fails in patients with comorbidities. Tissue engineering combining functional cells, biomaterials and osteoinductive cues may provide alternative treatment strategies. We have recently demonstrated that stromal cell-derived factor-1β (SDF-1β) works in concert with bone morphogenetic protein-2 (BMP-2) to potentiate osteogenic differentiation of bone marrow-derived mesenchymal stem/stromal cells (BMSCs). Here, we test the hypothesis that SDF-1β overexpressed in Tet-Off-SDF-1β BMSCs, delivered on acellular dermal matrix (ADM), synergistically augments BMP-2-induced healing of critical-sized mouse calvarial defects. BMSC therapies alone showed limited bone healing, which was increased with co-delivery of BMP-2. This was further enhanced in Tet-Off-SDF-1β BMSCs + BMP-2. Only limited BMSC retention on ADM constructs was observed after 4 weeks in vivo, which was increased with BMP-2 co-delivery. In vitro cell proliferation studies showed that supplementing BMP-2 to Tet-Off BMSCs significantly increased the cell number during the first 24 h. Consequently, the increased cell numbers decreased the detectable BMP-2 levels in the medium, but increased cell-associated BMP-2. The data suggest that SDF-1β provides synergistic effects supporting BMP-2-induced, BMSC-mediated bone formation and appears suitable for optimization of bone augmentation in combination therapy protocols. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Synergism between sodium chloride, sucrose and tricalcium phosphate in the osmotic dehydration of oca (Oxalis tuberosa with and without chitosan coating

    Directory of Open Access Journals (Sweden)

    José Arroyo Portal

    2010-12-01

    Full Text Available We investigated the synergistic effect of three solutes (sodium chloride, sucrose, tricalcium phosphate in different combinations of concentration, on the moisture, solid gain and calcium gain in oca (Oxalis tuberosa with and without chitosan (CR and SR. In both cases applied the Simplex with Extended Centroid mixture design. Were used cylinders of oca of 0.9 cm of diameter and 3.4 cm of length. The kinetics of moisture, solid gain and calcium gain for 48 hours was evaluated. The effective diffusivity of water, solids and calcium was determined. We found that in samples CR is greater loss of water and less solid gain compared with SR samples mainly as sodium chloride or sucrose participate independently, while for the gain of calcium, in all cases, the CR samples gain more of calcium than SR samples. The effective diffusivities found are: water, 1.19E-09 m2 /s in samples CR and 1.34E-09 m2 /s in SR samples; for solid, 3.67E-09 m2 /s in samples CR and 5.43E-09 m2 /s in SR samples; and, for calcium 3.32E-11 m2 /s in samples CR and 1.57E-09 m2 /s in SR samples.

  6. A sustainable and green process for scouring of cotton fabrics using xylano-pectinolytic synergism: switching from noxious chemicals to eco-friendly catalysts.

    Science.gov (United States)

    Singh, Avtar; Kaur, Amanjot; Patra, Arun Kumar; Mahajan, Ritu

    2018-04-01

    The objective of this research was to develop an appropriate, eco-friendly, cost-effective bioscouring methodology for removing natural impurities from cotton fabric. Maximum bioscouring was achieved using 5.0 IU xylanase and 4.0 IU pectinase with material to liquid ratio of 1:15 in a 50 mM buffer (glycine-NaOH buffer, 1.0 mM EDTA and 1% Tween-80, pH 8.5) with a treatment time of 60 min at 50 °C and an agitation speed of 60 rpm. The bioscoured cotton fabrics showed a gain of 1.17% in whiteness, 3.23% in brightness and a reduction of 4.18% in yellowness in comparison to fabric scoured with an alkaline scouring method. Further, after bleaching, the whiteness, brightness and tensile strength of the bioscoured fabrics were increased by 2.18, 2.33 and 11.74% along with a decrease of 4.61% in yellowness of bioscoured plus bleached fabrics in comparison to chemically scoured plus bleached fabrics. From the results, it is clear that bioscouring is more efficient, energy saving and an eco-friendly process and has the potential to replace the environment-damaging scouring process with the xylano-pectinolytic bioscouring process.

