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Sample records for antimycobacterial agent tetrahydrolipstatin

  1. Antimycobacterial agents from selected Mexican medicinal plants.

    PubMed

    Rivero-Cruz, Isabel; Acevedo, Laura; Guerrero, José A; Martínez, Sergio; Bye, Robert; Pereda-Miranda, Rogelio; Franzblau, Scott; Timmermann, Barbara N; Mata, Rachel

    2005-09-01

    As part of the ICBG program Bioactive Agents from Dryland Biodiversity of Latin America, the present investigation was undertaken to explore the possible antimycobacterial potential of compounds derived from selected Mexican medicinal plants. Bioassay-guided fractionation of the crude extracts of Rumex hymenosepalus (Polygonaceae), Larrea divaricata (Zygophyllaceae), Phoradendron robinsonii (Loranthaceae) and Amphipteryngium adstringens (Julianiaceae) led to the isolation of several antimycobacterial compounds. Four stilbenoids, two flavan-3-ols and three anthraquinones were isolated from R. hymenosepalus. Two flavonols and nordihydroguaiaretic acid were obtained from L. divaricata. Sakuranetin was the antimycobacterial agent isolated from P. robinsonii. Two known triterpenoids and the novel natural product 3-dodecyl-1,8-dihydroxy-2-naphthoic acid were obtained from A. adstringens. In general, the isolates were identified by spectral means. The antimycobacterial activity of the secondary compounds isolated from the analysed species, as well as that of nine pure compounds previously isolated in our laboratories, was investigated; the MIC values ranged from 16 to 128 microg mL-1. Among the tested compounds, the glycolipids, sesquiterpenoids and triterpenoids showed the best antimycobacterial activity. The antimycobacterial property of the glycolipids is reported for the first time. Although the tested compounds showed moderate antimycobacterial activity, their presence in the analysed species provides the rationale for their traditional use in the treatment of tuberculosis.

  2. New agents with antimycobacterial activity.

    PubMed

    Marco-Contelles, José; Gómez-Sánchez, Elena

    2005-11-01

    In this paper, we report that a series of structurally simple a-halogenoacetamides show potent and excellent antimycobacterial activities against drug-sensitive Mycobacterium tuberculosis H(37)Rv and drug-resistant M. avium.

  3. Quinoline and quinolones: promising scaffolds for future antimycobacterial agents.

    PubMed

    Singh, Sandeep; Kaur, Gurpuneet; Mangla, Veenu; Gupta, Manish K

    2015-06-01

    Tuberculosis (TB) is still a major health concern worldwide. The increasing incidences of multi-drug-resistant tuberculosis (MDR-TB) necessitate the development of new anti-TB drugs acting via novel mode of action. The search of newer drugs for TB led to the identification of several quinoline-based antimycobacterial agents against both the drug-sensitive and MDR-TB. These agents have been designed by substituting quinoline scaffold with diverse chemical functionalities as well as by modifying quinoline/quinolone-based antibacterial drugs. Several of quinoline/quinolone derivatives displayed excellent antimycobacterial activity and were found free of cytotoxicity. This review highlights the critical aspects of design and structure-activity relationship of quinoline- and quinolone-based antimycobacterial agents.

  4. New Advances in Fatty Acids as Antimalarial, Antimycobacterial and Antifungal Agents

    PubMed Central

    Carballeira, N.M.

    2008-01-01

    This review deals with the most recent findings on the antimalarial, antimycobacterial, and antifungal properties of fatty acids, with particular emphasis on novel marine fatty acids. The first section deals with the most recent and some background literature on what has been the latest developments with respect to fatty acids as antimalarial agents and the importance of enzyme inhibition, in particular the inhibition of the enoyl-ACP-reductase (Fab I) of P. falciparum, the principal agent responsible for malaria. This section of the review also emphasizes the latest antimalarial research with the very long-chain Δ5,9 fatty acids from sponges. The second section of the review deals with the recent literature on the antimycobacterial activity of fatty acids and the importance of enzyme inhibition, in particular the inhibition of the enoyl-ACP-reductase (InhA) of M. tuberculosis for antimycobacterial activity. The inhibitory activities of the Δ5,9 fatty acids against InhA as well as that of the α-methoxylated fatty acids are also discussed. The importance of Δ5,9 fatty acids as topoisomerase I inhibitors and its connection to cancer is also reviewed. The last part of the review, the antifungal section, also emphasizes the most recent research with antifungal fatty acids and the importance of enzyme inhibition, in particular N-myristoyltransferase (NMT) inhibition, for antifungal activity. This last section of the review emphasizes the latest research with the α-methoxylated fatty acids but the importance of acetylenic fatty acids is also considered. PMID:18023422

  5. Recent progress on pyrazole scaffold-based antimycobacterial agents.

    PubMed

    Keri, Rangappa S; Chand, Karam; Ramakrishnappa, Thippeswamy; Nagaraja, Bhari Mallanna

    2015-05-01

    New and reemerging infectious diseases will continue to pose serious global health threats well into the 21st century and according to the World Health Organization report, these are still the leading cause of death among humans worldwide. Among infectious diseases, tuberculosis claims approximately 2 million deaths per year worldwide. Also, agents that reduce the duration and complexity of the current therapy would have a major impact on the overall cure rate. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat Mycobacterium tuberculosis. Subsequently, there is an urgent need for the development of new drug candidates with newer targets and alternative mechanism of action. In this perspective, pyrazole, one of the most important classes of heterocycles, has been the topic of research for thousands of researchers all over the world because of its wide spectrum of biological activities. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on the pyrazole core to provide an insight so that its full therapeutic potential can be utilized for the treatment of tuberculosis. In this article, the possible structure-activity relationship of pyrazole analogs for designing better antituberculosis (anti-TB) agents has been discussed and is also helpful for new thoughts in the quest for rational designs of more active and less toxic pyrazole-based anti-TB drugs.

  6. Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives.

    PubMed

    Krátký, Martin; Vinsova, Jarmila

    2016-01-01

    The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

  7. Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline.

    PubMed

    Cholo, Moloko C; Mothiba, Maborwa T; Fourie, Bernard; Anderson, Ronald

    2017-02-01

    Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F1/F0-ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.

  8. Nitrilase-catalyzed production of pyrazinoic acid, an antimycobacterial agent, from cyanopyrazine by resting cells of Rhodococcus rhodochrous J1.

    PubMed

    Kobayashi, M; Yanaka, N; Nagasawa, T; Yamada, H

    1990-10-01

    Using resting cells of Rhodococcus rhodochrous J1, in which a large amount of nitrilase is induced, a simple and efficient bioconversion process for the production of pyrazinoic acid, an antimycobacterial agent, through catalysis by a nitrilase was developed. The reaction conditions for production of pyrazinoic acid were optimized. Under optimum conditions, 3.5 M cyanopyrazine was converted to pyrazinoic acid, with a molar conversion yield of 100%. The highest yield achieved corresponded to 434 g of pyrazinoic acid per liter of reaction mixture. The synthesized pyrazinoic acid was isolated and identified physico-chemically.

  9. Facile synthesis of benzonitrile/nicotinonitrile based s-triazines as new potential antimycobacterial agents.

    PubMed

    Patel, Amit B; Chikhalia, Kishor H; Kumari, Premlata

    2014-05-22

    A common strategy to synthesize 4/6-(4-(4-methylpiperazin-1-yl)-6-(4-(4-oxo-2-phenylthiazolidin-3-yl)phenyl)-1,3,5-triazin-2-yloxy)benzonitriles/nicotinonitriles was developed by applying an efficient palladium-catalyzed C-C Suzuki coupling. Moreover, the synthesized compounds were also tested for their in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv using BACTEC MGIT and Lowenstein-Jensen MIC methods. Several compounds displayed profound antimycobacterial activity in combination with low toxicity towards mammalian cells. The best results were observed amongst the nicotinonitrile substituted s-triazine analogs and it could be a potential starting point to develop new lead compounds in the fight against M. tuberculosis H37Rv. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure-Activity Relationships and Membrane Targeting Properties.

    PubMed

    Yang, Tianming; Moreira, Wilfried; Nyantakyi, Samuel Agyei; Chen, Huan; Aziz, Dinah Binte; Go, Mei-Lin; Dick, Thomas

    2017-03-28

    Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress-inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.

  11. Comparison of CO2 Generation (BACTEC) and Viable-Count Methods To Determine the Postantibiotic Effect of Antimycobacterial Agents against Mycobacterium avium Complex

    PubMed Central

    Zhanel, George G.; Saunders, Marilyn H.; Wolfe, Joyce N.; Hoban, Daryl J.; Karlowsky, James A.; Kabani, Amin M.

    1998-01-01

    The postantibiotic effects (PAEs) of antimycobacterial agents determined with a BACTEC TB-460 instrument (CO2 production) and by a traditional viable-count method against Mycobacterium avium complex (MAC) were not significantly different (P > 0.05). The longest PAEs following a 2-h exposure to 2× the MIC were induced by amikacin (10.3 h), rifampin (9.7 h), and rifabutin (9.5 h), while the shortest PAEs resulted from clofazimine (1.7 h) and ethambutol (1.1 h) exposure. CO2 generation is a valid and efficient means of determining in vitro PAEs against MAC. PMID:9449284

  12. Beninese Medicinal Plants as a Source of Antimycobacterial Agents: Bioguided Fractionation and In Vitro Activity of Alkaloids Isolated from Holarrhena floribunda Used in Traditional Treatment of Buruli Ulcer

    PubMed Central

    Yemoa, Achille; Gbenou, Joachim; Affolabi, Dissou; Moudachirou, Mansourou; Bigot, André; Anagonou, Séverin; Portaels, Françoise; Martin, Anandi; Quetin-Leclercq, Joëlle

    2015-01-01

    Buruli ulcer (BU) imposes a serious economic burden on affected households and on health systems that are involved in diagnosing the disease and treating patients. Research is needed to find cost-effective therapies for this costly disease. Plants have always been an important source of new pharmacologically active molecules. Consequently we decided to undertake the study of plants used in traditional treatment of BU in Benin and investigate their antimycobacterial activity as well as their chemical composition. Extracts from forty-four (44) plant species were selected on account of reported traditional uses for the treatment of BU in Benin and were assayed for antimycobacterial activities. Crude hydroethanolic extract from aerial parts of Holarrhena floribunda (G. Don) T. Durand and Schinz was found to have significant antimycobacterial activity against M. ulcerans (MIC = 125 µg/mL). We describe here the identification of four steroidal alkaloids from Mycobacterium ulcerans growth-inhibiting fractions of the alkaloidal extract of the aerial parts of Holarrhena floribunda. Holadysamine was purified in sufficient amount to allow the determination of its MCI (=50 µg/mL). These results give some support to the use of this plant in traditional medicine. PMID:26180813

  13. Beninese Medicinal Plants as a Source of Antimycobacterial Agents: Bioguided Fractionation and In Vitro Activity of Alkaloids Isolated from Holarrhena floribunda Used in Traditional Treatment of Buruli Ulcer.

    PubMed

    Yemoa, Achille; Gbenou, Joachim; Affolabi, Dissou; Moudachirou, Mansourou; Bigot, André; Anagonou, Séverin; Portaels, Françoise; Martin, Anandi; Quetin-Leclercq, Joëlle

    2015-01-01

    Buruli ulcer (BU) imposes a serious economic burden on affected households and on health systems that are involved in diagnosing the disease and treating patients. Research is needed to find cost-effective therapies for this costly disease. Plants have always been an important source of new pharmacologically active molecules. Consequently we decided to undertake the study of plants used in traditional treatment of BU in Benin and investigate their antimycobacterial activity as well as their chemical composition. Extracts from forty-four (44) plant species were selected on account of reported traditional uses for the treatment of BU in Benin and were assayed for antimycobacterial activities. Crude hydroethanolic extract from aerial parts of Holarrhena floribunda (G. Don) T. Durand and Schinz was found to have significant antimycobacterial activity against M. ulcerans (MIC = 125 µg/mL). We describe here the identification of four steroidal alkaloids from Mycobacterium ulcerans growth-inhibiting fractions of the alkaloidal extract of the aerial parts of Holarrhena floribunda. Holadysamine was purified in sufficient amount to allow the determination of its MCI (=50 µg/mL). These results give some support to the use of this plant in traditional medicine.

  14. Synthesis of N-substituted 2-[(1E)-alkenyl]-4-(1H)-quinolone derivatives as antimycobacterial agents against non-tubercular mycobacteria

    PubMed Central

    Wube, Abraham A.; Bucar, Franz; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Hüfner, Antje

    2011-01-01

    In an effort to improve biological activities and to examine antimycobacterial-lipophilicity relationships of 2-[(1E)-alkenyl)]-4-(1H)-quinolones, we have synthesized a series of 30 quinolones by introducing several alkyl groups, an alkenyl and an alkynyl group at N-1. All synthetic compounds were first tested in vitro against Mycobacterium smegmatis and the most active compounds (MIC values ∼3.0–7.0 μM) were further examined against three other rapidly growing strains of mycobacteria using a microtiter broth dilution assay. The Clog P values of the synthetic compounds were calculated to provide an estimate of their lipophilicity. Compounds 18e, 19a and 19b displayed the most potent inhibitory effect against M. smegmatis mc2155 with an MIC value of ∼1.5 μM, which was twenty fold and thirteen fold more potent than isoniazid and ethambutol, respectively. On the other hand, compounds 17e, 18e and 19a were most active against Mycobacterium fortuitum and Mycobacterium phlei with an MIC value of ∼3.0 μM. In the human diploid embryonic lung cell line MRC-5 cytotoxicity assay, the derivatives showed moderate to strong cytotoxic activity. Although the antimycobacterial activity of our synthetic compounds could not be correlated with the calculated log P values, an increase in lipophilicity enhances the antimycobacterial activity and C13–C15 total chain length at positions 1 and 2 is required to achieve optimal inhibitory effect against the test strains. PMID:21429630

  15. High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

    PubMed Central

    Hahn, Juliane; Seeber, Frank; Kolodziej, Herbert; Ignatius, Ralf; Laue, Michael; Aebischer, Toni; Klotz, Christian

    2013-01-01

    Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC5024h = 2.8 µM) being more sensitive than WB-C6 (IC5024h = 6.2 µM). The effect was significantly more potent compared to MTZ (IC5024h = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis. PMID:23977083

  16. Antimycobacterial Activity and Mechanism of Action of NAS-91.

    PubMed

    Gratraud, Paul; Surolia, Namita; Besra, Gurdyal S; Surolia, Avadhesha; Kremer, Laurent

    2008-03-01

    The antimalarial agents NAS-91 and NAS-21 were found to express potent antimycobacterial activity, NAS-91 being more active than NAS-21. They partially inhibited mycolic acid biosynthesis and profoundly altered oleic acid production. The development of a cell-free assay for Delta 9-desaturase activity allowed direct demonstration of the inhibition of oleic acid biosynthesis by these compounds.

  17. Antimycobacterial neolignans isolated from Aristolochia taliscana.

    PubMed

    León-Díaz, Rosalba; Meckes, Mariana; Said-Fernández, Salvador; Molina-Salinas, Gloria Maria; Vargas-Villarreal, Javier; Torres, Javier; Luna-Herrera, Julieta; Jiménez-Arellanes, Adelina

    2010-02-01

    Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 microg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains.

  18. Tetrahydrolipstatin Inhibition, Functional Analyses, and Three-dimensional Structure of a Lipase Essential for Mycobacterial Viability

    SciTech Connect

    Crellin, Paul K.; Vivian, Julian P.; Scoble, Judith; Chow, Frances M.; West, Nicholas P.; Brammananth, Rajini; Proellocks, Nicholas I.; Shahine, Adam; Le Nours, Jerome; Wilce, Matthew C.J.; Britton, Warwick J.; Coppel, Ross L.; Rossjohn, Jamie; Beddoe, Travis

    2010-09-17

    The highly complex and unique mycobacterial cell wall is critical to the survival of Mycobacteria in host cells. However, the biosynthetic pathways responsible for its synthesis are, in general, incompletely characterized. Rv3802c from Mycobacterium tuberculosis is a partially characterized phospholipase/thioesterase encoded within a genetic cluster dedicated to the synthesis of core structures of the mycobacterial cell wall, including mycolic acids and arabinogalactan. Enzymatic assays performed with purified recombinant proteins Rv3802c and its close homologs from Mycobacterium smegmatis (MSMEG{_}6394) and Corynebacterium glutamicum (NCgl2775) show that they all have significant lipase activities that are inhibited by tetrahydrolipstatin, an anti-obesity drug that coincidently inhibits mycobacterial cell wall biosynthesis. The crystal structure of MSMEG{_}6394, solved to 2.9 {angstrom} resolution, revealed an {alpha}/{beta} hydrolase fold and a catalytic triad typically present in esterases and lipases. Furthermore, we demonstrate direct evidence of gene essentiality in M. smegmatis and show the structural consequences of loss of MSMEG{_}6394 function on the cellular integrity of the organism. These findings, combined with the predicted essentiality of Rv3802c in M. tuberculosis, indicate that the Rv3802c family performs a fundamental and indispensable lipase-associated function in mycobacteria.

  19. New trends in development of antimycobacterial compounds.

    PubMed

    Biava, M; Porretta, G C; Deidda, D; Pompei, R

    2006-06-01

    The resurgence of tuberculosis and the surge of multidrug-resistant clinical isolates of Mycobacterium tuberculosis have reaffirmed tuberculosis as a primary public health concern. In this review we describe some new findings on the pharmacological status of fluoroquinolones derivatives (Gatifloxacin, Moxifloxacin and Sitafloxacin), new macrolides (Clarithromycin, Azithromycin and Roxithromycin), new rifamycin derivatives (Rifapentin, Rifabutin and Rifalazil) and new oxazolidinones (Linezolid and PNU 100480). We describe also other type of agents that are being developed as antimycobacterial drugs. Some of these are under clinical investigation, while others are considered to be promising candidates for future development. Among them, nitroimidazopyrans, new ketolides, Isoxyl (ISO), pyrroles derived from BM 212, Mefloquine and Diarylquinoline R207910 are discussed. We also describe the mechanism of drug resistance in mycobacteria, as well as new potential targets.

  20. Antimycobacterial polyacetylenes from Levisticum officinale.

    PubMed

    Schinkovitz, Andreas; Stavri, Michael; Gibbons, Simon; Bucar, Franz

    2008-05-01

    No conflicts of interest concerning financial matters or personal relationships exist between the authors and those who might bias this work. The present work is in part included the PhD thesis of A. Schinkovitz (University of Graz) but has not been published elsewhere previously. The dichloromethane extract of the roots of Levisticum officinale L. (Apiaceae) exhibited significant antimycobacterial activity against Mycobacterium fortuitum and Mycobacterium aurum in a microtiter plate dilution assay and was further analysed following a bioassay-guided fractionation strategy. 3(R)-Falcarinol (3(R)-(-)-1,9-heptadecadien-4,6-diin-3-ol] and 3(R)-8(S)-falcarindiol [3(R)-8(S)-(+)-1,9-heptadecadien-4,6-diin-3,8-diol] could be identified as the active components in this extract. The minimal inhibitory concentration (MIC) of 3(R)-falcarinol against M. fortuitum and M. aurum was 16.4 microM while that of 3(R)-8(S)-falcarindiol was 30.7 microM against M. fortuitum and 61.4 microm against M. aurum, respectively. Previously, 3(R),8(R)-dehydrofalcarindiol was isolated from Artemisia monosperma and surprisingly this polyacetylene exhibited no antimycobacterial activity at 128 microg/mL. This indicates that the terminal methyl group is vital for retention of antimycobacterial activity. Reference antibiotics ethambutol and isoniazid exhibited an activity of 115.5 microM and 14.6 microM against M. fortuitum, and 3.4 microM and 29.2 microM against M. aurum, respectively.

  1. Antimycobacterial and Antibacterial Activity of Allium sativum Bulbs

    PubMed Central

    Viswanathan, V.; Phadatare, A. G.; Mukne, Alka

    2014-01-01

    Tuberculosis is one of the major public health problems faced globally. Resistance of Mycobacterium tuberculosis to antitubercular agents has called for an urgent need to investigate newer drugs to combat tuberculosis. Garlic (Allium sativum) is an edible plant which has generated a lot of curiosity throughout human history as a medicinal plant. Garlic contains sulfur compounds like allicin, ajoene, allylmethyltrisulfide, diallyltrisulfide, diallyldisulphide and others which exhibit various biological properties like antimicrobial, anticancer, antioxidant, immunomodulatory, antiinflammatory, hypoglycemic, and cardiovascular effects. According to various traditional systems of medicine, garlic is one of the established remedies for tuberculosis. The objective of the current study was to investigate in vitro antimycobacterial activity as well as anti-bacterial activity of various extracts rich in specific phytoconstituents from garlic. Preparation of garlic extracts was done based on the chemistry of the constituents and their stability. The estimation of in vitro antimycobacterial activity of different garlic extracts was done using Resazurin microtire plate assay technique whereas activity of garlic oil was evaluated by colony count method. The antibacterial activity of extracts and oil was estimated by zone of inhibition method. Extracts of garlic rich in allicin and ajoene showed appreciable antimycobacterial activity as compared to standard drugs. Garlic oil demonstrated significant antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus. PMID:25035540

  2. Antimycobacterial evaluation of pyrazinoic acid reversible derivatives.

    PubMed

    Dolezal, Martin; Kesetovic, Diana; Zitko, Jan

    2011-01-01

    Design, results of in vitro antimycobacterial evaluation, and study of structure-activity relationships of various pyrazinecarboxylic acid reversible derivatives are presented. This review deals with some pyrazinamide analogues/prodrugs derived from Nphenylpyrazine- 2-carboxamides (1), arylaminopyrazine-2,5-dicarbonitriles (2), aryl/alkylsulphanylpyrazines (3,4), and aroylpyrazines (5) effecting >50% inhibition in the primary antimycobacterial screen. The promising pyrazine candidates for further antimycobacterial evaluation were discovered. Results give good view onto structure-activity relationships of these analogues and promise even better activity of new compounds prepared after some structure optimization experiments.

  3. Benzimidazole-core as an antimycobacterial agent.

    PubMed

    Keri, Rangappa S; Rajappa, Chethana Kolambae; Patil, Siddappa A; Nagaraja, Bhari Mallanna

    2016-12-01

    Mycobacterium tuberculosis (Mtb) is considered as one of the precarious bacterial infections around the world. Through a projected 8.7 million new tuberculosis (TB) cases and 1.4 million mortalities per annum, this deadly infection resulted insubstantial amount of human deaths than any other single organism bacterial infections. TB is one of India's most threatening human health problems and it accounts for approximately 33% of the global health issues. Subsequently, for TB there is an imperative need for the improvement of existing drug candidates with newer targets and specified mechanism of action. Within the wide spectra of heterocycles, benzimidazole and its substituted analogues were evidenced promising biological efficacies enabling them to perform as new drug or prodrug candidates. Exceptional structural features of this class of heterocycle and versatile biological applications made it a privileged structural backbone in new drug design and discovery. Majorly, 2,5- and 2,6-disubstituted benzimidazole derivatives shown to induce significant antiTB potential. To seek more insights on this unique feature of benzimidazole candidates, there is an urgency to assemble the recent advances in this promising area. This review presents an overview of the recent advancements and focuses on the structural features responsible for unique antiTB applications and compiled published reports on benzimidazole derivatives emphasizing on different approaches employed for their syntheses in order to help medicinal and clinical chemists in designing next generation, yet effective and safer antiTB candidates.

  4. Phytosterols from Spondias mombin Linn with Antimycobacterial Activities

    PubMed Central

    Olugbuyiro, J. A. O; Moody, J. O; Hamann, M. T

    2016-01-01

    The growing problems of tuberculosis have led to the search for new anti-Mtb agents from higher plants. The stem bark of Spondias mombin was evaluated for its in vitro activity against Mycobacterium tuberculosis (H37Rv strain). Bioassay-guided fractionation of the methanol extract was carried out by Vacuum Liquid Chromatography (VLC) on Silica gel (230–400 mesh) and purification was done using HPLC and TLC. In vitro antimycobacterial susceptibility was performed by a fluorometric microplate alamar blue assay (MABA) and percentage mycobacterial inhibition was calculated. The structures of the isolated compounds were established by spectroscopic analysis. The active VLC fraction exhibited 91% inhibition against M. tuberculosis H37Rv at a concentration of 40 μg/mL. The HPLC fraction SMi-15 containing compounds 1 and 2 showed 92.8% inhibition against M. tuberculosis. Two new antimycobacterial phytosterols were isolated from the stem bark of S. mombin and the structures were identified as mombintane I (1) and mombintane II (2). The stem bark extractives of S. mombin contain antitubercular principles of the class phytosterol and support an important potential of triterpenoids. PMID:27818608

  5. Antimycobacterial susceptibility testing methods for natural products research

    PubMed Central

    Sánchez, Juan Gabriel Bueno; Kouznetsov, Vladimir V.

    2010-01-01

    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need of continuous developments on new and efficient methods to determine the susceptibility of isolates of M. tuberculosis in the search for novel antimicrobial agents. Natural products constitute an important source of new drugs, but design and implementation of antimycobacterial susceptibility testing methods are necessary for evaluate the different extracts and compounds. A number of biological assay methodologies are in current use, ranging from the classical disk diffusion and broth dilution assay format, to radiorespirometric (BACTEC), dye-based, and fluorescent/luminescence reporter assays. This review presents an analysis on the in vitro susceptibility testing methods developed for determinate antitubercular activity in natural products and related compounds (semi-synthetic natural products and natural products-derived compounds) and the criteria to select the adequate method for determination of biological activity of new natural products. PMID:24031490

  6. In vitro antimycobacterial activities of Physalis angulata L.

    PubMed

    Pietro, R C; Kashima, S; Sato, D N; Januário, A H; França, S C

    2000-07-01

    The HIV-tuberculosis co-infection has caused an impact on tuberculosis epidemiology all over the world and the efficacies of the therapeutic schemes traditionally prescribed in the treatment of tuberculosis, such as isoniazid, rifampicin and pyrazinamide, have decreased due to the appearance of multidrug-resistant M. tuberculosis strains (MDR). This work is part of research on natural antimicrobial agents from plant extracts through bioassay-guided fractionation, by in vitro determination of the minimum inhibitory concentration (MIC) using the microdilution method with Alamar blue oxidation-reduction dye. Crude CHCl3 Physalis angulata extracts and physalin-containing fractions displayed antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium kansasii, Mycobacterium malmoense and Mycobacterium intracellulare.

  7. Antimycobacterial physalins from Physalis angulata L. (Solanaceae).

    PubMed

    Januário, A H; Filho, E Rodrigues; Pietro, R C L R; Kashima, S; Sato, D N; França, S C

    2002-08-01

    Crude extracts and fractions from aerial parts of Physalis angulata have been bioassayed for antimycobacterial activity. Fraction A1-29-12 containing physalins B, F and D exhibited a minimum inhibitory concentration value (MIC) against Mycobacterium tuberculosis H(37)Rv strain of 32 microg/mL. Purified physalin B and physalin D were also tested showing MIC values against Mycobacterium tuberculosis H(37)Rv strain of > 128 microg/mL and 32 microg/mL respectively, suggesting that physalin D plays a relevant role in the antimycobacterial activity displayed. Structural elucidation of both physalins D and B was based on detailed (13)C and (1)H NMR spectral analysis with the aid of 2D-correlation spectroscopy ((1)H-(1)H, COSY, HSQC and HMBC). The assignment of the (13)C chemical shift for physalin D is reported here for the first time.

  8. Plants: a source for new antimycobacterial drugs.

    PubMed

    Santhosh, Ramachandran Sarojini; Suriyanarayanan, Balasubramanian

    2014-01-01

    Tuberculosis, also called TB, is currently a major health hazard due to multidrug-resistant forms of bacilli. Global efforts are underway to eradicate TB using new drugs with new modes of action, higher activity, and fewer side effects in combination with vaccines. For this reason, unexplored new sources and previously explored sources were examined and around 353 antimycobacterial compounds (Nat Prod Rep 2007; 24: 278-297) 7 have been previously reported. To develop drugs from these new sources, additional work is required for preclinical and clinical results. Since ancient times, different plant part extracts have been used as traditional medicines against diseases including tuberculosis. This knowledge may be useful in developing future powerful drugs. Plant natural products are again becoming important in this regard. In this review, we report 127 antimycobacterial compounds and their antimycobacterial activities. Of these, 27 compounds had a minimum inhibitory concentration of < 10 µg/mL. In some cases, the mechanism of activity has been determined. We hope that some of these compounds may eventually develop into effective new drugs against tuberculosis.

  9. meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

    PubMed

    Reyes-Melo, Karen; García, Abraham; Romo-Mancillas, Antonio; Garza-González, Elvira; Rivas-Galindo, Verónica M; Miranda, Luis D; Vargas-Villarreal, Javier; Favela-Hernández, Juan Manuel J; Camacho-Corona, María Del Rayo

    2017-10-15

    Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Antimycobacterial and cytotoxic activity of selected medicinal plant extracts

    PubMed Central

    Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac; Kissi-Twum, Abena

    2016-01-01

    Ethnopharmacological relevance Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. Material and methods The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. Results Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3 µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). Conclusion The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. PMID:26875647

  11. Antimycobacterial and cytotoxic activity of selected medicinal plant extracts.

    PubMed

    Nguta, Joseph M; Appiah-Opong, Regina; Nyarko, Alexander K; Yeboah-Manu, Dorothy; Addo, Phyllis G A; Otchere, Isaac; Kissi-Twum, Abena

    2016-04-22

    Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. A Mycobacterium marinum zone of inhibition assay as a method for screening potential antimycobacterial compounds from marine extracts.

    PubMed

    Barker, Lucia P; Lien, Benjamin A; Brun, Olivier S; Schaak, Damen D; McDonough, Kathleen A; Chang, Leng Chee

    2007-06-01

    A novel screening method for antimycobacterial agents using Mycobacterium marinum was developed. M. marinum was selected as a model organism because it has a close phylogenetic relationship to M. tuberculosis, a relatively rapid doubling time, similar drug susceptibilities to M. tuberculosis, and less stringent safety requirements. More than 1000 crude marine and plant extracts were screened against M. marinum in a Zone of Inhibition (ZOI) assay, and twenty-one target extracts were identified. The crude organic extract of the marine sponge, Haliclona sp.10, was chosen for further investigation as it yielded a ZOI of 20 mm at a concentration of 80 microg/disk. Following bioassay-guided fractionation, (-)-papuamine was isolated, and yielded a 15 mm ZOI at a concentration of 25 microg/disk. In standard assays using M. marinum, (-)-papuamine exhibited both an MIC and an MBC95 of 6.25 microg/mL. This is the first report of antimycobacterial activity for (-)-papuamine. In addition, when (-)-papuamine and other natural product extracts were tested for activity against both M. marinum and M. tuberculosis, activity was comparable between the two species. These data indicate that (-)-papuamine is a promising lead for the development of new antimycobacterial agents and that M. marinum is a useful surrogate for the screening of antimycobacterial compounds.

  13. Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis

    PubMed Central

    Drake, Wonder P.; Oswald-Richter, Kyra; Richmond, Bradley W.; Isom, Joan; Burke, Victoria E.; Algood, Holly; Braun, Nicole; Taylor, Thyneice; Pandit, Kusum V.; Aboud, Caroline; Yu, Chang; Kaminski, Naftali; Boyd, Alan S.; King, Lloyd E.

    2014-01-01

    IMPORTANCE Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis. OBJECTIVE To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions. DESIGN AND PARTICIPANTS A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention. SETTING A tertiary referral dermatology center in Nashville, Tennessee. INTERVENTIONS Participants were randomized to receive either the oral concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen or a comparative placebo regimen for 8 weeks with a 180-day follow-up. MAIN OUTCOMES AND MEASURES Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy. OBSERVATIONS In the intention-to-treat analysis, the CLEAR-treated group had a mean (SD) decrease in lesion diameter of −8.4 (14.0) mm compared with an increase of 0.07 (3.2) mm in the placebo-treated group (P = .05). The CLEAR group had a significant reduction in granuloma burden and experienced a mean (SD) decline of −2.9 (2.5) mm in lesion severity compared with a decline of −0.6 (2.1) mm in the placebo group (P = .02). CONCLUSIONS AND RELEVANCE Antimycobacterial therapy may result in significant reductions in chronic cutaneous sarcoidosis lesion diameter compared with placebo. These observed reductions, associated with a clinically significant improvement in symptoms, were present at the 180-day follow-up period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of pathways associated with disease severity and enhanced T-cell function following T

  14. The antimycobacterial constituents of dill (Anethum graveolens).

    PubMed

    Stavri, Michael; Gibbons, Simon

    2005-11-01

    As part of a project to characterize selected members of the Kuwaiti flora for their phytochemistry and antimycobacterial activity, a new furanocoumarin, 5-[4''-hydroxy-3''-methyl-2''-butenyloxy]-6,7-furocoumarin (3), was isolated from the whole herb of Anethum graveolens. The known compounds oxypeucedanin (1), oxypeucedanin hydrate (2) and falcarindiol (4) were also isolated from this plant. The structure of each compound was determined by interpretation of NMR and mass spectrometric data. The three known compounds exhibited antibacterial activity against a panel of rapidly growing mycobacteria with minimum inhibitory concentration (MIC) values in the range 2-128 microg/mL.

  15. Antimycobacterial Metabolites from Marine Invertebrates.

    PubMed

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Novel Thiazolidinone-Azole Hybrids: Design, Synthesis and Antimycobacterial Activity Studies

    PubMed Central

    Eroglu, Barbaros; Ozadali-Sari, Keriman; Unsal-Tan, Oya; Dharmarajan, Sriram; Yogeeswari, Perumal; Balkan, Ayla

    2016-01-01

    To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the reaction of Schiff bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to Knoevenagel condensation. To evaluate their structures 1H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 μM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity. PMID:28243274

  17. Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases.

    PubMed

    Abuzeid, Nadir; Kalsum, Sadaf; Koshy, Richin John; Larsson, Marie; Glader, Mikaela; Andersson, Henrik; Raffetseder, Johanna; Pienaar, Elsje; Eklund, Daniel; Alhassan, Muddathir S; AlGadir, Haidar A; Koko, Waleed S; Schön, Thomas; Ahmed Mesaik, M; Abdalla, Omer M; Khalid, Asaad; Lerm, Maria

    2014-11-18

    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases. Plants were harvested and ethanolic extracts were prepared. For selected extracts, fractionation with hydrophilic and hydrophobic solvents was undertaken. A luminometry-based assay was used for determination of mycobacterial growth in broth cultures and inside primary human macrophages in the presence or absence of plant extracts and fractions of extracts. Cytotoxicity was also assessed for active fractions of plant extracts. Of the tested extracts, three exhibited a significant inhibitory effect on an avirulent strain of Mycobacterium tubercluosis (H37Ra) at the initial screening doses (125 and 6.25µg/ml). These were bark and leaf extracts of Khaya senegalensis and the leaf extract of Rosmarinus officinalis L. Further fractions of these plant extracts were prepared with n-hexane, chloroform, ethyl acetate, n-butanol, ethanol and water, and the activity of these extracts was retained in hydrophobic fractions. Cytotoxicity assays revealed that the chloroform fraction of Khaya senegalensis bark was non-toxic to human monocyte-derived macrophages and other cell types at the concentrations used and hence, further analysis, including assessment of IC50 and intracellular activity was done with this fraction. These results encourage further investigations to identify the active compound(s) within the

  18. Resolution of chronic ocular sarcoidosis with antimycobacterial therapy

    PubMed Central

    Richmond, Bradley W.; Richter, Kyra; King, Lloyd E.; Drake, Wonder P.

    2014-01-01

    Ocular and cutaneous sarcoidosis is a chronic manifestation of sarcoidosis that remains difficult to treat. Recent investigations demonstrating efficacy with antimicrobial therapy in pulmonary and cutaneous sarcoidosis have been reported. Here, we report dual clinical improvement in cutaneous and ocular sarcoidosis following administration of oral antimycobacterial therapy. PMID:25580448

  19. Antimycobacterial activity of flavonoids from Lantana camara Linn.

    PubMed

    Begum, S; Wahab, A; Siddiqui, B S

    2008-04-15

    Linaroside (1) and lantanoside (2), two flavonoids isolated from Lantana camara and their common acetyl derivative (3) were examined for antimycobacterial activity against Mycobacterium tuberculosis, strain H(37)Rv. These compounds exhibited 30, 37 and 98% inhibition, respectively at 6.25 microg mL(-1) concentration. Among these flavonoids acetylated compound was found to be the most active.

  20. Antimycobacterial triterpenes from the Canadian medicinal plant Sarracenia purpurea.

    PubMed

    Morrison, Steven A; Li, Haoxin; Webster, Duncan; Johnson, John A; Gray, Christopher A

    2016-07-21

    The purple pitcher plant, Sarracenia purpurea, is a medicinal plant used by the Canadian First Nations to treat a wide variety of illnesses. The Mi'kmaq and Wolastoqiyik (Maliseet) peoples of Eastern Canada have traditionally used infusions of S. purpurea for the treatment of tuberculosis-like symptoms. Previous investigations have shown methanolic extracts of S. purpurea to possess antimycobacterial activity. To isolate and identify antimycobacterial constituents from S. purpurea. Methanolic extracts of S. purpurea were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry. The triterpenes betulinaldehyde, β-sitosterol, betulinic acid, and ursolic acid were isolated from S. purpurea. Betulinaldehyde, betulinic acid, and ursolic acid exhibited MICs of 450, 950, and 450μM and IC50s of 98, 169, and 93μM against M. tuberculosis H37Ra respectively whilst β-sitosterol was inactive (MIC and IC50 of >1000μM). Betulinaldehyde, betulinic acid, and ursolic acid were identified as the principal constituents responsible for the antimycobacterial activity of S. purpurea. This work is consistent with the ethnopharmacological use of S. purpurea by Canadian First Nations as a treatment against infectious diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteria.

    PubMed

    Mojib, Nazia; Philpott, Rachel; Huang, Jonathan P; Niederweis, Michael; Bej, Asim K

    2010-11-01

    In this study, we describe the antimycobacterial activity of two pigments, violacein, a purple violet pigment from Janthinobacterium sp. Ant5-2 (J-PVP), and flexirubin, a yellow-orange pigment from Flavobacterium sp. Ant342 (F-YOP). These pigments were isolated from bacterial strains found in the land-locked freshwater lakes of Schirmacher Oasis, East Antarctica. The minimum inhibitory concentrations (MICs) of these pigments for avirulent and virulent mycobacteria were determined by the microplate Alamar Blue Assay (MABA) and Nitrate Reductase Assay (NRA). Results indicated that the MICs of J-PVP and F-YOP were 8.6 and 3.6 μg/ml for avirulent Mycobacterium smegmatis mc²155; 5 and 2.6 μg/ml for avirulent Mycobacterium tuberculosis mc²6230; and 34.4 and 10.8 μg/ml for virulent M. tuberculosis H₃₇Rv, respectively. J-PVP exhibited a ~15 times lower MIC for Mycobacterium sp. than previously reported for violacein pigment from Chromobacterium violaceum, while the antimycobacterial effect of F-YOP remains undocumented. Our results indicate these pigments isolated from Antarctic bacteria might be valuable lead compounds for new antimycobacterial drugs used for chemotherapy of tuberculosis.

  2. Gut bacterium of Dendrobaena veneta (Annelida: Oligochaeta) possesses antimycobacterial activity.

    PubMed

    Fiołka, Marta J; Zagaja, Mirosław P; Piersiak, Tomasz D; Wróbel, Marek; Pawelec, Jarosław

    2010-09-01

    The new bacterial strain with antimycobacterial activity has been isolated from the midgut of Dendrobaena veneta (Annelida). Biochemical and molecular characterization of isolates from 18 individuals identified all as Raoultella ornithinolytica genus with 99% similarity. The bacterium is a possible symbiont of the earthworm D. veneta. The isolated microorganism has shown the activity against four strains of fast-growing mycobacteria: Mycobacterium butiricum, Mycobacterium jucho, Mycobacterium smegmatis and Mycobacterium phlei. The multiplication of the gut bacterium on plates with Sauton medium containing mycobacteria has caused a lytic effect. After the incubation of the cell free extract prepared from the gut bacterium with four strains of mycobacteria in liquid Sauton medium, the cells of all tested strains were deformed and divided to small oval forms and sometimes created long filaments. The effect was observed by the use of light, transmission and scanning microscopy. Viability of all examined species of mycobacteria was significantly decreased. The antimycobacterial effect was probably the result of the antibiotic action produced by the gut bacterium of the earthworm. The application of ultrafiltration procedure allowed to demonstrate that antimicrobial substance with strong antimycobacterial activity from bacterial culture supernatant, is a protein with the molecular mass above 100 kDa.

  3. Effects of Ascent to High Altitude on Human Antimycobacterial Immunity

    PubMed Central

    Aldridge, Robert W.; Siedner, Mark J.; Necochea, Alejandro; Leybell, Inna; Valencia, Teresa; Herrera, Beatriz; Wiles, Siouxsie; Friedland, Jon S.; Gilman, Robert H.; Evans, Carlton A.

    2013-01-01

    Background Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity. Methods Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants’ whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants’ whole blood versus positive-control culture broth and versus negative-control plasma. Results Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents. Conclusions An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or

  4. Interplay of mycolic acids, antimycobacterial compounds and pulmonary surfactant membrane: a biophysical approach to disease.

    PubMed

    Pinheiro, Marina; Giner-Casares, Juan J; Lúcio, Marlene; Caio, João M; Moiteiro, Cristina; Lima, José L F C; Reis, Salette; Camacho, Luis

    2013-02-01

    This work focuses on the interaction of mycolic acids (MAs) and two antimycobacterial compounds (Rifabutin and N'-acetyl-Rifabutin) at the pulmonary membrane level to convey a biophysical perspective of their role in disease. For this purpose, accurate biophysical techniques (Langmuir isotherms, Brewster angle microscopy, and polarization-modulation infrared reflection spectroscopy) and lipid model systems were used to mimic biomembranes: MAs mimic bacterial lipids of the Mycobacterium tuberculosis (MTb) membrane, whereas Curosurf® was used as the human pulmonary surfactant (PS) membrane model. The results obtained show that high quantities of MAs are responsible for significant changes on PS biophysical properties. At the dynamic inspiratory surface tension, high amounts of MAs decrease the order of the lipid monolayer, which appears to be a concentration dependent effect. These results suggest that the amount of MAs might play a critical role in the initial access of the bacteria to their targets. Both molecules also interact with the PS monolayer at the dynamic inspiratory surface. However, in the presence of higher amounts of MAs, both compounds improve the phospholipid packing and, therefore, the order of the lipid surfactant monolayer. In summary, this work discloses the putative protective effects of antimycobacterial compounds against the MAs induced biophysical impairment of PS lipid monolayers. These protective effects are most of the times overlooked, but can constitute an additional therapeutic value in the treatment of pulmonary tuberculosis (Tb) and may provide significant insights for the design of new and more efficient anti-Tb drugs based on their behavior as membrane ordering agents. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART.

    PubMed

    Kampmann, Beate; Tena-Coki, Gwen N; Nicol, Mark P; Levin, Michael; Eley, Brian

    2006-04-24

    Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette-Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants did not reflect this response; however, a decline in TNF-alpha was observed. This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.

  6. A review of antimycobacterial drugs in development.

    PubMed

    Asif, Mohammad

    2012-11-01

    The needs of newly developed antitubercular agents are required for the control of tuberculosis in the present time. In the discovery of new antitubercular drugs, the emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) has encouraged the researchers to intensify the efforts to discover novel antitubercular drugs. These novel drugs will predominantly target the persistent state of mycobacterium strains, which are resistant to conventional drugs including non resistant mycobacterium strains. In the last three to four decades no new effective drug has been developed for the treatment of resistant tuberculosis. However, in recent years, the research and development programs for the control of TB, there is a lot works is going on to enhancement of the anti-TB activity of new drugs particularly against resistant mycobacterium strains. Simultaneously, practical usefulness of some new targets is being identified and validated for the treatment of TB. Some compounds are presently in clinical trials, while others are being investigated in an attempt to explore new compounds for the target based treatment. The present review provides an overview of the new anti-TB agents with different molecular structures that are being clinically used and advanced stages of preclinical as well as clinical stages and also attempted to highlight the efforts that are being made in the development of new drug molecules as lead anti-TB agents.

  7. Synergistic Antimycobacterial Actions of Knowltonia vesicatoria (L.f) Sims

    PubMed Central

    Labuschagné, Antoinette; Hussein, Ahmed A.; Rodríguez, Benjamín; Lall, Namrita

    2012-01-01

    Euclea natalensis A.DC., Knowltonia vesicatoria (L.f) Sims, and Pelargonium sidoides DC. are South African plants traditionally used to treat tuberculosis. Extracts from these plants were used in combination with isoniazid (INH) to investigate the possibility of synergy with respect to antimycobacterial activity. The ethanol extract of K. vesicatoria was subjected to fractionation to identify the active compounds. The activity of the Knowltonia extract remained superior to the fractions with a minimum inhibitory concentration (MIC) of 625.0 μg/mL against Mycobacterium smegmatis and an MIC of 50.00 μg/mL against M. tuberculosis. The K. vesicatoria extract was tested against two different drug-resistant strains of M. tuberculosis, which resulted in an MIC of 50.00 μg/mL on both strains. The combination of K. vesicatoria with INH exhibited the best synergistic antimycobacterial activity with a fractional inhibitory concentration index of 0.25 (a combined concentration of 6.28 μg/mL). A fifty percent inhibitory concentration of this combination against U937 cells was 121.0 μg/mL. Two compounds, stigmasta-5,23-dien-3-ol (1) and 5-(hydroxymethyl)furan-2(5H)-one (2), were isolated from K. vesicatoria as the first report of isolation for both compounds from this plant and the first report of antimycobacterial activity. Compound (1) was active against drug-sensitive M. tuberculosis with an MIC of 50.00 μg/mL. PMID:22611433

  8. In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening.

    PubMed

    Taira, Junichi; Ito, Takashi; Nakatani, Hitomi; Umei, Tomohiro; Baba, Hiroki; Kawashima, Shotaro; Maruoka, Taira; Komatsu, Hideyuki; Sakamoto, Hiroshi; Aoki, Shunsuke

    2017-01-01

    Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined. With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

  9. Improved antimycobacterial activity of rifampin using solid lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Aboutaleb, Ehsan; Noori, Massoumeh; Gandomi, Narges; Atyabi, Fatemeh; Fazeli, Mohammad Reza; Jamalifar, Hossein; Dinarvand, Rassoul

    2012-10-01

    Rifampin (RIF) is one of the front-line drugs in therapy of tuberculosis (TB). The emergence of multidrug-resistant strains of mycobacteria has greatly contributed to the increased incidence of TB. Nano-based formulation of several antimicrobials has been shown to improve either antibacterial efficacy or pharmacokinetic behavior. In this study, RIF-loaded solid lipid nanoparticles (SLNs) were prepared by a modified microemulsion-based method and their particle size, zeta potential, encapsulation efficiency, morphology, and antibacterial activity against Mycobacterium fortuitum were evaluated. The resulting SLNs were spherical with diameter of about 100 nm, with low negative zeta potential, and an encapsulation efficiency of 82%. The formulation also sustained the drug release for 72 h. The antimycobacterial efficacy was greatly improved against M. fortuitum, and the minimum inhibitory concentration of drug-loaded SLNs was eight times less than free RIF. Drug-free SLNs and the ingredients showed no antibacterial effect. It can be concluded that as expected, solid lipid nanoparticles are promising vehicles for enhanced antimycobacterial effect of rifampin.

  10. In vitro antimycobacterial and cytotoxic data on medicinal plants used to treat tuberculosis

    PubMed Central

    Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac D.; Kissi-Twum, Abena

    2016-01-01

    This article contains data on in vitro antimycobacterial activity and cytotoxicity of hydroethanolic crude extracts from five selected medicinal plant species traditionally used to treat tuberculosis in Ghanaian ethnomedicine, see “Medicinal plants used to treat TB in Ghana” [1]. The interpretation and discussion of these data and further extensive insights into drug discovery against tuberculosis from natural products of plant biodiversity can be found in “Antimycobacterial and cytotoxic activity of selected medicinal plant extracts” [2]. PMID:27115026

  11. A Novel Antimycobacterial Compound Acts as an Intracellular Iron Chelator

    PubMed Central

    Dragset, Marte S.; Poce, Giovanna; Alfonso, Salvatore; Padilla-Benavides, Teresita; Ioerger, Thomas R.; Kaneko, Takushi; Sacchettini, James C.; Biava, Mariangela; Parish, Tanya; Argüello, José M.

    2015-01-01

    Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis. Mycobacterial iron uptake and metabolism are therefore attractive targets for antitubercular drug development. Resistance mutations against a novel pyrazolopyrimidinone compound (PZP) that is active against M. tuberculosis have been identified within the gene cluster encoding the ESX-3 type VII secretion system. ESX-3 is required for mycobacterial iron acquisition through the mycobactin siderophore pathway, which could indicate that PZP restricts mycobacterial growth by targeting ESX-3 and thus iron uptake. Surprisingly, we show that ESX-3 is not the cellular target of the compound. We demonstrate that PZP indeed targets iron metabolism; however, we found that instead of inhibiting uptake of iron, PZP acts as an iron chelator, and we present evidence that the compound restricts mycobacterial growth by chelating intrabacterial iron. Thus, we have unraveled the unexpected mechanism of a novel antimycobacterial compound. PMID:25645825

  12. Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations.

    PubMed Central

    Moghazeh, S L; Pan, X; Arain, T; Stover, C K; Musser, J M; Kreiswirth, B N

    1996-01-01

    A collection of 24 rifampin-resistant clinical isolates of Mycobacterium tuberculosis with characterized RNA polymerase beta-subunit (rpoB) gene mutations was tested against the antimycobacterial agents rifampin, rifapentine, and KRM-1648 to correlate levels of resistance with specific rpoB genotypes. The results indicate that KRM-1648 is more active in vitro than rifampin and rifapentine, and its ability to overcome rifampin resistance in strains with four different genetic alterations may prove to be useful in understanding structure-function relationships. PMID:8913484

  13. Antimycobacterial Activity of a New Peptide Polydim-I Isolated from Neotropical Social Wasp Polybia dimorpha.

    PubMed

    das Neves, Rogerio Coutinho; Trentini, Monalisa Martins; de Castro e Silva, Juliana; Simon, Karina Smidt; Bocca, Anamelia Lorenzetti; Silva, Luciano Paulino; Mortari, Marcia Renata; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2016-01-01

    Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40-90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment.

  14. Synthesis and Antimycobacterial Activity of some Triazole Derivatives–New Route to Functionalized Triazolopyridazines

    PubMed Central

    Tehrani, Kamaleddin Haj Mohammad Ebrahim; Mashayekhi, Vida; Azerang, Parisa; Minaei, Somayeh; Sardari, Soroush; Kobarfard, Farzad

    2015-01-01

    A series of cyclic analogues of bioactive thiosemicarbazide derivatives have been synthesized as potential antimycobacterial agents. The 4-amino-1,2,4-triazole-5-thione analogues (Ia-f) were prepared by heating a mixture of thiocarbohydrzide and appropriate carboxylic acids. Reaction of thiocarbohydrazide with γ-ketoesters in the presence of sodium methoxide furnished triazolopyridazine derivatives IIa-b. Finally, condensation of 4-amino-1,2,4-triazole-5-thione with some aldehydes gave Schiff bases IIIa-e. After characterization by different spectroscopic and analytical methods, the derivatives were tested for their inhibitory activity against Mycobacterium bovis BCG. Among the derivatives, compound Ib proved to be the most potent derivatives with MIC value of 31.25 µg/mL. Given the fact that 4-amino-1,2,4-triazole-5-thiones Ia-f were the most active derivatives, it could be suggested that this group of derivatives have the potential to be considered as lead compounds for future optimization efforts. PMID:26185506

  15. Antimycobacterial Activity of a New Peptide Polydim-I Isolated from Neotropical Social Wasp Polybia dimorpha

    PubMed Central

    das Neves, Rogerio Coutinho; Trentini, Monalisa Martins; de Castro e Silva, Juliana; Simon, Karina Smidt; Bocca, Anamelia Lorenzetti; Silva, Luciano Paulino; Mortari, Marcia Renata; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2016-01-01

    Mycobacterium abscessus subsp. massiliense, a rapidly growing mycobacteria (RGM) that is becoming increasingly important among human infectious diseases, is virulent and pathogenic and presents intrinsic resistance to several antimicrobial drugs that might hamper their elimination. Therefore, the identification of new drugs to improve the current treatment or lower the risk of inducing resistance is urgently needed. Wasp venom primarily comprises peptides that are responsible for most of the biological activities in this poison. Here, a novel peptide Polydim-I, from Polybia dimorpha Neotropical wasp, was explored as an antimycobacterial agent. Polydim-I provoked cell wall disruption and exhibited non-cytotoxicity towards mammalian cells. Polydim-I treatment of macrophages infected with different M. abscessus subsp. massiliense strains reduced 40 to 50% of the bacterial load. Additionally, the Polydim-I treatment of highly susceptible mice intravenously infected with M. abscessus subsp. massiliense induced 0.8 to 1 log reduction of the bacterial load in the lungs, spleen, and liver. In conclusion, this is the first study to show the therapeutic potential of a peptide derived from wasp venom in treating mycobacteria infections. Polydim-I acts on the M. abscessus subsp. massiliense cell wall and reduce 40–90% of the bacterial load both in vitro and in vivo. The presented results encourage further studies on the use of Polydim-I as one of the components for M. abscessus subsp. massiliense treatment. PMID:26930596

  16. Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG.

    PubMed

    Gajadeera, Chathurada; Willby, Melisa J; Green, Keith D; Shaul, Pazit; Fridman, Micha; Garneau-Tsodikova, Sylvie; Posey, James E; Tsodikov, Oleg V

    2015-03-01

    Owing to the rise in drug resistance in tuberculosis combined with the global spread of its causative pathogen, Mycobacterium tuberculosis (Mtb), innovative anti mycobacterial agents are urgently needed. Recently, we developed a novel primase-pyrophosphatase assay and used it to discover inhibitors of an essential Mtb enzyme, primase DnaG (Mtb DnaG), a promising and unexplored potential target for novel antituberculosis chemotherapeutics. Doxorubicin, an anthracycline antibiotic used as an anticancer drug, was found to be a potent inhibitor of Mtb DnaG. In this study, we investigated both inhibition of Mtb DnaG and the inhibitory activity against in vitro growth of Mtb and M. smegmatis (Msm) by other anthracyclines, daunorubicin and idarubicin, as well as by less cytotoxic DNA intercalators: aloe-emodin, rhein and a mitoxantrone derivative. Generally, low-μM inhibition of Mtb DnaG by the anthracyclines was correlated with their low-μM minimum inhibitory concentrations. Aloe-emodin displayed threefold weaker potency than doxorubicin against Mtb DnaG and similar inhibition of Msm (but not Mtb) in the mid-μM range, whereas rhein (a close analog of aloe-emodin) and a di-glucosylated mitoxantrone derivative did not show significant inhibition of Mtb DnaG or antimycobacterial activity. Taken together, these observations strongly suggest that several clinically used anthracyclines and aloe-emodin target mycobacterial primase, setting the stage for a more extensive exploration of this enzyme as an antibacterial target.

  17. Antifungal, antibacterial and antimycobacterial activity of Entada abysinnica Steudel ex A. Rich (Fabaceae) methanol extract

    PubMed Central

    Mariita, Richard M.; Orodho, John A.; Okemo, Paul O.; Mbugua, Paul K.

    2010-01-01

    The purpose of the study was to investigate the antifungal, antibacterial and antimycobacterial properties of methanol extract of Entada abysinnica steudel ex. A. Rich (Fabaceae) leaves used by herbalists from the Lake Victoria region, Kenya. The extract was tested against four strains of mycobacteria (Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium fortuitum, and Mycobacterium smegmatis) using BACTEC Mycobacteria Growth Indicator Tube (MGIT) 960 system and the proportional method. Standard procedures were used to determine the zones of inhibition, minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBCs/MFCs) for Candida albicans, Salmonella typhi, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. The extract showed activity against some mycobacteria strains, especially M. tuberculosis. It also showed strong antimicrobial activity (zones of inhibition were between 9.00 and 14.10 mm) against C. albicans, Sa. typhi, and St. aureus. The extract gave a better zone of inhibition against C. albicans than fluconazole whose zone of inhibition was 13.00 mm. The MICs and MBCs for C. albicans and Sa. typhi were good. The crude extracts were also analyzed for the presence of phytochemicals. Phytochemical screening indicated that the extract most abundantly contained tannins, saponins, and flavonoids. The data suggest that the methanolic leaves extract of E. abysinnica could be a rich source of antimicrobial agents, especially antifungals. The results further show that there is some merit in the use of the plant in alternative medical practices. However, bioassays of isolated compounds are underway and will be reported during subsequent communications. PMID:21808560

  18. Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds.

    PubMed

    Pérez-González, Mariana Z; Gutiérrez-Rebolledo, Gabriel A; Yépez-Mulia, Lilián; Rojas-Tomé, Irma S; Luna-Herrera, Julieta; Jiménez-Arellanes, María A

    2017-05-01

    Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects. Chemical identification of isolated compounds was performed by (1)H- and (13)C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice. Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone were the main compounds isolated. The CHCl3:MeOH extract showed antiprotozoal (IC50≤65.29μg/mL), antimycobacterial (MIC≤50μg/mL), and anti-inflammatory activities (ED50=1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25μg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC50≤71.70μg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxy-flavanone were more active than the extract against E

  19. Differential characterization using readily accessible NMR experiments of novel N- and O-alkylated quinolin-4-ol, 1,5-naphthyridin-4-ol and quinazolin-4-ol derivatives with antimycobacterial activity.

    PubMed

    Pitta, Eleni; Balabon, Olga; Rogacki, Maciej K; Gómez, Jesús; Cunningham, Fraser; Joosens, Jurgen; Augustyns, Koen; van der Veken, Pieter; Bates, Robert

    2017-01-05

    During the construction of bioactive molecules, regioselective alkylation of heterocyclic, N/O ambident nucleophiles is a frequently encountered synthetic transformation. In this framework, specific attention is required to unambiguously determine the structures of obtained reaction products. As part of our project on quinoloxyacetamide based antimycobacterial agents, a series of N- or O- alkylated quinolin-4-ol, 1,5-naphthyridin-4-ol and quinazolin-4-ol derivatives were prepared during the course of which we observed unexpected selectivity issues. After finding that no consistent procedure existed in the literature for assigning regioisomers of this type, we applied three readily accessible NMR experiment types ((13)C NMR, HSQC/HMBC and NOE) to resolve any uncertainties regarding the obtained regioisomeric structures. Furthermore, the antimycobacterial activity of all final compounds was evaluated with the best compound 23 showing potent antitubercular activity (MIC = 1.25 μM) without cytotoxic effects.

  20. Preliminary antimycobacterial study on selected Turkish plants (Lamiaceae) against Mycobacterium tuberculosis and search for some phenolic constituents

    PubMed Central

    2013-01-01

    Background The global resurgence of tuberculosis is a significant threat. Lamiaceae members have been used in folk remedies for centuries. This study was designed to assess the in-vitro antimycobacterial activity of eighteen crude extracts from six plants (Lamiaceae) and to characterize their phenolic and flavonoid compounds. Methods Six Turkish medicinal plants of the family Lamiaceae (Stachys tmolea Boiss., Stachys thirkei C. Koch, Ballota acetabulosa (L.) Benth., Thymus sipthorpii Benth., Satureja aintabensis P.H. Davis, and Micromeria juliana (L.) Benth. ex Reich.) were collected in 2009 – 2010. Dried and crushed plant samples were subjected to sequential extraction with petroleum ether, ethyl acetate, and methanol in order of increasing polarity. A broth microdilution method was employed to screen extracts against four mycobacterial strains of Mycobacterium tuberculosis. Phenolic and flavonoid compounds were characterized by liquid chromatography–mass spectrometry. Results S. aintabensis, T. sibthorpii, and M. juliana were found to develop considerable activity against the four strains of M. tuberculosis with the minimal inhibitory concentrations value of 12.5-100 μg/ml. S. aintabensis and T. sibthorpii extracts killed M. tuberculosis with the minimum bactericidal concentration value of 50–800 μg/ml. On the basis of these prominent antimycobacterial activity, we suggest that they could be a source of natural anti-tuberculosis agents. Conclusion S. aintabensis and T. sibthorpii showed activity by killing Mycobacteria strains. The major phenolic compound was rosmarinic for T. sibthorpii and S. aintabensis. Flavonoids might be “a modal” for the drug design. PMID:24359458

  1. A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.

    PubMed

    Wagh, Sandip J; Chowdhury, Raghunath; Mukhopadhyay, Sulekha; Ghosh, Sunil K

    2013-11-01

    Deuterium-labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl-d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2 O combination with high yield and isotopic purity. The 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one was obtained from the adduct of methyl-d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran-2-one is the precursor for geminal (2) H2 -labeled (+)-4-hydroxy-6-undecyl-tetrahydropyran-2-one, an advanced intermediate for gem-dideutero (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide syntheses. Copyright © 2013 John Wiley & Sons, Ltd.

  2. The complex mechanism of antimycobacterial action of 5-fluorouracil.

    PubMed

    Singh, Vinayak; Brecik, Miroslav; Mukherjee, Raju; Evans, Joanna C; Svetlíková, Zuzana; Blaško, Jaroslav; Surade, Sachin; Blackburn, Jonathan; Warner, Digby F; Mikušová, Katarína; Mizrahi, Valerie

    2015-01-22

    A combination of chemical genetic and biochemical assays was applied to investigate the mechanism of action of the anticancer drug 5-fluorouracil (5-FU), against Mycobacterium tuberculosis (Mtb). 5-FU resistance was associated with mutations in upp or pyrR. Upp-catalyzed conversion of 5-FU to FUMP was shown to constitute the first step in the mechanism of action, and resistance conferred by nonsynonymous SNPs in pyrR shown to be due to derepression of the pyr operon and rescue from the toxic effects of FUMP and downstream antimetabolites through de novo production of UMP. 5-FU-derived metabolites identified in Mtb were consistent with the observed incorporation of 5-FU into RNA and DNA and the reduced amount of mycolyl arabinogalactan peptidoglycan in 5-FU-treated cells. Conditional depletion of the essential thymidylate synthase ThyX resulted in modest hypersensitivity to 5-FU, implicating inhibition of ThyX by fluorodeoxyuridylate as a further component of the mechanism of antimycobacterial action of this drug.

  3. Air Pollution Particulate Matter Alters Antimycobacterial Respiratory Epithelium Innate Immunity

    PubMed Central

    Rivas-Santiago, César E.; Sarkar, Srijata; Cantarella, Pasquale; Osornio-Vargas, Álvaro; Quintana-Belmares, Raúl; Meng, Qingyu; Kirn, Thomas J.; Ohman Strickland, Pamela; Chow, Judith C.; Watson, John G.; Torres, Martha

    2015-01-01

    Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB. PMID:25847963

  4. Air pollution particulate matter alters antimycobacterial respiratory epithelium innate immunity.

    PubMed

    Rivas-Santiago, César E; Sarkar, Srijata; Cantarella, Pasquale; Osornio-Vargas, Álvaro; Quintana-Belmares, Raúl; Meng, Qingyu; Kirn, Thomas J; Ohman Strickland, Pamela; Chow, Judith C; Watson, John G; Torres, Martha; Schwander, Stephan

    2015-06-01

    Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.

  5. Determining the mode of action of anti-mycobacterial C17 diyne natural products using expression profiling: evidence for fatty acid biosynthesis inhibition.

    PubMed

    Li, Haoxin; Cowie, Andrew; Johnson, John A; Webster, Duncan; Martyniuk, Christopher J; Gray, Christopher A

    2016-08-11

    The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, their mode of action remains largely undetermined in microbes. Gene expression profiling was therefore used to determine the transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol and panaxydol to better characterize the mode of action of these C17 diynes. Our analyses identified 704 and 907 transcripts that were differentially expressed in M. smegmatis after treatment with falcarinol and panaxydol respectively. Principal component analysis suggested that the C17 diynes exhibit a mode of action that is distinct to commonly used antimycobacterial drugs. Functional enrichment analysis and pathway enrichment analysis revealed that cell processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid synthesis were responsive to falcarinol and panaxydol treatment at the transcriptome level in M. smegmatis. The modes of action of the two C17 diynes were also predicted through Prediction of Activity Spectra of Substances (PASS). Based upon convergence of these three independent analyses, we hypothesize that the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid synthesis, in mycobacteria. Based on transcriptomic responses, it is suggested that the C17 diynes act differently than other anti-mycobacterial compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis.

  6. Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl-4(1H)-quinolones

    PubMed Central

    Wube, Abraham A.; Hüfner, Antje; Thomaschitz, Christina; Blunder, Martina; Kollroser, Manfred; Bauer, Rudolf; Bucar, Franz

    2011-01-01

    A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11–13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0 mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure–activity relationships. PMID:21106378

  7. Malabsorption of antimycobacterial drugs as a cause of treatment failure in tuberculosis.

    PubMed

    Bento, João; Duarte, Raquel; Brito, Maria Céu; Leite, Sónia; Lobato, Maria Rosário; Caldeira, Maria do Carmo; Carvalho, Aurora

    2010-09-29

    Malabsorption of oral antimycobacterial drugs is a rare cause of treatment failure in tuberculosis (TB). Several predisposing comorbidities have been recognised. HIV infection is the most important risk factor referred in the literature. There are few reports about antimycobacterial drugs malabsorption, particularly in the absence of predisposing comorbidities. The authors present a clinical case of oral treatment failure in TB due to malabsorption; however, what caused the failure remained unclear. Possible causes of malabsorption are discussed under various sections. Purpose of this case report is to point to this rare situation that can easily go unnoticed unless a very high level of suspicion is present.

  8. Design, Synthesis, and Antimycobacterial Activity of Novel Theophylline-7-Acetic Acid Derivatives With Amino Acid Moieties.

    PubMed

    Stavrakov, Georgi; Valcheva, Violeta; Voynikov, Yulian; Philipova, Irena; Atanasova, Mariyana; Konstantinov, Spiro; Peikov, Plamen; Doytchinova, Irini

    2016-03-01

    The theophylline-7-acetic acid (7-TAA) scaffold is a promising novel lead compound for antimycobacterial activity. Here, we derive a model for antitubercular activity prediction based on 14 7-TAA derivatives with amino acid moieties and their methyl esters. The model is applied to a combinatorial library, consisting of 40 amino acid and methyl ester derivatives of 7-TAA. The best three predicted compounds are synthesized and tested against Mycobacterium tuberculosis H37Rv. All of them are stable, non-toxic against human cells and show antimycobacterial activity in the nanomolar range being 60 times more active than ethambutol. © 2015 John Wiley & Sons A/S.

  9. Malabsorption of antimycobacterial drugs as a cause of treatment failure in tuberculosis

    PubMed Central

    Bento, João; Duarte, Raquel; Brito, Maria Céu; Leite, Sónia; Lobato, Maria Rosário; do Carmo Caldeira, Maria; Carvalho, Aurora

    2010-01-01

    Malabsorption of oral antimycobacterial drugs is a rare cause of treatment failure in tuberculosis (TB). Several predisposing comorbidities have been recognised. HIV infection is the most important risk factor referred in the literature. There are few reports about antimycobacterial drugs malabsorption, particularly in the absence of predisposing comorbidities. The authors present a clinical case of oral treatment failure in TB due to malabsorption; however, what caused the failure remained unclear. Possible causes of malabsorption are discussed under various sections. Purpose of this case report is to point to this rare situation that can easily go unnoticed unless a very high level of suspicion is present. PMID:22778380

  10. Agents.

    PubMed

    Chambers, David W

    2002-01-01

    Although health care is inherently an economic activity, it is inadequately described as a market process. An alternative, grounded in organizational economic theory, is to view professionals and many others as agents, contracted to advance the best interests of their principals (patients). This view untangles some of the ethical conflicts in dentistry. It also helps identify major controllable costs in dentistry and suggests that dentists can act as a group to increase or decrease agency costs, primarily by controlling the bad actors who damage the value of all dentists.

  11. Antimycobacterial, anti-inflammatory and genotoxicity evaluation of plants used for the treatment of tuberculosis and related symptoms in South Africa.

    PubMed

    Madikizela, B; Ndhlala, A R; Finnie, J F; Van Staden, J

    2014-04-28

    Emergence of drug-resistant tuberculosis strains and long duration of treatment has established an urgent need to search for new effective agents. The great floral diversity of South Africa has potential for producing new bioactive compounds, therefore pharmacological screening of plant extracts within this region offers much potential. To assess the in vitro antimycobacterial, anti-inflammatory and genotoxicity activity of selected plants that are used for the treatment of TB and related symptoms in South Africa. Ground plant materials from 10 plants were extracted sequentially with four solvents (petroleum ether, dichloromethane, 80% ethanol and water) and a total of 68 extracts were produced. A broth microdilution method was used to screen extracts against Mycobacterium tuberculosis H37Ra. The cyclooxygenase-2 (COX-2) enzyme was used to evaluate the anti-inflammatory activity of the extracts and the Salmonella microsome assay using two Salmonella typhimurium strains (TA98 and TA100) to establish genotoxicity. Six out of 68 extracts showed good antimycobacterial activity. Three extracts showed good inhibition (>70%) of COX-2 enzyme. All the extracts tested were non-genotoxic against the tested Salmonella strains. The results observed in this study indicate that some of the plants such as Abrus precatorius subsp. africanus, Ficus sur, Pentanisia prunelloides and Terminalia phanerophlebia could be investigated further against drug-resistant TB strains. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Synthesis and antimycobacterial activity of azetidine-, quinazoline-, and triazolo-thiadiazole-containing pyrazines.

    PubMed

    Bonde, Chandrakant G; Peepliwal, Ashok; Gaikwad, Naresh J

    2010-04-01

    The re-emergence of tuberculosis (TB) as a global health problem over the past few decades, accompanied by the rise of drug-resistant strains of Mycobacterium tuberculosis, emphasizes the need for the discovery of new therapeutic drugs against this disease. The emerging serious problem both in terms of TB control and clinical management prompted us to synthesize a novel series of N-[2-(substituted aryl)-3-chloro-4-oxoazetidin-1-yl]-2-(pyrazin-2-yloxy)acetamide, 6-(substituted aryl)-3-[(pyrazin-2-yloxy)methyl][1,2,4]triazolo[3,4-b][1,3,4]thiadiazole, and N-[6-({2-[(pyrazin-2-yloxy)acetyl] hydrazino}sulfonyl)-2-methyl-4-oxo-1,4-dihydroquinazolin-3(2H)yl]-substituted aryl sulfonamides. The compounds were synthesized using the appropriate synthetic route. All synthesized compounds were assayed in vitro for antimycobacterial activity against the H37 Rv strain of Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for the reference standards. The compound which exhibited good antimycobacterial activity contains the substituents fluorine and methoxy. These electron-withdrawing or -donating substituents amend the lipophilicity of the test compounds which, in turn, alter the permeability across the bacterial cell membrane. Compounds 28, 37, and 43 showed good antimycobacterial activity while compound 51 showed a promising antimycobacterial activity.

  13. Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Ocotea notata from Brazilian Restinga

    PubMed Central

    Costa, Isabela Francisca Borges; Calixto, Sanderson Dias; Heggdorne de Araujo, Marlon; Konno, Tatiana Ungaretti Paleo; Tinoco, Luzineide Wanderley; Guimarães, Denise Oliveira; Lasunskaia, Elena B.; Leal, Ivana Ramos Correa; Muzitano, Michelle Frazão

    2015-01-01

    The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti-inflammatory activity with inhibition of COX-1, COX-2, and LOX-5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid-liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively. PMID:25789338

  14. Antimycobacterial screening of traditional medicinal plants using the microplate resazurin assay.

    PubMed

    Webster, Duncan; Lee, Timothy D G; Moore, Jill; Manning, Tracy; Kunimoto, Dennis; LeBlanc, Darren; Johnson, John A; Gray, Christopher A

    2010-06-01

    Multidrug-resistant Mycobacterium tuberculosis strains have rapidly become a global health concern. North American First Nations communities have used traditional medicines for generations to treat many pulmonary infections. In this study, we evaluated the antimycobacterial activity of 5 medicinal plants traditionally used as general therapeutics for pulmonary illnesses and specifically as treatments for tuberculosis. Aqueous extracts of Aralia nudicaulis, Symplocarpus foetidus, Heracleum maximum, Juniperus communis, and Acorus calamus were screened for antimycobacterial activity against Bacillus Calmette-Guérin, Mycobacterium avium, and M. tuberculosis H37Ra using the colorimetric microplate resazurin assay. Extracts of Acorus calamus and H. maximum root demonstrated significant antimycobacterial activity comparable to that of the rifampin control (2 microg/mL). Evaluation of the cytotoxicity of these 2 extracts using the MTT assay also showed that the extracts were less toxic to 3 human cell lines than was the DMSO positive control. This study demonstrates that aqueous extracts of the roots of H. maximum and Acorus calamus possess strong in vitro antimycobacterial activity, validates traditional knowledge, and provides potential for the development of urgently needed novel antituberculous therapeutics.

  15. Novel nicotine analogues with potential anti-mycobacterial activity.

    PubMed

    Gandhi, Paresh T; Athmaram, Thimmasandra Narayanappa; Arunkumar, Gundaiah Ramesh

    2016-04-15

    Tuberculosis (TB) is the second leading lethal infectious disease in the world after acquired immuno deficiency (AIDs). We have developed a series of twenty-five novel nicotine analogues with de-addiction property and tested them for their activity against Mycobacterium tuberculosis (MTB). In an effort to increase the specificity of action and directing nicotine analogues to target MTB, four promising compounds were further optimized via molecular docking studies against the Dihydrofolate reductase of MTB. After lead optimization, one nicotine analogue [3-(5-(3fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one] exhibited minimum inhibitory concentration of 1 μg/mL (2.86 nM) against M. tuberculosis (H37Rv strain), a human pathogenic strain of clinically significant importance. Pharmacokinetic analysis of [3-(5-(3fluorophenyl)nicotinoyl)-1methylpyrrolidin-2-one] with lowest MIC value via oral route in Wistar rats revealed that at a dosage of 5 mg/kg body weight gave a maximum serum drug concentration (Cmax) of 2.86 μg/mL, Tmax of one hour and a half-life (T1/2) of more than 24 h and Volume of distribution (Vd) of 27.36 L. Whereas the parenteral (intra venous) route showed a Cmax of 3.37 μg/mL, Tmax of 0.05 h, T1/2 of 24 h and Vd equivalent to 23.18 L. The acute oral toxicity and repeated oral toxicity studies in female Wistar rats had an LD50>2000 mg/kg body weight. Our data suggests that nicotine derivatives developed in the present study has good metabolic stability with tunable pharmacokinetics (PK) with therapeutic potential to combat MTB. However, further in vivo studies for anti-tuberculosis activity and elucidation of mode of action could result in more promising novel drug for treating MTB. To the best of our knowledge this is the first report revealing the anti-mycobacterial potential of nicotine analogue at potential therapeutic concentrations.