  7. Flt3 ligand synergizes with granulocyte-colony-stimulating factor in bone marrow mobilization to improve functional outcome after spinal cord injury in the rat

    Czech Academy of Sciences Publication Activity Database

    Urdzíková, Lucia; Mašínová, Katarína; Vaněček, Václav; Růžička, Jiří; Šedý, Jiří; Syková, Eva; Jendelová, Pavla

    2011-01-01

    Roč. 13, č. 9 (2011), s. 1090-1104 ISSN 1465-3249 R&D Projects: GA AV ČR IAA500390902; GA MŠk(CZ) LC554 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : axonal sprouting * bone marrow mobilization * Flt3 ligand Subject RIV: FH - Neurology Impact factor: 3.627, year: 2011

  8. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry

    International Nuclear Information System (INIS)

    Safarian, Diana; Carnec, Xavier; Tsamis, Fotini; Kajumo, Francis; Dragic, Tatjana

    2006-01-01

    HIV-1 coreceptors are attractive targets for novel antivirals. Here, inhibition of entry by two classes of CCR5 antagonists was investigated. We confirmed previous findings that HIV-1 isolates vary greatly in their sensitivity to small molecule inhibitors of CCR5-mediated entry, SCH-C and TAK-779. In contrast, an anti-CCR5 monoclonal antibody (PA14) similarly inhibited entry of diverse viral isolates. Sensitivity to small molecules was V3 loop-dependent and inversely proportional to the level of gp120 binding to CCR5. Moreover, combinations of the MAb and small molecules were highly synergistic in blocking HIV-1 entry, suggesting different mechanisms of action. This was confirmed by time course of inhibition experiments wherein the PA14 MAb and small molecules were shown to inhibit temporally distinct stages of CCR5 usage. We propose that small molecules inhibit V3 binding to the second extracellular loop of CCR5, whereas PA14 preferentially inhibits subsequent events such as CCR5 recruitment into the fusion complex or conformational changes in the gp120-CCR5 complex that trigger fusion. Importantly, our findings suggest that combinations of CCR5 inhibitors with different mechanisms of action will be central to controlling HIV-1 infection and slowing the emergence of resistant strains

  9. Synergism between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone on lung tumor incidence in mice

    International Nuclear Information System (INIS)

    Wang Yingjan; Chang Han; Kuo, Yu-Chun; Wang, Chien-Kai; Siao, Shih-He; Chang, Louis W.; Lin Pinpin

    2011-01-01

    Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen, TCDD only induced oxidative DNA damages. In our present study, we combined TCDD with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to investigate their tumorigenic effects on lung tumor formation in A/J mice. Application of NNK at a tumorigenic dose (2 mg/mouse) induced lung adenoma in both male and female A/J mice. Neither application of NNK at a non-tumorigenic dose (1 mg/mouse) nor repeated application of TCDD alone increased tumor incidence. Following the single injection of NNK at a non-tumorigenic dose (1 mg/mouse), repeated application of TCDD significantly increased the lung tumor incidence in female, but not in male, A/J mice 24 weeks later. Utilizing the real-time RT-PCR array, we found that P16 mRNA was significantly reduced in female lung, but not male lung, of NNK/TCDD co-treated A/J mice. With immunohistochemical staining, we confirmed that nuclear P16 protein was reduced in the lungs of NNK/TCDD co-treated female mice. These data suggest that P16 reduction at least partially contributed to synergistic effects of TCDD in lung tumorigenesis.

  10. Proceedings of the 12th Army Symposium on Solid Mechanics, ’Synergism of Mechanics Mathematics and Materials’ 4-7 November 1991, Plymouth, Massachusetts.