  16. Isolation of (-)-avenaciolide as the antifungal and antimycobacterial constituent of a Seimatosporium sp. Endophyte from the medicinal plant Hypericum perforatum .

    PubMed

    Clark, Trevor N; Bishop, Amanda I; McLaughlin, Mark; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2014-10-01

    An extract of Seimatosporium sp., an endophyte from the Canadian medicinal plant Hypericum perforatum, exhibited significant antifungal and antimycobacterial activity against Candida albicans and Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation led to the isolation of (-)-avenaciolide as the only bioactive constituent of the extract. This is the first report of both the antimycobacterial activity of avenaciolide and its isolation from a Seimatosporium sp. fungus.

  17. In vitro anti-mycobacterial activity of nine medicinal plants used by ethnic groups in Sonora, Mexico

    PubMed Central

    2013-01-01

    Background Sonoran ethnic groups (Yaquis, Mayos, Seris, Guarijíos, Pimas, Kikapúes and Pápagos) use mainly herbal based preparations as their first line of medicinal treatment. Among the plants used are those with anti-tuberculosis properties; however, no formal research is available. Methods Organic extracts were obtained from nine medicinal plants traditionally used by Sonoran ethnic groups to treat different kinds of diseases; three of them are mainly used to treat tuberculosis. All of the extracts were tested against Mycobacterium tuberculosis H37Rv using the Alamar Blue redox bioassay. Results Methanolic extracts from Ambrosia confertiflora, Ambrosia ambrosioides and Guaiacum coulteri showed minimal inhibitory concentration (MIC) values of 200, 790 and 1000 μg/mL, respectively, whereas no effect was observed with the rest of the methanolic extracts at the concentrations tested. Chloroform, dichloromethane, and ethyl acetate extracts from Ambrosia confertiflora showed a MIC of 90, 120 and 160 μg/mL, respectively. Conclusions A. confertiflora and A. ambrosioides showed the best anti-mycobacterial activity in vitro. The activity of Guaiacum coulteri is consistent with the traditional use by Sonoran ethnic groups as anti-tuberculosis agent. For these reasons, it is important to investigate a broader spectrum of medicinal plants in order to find compounds active against Mycobacterium tuberculosis. PMID:24267469

  18. Antimycobacterial activity of chemically defined natural substances from the Caribbean flora in Guadeloupe.

    PubMed

    Rastogi, N; Abaul, J; Goh, K S; Devallois, A; Philogène, E; Bourgeois, P

    1998-04-01

    Eight chemically defined, naturally occurring compounds were extracted from the tropical flora of the Caribbean island of Guadeloupe: pilocarpine, an alkaloid from Pilocarpus racemosus; heraclenol and isomeranzin, coumarins from Triphasia trifolia; lochnerin, an indole alkaloid from Rauwolfia biauriculata; ibogaine and voacangine, indole alkaloids from Tabernaemontana citrifolia; texalin, an oxazole from Amyris elemifera; and canellal, a sesquiterpene dialdehyde from Canella winterana. An essential oil fraction from Canella winterana was also tested. The antimycobacterial activity of these substances was tested against Mycobacterium tuberculosis, M. avium and M. kansasii using the Middlebrook 7H11 agar medium, the Bactec 460-TB radiometric methodology, and determination of bacterial viable counts. Three compounds, namely ibogaine, voacangine and texalin, showed antimycobacterial activity. Investigations on the structure-modification and structure-activity relationships of these compounds may help determine new targets for future drug development.

  19. Antimycobacterial activity of a Brevibacillus laterosporusstrain isolated from a moroccan soil.

    PubMed

    Hassi, Mohammed; Guendouzi, Souraya El; Haggoud, Abdelleatif; David, Susana; Ibnsouda, Saad; Houari, Abdellah; Iraqui, Mohammed

    2012-10-01

    The treatment of tuberculosis has become more difficult with the worldwide spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. Moreover, the prevalence of human disease caused by atypical mycobacteria has also increased in the past two decades and has further complicated the problem of the treatment of mycobacterial infections. It is therefore urgent to develop new highly active molecules against these bacteria. The present study reports the isolation from a Moroccan soil of a Bacillus strain that exhibits an important antimycobacterial activity. The strain was identified as Brevibacillus laterosporus using DNA sequencing of the 16S ribosomal RNA gene. The antimycobacterial activity was assigned to a substance with a protein nature. This nature was revealed using a liquid-liquid extraction with organic solvents, precipitation with ammonium sulfate and treatment with a protease. This study suggested the identification and the characterization of this active metabolite enabling therapeutic investigations further.

  20. Antimycobacterial activity of novel hydrazide-hydrazone derivatives with 2H-chromene and coumarin scaffold.

    PubMed

    Angelova, Violina T; Valcheva, Violeta; Vassilev, Nikolay G; Buyukliev, Rosen; Momekov, Georgi; Dimitrov, Ivan; Saso, Luciano; Djukic, Mirjana; Shivachev, Boris

    2017-01-15

    This study reports the synthesis of new 2H-chromene or coumarin based acylhydrazones, which were evaluated for their in vitro antimycobacterial activity against reference strain Mycobacterium tuberculosis H37Rv and compared to the first-line antituberculosis drugs, isoniazid (INH) and ethambutol (EMB). The most active compounds 7m (MIC 0.13μM), 7o (MIC 0.15μM) and 7k (MIC 0.17μM) demonstrated antimycobacterial activity at submicromolar concentration level and remarkably minimal associated cytotoxicity in the human embryonic kidney cell line HEK-293T. Structure-activity relationship for this class of compounds has been established. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

    PubMed

    Li, Haoxin; Jean, Stéphanie; Webster, Duncan; Robichaud, Gilles A; Calhoun, Larry A; Johnson, John A; Gray, Christopher A

    2015-11-25

    Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively).

  2. Evaluation of antimycobacterial, leishmanicidal and antibacterial activity of three medicinal orchids of Arunachal Pradesh, India.

    PubMed

    Bhatnagar, Manisha; Sarkar, Nandan; Gandharv, Nigam; Apang, Ona; Singh, Sarman; Ghosal, Sabari

    2017-08-01

    The ethnic population of Arunachal Pradesh uses a number of orchids as such, or in decoction for various ailments. Three untapped orchids namely, Rhynchostylis retusa, Tropidia curculioides and Satyrium nepalense, traditionally used in tuberculosis, asthma and cold stage of malaria in folk medicine, were selected for the present study. Dried material of each plant was divided into three parts. Solvent extraction and fractionation afforded altogether 30 extracts and fractions, which were evaluated against Mycobacterium tuberculosis (H37Rv and MDR strain) for antimycobacterial activity; promastigotes and amastigotes of Leishmania donovani for leishmanicidal activity and two gram positive and three gram negative clinical isolates for antibacterial activity. The most significant antimycobacterial activity was observed with n-hexane fraction of the flower of Satyrium nepalense with MIC of 15.7 μg/mL. The most promising leishmanicidal activity was observed with diethyl ether fraction of the roots of Rhynchostylis retusa with IC50 values of 56.04 and 18.4 μg/mL against promastigotes and intracellular amastigotes respectively. Evaluation of antibacterial activity identified S. nepalense flower n-hexane and R. retusa roots diethyl ether as potential fractions with MIC values of ≤100 μg/mL against selected clinical isolates. This is the first report of the plants possessing antimycobacterial and leishmanicidal activity. The investigation resulted in identification of S. nepalense as the most promising plant, which possessed all three activities in significant proportion. This laboratory outcome could be translated to marketable pharmaceutical products and also to produce maximum benefits to the local of nearby area. Antimycobacterial and leishmanicidal activity of medicinal orchids.

  3. The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins.

    PubMed

    O'Neill, Taryn; Johnson, John A; Webster, Duncan; Gray, Christopher A

    2013-05-02

    Heracleum maximum is amongst the most commonly used plants by the indigenous peoples of North America. The First Nations of the eastern Canada use infusions of Heracleum maximum roots for the treatment of respiratory ailments including tuberculosis. Previous investigations of extracts derived from the roots of Heracleum maximum have shown it to possess antimycobacterial activity. To isolate and identify antimycobacterial constituents from the roots of Heracleum maximum. A methanolic extract of Heracleum maximum roots was subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry. The polyacetylene (3R,8S)-falcarindiol and the furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were isolated from the Heracleum maximum root extract. (3R,8S)-Falcarindiol and 6-isopentenyloxyisobergapten exhibited MICs of 24 μM and 167 μM and IC50s of 6 μM and 27 μM against Mycobacterium tuberculosis H37Ra respectively. The remaining furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, and isopimpinellin were less active, with MICs of 925, 1850, 2149, 1859, 812 and 1625 μM and IC50s of 125, 344, 350, 351, 389 and 406 μM. (3R,8S)-Falcarindiol, bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were identified as the principal constituents responsible for the antimycobacterial activity of the roots of Heracleum maximum. This work supports the ethnopharmacological use of Heracleum maximum by Canadian First Nations and Native American communities as a treatment for infectious diseases, specifically tuberculosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes

    PubMed Central

    Jiménez-Arellanes, Adelina; León-Díaz, Rosalba; Meckes, Mariana; Tapia, Amparo; Molina-Salinas, Gloria María; Luna-Herrera, Julieta; Yépez-Mulia, Lilián

    2012-01-01

    We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 μg mL−1; the pure compounds eupomatenoid-1, fargesin, and (8R,8′R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 μg mL−1), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 μg mL−1). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC50 < 0.624 μg mL−1); in contrast, fargesin and (8R,8′R,9R)-cubebin were moderately active (IC50 < 275 μg mL−1). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity. PMID:22454670

  5. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity.

    PubMed

    Mantu, Dorina; Antoci, Vasilichia; Moldoveanu, Costel; Zbancioc, Gheorghita; Mangalagiu, Ionel I

    2016-01-01

    The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

  6. The influence of functional groups on the permeation and distribution of antimycobacterial rhodamine chelators.

    PubMed

    Moniz, T; Leite, A; Silva, T; Gameiro, P; Gomes, M S; de Castro, B; Rangel, M

    2017-10-01

    We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Antimycobacterial activity of Juglans regia, Juglans mollis, Carya illinoensis and Bocconia frutescens.

    PubMed

    Cruz-Vega, Delia Elva; Verde-Star, María Julia; Salinas-González, Noé; Rosales-Hernández, Bibiana; Estrada-García, Iris; Mendez-Aragón, Patricia; Carranza-Rosales, Pilar; González-Garza, María Teresa; Castro-Garza, Jorge

    2008-04-01

    Mycobacterium tuberculosis is a serious worldwide health threat, killing almost 2 million people per year. Alternative antimycobacterial drugs are urgently needed; studies have shown that medicinal plants traditionally used to treat respiratory diseases are a potential source of compounds to treat tuberculosis. This paper studied the antimycobacterial activity of 28 extracts from four different plant species that have been used in traditional Mexican medicine to treat tuberculosis. Bark and leaf crude extracts of Juglans regia L., Juglans mollis Engelm., Carya illinoensis (Wangenh) K. Koch and Bocconia frutescens showed in vitro anti-M. tuberculosis activity. Hexane bark extracts from C. illinoensis, J. mollis and J. regia were the most active with a minimal inhibitory concentration (MIC) of 31, 50 and 100 microg/mL, respectively. Ethanol bark extracts from C. illinoensis and J. mollis showed activity at 100 and 125 microg/mL, respectively. Leaf extracts had the lowest activity. Methanol and hexane leaves extracts from B. frutescens had a MIC of 125 microg/mL. None of the aqueous extracts showed antimycobacterial activity. (c) 2008 John Wiley & Sons, Ltd.

  8. Discovery of target based novel pyrrolyl phenoxy derivatives as antimycobacterial agents: an in silico approach.

    PubMed

    More, Uttam A; Joshi, Shrinivas D; Aminabhavi, Tejraj M; Kulkarni, Venkatrao H; Badiger, Aravind M; Lherbet, Christian

    2015-04-13

    A new series of pyrrolyl phenoxy derivatives bearing alkoxy linker were synthesized and evaluated for anti-tubercular activity (anti-TB) against Mycobacterium tuberculosis. Molecular modeling, pharmacophore constructed using GALAHAD to produce an effective alignment of data set and evaluated by Pareto ranking. The pharmacophore features were filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis, which is one of the key enzymes involved in type II fatty acid biosynthesis pathway of M. tuberculosis. Compound 6a27 showed the H-bond with NAD(+), whereas compound 6a26 showed H-bonds with Tyr158, Thr196, Met199 and NAD(+) that fitted well into the binding pocket of target InhA. The alkoxy linker bridge and acceptor groups with benzene ring were advantageous for anti-TB activity, which merit further investigation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Suppression of the NF-κB Pathway by Diesel Exhaust Particles Impairs Human Antimycobacterial Immunity

    PubMed Central

    Sarkar, Srijata; Song, Youngmia; Sarkar, Somak; Kipen, Howard M.; Laumbach, Robert J.; Zhang, Junfeng (Jim); Strickland, Pamela A. Ohman; Gardner, Carol R.; Schwander, Stephan

    2012-01-01

    Epidemiological studies suggest that chronic exposure to air pollution increases susceptibility to respiratory infections including tuberculosis in humans. A possible link between particulate air pollutant exposure and antimycobacterial immunity has not been explored in human primary immune cells. We hypothesized that exposure to diesel exhaust particles (DEP), a major component of urban fine particulate matter, suppresses antimycobacterial human immune effector cell functions by modulating TLR-signaling pathways and NF-κB activation. We show that DEP and H37Ra, an avirulent laboratory strain of M.tb, were both taken up by the same peripheral human blood monocytes. To examine the effects of DEP on M.tb-induced production of cytokines, PBMC were stimulated with DEP and M.tb or PPD (purified protein derivative). The production of M.tb and PPD-induced IFN-γ, TNF-α, IL-1β, and IL-6 was reduced in a DEP dose-dependent manner. In contrast, the production of anti-inflammatory IL-10 remained unchanged. Furthermore, DEP stimulation prior to M.tb infection altered the expression of TLR 3, 4, 5, 7 and 10 mRNAs and of a subset of M.tb-induced host genes including inhibition of expression of many NF-κB (e.g. CSF3, IFNG, IFNA, IFNB, IL1A, IL6, NFKBIA) and IRF (e.g. IFNG, IFNA1, IFNB1, CXCL10) pathway target genes. We propose that DEP down-regulate M.tb-induced host gene expression via MyD88-dependent (IL6, IL1A, PTGS2) as well as MyD88-independent (IFNA, IFNB) pathways. Pre-stimulation of PBMC with DEP suppressed the expression of proinflammatory mediators upon M.tb infection inducing a hypo-responsive cellular state. Therefore, DEP alters crucial components of antimycobacterial host immune responses, providing a possible mechanism by which air pollutants alter antimicrobial immunity. PMID:22345648

  10. Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity.

    PubMed

    Dow, Mark; Marchetti, Francesco; Abrahams, Katherine A; Vaz, Luis; Besra, Gurdyal S; Warriner, Stuart; Nelson, Adam

    2017-05-29

    A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  11. Antimicrobial and Antimycobacterial Activity of Cyclostellettamine Alkaloids from Sponge Pachychalina sp.

    PubMed Central

    de Oliveira, Jaine H. H. L.; Seleghim, Mirna H. R.; Timm, Christoph; Grube, Achim; Köck, Matthias; Nascimento, Gislene G.F.; Martins, Ana Claudia T.; Silva, Elissa G. O.; de Souza, Ana Olívia; Minarini, Paulo R. R.; Galetti, Fabio C. S.; Silva, Célio L.; Hajdu, Eduardo; Berlinck, Roberto G. S.

    2006-01-01

    Cyclostellettamines A – F (1 – 6) isolated from the sponge Pachychalina sp. and cyclostellettamines G - I, K and L (7 – 11) obtained by synthesis were evaluated in bioassays of antimicrobial activity against susceptible and antibiotic-resistant Staphylococcus aureus, Pseudomonas aeruginosa and antibiotic-susceptible Escherichia coli and Candida albicans, as well as in antimycobacterial activity against Mycobacterium tuberculosis H37Rv bioassays. The results obtained indicated that cyclostellettamines display different antimicrobial activity depending on the alkyl-chain size, suggesting that, if a mechanism-of action is implied, it is dependent on the distance between the two pyridinium moieties of cyclostellettamines.

  12. Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

    PubMed

    Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

    2013-05-01

    Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance.

  13. Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

    PubMed

    Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

    2015-01-01

    Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

  14. Antimycobacterial activity of constituents from Foeniculum vulgare var. dulce grown in Mexico.

    PubMed

    Esquivel-Ferriño, Patricia C; Favela-Hernández, Juan Manuel J; Garza-González, Elvira; Waksman, Noemí; Ríos, María Yolanda; del Rayo Camacho-Corona, María

    2012-07-13

    Bioassay guided fractionation of an antimycobacterial extract of Foeniculum vulgare var dulce (Apiaceae) led to the isolation and characterization of 5-hydroxyfurano-coumarin. The chemical structure of this compound was elucidated by 1H and 13C (1D and 2D) Nuclear Magnetic Resonance (NMR) spectroscopy. In addition, the active fractions were analyzed by GC-MS and seventy eight compounds were identified; the major compounds were 1,3-benzenediol, 1-methoxycyclohexene, o-cymene, sorbic acid, 2-hydroxy-3-methyl-2-cyclopenten-1-one, estragole, limonene-10-ol and 3-methyl-2-cyclopenten-1-one. Twenty compounds identified in the active fractions were tested against one sensitive and three MDR strains of Mycobacterium tuberculosis using the Alamar Blue microassay. Compounds that showed some degree of antimycobacterial activity against all strains tested were the following: linoleic acid (MIC 100 µg/mL), oleic acid (MIC 100 µg/mL), 1,3-benzenediol (MIC 100-200 µg/mL), undecanal (MIC 50-200 µg/mL), and 2,4-undecadienal (MIC 25-50 µg/mL), the last being the most active compound. To our knowledge, this is the first report of the presence of 5-hydroxy-furanocoumarin in F. vulgare.

  15. Synthesis and in vitro antimycobacterial activity of balofloxacin ethylene isatin derivatives.

    PubMed

    Feng, Lian-Shun; Liu, Ming-Liang; Wang, Bo; Chai, Yun; Hao, Xue-Qin; Meng, Shuai; Guo, Hui-Yuan

    2010-08-01

    A series of novel balofloxacin ethylene isatin derivatives with remarkable improvement in lipophilicity, as compared to the parent compound balofloxacin, were designed, synthesized and characterized by (1)H NMR, MS and HRMS. These derivatives were initially evaluated for their in vitro antimycobacterial activity against M. phlei CMCC 93201 and M. smegmatis CMCC 93202. Compounds 3b, 3d, 3g-j and 3l were chosen for further evaluation their in vitro activity against MTB 09710 clinical isolate, and then compounds 3h and 3g against MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than balofloxacin against M. phlei CMCC 93201 and M. smegmatis CMCC 93202, but compounds 3g-j (MIC: <0.5-8 microg/mL) were more potent than balofloxacin (MIC: 16 microg/mL) against MTB 09710. In particular, compound 3h (MIC: 0.25- < 0.5 microg/mL) was found to be comparable to moxifloxacin, and >or=32 fold more potent than balofloxacin against MTB 09710 and MTB H37Rv ATCC 27294. The results demonstrated that the lipophilicity of the tested compounds was not the sole parameter affecting antimycobacterial activity, as well as the potential and importance of developing new fluoroquinolone derivatives against mycobacterial infections. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  16. New indolizines with phenanthroline skeleton: Synthesis, structure, antimycobacterial and anticancer evaluation.

    PubMed

    Danac, Ramona; Al Matarneh, Cristina M; Shova, Sergiu; Daniloaia, Teofil; Balan, Mihaela; Mangalagiu, Ionel I

    2015-05-15

    We report herein a feasible study concerning the design, synthesis, structure and in vitro antimycobacterial and anticancer activity of two new classes (containing four and five fused rings) of indolizine with phenanthroline skeleton. The preparation is straight and efficient, involving a Huisgen [3+2] dipolar cycloaddition of cycloimmonium ylides to alkynes or alkenes dipolarophiles. The cycloaddition reactions are highly stereo- or regioselective, according with the dipolarophiles nature. The structure of the new compounds was assigned unambiguously, X-ray analysis including. The primary antimycobacterial screening reveals that one of the thirteen tested compounds had a good activity against Mycobacterium tuberculosis H37Rv under aerobic conditions. The antiproliferative evaluation against a NCI 60 human tumor cell line panel, revealed that two indolizine with phenanthroline skeleton exhibit a selective and significant antitumor growth inhibitory activity against Breast Cancer (MCF7 and T-47D) and a slightly moderate activity against some forms of Leukemia, Non-Small Cell Lung Cancer, Renal Cancer and Breast Cancer (MDA-MB-468). The X-ray diffraction study of the indolizines with phenanthroline skeleton prove a flat coplanar structure which, corroborated with their anticancer activity, allow us to suggest that an interaction with DNA (via an intercalation mechanism) would be reasonable.

  17. Antimicrobial, antimycobacterial and antibiofilm properties of Couroupita guianensis Aubl. fruit extract

    PubMed Central

    2012-01-01

    Background Couroupita guianensis Aubl. (Lecythidaceae) is commonly called Ayahuma and the Cannonball tree. It is distributed in the tropical regions of northern South America and Southern Caribbean. It has several medicinal properties. It is used to treat hypertension, tumours, pain, inflammatory processes, cold, stomach ache, skin diseases, malaria, wounds and toothache. Methods The fruits of Couroupita guianensis were extracted with chloroform. Antimicrobial, antimycobacterial and antibiofilm forming activities of the chloroform extract were investigated. Quantitative estimation of Indirubin, one of the major constituent, was identified by HPLC. Results Chloroform extract showed good antimicrobial and antibiofilm forming activities; however it showed low antimycobacterial activity. The zones of inhibition by chloroform extract ranged from 0 to 26 mm. Chloroform extract showed effective antibiofilm activity against Pseudomonas aeruginosa starting from 2 mg/mL BIC, with 52% inhibition of biofilm formation. When the chloroform extract was subjected to HPLC-DAD analysis, along with Indirubin standard, in the same chromatographic conditions, it was found that Indirubin was one of the major compounds in this plant (0.0918% dry weight basis). Conclusions The chloroform extract showed good antimicrobial and antibiofilm properties. Chloroform extract can be evaluated further in drug development programmes. PMID:23206492

  18. Enhanced anti-mycobacterial immunity in children with erythema nodosum and a positive tuberculin skin test.

    PubMed

    Nicol, Mark P; Kampmann, Beate; Lawrence, Patricia; Wood, Kathy; Pienaar, Sandy; Pienaar, David; Eley, Brian; Levin, Michael; Beatty, David; Anderson, Suzanne T B

    2007-09-01

    Erythema nodosum (EN) may follow a variety of infections, but in regions with a high prevalence of tuberculosis, is frequently associated with a positive tuberculin skin test (TST) and tuberculosis infection. We aimed to investigate the immunological differences between patients with EN as a manifestation of primary tuberculosis, and those with progressive pulmonary tuberculosis (PTB) or asymptomatic infection. We studied the inflammatory response to both mycobacterial and non-mycobacterial antigens in 11 children with EN associated with a positive TST, 22 children with culture-confirmed tuberculosis, and 53 healthy skin test-positive children. In addition, we evaluated functional anti-mycobacterial immunity using an ex vivo assay of mycobacterial growth restriction in five children with EN and 15 with PTB. Patients with EN were distinguished by enhanced mycobacterial growth restriction on the functional assay, which was associated with a markedly increased production of IFNgamma in response to stimulation with purified protein derivative of Mycobacterium tuberculosis. Children presenting with EN and a positive TST show evidence of responses associated with enhanced anti-mycobacterial immunity.

  19. Newer tetracycline derivatives: synthesis, anti-HIV, antimycobacterial activities and inhibition of HIV-1 integrase.

    PubMed

    Sriram, Dharmarajan; Yogeeswari, Perumal; Senchani, Geetha; Banerjee, Debjani

    2007-04-15

    A series of new tetracycline derivatives has been synthesized by reacting appropriate tetracyclines, formaldehyde and secondary amino (piperazino) function of fluoroquinolones using microwave irradiation with the yield ranging from 41 evaluated for its anti-HIV, antimycobacterial activities and HIV-1 integrase (IN) enzyme inhibition studies. Among the synthesized compounds, compound 10 was found to be the most promising compound active against HIV-1 replication with EC(50) of 5.2 microM and was nontoxic to the CEM cells until 200 microM, and MIC of 0.2 microg/mL against Mycobacterium tuberculosis, with moderate inhibition of both 3'-processing and strand transfer steps of HIV-1 IN.

  20. Secondary metabolites from the unripe pulp of Persea americana and their antimycobacterial activities.

    PubMed

    Lu, Ying-Chen; Chang, Hsun-Shuo; Peng, Chien-Fang; Lin, Chu-Hung; Chen, Ih-Sheng

    2012-12-15

    The fruits of Persea americana (Avocado) are nowadays used as healthy fruits in the world. Bioassay-guided fractionation of the active ethyl acetate soluble fraction has led to the isolation of five new fatty alcohol derivatives, avocadenols A-D (1-4) and avocadoin (5) from the unripe pulp of P. americana, along with 12 known compounds (6-17). These structures were elucidated by spectroscopic analysis. Among the isolates, avocadenol A (1), avocadenol B (2), (2R,4R)-1,2,4-trihydroxynonadecane (6), and (2R,4R)-1,2,4-trihydroxyheptadec-16-ene (7) showed antimycobacterial activity against Mycobacterium tuberculosis H(37)R(V)in vitro, with MIC values of 24.0, 33.8, 24.9, and 35.7 μg/ml, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Screening of some New Caledonian and Vanuatu medicinal plants for antimycobacterial activity.

    PubMed

    Billo, M; Cabalion, P; Waikedre, J; Fourneau, C; Bouttier, S; Hocquemiller, R; Fournet, A

    2005-01-04

    Twenty plants, belonging to sixteen families, used in traditional New Caledonian and Vanuatu medicine for treatment of symptoms potentially related to tuberculosis (cough, fever or inflammation) were screened for antimycobacterial activity. We also screened an original endemic plant, Amborella trichopoda, only member of the monogeneric family Amborellaceae and considered the most primitive living angiosperm. In total, 55 extracts were evaluated for inhibitory activity against Mycobacterium bovis BCG strain at a concentration of 100 microg/ml. Methanolic and dichloromethane extracts of Amborella trichopoda, Codiaeum peltatum, Myristica fatua, and essential oils Myoporum crassifolium showed an activity at this concentration. Methanolic extract of Amborella trichopoda fruits presented a significant activity with a minimal inhibitory concentration included between 1 and 2.5 microg/ml. In the same conditions, this activity was comparable with those of the reference drugs pyrazynamide and ethambutol, at 20 and 2.5 microg/ml, respectively.

  2. Quantitative structure-activity relationships for the in vitro antimycobacterial activity of pyrazinoic acid esters.

    PubMed

    Bergmann, K E; Cynamon, M H; Welch, J T

    1996-08-16

    Substituted pyrazinoic acid esters have previously been reported to have in vitro activity against Mycobacterium avium and Mycobacterium kansasii as well as Mycobacterium tuberculosis. Modification of both the pyrazine nucleus and the ester functionality was successful in expanding the antimycobacterial activity associated with pyrazinamide to include M. avium and M. kansasii, organisms usually not susceptible to pyrazinamide. In an attempt to understand the relationship between the activity of the esters with the needed biostability, a quantitative structure-activity relationship has been developed. This derived relationship is consistent with the observation that tert-butyl 5-chloropyrazinoate (13) and 2'-(2'-methyldecyl) 5-chloropyrazinoate (25), compounds which are both 100-fold more active than pyrazinamide against M. tuberculosis and possess a serum stability 900-1000 times greater than the lead compounds in the series.

  3. Synthesis and in-vitro antimycobacterial activity of fluoroquinolone derivatives containing a coumarin moiety.

    PubMed

    Guo, Qiang; Liu, Ming-Liang; Feng, Lian-Shun; Lv, Kai; Guan, Yan; Guo, Hui-Yuan; Xiao, Chun-Ling

    2011-12-01

    A series of gatifloxacin, ciprofloxacin, and 8-OCH(3) ciprofloxacin coumarin derivatives with remarkable improvement in lipophilicity as compared to the parent fluoroquinolones was designed, synthesized, and characterized by (1) H-NMR, MS, and HRMS. These derivatives were evaluated for their in-vitro activity against Mycobacterium smegmatis CMCC 93202 and MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than the parent compounds against M. smegmatis CMCC 93202, but the activity of compound 6 was found to be 2-8-fold more potent than ciprofloxacin, 8-OCH(3) ciprofloxacin, moxifloxacin, and rifampin, and comparable to gatifloxacin against MTB H37Rv ATCC 27294. These results indicated that the lipophilicity of the tested compounds is not the sole parameter affecting antimycobacterial activity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Adult pulmonary tuberculosis as a pathological manifestation of hyperactive antimycobacterial immune response.

    PubMed

    Kumar, Pawan

    2016-12-01

    The intricate relationship between tuberculosis (TB) and immune system remains poorly understood. It is generally believed that weakening of the immune response against Mycobacterium tuberculosis leads to reactivation of latent infection into the active pulmonary disease. However, heterogeneous nature of TB and failure of rationally designed vaccines in clinical trials raises serious questions against the simplistic view of TB as an outcome of weakened immunity. In the wake of accumulating human TB data, it is argued here that a hyperactive antimycobacterial immune response is to blame for the pathogenesis of pulmonary TB in immunocompetent adults. Direct and indirect evidence supporting this notion is presented in this article. Revisiting the role of immune system in TB pathogenesis will pave the way for effective anti-TB vaccines.

  5. Ceanothane- and lupane-type triterpenes with antiplasmodial and antimycobacterial activities from Ziziphus cambodiana.

    PubMed

    Suksamrarn, Sunit; Panseeta, Panomwan; Kunchanawatta, Soykam; Distaporn, Thanomsin; Ruktasing, Saovaluk; Suksamrarn, Apichart

    2006-04-01

    One new and eight known ceanothane- and lupane-type triterpenes were isolated from the root bark of Ziziphus cambodiana PIERRE (Rhamnaceae). Based on spectral analyses, the structure of the new compound was elucidated as 3-O-(4-hydroxy-3-methoxybenzoyl)ceanothic acid (3-O-vanillylceanothic acid) (1), while the known compounds were identified as lupeol (2), betulinaldehyde (3), betulinic acid (4), 2-O-E-p-coumaroyl alphitolic acid (5), alphitolic acid (6), zizyberanalic acid (7), zizyberenalic acid (8) and ceanothic acid (9). Compounds 1, 5 and 8 exhibited significant in vitro antiplasmodial activity against the parasite Plasmodium falciparum, with inhibitory concentration (IC50) values of 3.7, 0.9 and 3.0 microg/ml, respectively. Compounds 1 and 3-8 showed antimycobacterial activity against Mycobacterium tuberculosis with respective MIC values of 25, 25, 25, 12.5, 50, 50 and 100 microg/ml.

  6. Synthesis, antimycobacterial and antibacterial activity of ciprofloxacin derivatives containing a N-substituted benzyl moiety.

    PubMed

    Wang, Shuo; Jia, Xue-Dong; Liu, Ming-Liang; Lu, Yu; Guo, Hui-Yuan

    2012-09-15

    We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was evaluated. Results reveal that compound 4f has good in vitro activity against all of the tested Gram-positive strains including MRSA and MRSE (MICs: 0.06-32 μg/mL) which is two to eightfold more potent than or comparable to the parent drug CPFX (MICs: 0.25-128 μg/mL), Gram-negative bacteria P. aeruginosa (MICs: 0.5-4 μg/mL) and M. tuberculosis H37Rv ATCC 27294 (MIC: 1 μg/mL). Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico

    PubMed Central

    Gómez-Cansino, Rocio; Espitia-Pinzón, Clara Inés; Campos-Lara, María Guadalupe; Guzmán-Gutiérrez, Silvia Laura; Segura-Salinas, Erika; Echeverría-Valencia, Gabriela; Torras-Claveria, Laura; Cuevas-Figueroa, Xochitl Marisol; Reyes-Chilpa, Ricardo

    2015-01-01

    The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were tested in vitro (50 µg/mL) against Mycobacterium tuberculosis H37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium fairly inhibited M. tuberculosis with IC50 of 1.87–2.35 µg/mL; but their IC50 against HIV-RT was 59.25–97.83 µg/mL. Calophyllum brasiliense, Vismia baccifera, and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02–3.64 µg/mL) and also inhibited RT-HIV (IC50 26.24–35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A. glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3β-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced by C. brasiliense can be attributed to the content of calanolides A, B, as well as soulatrolide. PMID:25983849

  8. Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico.

    PubMed

    Gómez-Cansino, Rocio; Espitia-Pinzón, Clara Inés; Campos-Lara, María Guadalupe; Guzmán-Gutiérrez, Silvia Laura; Segura-Salinas, Erika; Echeverría-Valencia, Gabriela; Torras-Claveria, Laura; Cuevas-Figueroa, Xochitl Marisol; Reyes-Chilpa, Ricardo

    2015-01-01

    The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were tested in vitro (50 µg/mL) against Mycobacterium tuberculosis H37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium fairly inhibited M. tuberculosis with IC50 of 1.87-2.35 µg/mL; but their IC50 against HIV-RT was 59.25-97.83 µg/mL. Calophyllum brasiliense, Vismia baccifera, and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02-3.64 µg/mL) and also inhibited RT-HIV (IC50 26.24-35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A. glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3β-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced by C. brasiliense can be attributed to the content of calanolides A, B, as well as soulatrolide.

  9. Antimycobacterial activity of new N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives.

    PubMed

    Zampieri, Daniele; Mamolo, Maria Grazia; Vio, Luciano; Romano, Maurizio; Skoko, Nataša; Baralle, Marco; Pau, Valentina; De Logu, Alessandro

    2016-07-15

    N(1)-[1-[1-aryl-3-[4-(1H-imidazol-1-yl)phenyl]-3-oxo]propyl]-pyridine-2-carboxamidrazone derivatives were design, synthesized and tested for their in vitro antimycobacterial activity. The new compounds showed a moderate antimycobacterial activity against the tested strain of Mycobacterium tuberculosis H37Ra and a significant antimycobacterial activity against several mycobacteria other than tuberculosis strains. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Synthesis, characterization and antimycobacterial activity of Ag(I)-aspartame, Ag(I)-saccharin and Ag(I)-cyclamate complexes.

    PubMed

    Cavicchioli, Maurício; Leite, Clarice Q F; Sato, Daisy N; Massabni, Antonio C

    2007-10-01

    The present work describes the synthesis and antimycobacterial activity of three Ag(I)-complexes with the sweeteners aspartame, saccharin, and cyclamate as ligands, with the aim of finding new candidate substances for fighting tuberculosis and other mycobacterial infections. The minimal inhibitory concentration of these three complexes was investigated in order to determine their in-vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium malmoense, and Mycobacterium kansasii. The MIC values were determined using the Microplate Alamar Blue Assay. The best MIC values found for the complexes were 9.75 microM for Ag(I)-aspartame against M. kansasii and 15.7 microM for Ag(I)-cyclamate against M. tuberculosis.

  11. The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity.

    PubMed

    Wilson, Gillian J; Marakalala, Mohlopheni J; Hoving, Jennifer C; van Laarhoven, Arjan; Drummond, Rebecca A; Kerscher, Bernhard; Keeton, Roanne; van de Vosse, Esther; Ottenhoff, Tom H M; Plantinga, Theo S; Alisjahbana, Bachti; Govender, Dhirendra; Besra, Gurdyal S; Netea, Mihai G; Reid, Delyth M; Willment, Janet A; Jacobs, Muazzam; Yamasaki, Sho; van Crevel, Reinout; Brown, Gordon D

    2015-02-11

    The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8-/- mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8-/- mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man.

  12. Synthesis, antimicrobial and antimycobacterial evaluation of [2-(substituted phenyl)-imidazol-1-yl]-pyridin-3-yl-methanones.

    PubMed

    Narasimhan, Balasubramanian; Sharma, Deepika; Kumar, Pradeep; Yogeeswari, Perumal; Sriram, Dharmarajan

    2011-10-01

    A series of [2-(substituted phenyl)-imidazol-1-yl]-pyridin-3-yl-methanones (1-11) were synthesized and screened for their antimicrobial and antimycobacterial activities. Further, a series of [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones (12-20) reported in our earlier study was also screened for their antimycobacterial activity. The antimycobacterial activity results indicated that [2-(4-Nitro-phenyl)-imidazol-1-yl]-pyridin-3-yl-methanone (8, minimum inhibitory concentration [MIC] = 3.13 µg) was equipotent as standard drug ciprofloxacin and [2-(4-Nitro-phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanone (16, MIC = 1.56 µg) was equipotent as standard drug ethambutol. The results of antimicrobial screening demonstrated that 2-[1-(Pyridine-3-carbonyl)-1H-imidazol-2-yl]-benzoic acid (compound 11, MIC = 0.002 µg) was two times more effective than standard drug ciprofloxacin (MIC = 0.004 µg) against tested bacterial strains and [2-(2,5-Dimethyl-phenyl)-imidazol-1-yl]-pyridin-3-yl-methanone (compound 3, MIC = 0.005 µg) was equipotent to the reference compound, fluconazole against tested fungal strains.

  13. Antimycobacterial, docking and molecular dynamic studies of pentacyclic triterpenes from Buddleja saligna leaves.

    PubMed

    Singh, Alveera; Venugopala, Katharigatta N; Khedr, Mohammed A; Pillay, Mellendran; Nwaeze, Kenneth U; Coovadia, Yacoob; Shode, Francis; Odhav, Bharti

    2017-09-01

    Buddleja saligna (family Buddlejaceae) is a medicinal plant endemic to South Africa. Two isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were isolated from the leaves of B. saligna using silica gel column chromatography. Compounds oleanolic acid and ursolic acid were subjected to derivatization with acetic anhydride in the presence of pyridine to obtain oleanolic acid-3-acetate and ursolic acid-3-acetate, respectively. The structures of these compounds were fully characterized by detailed nuclear magnetic resonance (NMR) investigations, which included (1)H and (13)C NMR. Molecular docking studies predicted the free binding energy of the four triterpenes inside the steroid binding pocket of Mycobacterium tuberculosis fadA5 thiolase compared to a reported inhibitor. Thus, their ability to inhibit the growth of M. tuberculosis was predicted and was confirmed to possess significant antimycobacterial activity when tested against Mycobacterium smegmatis, M. tuberculosis H37Rv (ATCC 25177), clinical isolates of multi-drug-resistant M. tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis (XDR-TB) using the Micro Alamar Blue Assay. Ursolic acid was isolated from this plant for the first time.

  14. Preparation, Characterization and in Vivo Antimycobacterial Studies of Panchovillin-Chitosan Nanocomposites

    PubMed Central

    Rwegasila, Edward; Mubofu, Egid B.; Nyandoro, Stephen S.; Erasto, Paul; Munissi, Joan J. E.

    2016-01-01

    Chitosan (CS, molecular weight 20.2 kDa, degree of deacylation (DD) 73.31%) was successfully obtained by deacetylation of chitin extracted from shrimp (Litopenaeus vannamei) shell wastes. The encapsulation of the bioactive natural product, panchovillin (PANV), isolated from Erythrina schliebenii, on a chitosan-tripolyphosphate (CS/TPP) nano-framework was achieved by ionotropic gelation. Characterization of pure CS, CS/TPP and PANV-CS/TPP nanocomposites was performed by FTIR, SEM and XRD. The molecular weight of chitosan and the thermal stability of the materials were determined by MALDI-TOF-MS and simultaneous thermal analyzer (STA)/DTG, respectively. The respective encapsulation efficiency and loading capacity of the PANV were found to be 70% and 0.36%. The in vitro release studies showed an initial burst of 42% of PANV in the first six hours. This was followed by a slow and sustained release up to 72 h. The in vivo antimycobacterial activities of both PANV and PANV-CS/TPP nanocomposite against Mycobacterium indicus pranii (MIP) using Galleria mellonella larvae as an in vivo infection model are reported in this paper. PMID:27689997

  15. Penicillium chrysogenum DSOA associated with marine sponge (Tedania anhelans) exhibit antimycobacterial activity.

    PubMed

    Visamsetti, Amarendra; Ramachandran, Santhosh Sarojini; Kandasamy, Dhevendaran

    2016-04-01

    A strain of Penicillium chrysogenum was isolated from Tedania anhelans (marine sponge) collected from Indian Ocean (8°22'30″N latitude and 76°59'16″ longitude) and deposited in culture collection centers. The strain subjected to different culture conditions for production of extrolites were extracted using ethyl acetate and chloroform. When both extracts were subjected for antibacterial activity, latter had high activity. Minimum inhibitory concentration of chloroform extract ranged from 31.25-1000 μg/mL in tested microbes such as, Mycobacterium tuberculosis H37Ra, Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium smegmatis, Mycobacterium vaccae, Staphylococcus aureus, Aeromonas hydrophila, Pseudomonas aeruginosa and Vibrio cholerae. No cytotoxicity was observed in Vero cell line up to 399.10 μg/mL. Antibacterial activity previously reported by Parameswaran et al. in 1997 from ethyl acetate extract of T. anhelans might be due to the diketopiperazines, Cyclo-(L-Pro-L-Phe) and Cyclo-(L-Leu-L-Pro) produced by the associated fungi-P. chrysogenum DSOA. It is producing a metabolites having antimycobacterial activity, a first report.

  16. Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule

    PubMed Central

    Bilham, Kirstin; Boyd, Amy C.; Preston, Stephen G.; Buesching, Christina D.; Newman, Chris; Macdonald, David W.; Smith, Adrian L.

    2017-01-01

    The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers. PMID:28382943

  17. Gatifloxacin derivatives: synthesis, antimycobacterial activities, and inhibition of Mycobacterium tuberculosis DNA gyrase.

    PubMed

    Sriram, Dharmarajan; Aubry, Alexandra; Yogeeswari, Perumal; Fisher, L M

    2006-06-01

    Sixteen 7-substituted gatifloxacin derivatives were synthesized and evaluated for antimycobacterial activity in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. tuberculosis. Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy-7-[[[N4-[1'-(5-isatinyl-beta-semicarbazo)]methyl]3-methyl]N1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (3d) was found to be the most active compound in vitro with an MIC of 0.0125 microg/mL against MTB and MTR-TB. In the in vivo animal model 3d decreased the bacterial load in lung and spleen tissues with 3.62- and 3.76-log10 protections, respectively. Compound 3d was also found to be equally active as gatifloxacin in the inhibition of the supercoiling activity of wild-type M. tuberculosis DNA gyrase with an IC50 of 3.0 microg/mL. The results demonstrate the potential and importance of developing new quinolone derivatives against mycobacterial infections.

  18. Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.

    PubMed

    Bilham, Kirstin; Boyd, Amy C; Preston, Stephen G; Buesching, Christina D; Newman, Chris; Macdonald, David W; Smith, Adrian L

    2017-04-06

    The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers.

  19. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds.

    PubMed

    Alvin, Alfonsus; Miller, Kristin I; Neilan, Brett A

    2014-01-01

    Natural product drug discovery has regained interest due to low production costs, structural diversity, and multiple uses of active compounds to treat various diseases. Attention has been directed towards medicinal plants as these plants have been traditionally used for generations to treat symptoms of numerous diseases. It is established that plants harbour microorganisms, collectively known as endophytes. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel compounds. The concept of natural products targeting microbial pathogens has been applied to isolate novel antimycobacterial compounds, and the rapid development of drug-resistant Mycobacterium tuberculosis has significantly increased the need for new treatments against this pathogen. It remains important to continuously screen for novel compounds from natural sources, particularly from rarely encountered microorganisms, such as the endophytes. This review focuses on bioprospecting for polyketides and small peptides exhibiting antituberculosis activity, although current treatments against tuberculosis are described. It is established that natural products from these structure classes are often biosynthesised by microorganisms. Therefore it is hypothesised that some bioactive polyketides and peptides originally isolated from plants are in fact produced by their endophytes. This is of interest for further endophyte natural product investigations.

  20. Enabling faster Go/No-Go decisions through secondary screens in anti-mycobacterial drug discovery.

    PubMed

    Mukherjee, Raju; Chandra Pal, Anup; Banerjee, Mousumi

    2017-09-01

    Management of tuberculosis, already a global health emergency, is becoming increasingly challenging with extensive misuse of second line drugs and their inaccessibility to eighty percent of the eligible patients. Rising statistics of antimicrobial resistance underscores the need for a set of completely new and more effective class of compounds with novel mechanisms of action that can be administered in combination to replace and shorten the present intensive six months regimen. In this review, we stress on the importance and the successes of phenotypic screening for discovery of anti-mycobacterial compound and discuss the importance of performing secondary screens and counter screens to get early estimate on compound's potentials for a successful development. We also highlight the recent advances and the related caveats in the assays that have been developed and discuss new screening modalities that can be incorporated during hit-selection to gain a quick insight into the mechanism of action, thus enabling quicker decisions in a hit triage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Anti-mycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica.

    PubMed

    Singh, Rambir; Hussain, Shariq; Verma, Rajesh; Sharma, Poonam

    2013-05-13

    To find out the anti-mycobacterial potential of Cassia sophera (C. sophera), Urtica dioica (U. dioica), Momordica dioica, Tribulus terrestris and Coccinia indica plants against multi-drug resistant (MDR) strain of Mycobacterium tuberculosis (M. tuberculosis). Plant materials were extracted successively with solvents of increasing polarity. Solvent extracts were screened for anti-mycobacterial activity against fast growing, non-pathogenic mycobacterium strain, Mycobacterium semegmatis, by disk diffusion method. The active extracts were tested against MDR and clinical isolates of M. tuberculosis by absolute concentration and proportion methods. The active extracts were subjected to bio-autoassay on TLC followed by silica column chromatography for isolation of potential drug leads. Hexane extract of U. dioica (HEUD) and methanol extract of C. sophera (MECS) produced inhibition zone of 20 mm in disc diffusion assay and MIC of 250 and 125 μ g/mL respectively in broth dilution assay against Mycobacterium semegmatis. Semipurified fraction F2 from MECS produced 86% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. F18 from HEUD produced 81% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. Phytochemical analysis indicated that anti-mycobacterial activity of MECS may be due to presence of alkaloids or flavonoids and that of HEUD due to terpenoids. C. sophera and U. dioica plant extracts exhibited promising anti-mycobacterial activity against MDR strain of M. tuberculosis. This is the first report of anti-mycobacterial activity form C. sophera. This study showed possibility of purifying novel anti-mycobacterial compound(s) from C. sophera and U. dioica. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  2. Isolation of anti-mycobacterial compounds from Curtisia dentata (Burm.f.) C.A.Sm (Curtisiaceae).

    PubMed

    Fadipe, Victor O; Mongalo, Nkoana I; Opoku, Andy R; Dikhoba, Preachers M; Makhafola, Tshepiso J

    2017-06-12

    Tuberculosis is counted amongst the most infectious and lethal illnesses worldwide and remains one of the major threats to human health. The aim of the current study was to isolate and characterize anti-mycobacterial compounds present in Curtisia dentata (Burm.f.) C.A.Sm , a medicinal plant reportedly used in the treatment of tuberculosis, stomach ailments and sexually transmitted infections. The bioassay guided principle was followed to isolate the anti-mycobacterial compounds. The crude ethanol extracts of the leaves was partitioned with various solvents four compounds such as β-sitosterol, betulinic acid, ursolic acid and lupeol were successfully isolated. The compounds and their derivatives were evaluated for anti-mycobacterial activity using Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37RV (ATCC 27294). Furthermore, the derivatives were investigated for their toxicity against HepG2 and HEK293 using the MTT assay. The methanol fraction had the lowest minimum inhibitory concentration (MIC) of 22.2 μg/ml against the selected Mycobacterium strain when compared to other fractions. Ursolic acid acetate (UAA) was the most active compound with MIC value of 3.4 μg/ml. The derivatives had varying degrees of toxicity, but were generally non-toxic to the selected cell lines. Derivatives also exhibited highest selectivity index and offers a higher safety margin. The derivatives had better antimicrobial activity and low cytotoxic effects compared to isolated compounds. These increased their selectivity. It appears that acetylation of both betulinic acid and ursolic acid increased their activity against the selected Mycobacterium species. The results obtained in this study gives a clear indication that Curtisia dentata may serve as major source of new alternative medicines that may be used to treat TB. Furthermore, there is a need to explore the activity of these tested plant against other pathogenic Mycobacterium species.

  3. Unnatural amino acid analogues of membrane-active helical peptides with anti-mycobacterial activity and improved stability.

    PubMed

    Khara, Jasmeet Singh; Priestman, Miles; Uhía, Iria; Hamilton, Melissa Shea; Krishnan, Nitya; Wang, Ying; Yang, Yi Yan; Langford, Paul R; Newton, Sandra M; Robertson, Brian D; Ee, Pui Lai Rachel

    2016-08-01

    The emergence of MDR-TB, coupled with shrinking antibiotic pipelines, has increased demands for new antimicrobials with novel mechanisms of action. Antimicrobial peptides have increasingly been explored as promising alternatives to antibiotics, but their inherent poor in vivo stability remains an impediment to their clinical utility. We therefore systematically evaluated unnatural amino acid-modified peptides to design analogues with enhanced anti-mycobacterial activities. Anti-mycobacterial activities were evaluated in vitro and intracellularly against drug-susceptible and MDR isolates of Mycobacterium tuberculosis using MIC, killing efficacy and intracellular growth inhibition studies. Toxicity profiles were assessed against mammalian cells to verify cell selectivity. Anti-mycobacterial mechanisms were investigated using microfluidic live-cell imaging with time-lapse fluorescence microscopy and confocal laser-scanning microscopy. Unnatural amino acid incorporation was well tolerated without an appreciable effect on toxicity profiles and secondary conformations of the synthetic peptides. The modified peptides also withstood proteolytic digestion by trypsin. The all d-amino acid peptide, i(llkk)2i (II-D), displayed superior activity against all six mycobacterial strains tested, with a 4-fold increase in selectivity index as compared with the unmodified l-amino acid peptide in broth. II-D effectively reduced the intracellular bacterial burden of both drug-susceptible and MDR clinical isolates of M. tuberculosis after 4 days of treatment. Live-cell imaging studies demonstrated that II-D permeabilizes the mycobacterial membrane, while confocal microscopy revealed that II-D not only permeates the cell membrane, but also accumulates within the cytoplasm. Unnatural amino acid modifications not only decreased the susceptibility of peptides to proteases, but also enhanced mycobacterial selectivity. © The Author 2016. Published by Oxford University Press on behalf of the

  4. Potent antimycobacterial activity of the pyridoxal isonicotinoyl hydrazone analog 2-pyridylcarboxaldehyde isonicotinoyl hydrazone: a lipophilic transport vehicle for isonicotinic acid hydrazide.

    PubMed

    Ellis, Samantha; Kalinowski, Danuta S; Leotta, Lisa; Huang, Michael L H; Jelfs, Peter; Sintchenko, Vitali; Richardson, Des R; Triccas, James A

    2014-02-01

    The rise in drug-resistant strains of Mycobacterium tuberculosis is a major threat to human health and highlights the need for new therapeutic strategies. In this study, we have assessed whether high-affinity iron chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class can restrict the growth of clinically significant mycobacteria. Screening a library of PIH derivatives revealed that one compound, namely, 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH), exhibited nanomolar in vitro activity against Mycobacterium bovis bacille Calmette-Guérin and virulent M. tuberculosis. Interestingly, PCIH is derived from the condensation of 2-pyridylcarboxaldehyde with the first-line antituberculosis drug isoniazid [i.e., isonicotinic acid hydrazide (INH)]. PCIH displayed minimal host cell toxicity and was effective at inhibiting growth of M. tuberculosis within cultured macrophages and also in vivo in mice. Further, PCIH restricted mycobacterial growth at high bacterial loads in culture, a property not observed with INH, which shares the isonicotinoyl hydrazide moiety with PCIH. When tested against Mycobacterium avium, PCIH was more effective than INH at inhibiting bacterial growth in broth culture and in macrophages, and also reduced bacterial loads in vivo. Complexation of PCIH with iron decreased its effectiveness, suggesting that iron chelation may play some role in its antimycobacterial efficacy. However, this could not totally account for its potent efficacy, and structure-activity relationship studies suggest that PCIH acts as a lipophilic vehicle for the transport of its intact INH moiety into the mammalian cell and the mycobacterium. These results demonstrate that iron-chelating agents such as PCIH may be of benefit in the treatment and control of mycobacterial infection.

  5. Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides.

    PubMed

    Brucoli, Federico; Guzman, Juan D; Maitra, Arundhati; James, Colin H; Fox, Keith R; Bhakta, Sanjib

    2015-07-01

    The alarming rise of extensively drug-resistant tuberculosis (XDR-TB) strains, compel the development of new molecules with novel modes of action to control this world health emergency. Distamycin analogues containing N-terminal biaryl-motifs 2(1-5)(1-7) were synthesised using a solution-phase approach and evaluated for their anti-mycobacterial activity and DNA-sequence selectivity. Thiophene dimer motif-containing polyamide 2(2,6) exhibited 10-fold higher inhibitory activity against Mycobacterium tuberculosis compared to distamycin and library member 2(5,7) showed high binding affinity for the 5'-ACATAT-3' sequence.

  6. Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides.

    PubMed

    Krasnov, Victor P; Vigorov, Alexey Yu; Musiyak, Vera V; Nizova, Irina A; Gruzdev, Dmitry A; Matveeva, Tatyana V; Levit, Galina L; Kravchenko, Marionella A; Skornyakov, Sergey N; Bekker, Olga B; Danilenko, Valery N; Charushin, Valery N

    2016-06-01

    Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia). N-(2-Aminopurin-6-yl)- and N-(purin-6-yl)-glycyl-(S)-glutamic acids were the most active compounds.

  7. Synthetic modifications of the immunomodulating peptide thymopentin to confer anti-mycobacterial activity.

    PubMed

    Wang, Ying; Ke, Xi-Yu; Khara, Jasmeet S; Bahety, Priti; Liu, Shaoqiong; Seow, See Voon; Yang, Yi Yan; Ee, Pui Lai Rachel

    2014-03-01

    Effective global control of tuberculosis (TB) is increasingly threatened by the convergence of multidrug-resistant TB and the human immunodeficiency virus (HIV) infection. TB/HIV coinfections exert a tremendous burden on the host's immune system, and this has prompted the clinical use of immunomodulators to enhance host defences as an alternative therapeutic strategy. In this study, we modified the clinically used synthetic immunomodulatory pentapeptide, thymopentin (TP-5, RKDVY), with six arginine residues (RR-6, RRRRRR) at the N- and C-termini to obtain the cationic peptides, RR-11 (RKDVYRRRRRR-NH2) and RY-11 (RRRRRRRKDVY-NH2), respectively. The arginine residues conferred anti-mycobacterial activity to TP-5 in the peptides as shown by effective minimum inhibitory concentrations of 125 mg/L and killing efficiencies of >99.99% against both rifampicin-susceptible and -resistant Mycobacterium smegmatis. The immunomodulatory action of the peptides remained unaffected as shown by their ability to stimulate TNF-α production in RAW 264.7 mouse macrophage cells. A distinct change in surface morphology after peptide treatment was observed in scanning electron micrographs, while confocal microscopy and dye leakage studies suggested bacterial membrane disruption by the modified peptides. The modified peptides were non-toxic and did not cause hemolysis of rat red blood cells up to a concentration of 2000 mg/L. Moreover, RY-11 showed synergism with rifampicin and reduced the effective concentration of rifampicin, while preventing the induction of rifampicin resistance. The synthetic peptides may have a potential application in both immunocompetent and immunocompromised TB patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Validation of Antimycobacterial Plants Used by Traditional Healers in Three Districts of the Limpopo Province (South Africa)

    PubMed Central

    Masoko, Peter; Nxumalo, Kulani Mashudu

    2013-01-01

    The aim of the study was to scientifically evaluate the antimycobacterial activity of selected indigenous medicinal plants from the Limpopo Province used for the treatment of humans with symptoms of Mycobacterium tuberculosis. The leaves of five plant species (Apodytes dimidiata, Artemisia, Combretum hereroense, Lippia javanica, and Zanthoxylum capense) were collected from the Lowveld National Botanical Garden in Nelspruit, South Africa. The dried leaves were powdered and extracted using hexane, dichloromethane, acetone, and methanol. Antimycobacterial activity was evaluated using microdilution assay and bioautography and ρ-iodonitrotetrazolium violet (INT) as indicator. Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH). Phytochemical content of extracts was further evaluated. The acetone extracts of L. javanica displayed antioxidant activity on BEA chromatogram. T Acetone extracts of A. afra had MIC value of 0.39 mg/mL against Mycobacterium smegmatis ATCC 1441. Acetone extracts of C. hereroense and L. javanica had MIC value of 0.47 mg/mL. Four bands that inhibited the growth of M. smegmatis were observed at Rf values of 0.12, 0.63, and 0.87 on BEA and 0.73 on EMW. The plant species A. dimidiata, A. afra, C. hereroense, and L. javanica in this study demonstrated their potential as sources of anti-TB drug leads. PMID:23956776

  9. Evaluation of in vivo antimycobacterial activity of some folklore medicinal plants and enumeration of colony forming unit in murine model

    PubMed Central

    Barua, Acheenta Gohain; Raj, Himangshu; Konch, Pranab; Hussain, P.; Barua, Chandana C.

    2016-01-01

    Objectives: The present study was carried out to investigate the in vivo antimycobacterial activity of methanol extract of Alstonia scholaris and Mucuna imbricata in murine model. Materials and Methods: Female BALB/c mice were infected with the Mycobacterium tuberculosis H37Rv suspension. Extracts were administered orally for 2 weeks from 7th day postinfection at a dose of 200 mg/kg and rifampicin at 20 mg/kg as standard. The synergistic groups were 10 and 100 mg/kg for rifampicin and extract, respectively. Results: The final body weight of mycobacteria-infected group was significantly reduced (15.41 ± 0.42, P < 0.01), but following treatment with the plant extract plus rifampicin could elevate the body weight. Colony forming unit (CFU) count of lung (8.71 ± 0.01) and spleen (8.59 ± 0.01) was significantly higher in infected and untreated group (P < 0.01). It was observed that activity of the synergistic group displayed powerful and maximum response against tuberculosis (TB) infection with lower CFU counts. Histopathology study showed cells such as lymphocytes, epithelioid, Langhans giant cell, and fibrous tissue proliferation in lungs; depletion of lymphocytes in the spleen. Conclusions: The data indicate that methanol extract of A. scholaris has potential antimycobacterial activity, and the synergistic group consisting of rifampicin and A. scholaris could be a rational choice for the treatment of TB. PMID:27721538

  10. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    NASA Astrophysics Data System (ADS)

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-07-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis.

  11. Evaluation of in vivo antimycobacterial activity of some folklore medicinal plants and enumeration of colony forming unit in murine model.

    PubMed

    Barua, Acheenta Gohain; Raj, Himangshu; Konch, Pranab; Hussain, P; Barua, Chandana C

    2016-01-01

    The present study was carried out to investigate the in vivo antimycobacterial activity of methanol extract of Alstonia scholaris and Mucuna imbricata in murine model. Female BALB/c mice were infected with the Mycobacterium tuberculosis H37Rv suspension. Extracts were administered orally for 2 weeks from 7(th) day postinfection at a dose of 200 mg/kg and rifampicin at 20 mg/kg as standard. The synergistic groups were 10 and 100 mg/kg for rifampicin and extract, respectively. The final body weight of mycobacteria-infected group was significantly reduced (15.41 ± 0.42, P < 0.01), but following treatment with the plant extract plus rifampicin could elevate the body weight. Colony forming unit (CFU) count of lung (8.71 ± 0.01) and spleen (8.59 ± 0.01) was significantly higher in infected and untreated group (P < 0.01). It was observed that activity of the synergistic group displayed powerful and maximum response against tuberculosis (TB) infection with lower CFU counts. Histopathology study showed cells such as lymphocytes, epithelioid, Langhans giant cell, and fibrous tissue proliferation in lungs; depletion of lymphocytes in the spleen. The data indicate that methanol extract of A. scholaris has potential antimycobacterial activity, and the synergistic group consisting of rifampicin and A. scholaris could be a rational choice for the treatment of TB.

  12. Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity

    PubMed Central

    Inokoshi, Junji; Koyama, Nobuhiro; Miyake, Midori; Shimizu, Yuji; Tomoda, Hiroshi

    2016-01-01

    Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships. The mutational analysis revealed that four amino acid residues (Gly1, Arg7, Glu8, and Trp9) in lariatin A are essential for the maturation and production in the biosynthetic machinery. Furthermore, the study on structure-activity relationships demonstrated that Tyr6, Gly11, and Asn14 are responsible for the anti-mycobacterial activity, and the residues at positions 15, 16 and 18 in lariatin A are critical for enhancing the activity. This study will not only provide a useful platform for genetically engineering Gram-positive bacterium-producing lasso peptides, but also an important foundation to rationally design more promising drug candidates for combatting tuberculosis. PMID:27457620

  13. Antimycobacterial activity assessment of three ethnobotanical plants against Mycobacterium Tuberculosis: An In Vitro study.

    PubMed

    Arjomandzadegan, Mohammad; Emami, Navid; Habibi, Ghasem; Farazi, Ali Asghar; Kahbazi, Manijeh; Sarmadian, Hossein; Jabbari, Mansooreh; Hosseini, Hossein; Ramezani, Mona

    2016-12-01

    Resistances to herbal medicines are still not defined and finding natural remedies against drug resistant Mycobacterium tuberculosis (MTB) has research priority. The antimycobacterial susceptibility method for herbal extracts is unclearly defined and there is no standard method for assessment of the materials against bacteria. In the present study, time kill of three medicinal plants was determined against MTB. The clinical isolate of MTB from a patient who harbored confirmed tuberculosis was used in the study. Aqueous extracts of Aloe vera leaves, mint, and Hypericum perforatum were prepared using reflux distillation. Disk diffusion methods were conducted in Petri dishes and McCartney bottles containing Löwenstein-Jensen medium to measure the sensitivity of plant extracts in serial concentrations of 0.25-8mg/mL. A pour plate method was performed by mixing 0.7mL of each concentration of extract in 5mL Löwenstein-Jensen medium followed by surface culturing of MTB fresh cells. The time kill method was conducted by bacterial suspension in equal amounts of the extract and viable evaluation in fresh culture at the beginning, and at 24-h, 48-h, 72-h, and 1-week intervals. All cultures were incubated at 37°C for 4weeks. Inoculum concentrations were considered as a variable. The zones of inhibition of A. vera, H. perforatum, and mint extracts in the disk diffusion method in McCartney bottles were 60mm, 41mm, and zero, respectively, but Petri dishes did not have repeatable results. In the pour plate method, an extract concentration up to 1mg/mL could inhibit cell growth. In mint extract, colony forming was four times more than the others at 0.5mg/mL. Time kill of 95% of cells occurred when exposed to extracts of A. vera and H. perforatum separately, but was 50% in 24 h and 20% in 10 min. The time kill for mint was 95% in 1week. The results give some scientific basis to the use of plant extracts for growth control of MTB cells. Clinical trials are recommended for

  14. The 15-lipoxygenase inhibitory, antioxidant, antimycobacterial activity and cytotoxicity of fourteen ethnomedicinally used African spices and culinary herbs.

    PubMed

    Dzoyem, Jean Paul; Kuete, Victor; McGaw, Lyndy J; Eloff, Jacobus N

    2014-10-28

    Culinary herbs and spices are widely used ethnomedically across Africa. They are traditionally employed in the treatment of several ailments including inflammation disorders, pain alleviation and infectious diseases. Pharmacological studies are necessary to provide a scientific basis to substantiate their traditional use and safety. In this study, the 15-lipoxygenase inhibitory, antioxidant, antimycobacterial and the cytotoxic activities, total phenolic and flavonoid contents of fourteen edible plants were investigated. The 15-lipoxygenase inhibitory activity was evaluated by the ferrous oxidation-xylenol orange (FOX) assay method. The antioxidant activity was determined using free-radical scavenging assays. The antimycobacterial activity was determined by a broth microdilution method against three species of mycobacteria: Mycobacterium smegmatis, Mycobacterium aurum and Mycobacterium fortuitum using tetrazolium violet as growth indicator. The cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Vero monkey kidney cells. All the extracts tested had some 15-lipoxygenase inhibitory activity ranging from 32.9 to 78.64%. Adansonia digitata (fruit) had the highest antioxidant capacity (IC₅₀ values of 8.15 μg/mL and 9.16 μg/mL in the DPPH and ABTS assays respectively; TEAC of 0.75 in the FRAP assay) along with the highest amount of total phenolics (237.68 mg GAE/g) and total flavonoids (16.14 mg E/g). There were good correlations between DPPH and ABTS values (R(2) 0.98) and between total phenolics and total flavonoids (R(2) 0.94). Tamarindus indica had significant antimycobacterial activity against Mycobacterium aurum (MIC 78 μg/mL). As could be expected with edible plants, all the extracts had a relatively low cytotoxicity with LC₅₀ values higher than 102 μg/mL with the exception of the two Aframomum species (33 and 74 μg/mL). This study provides scientific support for some of the the traditional uses

  15. Antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of Psidium guineense Sw. and spathulenol.

    PubMed

    do Nascimento, Kamilla Felipe; Moreira, Flora Martinez Figueira; Alencar Santos, Joyce; Kassuya, Candida Aparecida Leite; Croda, Julio Henrique Rosa; Cardoso, Claudia Andrea Lima; Vieira, Maria do Carmo; Góis Ruiz, Ana Lúcia Tasca; Ann Foglio, Mary; de Carvalho, João Ernesto; Formagio, Anelise Samara Nazari

    2017-08-24

    Leaves from Psidium guineense Sw. are used in popular medicine for the treatment of inflammatory disease. However, there is no scientific evidence demonstrating this activity. To evaluate the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of P. guineense and spathulenol (a major constituent). The study was conducted in part to provide evidence supporting the ethnobotanical use of the leaves of this species. The essential oil (EOPG) was extracted from the leaves of P. guineense by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). The major compound, spathulenol (PG-1), was isolated in a chromatographic column and characterized by nuclear magnetic resonance (NMR). EOPG and PG-1 were evaluated in vitro for antioxidant activity by DPPH, ABTS and MDA methods; anti-inflammatory potential was assessed using two models, including pleurisy and oedema, in mice. The impact of EOPG and PG-1 on cell proliferation was determined via spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay, and anti-Mycobacterium tuberculosis activity was determined using the REMA method. A total of 38 components were identified from the EOPG, with the sesquiterpenic alcohol spathulenol (PG-1) (80.7%) being the major constituent. EOPG and PG-1 exhibited the highest antioxidant activities in the DPPH and MDA system compared with reference standard, with IC50 values ranging from 26.13 to 85.60μg/mL. Oral administration of EOPG and PG-1 showed significant inhibition in the Cg-induced mice paw oedema and pleurisy model. The EOPG (GI50 = 0.89μg/mL) and PG-1 (GI50 = 49.30μg/mL) were particularly effective against the ovarian cancer cell line. Both showed moderate antimycobacterial activity. For the first time, this study demonstrated the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial properties of the essential oil of P. guineense (leaves were

  16. In vitro Anti-mycobacterial activity of selected medicinal plants against Mycobacterium tuberculosis and Mycobacterium bovis Strains

    PubMed Central

    2013-01-01

    Background Tuberculosis (TB) is a global burden with one –third of the world’s population infected with the pathogen Mycobacterium tuberculosis complex and annually 1.4 million deaths occur due to the disease. This high incidence of infection and the increased rate of multi-drug resistant and extensively-drug resistant strains of the organism further complicated the problem of TB control and have called for an urgent need to develop new anti-TB drugs from plants. In this study, the in vitro activity of root of Calpurnia aurea, seeds of Ocimum basilicum, leaves of Artemisia abyssinica, Croton macrostachyus, and Eucalyptus camaldulensis were evaluated against M. tuberculosis and M. bovis strains. Methods Five Ethiopian medicinal plants, root of Calpurnia aurea, seeds of Ocimum basilicum, leaves of Artemisia abyssinica, Croton macrostachyus, and Eucalyptus camaldulensis used locally for the management of TB. They were investigated for in vitro antimycobacterial activity against M. tuberculosis and M. bovis strains. 80% methanolic extracts of the plant materials were obtained by maceration. The antimycobacterial activity was determined using 96 wells of microplate with the help of visual Resazurin Microtiter Assay. Results The crude 80% methanolic extracts of the root of C. aurea, seeds of O. basilicum, and leaves of A. abyssinica, C. macrostachyus, and E. camaldulensis had anti-mycobacterial activity with minimum inhibitory concentration (MIC) ranging from 6.25–100 μg/mL. The MIC of 80% methanol extracts in the order mentioned above ranged 25-100 μg/ml and 12.5-75 μg/mL, 25–100 μg/mL and 25–50 μg/mL, 6.25-50 μg/mL and 12.5-50 μg/mL, 12.5-100 μg/mL and 18.25-50 μg/mL and 6.25-50 μg/mL and 12.5-50 μg/mL, respectively for M. tuberculosis and M. bovis strains. Conclusions The results support the local use of these plants in the treatment of TB and it is suggested that these plants may have therapeutic value in the treatment of TB. However

  17. Antimycobacterial activity of two natural alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian shrub Adhatoda vasica Ness. leaves.

    PubMed

    Ignacimuthu, S; Shanmugam, N

    2010-12-01

    In folk medicine, Adhatoda vasica Ness. (Acanthaceae) is used to treat asthma and cough. The leaves of A. vasica were powdered and extracted with hexane, ethyl acetate and methanol. The hexane extract showed 97 percent reduction in colony-forming units (CFU) at 100 microg/ml. The hexane extract was subjected to column chromatography. Two natural compounds, vasicine acetate and 2-acetyl benzylamine, were isolated from it. They were bioassayed against Mycobacterium tuberculosis. The two compounds showed strong antimycobacterial activity. Vasicine acetate and 2-acetyl benzylamine isolated from hexane extract of A. vasica leaves, significantly inhibited M. tuberculosis and one multi-drug-resistant (MDR) strain and one sensitive strain at 200 and 50 microg/ml, respectively. Our study demonstrated that both the compounds, vasicine acetate and 2-acetyl benzylamine, could be evaluated further for developing a drug to control M. tuberculosis.

  18. Antibacterial agents: patent highlights January to June 2004.

    PubMed

    Phillips, Oludotun A

    2004-08-01

    This review presents highlights of 32 patents, published between January and June 2004, detailing different classes of antibacterial agents. Disclosures on novel oxazolidinone derivatives with antibacterial activity continue to dominate patent publications in recent years. Novel oxazolidinone derivatives active against linezolid-resistant cocci are reviewed. Patents on beta-lactam antibiotics focused mainly on developing new processes and formulations to improve cost, purity and pharmacokinetic parameters of existing clinical agents. Disclosures on novel potential dual-acting macrolide-quinolone hybrids designed to overcome erythromycin resistance, and new macrolide derivatives with antimycobacterial activity are described. Also presented are novel antibacterial agents, including peptide deformylase and cell-wall inhibitors, and those with undefined mechanisms of action as potential lead compounds, as well as quinolone and quinoline derivatives.

  19. Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases.

    PubMed

    Jose, Gilish; Suresha Kumara, Tholappanavara H; Sowmya, Haliwana B V; Sriram, Dharmarajan; Guru Row, Tayur N; Hosamani, Amar A; More, Sunil S; Janardhan, Bhavya; Harish, B G; Telkar, Sandeep; Ravikumar, Yalegara Siddappa

    2017-05-05

    In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by (1)H NMR, (13)C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4](+2), H2O). The in vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using Agar diffusion method and Broth micro dilution method. Compounds 7e, 7f, 7r, 7t, and 7u were showed good Gram-positive antibacterial activity against S. aureus, B. flexus, C. sporogenes and S. mutans. Furthermore, in vitro antimycobacterial activity was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) using MABA. Compounds 7r, 7t, and 7u were showed good antitubercular activity against Mtb (MIC ≥6.25 μg/mL). Among the tested compounds, 1-((4-chloro-2-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)methyl)piperidine-3-carboxamide (7t) was showed excellent antimycobacterial activity against Mtb (MIC <0.78 μg/mL) and low cytotoxicity against the HEK-293T cell line (SI >25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro.

  20. Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity.

    PubMed

    Dasgupta, Queeny; Madras, Giridhar; Chatterjee, Kaushik

    2016-01-01

    Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are

  1. Modulation of macrophage apoptosis by antimycobacterial therapy: physiological role of apoptosis in the control of Mycobacterium tuberculosis.

    PubMed

    Gil, Diana; Garcia, Luis F; Rojas, Mauricio

    2003-07-15

    Apoptosis is a form of cell death that avoids inflammatory responses. We had previously reported that Mycobacterium tuberculosis (Mtb) and Purified Protein Derivative (PPD) induce apoptosis in murine macrophages. The production of TNFalpha and IL-10 in response to Mtb infection modulates apoptosis by controlling nitric oxide production and caspase activation. Furthermore, Mtb triggers calcium influx responsible for mitochondrial alterations, an early pathway of apoptosis, independently of TNFalpha and IL-10. In tuberculosis patients apoptotic macrophages are found in granulomas and bronchoalveolar lavages, suggesting that apoptosis may participate in the control of Mtb. To further explore the role of macrophage apoptosis in tuberculosis, we studied the capacity of standard antimycobacterial drugs to modulate different events associated with the induction of apoptosis. The B10R murine macrophage line was infected or not with Mtb (5:1 bacteria to macrophage ratio) or exposed to PPD (10 microg/ml), in the presence or absence of varying concentrations (1-20 microg/ml) of anti mycobacterial drugs (isoniazid, rifampin, thiacetazone, streptomycin, and ethambutol). Inhibition of the intracellular growth of M. tuberculosis by all drugs studied/correlated with inhibition of permeability transition (PT) alterations; TNFalpha, IL-10, and nitric oxide production, and caspase-1 activation. However, these drugs did not affect PPD-induced apoptosis or its associated events, suggesting that the ability of antimycobacterial drugs to block macrophage apoptosis could be explained by their effects on the metabolic activities of Mtb. All drugs, except isoniazid, at higher concentrations, induced PT alterations in noninfected macrophages in a way that appears to be dependent of calcium, since a calcium chelator prevented it. The results presented herein suggest that the pharmacological manipulation of pathways associated with macrophage apoptosis may affect the intracellular growth of

  2. S-substituted 3,5-dinitrophenyl 1,3,4-oxadiazole-2-thiols and tetrazole-5-thiols as highly efficient antitubercular agents.