    Science.gov (United States)

    1991-11-07

    Bands in A1SI 4340 Steel: Microstructural Observations - C.O. Mgbokwere, SIR . Nutt and J. Duffy ..................................................... 299...using a Newton -Raphson iteration. The instability strain (El) is plotted versus grain size in Figure 6, along with values of Ei determined experimentally...Instability Mechanisms in High Hardness Steel," US Government Report MTL-TR 87-2, January 1987. 6. S. Nemat-Nasser, J.B. Issacs , and J.E. Starrett

  11. In vitro synergism of a water insoluble fraction of Uncaria tomentosa combined with fluconazole and terbinafine against resistant non-Candida albicans isolates.

    Science.gov (United States)

    Moraes, Renata Cougo; Carvalho, Anderson Ramos; Lana, Aline Jacobi Dalla; Kaiser, Samuel; Pippi, Bruna; Fuentefria, Alexandre Meneghello; Ortega, George González

    2017-12-01

    Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance. The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated. TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis. The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0 μg/mL) and WIF and FLZ (1.95:8.0 μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700-800 cm -1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF. DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat's claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.

  12. Synergic induction of human periodontal ligament fibroblast cell death by nitric oxide and N-methyl-D-aspartic acid receptor antagonist.

    Science.gov (United States)

    Seo, Taegun; Cha, Seho; Woo, Kyung Mi; Park, Yun-Soo; Cho, Yun-Mi; Lee, Jeong-Soon; Kim, Tae-Il

    2011-02-01

    Nitric oxide (NO) has been known as an important regulator of osteoblasts and periodontal ligament cell activity. This study was performed to investigate the relationship between NO-mediated cell death of human periodontal ligament fibroblasts (PDLFs) and N-methyl-D-aspartic acid (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK801). Human PDLFs were treated with various concentrations (0 to 4 mM) of sodium nitroprusside (SNP) with or without 200 µM MK801 in culture media for 16 hours and the cell medium was then removed and replaced by fresh medium containing MTS reagent for cell proliferation assay. Western blot analysis was performed to investigate the effects of SNP on the expression of Bax, cytochrome c, and caspase-3 proteins. The differences for each value among the sample groups were compared using analysis of variance with 95% confidence intervals. In the case of SNP treatment, as a NO donor, cell viability was significantly decreased in a concentration-dependent manner. In addition, a synergistic effect was shown when both SNP and NMDA receptor antagonist was added to the medium. SNP treated PDLFs exhibited a round shape in culture conditions and were dramatically reduced in cell number. SNP treatment also increased levels of apoptotic marker protein, such as Bax and cytochrome c, and reduced caspase-3 in PDLFs. Mitogen-activated protein kinase signaling was activated by treatment of SNP and NMDA receptor antagonist. These results suggest that excessive production of NO may induce apoptosis and that NMDA receptor may modulate NO-induced apoptosis in PDLFs.

  13. In vitro antifungal activity of different components of Centratherum anthelminticum and Ocimum sanctum seed oils and their synergism against oral pathogenic fungi.

    Science.gov (United States)

    H Gopalkrishna, Aparna; M, Seshagiri; Muddaiah, Sunil; R, Shashidara

    2016-01-01

    Background. Opportunistic fungal infections like candidiasis are common in the oral cavity. In recent years Candida species have shown resistance against a number of synthetic drugs. This study assessed the antifungal activity of Centratherum anthelminticum and Ocimum sanctum seed oils against six common pathogenic Candida strains. Synergistic activity of the major oil components was also studied. Methods. Antifungal activity of Centratherum anthelminticum and Ocimum sanctum seed oils were tested against six oral fungal pathogens, Candida albicans ATCC 90028, Candida krusei 6258, Candida tropicalis 13803, Candida parapsilosis22019, Candida glabrata 90030 and Candida dubliniensis MYA 646, by disc diffusion and broth microdilution methods to determine the diameter of inhibition zone (DIZ) and minimum inhibitory concentration (MIC), respectively. The oil was extracted using Soxhlet apparatus from seeds subjected to columnchromatography (CC) and thin layer chromatography (TLC) and major components were separated and quantified. Results. All the six Candida strains showed growth inhibition to a variable degree when tested with both seed oils. Both seed oils showed antifungal activity. For Centratherum anthelminticum seed oil maximum DIZ at 7 μL was recorded at 75.7 mm for Candida albicans ATCC 90028, and the least DIZ was 45.7 mm for Candida dubliniensis MYA 646. For Ocimum sanctum seed oil maximum DIZ at 7 μL was 61.0 mm for Candida krusei ATCC 6258 and the least DIZ was 46.7 mm for Candida tropicalis ATCC 13803. The mixtures of phospholipids and unsaponifiable matter exhibitedMIC values at 1.25 μL for both oils, whereas neutral lipids fraction and unsaponifiable matter exhibited similar MIC at 2.5 μL against Candida albicans and Candida krusei. Conclusion. Centratherum anthelminticum and Ocimum sanctumseed oils exhibited strong antifungal activity against six different species of Candida and this may be attributed to various active components in the oil and their synergistic activity.