    PubMed

    Karabanovich, Galina; Němeček, Jan; Valášková, Lenka; Carazo, Alejandro; Konečná, Klára; Stolaříková, Jiřina; Hrabálek, Alexandr; Pavliš, Oto; Pávek, Petr; Vávrová, Kateřina; Roh, Jaroslav; Klimešová, Věra

    2017-01-27

    Two new classes of antitubercular agents, namely 5-alkylsulfanyl-1-(3,5-dinitrophenyl)-1H-tetrazoles and 2-alkylsulfanyl-5-(3,5-dinitrophenyl)-1,3,4-oxadiazoles, and their structure-activity relationships are described. These compounds possessed excellent activity against Mycobacterium tuberculosis, including the clinically isolated multidrug (MDR) and extensively drug-resistant (XDR) strains, with no cross resistance with first or second-line anti-TB drugs. The minimum inhibitory concentration (MIC) values of the most promising compounds reached 0.03 μM. Furthermore, these compounds had a highly selective antimycobacterial effect because they were completely inactive against 4 gram positive and 4 gram negative bacteria and eight fungal strains and had low in vitro toxicity for four mammalian cell lines, including hepatic cell lines HepG2 and HuH7. Although the structure-activity relationship study showed that the presence of two nitro groups is highly beneficial for antimycobacterial activity, the analogues with a trifluoromethyl group instead of one of the nitro groups maintained a high antimycobacterial activity, which indicates the possibility for further structural optimization of this class of antitubercular agents.

  3. Synthesis and anti-mycobacterial activity of new 4-thiazolidinone and 1,3,4-oxadiazole derivatives of isoniazid.

    PubMed

    Bhat, Mashooq A

    2014-01-01

    A new series of 4-thiazolidinone (3a-e) and 1,3,4-oxadiazole (4a-e) derivatives of isoniazid were synthesized and evaluated for their in vitro anti-mycobacterial activity. The structures of the compounds were confirmed on the basis of spectral data and elemental analysis. Some compounds showed interesting activity against four Mycobacterium strains: M. intercellulari (ATCC 35743), M. xenopi (ATCC 14470), M. cheleneo (ATCC 35751) and M. smegmatis (ATCC 35797). Compounds 3e, N-(4-oxo-2-undecylthiazolidin-3-yl) isonicotinamide and 4e N-acetyl-4-(5-undecyl-1,3,4-oxadiazol-2-yl) pyridine with minimum inhibitory concentration (MIC), 6.0 μg/mL were found to be more potent than isoniazid under the in vitro investigational conditions. Compound 3e and 4e bear a high lipophilic chain bonded to the 5-position of the thiazolidinone and 1,3,4-oxadiazole moiety, respectively. This fact indicates that there exists a contribution of lipophilicity, which would facilitate the transport of these molecules through membranes.

  4. An In Silico Approach for Identification of Potential Anti-Mycobacterial Targets of Vasicine and Related Chemical Compounds.

    PubMed

    Chaliha, Amrita Kashyap; Gogoi, Dhrubajyoti; Chetia, Pankaj; Sarma, Diganta; Buragohain, Alak Kumar

    2016-01-01

    Tuberculosis (TB) is known to mankind as one of the most pervasive and persistent of diseases since the early days of civilization. The growing resistance of the causative pathogen Mycobacterium tuberculosis to the standard drug regimen for TB poses further difficulty in its treatment and control. Screening of novel plant-derived compounds with promising anti-tubercular activity has been cited as a prospective route for new anti-tubercular drug discovery and design. Justicia adhatoda L. is a perennial evergreen shrub which is widely mentioned in scientific literature on account of its potent anti-mycobacterial properties. In the present study, we have employed a series of computational methodologies to reveal the probable molecular interactions of vasicine, the principal alkaloid of Justicia adhatoda L., and two of its close natural derivatives- vasicinone and deoxyvasicine, with certain biological targets in M. tuberculosis. Targets were identified from literature and through a reverse Pharmacophore-based approach. Subsequent comparative molecular docking to identify the best ligand-target interactions revealed Antigen 85C of M. tuberculosis as the most potent biological target of vasicine on the basis of optimum molecular docking values. A chemogenomics approach was also employed to validate the molecular interactions between the same class of chemical compounds as vasicine and Antigen 85C. Further, a library of structural analogs of vasicine was created by bioiosterism-based drug design to identify structural analogs with better inhibitory potential against Antigen 85C.

  5. Enhancement of antimycobacterial Th1-cell responses by a Mycobacterium bovis BCG prime-protein boost vaccination strategy.

    PubMed

    Lu, Miao; Xia, Zhi Yang; Bao, Lang

    2013-01-01

    Tuberculosis is a major global health problem, and the only available vaccine Bacille Calmette-Guérin (BCG) is not sufficiently effective against the disease. It is extremely urgent to develop novel vaccine approaches. Previous research demonstrated that there were several Regions of Difference (RD1-16) between the substrains of BCG and Mycobacterium tuberculosis or Mycobacterium bovis. The ORFs Rv1769 and Rv1772 are located in the RD14 deletions and have not been major targets of study. However, some studies have demonstrated that the two genes (Rv1769 and Rv1772) are excellent T cell antigens, which might induce an immune response. What kind of role these ORFs might play in anti-mycobacterial immunity, however, is still unknown. In our research we used the BCG prime-protein boost strategy to immunize BALB/c mice and evaluated its immunogenicity. Our data suggest that our novel BCG-P+PRO69 vaccine could elicit the most long-lasting and strongest Th1 type cellular immune responses. This response is characterized by a strong antibody response, the proliferation rate of splenocytes, a high percentage of CD4+ and CD8+ T cells and high levels of IFN-γ in antigen-stimulated splenocyte cultures. These results indicate that prime-boost is a potent strategy and the protein of gene Rv1769 is a potential antigen or subunit vaccine to TB for further study.

  6. Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct mycobacteria growth indicator tube and phage amplified biological assay compared to BACTEC 460 TB.

    PubMed

    El-Sayed Zaki, Maysaa; Goda, Tarek

    2007-03-01

    The performance of antimycobacterial susceptibility testing for the first line drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria growth indicator tube (MGIT) and by bacteriophage amplified biological assay by FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system. This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN) smears. Sputum samples were subjected to culture and antimycobacterial susceptibility testing by BACTEC 460 TB. Samples were also tested by direct susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and streptomycine by MGIT. Sensitive and resistant isolates for RIF were further studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or in combination with other drugs. Multiple drugs resistance was 20%. The agreement between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST-plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the sensitive strains. For majority of strains direct susceptibility tests were available within 6.34-6.404 days (95% confidence interval) with direct mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5-11.5 days from the time that the sputum was received in the laboratory (95% confidence interval). From this study, we could conclude that direct MGIT AST is the quickest method for screening antimycobacterial susceptibility pattern for the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for detection of rifampicin resistance after primary culture which can be used as a surrogate marker for presence of MDR strains and the results were available within 10.5-11.5 days.

  7. [Long-term results of treatment of tuberculosis in patients who had not received a full basic course of antimycobacterial therapy].

    PubMed

    Valets'kyĭ, Iu M

    2002-01-01

    In those TB patients who had not received a full basic course of antimycobacterial therapy, long-term results of treatment are much worse (development of early and late recurrences comes to be more commonly seen--by as high as 6.43 and 5.03% respectively; transition to a chronic form by 20.29%, case mortality by 6.04%, with clinical cure recordable by 37.75% more seldom) than in those patients having received a full basic course of the above therapy.

  8. Antimycobacterial activity of methanolic plant extract of Artemisia capillaris containing ursolic acid and hydroquinone against Mycobacterium tuberculosis.

    PubMed

    Jyoti, Md Anirban; Nam, Kung-Woo; Jang, Woong Sik; Kim, Young-Hee; Kim, Su-Kyung; Lee, Byung-Eui; Song, Ho-Yeon

    2016-04-01

    In order to protect against Mycobacterium tuberculosis (MTB) infection, novel drugs and new targets should be screened from the vast source of plants. We investigated the potentiality of the herbal plant of Artemisia capillaris extract (AC) against Mycobacterium tuberculosis. In this study, we isolated ursolic acid and hydroquinone by bio-activity guided fractionation from the methanol extracts of AC, and tested the inhibitory effects against several strains of MTB. Anti-mycobacterial evaluation of these compounds was carried out using the MGIT™ 960 and resazurin assay. Mycobacterial morphological changes due to the treatment of these compounds were further evaluated by Transmission electron microscopy (TEM). Ursolic acid (UA) and hydroquinone (HQ) inhibited the growth of both susceptible and resistant strains of M. tuberculosis. The MIC (minimum inhibitory concentration) values of both UA and HQ were 12.5 μg/ml against the susceptible strains of M. tuberculosis. Also both UA and HQ showed 12.5-25 μg/ml of MIC values against MDR/XDR MTB strains. However, against clinical strains of MTB, UA was found sensitive against those strains that are sensitive against both INH and RFP but resistant against those strains that are resistant to INH. On the other hand HQ was sensitive against all clinical strains. TEM image-analysis of the strain H37Ra after treatment with UA revealed cell wall lysis, whereas HQ-treated cells showed deformed cytoplasmic morphology. All these results indicate that AC extracts containing UA and HQ possess promising chemotherapeutic potency against MTB for future use. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

    NASA Astrophysics Data System (ADS)

    Tran, Anh T.; Watson, Emma E.; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J.; Giltrap, Andrew M.; Pang, Angel; Wong, Weng Ruh; Linington, Roger G.; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A.; West, Nicholas P.; Bugg, Timothy D. H.; Tod, Julie; Dowson, Christopher G.; Roper, David I.; Crick, Dean C.; Britton, Warwick J.; Payne, Richard J.

    2017-03-01

    Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.

  10. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

    PubMed Central

    Tran, Anh T.; Watson, Emma E.; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J.; Giltrap, Andrew M.; Pang, Angel; Wong, Weng Ruh; Linington, Roger G.; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A.; West, Nicholas P.; Bugg, Timothy D. H.; Tod, Julie; Dowson, Christopher G.; Roper, David I.; Crick, Dean C.; Britton, Warwick J.; Payne, Richard J.

    2017-01-01

    Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis. PMID:28248311

  11. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis.

    PubMed

    Tran, Anh T; Watson, Emma E; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J; Giltrap, Andrew M; Pang, Angel; Wong, Weng Ruh; Linington, Roger G; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A; West, Nicholas P; Bugg, Timothy D H; Tod, Julie; Dowson, Christopher G; Roper, David I; Crick, Dean C; Britton, Warwick J; Payne, Richard J

    2017-03-01

    Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.

  12. Evaluation of a human BCG challenge model to assess antimycobacterial immunity induced by BCG and a candidate tuberculosis vaccine, MVA85A, alone and in combination.

    PubMed

    Harris, Stephanie A; Meyer, Joel; Satti, Iman; Marsay, Leanne; Poulton, Ian D; Tanner, Rachel; Minassian, Angela M; Fletcher, Helen A; McShane, Helen

    2014-04-15

    A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosis vaccine MVA85A. Participants were challenged with intradermal BCG 4 weeks after those who received MVA85A. Skin biopsies of the challenge site were taken 2 weeks post challenge and BCG load quantified by culture and quantitative polymerase chain reaction (qPCR). Volunteers with a history of BCG showed some degree of protective immunity to challenge, having lower BCG loads compared with volunteers without prior BCG, regardless of MVA85A status. There was a significant inverse correlation between antimycobacterial immunity at peak response after MVA85A and BCG load detected by qPCR. Our results support previous findings that this BCG challenge model is able to detect differences in antimycobacterial immunity induced by vaccination and could aid in the selection of candidate tuberculosis vaccines for field efficacy testing.

  13. A facile stereoselective synthesis of dispiro-indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids and evaluation of their antimycobacterial, anticancer and AchE inhibitory activities.

    PubMed

    Bharkavi, Chelliah; Vivek Kumar, Sundaravel; Ashraf Ali, Mohamed; Osman, Hasnah; Muthusubramanian, Shanmugam; Perumal, Subbu

    2016-11-15

    A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.

  14. Antimycobacterial activity of Citrullus colocynthis (L.) Schrad. against drug sensitive and drug resistant Mycobacterium tuberculosis and MOTT clinical isolates.

    PubMed

    Mehta, Archana; Srivastva, Garima; Kachhwaha, Sumita; Sharma, Meenakshi; Kothari, S L

    2013-08-26

    Citrullus colocynthis (Cucurbitaceae), a folk herbal medicine and traditionally used natural remedy for tuberculosis in India has been studied to validate its antitubercular activity against drug sensitive and drug resistant (including multidrug resistant) Mycobacterium tuberculosis and Mycobacterium other than tuberculosis (MOTT) bacilli. Inhibitory and bactericidal activities of crude extracts, fractions and compounds of Citrullus colocynthis plant, consisting of aerial parts and ripe deseeded fruits were performed against the drug sensitive standard strain of Mycobacterium tuberculosis H37Rv (ATCC 27294), 16 drug resistant strains of Mycobacterium tuberculosis and two MOTT strains, using radiometric BACTEC 460TB system. Methanolic extract of ripe deseeded fruit of Citrullus colocynthis has shown good activity (MIC ≤ 62.5 µg/ml), whereas among the bioactive fractions, FC IX demonstrated the best activity (MIC 31.2 µg/ml) against Mycobacterium tuberculosis H37Rv. Bioactive FC III, IX and X also inhibited 16 clinical isolates of Mycobacterium tuberculosis consisting of seven non-multidrug resistants, eight multidrug resistants, one extensively drug resistant and two of MOTTs with MICs in the range of 50-125, 31.2-125 and 62.5-125 µg/ml, respectively. Ursolic acid and cucurbitacin E 2-0-β-d-glucopyranoside were identified as the main biomarkers active against Mycobacterium tuberculosis H37Rv (MICs 50 and 25 µg/ml respectively), as well as against the 18 clinical isolates. FC III and FC IX showed better inhibition of drug resistant and MOTT clinical isolates. Minimal bactericidal concentrations of extracts, fractions and compound C-2 were ≥ two-fold MIC values. The study provides a scientific rationale for the traditional use of Citrullus colocynthis fruit in the treatment of tuberculosis. In addition, the study elucidates a broad spectrum antimycobacterial action of Citrullus colocynthis fruit, which can contribute to the development of improved preparation

  15. Synthesis, biological evaluation and structure-activity relationship of 2-styrylquinazolones as anti-tubercular agents.

    PubMed

    Jadhavar, Pradeep S; Dhameliya, Tejas M; Vaja, Maulikkumar D; Kumar, Dinesh; Sridevi, Jonnalagadda Padma; Yogeeswari, Perumal; Sriram, Dharmarajan; Chakraborti, Asit K

    2016-06-01

    2-Styrylquinazolones are reported as a novel class of potent anti-mycobacterial agents. Forty-six target compounds have been synthesized using one pot reaction involving isatoic anhydride, amine, and triethyl orthoacetate followed by aldehyde to construct the 2-styrylquinazolone scaffold. The anti-mycobacterial potency of the compounds was determined against H37Rv strain. Twenty-six compounds exhibited anti-Mtb activity in the range of 0.40-6.25μg/mL. Three compounds 8c, 8d and 8ab showed MIC of 0.78μg/mL and were found to be non-toxic (<50% inhibition at 50μg/mL) to HEK 293T cell lines with the therapeutic index >64. The most potent compound 8ar showed MIC of 0.40μg/mL with the therapeutic index >125. An early structure activity relationship for this class of compounds has been established. The computational studies indicate the possibility of these compounds binding to the penicillin binding proteins (PBPs).

  16. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... Orange Parkinson’s Awareness Month Were you exposed to herbicides during service and have Parkinson’s disease? You may ...

  17. Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh.

    PubMed

    Biá Ventura, Thatiana Lopes; da Silva Machado, Fernanda Lacerda; de Araujo, Marlon Heggdorne; de Souza Gestinari, Lísia Mônica; Kaiser, Carlos Roland; de Assis Esteves, Francisco; Lasunskaia, Elena B; Soares, Angélica Ribeiro; Muzitano, Michelle Frazão

    2015-10-01

    Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis. In the present study, we evaluated the inhibition of nitric oxide (NO) and tumor necrosis factor-α production and the anti-mycobacterial activity of crude extracts from the red Alga Laurencia dendroidea (from the South-Eastern coast of Brazil). Halogenated sesquiterpenes elatol (1), obtusol (2) and cartilagineol (3), previously isolated from this Alga by our group, were also studied. The lipopolysaccharide-activated macrophage cells (RAW 264.7) were used as inflammation model. Cytotoxic effect was determined using a commercial lactate dehydrogenase (LDH) kit and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The growing Mycobacterium inhibition was verified against Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H37 Rv strains. The crude extract from Alga collected at Angra dos Reis, RJ, Brazil, was the most active inhibitor of both mycobacterial growth (half maximal inhibitory concentration [IC50] 8.7 ± 1.4 μg/mL) and NO production by activated macrophages (IC50 5.3 ± 1.3 μg/mL). The assays with isolated compounds revealed the anti-mycobacterial activity of obtusol (2), whereas (-)-elatol (1) inhibited the release of inflammatory mediators, especially NO. To our knowledge, this is the first report describing an anti-mycobacterial effect of L. dendroidea extract and demonstrating the association of this activity with obtusol (2). The described effects of active compounds from L. dendroidea are promising for the control of inflammation in infectious diseases and specifically, against mycobacterial infections associated with exacerbated inflammation. Inflammation is strongly involved

  18. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

    PubMed Central

    Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

    2014-01-01

    The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis. PMID:25114509

  19. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites.

    PubMed

    Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

    2014-01-01

    The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.

  20. Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay.

    PubMed

    Ferrari, Michela De Luca; Telles, Maria Alice da Silva; Ferrazoli, Lucilaine; Levy, Carlos Emílio; Villares, Maria Cecília Barison; Moretti, Maria Luiza; Resende, Mariângela Ribeiro

    2010-08-01

    We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960 system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources.

  1. β-CA-specific inhibitor dithiocarbamate Fc14-584B: a novel antimycobacterial agent with potential to treat drug-resistant tuberculosis.

    PubMed

    Aspatwar, Ashok; Hammarén, Milka; Koskinen, Sanni; Luukinen, Bruno; Barker, Harlan; Carta, Fabrizio; Supuran, Claudiu T; Parikka, Mataleena; Parkkila, Seppo

    2017-12-01

    Inhibition of novel biological pathways in Mycobacterium tuberculosis (Mtb) creates the potential for alternative approaches for treating drug-resistant tuberculosis. In vitro studies have shown that dithiocarbamate-derived β-carbonic anhydrase (β-CA) inhibitors Fc14-594 A and Fc14-584B effectively inhibit the activity of Mtb β-CA enzymes. We screened the dithiocarbamates for toxicity, and studied the in vivo inhibitory effect of the least toxic inhibitor on M. marinum in a zebrafish model. In our toxicity screening, Fc14-584B emerged as the least toxic and showed minimal toxicity in 5-day-old larvae at 300 µM concentration. In vitro inhibition of M. marinum showed that both compounds inhibited growth at a concentration of 75 µM. In vivo inhibition studies using 300 µM Fc14-584B showed significant (p > .05) impairment of bacterial growth in zebrafish larvae at 6 days post infection. Our studies highlight the therapeutic potential of Fc14-584B as a β-CA inhibitor against Mtb, and that dithiocarbamate compounds may be developed into potent anti-tuberculosis drugs.

  2. Antimycobacterial activity of 'Virkon'.

    PubMed

    Broadley, S J; Furr, J R; Jenkins, P A; Russell, A D

    1993-03-01

    The peroxygen-based disinfectant, 'Virkon' (at concentrations of 2, 3 and 4%) was tested against Mycobacterium tuberculosis and M. avium-intracellulare over exposure times ranging between 30 and 120 min. Two test procedures were used: (a) a standard plate method, (b) a method incorporating the use of the 'Bactec' 460 radiometric system to chart bacterial growth following exposure to 'Virkon'. In our hands and under the conditions of the two test methods, 'Virkon' did not produce a satisfactory kill of the test strains over 60 or 120 min.

  3. Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

    PubMed Central

    Abdel-Aziz, Hatem A.; Eldehna, Wagdy M.; Fares, Mohamed; Al-Rashood, Sara T. A.; Al-Rashood, Khalid A.; Abdel-Aziz, Marwa M.; Soliman, Dalia H.

    2015-01-01

    In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones. PMID:25903147

  4. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    PubMed

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. [Advances in the development of new antitubercular agents from orthocondensed heterocyclic compounds. Part 3. Substances containing several types of heteroatoms in the six-membered ring].

    PubMed

    Waisser, K; Bures, O; Holý, P

    2001-11-01

    Tuberculosis and other mycobacterial diseases are considered to be one of the most important problems of contemporary health service. Since 1985 and particularly in the 1990s and at present the search for new structures of antimycobacterial agents have ranked among the foremost areas of chemotherapeutic research. The present review paper is already the 18th communication in a group of review papers about substances with antituberculotic effects, and the third, final, communication devoted in this series about the development of new antimycobacterial agents to ortho-condensed heterocyclic compounds in recent 15 years. The classification of ortho-condensed compounds is based on six-membered heterocyclic substructural fragments and the present study deals with the substructural fragments containing a greater number of different heteroatoms. The literature search is based on the journal Chemical Abstracts, Current Awareness in Biomedicine, part Mycobacteria, and original papers. Current Awareness in Biomedicine is, however, a very imperfect literature search source, recording only a fraction of communications. Review papers about five-membered heterocyclic antituberculotic ortho-condensed compounds was published in the present journal in 1999.

  6. Biological Agents

    MedlinePlus

    ... is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ... OSHA offers, visit OSHA's Workers' page. In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ...

  7. [Determination of antimycobacterial activities of fluoroquinolones against clinical isolates of Mycobacterium tuberculosis: comparative determination with egg-based Ogawa and agar-based Middlebrook 7H10 media].

    PubMed

    Yamane, N; Chilima, B Z; Tosaka, M; Okazawa, Y; Tanno, K

    1996-08-01

    The minimum inhibitory concentrations (MICs) to the fluoroquinolones, ofloxacin (OFLX), ciprofloxacin (CPFX), sparfloxacin (SPFX), norfloxacin (NFLX), balofloxacin (BLFX) and CS-940, were determined in 100 clinical isolates of Mycobacterium tuberculosis. The MICs were determined with 1% egg-based Ogawa or agar-based Middlebrook 7H10 and each of them supplemented with oxidation-reduction color dye, 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC) by using the microculture technique. The MICs determined with Ogawa medium were approximately two- to four-fold higher when compared to those determined with Middlebrook agar medium. The supplement with STC slightly increased the MICs, probably as a result of easily recognizing small initial colonies. Among the six fluoroquinolones, CS-940 and SPFX showed the greatest antimycobacterial activities with inhibition of 50% of all the isolates at the concentrations between 0.25 to 0.5 microgram/ml. OFLX, CPFX and BLFX followed in potency at 0.5 to 2.0 micrograms /ml. NFLX was less potent requiring 8 to 16 micrograms/ml to inhibit 50% of the isolates.

  8. Doubly end-on azido bridged mixed-valence cobalt trinuclear complex: Spectral study, VTM, inhibitory effect and antimycobacterial activity on human carcinoma and tuberculosis cells

    NASA Astrophysics Data System (ADS)

    Datta, Amitabha; Das, Kuheli; Sen, Chandana; Karan, Nirmal Kumar; Huang, Jui-Hsien; Lin, Chia-Her; Garribba, Eugenio; Sinha, Chittaranjan; Askun, Tulin; Celikboyun, Pinar; Mane, Sandeep B.

    2015-09-01

    Doubly end-on azido-bridged mixed-valence trinuclear cobalt complex, [Co3(L)2(N3)6(CH3OH)2] (1) is afforded by employing a potential monoanionic tetradentate-N2O2 Schiff base precursor (2-[{[2-(dimethylamino)ethyl]imino}methyl]-6-methoxyphenol; HL). Single crystal X-ray structure reveals that in 1, the adjacent CoII and CoIII ions are linked by double end-on azido bridges and thus the full molecule is generated by the site symmetry of a crystallographic twofold rotation axis. Complex 1 is subjected on different spectral analysis such as IR, UV-vis, emission and EPR spectroscopy. On variable temperature magnetic study, we observe that during cooling, the χMT values decrease smoothly until 15 K and then reaches to the value 1.56 cm3 K mol-1 at 2 K. Complex 1 inhibits the cell growth on human lung carcinoma (A549 cells), human colorectal (COLO 205 and HT-29 cells), and human heptacellular (PLC5 cells) carcinoma cells. Complex 1 exhibits anti-mycobacterial activity and considerable efficacy on Mycobacterium tuberculosis H37Rv ATCC 27294 and H37Ra ATCC 25177 strains.

  9. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  10. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  11. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  12. An Increase in Antimycobacterial Th1-Cell Responses by Prime-Boost Protocols of Immunization Does Not Enhance Protection against Tuberculosis

    PubMed Central

    Majlessi, Laleh; Simsova, Marcela; Jarvis, Zdenka; Brodin, Priscille; Rojas, Marie-Jésus; Bauche, Cécile; Nouzé, Clémence; Ladant, Daniel; Cole, Stewart T.; Sebo, Peter; Leclerc, Claude

    2006-01-01

    Bordetella pertussis adenylate cyclase (CyaA) toxoid is a powerful nonreplicative immunization vector targeting dendritic cells, which has already been used successfully in prophylactic and therapeutic vaccination in various preclinical animal models. Here, we investigated the potential of CyaA, harboring strong mycobacterial immunogens, i.e., the immunodominant regions of antigen 85A or the complete sequence of the 6-kDa early secreted antigenic target (ESAT-6) protein, to induce antimycobacterial immunity. By generating T-cell hybridomas or by using T cells from mice infected with mycobacteria, we first demonstrated that the in vitro delivery of 85A or ESAT-6 to antigen-presenting cells by CyaA leads to processing and presentation, by major histocompatibility complex class II molecules, of the same epitopes as those displayed upon mycobacterial infection. Importantly, compared to the recombinant protein alone, the presentation of ESAT-6 in vitro was 100 times more efficient upon its delivery to antigen-presenting cells in fusion to CyaA. Immunization with CyaA-85A or CyaA-ESAT-6 in the absence of any adjuvant induced strong antigen-specific lymphoproliferative, interleukin-2 (IL-2) and gamma interferon (IFN-γ) cytokine responses, in the absence of any IL-4 or IL-5 production. When used as boosters after priming with a BCG expressing ESAT-6, the CyaA-85A and CyaA-ESAT-6 proteins were able to strikingly increase the sensitivity and intensity of proliferative and Th1-polarized responses and notably the frequency of antigen-specific IFN-γ-producing CD4+ T cells. However, immunization with these CyaA constructs as subunit vaccines alone or as boosters did not allow induction or improvement of protection against Mycobacterium tuberculosis infection. These results question the broadly admitted correlation between the frequency of IFN-γ-producing CD4+ T cells and the level of protection against tuberculosis. PMID:16552042

  13. Synthesis and biological activity of quaternary ammonium salt-type agents containing cholesterol and terpenes.

    PubMed

    Novotná, Eva; Waisser, Karel; Kuneš, Jiří; Palát, Karel; Buchta, Vladimír; Stolaříková, Jiřina; Beckert, Rainer; Wsól, Vladimír

    2014-06-01

    New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized. The compounds showed promising antibacterial and antimycobacterial activities. Those compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium. On the contrary, the antimycobacterial activity increased with the presence of the terpene unit in the molecule.

  14. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  15. Discovery of novel N-phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity.

    PubMed

    Lentz, Fabian; Hemmer, Marc; Reiling, Norbert; Hilgeroth, Andreas

    2016-12-15

    There is an urgent need for novel drugs for the treatment of tuberculosis (TB) due to the increasing prevalence of antibiotic resistance among Mycobacterium tuberculosis (Mtb) strains against first-line and second-line therapeutics. We developed novel N-phenyl 1,4-dihydropyridines as potential antituberculotic agents. The observed activity depends on the substitution patterns of the aromatic residues. N-unsubstituted 1,4-dihydropyridines are known inhibitors of the cancer-relevant transmembrane efflux pump ABCB1. Based on the similarity of ABCB1 amino acids sequences relevant to 1,4-dihydropyridine binding and the MTb efflux pump Rv0194, we determined ABCB1-inhibitory properties of our compounds in a cell line model. We identified one compound, which substantially increased the activity of two antituberculotic drugs which are substrates of ABCB1. The data indicate that our N-phenyl 1,4-dihydropyridines represent a novel compound class which improves the efficacy of anti-TB drugs by interfering with transmembrane efflux pumps in Mtb. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Antimycobacterial, antimicrobial activity, experimental (FT-IR, FT-Raman, NMR, UV-Vis, DSC) and DFT (transition state, chemical reactivity, NBO, NLO).

    PubMed

    Rawat, Poonam; Singh, R N; Ranjan, Alok; Ahmad, Sartaj; Saxena, Rajat

    2017-02-11

    As part of a study of pyrrole hydrazone, we have investigated quantum chemical calculations, molecular geometry, relative energy, vibrational properties and antimycobacterial/antimicrobial activity of pyrrole-2-carboxaldehyde isonicotinyl hydrazone (PCINH), by applying the density functional theory (DFT) and Hartree Fock (HF). Good reproduction of experimental values is obtained and with small percentage error in majority of the cases in comparison to theoretical result (DFT). The experimental FT-IR and Raman wavenumbers were compared with the respective theoretical values obtained from DFT calculations and found to agree well. In crystal structure studies the hydrated PCINH (syn-syn conformer) shows different conformation than from anhydrous form (syn-anti conformer). The rotational barrier between syn-syn and syn-anti conformers of PCINH is 12.7kcal/mol in the gas phase. In this work, use of FT-IR, FT-Raman, (1)H NMR, (13)C NMR and UV-Vis spectroscopies has been made for full characterization of PCINH. A detailed interpretation of the vibrational spectrum was carried out with the aid of normal coordinate analysis using single scaling factor. Our results support the hydrogen bonding pattern proposed by reported crystalline structure. The calculated nature of electronic transitions within molecule found to be π→π*. The electronic descriptors study indicates that PCINH can be used as robust synthon for synthesis of new heterocyclic compounds. The first static hyperpolarizability (β0) of PCINH is calculated as 33.89×10(-30)esu, (gas phase); 68.79×10(-30) (CHCl3), esu; 76.76×10(-30)esu (CH2Cl2), 85.16×10(-30)esu (DMSO). The solvent induced effects on the first static hyperpolarizability were studied and found to increase as dielectric constants of the solvents increases. Investigated molecule shows better NLO value than Para nitroaniline (PNA). The compound PCINH shows good antifungal and antibacterial activity against Aspergillus niger and gram

  17. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  18. Detecting agents.

    PubMed Central

    Johnson, Susan C

    2003-01-01

    This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed. PMID:12689380

  19. Mutation of Rv2887, a marR-Like Gene, Confers Mycobacterium tuberculosis Resistance to an Imidazopyridine-Based Agent

    PubMed Central

    Winglee, Kathryn; Lun, Shichun; Pieroni, Marco; Kozikowski, Alan

    2015-01-01

    Drug resistance is a major problem in Mycobacterium tuberculosis control, and it is critical to identify novel drug targets and new antimycobacterial compounds. We have previously identified an imidazo[1,2-a]pyridine-4-carbonitrile-based agent, MP-III-71, with strong activity against M. tuberculosis. In this study, we evaluated mechanisms of resistance to MP-III-71. We derived three independent M. tuberculosis mutants resistant to MP-III-71 and conducted whole-genome sequencing of these mutants. Loss-of-function mutations in Rv2887 were common to all three MP-III-71-resistant mutants, and we confirmed the role of Rv2887 as a gene required for MP-III-71 susceptibility using complementation. The Rv2887 protein was previously unannotated, but domain and homology analyses suggested it to be a transcriptional regulator in the MarR (multiple antibiotic resistance repressor) family, a group of proteins first identified in Escherichia coli to negatively regulate efflux pumps and other mechanisms of multidrug resistance. We found that two efflux pump inhibitors, verapamil and chlorpromazine, potentiate the action of MP-III-71 and that mutation of Rv2887 abrogates their activity. We also used transcriptome sequencing (RNA-seq) to identify genes which are differentially expressed in the presence and absence of a functional Rv2887 protein. We found that genes involved in benzoquinone and menaquinone biosynthesis were repressed by functional Rv2887. Thus, inactivating mutations of Rv2887, encoding a putative MarR-like transcriptional regulator, confer resistance to MP-III-71, an effective antimycobacterial compound that shows no cross-resistance to existing antituberculosis drugs. The mechanism of resistance of M. tuberculosis Rv2887 mutants may involve efflux pump upregulation and also drug methylation. PMID:26303802

  20. Synthesis, in vitro antimycobacterial evaluation and docking studies of some new 5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one schiff bases.

    PubMed

    Malothu, Narender; Bhandaru, Jaswanth S; Kulandaivelu, Umasankar; Jojula, Malathi; Adidala, Raghuram Reddy; K R, Umadevi; A V N, Dusthackeer; Kaki, Venkat Rao; Akkinepally, Raghuram R

    2016-02-01

    Development of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) has been considered as major health burden, globally. In order to develop novel, potential molecules against drug resistant TB, twenty two (22) new 3-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (6a-k) and 3-substituted-7-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one (7a-k) derivatives were designed and synthesized by using appropriate synthetic protocols. Pantothenate synthetase (PS) was considered as the target for the molecular docking studies and evaluated the binding pattern at active site, as PS plays a significant role in the biosynthesis of pantothenate in Mycobacterium tuberculosis (MTB). The preliminary in vitro antibacterial screening of test compounds was carried out against two strains of Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. The antimycobacterial screening was performed against MTB H37Rv and an isoniazid-resistant clinical isolate of MTB. The compounds 6b, 6c, 6d, 6k, 7b, 7c, 7d and 7k exhibited promising antibacterial activity MIC in the range of 15-73 μM against all bacterial strains used and compounds 6d and 7b showed antimycobacterial activity (IC50 <340 μM in LRP assay) and (MIC <9 μM in broth microdilution method).

  1. Design of novel dispirooxindolopyrrolidine and dispirooxindolopyrrolothiazole derivatives as potential antitubercular agents.

    PubMed

    Mhiri, Chourouk; Boudriga, Sarra; Askri, Moheddine; Knorr, Michael; Sriram, Dharmarajan; Yogeeswari, Perumal; Nana, Frédéric; Golz, Christopher; Strohmann, Carsten

    2015-10-01

    With the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (Z)-3-arylidenebenzofuran-2-ones, substituted isatin derivatives and α-aminoacids. The stereochemistry of the spiroadducts has been confirmed by an X-ray diffraction analysis. All the target heterocycles were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the most active compounds were subjected to cytotoxicity studies against (RAW 264.7) cell lines. Among them, twelve compounds showed potent anti-tubercular activity with MIC ranging from 1.56 to 6.25 μg/mL. In particular dispirooxindolopyrrolothiazole derivatives 5c and 5f were found to be the most active (MIC of 1.56 μg/mL) with a good safety profile (27.53% and 20.74% at 50 μM, respectively). This is the first report demonstrating the benzofuranone oxindole hybrids as potential antimycobacterial agents.

  2. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  3. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  4. Antimycobacterial activity of lichen substances.

    PubMed

    Honda, N K; Pavan, F R; Coelho, R G; de Andrade Leite, S R; Micheletti, A C; Lopes, T I B; Misutsu, M Y; Beatriz, A; Brum, R L; Leite, C Q F

    2010-04-01

    We describe here the extraction and identification of several classes of phenolic compounds from the lichens Parmotrema dilatatum (Vain.) Hale, Parmotrema tinctorum (Nyl.) Hale, Pseudoparmelia sphaerospora (Nyl.) Hale and Usnea subcavata (Motyka) and determined their anti-tubercular activity. The depsides (atranorin, diffractaic and lecanoric acids), depsidones (protocetraric, salazinic, hypostictic and norstictic acids), xanthones (lichexanthone and secalonic acid), and usnic acid, as well seven orsellinic acid esters, five salazinic acid 8',9'-O-alkyl derivatives and four lichexanthone derivatives, were evaluated for their activity against Mycobacterium tuberculosis. Diffractaic acid was the most active compound (MIC value 15.6mug/ml, 41.6 microM), followed by norstictic acid (MIC value 62.5 microg/ml, 168 microM) and usnic acid (MIC value 62.5 microg/ml, 182 microM). Hypostictic acid (MIC value 94.0 microg/ml, 251 microM) and protocetraric acid (MIC value 125 microg/ml, 334 microM) showed moderate inhibitory activity. The other compounds showed lower inhibitory activity on the growth of M. tuberculosis, varying from MIC values of 250 to 1370 microM. Copyright 2009 Elsevier GmbH. All rights reserved.

  5. Methyl-Hydroxylamine as an Efficacious Antibacterial Agent That Targets the Ribonucleotide Reductase Enzyme

    PubMed Central

    Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

    2015-01-01

    The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme. PMID:25782003

  6. Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.

    PubMed

    Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

    2015-01-01

    The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.

  7. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  8. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  9. Chemical warfare agents.

    PubMed

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  10. Identification, synthesis, and pharmacological evaluation of tetrahydroindazole based ligands as novel antituberculosis agents.

    PubMed

    Guo, Songpo; Song, Yang; Huang, Qingqing; Yuan, Hai; Wan, Baojie; Wang, Yuehong; He, Rong; Beconi, Maria G; Franzblau, Scott G; Kozikowski, Alan P

    2010-01-28

    The resurgence of tuberculosis (TB), the incidence of drug-resistant strains of Mycobacterium tuberculosis (MTB), and the coinfection between TB and HIV have led to serious infections, high mortality, and a global health threat, resulting in the urgent search for new classes of antimycobacterial agents. Herein, we report the identification of a novel class of tetrahydroindazole based compounds as potent and unique inhibitors of MTB. Compounds 6a, 6m, and 6q exhibited activity in the low micromolar range against replicating Mycobacterium tuberculosis (R-TB) phenotype, with minimum inhibitory concentrations (MICs) of 1.7, 1.9, and 1.9 muM, respectively, while showing no toxicity to Vero Ccells. Moreover, studies aimed to assess the in vitro metabolic stability of 6a and 6m in mouse liver microsomes and in vivo pharmacokinetic profiles in plasma levels gave satisfactory results. This research suggests that tetrahydroindazole based anti-TB compounds can serve as a promising lead scaffold in developing new drugs to combat tuberculosis infections.

  11. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  12. Intelligent Agents: A Primer.

    ERIC Educational Resources Information Center

    Yu, Edmund; Feldman, Susan

    1999-01-01

    Provides an in-depth introduction to the various technologies that are bringing intelligent agents into the forefront of information technology, explaining how such agents work, the standards involved, and how agent-based applications can be developed. (Author/AEF)

  13. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  14. Ultrasound Contrast Agents

    NASA Astrophysics Data System (ADS)

    Cachard, Christian; Basset, Olivier

    While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.

  15. Moral actor, selfish agent.

    PubMed

    Frimer, Jeremy A; Schaefer, Nicola K; Oakes, Harrison

    2014-05-01

    People are motivated to behave selfishly while appearing moral. This tension gives rise to 2 divergently motivated selves. The actor-the watched self-tends to be moral; the agent-the self as executor-tends to be selfish. Three studies present direct evidence of the actor's and agent's distinct motives. To recruit the self-as-actor, we asked people to rate the importance of various goals. To recruit the self-as-agent, we asked people to describe their goals verbally. In Study 1, actors claimed their goals were equally about helping the self and others (viz., moral); agents claimed their goals were primarily about helping the self (viz., selfish). This disparity was evident in both individualist and collectivist cultures, attesting to the universality of the selfish agent. Study 2 compared actors' and agents' motives to those of people role-playing highly prosocial or selfish exemplars. In content (Study 2a) and in the impressions they made on an outside observer (Study 2b), actors' motives were similar to those of the prosocial role-players, whereas agents' motives were similar to those of the selfish role-players. Study 3 accounted for the difference between the actor and agent: Participants claimed that their agent's motives were the more realistic and that their actor's motives were the more idealistic. The selfish agent/moral actor duality may account for why implicit and explicit measures of the same construct diverge, and why feeling watched brings out the better angels of human nature.

  16. Chemical warfare agents.

    PubMed

    Chauhan, S; Chauhan, S; D'Cruz, R; Faruqi, S; Singh, K K; Varma, S; Singh, M; Karthik, V

    2008-09-01

    Chemical warfare agents (CWA's) are defined as any chemical substance whose toxic properties are utilised to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have been used in war since times immemorial, but their use reached a peak during World War I. During World War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There has been a legislative effort worldwide to ban the use of CWA's under the chemical weapons convention which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are classified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants, choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating as a nuclear bomb. In addition to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briefly about the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity, clinical features of exposure and pharmacological management of casualties caused by chemical agents. Copyright © 2008 Elsevier B.V. All rights reserved.

  17. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  18. Decontamination Data - Blister Agents

    EPA Pesticide Factsheets

    Decontamination efficacy data for blister agents on various building materials using various decontamination solutionsThis dataset is associated with the following publication:Stone, H., D. See, A. Smiley, A. Ellingson, J. Schimmoeller, and L. Oudejans. Surface Decontamination of Blister Agents Lewisite, Sulfur Mustard and Agent Yellow, a Lewisite and Sulfur Mustard Mixture. JOURNAL OF HAZARDOUS MATERIALS. Elsevier Science Ltd, New York, NY, USA, 1-5, (2015).

  19. Synthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds.

    PubMed

    Verbitskiy, Egor V; Cheprakova, Ekaterina M; Slepukhin, Pavel A; Kravchenko, Marionella A; Skornyakov, Sergey N; Rusinov, Gennady L; Chupakhin, Oleg N; Charushin, Valery N

    2015-06-05

    Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SN(H)) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from commercially available 5-bromopyrimidine. All new pyrimidines were found to be active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice have been obtained for these compounds which appear to be promising antitubercular agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  1. Etiological agents of diarrhoea.

    PubMed

    Ghosh, A R; Paul, M; Pal, S C; Sen, D

    1990-01-01

    Two decades of research have established newer pathogens and techniques in establishing several organisms of diarrhoeal diseases as aetiological agents. It is now possible to detect an agent in 80% of the situation of diarrhoea in a standard laboratory. The brief review describes the list of pathogens, their diagnostic techniques with short description on clinical and epidemiological status.

  2. Detecting biological warfare agents.

    PubMed

    Song, Linan; Ahn, Soohyoun; Walt, David R

    2005-10-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array.

  3. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  4. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  5. Differences among immunosuppressive agents.

    PubMed Central

    Hitchings, G H

    1982-01-01

    Immunosuppressive agents have diverse (although often multiple) sites of action in the cell sequences that are involved in immune responses. New routes to selectivity are apparent at both the cellular and the biochemical level. Meanwhile, clinical work is finding new uses and more selective employment of the currently available agents. PMID:6802083

  6. Detecting Biological Warfare Agents

    PubMed Central

    Song, Linan; Ahn, Soohyoun

    2005-01-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

  7. Ferrimagnetic susceptibility contrast agents.

    PubMed

    Bach-Gansmo, T

    1993-01-01

    Contrast agents based on superparamagnetic particles have been in clinical development for more than 5 years, and the complexity of their effects is still not elucidated. The relaxivities are frequently used to give an idea of their efficacy, but these parameters can only be used if they are concentration independent. For large superparamagnetic systems, the evolution of the transverse magnetization is biexponential, after an initial loss of magnetization. Both these characteristics of large superparamagnetic systems should lead to prudence in using the relaxivities as indicators of contrast medium efficacy. Susceptibility induced artefacts have been associated with the use of superparamagnetic contrast agents since the first imaging evaluation took place. The range of concentrations where good contrast effect was achieved without inducing artefacts, as well as blurring and metal artefacts were evaluated. The influence of motion on the induction of artefacts was studied, and compared to the artefacts induced by a paramagnetic agent subject to motion. With a suitable concentration of a negative contrast agent, a signal void could be achieved in the region prone to motion, and no artefacts were induced. If the concentration was too high, a displacement of the region close to the contrast agent was observed. The artefacts occurred in a volume surrounding the contrast agent, i.e., also outside the imaging plane. In comparison a positive, paramagnetic contrast agent induced heavy artefacts in the phase encoding direction, appearing as both high intensity regions and black holes, in a mosaic pattern. Clinical trials of the oral contrast agent OMP for abdominal MR imaging showed this agent to be safe and efficacious. OMP increased the diagnostic efficacy of abdominal MR imaging in 2 of 3 cases examined, with a significant decrease in motion artefacts. Susceptibility contrast agents may also be of use in the evaluation of small lesions in the liver. Particulate material

  8. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  9. Synthesis of potent inhibitors of β-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents.

    PubMed

    Liu, Yan; Zhong, Wu; Li, Rui-Juan; Li, Song

    2012-04-25

    Mycobacterium tuberculosis FabH, an essential enzyme in the mycolic acid biosynthetic pathway, is an attractive target for novel anti-tubercolosis agents. Structure-based design and synthesis of 1-(4-carboxybutyl)-4-(4-(substituted benzyloxy)phenyl)-1H-pyrrole-2-carboxylic acid derivatives 7a-h, a subset of eight potential FabH inhibitors, is described in this paper. The Vilsmeier-Haack reaction was employed as a key step. The structures of all the newly synthesized compounds were identified by IR, ¹H-NMR, ¹³C-NMR, ESI-MS and HRMS. The alamarBlue™ microassay was employed to evaluate the compounds 7a-h against Mycobacterium tuberculosis H₃₇Rv. The results demonstrate that the compound 7d possesses good in vitro antimycobacterial activity against Mycobacterium tuberculosis H₃₇Rv (Minimum Inhibitory Concentration value [MIC], 12.5 µg/mL).These compounds may prove useful in the discovery and development of new anti-tuberculosis drugs.

  10. Structure-activity relationships of quinolone agents against mycobacteria: effect of structural modifications at the 8 position.

    PubMed Central

    Renau, T E; Gage, J W; Dever, J A; Roland, G E; Joannides, E T; Shapiro, M A; Sanchez, J P; Gracheck, S J; Domagala, J M; Jacobs, M R; Reynolds, R C

    1996-01-01

    A series of quinolones with substitutions at the 8 position has been prepared as part of a study to examine the relationship between structural modifications at this position and activity against mycobacteria. The compounds were prepared by procedures described in the literature and were evaluated for their activities against Mycobacterium fortuitum and Mycobacterium smegmatis. The activities of the compounds against these two organisms were used as a measure of Mycobacterium tuberculosis activity. The results demonstrate that the contribution of the 8 position to antimycobacterial activity was dependent on the substituent at N-1 and was in the order (i) COMe approximately CBr > CCI > CH approximately CF approximately COEt > N > CCF3 when N-1 was cyclopropyl; (ii) N approximately CH > CF > COMe when N-1 was 2,4-difluorophenyl; (iii) N > or = CH when N-1 was tert-butyl; and (iv) N > CH when N-1 was ethyl. In general, derivatives with piperazine substitutions at C-7 were slightly less active against mycobacteria than the analogs with pyrrolidine substitutions, regardless of the pattern of substitution at the 8 position. Several of the best compounds were evaluated for their potential side effects as well as their activities against Mycobacterium aurum, Mycobacterium avium-M. intracellulare, and M. tuberculosis. These agents exhibited biological profiles similar to or better than those of the positive controls ciprofloxacin and sparfloxacin. PMID:8891145

  11. Biological warfare agents.

    PubMed

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-07-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  12. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  13. Topical hemostatic agents: a review.

    PubMed

    Palm, Melanie D; Altman, Jeffrey S

    2008-04-01

    Topical hemostatic agents play an important role in both common and specialized dermatologic procedures. These agents can be classified based on their mechanism of action and include physical or mechanical agents, caustic agents, biologic physical agents, and physiologic agents. Some agents induce protein coagulation and precipitation resulting in occlusion of small cutaneous vessels, while others take advantage of latter stages in the coagulation cascade, activating biologic responses to bleeding. Traditional and newer topical hemostatic agents are discussed in this review, and the benefits and costs of each agent will be provided.

  14. Anti-mycobacterial activity of garlic (Allium sativum) against multi-drug resistant and non-multi-drug resistant mycobacterium tuberculosis.

    PubMed

    Hannan, Abdul; Ikram Ullah, Muhammad; Usman, Muhammad; Hussain, Shahid; Absar, Muhammad; Javed, Khursheed

    2011-01-01

    Emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) TB throughout the developing world is very disturbing in the present scenario of TB management. There is a fundamental need to explore alternative anti-TB agents. Hence natural plants should be investigated to understand their antimicrobial properties and safety. Garlic (Allium sativum) is one of natural plant which possesses variety of biological properties like anti-tumor, anti-hyperlipedemic and anti-microbial etc. The present study was evaluated for anti-bacterial activity of garlic against non-MDR and MDR isolates of M. tuberculosis. A total of 20 clinical isolates of MTB including 15 MDR and 5 non-MDR were investigated. Ethanolic extract of garlic was prepared by maceration method. Minimum inhibitory concentration (MIC) was performed by using 7H9 middle brook broth dilution technique. MIC of garlic extract was ranged from 1 to 3 mg/ml; showing inhibitory effects of garlic against both non-MDR and MDR M. tuberculosis isolates. Alternate medicine practices with plant extracts including garlic should be considered to decrease the burden of drug resistance and cost in the management of diseases. The use of garlic against MDR-TB may be of great importance regarding public health.

  15. Drug Hepatotoxicity: Newer Agents.

    PubMed

    Bunchorntavakul, Chalermrat; Reddy, K Rajender

    2017-02-01

    Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents. Nevertheless, cases of severe hepatotoxicity have been reported due to some of these newer agents, including, trastuzumab, ipilimumab, infliximab, imatinib, bosutinib, dasatinib, gefitinib, erlotinib, sunitinib, ponatinib, lapatinib, vemurafenib, dabigatran, rivaroxaban, felbamate, lamotrigine, levetiracetam, venlafaxine, duloxetine, darunavir, and maraviroc. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  17. Delta agent (Hepatitis D)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  18. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  19. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  20. Encapsulation of zinc-rifampicin complex into transferrin-conjugated silver quantum-dots improves its antimycobacterial activity and stability and facilitates drug delivery into macrophages

    PubMed Central

    Pati, Rashmirekha; Sahu, Rojalin; Panda, Jagannath; Sonawane, Avinash

    2016-01-01

    In order to improve the chemotherapy of tuberculosis, there is an urgent need to enhance the efficacy of existing agents and also to develop more efficient drug delivery systems. Here, we synthesized a novel anti-TB drug complex consisting of zinc and rifampicin (Zn-RIF), and encapsulated it into transferrin-conjugated silver quantum-dots (Zn-RIF-Tf-QD) to improve delivery in macrophages. Successful synthesis of Zn-RIF and Zn-RIF-Tf-QD was confirmed by UV/Vis-spectroscopy, TEM, FTIR, photoluminescence, XRD, XPS, and NMR. The sizes of silver QDs and transferrin-conjugated QDs were found to be in the range of 5–20 nm. Activity assays showed that Zn-RIF-Tf-QD exhibited 10-fold higher antibacterial activity against Mycobacterium smegmatis and Mycobacterium bovis-BCG as compared to Zn-RIF, RIF and Zn. Immunofluorescence studies showed that Zn-RIF-Tf-QD-conjugates were actively endocytosed by macrophages and dendritic cells, but not by lung epithelial cells. Treatment with Zn-RIF-Tf-QD efficiently killed mycobacteria residing inside macrophages without exhibiting cytotoxicity and genotoxicity. Moreover, the conjugates remained stable for upto 48 h, were taken up into the late endosomal compartment of macrophages, and released the drug in a sustainable manner. Our data demonstrate that Zn-RIF-Tf-QDs have a great potential as anti-TB drugs. In addition, transferrin-conjugated QDs may constitute an effective drug delivery system for tuberculosis therapy. PMID:27113139

  1. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  2. Sunscreening agents: a review.

    PubMed

    Latha, M S; Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B R

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents.

  3. Hybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: SAR and docking studies.

    PubMed

    Pisal, Mahesh M; Nawale, Laxman U; Patil, Manoj D; Bhansali, Sujit G; Gajbhiye, Jayant M; Sarkar, Dhiman; Chavan, Subhash P; Borate, Hanumant B

    2017-02-15

    A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11-14 exhibited antitubercular activity in vitro (MIC 7.6-19.1 μg/mL, 12-35 μM) against dormant stage while the compound 15 exhibited antitubercular activity in vitro against dormant (MIC 23.4 μg/mL, 41 μM) as well as active (MIC 25.4 μg/mL, 45 μM) stage. Structural modifications of the compound 15 were carried out to study the structure-activity relationship and it was observed that the compound 18 exhibited antitubercular activity comparable to the compound 15. Cytotoxicity studies revealed that these molecules were non-toxic. The docking study of the compound 15 showed that there was binding with the active site of mycobacterial pantothenate synthetase. Further docking studies led to the synthesis of the compounds 16 and 17 and the antitubercular activity screening results showed that these compounds have significant antitubercular activity. The compounds 15-18 (MIC 11-29 μg/mL, 19-51 μM) can be used as starting points for further optimization. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures and the present results will be very useful in the development of a new class of antimycobacterial agents.

  4. Antimycobacterial, antimicrobial activity, experimental (FT-IR, FT-Raman, NMR, UV-Vis, DSC) and DFT (transition state, chemical reactivity, NBO, NLO) studies on pyrrole-isonicotinyl hydrazine

    NASA Astrophysics Data System (ADS)

    Rawat, Poonam; Singh, R. N.; Ranjan, Alok; Ahmad, Sartaj; Saxena, Rajat

    2017-05-01

    As part of a study of pyrrole hydrazone, we have investigated quantum chemical calculations, molecular geometry, relative energy, vibrational properties and antimycobacterial/antimicrobial activity of pyrrole-2-carboxaldehyde isonicotinyl hydrazone (PCINH), by applying the density functional theory (DFT) and Hartree Fock (HF). Good reproduction of experimental values is obtained and with small percentage error in majority of the cases in comparison to theoretical result (DFT). The experimental FT-IR and Raman wavenumbers were compared with the respective theoretical values obtained from DFT calculations and found to agree well. In crystal structure studies the hydrated PCINH (syn-syn conformer) shows different conformation than from anhydrous form (syn-anti conformer). The rotational barrier between syn-syn and syn-anti conformers of PCINH is 12.7 kcal/mol in the gas phase. In this work, use of FT-IR, FT-Raman, 1H NMR, 13C NMR and UV-Vis spectroscopies has been made for full characterization of PCINH. A detailed interpretation of the vibrational spectrum was carried out with the aid of normal coordinate analysis using single scaling factor. Our results support the hydrogen bonding pattern proposed by reported crystalline structure. The calculated nature of electronic transitions within molecule found to be π → π*. The electronic descriptors study indicates that PCINH can be used as robust synthon for synthesis of new heterocyclic compounds. The first static hyperpolarizability (β0) of PCINH is calculated as 33.89 × 10- 30 esu, (gas phase); 68.79 × 10- 30 (CHCl3), esu; 76.76 × 10- 30 esu (CH2Cl2), 85.16 × 10- 30 esu (DMSO). The solvent induced effects on the first static hyperpolarizability were studied and found to increase as dielectric constants of the solvents increases. Investigated molecule shows better NLO value than Para nitroaniline (PNA). The compound PCINH shows good antifungal and antibacterial activity against Aspergillus niger and gram

  5. [Preparation of antineoplastic agents].

    PubMed

    Descoutures, J-M

    2006-01-01

    In the last fifteen years, the preparation of antineoplastic agents has tended to be centralized in the hospital pharmacy for two main reasons: to enable better protection for the staff, to enable better safety for the patient. The consequences of this organization have led to standardization of techniques, implementation of a quality system and also a better use of antineoplastic agents. After protocols have been standardized by the physician and validated by the pharmacist, four main steps are necessary: phamaceutical validation of the prescription, preparation of IV admixtures according to a production file, control of the final product, dispatching of the preparation to the patient. Computer-controlled processes guarantee the safety of these different steps. The centralized preparations are made either with a vertical laminar flow hood or with an isolator. With the implementation of the National Cancer Plan, antineoplastic agents for patients on home treatments will also be prepared in centralized hospital pharmacies.

  6. Polyphenols as antimicrobial agents.

    PubMed

    Daglia, Maria

    2012-04-01

    Polyphenols are secondary metabolites produced by higher plants, which play multiple essential roles in plant physiology and have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents. In the present review the antibacterial, antiviral, and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship. Moreover, considering that the microbial resistance has become an increasing global problem, and there is a compulsory need to find out new potent antimicrobial agents as accessories to antibiotic therapy, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms is discussed.

  7. MpcAgent

    SciTech Connect

    Nutaro, James

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of the building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.

  8. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  9. Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents report: nationwide study

    Treesearch

    Deborah J. Chavez; Joanne F. Tynon

    2007-01-01

    This is the fourth in a series of studies to evaluate perceptions of U.S. Department of Agriculture Forest Service law enforcement personnel of the roles, responsibilities, and issues related to their jobs. An e-mail survey was administered to the 89 Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents...

  10. Model Checking Normative Agent Organisations

    NASA Astrophysics Data System (ADS)

    Dennis, Louise; Tinnemeier, Nick; Meyer, John-Jules

    We present the integration of a normative programming language in the MCAPL framework for model checking multi-agent systems. The result is a framework facilitating the implementation and verification of multi-agent systems coordinated via a normative organisation. The organisation can be programmed in the normative language while the constituent agents may be implemented in a number of (BDI) agent programming languages.

  11. Thrombolytic agents in development.

    PubMed

    Verstraete, M; Lijnen, H R; Collen, D

    1995-07-01

    The quest continues for thrombolytic agents with a higher thrombolytic potency, specific thrombolytic activity and/or a better fibrin selectivity. Several lines of research towards improvement of thrombolytic agents are being explored, including the construction of mutants and variants of plasminogen activators (PAs), chimaeric PAs, conjugates of PAs with monoclonal antibodies, and PAs from animal or bacterial origin. Some of these new thrombolytic agents have shown promise in animal models of venous or arterial thrombosis and in pilot clinical studies. Such molecules include numerous mutants of tissue-type PA (t-PA) with prolonged in vivo half-life and/or resistance to protease inhibitors, and chimaeric PAs consisting of different regions of t-PA and of urokinase-type PA (u-PA). Several molecular forms of the thrombolytic substance in the saliva of the vampire bat have been characterised and cloned. Vampire bat PA exhibits 85% homology to human t-PA but lacks kringle 2 and the plasmin-sensitive cleavage site. A thrombolytic enzyme of 203 amino acids is present in the venom of a southern copperhead snake. This polypeptide, termed fibrolase, is now produced by recombinant technology. Fibrolase does not activate plasminogen or protein C, but directly degrades the alpha and beta chains of fibrin and fibrinogen. Recombinant staphylokinase is not an enzyme, but it forms a 1:1 stoichiometric complex with plasminogen, which becomes active after conversion of plasminogen to plasmin. It is a potent and highly fibrin specific thrombolytic agent in animals and patients.

  12. Hair regrowth. Therapeutic agents.

    PubMed

    Shapiro, J; Price, V H

    1998-04-01

    Today there are new classes of hair growth promotors with proven efficacy. This article reviews the current state of the art agents for treatment of two of the most common forms of hair loss encountered in clinical practice, androgenetic alopecia and alopecia areata. Current therapeutic strategies are based on recent advances in the understanding of disordered hair growth. Practical treatment protocols are presented.

  13. E-Learning Agents

    ERIC Educational Resources Information Center

    Gregg, Dawn G.

    2007-01-01

    Purpose: The purpose of this paper is to illustrate the advantages of using intelligent agents to facilitate the location and customization of appropriate e-learning resources and to foster collaboration in e-learning environments. Design/methodology/approach: This paper proposes an e-learning environment that can be used to provide customized…

  14. Can Subscription Agents Survive?

    ERIC Educational Resources Information Center

    Tuttle, Marcia

    1985-01-01

    With the saturation of traditional markets for their services, subscription agents have evolved from orders and invoices to serving customers by communicating with librarians and publishers and making automated and paper products available. Magazine fulfillment centers, publisher discounts, and electronic publishing will influence the subscription…

  15. Remote Agent Experiment

    NASA Technical Reports Server (NTRS)

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)

    2000-01-01

    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  16. Validating the Autonomous Science Agent

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Cichy, Benjamin; Schaffer, Steve; Tran, Danny; Rabideau, Gregg; Sherwood, Rob; Bote, Robert; Mandl, Dan; Frye, Stu; Shulman, Seth; hide

    2003-01-01

    This paper describes the validation process for the Autonomous Science Agent, a software agent that will fly onboard the EO-1 spacecraft from 2003-2004. This agent will recognize science events, retarget the spacecraft to respond to the science events, and reduce data downlink to only the highest value science data. The autonomous science agent has been designed using a layered architectural approach with specific redundant safeguards to reduce the risk of an agent malfunction to the EO-1 spacecraft. This 'safe' design is also in the process of being thoroughly validated by informal validation methods and extensive testing. This paper describes the analysis used to define agent safety, elements of the design that increase the safety of the agent, and the process being used to validate agent safety prior to the agent software controlling the spacecraft.

  17. Pharmacology of antiplatelet agents.

    PubMed

    Kalra, Kiran; Franzese, Christopher J; Gesheff, Martin G; Lev, Eli I; Pandya, Shachi; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

    2013-12-01

    Pharmacotherapies with agents that inhibit platelet function have proven to be effective in the treatment of acute coronary syndromes, and in the prevention of complications during and after percutaneous coronary intervention. Because of multiple synergetic pathways of platelet activation and their close interplay with coagulation, current treatment strategies are based not only on platelet inhibition, but also on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current strategies can be broadly categorized as anticoagulants, antiplatelet agents, and fibrinolytics. This review focuses on the pharmacology of current antiplatelet therapy primarily targeting the inhibition of the enzyme cyclooxygenase 1, the P2Y12 receptor, the glycoprotein IIb/IIIa receptor, and protease-activated receptor 1.

  18. [The antiretroviral agent Fullevir].

    PubMed

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  19. FEIBA: a prohemostatic agent.

    PubMed

    Cromwell, Caroline; Aledort, Louis M

    2012-04-01

    Factor eight inhibitor bypassing activity (FEIBA), Anti-Inhibitor Coagulation Complex has been used for over 30 years in hemophiliac patients with inhibitors. The history of its use is reviewed here, including issues related to thrombosis, efficacy, and comparison to alternative bypassing agents. The need for surrogate assays to monitor effective hemostasis with the use of FEIBA remains. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. Intelligent Agent Integration Technology

    DTIC Science & Technology

    1998-04-01

    and Manipulation Language (KQML) specification under the DARPA-sponsored Knowledge Sharing Initiative and the developing of a scaleable and an... Shared Communication Ontology ’$" 10.3 IMPLEMENTATION 151 10.3.1 Intelligent Resource Agent Architecture ^ 10.3.2 Application to K-12 Education 153...DARPA-sponsored Knowledge Sharing Initiative, the developing a scaleable and an efficient implementation of information system components for

  1. Agents Technology Research

    DTIC Science & Technology

    2010-02-01

    62702F 6. AUTHOR(S) Robert Wright, Jeffrey Hudack, Nathaniel Gemelli, Steven Loscalzo, and Tsu Kong Lue 5d. PROJECT NUMBER 558S 5e. TASK...NAME OF RESPONSIBLE PERSON Robert Wright a. REPORT U b. ABSTRACT U c. THIS PAGE U 19b. TELEPHONE NUMBER (Include area code) N/A...avoided by the other agents removing the incentive to lie or free-load. This phenomenon is termed as the shadow of the future and was shown in Robert

  2. Vaporizing Fire Extinguishing Agents

    DTIC Science & Technology

    1950-08-18

    the pro- ject under contract included: Dr. Earl T. McBee, Head, Chemistry Department; Dr. Zara D. Welch, Researbh Supervisor; and Dr’s T. R. Santelli...Aeronautics Authority kxperimental Station, Indianapolis, Indiana, which has supplied test data for inclusion in this report. The Medical Division of the...Development of sources of supply for agent anAL con- tainers. f. Service testing. This report oovers technical phases a, b, and a to 1 April 1950, and

  3. Deals Among Rational Agents,

    DTIC Science & Technology

    1985-03-01

    8217.--..- .--. ..... .. ......-..- . .-- .. : .. ., . . . - .. .. ....-. . . . Theorem 2 will not hold under minimal deal rationality. Imagine that a perverse opponent chooses his offer group as follows: 1. If you include in your...agents’ behavior (citing the similarity with [25]): (A3). If a game has a single Pareto equilibrium, the players will choose the strategy which...prominent solution. [A Taxonomy of 2 x 2 Games] In short, game theory has been willing to take for granted certain types of behavior without

  4. Animal Capture Agents

    DTIC Science & Technology

    1990-01-01

    Vetalartm) a. Composition: Ketamine hydrochloride is a rapid-acting non-narcotic, nonbarbiturate agent for anesthetic use in cats and for restraint in...mean that the animal cannot feel pain. Ketamine has been aduinistered principally to cats and man, although its use in mice, rats, dogs, primates...minutes after administration to cats . Can cause convulsions and barking fits in dogs, which do not occur when it is added to other psychotropic drugs

  5. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  6. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  7. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  8. [Antimicrobial agents in eyedrops].

    PubMed

    Sklubalová, Z

    2004-05-01

    Microbial contamination of ophthalmic drops means a risk of serious injury to the eye. Ophthalmic drops must therefore comply with sterility requirements. Protection of multiple-dose drops against secondary contamination is ensured by an addition of an antimicrobial agent. Selection of a suitable antimicrobial agent is conditioned by many factors, such as the spectrum of effect, properties of the preparation, compatibility with the components of the preparation and the container, and the technology of manufacture. Although the added antimicrobial substance ensures the safety of the preparation, on the other hand it can produce a number of negative effects in the eye tissue. The present paper summarizes pharmacopoeial requirements for microbial quality of ophthalmic drops, outlining the properties and efficacy of antimicrobial substances commonly used in ophthalmic drops (benzalkonium chloride BAC, cetrimide CTM, phenyl mercuric salts PHg, thiomersal TM, chlorobutanol ChB, benzyl alcohol BA, phenyl ethyl alcohol PEA, chlorohexidin ChX, parabens PB), their typical concentrations and combinations, including the parameters of formulation and the interactions which affect their activity. It deals with the toxicity of these antimicrobial substances, side effects on the eye tissue, and alternatives to the use of antimicrobial agents.

  9. Advanced scale conditioning agents

    SciTech Connect

    Davis, Jeff; Battaglia, Philip J.

    2004-06-01

    A technical description of Advanced Scale Conditioning Agents (ASCA) technology was published in the May-June 2003 edition of the Nuclear Plant Journal. That article described the development of programs of advanced scale conditioning agents and specific types to maintain the secondary side of steam generators within a pressurized water reactor free of deposited corrosion products and corrosion-inducing contaminants to ensure their long-term operation. This article describes the first two plant applications of advanced scale conditioning agents implemented at Southern Nuclear Operating Company's Vogtle Units 1 and 2 during their 2002 scheduled outages to minimize tube degradation and maintain full power operation using the most effective techniques while minimizing outage costs. The goal was to remove three to four fuel cycles of deposits from each steam generator so that after future chemical cleaning activities, ASCAs could be used to maintain the cleanliness of the steam generators without the need for additional chemical cleaning efforts. The goal was achieved as well as several other benefits that resulted in cost savings to the plant.

  10. Newer antifungal agents.

    PubMed

    Türel, Ozden

    2011-03-01

    The frequency and spectrum of fungal infections have been increasing steadily over the last several decades. The reason for this increase may be explained by the increase in the number of immunocompromised patients due to malignancies, AIDS, invasive surgical procedures and transplantation. In parallel with this increase, several therapeutic options have become available but problems such as intrinsic or acquired antifungal resistance have led researchers to develop new antifungal drugs with expanded effectiveness. Reduced toxicity, enhancement of bioavailability and counteraction of resistance are features desired by clinicians. The aim of this article is to summarize the studies involving isavuconazole, ravuconazole, albaconazole, aminocandin and some other investigational antifungal agents. Most data on the clinical use of ravuconazole, isavuconazole and albaconazole are mainly available as meeting abstracts or limited to animal studies or Phase I/II studies in humans. These new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. In addition to activity against Candida and Aspergillus spp., they have a broad spectrum of activity including activity against resistant and emerging pathogens. The real possibilities of these agents will only be fully understood after adequate randomized clinical trials.

  11. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  12. Collaborating with Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Cross, Charles D.; Fan, Henry; Hempley, Lucas E.; Motter, Mark A.; Neilan, James H.; Qualls, Garry D.; Rothhaar, Paul M.; Tran, Loc D.; Allen, B. Danette

    2015-01-01

    With the anticipated increase of small unmanned aircraft systems (sUAS) entering into the National Airspace System, it is highly likely that vehicle operators will be teaming with fleets of small autonomous vehicles. The small vehicles may consist of sUAS, which are 55 pounds or less that typically will y at altitudes 400 feet and below, and small ground vehicles typically operating in buildings or defined small campuses. Typically, the vehicle operators are not concerned with manual control of the vehicle; instead they are concerned with the overall mission. In order for this vision of high-level mission operators working with fleets of vehicles to come to fruition, many human factors related challenges must be investigated and solved. First, the interface between the human operator and the autonomous agent must be at a level that the operator needs and the agents can understand. This paper details the natural language human factors e orts that NASA Langley's Autonomy Incubator is focusing on. In particular these e orts focus on allowing the operator to interact with the system using speech and gestures rather than a mouse and keyboard. With this ability of the system to understand both speech and gestures, operators not familiar with the vehicle dynamics will be able to easily plan, initiate, and change missions using a language familiar to them rather than having to learn and converse in the vehicle's language. This will foster better teaming between the operator and the autonomous agent which will help lower workload, increase situation awareness, and improve performance of the system as a whole.

  13. Antimycobacterials from lovage root (Ligusticum officinale Koch).

    PubMed

    Guzman, Juan David; Evangelopoulos, Dimitrios; Gupta, Antima; Prieto, Jose M; Gibbons, Simon; Bhakta, Sanjib

    2013-07-01

    The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc²155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H₃₇Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.7 murine macrophage cells was employed for assessing their degree of selectivity. Falcarindiol was the most potent compound with a minimum inhibitory concentration (MIC) value of 20 mg/L against the virulent H₃₇Rv strain; however, it was found to be cytotoxic with a half-growth inhibitory concentration (GIC₅₀) in the same order of magnitude (SI < 1). Interestingly the sesquiterpene alcohol α-prethapsenol was found to inhibit the growth of the pathogenic mycobacteria with an MIC value of 60 mg/L, being more specific towards mycobacteria than mammalian cells (SI ~ 2). Colony forming unit analysis at different concentrations of this phytochemical showed mycobacteriostatic mode of action. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Antimycobacterial N-alkoxyphenylhydroxynaphthalenecarboxamides affecting photosystem II.

    PubMed

    Gonec, Tomas; Kralova, Katarina; Pesko, Matus; Jampilek, Josef

    2017-03-21

    N-(Alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides (series A) and N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides (series B) affecting photosystem (PS) II inhibited photosynthetic electron transport (PET) in spinach chloroplasts. Their inhibitory activity depended on the compound lipophilicity as well as on the position of the alkoxy substituent. The most potent PET inhibitors were 2-hydroxy-N-phenylnaphthalene-1-carboxamide and N-[3-(but-2-yloxy)phenyl]-2-hydroxynaphthalene-1-carboxamide within series A (IC50=28.9 and 42.5µM, respectively) and 1-hydroxy-N-(3-propoxyphenyl)naphthalene-2-carboxamide and 1-hydroxy-N-(3-ethoxyphenyl)-naphthalene-2-carboxamide (IC50=2.0 and 3.1µM, respectively) within series B. The inhibitory activity of C'(3) or C'(4) alkoxy substituted compounds of series B was considerably higher than that of C'(2) ones within series A. The PET-inhibiting activities of both series were compared with the PET inhibition of isomeric N-alkoxyphenyl-3-hydroxynaphthalene-2-carboxamides (series C) reported recently. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PSII can be suggested as the site of action of the compounds.

  15. Chemical warfare agents

    PubMed Central

    Ganesan, K.; Raza, S. K.; Vijayaraghavan, R.

    2010-01-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  16. Pharmacologic agents targeting autophagy

    PubMed Central

    Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying

    2015-01-01

    Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies. PMID:25654545

  17. Chemical warfare agents.

    PubMed

    Ganesan, K; Raza, S K; Vijayaraghavan, R

    2010-07-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided.

  18. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for... will appoint or cause to be appointed agent(s) to perform functions necessary to market and service... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  19. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA Financial... financial markets to determine those factors that will minimize or reduce the cost of funding Debentures...) Agents. SBA may appoint or cause to be appointed agent(s) to perform functions necessary to market...

  20. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA Financial... financial markets to determine those factors that will minimize or reduce the cost of funding Debentures...) Agents. SBA may appoint or cause to be appointed agent(s) to perform functions necessary to market...

  1. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for... will appoint or cause to be appointed agent(s) to perform functions necessary to market and service... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  2. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    DOEpatents

    Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

    2005-01-25

    The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  3. Antineoplastic agents and thrombotic microangiopathy.

    PubMed

    Garcia, Gwenalyn; Atallah, Jean Paul

    2017-03-01

    Thrombotic microangiopathy is an uncommon but reported adverse effect of a variety of antineoplastic drugs, including chemotherapy agents such as mitomycin C and gemcitabine, and newer targeted agents such as the vascular endothelial growth factor inhibitors. We present a review of thrombotic microangiopathy associated with antineoplastic agents and its implications in current cancer therapy.

  4. Holograms as Teaching Agents

    NASA Astrophysics Data System (ADS)

    Walker, Robin A.

    2013-02-01

    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  5. Model Checking Agent Communication

    NASA Astrophysics Data System (ADS)

    Bentahar, J.; Meyer, J.-J. Ch.; Wan, W.

    Model checking is a formal and automatic technique used to verify computational systems (e.g. communication protocols) against given properties. The purpose of this chapter is to describe a model checking algorithm to verify communication protocols used by autonomous agents interacting using dialogue games, which are governed by a set of logical rules. We use a variant of Extended Computation Tree Logic CTL* for specifying these dialogue games and the properties to be checked. This logic, called ACTL*, extends CTL* by allowing formulae to constrain actions as well as states. The verification method uses an on-the-fly efficient algorithm. It is based on translating formulae into a variant of alternating tree automata called Alternating Büchi Tableau Automata (ABTA). We present a tableau-based version of this algorithm and provide the soundness, completeness, termination and complexity results. Two case studies are discussed along with their respective implementations to illustrate the proposed approach. The first one is about an agent-based negotiation protocol and the second one considers a modified version of the NetBill protocol.

  6. [Bacteriophages as antibacterial agents].

    PubMed

    Shasha, Shaul M; Sharon, Nehama; Inbar, Michael

    2004-02-01

    Bacteriophages are viruses that only infect bacteria. They have played an important role in the development of molecular biology and have been used as anti-bacterial agents. Since their independent discovery by Twort and d'Herelle, they have been extensively used to prevent and treat bacterial infections, mainly in Eastern Europe and the former Soviet Union. In western countries this method has been sporadically employed on humans and domesticated animals. However, the discovery and widespread use of antibiotics, coupled with doubts about the efficacy of phage therapy, led to an eclipse in the use of phage in medicine. The emergence of antibiotic resistant bacteria, especially strains that are multiply resistant, has resulted in a renewed interest in alternatives to conventional drugs. One of the possible replacements for antibiotics is the use of bacteriophages as antimicrobial agents. This brief review aims to describe the history of bacteriophage and early clinical studies on their use in bacterial disease prophylaxis and therapy, and discuss the advantages and disadvantages of bacteriophage in this regard.

  7. [New agents for hypercholesterolemia].

    PubMed

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity.

  9. Agent-Based Automated Algorithm Generator

    DTIC Science & Technology

    2010-01-12

    Detection and Isolation Agent (FDIA), Prognostic Agent (PA), Fusion Agent (FA), and Maintenance Mining Agent (MMA). FDI agents perform diagnostics...manner and loosely coupled). The library of D/P algorithms will be hosted in server-side agents, consisting of four types of major agents: Fault

  10. Learning models of intelligent agents

    SciTech Connect

    Carmel, D.; Markovitch, S.

    1996-12-31

    Agents that operate in a multi-agent system need an efficient strategy to handle their encounters with other agents involved. Searching for an optimal interactive strategy is a hard problem because it depends mostly on the behavior of the others. In this work, interaction among agents is represented as a repeated two-player game, where the agents` objective is to look for a strategy that maximizes their expected sum of rewards in the game. We assume that agents` strategies can be modeled as finite automata. A model-based approach is presented as a possible method for learning an effective interactive strategy. First, we describe how an agent should find an optimal strategy against a given model. Second, we present an unsupervised algorithm that infers a model of the opponent`s automaton from its input/output behavior. A set of experiments that show the potential merit of the algorithm is reported as well.

  11. Flexible, secure agent development framework

    DOEpatents

    Goldsmith,; Steven, Y [Rochester, MN

    2009-04-07

    While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

  12. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  13. Ultrasound contrast agents

    PubMed Central

    Ignee, Andre; Atkinson, Nathan S. S.; Schuessler, Gudrun; Dietrich, Christoph F.

    2016-01-01

    Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed. PMID:27824024

  14. [Chemotherapeutic agents under study].

    PubMed

    Kawahara, S

    1998-12-01

    The development of new drugs with strong antituberculous activity and fewer side effects which are not cross-resistant to conventional antituberculosis drugs is urgently desired now. The chemotherapeutic agents under study which are considered a candidate for a new antituberculosis drug are listed below. 1) Rifamycin derivatives: rifabutin, rifapentin, KRM-1648, FCE-22250, 22807, CGP-7040, 27557, 29035, 29861, P-DEA, SPA-S-565, R-76-1. 2) New quinolones: ofloxacin, ciprofloxacin, levofloxacin, sparfloxacin, gatifloxacin, CS-940, Du-6859a. 3) Phenazines: clofazimine, B746, B4101, B4154, B4157. 4) Pyrazinamide derivatives: N-hydroxy pyrazinamide, N-hydroxy pyrazinamide-4-oxide. 5) Nitroimidazole derivatives: metronidazole et al.

  15. Infectious agents and neurodegeneration.

    PubMed

    De Chiara, Giovanna; Marcocci, Maria Elena; Sgarbanti, Rossella; Civitelli, Livia; Ripoli, Cristian; Piacentini, Roberto; Garaci, Enrico; Grassi, Claudio; Palamara, Anna Teresa

    2012-12-01

    A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host's specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.

  16. Peptide Antimicrobial Agents

    PubMed Central

    Jenssen, Håvard; Hamill, Pamela; Hancock, Robert E. W.

    2006-01-01

    Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents. PMID:16847082

  17. [Unconventional antidiabetic agents].

    PubMed

    Rustenbeck, Ingo

    2007-04-01

    The current pharmacological therapy of type 2 diabetes reduces the risk of diabetic complications, but is not able to achieve a long-lasting normalization of the metabolic disorder. Thus diabetic patients in increasing numbers are taking dietary supplements and herbs from which they expect additional health benefits. These unconventional antidiabetic agents consist mainly in trace metals like chromium, vanadium and zinc and a heterogeneous group of traditionally used antidiabetic herbs (e. g. Momordica charantia, Gymnema sylvestre, Trigonella foenum-graecum) often derived from the ayurvedic medicine. In this overview the current evidence for the antidiabetic effect is presented. The trace elements chromium and vanadium have a number of potentially antidiabetic actions in vitro, however, the results obtained with diabetic patients are not convincing so far. Similarly, the available data on the therapeutic use of herbs suggest that in principle a number of them possess a blood glucose-lowering effect, but at present no firm conclusions as to their efficacy and safety can be made. To set up reliable dose-effect relationships requires the identification of the relevant antidiabetic molecules as was apparently achieved by isolating 4-hydroxyisoleucine from the seeds of T. foenum-graecum. This requirement is also valid in the case of the antidiabetic action of cinnamon. Coffee and a moderate alcohol consumption were found to be surprisingly effective in lowering the risk of type 2 diabetes manifestation, their effect being roughly equal to that of conventional drugs used in diabetes prevention trials. Diabetic patients should inform their physician about the use of unconventional agents and should be warned against uncontrolled starting or stopping their use.

  18. Agent-based enterprise integration

    SciTech Connect

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  19. Agent-based enterprise integration

    SciTech Connect

    N. M. Berry; C. M. Pancerella

    1999-05-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. Their enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; intelligently locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of their effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses their planned future work.

  20. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  1. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  2. Polymeric gastrointestinal MR contrast agents.

    PubMed

    Tilcock, C; Unger, E C; Ahkong, Q F; Fritz, T; Koenig, S H; Brown, R D

    1991-01-01

    Combining either paramagnetic (gadolinium chelates) or superparamagnetic (ferrite) contrast agents with polymers such as polyethylene glycol or cellulose, or with simple sugars such as dextrose, results in mixtures that exhibit improved T1 and/or T2 relaxivity compared with that of the contrast agent alone. It is suggested that the addition of such inexpensive and nontoxic polymers or saccharides may improve the effectiveness and decrease the cost of enteric contrast agents.

  3. Antithrombotic agents: implications in dentistry.

    PubMed

    Little, James W; Miller, Craig S; Henry, Robert G; McIntosh, Bruce A

    2002-05-01

    Thrombosis and the complicating emboli that can result are important causes of illness and death. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Agents such as heparin, low-molecular weight heparin, warfarin, aspirin, ticlopidine, clopidogrel, and tirofiban are used to prevent venous or arterial thrombosis. Patients taking these antithrombotic agents may be at risk for excessive bleeding after invasive dental procedures. The current antithrombotic agents used in medicine are reviewed, and the dental management of patients taking these agents is discussed.

  4. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  5. The Agent of Change: The Agent of Conflict.

    ERIC Educational Resources Information Center

    Hatfield, C. R., Jr.

    This speech examines the role of change agents in third world societies and indicates that the change agent must, to some extent, manipulate the social situation, even if his view of society is a more optimistic one than he finds in reality. If he considers strains and stresses to be the lubricants of change, then his focus on conflict as a…

  6. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  7. Clients as conversational agents.

    PubMed

    Massfeller, Helen F; Strong, Tom

    2012-08-01

    Conversational agency is our invented term that orients us to ways in which clients participate in therapeutic dialogues. In this study we examined how clients' conversational correctives and initiatives influenced collaborative therapeutic consultations. Thirty-five single-session lifestyle consultations were videotaped in which adult clients volunteered to discuss concerns of non-clinical severity with a counselor. We discursively microanalyzed excerpts where clients initiated topic shifts or corrected counselor misunderstandings and how counselors responded to them. Clients were actively involved in co-managing conversational developments during the consultations. They influenced the content and course of the conversations with the counselors by correcting, interrupting, or speaking from positions contrary or unrelated to those of the counselors. Clients observably influenced the conversational agenda through their correctives and initiatives if counselors were responsive during face-to-face consultations. Clinicians should demonstrate increased sensitivity and relational responsivity by intentionally engaging with clients' agentive contributions to consultative dialogues. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  9. Contrast agents for MRI.

    PubMed

    Shokrollahi, H

    2013-12-01

    Contrast agents are divided into two categories. The first one is paramagnetic compounds, including lanthanides like gadolinium, which mainly reduce the longitudinal (T1) relaxation property and result in a brighter signal. The second class consists of super-paramagnetic magnetic nanoparticles (SPMNPs) such as iron oxides, which have a strong effect on the transversal (T2) relaxation properties. SPMNPs have the potential to be utilized as excellent probes for magnetic resonance imaging (MRI). For instance, clinically benign iron oxide and engineered ferrite nanoparticles provide a good MRI probing capability for clinical applications. Furthermore, the limited magnetic property and inability to escape from the reticuloendothelial system (RES) of the used nanoparticles impede their further advancement. Therefore, it is necessary to develop the engineered magnetic nanoparticle probes for the next-generation molecular MRI. Considering the importance of MRI in diagnosing diseases, this paper presents an overview of recent scientific achievements in the development of new synthetic SPMNP probes whereby the sensitive and target-specific observation of biological events at the molecular and cellular levels is feasible.

  10. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  11. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    NASA Astrophysics Data System (ADS)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  12. Oral contraceptive agents.

    PubMed

    Shearman, R P

    1986-02-17

    The history of the development of oral contraceptives (OCs) has been a progressive reduction in dosage to what is now probably the lowest does that is compatible with the desired therapeutic effect -- to inhibit ovluation. Yet, controversy and argument continue. A table lists the OCs that are available in Australia. Many of these preparations, although having different trade names, have an identical composition. Since the withdrawal of sequential OCs from the Australian market, there are only 2 generic types. These are the progestogen only (mini) OCs, which consist of either 30 mcg of levonorgestrel or 350 mcg of norethisterone given at the same time every day; and the combined OCs, which contain an estrogen and a progestogen. In the last 12 months, some of the older high-dose OCs have been withdrawn, and it seems likely that further withdrawals will follow. Only 2 estrogens are used in the formulation of the OC, but there is a greater variety of progestogens. Ethinyl estradiol is used in most preparations. A small minority of OCs contain mestranol, the 3-methyl ether of ethinyl estradiol. Currently, there are only 4 OC agents that are available in Australia that contain mestranol and 2 of these contain the high doses of 100 mcg. Fundamentally, there are 2 types of progestogens -- those that contain, or are metabolized to, norethisterone and those that contain norgestrel or its close relative, desogestrel. With the exception of the norgestrel group and desogestrel, all other progestins, including norethisterone itself, are effective in vivo after they have been metablized to norethisterone. Mestranol is effective in humans after demethylation to ethinyl estradiol. In the norgesterel group, since d-norgestrel is inert endocrinologically, 250 mcg of levonorgestrel and 500 mcg of dl-norgestrel are equivalent. Levonorgestrel and desogestrel are of approximately equal potency. With the combined OC agents, the overwhelming mechanism of action is by the inhibition of the

  13. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs.

  14. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  15. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial markets..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs... or cause to be appointed agent(s) to perform functions necessary to market and service Debentures...

  16. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial markets..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs... or cause to be appointed agent(s) to perform functions necessary to market and service Debentures...

  17. Multimodal nanoparticulate bioimaging contrast agents.

    PubMed

    Sharma, Parvesh; Singh, Amit; Brown, Scott C; Bengtsson, Niclas; Walter, Glenn A; Grobmyer, Stephen R; Iwakuma, Nobutaka; Santra, Swadeshmukul; Scott, Edward W; Moudgil, Brij M

    2010-01-01

    A wide variety of bioimaging techniques (e.g., ultrasound, computed X-ray tomography, magnetic resonance imaging (MRI), and positron emission tomography) are commonly employed for clinical diagnostics and scientific research. While all of these methods use a characteristic "energy-matter" interaction to provide specific details about biological processes, each modality differs from another in terms of spatial and temporal resolution, anatomical and molecular details, imaging depth, as well as the desirable material properties of contrast agents needed for augmented imaging. On many occasions, it is advantageous to apply multiple complimentary imaging modalities for faster and more accurate prognosis. Since most imaging modalities employ exogenous contrast agents to improve the signal-to-noise ratio, the development and use of multimodal contrast agents is considered to be highly advantageous for obtaining improved imagery from sought-after imaging modalities. Multimodal contrast agents offer improvements in patient care, and at the same time can reduce costs and enhance safety by limiting the number of contrast agent administrations required for imaging purposes. Herein, we describe the synthesis and characterization of nanoparticulate-based multimodal contrast agent for noninvasive bioimaging using MRI, optical, and photoacoustic tomography (PAT)-imaging modalities. The synthesis of these agents is described using microemulsions, which enable facile integration of the desired diversity of contrast agents and material components into a single entity.

  18. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  19. Field Agent Activities: Level 1.

    ERIC Educational Resources Information Center

    Gussett, James

    One of a series of monographs providing information about the Delaware Model: A Systems Approach to Science Education (Del Mod System), this monograph describes the role of field agents. These agents are responsible for individual teachers who express a desire for involvement in improving teacher effectiveness and to be involved in the teaching of…

  20. Dialogue Games for Agent Argumentation

    NASA Astrophysics Data System (ADS)

    McBurney, Peter; Parsons, Simon

    The rise of the Internet and the growth of distributed computing have led to a major paradigm shift in software engineering and computer science. Until recently, the notion of computation has been variously construed as numerical calculation, as information processing, or as intelligent symbol analysis, but increasingly, it is now viewed as distributed cognition and interaction between intelligent entities [60]. This new view has major implications for the conceptualization, design, engineering and control of software systems, most profoundly expressed in the concept of systems of intelligent software agents, or multi-agent systems [99]. Agents are software entities with control over their own execution; the design of such agents, and of multi-agent systems of them, presents major research and software engineering challenges to computer scientists.

  1. Markov Tracking for Agent Coordination

    NASA Technical Reports Server (NTRS)

    Washington, Richard; Lau, Sonie (Technical Monitor)

    1998-01-01

    Partially observable Markov decision processes (POMDPs) axe an attractive representation for representing agent behavior, since they capture uncertainty in both the agent's state and its actions. However, finding an optimal policy for POMDPs in general is computationally difficult. In this paper we present Markov Tracking, a restricted problem of coordinating actions with an agent or process represented as a POMDP Because the actions coordinate with the agent rather than influence its behavior, the optimal solution to this problem can be computed locally and quickly. We also demonstrate the use of the technique on sequential POMDPs, which can be used to model a behavior that follows a linear, acyclic trajectory through a series of states. By imposing a "windowing" restriction that restricts the number of possible alternatives considered at any moment to a fixed size, a coordinating action can be calculated in constant time, making this amenable to coordination with complex agents.

  2. Intelligent Agents in Physics Education

    NASA Astrophysics Data System (ADS)

    Sánchez-Guzmán, D.; Mora, César

    2010-07-01

    Intelligent Agents are being applied in a wide range of processes and everyday applications. Their development is not new, in recent years they have had an increased attention and design; like learning and mentoring tools. In this work we discuss the definition of what an intelligent agent is; how they are applied; how they look like; recent implementations of agents; agents as support in the learning process, more precisely intelligent tutors; their state in Latin-American countries and future developments and trends that will permit a better communication between people and agents. Also we present an Intelligent Tutor applied as a tool for improving high-school students' skills and reasoning for the first five topics of Mechanics curricula.

  3. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  4. Knowledge focus via software agents

    NASA Astrophysics Data System (ADS)

    Henager, Donald E.

    2001-09-01

    The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be

  5. Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent

    SciTech Connect

    Bettmann, M.A.; Bourdillon, P.D.; Barry, W.H.; Brush, K.A.; Levin, D.C.

    1984-12-01

    The effects on cardiac hemodynamics and of a standard contrast agent, sodium methylglucamine diatrizoate (Renografin 76) were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patietns undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk.

  6. Agent Communications using Distributed Metaobjects

    SciTech Connect

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

    There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

  7. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

    1997-12-30

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

  8. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

    1997-01-01

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

  9. Requirements Modeling with Agent Programming

    NASA Astrophysics Data System (ADS)

    Dasgupta, Aniruddha; Krishna, Aneesh; Ghose, Aditya K.

    Agent-oriented conceptual modeling notations are highly effective in representing requirements from an intentional stance and answering questions such as what goals exist, how key actors depend on each other, and what alternatives must be considered. In this chapter, we review an approach to executing i* models by translating these into set of interacting agents implemented in the CASO language and suggest how we can perform reasoning with requirements modeled (both functional and non-functional) using i* models. In this chapter we particularly incorporate deliberation into the agent design. This allows us to benefit from the complementary representational capabilities of the two frameworks.

  10. Diamine curing agents for polyurethanes

    NASA Technical Reports Server (NTRS)

    Bell, V. L.; St. Clair, T. L.

    1975-01-01

    Three aromatic diamines have properties that make them promising candidates as curing agents for converting isocyanates to polyurethanes with higher adhesive strengths, higher softening temperatures, better toughness, and improved abrasion resistance.

  11. Anti-Clotting Agents Explained

    MedlinePlus

    ... becomes potentially life-threatening. Anti platelet agents, including aspirin , clopidogrel, dipyridamole and ticlopidine, work by inhibiting the production of thromboxane. Aspirin is highly recommended for preventing a first stroke, ...

  12. Agent-based forward analysis

    SciTech Connect

    Kerekes, Ryan A.; Jiao, Yu; Shankar, Mallikarjun; Potok, Thomas E.; Lusk, Rick M.

    2008-01-01

    We propose software agent-based "forward analysis" for efficient information retrieval in a network of sensing devices. In our approach, processing is pushed to the data at the edge of the network via intelligent software agents rather than pulling data to a central facility for processing. The agents are deployed with a specific query and perform varying levels of analysis of the data, communicating with each other and sending only relevant information back across the network. We demonstrate our concept in the context of face recognition using a wireless test bed comprised of PDA cell phones and laptops. We show that agent-based forward analysis can provide a significant increase in retrieval speed while decreasing bandwidth usage and information overload at the central facility. n

  13. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  14. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  15. Launch Commit Criteria Monitoring Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Kelly, Andrew O.; Boeloeni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed a software agent to monitor the Space Shuttle's ground processing telemetry stream. The application, the Launch Commit Criteria Monitoring Agent, increases situational awareness for system and hardware engineers during Shuttle launch countdown. The agent provides autonomous monitoring of the telemetry stream, automatically alerts system engineers when predefined criteria have been met, identifies limit warnings and violations of launch commit criteria, aids Shuttle engineers through troubleshooting procedures, and provides additional insight to verify appropriate troubleshooting of problems by contractors. The agent has successfully detected launch commit criteria warnings and violations on a simulated playback data stream. Efficiency and safety are improved through increased automation.

  16. Triggered pore-forming agents

    DOEpatents

    Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

    1998-01-01

    An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

  17. Peripheral Neuropathy and Agent Orange

    MedlinePlus

    ... ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  18. Family as Economic Socialization Agent.

    ERIC Educational Resources Information Center

    Rettig, Kathryn Dalbey

    1983-01-01

    The family operates as an economic socialization agent through the provision of (1) economic information networks, (2) grants and exchanges of resources, (3) economic role models, and (4) an environment for the development of individual human resource attributes. (SK)

  19. Bulking agents in sludge composting

    SciTech Connect

    De Bertoldi, M.; Citernesi, U.; Griselli, M.

    1980-01-01

    Composting is one of the most effective ways of disposing of sludge in agriculture. Three bulking agents were studied: (1) the organic fraction of solid wastes, (2) solid agricultural and forestry waste (straw, maize cobs, sawdust, cork, pine cones, etc.), and (3) recyclable inert substrates (polystyrene or polyethylene balls, porous clay balls, etc.). The sole purpose of the inert bulking agent is to aid in the aeration and drying of the composting material.

  20. Handling of injectable antineoplastic agents.

    PubMed Central

    Knowles, R S; Virden, J E

    1980-01-01

    Although the clinical toxicity of antineoplastic drugs has been well documented there is little or no information on the problems that may arise on the handling and mishandling of such agents. This paper attempts to highlight the importance of taking precautions to prevent adverse effects resulting from contact with cytotoxic drugs during handling and to suggest a practical guide for the handling of such agents. PMID:7427382

  1. Clinically Approved Nanoparticle Imaging Agents

    PubMed Central

    Thakor, Avnesh S.; Jokerst, Jesse V.; Ghanouni, Pejman; Campbell, Jos L.; Mittra, Erik

    2016-01-01

    Nanoparticles are a new class of imaging agent used for both anatomic and molecular imaging. Nanoparticle-based imaging exploits the signal intensity, stability, and biodistribution behavior of submicron-diameter molecular imaging agents. This review focuses on nanoparticles used in human medical imaging, with an emphasis on radionuclide imaging and MRI. Newer nanoparticle platforms are also discussed in relation to theranostic and multimodal uses. PMID:27738007

  2. What makes virtual agents believable?

    NASA Astrophysics Data System (ADS)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  3. Learning in multi-agent systems

    SciTech Connect

    Goldman, C.V.

    1996-12-31

    Learning agents acting in a multi agent environment can improve their performance. These agents might decide upon their course of action by learning about other agents with whom they interact. The learning agents can learn about the others information and rules of behavior. The agents will not need to plan their actions beforehand, each time they are asked to solve the same problem they have already solved or when dealing with similar problems.

  4. Validating the autonomous EO-1 science agent

    NASA Technical Reports Server (NTRS)

    Cichy, Benjamin; Chien, Steve; Rabideau, Gregg; Tran, Daniel

    2004-01-01

    This paper describes the validation process for the Autonomous Science Agent, a software agent that is currently flying onboard NASA EO-1 spacecraft. The agent autonomously collects, analyzes, and reacts to onboard science data. The Autonomous Science Agent has been designed using a layered architectural approach with specific redundant safeguards to reduce the risk of an agent malfunction to the EO-1 spacecraft. This safe design has been thoroughly validated by informal validation methods supplemented by sub-system and system-level testing. This paper describes the analysis used to define agent safety, elements of the design that increase the safety of the agent, and the process used to validate agent safety.

  5. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  6. Collective behavior of predictive agents

    NASA Astrophysics Data System (ADS)

    Kephart, Jeffrey O.; Hogg, Tad; Huberman, Bernardo A.

    1990-06-01

    We investigate the effect of predictions upon a model of coevolutionary systems which was originally inspired by computational ecosystems. The model incorporates many of the features of distributed resource allocation in systems comprised of many individual agents, including asynchrony, resource contention, and decision-making based upon incomplete knowledge and delayed information. Previous analyses of a similar model of non-predictive agents have demonstrated that periodic or chaotic oscillations in resource allocation can occur under certain conditions, and that these oscillations can affect the performance of the system adversely. In this work, we show that the system performance can be improved if the agents do an adequate job of predicting the current state of the system. We explore two plausible methods for prediction - technical analysis and system analysis. Technical analysts are responsive to the behavior of the system, but suffer from an inability to take their own behavior into account. System analysts perform extremely well when they have very accurate information about the other agents in the system, but can perform very poorly when their information is even slightly inaccurate. By combining the strengths of both methods, we obtain a successful hybrid of the two prediction methods which adapts its model of other agents in response to the observed behavior of the system.

  7. Next Generation Remote Agent Planner

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari K.; Muscettola, Nicola; Morris, Paul H.; Rajan, Kanna

    1999-01-01

    In May 1999, as part of a unique technology validation experiment onboard the Deep Space One spacecraft, the Remote Agent became the first complete autonomous spacecraft control architecture to run as flight software onboard an active spacecraft. As one of the three components of the architecture, the Remote Agent Planner had the task of laying out the course of action to be taken, which included activities such as turning, thrusting, data gathering, and communicating. Building on the successful approach developed for the Remote Agent Planner, the Next Generation Remote Agent Planner is a completely redesigned and reimplemented version of the planner. The new system provides all the key capabilities of the original planner, while adding functionality, improving performance and providing a modular and extendible implementation. The goal of this ongoing project is to develop a system that provides both a basis for future applications and a framework for further research in the area of autonomous planning for spacecraft. In this article, we present an introductory overview of the Next Generation Remote Agent Planner. We present a new and simplified definition of the planning problem, describe the basics of the planning process, lay out the new system design and examine the functionality of the core reasoning module.

  8. Agent review phase one report.

    SciTech Connect

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell

    2009-12-01

    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  9. Adaptive networks of trading agents.

    PubMed

    Burda, Z; Krzywicki, A; Martin, O C

    2008-10-01

    Multiagent models have been used in many contexts to study generic collective behavior. Similarly, complex networks have become very popular because of the diversity of growth rules giving rise to scale-free behavior. Here we study adaptive networks where the agents trade "wealth" when they are linked together while links can appear and disappear according to the wealth of the corresponding agents; thus the agents influence the network dynamics and vice versa. Our framework generalizes a multiagent model of Bouchaud and Mézard [Physica A 282, 536 (2000)], and leads to a steady state with fluctuating connectivities. The system spontaneously self-organizes into a critical state where the wealth distribution has a fat tail and the network is scale free; in addition, network heterogeneities lead to enhanced wealth condensation.

  10. Dual Rationality and Deliberative Agents

    NASA Astrophysics Data System (ADS)

    Debenham, John; Sierra, Carles

    Human agents deliberate using models based on reason for only a minute proportion of the decisions that they make. In stark contrast, the deliberation of artificial agents is heavily dominated by formal models based on reason such as game theory, decision theory and logic—despite that fact that formal reasoning will not necessarily lead to superior real-world decisions. Further the Nobel Laureate Friedrich Hayek warns us of the ‘fatal conceit’ in controlling deliberative systems using models based on reason as the particular model chosen will then shape the system’s future and either impede, or eventually destroy, the subtle evolutionary processes that are an integral part of human systems and institutions, and are crucial to their evolution and long-term survival. We describe an architecture for artificial agents that is founded on Hayek’s two rationalities and supports the two forms of deliberation used by mankind.

  11. [Anti-influenza virus agent].

    PubMed

    Nakamura, Shigeki; Kohno, Shigeru

    2012-04-01

    The necessity of newly anti-influenza agents is increasing rapidly after the prevalence of pandemic influenza A (H1N1) 2009. In addition to the existing anti-influenza drugs, novel neuraminidase inhibitors such as peramivir (a first intravenous anti-influenza agent) and laninamivir (long acting inhaled anti-influenza agent) can be available. Moreover favipiravir, which shows a novel anti-influenza mechanism acting as RNA polymerase inhibitor, has been developing. These drugs are expected to improve the prognosis of severe cases caused by not only seasonal influenza but pandemic influenza A (H1N1) 2009 virus and H5N1 avian influenza, and also treat oseltamivir-resistant influenza effectively.

  12. Learning Agents in Automated Negotiations

    NASA Astrophysics Data System (ADS)

    Chandrashekhar, Hemalatha; Bhasker, Bharat

    In bilateral multi-issue negotiations involving two-sided information uncertainty, selfish agents participating in a distributed search of the solution space need to learn the opponent’s preferences from the on-going negotiation interactions and utilize such knowledge to construct future proposals in order to hope to arrive at efficient outcomes. Besides, negotiation support systems that inhibit strategic misrepresentation of information need to be in place in order to assist the protagonists to obtain truly efficient solutions. To this end, this work suggests an automated negotiation procedure that while protecting the information privacy of the participating agents encourages truthful revelation of information through successive proposals. Further we present an algorithm for proposal construction in the case of two continuous issues. When both the negotiating agents implement the algorithm the negotiation trace shall be confined to the Pareto frontier. The Pareto-optimal deal close to the Nash solution shall be located whenever such a deal exists.

  13. Thyroid Dysfunction from Antineoplastic Agents

    PubMed Central

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  14. Autonomous sensor manager agents (ASMA)

    NASA Astrophysics Data System (ADS)

    Osadciw, Lisa A.

    2004-04-01

    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  15. Landslides as agents of diversity

    NASA Astrophysics Data System (ADS)

    Geertsema, Marten

    2016-04-01

    Landslides, often destructive and damaging, are also agents of change that introduce diversity to landscapes. I discuss landslide diversity at three levels: site diversity, soil diversity, and habitat diversity. There are many landslide types involving different materials and rates and styles of movement. Landscape diversity varies with different types of landslides. Landslides, at the same time depositional and erosional agents, influence sites by redistributing materials and changing microtopography. Eroded portions of landslides, with exposed parent material, revert to the initial stages of soil development and ecological succession. Landslides can also alter soil properties including, surface texture, chemistry and porosity. Landslides influence habitat diversity by creating ecosystem mosaics.

  16. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future. © 2011 Future Medicine Ltd

  17. Software Agents for Coalition Forces

    DTIC Science & Technology

    2002-04-01

    T. Ksiezyk, G. Martin, M . Nodine, M . Rashid, M . Rusinkiewicz, R. Shea, C. Unnikrishnan , A. Unruh, and D. Woelk. Infosleuth: Semantic integration of...IoI (Help-Agent) Communication layerQu°eries CCIS-Agent e 1 processing CreatioS e -DtL - Ads. Intra."Su -~ Req uest s m o ul m od ula e A- e-n-- A v...1996] F. Buschmann, R. Meunier, H. Rohnet, P. Sommerland, and M . Stal. Pattern- Oriented Software Architecture. John Wiley and Sons Ltd., 1996. [Chawathe

  18. Clustering recommendations to compute agent reputation

    NASA Astrophysics Data System (ADS)

    Bedi, Punam; Kaur, Harmeet

    2005-03-01

    Traditional centralized approaches to security are difficult to apply to multi-agent systems which are used nowadays in e-commerce applications. Developing a notion of trust that is based on the reputation of an agent can provide a softer notion of security that is sufficient for many multi-agent applications. Our paper proposes a mechanism for computing reputation of the trustee agent for use by the trustier agent. The trustier agent computes the reputation based on its own experience as well as the experience the peer agents have with the trustee agents. The trustier agents intentionally interact with the peer agents to get their experience information in the form of recommendations. We have also considered the case of unintentional encounters between the referee agents and the trustee agent, which can be directly between them or indirectly through a set of interacting agents. The clustering is done to filter off the noise in the recommendations in the form of outliers. The trustier agent clusters the recommendations received from referee agents on the basis of the distances between recommendations using the hierarchical agglomerative method. The dendogram hence obtained is cut at the required similarity level which restricts the maximum distance between any two recommendations within a cluster. The cluster with maximum number of elements denotes the views of the majority of recommenders. The center of this cluster represents the reputation of the trustee agent which can be computed using c-means algorithm.

  19. Topical hemostatic agents for dermatologic surgery.

    PubMed

    Larson, P O

    1988-06-01

    Topical hemostatic agents are very helpful in attaining capillary and small vessel hemostasis in dermatologic surgery. The commonly used topical hemostatic agents, including oxidized cellulose, absorbable gelatin, and thrombin are reviewed, along with newer agents such as microfibrillar collagen, fibrin sealants, and acrylates. Agents best suited for certain situations are recommended.

  20. 31 CFR 597.301 - Agent.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Agent. 597.301 Section 597.301 Money... Definitions § 597.301 Agent. (a) The term agent means: (1) Any person owned or controlled by a foreign... term agent includes, but is not limited to, any person determined by the Director of the Office of...

  1. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Agent. 221.11 Section 221.11 Aeronautics... REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and file... publications, under authority of their powers of attorney given to such issuing agent as provided in § 221.150...

  2. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  3. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Agent. 221.11 Section 221.11 Aeronautics... REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and file... publications, under authority of their powers of attorney given to such issuing agent as provided in § 221.150...

  4. 31 CFR 597.301 - Agent.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Agent. 597.301 Section 597.301 Money... Definitions § 597.301 Agent. (a) The term agent means: (1) Any person owned or controlled by a foreign... term agent includes, but is not limited to, any person determined by the Director of the Office of...

  5. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Agent. 221.11 Section 221.11 Aeronautics... REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and file... publications, under authority of their powers of attorney given to such issuing agent as provided in § 221.150...

  6. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  7. 46 CFR Sec. 2 - General Agent's requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false General Agent's requirements. Sec. 2 Section 2 Shipping... General Agent's requirements. The General Agent shall: (a) Obtain from the Master, a requisition for slop.... (d) Submit to the Coast Director in the district in which the General Agent is located, upon...

  8. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  9. 46 CFR Sec. 3 - General Agents' responsibilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false General Agents' responsibilities. Sec. 3 Section 3... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 3 General Agents... $5,000, requests for approval shall be transmitted by General Agents by cable or wire addressed to...

  10. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false General Agents' authority. Sec. 2 Section 2 Shipping... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 2 General Agents' authority. The General Agents are hereby delegated authority to undertake for the account of the National...

  11. 31 CFR 597.301 - Agent.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Agent. 597.301 Section 597.301 Money... Definitions § 597.301 Agent. (a) The term agent means: (1) Any person owned or controlled by a foreign... term agent includes, but is not limited to, any person determined by the Director of the Office of...

  12. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production of...

  13. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false General Agents' authority. Sec. 2 Section 2 Shipping... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE IN CONTINENTAL UNITED STATES PORTS VOYAGE REPAIRS AND SERVICE... AGREEMENT Sec. 2 General Agents' authority. The General Agents are: (a) Hereby delegated authority to...

  14. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Agent. 221.11 Section 221.11 Aeronautics... REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and file... publications, under authority of their powers of attorney given to such issuing agent as provided in § 221.150...

  15. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Agent. 221.11 Section 221.11 Aeronautics... REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and file... publications, under authority of their powers of attorney given to such issuing agent as provided in § 221.150...

  16. 13 CFR 120.952 - Fiscal agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Fiscal agent. 120.952 Section 120... Loan Program (504) Debenture Sales and Service Agents § 120.952 Fiscal agent. SBA shall appoint a Fiscal Agent to assess the financial markets, minimize the cost of sales, arrange for the production...

  17. Topical hemostatic agents in otolaryngologic surgery.

    PubMed

    Acar, Baran; Babademez, Mehmet Ali; Karabulut, Hayriye

    2010-01-01

    Topical hemostatic agents are largely used to reduce blood loss during otolaryngologic surgery. These agents play an important role in both keeping the patient's hemodynamic equilibrium and allowing for a better view of the surgical field. These agents can be classified based on their mechanism of action, and include physical or mechanical agents. Most complications of topical hemostatic agents are sustained because of the antigenic reaction of those products. This paper reviews traditional and newer topical hemostatic agents with regard to their chemical properties, their mechanisms of action, and the benefits and complications of topical agents.

  18. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  19. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Funding Leverage by Use of Sba-Guaranteed Trust Certificates (âtcsâ) § 107.1620... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  20. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  1. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Funding Leverage by Use of Sba-Guaranteed Trust Certificates (âtcsâ) § 107.1620... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  2. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for Licensees (Leverage) Funding Leverage by Use of Sba-Guaranteed Trust Certificates (âtcsâ) § 107.1620... Fiscal Agent to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the...

  3. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  4. Triggered pore-forming agents

    DOEpatents

    Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

    1998-07-07

    An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

  5. Nucleotide cleaving agents and method

    DOEpatents

    Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

    2000-01-01

    The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

  6. An Introduction to Software Agents

    DTIC Science & Technology

    2008-02-01

    applicable to modelling red force entities for VMSA. This paper provides an overview of software agents and represents the first step in the...ordinateur, et que la simulation en cours modélise leurs capteurs , leurs armes et leurs caractéristiques matérielles. vi DRDC Atlantic TM...34 9 Sample Applications

  7. An Autonomous Spacecraft Agent Prototype

    NASA Technical Reports Server (NTRS)

    Pell, Barney; Bernard, Douglas E.; Chien, Steve A.; Gat, Erann; Muscettola, Nicola; Nayak, P. Pandurang; Wagner, Michael D.; Williams, Brian C.

    1997-01-01

    This paper describes the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. This architecture integrates traditional real-time monitoring and control with constraint-based planning and scheduling, robust multi-threaded execution, and model-based diagnosis and reconfiguration.

  8. Nanospheric Chemotherapeutic and Chemoprotective Agents

    DTIC Science & Technology

    2008-09-01

    including anti-tumor agents, anti-depressants and statins , are lipophilic and therefore require a solubilization process to enable their parenteral...and can lead to clinically important adverse effects, including acute hypersensitivity reactions and peripheral neuropathy.(28) It is postulated

  9. Antibacterial activities of antineoplastic agents.

    PubMed Central

    Bodet, C A; Jorgensen, J H; Drutz, D J

    1985-01-01

    Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens. Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities. PMID:2416271

  10. Novel piperidinyloxy oxazolidinone antimicrobial agents.

    PubMed

    Weidner-Wells, M A; Boggs, C M; Foleno, B D; Wira, E; Bush, K; Goldschmidt, R M; Hlasta, D J

    2001-07-23

    Oxazolidinone antibacterial agents, where the N-substituted piperazinyl group of eperezolid was replaced with a N-substituted piperidinyloxy moiety, were synthesized and shown to be active against a variety of resistant and susceptible Gram-positive organisms. The effect of ring size, positional isomerism, and fluorine substitution on antibacterial activity was examined.

  11. Training and Supporting Linking Agents.

    ERIC Educational Resources Information Center

    Crandall, David P.

    The purpose of this chapter is to present a view of the realities facing those playing linking roles and to give direction to renewed efforts to develop training and support mechanisms for linking agents. The first section of the chapter presents the assumptions underlying the paper. The second consists of four principal subsections. The first…

  12. Superintendents: The Key Influence Agents.

    ERIC Educational Resources Information Center

    Powell, Randy

    1990-01-01

    By the nature of their positions in schools, administrators are either influence agents or targets. Based on personal interviews with 140 Oregon administrators and a survey of 319 administrators around the state, this article highlights administrators' comments about their administrative influence and about constraints on their influence.…

  13. SEM: A Cultural Change Agent

    ERIC Educational Resources Information Center

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  14. Foodborne illness and microbial agents

    USDA-ARS?s Scientific Manuscript database

    Foodborne illnesses result from the consumption of food containing microbial agents such as bacteria, viruses, parasites or food contaminated by poisonous chemicals or bio-toxins. Pathogen proliferation is due to nutrient composition of foods, which are capable of supporting the growth of microorgan...

  15. Agent Supported Serious Game Environment

    ERIC Educational Resources Information Center

    Terzidou, Theodouli; Tsiatsos, Thrasyvoulos; Miliou, Christina; Sourvinou, Athanasia

    2016-01-01

    This study proposes and applies a novel concept for an AI enhanced serious game collaborative environment as a supplementary learning tool in tertiary education. It is based on previous research that investigated pedagogical agents for a serious game in the OpenSim environment. The proposed AI features to support the serious game are the…

  16. Other Viruses and Viruslike Agents

    USDA-ARS?s Scientific Manuscript database

    The diseases reported under 'Virus and Virus-like Agents' in the first volume of this compendium, with the exception of Cherry rasp leaf virus and Rubus chinese seed-borne virus, should be considered oddities since there are no known type isolates available for these reported viruses. Without a po...

  17. SEM: A Cultural Change Agent

    ERIC Educational Resources Information Center

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  18. Voter models with contrarian agents.

    PubMed

    Masuda, Naoki

    2013-11-01

    In the voter and many other opinion formation models, agents are assumed to behave as congregators (also called the conformists); they are attracted to the opinions of others. In this study I investigate linear extensions of the voter model with contrarian agents. An agent is either congregator or contrarian and assumes a binary opinion. I investigate three models that differ in the behavior of the contrarian toward other agents. In model 1, contrarians mimic the opinions of other contrarians and oppose (i.e., try to select the opinion opposite to) those of congregators. In model 2, contrarians mimic the opinions of congregators and oppose those of other contrarians. In model 3, contrarians oppose anybody. In all models, congregators are assumed to like anybody. I show that even a small number of contrarians prohibits the consensus in the entire population to be reached in all three models. I also obtain the equilibrium distributions using the van Kampen small-fluctuation approximation and the Fokker-Planck equation for the case of many contrarians and a single contrarian, respectively. I show that the fluctuation around the symmetric coexistence equilibrium is much larger in model 2 than in models 1 and 3 when contrarians are rare.

  19. Preventing erosion with novel agents.

    PubMed

    Wang, X; Megert, B; Hellwig, E; Neuhaus, K W; Lussi, A

    2011-02-01

    This in vitro study aimed to investigate the protective effect of four commercial novel agents against erosion. Ninety human molars were distributed into 9 groups, and after incubation in human saliva for 2 h, a pellicle was formed. Subsequently, the specimens were submitted to demineralization (orange juice, pH 3.6, 3 min) and remineralization (paste slurry containing one of the tested novel agents, 3 min) cycles, two times per day, for 4 days. The tested agents were: (1) DenShield Tooth; active ingredient: 7.5% W/W NovaMin(®) (calcium sodium phosphosilicate); (2) Nanosensitive hca; active ingredient: 7.5% W/W NovaMin(®); (3) GC Tooth Mousse; active ingredient: 10% Recaldent™ (CPP-ACP); (4) GC MI Paste Plus; active ingredients: 10% Recaldent™, 900 ppm fluoride. Two experimental procedures were performed: in procedure 1, the tested agents were applied prior to the erosive attack, and in procedure 2 after the erosive attack. A control group receiving no prophylactic treatment was included. Surface nanohardness (SNH) of enamel specimens was measured after pellicle formation and after completion of daily cyclic treatment. SNH significantly decreased at the end of the experiment for all groups (p<0.05). In both procedures, there was no statistically significant difference between the control group and those treated with paste slurries (p>0.05). In addition, the changes in SNH (ΔSNH=SNHbaseline-SNHfinal) did not show statistically significant difference between both procedures (p>0.05). Tooth erosion cannot be prevented or repaired by these novel agents, regardless of fluoride content. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Halide test agent replacement study

    SciTech Connect

    Banks, E.M.; Freeman, W.P.; Kovach, B.J.

    1995-02-01

    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  1. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, G.W.; Carter, R.D.; Hand, T.E.; Powers, M.T.

    1996-05-07

    The present invention is a tetrahydrofurfuryl alcohol and limonene or terpineol cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  2. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, G.W.; Carter, R.D.; Hand, T.E.; Powers, M.T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  3. Limonene and tetrahydrofurfurly alcohol cleaning agent

    DOEpatents

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  4. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1996-05-07

    The present invention is a tetrahydrofurfuryl alcohol and limonene or terpineol cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  5. Laser interrogation of surface agents (LISA) for chemical agent reconnaissance

    NASA Astrophysics Data System (ADS)

    Higdon, N. S.; Chyba, Thomas H.; Richter, Dale A.; Ponsardin, Patrick L.; Armstrong, Wayne T.; Lobb, C. T.; Kelly, Brian T.; Babnick, Robert D.; Sedlacek, Arthur J., III

    2002-06-01

    Laser Interrogation of Surface Agents (LISA) is a new technique which exploits Raman scattering to provide standoff detection and identification of surface-deposited chemical agents. ITT Industries, Advanced Engineering and Sciences Division is developing the LISA technology under a cost-sharing arrangement with the US Army Soldier and Biological Chemical Command for incorporation on the Army's future reconnaissance vehicles. A field-engineered prototype LISA-Recon system is being designed to demonstrate on-the- move measurements of chemical contaminants. In this article, we will describe the LISA technique, data form proof-of- concept measurements, the LISA-Recon design, and some of the future realizations envisioned for military sensing applications.

  6. Innovative agents in cancer prevention.

    PubMed

    Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

    2005-01-01

    There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

  7. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    ERIC Educational Resources Information Center

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  8. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    ERIC Educational Resources Information Center

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  9. Does an Agent Matter? The Effects of Animated Pedagogical Agents on Multimedia Environments.

    ERIC Educational Resources Information Center

    Craig, Scotty D.; Gholson, Barry

    Data are presented on the effects of Animated Agents on multimedia learning environments with specific concerns of split attention and modality effects. The study was a 3 (agent properties: agent only, agent with gestures, no agent) x 3 (picture features: static picture, sudden onset, animation) factorial design with outcome measures of mental…

  10. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    NASA Technical Reports Server (NTRS)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  11. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    NASA Technical Reports Server (NTRS)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  12. Needs, Pains, and Motivations in Autonomous Agents.

    PubMed

    Starzyk, Janusz A; Graham, James; Puzio, Leszek

    2016-08-17

    This paper presents the development of a motivated learning (ML) agent with symbolic I/O. Our earlier work on the ML agent was enhanced, giving it autonomy for interaction with other agents. Specifically, we equipped the agent with drives and pains that establish its motivations to learn how to respond to desired and undesired events and create related abstract goals. The purpose of this paper is to explore the autonomous development of motivations and memory in agents within a simulated environment. The ML agent has been implemented in a virtual environment created within the NeoAxis game engine. Additionally, to illustrate the benefits of an ML-based agent, we compared the performance of our algorithm against various reinforcement learning (RL) algorithms in a dynamic test scenario, and demonstrated that our ML agent learns better than any of the tested RL agents.

  13. CATS-based Agents That Err

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  14. Chaotic neurodynamics for autonomous agents.

    PubMed

    Harter, Derek; Kozma, Robert

    2005-05-01

    Mesoscopic level neurodynamics study the collective dynamical behavior of neural populations. Such models are becoming increasingly important in understanding large-scale brain processes. Brains exhibit aperiodic oscillations with a much more rich dynamical behavior than fixed-point and limit-cycle approximation allow. Here we present a discretized model inspired by Freeman's K-set mesoscopic level population model. We show that this version is capable of replicating the important principles of aperiodic/chaotic neurodynamics while being fast enough for use in real-time autonomous agent applications. This simplification of the K model provides many advantages not only in terms of efficiency but in simplicity and its ability to be analyzed in terms of its dynamical properties. We study the discrete version using a multilayer, highly recurrent model of the neural architecture of perceptual brain areas. We use this architecture to develop example action selection mechanisms in an autonomous agent.

  15. Mechanisms of contrast agent destruction.

    PubMed

    Chomas, J E; Dayton, P; Allen, J; Morgan, K; Ferrara, K W

    2001-01-01

    Various applications of contrast-assisted ultrasound, including blood vessel detection, perfusion estimation, and drug delivery, require controlled destruction of contrast agent microbubbles. The lifetime of a bubble depends on properties of the bubble shell, the gas core, and the acoustic waveform impinging on the bubble. Three mechanisms of microbubble destruction are considered: fragmentation, acoustically driven diffusion, and static diffusion. Fragmentation is responsible for rapid destruction of contrast agents on a time scale of microseconds. The primary characteristics of fragmentation are a very large expansion and subsequent contraction, resulting in instability of the bubble. Optical studies using a novel pulsed-laser optical system show the expansion and contraction of ultrasound contrast agent microbubbles with the ratio of maximum diameter to minimum diameter greater than 10. Fragmentation is dependent on the transmission pressure, occurring in over 55% of bubbles insonified with a peak negative transmission pressure of 2.4 MPa and in less than 10% of bubbles insonified with a peak negative transmission pressure of 0.8 MPa. The echo received from a bubble decorrelates significantly within two pulses when the bubble is fragmented, creating an opportunity for rapid detection of bubbles via a decorrelation-based analysis. Preliminary findings with a mouse tumor model verify the occurrence of fragmentation in vivo. A much slower mechanism of bubble destruction is diffusion, which is driven by both a concentration gradient between the concentration of gas in the bubble compared with the concentration of gas in the liquid, as well as convective effects of motion of the gas-liquid interface. The rate of diffusion increases during insonation, because of acoustically driven diffusion, producing changes in diameter on the time scale of the acoustic pulse length, thus, on the order of microseconds. Gas bubbles diffuse while they are not being insonified, termed

  16. Safety Pharmacology of Anticancer Agents.

    PubMed

    Martin, Pauline L

    2015-01-01

    The safety pharmacology testing for anticancer agents has historically differed for small molecule pharmaceutical drugs versus large-molecule biopharmaceuticals. For pharmaceutical drugs, dedicated safety pharmacology studies have been conducted according to the ICH M3 (R2), ICH 7A, and ICH S7B guidance documents. For biopharmaceuticals, safety pharmacology endpoints have been incorporated into the repeated-dose toxicology studies according to ICHS6 (R1). However, the introduction of the ICH S9 guidance document for the nonclinical evaluation for anticancer pharmaceuticals has allowed for a streamlined approach for both types of molecules to facilitate access of new potential therapeutics to cancer patients and to reduce the number of animal studies. Examples of the testing strategies that have previously been employed for some representative anticancer agents are provided, and their predictivity to adverse events noted in the clinic is discussed.

  17. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  18. Novel Antiangiogenic Agents in Dermatology

    PubMed Central

    Berrios, Ricardo L.; Arbiser, Jack L.

    2011-01-01

    Because angiogenesis underlies the pathogenesis of numerous conditions (cancer, psoriasis, macular degeneration), there is a pressing need for continued investigations into angiogenic signaling and potential drug targets. Antiangiogenic agents can be classified as either direct or indirect. Direct antiangiogenics act on untransformed endothelial cells to prevent differentiation and proliferation; indirect antiangiogenics act to inhibit factors involved in proangiogenic signaling. Agents currently available with dermatologic indications are few, while several established and novel biologics targeting various proangiogenic factors are currently being investigated for potential dermatologic uses, but the jury is still out on their efficacy and safety. In this review, we highlight our experience with a group of existing and novel, small molecules that combine several modes of action against angiogenesis in addition to other properties – triarylmethane dyes and fulvene derivatives. PMID:21172300

  19. Antisense Treatments for Biothreat Agents

    DTIC Science & Technology

    2006-08-01

    oligomers (ASOs) represent a promising technology to treat viral and bacterial infections, and have already been shown to be successful against a...viral and bacterial agents have a history of state- sponsored ’weaponization’, including Marburg, Ebola, Junin, Machupo, yellow fever viruses and...14. ABSTRACT Antisense oligomers (ASOs) represent a promising technology to treat viral and bacterial infections, and have already been shown to be

  20. New Disinfection Agents for Water

    DTIC Science & Technology

    1984-10-01

    oo20 7 Effect of Agent I and HTII on Viability of Entamoeba invadens ..... ................ o...type I and rotavirus), protozoa ( Entamoeba invadens and Giardia lamblia), and fungi (Rhodotorula rubra and Candida albicans). Variables in the study...sufficiently long contact time. PROTOZOA STUDIES The IP-1 strain of Entamoeba invadens and the Portland strain of Giardia lamblia were grown in 15 mL

  1. Characteristics of Mustard (Blister) Agents

    DTIC Science & Technology

    2007-10-01

    aerosol drops won’t touch skin or clothing, but the fragrance is still detectable. That fragrance is the vapor. What are the signs of exposure? Symptoms...lung tissue and blisters the skin . In amounts approaching the lethal dose, injury to bone marrow, lymph nodes and spleen may occur. Mustard agent is...colorless liquid with an odor similar to Geraniums. Exposure causes irritation to eyes, skin , respiratory tract and circulatory system and the

  2. Firefighting Agent Research, Phase I

    DTIC Science & Technology

    2007-04-01

    10 Figure 8: Venn diagram showing the trans (left) and gauche (right) conformations........ 11 Figure 9: Perfluorinated octanoic acid (PFOA...fluorosurfactants used in the 3M formulations have been removed from production due to environmental concerns.5 The fluorosurfactants used by the manufacturers...fighting foams. Modeling the behavior and properties of compounds in fire fighting agents such as perfluorinated surfactants in aqueous and/or organic

  3. Multi-agent autonomous system

    NASA Technical Reports Server (NTRS)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  4. Thrombotic microangiopathies and antineoplastic agents.

    PubMed

    Grangé, Steven; Coppo, Paul

    2017-04-01

    Thrombotic microangiopathy is a well-described complication of cancer treatment. Its incidence has increased these last decades, as a result of a better awareness of this complication in cancer patients in one hand, but also of a larger array of therapeutic compounds including anti-vascular endothelium growth factor (VEGF) drugs. It is therefore mandatory to recognize these conditions since they have a significant impact in thrombotic microangiopathies management and prognosis. Practitioners should be aware of the more classical antineoplastic agents associated with thrombotic microangiopathies, the mechanisms by which they induce them, and the resulting management and prognosis. Since malignancy itself can induce thrombotic microangiopathies, it is also mandatory to know how to distinguish rapidly those caused by antineoplastic agents from those associated with cancer, for an adapted management. Thrombotic microangiopathies associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of thrombotic microangiopathies, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  5. New agents in HSC mobilization.

    PubMed

    Domingues, Mélanie J; Nilsson, Susan K; Cao, Benjamin

    2017-02-01

    Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions. AMD3100 (plerixafor), a small molecule that selectively inhibits the chemokine receptor CXCR4 is approved for mobilization in combination with G-CSF in patients with Non-Hodgkin's lymphoma and multiple myeloma. Nevertheless, identifying mobilization strategies that not only enhance HSC number, but are rapid and generate an optimal "mobilized product" for improved transplant outcomes remains an area of clinical importance. In recent times, new agents based on recombinant proteins, peptides and small molecules have been identified as potential candidates for therapeutic HSC mobilization. In this review, we describe the most recent developments in HSC mobilization agents and their potential impact in HSC transplantation.

  6. Pharmacologic Agents for Chronic Diarrhea.

    PubMed

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.

  7. Pharmacologic Agents for Chronic Diarrhea

    PubMed Central

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  8. Agent planning in AgScala

    NASA Astrophysics Data System (ADS)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  9. Expressing Quality of Service in Agent Communication

    DTIC Science & Technology

    2001-06-01

    many criteria within a multi - agent system . It can be used to express timing capabilties of an agent, or the accuracy of a response that an agent can...upon a model of a real-time multi - agent system (RTMAS) that we have developed [3]. The model is based on the assumption that agents may be able to...Providence, RI, July 1997. [3] L.C. DiPippo, V. F.-Wolfe, L. Nair, E. Hodys and O. Uvarov. A Real-Time Multi - Agent System Architecture for E- Commerce

  10. Learning other agents` preferences in multiagent negotiation

    SciTech Connect

    Bui, H.H.; Kieronska, D.; Venkatesh, S.

    1996-12-31

    In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complement knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).

  11. Preoperative management of anticoagulation and antiplatelet agents.

    PubMed

    Gleason, Lauren Jan; Friedman, Susan M

    2014-05-01

    This article describes current literature and treatment plans for managing anticoagulation and antiplatelet agents in patients presenting with hip fractures. Indications for anticoagulation and antiplatelet agents are discussed, and management techniques for when patients present with hip fractures are reviewed.

  12. What Are Anticoagulants and Antiplatelet Agents?

    MedlinePlus

    ... by heart Treatments + Tests What Are Anticoagulants and Antiplatelet Agents? Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. Blood clots can block the ...

  13. Intelligent Agent Architectures: Reactive Planning Testbed

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kahn, Philip

    1993-01-01

    An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

  14. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  15. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  16. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  17. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  18. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  19. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  20. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  1. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  2. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  3. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  4. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  5. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  6. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  7. Intraperitoneal contrast agents for computed tomography

    SciTech Connect

    Stork, J.

    1985-08-01

    Intraperitoneal contrast agents have been used to diagnose mass lesions, adhesions, and hernias using conventional radiographic techniques. The use of intraperitoneal contrast agents in conjunction with computed tomography (CT) has been limited and is the subject of this report.

  8. Security Measures to Protect Mobile Agents

    NASA Astrophysics Data System (ADS)

    Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

    2010-11-01

    The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

  9. Extinguishing agent for combustible metal fires

    DOEpatents

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

    A low chloride extinguishing agent for combustible metal fires comprising from substantially 75 to substantially 94 weight percent of sodium carbonate as the basic fire extinguishing material, from substantially 1 to substantially 5 weight percent of a water-repellent agent such as a metal stearate, from substantially 2 to substantially 10 weight percent of a flow promoting agent such as attapulgus clay, and from substantially 3 to substantially 15 weight percent of a polyamide resin as a crusting agent.

  10. [Advances in the development of new antitubercular agents from a group of 5-membered heterocyclic compounds containing various heteroatoms].

    PubMed

    Waisser, K; Drhová, L

    1999-09-01

    Tuberculosis and other antimycobacterial diseases are considered to be one of the most important problems of the health service at present. Since 1985, and in particular in the 1990s, a search for new structures of antimycobacterial substances has ranked among the prior fields of chemotherapeutic research. The present review paper links up with the previous communications, and surveys the studies carried out in the field of five-membered heterocyclic compounds containing more heteroatoms since 1984. The most frequently investigated field is thiazole derivatives but the most successful papers originated in the group of oxazoles, where effective antituberculotics for clinical use can be expected in the future. The present research is based on the journal Chemical Abstracts and original papers.

  11. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  12. Honey - A Novel Antidiabetic Agent

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

    2012-01-01

    Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

  13. Quality control of decontaminating agents.

    PubMed

    Arancegui, N; Cabanillas, M; Martinez, A; Funosas, E; Maestri, L; Hermida Lucena, P

    1999-01-01

    The present study evaluates the efficiency of the following decontaminating agents for the multiresistant, locally circulating bacterium Pseudomonas aeruginosa: glutaraldehyde 2%--makes A and B-, glutaraldehyde-formaldehyde; povidone-iodine-makes A, B and C-; sodium hypochloride; chloroxylenol--makes A and B-; and lapire chloride. The 9027 ATCC strain was used as a standard. A modification of the method of Kelsey and Sykes (1) was used to evaluate decontaminating efficiency. Highly satisfactory results were obtained with glutaraldehide 2% A and B, glutaraldehyde-formaldehyde and sodium hypochlorite. The results for povidone-iodine A, B and C were satisfactory but were unsatisfactory for chloroxylenol and lapirium chloride.

  14. Method For Detecting Biological Agents

    DOEpatents

    Chen, Liaohai; McBranch, Duncan W.; Wang, Hsing-Lin; Whitten, David G.

    2005-12-27

    A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

  15. Pathogenic rickettsiae as bioterrorism agents.

    PubMed

    Azad, Abdu F

    2007-07-15

    Because of their unique biological characteristics, such as environmental stability, small size, aerosol transmission, persistence in infected hosts, low infectious dose, and high associated morbidity and mortality, Rickettsia prowazekii and Coxiella burnetii have been weaponized. These biological attributes would make the pathogenic rickettsiae desirable bioterrorism agents. However, production of highly purified, virulent, weapon-quality rickettsiae is a daunting task that requires expertise and elaborate, state-of-the art laboratory procedures to retain rickettsial survival and virulence. Another drawback to developing rickettsial pathogens as biological weapons is their lack of direct transmission from host to host and the availability of very effective therapeutic countermeasures against these obligate intracellular bacteria.

  16. Cardiotoxicity of Molecularly Targeted Agents

    PubMed Central

    Hedhli, Nadia; Russell, Kerry S

    2011-01-01

    Cardiac toxicity of molecularly targeted cancer agents is increasingly recognized as a significant side effect of chemotherapy. These new potent therapies may not only affect the survival of cancer cells, but have the potential to adversely impact normal cardiac and vascular function. Unraveling the mechanisms by which these therapies affect the heart and vasculature is crucial for improving drug design and finding alternative therapies to protect patients predisposed to cardiovascular disease. In this review, we summarize the classification and side effects of currently approved molecularly targeted chemotherapeutics. PMID:22758623

  17. Hypersensitivity reactions to biologic agents.

    PubMed

    Vultaggio, Alessandra; Castells, Mariana C

    2014-08-01

    Biologic agents (BAs) are important therapeutic tools; their use has rapidly expanded and they are used in oncology, immunology, and inflammatory diseases. Their use may be limited, however, by adverse drug reactions. This article reviews the current literature on clinical presentation and pathogenic mechanisms of both acute and delayed reactions. In addition, procedures for management of BA-induced reactions, including preventive and diagnostic work-up, are provided. Lastly, this article summarizes the current knowledge of desensitization to several widely used monoclonal antibodies. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Analysis of commercial plastination agents.

    PubMed

    Chaynes, P; Mingotaud, A-F

    2004-06-01

    S3, S6 and S10 are the most commonly used agents for tissue plastination. Surprisingly, their chemical structures are not known. We therefore decided to fully characterize these products by standard analytical methods: multinucleus magnetic resonance, infrared spectroscopy and size exclusion chromatography. These experiments have shown that Biodur S10 is a polydimethylsiloxane with a molecular weight of 27,200 and silanol functionalities, Biodur S6 is tetraethoxysilane, and Biodur S3 is a mixture the main component of which is dibutyltindilaurate.

  19. [Antiangiogenic agents in ARMD treatment].

    PubMed

    Coroi, Mihaela-Cristiana; Demea, Sorina; Todor, Meda; Apopei, Emmanuela

    2012-01-01

    The aim of antiangiogenic agents in the treatment of age related senile macular degeneration is to destroy coroidian neoformation vessels by minimally affecting the central vision. We present a case of important central vision recovery after 3 intravitreal injections of Avastin. The therapeutic decision and patient monitoring have been made using imaging studies, such as OCT and AFG. A modern therapeutic approach of neovascular forms of age related macular degeneration, backed up by AFG and OCT is a modern treatment method of this disabling illness which brings patients optimal functional and structural improvement.

  20. Online Deception Detection Using BDI Agents

    ERIC Educational Resources Information Center

    Merritts, Richard A.

    2013-01-01

    This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

  1. Construction and Evaluation of Animated Teachable Agents

    ERIC Educational Resources Information Center

    Bodenheimer, Bobby; Williams, Betsy; Kramer, Mattie Ruth; Viswanath, Karun; Balachandran, Ramya; Belynne, Kadira; Biswas, Gautam

    2009-01-01

    This article describes the design decisions, technical approach, and evaluation of the animation and interface components for an agent-based system that allows learners to learn by teaching. Students learn by teaching an animated agent using a visual representation. The agent can answer questions about what she has been taught and take quizzes.…

  2. An Agent for the Prospect Presentation Problem

    DTIC Science & Technology

    2014-05-01

    machine learning to adapt them to our domain. We perform an extensive evaluation of our agent in comparison to other baseline agents and show that presentation can indeed affect the acceptance rate of propositions and that the agent we propose succeeds in selecting beneficial

  3. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  4. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  5. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  6. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  7. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  8. Verifiable Middleware for Secure Agent Interoperability

    DTIC Science & Technology

    2002-10-01

    bandwidth commu- nication links. However, agents technology carries with it associated security vulnerabilities. Distributed computing in general...carries with it risks such as denial of service, Trojan horses, information leaks, and malicious code. Agents technology , by introducing autonomy and code... technology to industry because security is a necessary pre- requisite for distributed computing. To make agent-based systems economically viable, it is

  9. The Ontogenesis of Agent: Linguistic Expression.

    ERIC Educational Resources Information Center

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  10. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  11. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  12. Infants Attribute to Agents Goals and Dispositions

    ERIC Educational Resources Information Center

    Luo, Yuyan; Choi, You-jung

    2012-01-01

    This commentary article is to be published alongside: Hernik, M., & Southgate, V. (2012). What do infants know about agents' goals? The authors see this issue consisting of two closely related questions. First, what is an agent to infants? Second, how do infants attribute goals to agents? Hernik and Southgage (H&S) focused on the second question.…

  13. Agent-based modeling of complex infrastructures

    SciTech Connect

    North, M. J.

    2001-06-01

    Complex Adaptive Systems (CAS) can be applied to investigate complex infrastructures and infrastructure interdependencies. The CAS model agents within the Spot Market Agent Research Tool (SMART) and Flexible Agent Simulation Toolkit (FAST) allow investigation of the electric power infrastructure, the natural gas infrastructure and their interdependencies.

  14. 46 CFR Sec. 2 - General Agent's requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false General Agent's requirements. Sec. 2 Section 2 Shipping... General Agent's requirements. The General Agent shall: (a) Obtain from the Master, a requisition for slop..., together with a copy of the vendor's invoice showing items, units, unit cost and totals. (c) Furnish the...

  15. 46 CFR Sec. 2 - General Agent's requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false General Agent's requirements. Sec. 2 Section 2 Shipping... General Agent's requirements. The General Agent shall: (a) Obtain from the Master, a requisition for slop..., together with a copy of the vendor's invoice showing items, units, unit cost and totals. (c) Furnish the...

  16. 13 CFR 120.951 - Selling agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Selling agent. 120.951 Section 120.951 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Debenture Sales and Service Agents § 120.951 Selling agent. The CDC, with...

  17. 13 CFR 120.951 - Selling agent.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Selling agent. 120.951 Section 120.951 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Debenture Sales and Service Agents § 120.951 Selling agent. The CDC, with...

  18. 13 CFR 120.951 - Selling agent.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Selling agent. 120.951 Section 120.951 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Debenture Sales and Service Agents § 120.951 Selling agent. The CDC, with...

  19. 13 CFR 120.951 - Selling agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Selling agent. 120.951 Section 120.951 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Debenture Sales and Service Agents § 120.951 Selling agent. The CDC, with...

  20. 13 CFR 120.951 - Selling agent.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Selling agent. 120.951 Section 120.951 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Debenture Sales and Service Agents § 120.951 Selling agent. The CDC, with...

  1. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  2. Online Deception Detection Using BDI Agents

    ERIC Educational Resources Information Center

    Merritts, Richard A.

    2013-01-01

    This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

  3. 31 CFR 561.311 - Agent.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Agent. 561.311 Section 561.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS... Agent. For purposes of this part, the term agent includes an entity established by a person for purposes...

  4. 7 CFR 958.84 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 958.84 Section 958.84 Agriculture Regulations... Agents. The Secretary may, by designation in writing, name any person, including any officer or employee... agent or representative in connection with any of the provisions of this part. ...

  5. 7 CFR 924.68 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 924.68 Section 924.68 Agriculture Regulations... WASHINGTON AND IN UMATILLA COUNTY, OREGON Order Regulating Handling Miscellaneous Provisions § 924.68 Agents... name any agency or division in the United States Department of Agriculture, to act as his agent or...

  6. 7 CFR 989.89 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 989.89 Section 989.89 Agriculture Regulations... CALIFORNIA Order Regulating Handling Miscellaneous Provisions § 989.89 Agents. The Secretary may, by a... name any bureau or division in the United States Department of Agriculture, to act as his agent or...

  7. 7 CFR 930.87 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 930.87 Section 930.87 Agriculture Regulations... Miscellaneous Provisions § 930.87 Agents. The Secretary may, by designation in writing, name any officer or... as the Secretary's agent or representative in connection with any provisions of this part. ...

  8. 7 CFR 985.67 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 985.67 Section 985.67 Agriculture Regulations... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Miscellaneous Provisions § 985.67 Agents... name any agency or division in the U.S. Department of Agriculture, to act as the Secretary's agent or...

  9. 7 CFR 905.86 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 905.86 Section 905.86 Agriculture Regulations... TANGELOS GROWN IN FLORIDA Order Regulating Handling Miscellaneous Provisions § 905.86 Agents. The Secretary..., or name any bureau or division in the United States Department of Agriculture, to act as his agent or...

  10. 31 CFR 332.12 - Fiscal agents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Fiscal agents. 332.12 Section 332.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE....12 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of the...

  11. 7 CFR 959.88 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 959.88 Section 959.88 Agriculture Regulations... Handling Miscellaneous Provisions § 959.88 Agents. The Secretary may, by designation in writing, name any... agent or representative in connection with any of the provisions of this subpart. ...

  12. 7 CFR 953.79 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 953.79 Section 953.79 Agriculture Regulations... Order Regulating Handling Miscellaneous Provisions § 953.79 Agents. The Secretary may, by designation in... division in the United States Department of Agriculture, to act as his agent or representative in...

  13. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Acidifying agents. 58.720 Section 58.720 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food and...

  14. 31 CFR 316.12 - Fiscal agents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Fiscal agents. 316.12 Section 316.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... § 316.12 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of...

  15. 7 CFR 985.67 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 985.67 Section 985.67 Agriculture Regulations... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Miscellaneous Provisions § 985.67 Agents... name any agency or division in the U.S. Department of Agriculture, to act as the Secretary's agent or...

  16. 7 CFR 945.87 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 945.87 Section 945.87 Agriculture Regulations... Agents. The Secretary may, by designation in writing, name any person, including any officer or employee... act as his agent or representative in connection with any of the provisions of this subpart. ...

  17. 7 CFR 993.88 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 993.88 Section 993.88 Agriculture Regulations... Regulating Handling Miscellaneous Provisions § 993.88 Agents. (a) Authorization by Secretary. The Secretary... as his agent or representative in connection with any of the provisions of this subpart. (b...

  18. 7 CFR 947.84 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 947.84 Section 947.84 Agriculture Regulations... Miscellaneous Provisions § 947.84 Agents. The Secretary may, by designation in writing, name any person... Agriculture, to act as his agent or representative in connection with any of the provisions of this subpart. ...

  19. 7 CFR 987.81 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 987.81 Section 987.81 Agriculture Regulations... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Miscellaneous Provisions § 987.81 Agents. The... as his agent or representative in connection with any of the provisions of this part. ...

  20. 31 CFR 561.311 - Agent.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Agent. 561.311 Section 561.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS... Agent. The term agent includes an entity established by a person for purposes of conducting transactions...

  1. 7 CFR 927.76 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 927.76 Section 927.76 Agriculture Regulations... Regulating Handling Miscellaneous Provisions § 927.76 Agents. The Secretary may name, by designation in... Department of Agriculture to act as his or her agent or representative in connection with any of the...

  2. 7 CFR 958.84 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 958.84 Section 958.84 Agriculture Regulations... Agents. The Secretary may, by designation in writing, name any person, including any officer or employee... agent or representative in connection with any of the provisions of this part. ...

  3. 7 CFR 956.92 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 956.92 Section 956.92 Agriculture Regulations... OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Miscellaneous Provisions § 956.92 Agents. The Secretary..., or name any agency in the United States Department of Agriculture, to act as the Secretary's agent or...

  4. 7 CFR 905.86 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 905.86 Section 905.86 Agriculture Regulations... TANGELOS GROWN IN FLORIDA Order Regulating Handling Miscellaneous Provisions § 905.86 Agents. The Secretary..., or name any bureau or division in the United States Department of Agriculture, to act as his agent or...

  5. 12 CFR 9.20 - Transfer agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Transfer agents. 9.20 Section 9.20 Banks and... Regulations § 9.20 Transfer agents. (a)(1) Registration. An application for registration under Section 17A(c) of the Securities Exchange Act of 1934 of a transfer agent for which the OCC is the appropriate...

  6. 7 CFR 956.92 - Agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Agents. 956.92 Section 956.92 Agriculture Regulations... OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Miscellaneous Provisions § 956.92 Agents. The Secretary..., or name any agency in the United States Department of Agriculture, to act as the Secretary's agent or...

  7. 24 CFR 35.94 - Agent responsibilities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false Agent responsibilities. 35.94...-Based Paint and/or Lead-Based Paint Hazards Upon Sale or Lease of Residential Property § 35.94 Agent responsibilities. (a) Each agent shall ensure compliance with all requirements of this subpart. To ensure...

  8. 7 CFR 906.59 - Agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Agents. 906.59 Section 906.59 Agriculture Regulations... GRANDE VALLEY IN TEXAS Order Regulating Handling Miscellaneous Provisions § 906.59 Agents. The Secretary... States, or name any agency in the United States Department of Agriculture, to act as his agent or...

  9. 31 CFR 342.9 - Fiscal agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Fiscal agents. 342.9 Section 342.9 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of the United States...

  10. 44 CFR 62.3 - Servicing agent.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Servicing agent. 62.3 Section... OF CLAIMS Issuance of Policies § 62.3 Servicing agent. (a) Pursuant to sections 1345 and 1346 of the Act, the Federal Insurance Administrator has entered into the Agreement with a servicing agent to...

  11. 7 CFR 987.81 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 987.81 Section 987.81 Agriculture Regulations... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Miscellaneous Provisions § 987.81 Agents. The... as his agent or representative in connection with any of the provisions of this part. ...

  12. 31 CFR 339.6 - Fiscal agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Fiscal agents. 339.6 Section 339.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... H § 339.6 Fiscal agents. Federal Reserve Banks and Branches, as fiscal agents of the United States...

  13. 7 CFR 985.67 - Agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Agents. 985.67 Section 985.67 Agriculture Regulations... SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Miscellaneous Provisions § 985.67 Agents... name any agency or division in the U.S. Department of Agriculture, to act as the Secretary's agent or...

  14. 31 CFR 330.9 - Fiscal agents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 2 2013-07-01 2013-07-01 false Fiscal agents. 330.9 Section 330.9... OF UNITED STATES SAVINGS BONDS AND UNITED STATES SAVINGS NOTES (FREEDOM SHARES) § 330.9 Fiscal agents... agents of the United States. These Federal Reserve Banks shall perform such services in connection with...

  15. 7 CFR 959.88 - Agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Agents. 959.88 Section 959.88 Agriculture Regulations... Handling Miscellaneous Provisions § 959.88 Agents. The Secretary may, by designation in writing, name any... agent or representative in connection with any of the provisions of this subpart. ...

  16. 31 CFR 339.6 - Fiscal agents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance: Treasury 2 2014-07-01 2014-07-01 false Fiscal agents. 339.6 Section 339.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE..., SERIES H § 339.6 Fiscal agents. Federal Reserve Banks and Branches, as fiscal agents of the United States...

  17. 31 CFR 339.6 - Fiscal agents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 2 2011-07-01 2011-07-01 false Fiscal agents. 339.6 Section 339.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... H § 339.6 Fiscal agents. Federal Reserve Banks and Branches, as fiscal agents of the United States...

  18. 31 CFR 316.12 - Fiscal agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 2 2012-07-01 2012-07-01 false Fiscal agents. 316.12 Section 316.12 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE....12 Fiscal agents. (a) Federal Reserve Banks and Branches referred to below, as fiscal agents of the...

  19. 7 CFR 948.88 - Agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Agents. 948.88 Section 948.88 Agriculture Regulations... Regulating Handling Miscellaneous Provisions § 948.88 Agents. The Secretary may, by designation in writing... United States Department of Agriculture, to act as his agent or representative in connection with any of...

  20. 44 CFR 62.3 - Servicing agent.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Servicing agent. 62.3 Section... OF CLAIMS Issuance of Policies § 62.3 Servicing agent. (a) Pursuant to sections 1345 and 1346 of the Act, the Federal Insurance Administrator has entered into the Agreement with a servicing agent to...