  14. CIB1 synergizes with EphrinA2 to regulate Kaposi's sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Chirosree Bandyopadhyay

    2014-02-01

    Full Text Available KSHV envelope glycoproteins interact with cell surface heparan sulfate and integrins, and activate FAK, Src, PI3-K, c-Cbl, and Rho-GTPase signal molecules in human microvascular dermal endothelial (HMVEC-d cells. c-Cbl mediates the translocation of virus bound α3β1 and αVβ3 integrins into lipid rafts (LRs, where KSHV interacts and activates EphrinA2 (EphA2. EphA2 associates with c-Cbl-myosin IIA and augmented KSHV-induced Src and PI3-K signals in LRs, leading to bleb formation and macropinocytosis of KSHV. To identify the factor(s coordinating the EphA2-signal complex, the role of CIB1 (calcium and integrin binding protein-1 associated with integrin signaling was analyzed. CIB1 knockdown did not affect KSHV binding to HMVEC-d cells but significantly reduced its entry and gene expression. In contrast, CIB1 overexpression increased KSHV entry in 293 cells. Single virus particle infection and trafficking during HMVEC-d cell entry was examined by utilizing DiI (envelope and BrdU (viral DNA labeled virus. CIB1 was associated with KSHV in membrane blebs and in Rab5 positive macropinocytic vesicles. CIB1 knockdown abrogated virus induced blebs, macropinocytosis and virus association with the Rab5 macropinosome. Infection increased the association of CIB1 with LRs, and CIB1 was associated with EphA2 and KSHV entry associated signal molecules such as Src, PI3-K, and c-Cbl. CIB1 knockdown significantly reduced the infection induced EphA2, Src and Erk1/2 activation. Mass spectrometry revealed the simultaneous association of CIB1 and EphA2 with the actin cytoskeleton modulating myosin IIA and alpha-actinin 4 molecules, and CIB1 knockdown reduced EphA2's association with myosin IIA and alpha-actinin 4. Collectively, these studies revealed for the first time that CIB1 plays a role in virus entry and macropinocytosis, and suggested that KSHV utilizes CIB1 as one of the key molecule(s to coordinate and sustain the EphA2 mediated signaling involved in its entry, and CIB1 is an attractive therapeutic target to block KSHV infection.

  15. Inhibitors of pan PI3K signaling synergize with BRAF or MEK inhibitors to prevent BRAF-mutant melanoma cell growth

    Directory of Open Access Journals (Sweden)

    Melanie eSweetlove

    2015-06-01

    Full Text Available BRAF and MEK inhibitors have improved outcomes for patients with BRAF-mutant melanoma, but their efficacy is limited by both intrinsic and acquired resistance. Activation of the PI3K pathway can mediate resistance to these agents, providing a strong rationale for combination therapy in melanoma. Here, a panel of 9 low passage human metastatic melanoma cell lines with BRAF mutations were tested in cell proliferation and protein expression assays for sensitivity to inhibitors of MEK (selumetinib and BRAF (vemurafenib as single agents and in combination with inhibitors of pan-PI3K (ZSTK474, pan-PI3K/mTOR (BEZ235, individual PI3K isoforms (p110α, A66; p110β, TGX-221; p110γ, AS-252424; p110δ, idelalisib, or mTORC1/2 (KU-0063794. Selumetinib and vemurafenib potently inhibited cell proliferation in all cell lines, especially in those that expressed low levels of pAKT. ZSTK474 and BEZ235 also inhibited cell proliferation in all cell lines and enhanced the antitumor activity of selumetinib and vemurafenib in the majority of lines by either interacting synergistically or additively to increase potency or by inducing cytotoxicity by significantly increasing the magnitude of cell growth inhibition. Furthermore, ZSTK474 or BEZ235 combined with selumetinib to produce robust inhibition of pERK, pAKT and pS6 expression and synergistic inhibition of NZM20 tumor growth. The inhibitors of individual PI3K isoforms or mTORC1/2 were less effective at inhibiting cell proliferation either as single agents or in combination with selumetinib or vemurafenib, although KU-0063794 synergistically interacted with vemurafenib and increased the magnitude of cell growth inhibition with selumetinib or vemurafenib in certain cell lines. Overall, these results suggest that the sensitivity of BRAF-mutant melanoma cells to BRAF or MEK inhibitors is at least partly mediated by activation of the PI3K pathway and can be enhanced by combined inhibition of the BRAF/MEK and PI3K/mTOR signaling pathways.

  16. Synergism of cattle and bison inoculum on ruminal fermentation and select bacterial communities in an artificial rumen (Rusitec fed barley straw

    Directory of Open Access Journals (Sweden)

    Daniela B Oss

    2016-12-01

    Full Text Available This study evaluated the effect of increasing the proportion of bison relative to cattle inoculum on fermentation and microbial populations within an artificial rumen (Rusitec. The experiment was a completely randomized design with a factorial treatment structure (proportion cattle:bison inoculum; 0:100, 33:67, 67:33 and 100:0 replicated in two Rusitec apparatuses (n=8 fermenters. The experiment was 15 d with 8 d of adaptation and 7 d of sampling. Fermenters were fed a diet of 70:30 barley straw:concentrate (DM basis. True digestibility of DM was determined after 48 h of incubation from d 13-15, and daily ammonia (NH3 and volatile fatty acid (VFA production were measured on d 9-12. Protozoa counts were determined at d 9, 11, 13 and 15 and particle-associated bacteria (PAB from d 13-15. Select bacterial populations in the PAB were measured using RT-qPCR. Fermenter was considered the experimental unit and day of sampling as a repeated measure. Increasing the proportion of bison inoculum resulted in a quadratic effect (P0.05. Increasing bison inoculum linearly increased (P<0.05 concentrate aNDF disappearance, total and concentrate N disappearance as well as total daily VFA and acetate production. A positive quadratic response (P<0.05 was observed for daily NH3-N, propionate, butyrate, valerate, isovalerate and isobutyrate production, as well as the acetate:propionate ratio. Increasing the proportion of bison inoculum linearly increased (P<0.05 total protozoa numbers. No effects were observed on pH, total gas and methane production, microbial N synthesis, or copies of 16S rRNA associated with total bacteria, Selenomonas ruminantium or Prevotella bryantii. Increasing bison inoculum had a quadratic effect (P<0.05 on Fibrobacter succinogenes, and tended to linearly (P<0.10 increase Ruminococcus flavefaciens and decrease (P<0.05 Ruminococcus albus copy numbers. In conclusion, bison inoculum increased the degradation of feed protein and fibre. A mixture of cattle and bison rumen inoculum acted synergistically, increasing the DM and aNDF disappearance of barley straw.

  17. ETME, a novel β-elemene derivative, synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway

    Directory of Open Access Journals (Sweden)

    Zhiying Yu

    2014-12-01

    Full Text Available Arsenic trioxide (ATO has been identified as an effective treatment for acute promyelocytic leukemia (APL but is much less effective against solid tumors such as hepatocellular carcinoma (HCC. In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yltryptophan methyl ester (ETME. Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulat