Sample records for antitubercular agents

  1. Phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents

    Singh R


    Full Text Available Richa Singh,1 Laxman Nawale,2 Manisha Arkile,2 Sweety Wadhwani,1 Utkarsha Shedbalkar,1 Snehal Chopade,1 Dhiman Sarkar,2 Balu Ananda Chopade1,3 1Department of Microbiology, Savitribai Phule Pune University, 2Combichem-Bioresource Center, Organic Chemistry Division, National Chemical Laboratory, Pune, 3Dr Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Purpose: Multi- and extensively drug-resistant tuberculosis (TB is a global threat to human health. It requires immediate action to seek new antitubercular compounds and devise alternate strategies. Nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. In view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria. Methods: Silver (AgNPs, gold (AuNPs, and gold–silver bimetallic (Au–AgNPs nanoparticles synthesized from medicinal plants, such as Barleria prionitis, Plumbago zeylanica, and Syzygium cumini, were tested against Mycobacterium tuberculosis and M. bovis BCG. In vitro and ex vivo macrophage infection model assays were designed to determine minimum inhibitory concentration (MIC and half maximal inhibitory concentration of nanoparticles. Microscopic analyses were carried out to demonstrate intracellular uptake of nanoparticles in macrophages. Besides this, biocompatibility, specificity, and selectivity of nanoparticles were also established with respect to human cell lines. Results: Au–AgNPs exhibited highest antitubercular activity, with MIC of <2.56 µg/mL, followed by AgNPs. AuNPs did not show such activity at concentrations of up to 100 µg/mL. In vitro and ex vivo macrophage infection model assays revealed the inhibition of both active and dormant stage mycobacteria on exposure to Au–AgNPs. These nanoparticles were capable of entering macrophage cells and exhibited up to 45% cytotoxicity at 30 µg/mL (ten times MIC concentration after 48 hours

  2. Phytogenic silver, gold, and bimetallic nanoparticles as novel antitubercular agents

    Singh, Richa; Nawale, Laxman; Arkile, Manisha; Wadhwani, Sweety; Shedbalkar, Utkarsha; Chopade, Snehal; Sarkar, Dhiman; Chopade, Balu Ananda


    Purpose Multi- and extensively drug-resistant tuberculosis (TB) is a global threat to human health. It requires immediate action to seek new antitubercular compounds and devise alternate strategies. Nanomaterials, in the present scenario, have opened new avenues in medicine, diagnosis, and therapeutics. In view of this, the current study aims to determine the efficacy of phytogenic metal nanoparticles to inhibit mycobacteria. Methods Silver (AgNPs), gold (AuNPs), and gold–silver bimetallic (Au–AgNPs) nanoparticles synthesized from medicinal plants, such as Barleria prionitis, Plumbago zeylanica, and Syzygium cumini, were tested against Mycobacterium tuberculosis and M. bovis BCG. In vitro and ex vivo macrophage infection model assays were designed to determine minimum inhibitory concentration (MIC) and half maximal inhibitory concentration of nanoparticles. Microscopic analyses were carried out to demonstrate intracellular uptake of nanoparticles in macrophages. Besides this, biocompatibility, specificity, and selectivity of nanoparticles were also established with respect to human cell lines. Results Au–AgNPs exhibited highest antitubercular activity, with MIC of <2.56 μg/mL, followed by AgNPs. AuNPs did not show such activity at concentrations of up to 100 μg/mL. In vitro and ex vivo macrophage infection model assays revealed the inhibition of both active and dormant stage mycobacteria on exposure to Au–AgNPs. These nanoparticles were capable of entering macrophage cells and exhibited up to 45% cytotoxicity at 30 μg/mL (ten times MIC concentration) after 48 hours. Among these, Au–AgNPs synthesized from S. cumini were found to be more specific toward mycobacteria, with their selectivity index in the range of 94–108. Conclusion This is the first study to report the antimycobacterial activity of AuNPs, AgNPs, and Au–AgNPs synthesized from medicinal plants. Among these, Au–AgNPs from S. cumini showed profound efficiency, specificity, and

  3. Tuberculosis: current treatment, diagnostics, and newer antitubercular agents in clinical trials.

    Ahsan, Mohamed Jawed; Ansari, Mohammad Yousuf; Yasmin, Sabina; Jadav, Surender Singh; Kumar, Pradeep; Garg, Shiv Kumar; Aseri, Ajay; Khalilullah, Habibullah


    Tuberculosis (TB), a dreadful disease is one of the most important health problems worldwide, and is responsible for approximately 1.3 million death tolls in 2012. DOTS is the currently used drug therapy in TB and the long term drug regimens and patients' poor compliance lead to emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB, which invigorates the research efforts to address the urgent need for the quick diagnosis and for newer antitubercular agents and vaccines to completely eradicate TB. Today we have at least 20 new diagnostic test platforms, 14 TB vaccine candidates in clinical trials and over 35 candidates in preclinical development, and among the antitubercular agents under clinical investigation, 4 anti-TB agents are in Phase III (efficacy) trials and 7 anti-TB agents are in Phase II, early bactericidal activity and sputum culture conversion trials (rifapentine is in a Phase II and a Phase III trial), 5 anti-TB agents in preclinical development and 3 anti-TB agents in Good Laboratory Practice toxicity evaluation. Recently US FDA has approved TMC207 as a part of combination therapy to treat adults with MDR pulmonary TB in the absence of other alternatives. We provide here the concise review on the chemical entities currently in the clinical trials, the new vaccines in the developmental pipeline, and the new diagnostic test. PMID:25246035

  4. Pharmacophore combination as a useful strategy to discover new antitubercular agents

    Rana, D. N.; Chhabria, M. T.; Shah, N. K.; Brahmkshatriya, Pathik


    Roč. 23, č. 1 (2014), s. 370-381. ISSN 1054-2523 Institutional support: RVO:61388963 Keywords : antitubercular * benzoxazole * interaction energy * molecular docking * pharmacophore * pyrazoline Subject RIV: CC - Organic Chemistry Impact factor: 1.402, year: 2014

  5. Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents

    Kar, Sidhartha S; Bhat G, Varadaraj; Rao, Praveen PN; Shenoy, Vishnu P; Bairy, Indira; Shenoy, G Gautham


    A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs. PMID:27486307

  6. Facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.

    Subhedar, Dnyaneshwar D; Shaikh, Mubarak H; Arkile, Manisha A; Yeware, Amar; Sarkar, Dhiman; Shingate, Bapurao B


    We have developed, highly efficient, one-pot, solvent-free, [Et3NH][HSO4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. For the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis dormant MTB H37Ra and Mycobacterium bovis BCG strains. Among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays promising antitubercular activity along with no significant cytotoxicity against the cell lines MCF-7, A549 and HCT-116. PMID:26927426

  7. Natural product inspired diversity oriented synthesis of tetrahydroquinoline scaffolds as antitubercular agent.

    Kumar, Atul; Srivastava, Suman; Gupta, Garima; Chaturvedi, Vinita; Sinha, Sudhir; Srivastava, R


    An efficient natural product inspired diversity oriented syn thesis of tetrahydroquinoline analogues has been developed using the natural carbohydrate derived solid acid catalyst via multicomponent aza-Diels-Alder reaction of imine (generated in situ from aromatic amine and aldehyde) with dienophile in acetonitrile in a diastereoselective manner. The use of water as solvent reverses the diastereoselectivity toward the cis isomer. Interestingly, tricyclic pyrano/furano benzopyran with cis diastereoselectivity is obtained when salicylaldehyde is used as an alternative of aromatic aldehyde under the same condition. These synthesized quinolines and benzopyrans analogues have been evaluated for their Antitubercular activity against M. tuberculosis H₃₇Ra, and M. tuberculosis H₃₇Rv, and some of the analogues shows better activity profile than their natural product analogues. The protocol is not only mild, efficient, ecofriendly, but also involves reusable and biodegradable catalyst and provides route for both the diastereoisomer. PMID:21247127

  8. Discovery of new antitubercular agents by combining pyrazoline and benzoxazole pharmacophores: design, synthesis and insights into the binding interactions

    Rana, D. N.; Chhabria, M. T.; Shah, N. K.; Brahmkshatriya, Pathik


    Roč. 23, č. 5 (2014), s. 2218-2228. ISSN 1054-2523 Institutional support: RVO:61388963 Keywords : antitubercular * benzoxazole * interaction energy * molecular docking * pharmacophore * pyrazoline Subject RIV: CC - Organic Chemistry Impact factor: 1.402, year: 2014

  9. Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of ABC and Solute Carrier Transporters.

    Sasabe, Hiroyuki; Shimokawa, Yoshihiko; Shibata, Masakazu; Hashizume, Kenta; Hamasako, Yusuke; Ohzone, Yoshihiro; Kashiyama, Eiji; Umehara, Ken


    Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as the substrates and inhibitors of various transporters were evaluated in vitro Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion-transporting polypeptides, or organic cation transporter 1. Similarly, metabolite 1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2 inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory concentrations (M1, 4.65 and 5.71 μmol/liter, respectively; M2, 7.80 and 6.02 μmol/liter, respectively), well above the corresponding maximum concentration in plasma values observed following the administration of multiple doses in clinical trials. M3 and M4 did not affect the activities of any of the transporters tested. These in vitro data suggest that delamanid is unlikely to have clinically relevant interactions with drugs for which absorption and disposition are mediated by this group of transporters. PMID:27021329

  10. Seeking potent anti-tubercular agents: Design, synthesis, anti-tubercular activity and docking study of various ((triazoles/indole)-piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole derivatives.

    Naidu, Kalaga Mahalakshmi; Srinivasarao, Singireddi; Agnieszka, Napiórkowska; Ewa, Augustynowicz-Kopeć; Kumar, Muthyala Murali Krishna; Chandra Sekhar, Kondapalli Venkata Gowri


    A series of thirty eight novel 3-(4-((substituted-1H-1,2,3-triazol-4-yl)methyl)piperazin-1-yl/1,4-diazepan-1-yl)benzo[d]isoxazole and 1-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl/1,4-diazepan-1-yl)-2-(1H-indol-3-yl)substituted-1-one analogues were synthesised, characterised using various analytical techniques and evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two 'wild' strains Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 6.16 to >200μM. Among the tested compounds, 7i, 7y and 7z exhibited moderate activity (MIC=24.03-29.19μM) and 7j exhibited very good anti-tubercular activity (MIC=6.16μM). Furthermore, 7i, 7j, 7y and 7z were found to be non-toxic against mouse macrophage cell lines when screened for toxicity. All the synthesised compounds were docked to pantothenate synthetase enzyme site to know deferent binding interactions with the receptor. PMID:27020525

  11. QSAR study of some 5-methyl/trifluoromethoxy- 1H-indole-2,3-dione-3-thiosemicarbazone derivatives as anti-tubercular agents

    Shahlaei, M.; Fassihi, A.; Nezami, A.


    In the present study, quantitative relationships between molecular structure and anti-tubercular activity of some 5-methyl/trifluoromethoxy-1H-indole-2,3-dione-3-thiosemicarbazone derivatives were discovered. The detailed application of an efficient linear method and principal component regression (PCR) for the evaluation of quantitative structure activity relationships of the studied compounds is demonstrated. Components produced by principal component analysis were used as the input for a l...

  12. Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.

    Desai, N C; Somani, Hardik; Trivedi, Amit; Bhatt, Kandarp; Nawale, Laxman; Khedkar, Vijay M; Jha, Prakash C; Sarkar, Dhiman


    A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization. PMID:26920799

  13. QSAR study of some 5-methyl/trifluoromethoxy- 1H-indole-2,3-dione-3-thiosemicarbazone derivatives as anti-tubercular agents

    Shahlaei, M.; Fassihi, A.; Nezami, A.


    In the present study, quantitative relationships between molecular structure and anti-tubercular activity of some 5-methyl/trifluoromethoxy-1H-indole-2,3-dione-3-thiosemicarbazone derivatives were discovered. The detailed application of an efficient linear method and principal component regression (PCR) for the evaluation of quantitative structure activity relationships of the studied compounds is demonstrated. Components produced by principal component analysis were used as the input for a linear model development. Results indicate a linear relationship between the principal components obtained from molecular descriptors and the inhibitory activity of this set of molecules. The maximum variance in the activity of the molecules in PCR method was 73%. The performance of the developed model was tested by several validation methods. PMID:21589807


    Kapupara Pankaj P


    Full Text Available Tuberculosis, due to its relentless nature, is now a major public health threat. The concomitant resurgence of TB with the MDR- or XDR-TB and HIV/AIDS pandemic has exposed the frailties of the current drug armatorium. Based on good structural similarity between BM-212, a novel antimycobacterial agent undergoing clinical trials, and diaryl thiophenes, we have designed novel diaryl thiophenes. Alkyl or aryl isothiocyanates were reacted with substituted phenylacetonitrile in the presence of NaH to afforded 3-mercapto-3-(substitutedamino-2- [(unsubstitutedphenyl]acrylonitrile (5a-h. The designed molecules, 3-amino-2-cyano-5-(substitutedamino-4- [(unsubstitutedphenyl]thiophenes (6a-h were synthesized by cyclocondention of 3-mercapto-3-(substitutedamino- 2-[(unsubstitutedphenyl]acrylonitrile (5a-h with chloroacetonitrile in ethanol. All the compounds were screened for their antimycobacterial activity on mycobacterium tuberculosis using H37Rv strain by 1% proportion method. Some of the synthesized compounds exhibited potent antimycobacterial activity with MIC values in the range of 12.5-100 µg/mL.

  15. Design, Synthesis, Toxicity Estimation and Molecular Docking Studies of N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimine as Antitubercular Agents

    B Mathew; Suresh, J.; Mathew, Githa E; George Sonia; G K Krishnan


    A series of novel N-(furan-2-yl)-1-(5-substituted) phenyl-1,3,4-oxadiazol-2-yl) methanimines (Fa-e) were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (H 37 Rv) strain by using alamar blue assay. The synthesized compounds were characterized based on IR, 1 HMR and mass spectral analysis. The toxicity profile was predicted by organic chemistry portal, a web based application for predicting in silico absorption, distribution, metabolism, excretion and t...

  16. Design, synthesis, toxicity estimation and molecular docking studies of N-(Furan-2-yl-1-(5-substituted phenyl-1,3,4-oxadiazol-2-yl methanimine as antitubercular agents

    B Mathew


    Full Text Available A series of novel N-(furan-2-yl-1-(5-substituted phenyl-1,3,4-oxadiazol-2-yl methanimines (Fa-e were synthesized and evaluated for antitubercular activity against Mycobacterium tuberculosis (H 37 Rv strain by using alamar blue assay. The synthesized compounds were characterized based on IR, 1 HMR and mass spectral analysis. The toxicity profile was predicted by organic chemistry portal, a web based application for predicting in silico absorption, distribution, metabolism, excretion and toxicity, and the novel derivatives under study did not show any toxicity issues. The mechanism of action of the titled derivatives was predicted by docking on the Mycobacterium tuberculosis Enoyl-ACP reductase enzyme. The docking study concluded that Fb and Fa possessed good binding energy indicating more prominent interaction towards the active sites NAD and TYR 158. The antitubercular studies showed that the both Fa and Fb possessed significant activity with the MIC as low as 3.125 μg/ml.

  17. Stable Tricyclic Antitubercular Ozonides Derived from Artemisinin.

    Chaudhary, Sandeep; Sharma, Vashundhra; Jaiswal, Pradeep K; Gaikwad, Anil N; Sinha, Sudhir K; Puri, Sunil K; Sharon, Ashoke; Maulik, Prakas R; Chaturvedi, Vinita


    New, highly stable tricyclic antitubercular ozonides 9 and 10 derived from artemisinin are reported in 39 and 9% yields, respectively. The ozonide groups of 9 and 10 were found to be stable under strong basic and acidic conditions. The absolute configuration of ozonides 9 was confirmed by X-ray crystallography. Ozonide 10 shows promising antitubercular activity against M. tuberculosis H37Ra and M. tuberculosis H37Rv with MIC values of 0.39 and 3.12 μg/mL, respectively. PMID:26430796


    S. Rajasekaran*, Gopalkrishna Rao and H.S. Niranjan


    Full Text Available In recent years, there is a tremendous increase of drug resistant pathogens, leading to the design and development of newer antitubercular agents. A series of 2-(substituted-phenyl-1,3-benzoxazin-4-ones and 3-amino-2-(substituted-phenylquinazolin-4(3H-ones were synthesized by the reaction of substituted benzoyl chloride with anthranilic acid and 2- (substituted phenyl-1,3-benzoxazin-4-one with hydrazine hydrate in absolute alcohol respectively. The title compounds 2-substituted phenyl-3-(thiophen-2-ylmethyleneamino quinazolin-4(3H-ones and 2-(substituted phenyl-3-(1-(furan-2-ylethylideneamino quinazolin-4(3H-ones were obtained by reacting 3-amino-2-(substituted phenyl quinazolin-4(3H-one with thiophene-2-carboxaldehyde and 2-acetyl furan respectively. The title compounds have been characterized by UV, IR, 1H-NMR and Mass spectra. The synthesized compounds have been evaluated for their antitubercular activity. Few of the compounds exhibited significant antitubercular while other compounds showed moderate activity.

  19. Effect of AND#945;-tocopherol on antitubercular drugs induced hepatotoxicity

    Rajiv Nehra


    Conclusions: and #945;-tocopherol (200 mg/kg bw, oral was found to have hepatoprotective effect against antitubercular drugs induced hepatotoxicity in albino rabbits. [Int J Res Med Sci 2016; 4(4.000: 1158-1162

  20. Triterpenes and antitubercular activity of Byrsonima crassa

    We evaluated the potential antitubercular activity of triterpenes obtained from leaves and bark of Byrsonima crassa. From chloroform extracts of the leaves, by bioassay-guided fractionation, we obtained mixtures of known triterpenes: alpha-amyrin, beta-amyrin and their acetates, lupeol, oleanolic acid, ursolic acid and alpha-amyrinone. Tested against Mycobacterium tuberculosis, the triterpenes exhibited minimum inhibitory concentrations (MICs) of 31.25 - 312.25 mug/mL. beta-amyrin and friedelin, isolated from the chloroform extract of bark, showed MICs of 312.25 and 125 mug/mL respectively. This is the first report of the identification and determination of the activity of B. crassa triterpenes against M. tuberculosis. (author)

  1. Triterpenes and antitubercular activity of Byrsonima crassa

    Higuchi, Celio Takashi; Pavan, Fernando Rogerio; Leite, Clarice Queico Fujimura [Universidade Estadual Paulista, Araraquara, SP (Brazil). Fac. de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas]. E-mail:; Sannomiya, Miriam; Vilegas, Wagner; Leite, Sergio Roberto de Andrade [Universidade Estadual Paulista (UNESP), Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica Geral e Inorganica; Sacramento, Luis Vitor S. [Universidade Estadual Paulista (UNESP), Araraquara, SP (Brazil). Fac. de Ciencias Farmaceuticas. Dept. de Principios Ativos Naturais e Toxicologia; Sato, Daisy Nakamura [Instituto Adolfo Lutz de Ribeirao Preto, SP (Brazil)


    We evaluated the potential antitubercular activity of triterpenes obtained from leaves and bark of Byrsonima crassa. From chloroform extracts of the leaves, by bioassay-guided fractionation, we obtained mixtures of known triterpenes: alpha-amyrin, beta-amyrin and their acetates, lupeol, oleanolic acid, ursolic acid and alpha-amyrinone. Tested against Mycobacterium tuberculosis, the triterpenes exhibited minimum inhibitory concentrations (MICs) of 31.25 - 312.25 mug/mL. beta-amyrin and friedelin, isolated from the chloroform extract of bark, showed MICs of 312.25 and 125 mug/mL respectively. This is the first report of the identification and determination of the activity of B. crassa triterpenes against M. tuberculosis. (author)

  2. Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates

    Patel, Rahul V.; Keum, Y.S.; Park, S.W.


    Roč. 15, č. 14 (2015), s. 1174-1186. ISSN 1389-5575 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Antitubercular drugs * delamanid * fluorine-containing drugs Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.903, year: 2014

  3. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor.

    Martínez-Hoyos, María; Perez-Herran, Esther; Gulten, Gulcin; Encinas, Lourdes; Álvarez-Gómez, Daniel; Alvarez, Emilio; Ferrer-Bazaga, Santiago; García-Pérez, Adolfo; Ortega, Fátima; Angulo-Barturen, Iñigo; Rullas-Trincado, Joaquin; Blanco Ruano, Delia; Torres, Pedro; Castañeda, Pablo; Huss, Sophie; Fernández Menéndez, Raquel; González Del Valle, Silvia; Ballell, Lluis; Barros, David; Modha, Sundip; Dhar, Neeraj; Signorino-Gelo, François; McKinney, John D; García-Bustos, Jose Francisco; Lavandera, Jose Luis; Sacchettini, James C; Jimenez, M Soledad; Martín-Casabona, Nuria; Castro-Pichel, Julia; Mendoza-Losana, Alfonso


    Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment. PMID:27428438

  4. Tenuazonic acid: a promising antitubercular principle from Alternaria alternate

    Visalakchi Sonaimuthu


    Full Text Available Bioactivity guided isolation of dichloromethane extract of Alternaria alternata identified tenuazonic acid (1 as potentially active against Mycobacterium tuberculosis H37Rv, MIC at 250 μg/mL concentration. This active metabolite 1, was also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that this fungal metabolite showing antitubercular activity exhibited concentration dependent toxicity to human erythrocytes.

  5. Cervical Lymphadenopathy—Pitfalls of Blind Antitubercular Treatment

    Pandit, Sudipta; Choudhury, Sabyasachi; Das, Anirban; Das, Sibes Kumar; Bhattacharya, Soumya


    Tuberculosis (TB) is the most common cause of cervical lymphadenopathy in the TB-endemic zone, like India but it can also mimic other diseases. Four cases of cervical lymphadenopathy presented to us as initial treatment failure after completion of six months of antitubercular drugs (ATD), including rifampicin, isoniazid, pyrazinamide, and ethambutol. All were diagnosed as having tuberculosis either by fine needle aspiration cytology or clinically from outside our institution. In one case, tub...

  6. Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues.

    Geoffrey D Coxon

    Full Text Available Defining the pharmacological target(s of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61 or HadC (at Val85, Lys157 or Thr123, which are components of the β-hydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors.

  7. Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

    Periwal Vinita


    Full Text Available Abstract Background Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb, affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR and extensively drug-resistant (XDR strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. Results We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. Conclusions This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

  8. Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

    Sílvia H. Cardoso


    Full Text Available A series of 13 compounds analogous of isoniazid condensed with carbohydrate was synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC90 in μg/mL. Several compounds exhibited antitubercular activity (0.31-3.12 μg/mL when compared with first line drugs such as isoniazid (INH and rifampicin (RIP and could be a good starting point to develop new compounds against tuberculosis.

  9. Plumbagin analogs-synthesis, characterization, and antitubercular activity

    Nishi Nayak


    Full Text Available Considering the emerging problem of drug resistance in tuberculosis, there is an urgent need of development of new analogs that are useful in curing drug resistant tuberculosis. In India, tuberculosis continues to remain one of the most pressing health problems. India is the highest tuberculosis burden country in the world, accounting one fifth of global incidence - estimated 2.0-2.5 million cases annually. In 2011, approximately 8.7 million new cases of tuberculosis and 1.4 million people die from tuberculosis each year worldwide. Current antitubercular therapies are successful against normal tuberculosis but it is not suitable for drug resistant tuberculosis. In this study Plumbagin analogs, obtained from Plumbago zeylanica (Family-Plumbaginaceae, have been synthesized. Out of the various synthesized analogs, the antitubercular activity of compound a and b was evaluated using standard H 37 Rv and S, H, R, and E sensitive M tuberculosis strains using LRF assay method. Compound a showed strong activity against both standard H 37 Rv and S, H, R and E sensitive M. tuberculosis strains as compared to standard Rifampicin. The other compounds are proved to be more active against standard H 37 Rv and S, H, R and E sensitive M. tuberculosis strain as compared to Rifampicin.

  10. Inhalable Antitubercular Therapy Mediated by Locust Bean Gum Microparticles.

    Alves, Ana D; Cavaco, Joana S; Guerreiro, Filipa; Lourenço, João P; Rosa da Costa, Ana M; Grenha, Ana


    Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy. PMID:27240337

  11. Multinuclear NMR analysis of the antitubercular drug ethionamide

    Vale, Nuno; Correia, Alexandra; Figueiredo, Patrícia; Santos, Hélder A.


    Tuberculosis remains as the deadliest bacterial infection in developing countries, a situation that is particularly aggravated by the increasing spread of multidrug resistant mycobacteria (MDR-TB). In this view, not only new anti-tubercular drugs are urgently needed, but also a better understanding of the existing ones may aid in the future design of more efficient derivatives or surrogates. Ethionamide (ETA) is an anti-tubercular pro-drug used as second-line therapy against MDR-TB, being bio-activated by the mycobacterial monooxygenase EtA. ETA has been the focus of several research works, devoted either to the identification of ETA's metabolites or to the development of novel derivatives potentially useful to fight against tuberculosis. In either case, structural analysis of ETA and related structures is of undeniable relevance, while the presence of sulfur in ETA's structure brings about the possibility of including 33S-NMR in the toolbox of structural analysis techniques. In this work, we have engaged into a multinuclear NMR characterization of ETA, through the study of the drug's solubility in seven deuterated solvents, and of the chemical shifts for different nuclei in ETA. Results showed which are the best conditions to study ETA by NMR and provided some important evidence on the low reactivity of the drug's thioamide group, which may be of relevance for future drug derivatization approaches.

  12. Tuberculosis after gastrectomy, plasmatic concentration of antitubercular drugs.

    Vittorio, De Socio Giuseppe; Antonio, D'Avolio; Alessio, Sgrelli; Lorena, Baietto; Malincarne, Lisa; Giovanni, Di Perri; Franco, Baldelli


    We report pharmacokinetic data on two gastrectomized, patients affected by tuberculosis. Drugs plasmatic concentrations were measured after seven days of oral therapy by a validated high performance liquid chromatography-mass spectrometry (HPLC-MS) method and the area under the concentration-time-curve (AUC) over 24 hours (AUC(0-24)) was calculated. A sub-therapeutic level of isoniazid was found in a patient with total gastrectomy with a C(max) of 0,395 mg\\L and AUC(0-24) level of 4.75 hr*mg/L. The level of the other antitubercular drugs was adequate. These findings support the need to monitor anti tubercular drug levels to facilitate early detection of therapeutic failure, above all in patients treated with isoniazid and with potential problems on oral drugs absorption. PMID:22348189

  13. Protective Effect of Allium sativum against Liver Injury Induced by Anti-Tubercular Drugs in Rats

    Bello, B; A.M. Wudil


    Allium sativum has been reported to have a lot of therapeutic potentials such as antihypertensive, antimicrobial and hypocholesterolemic. This study has investigated its effect on anti-tubercular drugs hepatotoxicity. Wistar albino rats were pretreated and co-administered orally with aqueous solution of Allium sativum. Eighteen rats were divided into six groups of three rats each. Group 1 were normal, while Group 2 were test control administered with anti-tubercular drugs; isoniazid (27 mg/kg...

  14. Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria.

    Anuradha Alahari

    Full Text Available BACKGROUND: Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs. The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. METHODOLOGY/PRINCIPLE FINDINGS: We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC, and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strain Mycobacterium bovis BCG, as well as in the related pathogenic species Mycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR analyses of mycolic acids purified from drug-treated mycobacteria showed a significant loss of cyclopropanation in both the alpha- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclopropanation, suggesting that the drugs act directly on CMASs. CONCLUSIONS/SIGNIFICANCE: This

  15. Discovery of antitubercular 2,4-diphenyl-1H-imidazoles from chemical library repositioning and rational design.

    Pieroni, Marco; Wan, Baojie; Zuliani, Valentina; Franzblau, Scott G; Costantino, Gabriele; Rivara, Mirko


    TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. The co-infection with HIV and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. In the attempt to respond to the constant need of novel therapeutic options, we herein report the discovery of 2,4-diphenyl-1H-imidazoles as effective antitubercular agents, with MIC in the low micromolar range against actively replicating and persistent M. tuberculosis strains. The good activity, along with the lack of toxicity and the feasible synthesis, underscore their value as novel scaffolds for the development of new anti-TB drugs. PMID:26071857

  16. Antioxidant, Antitubercular and Cytotoxic Activities of Piper imperiale

    Sanjib Bhakta


    Full Text Available Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC50ABTS = 15.6 µg/mL, EC50DPPH = 27.3 µg/mL with EC50 in the same order of magnitude as the hydroxyquinone (EC50ABTS = 10.2 µg/mL, EC50DPPH = 15.7 µg/mL. The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H37Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities.

  17. Antitubercular activity and phytochemical screening of selected medicinal plants

    Rajandeep Kaur


    Full Text Available Medicinal plants offer a hope for developing alternate medicines for the treatment of Tuberculosis.. The present study was done to evaluate in vitro anti-tubercular activity of five medicinal plants viz., Syzygium aromaticum, Piper nigrum, Glycyrrhiza glabra, Aegele marmelos and Lawsonia inermis. Solvent extracts of Syzygium aromaticum, Piper nigrum, Glycyrrhiza glabra, Aegele marmelos and Lawsonia inermis were tested in vitro for their activity against Mycobacterium tuberculosis H37Rv strain using Microplate Alamar Blue Assay. Activity in MABA was evaluated by lowest concentration of sample that prevents color change to pink. Extracts of all the five plants Syzygium aromaticum, Piper nigrum, Glycyrrhiza glabra, Aegele marmelos and Lawsonia inermis exhibited anti-tuberculosis activity, the proportion of inhibition of these plants extracts for M. tuberculosis H37Rv, inhibition was found to be 0.8µg/ml, 50µg/ml, 12.5µg/ml and 50µg/ml respectively. Our findings showed that all these plants exhibited activity against MDR isolates of H37Rv M. tuberculosis strain. Further studies aimed at isolation and identification of active substances from the extracts needs to be carried out

  18. Novel application of Wiener vis-à-vis Szeged indices: Antitubercular activities of quinolones

    Vijay K Agarwal; Shahnaz Bano; Keshav C Mathur; Padmakar V Khadikar


    The paper gives a brief account of the recently introduced Szeged index (Sz). Using this index antitubercular activities of N-2,4-difluorophenyl quinolones are subjected to quantitative structure-activity relationship analysis. The potential of Sz related to the Wiener index (W) is critically discussed. In addition, Huckel molecular orbital energies: HOMO, LUMO and total were also used for comparing and modelling antitubercular activities of the quinolones. The results, based on univariate as well as multivariate regressions, have shown that W, Sz and total give better results and that the correlations improve in multivariate regression analyses.

  19. Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights#

    Li, Shao-Gang; Vilchèze, Catherine; Chakraborty, Sumit; Wang, Xin; Kim, Hiyun; Anisetti, Monica; Ekins, Sean; Rhee, Kyu Y.; Jacobs, William R.; Freundlich, Joel S.


    The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights. PMID:26257441

  20. Effect of Lagenaria siceraria fruit extract (Bottle gourd on hepatotoxicity induced by antitubercular drugs in albino rats

    Satyajeet K. Funde


    Conclusion: Ethanolic extract of Lagenaria siceraria fruit possesses significant hepatoprotective and antioxidant activity in antitubercular drugs induced hepatotoxicity. [Int J Basic Clin Pharmacol 2013; 2(6.000: 728-734

  1. Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives.

    Horita, Yasuhiro; Takii, Takemasa; Kuroishi, Ryuji; Chiba, Taku; Ogawa, Kenji; Kremer, Laurent; Sato, Yasuo; Lee, YooSa; Hasegawa, Tomohiro; Onozaki, Kikuo


    The present study was undertaken to optimize the anti-tubercular activity of 2-acetamido-2-deoxy-β-D-glucopyranosyl N,N-dimethyldithiocarbamate (OCT313, Glc-NAc-DMDC), a lead compound previously reported by us. Structural modifications of OCT313 included the replacements of the DMDC group at C-1 by pyrrolidine dithiocarbamate (PDTC) and the acetyl group at C-2 by either propyl, butyl, benzyl or oleic acid groups. The antimycobacterial activities of these derivatives were evaluated against Mycobacterium tuberculosis (MTB). Glc-NAc-pyrrolidine dithiocarbamate (OCT313HK, Glc-NAc-PDTC) exhibited the most potent anti-tubercular activity with the minimal inhibitory concentration (MIC) of 6.25-12.5 μg/ml. The antibacterial activity of OCT313HK was highly specific to MTB and Mycobacterium bovis BCG, but not against Mycobacterium avium, Mycobacterium smegmatis, Staphylococcus aureus or Escherichia coli. Importantly, OCT313HK was also effective against MTB clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Interestingly, OCT313HK was exerted the primary bactericidal activity, and it was also exhibited the bacteriolytic activity at high concentrations. We next investigated whether the mycobacterial monooxygenase EthA, a common activator of thiocarbamide-containing anti-tubercular drugs, also activated OCT313HK. Contrary to our expectations, the anti-tubercular activity of dithiocarbamate sugar derivatives and dithiocarbamates were not dependent on ethA expression, in contrast to thiocarbamide-containing drugs. Overall, this study presents OCT313HK as a novel and potent compound against MTB, particularly promising to overcome drug resistance. PMID:21232949

  2. Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid

    Hearn, Michael J.; Cynamon, Michael H.; Chen, Michaeline F.; Coppins, Rebecca; Davis, Jessica; Kang, Helen Joo-On; Noble, Abigail; Tu-Sekine, Becky; Terrot, Marianne S.; Trombino, Daniella; Thai, Minh; Webster, Eleanor R.; Wilson, Rebecca


    Structural modification of the frontline antitubercular isonicotinic acid hydrazide (INH) provides lipophilic adaptations (3-46) of the drug in which the hydrazine moiety of the parent compound has been chemically blocked from the deactivating process of N2-acetylation by N-arylaminoacetyl transferases. As a class, these compounds show high levels of activity against Mycobacterium tuberculosis in vitro and in tuberculosis-infected macrophages. They provide strong protection in tuberculosis-in...

  3. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Deepa Gupta; Jain, D. K.


    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antif...

  4. [The epidemiology of tuberculosis and of the resistance to antitubercular agents].

    Aït Khaled, N; Enarson, D; Billo, N


    Tuberculosis is once more a subject of world wide preoccupation; since 1985 a disturbing recrudescence of this disease has been noted in numerous countries related to population growth and the worsening of poverty in those countries without natural resources, and disadvantaged groups living on the margins of society in rich countries, along with the occurrence of an epidemic of HIV (VIH). In numerous developed countries where tuberculosis no longer represents a public health problem, the care services have little by little been closed or re-orientated and the principles of treatment of tuberculosis have been forgotten. The direct consequence of this has often been inadequate treatment and its corollary: the emergence of strains multiresistant to Isoniazid and Rifampicin. If the current epidemiological tendencies are confirmed and no supplementary action is taken, the WHO (OMS) has estimated that during the ten years between 1990 and the millennium there will be 88 million new cases of tuberculosis and 30 million people will die of tuberculosis. However the tendencies can be reversed and tuberculosis could still be eliminated. The struggle against tuberculosis is a world wide emergency and the hope of controlling the situation before an increase in multiresistant strains which would render the trend irreversible, rests on a general application of correct and coherent national programmes. Such a programme as the UICTMR model had already been carried out as has the proof of their efficacy. PMID:9496587

  5. Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents

    SS Kar; Bhat G V; Rao PP; Shenoy VP; Bairy I; Shenoy GG


    Sidhartha S Kar,1 Varadaraj Bhat G,1 Praveen PN Rao,2 Vishnu P Shenoy,3 Indira Bairy,4 G Gautham Shenoy1 1Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India; 2School of Pharmacy, Health Sciences Campus, University of Waterloo, Waterloo, ON, Canada; 3Department of Microbiology, Kasturba Medical College, Manipal, 4Melaka-Manipal Medical College, Manipal University, Manipal, India Abstract: A series of triclosan mimic diphenyl...

  6. Dry powder inhalable formulations for anti-tubercular therapy.

    Parumasivam, Thaigarajan; Chang, Rachel Yoon Kyung; Abdelghany, Sharif; Ye, Tian Tian; Britton, Warwick John; Chan, Hak-Kim


    Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB. Pulmonary delivery is non-invasive, avoids first-pass metabolism in the liver and enables targeting of therapeutic agents to the infection site. Inhaled delivery also potentially reduces the dose requirement and the accompanying side effects. Dry powder is a stable formulation of drug that can be stored without refrigeration compared to liquids and suspensions. The dry powder inhalers are easy to use and suitable for high-dose formulations. This review focuses on the current innovations of inhalable dry powder formulations of drug and vaccine delivery for TB, including the powder production method, preclinical and clinical evaluations of inhaled dry powder over the last decade. Finally, the risks associated with pulmonary therapy are addressed. A novel dry powder formulation with high percentages of respirable particles coupled with a cost effective inhaler device is an appealing platform for TB drug delivery. PMID:27212477

  7. Evaluation of antitubercular drug-loaded surfactants as inhalable drug-delivery systems for pulmonary tuberculosis.

    Chimote, G; Banerjee, R


    Pulmonary tuberculosis is associated with a year-long chemotherapy, poor alveolar drug levels, drug-related systemic toxicity, and patient noncompliance. In this study, exogenous pulmonary surfactant is proposed as a drug carrier for antitubercular drugs. Dipalmitoylphosphatidylcholine (DPPC), the major lung-surfactant lipid, has been combined with antitubercular drugs isoniazid (INH), rifampicin (RFM), and ethambutol (ETH) in 1:1 ratio by weight, in which drugs had a ratio of 1:2:3 by weight. At 37 degrees C, the formulation had better surfactant function with quicker reduction of surface tension on adsorption (32.71 +/- 0.65 mN/m) than DPPC liposomes (44.67 +/- 0.57 mN/m) and maintained 100% airway patency in a capillary surfactometer. Drug-loaded surfactant liposomes were about 2 microm and had entrapment efficiency of 30.04% +/- 2.05%, 18.85% +/- 2.92%, and 61.47% +/- 3.32% for INH, RFM, and ETH, respectively. Sustained release of the drugs from surfactants was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger showed 12.06% +/- 1.87% of INH, 43.30% +/- 0.87% of RFM, and 22.07% +/- 2.02% of ETH deposited in the alveolar chamber upon nebulization for a minute using a jet nebulizer. The formulation was biocompatible and stable with physicochemical properties being retained even after storage for a month at 4 degrees C. Antitubercular drug-loaded surfactants developed could serve dual purposes of alveolar stabilization due to surfactant action and better reach of these drugs to the alveoli due to antiatelectatic effect of the surfactant. PMID:18431766

  8. Evaluation of Protective Effect of Thymoquinone against Anti-tubercular Drug Induced Nephrotoxicity in Rats

    Arvind Chansoria


    Full Text Available Present study was done to see the protective effect of thymoquinone against antitubercular drugs induced nephrotoxicity in rats. Thymoquinone significantly reduced serum urea, serum creatinine and K+ levels in ATT induced renal toxicity. No effect was seen in serum serum Na+ level. Higher dose was found to reduce serum urea to greater extent than 5 mg TQ dose. The nephroprotective effect of thymoquinone was found to be significant. Hence the present study throws light on usefulness of TQ in protection against ATT induced renal injury. This might prove useful for combating the serious renal adverse effects of ATT regimen without eliminating the use of standard first line drugs.

  9. Antitubercular and fluorescence studies of copper(II) complexes with quinolone family member, ciprofloxacin

    Kharadi, G. J.


    Four new mixed-ligand complexes of Cu(II) with ciprofloxacin (Cip) and uninegative bidentate ligands have been synthesized and characterized. The structure of mixed-ligand complexes was investigated using spectroscopic method, physicochemical and elemental analyses. The fluorescence spectra of complexes show red shift, which may be due to the chelation by the ligands to the metal ion. It enhances ligand ability to accept electrons and decreases the electron transition energy. Antimycobacterial screening of ligand and its copper compound against Mycobacterium tuberculosis shows clear enhancement in the antitubercular activity upon copper complexation.

  10. Review: Treatment of toxicity caused by anti-tubercular drugs by use of different herbs

    Radhika Sharma


    Full Text Available Tuberculosis is a familiar ailment in India and worldwide and is chief cause of mortality among all the infectious diseases. In present scenario therapy of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol are commonly recommended against TB. These drugs lead to many adverse reactions which are one of the major reasons for non adherence of patients to these drugs that may lead to development of MDR. With the current scenario of MDR cases rising, this problem of adverse drug reactions cannot be taken lightly. Due to lack of successful drugs for treatment of toxicity caused by anti-TB drugs we have to turn towards traditional medicine. Ayurveda is an ancient system of natural and holistic medicine. Ayurvedic herbs have still being used as a part of treatment regimen in many parts of world. Local people still use these herbs as they are full of curative properties. Because anti-tubercular drugs induced toxicity leads to oxidative enzymes imbalance also leads to necrosis in liver tissue and many other degenerative changes, herbal extracts were experimented upon to test their ability to ameliorate toxicity by activating protective pathways. In this review we have summarized few of such herbs whose extracts were tested for their curative properties against anti-tubercular drugs induced toxicity.The main constituents in extracts that were responsible for protective effects have also been summarized along with their mechanisms of action.

  11. Microwave-assisted synthesis, molecular docking and antitubercular activity of 1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives

    Mohan, S. B.; Kumar, B. V. V. R.; Dinda, S. C.; Naik, D.; Seenivasan, S. P.; Kumar, V.; Rana, D. N.; Brahmkshatriya, Pathik


    Roč. 22, č. 24 (2012), s. 7539-7542. ISSN 0960-894X Institutional research plan: CEZ:AV0Z40550506 Keywords : antitubercular * binding interactions * luciferase reporter phage (LRP) assay * microwave-assisted * molecular docking Subject RIV: CC - Organic Chemistry Impact factor: 2.338, year: 2012

  12. Unproved tuberculous lesion of penis: A rare cause of saxophone penis treated by a therapeutic trial of anti-tubercular therapy

    Srinivasan Narayanaswamy


    We report a case of a 25 year old male patient who came with multiple discharging sinuses and an urethrocutaneous fistula over the penis treated by a therapeutic trial of Anti-tubercular therapy (ATT.

  13. Inhalable chitosan nanoparticles as antitubercular drug carriers for an effective treatment of tuberculosis.

    Garg, Tarun; Rath, Goutam; Goyal, Amit K


    The aim of this study was to prepare and characterize spray dried inhalable chitosan nanoparticles (CNPs) for sustained delivery of anti-tubercular drugs, isoniazid (INH) and rifampicin (RIF), to the lungs. CNPs were prepared by ionic gelation technique followed spray drying. Results showed that the CNPs obtained had a smooth spherical shape with an average size of 230 ± 4.5 nm, with a poly dispersity index of 0.180 ± 0.021. Both drugs, were detected in various organs (lungs, liver, spleen and kidney) until 24 h post nebulization. The chemotherapeutic efficacy of a single dose of drug-loaded CNPs suggested that they are more effective against the mycobacterium than free drugs. PMID:25682840

  14. Comparative efficacy and acceptability of five anti-tubercular drugs in treatment of multidrug resistant tuberculosis: a network meta-analysis

    Wang, Huaidong; Zhang, Xiaotian; Bai, Yuanxiang; Duan, Zipeng; Lin, Yan; Wang, Guoqing; Li, Fan


    Multidrug resistant tuberculosis (MDR-TB) is a serious form of tuberculosis (TB). There is no recognized effective treatment for MDR-TB, although there are a number of publications that have reported positive results for MDR-TB. We performed a network meta-analysis to assess the efficacy and acceptability of potential antitubercular drugs. We conducted a network meta-analysis of randomized controlled clinical trials to compare the efficacy and acceptability of five antitubercular drugs, bedaq...

  15. Biodegradable Polymer-Coated, Gelatin Hydrogel/Bioceramics Ternary Composites for Antitubercular Drug Delivery and Tissue Regeneration

    Mintao Xue; Hongtao Hu; Yuanquan Jiang; Jichun Liu; Hailong He; Xiaojian Ye


    A simple and effective strategy for the treatment of osteoarticular tuberculosis is proposed through combining tissue engineering approach with anti-tuberculosis drug therapy. A series of tricalcium phosphate bioceramics (TPB) composites, coated by degradable polymer outside and loaded with rifampicin (RFP)-containing gelatin hydrogel inside, were thus fabricated and successfully applied to deliver antitubercular drug RFP into osseous lesion and concomitantly to induce tissue regeneration. RF...

  16. Synthesis and anti-tubercular activity of 3-substituted benzo[b]thiophene-1,1-dioxides

    N. Susantha Chandrasekera


    Full Text Available We demonstrated that the 3-substituted benzothiophene-1,1-dioxide class of compounds are effective inhibitors of Mycobacterium tuberculosis growth under aerobic conditions. We examined substitution at the C-3 position of the benzothiophene-1,1-dioxide series systematically to delineate structure–activity relationships influencing potency and cytotoxicity. Compounds were tested for inhibitory activity against virulent M. tuberculosis and eukaryotic cells. The tetrazole substituent was most potent, with a minimum inhibitory concentration (MIC of 2.6 µM. However, cytotoxicity was noted with even more potency (Vero cell TC50 = 0.1 µM. Oxadiazoles had good anti-tubercular activity (MICs of 3–8 µM, but imidazoles, thiadiazoles and thiazoles had little activity. Cytotoxicity did not track with anti-tubercular activity, suggesting different targets or mode of action between bacterial and eukaryotic cells. However, we were unable to derive analogs without cytotoxicity; all compounds synthesized were cytotoxic (TC50 of 0.1–5 µM. We conclude that cytotoxicity is a liability in this series precluding it from further development. However, the series has potent anti-tubercular activity and future efforts towards identifying the mode of action could result in the identification of novel drug targets.

  17. Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities.

    Karad, Sharad C; Purohit, Vishal B; Thakor, Parth; Thakkar, Vasudev R; Raval, Dipak K


    A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level. PMID:26900659

  18. Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

    Massimo Calderazzo


    Full Text Available We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6. The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml.

  19. Antioxidant and hepatoprotective effects of Garcinia indica fruit rind in antitubercular drug-induced liver injury in rats

    Panda VS; Ashar HD; Sharan A


    Vandana S Panda,1 Hardik D Ashar,1 Anita Sharan2 1Department of Pharmacology and Toxicology, Prin KM Kundnani College of Pharmacy, Colaba, Mumbai, India; 2Department of Pathology, Dr DY Patil Medical College, Nerul, Navi Mumbai, India Abstract: The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE) in antitubercular drug (ATD)-induced liver injury were investigated in rats. GIE (400 mg/kg and 800 mg/kg) and the reference drug Liv.52 (500 mg/kg) were administere...

  20. Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis.

    Rajput, Vikrant S; Mehra, Rukmankesh; Kumar, Sanjay; Nargotra, Amit; Singh, Parvinder Pal; Khan, Inshad Ali


    Shikimate kinase of Mycobacterium tuberculosis is involved in the biosynthesis of aromatic amino acids through shikimate pathway. The enzyme is essential for the survival of M. tuberculosis and is absent from mammals, thus providing an excellent opportunity for identifying new chemical entities to combat tuberculosis with a novel mechanism of action. In this study, an antitubercular library of 1000 compounds was screened against M. tuberculosis shikimate kinase (MtSK). This effort led to the identification of 20 inhibitors, among which five promising leads exhibited half maximal inhibitory concentration (IC50) values below 10 μM. The most potent inhibitor ("5631296") showed an IC50 value of 5.10 μM ± 0.6. The leads were further evaluated for the activity against multidrug-resistant (MDR)-TB, Gram-positive and Gram-negative bacterial strains, mode of action, docking simulations, and combinatorial study with three frontline anti-TB drugs. Compound "5491210" displayed a nearly synergistic activity with rifampicin, isoniazid, and ethambutol while compound "5631296" was synergistic with rifampicin. In vitro cytotoxicity against HepG2 cell line was evaluated and barring one compound; all were found to be non-toxic (SI > 10). In order to rule out mitochondrial toxicity, the promising inhibitors were also evaluated for cell cytotoxicity using galactose medium where compounds "5631296" and "5122752" appeared non-toxic. Upon comprehensive analysis, compound "5631296" was found to be the most promising MtSK inhibitor that was safe, synergistic with rifampicin, and bactericidal against M. tuberculosis. PMID:26887318

  1. Adverse Drug Reactions to First Line Anti-Tubercular Drugs - A Pharmacovigilance Study

    Dr. Umeshchandra C Honnaddi


    Full Text Available Introduction: Tuberculosis is one of the major health problems in India and developing countries. It is the second leading infectious cause of morbidity and mortality in the world.Objective: The present study was undertaken to study the Adverse Drug Reactions (ADRs to first line Anti-tubercular drugs (ATTs prescribed to tuberculosis patients admitted to Medicine Department, BTGH, attached to M.R. Medical College, Gulbarga.Materials and Methods: A Prospective Observational study was carried among tuberculosis patients on Directly Observed Short Course Chemotherapy (DOTS, admitted to Medicine Department, BTGH, attached to M.R. Medical College; Gulbarga.120 Patients were included during the study period of 9 months from 1st October 2014 to 30th June 2015. The data was collected in a Proforma which included questionnaire.Results: A total of 120 tuberculosis patients on DOTS were enrolled for the study. Out of 107 patients, 63 patients (58.87% developed ADRs. Out of 63 patients, 32 patients (51% developed Gastro-intestinal problems, 14 patients developed CNS problems (22%, 11 patients (18% developed Hepatitis, 4 patients (6% developed Fever and 2 patients (3% developed Pancreatitis. The most serious ADR was Hepatitis.Conclusion: Results of the study reveals that about 58.87% of patients developed ADRs during the study period. These ADRs will lead to stoppage of drugs, development of Drug resistance and Therapeutic Failure. If a proper Pharmacovigilance system is implemented in the hospital, most of the patients may report their ADRs and thereby we can improve the patient adherence and treatment outcome.

  2. Design, development, drug-likeness, and molecular docking studies of novel piperidin-4-imine derivatives as antitubercular agents

    Revathi R; Venkatesha Perumal R; Pai KSR; Arunkumar G; Sriram D; Kini SG


    Rajappan Revathi,1 Ramachandran Venkatesha Perumal,2 Karkala Sreedhara Ranganath Pai,3 Govindakarnavar Arunkumar,4 Dharmarajan Sriram,5 Suvarna Ganesh Kini1 1Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 2Bharathi College of Pharmacy, Bharathi Nagara, 3Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 4Manipal Centre of Virus Research, Manipal University, Manipal, Karnataka, ...

  3. Antioxidant and hepatoprotective effects of Garcinia indica fruit rind in antitubercular drug-induced liver injury in rats

    Panda VS


    Full Text Available Vandana S Panda,1 Hardik D Ashar,1 Anita Sharan2 1Department of Pharmacology and Toxicology, Prin KM Kundnani College of Pharmacy, Colaba, Mumbai, India; 2Department of Pathology, Dr DY Patil Medical College, Nerul, Navi Mumbai, India Abstract: The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE in antitubercular drug (ATD-induced liver injury were investigated in rats. GIE (400 mg/kg and 800 mg/kg and the reference drug Liv.52 (500 mg/kg were administered orally for 29 days to ATD (isoniazid 7.5 mg/kg, rifampicin 10 mg/kg, and pyrazinamide 35 mg/kg-treated rats. GIE attenuated significantly the ATD-elevated levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase, bilirubin, and malondialdehyde and restored the ATD-depleted levels of glutathione (GSH, superoxide dismutase, catalase, GSH peroxidase, and GSH reductase. The present findings indicate that the hepatoprotective effect of GIE in ATD-induced oxidative damage may be due to its antioxidant activity. Keywords: Garcinia indica fruit, antitubercular drugs, Liv.52, hepatoprotective, antioxidant activity

  4. Ameliorating effects of Tamarindus indica fruit extract on anti-tubercular drugs induced liver toxicity in rats.

    Amir, Mohd; Khan, Mohammad Ahmed; Ahmad, Sayeed; Akhtar, Mohd; Mujeeb, Mohd; Ahmad, Aftab; Khan, Shah Alam; Al-Abbasi, Fahad A


    The study aimed to evaluate the hepatoprotective potential of aqueous extract of Tamarindus indica fruit against combination of two antitubercular drugs viz. Isoniazid and Rifampicin induced hepatotoxicity in rats. In vitro antioxidant activity of aqueous extract of T. indica by DPPH-HPLC method was found to be 81.48%. Treatment with aqueous extract of T. indica significantly reduced the elevated levels of biochemical markers such as SGOT, SGPT, ALP, bilirubin, TBARS and increased the albumin level as well antioxidant activities of SOD, CAT and GSH in intoxicated rats. The biochemical changes were supported by histological observations. Results of this study clearly demonstrate that aqueous extract of T. indica fruit protects against anti tuberculosis induced oxidative liver damage in rats and thus possess significant hepatoprotective activity. Further, it could be suggested that supplementation with this food extract might prove beneficial in the individuals on anti-TB drugs. PMID:25978515

  5. Click-based synthesis and antitubercular evaluation of dibenzofuran tethered thiazolyl-1,2,3-triazolyl acetamides.

    Surineni, Goverdhan; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas


    A series of novel dibenzofuran tethered thiazolyl-1,2,3-triazolyl acetamides, designed by assembling antitubercular pharmacophoric fragments, dibenzofuran, 2-aminothiazole and substituted triazoles in one molecular architecture, were evaluated against Mycobacterium tuberculosis. The new analogues 6a-p accomplished in four step synthetic sequence utilizing click chemistry in the penultimate step, was fully characterized by their NMR and mass spectral data. Among the compounds 6a-p screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, three compounds 6j (MIC: 1.56μg/mL); 6a and 6p (MIC: 3.13μg/mL) was found to be most active and exhibited lower cytotoxicity. Among these three, 6j could be a candidate to consider as a drug like hit analogue for further development. PMID:27317646

  6. Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents

    Talib Hussain; Ramesh K Gupta; Sweety K; Mohd Sajid Khan; Md Sarfaraj Hussain; Md Arif; Arshad Hussain; Md Faiyazuddin; Chandana Venkateswara Rao


    Objective:To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals. Methods:Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination. Results: The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration. Conclusions:The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

  7. Anti-tubercular activity of eleven aromatic and medicinal plants occurring in Colombia Actividad antituberculosa de plantas colombianas

    Wellman Ribón


    Full Text Available Introduction. Human tuberculosis is a contagious-infectious disease mainly caused by Mycobacterium tuberculosis. Although regimens exist for treating tuberculosis, they are far from ideal. Development of effective strategies for treatment of human tuberculosis has posed a challenge, considering the increase in infections associated with the human immunodeficiency virus and immunocompromised patients. Essential oils -volatile, aromatic oil extracts from plants-have been used in traditional treatment of many diseases; however careful investigation of these oils has not been undertaken with respect to treatments of tuberculosis.
    Objective. The in vitro antitubercular activity of essential oils from 11 medicinal plants grown in Colombia were assessed for efficacy as new medications (phytomedicines for treatment of M. tuberculosis H37Rv.
    Material and methods. Essential oil extraction and analysis were performed as described Stashenko et al. (2004. Minimal inhibitory concentrations were determined by a colorimetric macrodilution method, following the protocol described by Abate et al. (1998. Isoniazide and rifampin were used as control treatments. Bactericidal and bacteriostatic activity was measured using the method developed by the Clinical and Laboratory Standards Institute consigned in the M26-A protocol.
    Results. Essential oils from Achyrocline alata and Swinglea glutinosa were the most active with minimal inhibitory concentrations of 62.5±0.1 and 100±36 μg ml-1, respectively. Carvacrol, thymol, p-cymene, 1,8-cineole, limonene, and β-pinene were the major components ,most often identified in the 11 plant extracts of essential oils. Time-kill curve assays demonstrated the bacteriostatic activity of these essential oils.
    Conclusions. The essential oils from A. alata and S. glutinosa plants, and the components identified therein, are candidates as potential phytotherapeutic agents for human tuberculosis control

  8. Experimental models used for the study of antihepatotoxic agents

    Feroz Ahmad; Nahida Tabassum


    Both in vitro and in vivo liver models have been developed in the past years to study the hepatoprotective agents. These systems measure the ability of the test drug to prevent or cure liver toxicity (induced by various hepatotoxins) in experimental animals. In in vitro models fresh hepatocytes are treated with hepatotoxin and the effect of the test drug on the same is evaluated. In in vivo models, a toxic dose or repeated doses of a known hepatotoxin are administered to induce liver damage in experimental animals. The test substance is administered along with, prior to and/or after the toxin treatment. Various chemical agents normally used to induce hepatotoxicty in experimental animals for the evaluation of hepatoprotective agents include carbon tetrachloride, paracetamol, Acrylamide, adriamycin, alcohol, antitubercular drugs etc. The present article explains the mechanism of action of various hepatotoxic chemical/drugs, their dosage and route of administration.

  9. Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives

    Dong Cai


    Full Text Available A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities.

  10. Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2-a]pyrimidin-5-ones and Sulfonic Acid Derivatives.

    Cai, Dong; Zhang, Zhi-Hua; Chen, Yu; Yan, Xin-Jia; Zou, Liang-Jing; Wang, Ya-Xin; Liu, Xue-Qi


    A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H₂SO₄. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, ¹H-NMR, (13)C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities. PMID:26378507

  11. Persistent high mortality in advanced HIV/TB despite appropriate antiretroviral and antitubercular therapy: an emerging challenge.

    Bisson, Gregory P; Zetola, Nicola; Collman, Ronald G


    Approximately 1.1 million, or 13 %, of all TB cases in 2013 were coinfected with HIV, and in some African countries, such as Botswana and Swaziland, 60-80 % of TB cases are coinfected with HIV. Effective therapies for both HIV and TB exist, yet patients presenting with TB and advanced HIV still experience high rates of morbidity and mortality despite initiation of both antitubercular and antiretroviral therapy (ART). Previous reviews and research have focused largely on TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) as a type of complicated outcome on ART in advanced HIV/TB, but recent data indicate that immunologic failure despite suppressive ART is associated with early mortality. In this review, we examine recent findings regarding early mortality in HIV/TB and emerging concepts in the pathophysiology of TB-IRIS, in order to provide an integrated view of factors determining outcomes in coinfected people as well as highlight key needs for future research and therapeutic development. PMID:25772785

  12. Efficient Synthesis and Anti-Tubercular Activity of a Series of Spirocycles: An Exercise in Open Science.

    Katrina A Badiola

    Full Text Available Tuberculosis afflicts an estimated 2 billion people worldwide and causes 1.3 million deaths annually. Chemotherapeutic solutions rely on drugs developed many years ago, with only one new therapeutic having been approved in the last 40 years. Given the rise of drug-resistant strains, there is an urgent need for the development of a more robust drug development pipeline. GlaxoSmithKline recently placed the structures and activities of 177 novel anti-tubercular leads in the public domain, as well as the results of ongoing optimisation of some of the series. Since many of the compounds arose from screening campaigns, their provenance was unclear and synthetic routes were in many cases not reported. Here we present the efficient synthesis of several novel analogues of one family of the GSK compounds-termed "Spiros"-using an oxa-Pictet-Spengler reaction. The new compounds are attractive from a medicinal chemistry standpoint and some were potent against the virulent strain, suggesting this class is worthy of further study. The research was carried out using open source methodology, providing the community with full access to all raw experimental data in real time.

  13. Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Carboxamide Derivatives of 2-Quinolones

    Abhishek Kumar


    Full Text Available A series of novel substituted N-(3-acetyl-2-oxoquinolin-1(2H-ylbenzamide (AJQC1-AJQC12 have been synthesized upon refluxing 3-acetyl-1-amino-quinolin-2-one and substituted benzoic acid in the presence of dry redistilled pyridine and silicon tetra chloride as coupling agent. 3-acetyl-1-amino-quinolin-2-one (AJQ1-AJQ12 were synthesized from substituted 3-acetyl coumarin upon refluxing with hydrazine hydrate and ethanol. The structures of the final carboxamide derivatives were confirmed by IR, 1H NMR and mass spectra. The synthesized compounds were screened for their antimicrobial activity by tube dilution method and anti tubercular activity by microplate Alamar blue assay. Most of the compounds have exhibited promising antibacterial, anti fungal and anti tubercular activities.

  14. Antitubercular effect of 8-[(4-Chloro phenyl sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One in guinea pigs

    Parvati B Patel


    Full Text Available Objective: To evaluate the antitubercular efficacy and safety of New Chemical Entity (NCE: 8-[(4-Chloro phenyl sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One (CSHMC in guinea pigs. Materials and Methods: This pilot study was carried out in guinea pigs. They were infected with M. tuberculosis H 37 Rv (1.5 × 10 4 cfu/guinea pig via intramuscular route. After 30 days, infections were confirmed in 6 guinea pigs by histopathology of spleen, lung, and liver. After that CSHMC (5 and 20 mg/kg was administered for 1 month and its effect was compared with vehicle, rifampicin (60 mg/kg and isoniazid (30 mg/kg. Efficacy of CSHMC was evaluated on the basis of histopathologic scoring of lesion in lung, spleen, liver, and safety on the basis of measuring hemogram, liver and renal function parameters. Results: Isoniazid, rifampicin, and CSHMC (20 mg/kg significantly reduce the median lesion score in lung, spleen, and liver as compared to disease control group. Reduction in median lesion score for lung and spleen were not statistically significant for CSHMC 5 mg/kg. CSHMC (20 and 5 mg/kg did not produce any changes in hemogram, liver and renal function parameters with respect to normal values. Conclusions: CSHMC had shown significant antitubercular efficacy comparable to isoniazid and rifampicin and did not show hematological, hepato- and nephrotoxicity.

  15. Clinical deterioration during antitubercular treatment at a district hospital in South Africa: the importance of drug resistance and AIDS defining illnesses.

    Dominique J Pepper

    Full Text Available BACKGROUND: Clinical deterioration on drug therapy for tuberculosis is a common cause of hospital admission in Africa. Potential causes for clinical deterioration in settings of high HIV-1 prevalence include drug resistant Mycobacterium tuberculosis (M.tb, co-morbid illnesses, poor adherence to therapy, tuberculosis associated-immune reconstitution inflammatory syndrome (TB-IRIS and subtherapeutic antitubercular drug levels. It is important to derive a rapid diagnostic work-up to determine the cause of clinical deterioration as well as specific management to prevent further clinical deterioration and death. We undertook this study among tuberculosis (TB patients referred to an adult district level hospital situated in a high HIV-1 prevalence setting to determine the frequency, reasons and outcome for such clinical deterioration. METHOD: A prospective observational study conducted during the first quarter of 2007. We defined clinical deterioration as clinical worsening or failure to stabilise after 14 or more days of antitubercular treatment, resulting in hospital referral. We collected data on tuberculosis diagnosis and treatment, HIV-1 status and antiretroviral treatment, and investigated reasons for clinical deterioration as well as outcome. RESULTS: During this period, 352 TB patients met inclusion criteria; 296 were admitted to hospital accounting for 17% of total medical admissions (n = 1755. Eighty three percent of TB patients (291/352 were known to be HIV-1 co-infected with a median CD4 count of 89cells/mm(3 (IQR 38-157. Mortality among TB patients admitted to hospital was 16% (n = 48. The median duration of hospital admission was 9.5 days (IQR 4-18, longer than routine in this setting (4 days. Among patients in whom HIV-1 status was known (n = 324, 72% of TB patients (n = 232 had an additional illness to tuberculosis; new AIDS defining illnesses (n = 80 were the most frequent additional illnesses (n = 208 in HIV-1 co-infected patients (n

  16. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Deepa Gupta


    Full Text Available Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

  17. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

    Gupta, Deepa; Jain, D K


    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  18. Enabling the (3 + 2) cycloaddition reaction in assembling newer anti-tubercular lead acting through the inhibition of the gyrase ATPase domain: lead optimization and structure activity profiling.

    Jeankumar, Variam Ullas; Reshma, Rudraraju Srilakshmi; Janupally, Renuka; Saxena, Shalini; Sridevi, Jonnalagadda Padma; Medapi, Brahmam; Kulkarni, Pushkar; Yogeeswari, Perumal; Sriram, Dharmarajan


    DNA gyrase, the sole type II topoisomerase present in Mycobacterium tuberculosis, is absent in humans and is a well validated target for anti-tubercular drug discovery. In this study, a moderately active inhibitor of Mycobacterium tuberculosis GyrB, the pharmaceutically unexploited domain of DNA gyrase, was reengineered using a combination of molecular docking and medicinal chemistry strategies to obtain a lead series displaying considerable in vitro enzyme efficacy and bacterial kill against the Mycobacterium tuberculosis H37Rv strain. Biophysical investigations using differential scanning fluorimetry experiments re-ascertained the affinity of these molecules towards the GyrB domain. Furthermore, the molecules were completely devoid of hERG toxicity up to 30 μM, as evaluated in a zebra fish model with a good selectivity index, and from a pharmaceutical point of view, turned out as potential candidates against TB. PMID:25569565

  19. A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids.

    Rane, Rajesh A; Karunanidhi, Sivanandhan; Jain, Kavita; Shaikh, Mahamadhanif; Hampannavar, Girish; Karpoormath, Rajshekhar


    Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti-HIV, antiviral, anti-inflammatory, anti-Parkinson's and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued. PMID:26369813

  20. Agent engineering

    Liu, Jiming; Zhong, Ning; Wang, Patrick S P


    Agent engineering concerns the development of autonomous computational or physical entities capable of perceiving, reasoning, adapting, learning, cooperating and delegating in a dynamic environment. It is one of the most promising areas of research and development in information technology, computer science and engineering. This book addresses some of the key issues in agent engineering: What is meant by "autonomous agents"? How can we build agents with autonomy? What are the desirable capabilities of agents with respect to surviving (they will not die) and living (they will furthermore enjoy

  1. Antibiotic Agents

    ... either as public health or as non-public health antimicrobial agents. What is the difference between bacteriostats, sanitizers, disinfectants ... bacteria, however, there is considerable controversy surrounding their health benefits. The ... producing agents (Table of Antibacterials) have been used for many ...

  2. Agent, autonomous

    Luciani, Annie


    The expression autonomous agents, widely used in virtual reality, computer graphics, artificial intelligence and artificial life, corresponds to the simulation of autonomous creatures, virtual (i.e. totally computed by a program), or embodied in a physical envelope, as done in autonomous robots.

  3. Molecular cloning and cold shock induced overexpression of the DNA encoding phor sensor domain from Mycobacterium tuberculosis as a target molecule for novel anti-tubercular drugs

    Langi, Gladys Emmanuella Putri; Moeis, Maelita R.; Ihsanawati, Giri-Rachman, Ernawati Arifin


    Mycobacterium tuberculosis (Mtb), the sole cause of Tuberculosis (TB), is still a major global problem. The discovery of new anti-tubercular drugs is needed to face the increasing TB cases, especially to prevent the increase of cases with resistant Mtb. A potential novel drug target is the Mtb PhoR sensor domain protein which is the histidine kinase extracellular domain for receiving environmental signals. This protein is the initial part of the two-component system PhoR-PhoP regulating 114 genes related to the virulence of Mtb. In this study, the gene encoding PhoR sensor domain (SensPhoR) was subcloned from pGEM-T SensPhoR from the previous study (Suwanto, 2012) to pColdII. The construct pColdII SensPhoR was confirmed through restriction analysis and sequencing. Using the construct, SensPhoR was overexpressed at 15°C using Escherichia coli BL21 (DE3). Low temperature was chosen because according to the solubility prediction program of recombinant proteins from The University of Oklahama, the PhoR sensor domain has a chance of 79.8% to be expressed as insoluble proteins in Escherichia coli's (E. coli) cytoplasm. This prediction is also supported by other similar programs: PROSO and PROSO II. The SDS PAGE result indicated that the PhoR sensor domain recombinant protein was overexpressed. For future studies, this protein will be purified and used for structure analysis which can be used to find potential drugs through rational drug design.

  4. Antifungal agents.

    Ryder, N S


    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  5. Trading Agents

    Wellman, Michael


    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst

  6. Radioprotective Agents

    Ilker Kelle


    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  7. An agent framework for dynamic agent retraining: Agent academy

    Mitkas, P.; A. Symeonidis; Kechagias, D.; Athanasiadis, I.N.; Laleci, G.; KURT, G.; Kabak, Y.; Acar, A.; Dogac, A.


    Agent Academy (AA) aims to develop a multi-agent society that can train new agents for specific or general tasks, while constantly retraining existing agents in a recursive mode. The system is based on collecting information both from the environment and the behaviors of the acting agents and their related successes/failures to generate a body of data, stored in the Agent Use Repository, which is mined by the Data Miner module, in order to generate useful knowledge about the application domai...

  8. Synthesis and antitubercular activity of new N,N-diaryl-4-(4,5-dichloroimidazole-2-yl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxamides

    Amini M.


    Full Text Available Background and the purpose of the study: Dihydropyridines having carboxamides in 3 and 5 positions show anti-tuberculosis activity. The purpose of the present study was to synthesize new DHPs having possible anti-tuberculosis activity. Methods: 4,5-Dichloroimidazole-2-carboxaldehyde was condensed with N-arylaceto-acetamides and ammonium acetate in methanol to give N,N-diaryl-4-(4,5-dichloroimid-azole-2-yl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxamides. All compounds were screened for their antitubercular activity against Mycobacterium tuberculosis (H37Rv. Results and major conclusion: Some of the new synthesized compounds exhibited a moderate activity in comparison to rifampicin.

  9. Mycothiol: a promising antitubercular target.

    Nilewar, S S; Kathiravan, M K


    Tuberculosis (TB) is the world's second commonest cause of death next to HIV/AIDS. The increasing emergence of multi drug resistance and the recalcitrant nature of persistent infections pose an additional challenge for the treatment of TB. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. One such target is Mycothiol (MSH), a major low molecular-mass thiol in mycobacteria, an important cellular anti-oxidant. MSH is present only in actinomycetes and hence is a good target. This review explores mycothiol as a potential target against tuberculosis and various research ongoing worldwide. PMID:24368170

  10. Quinoline: a promising antitubercular target.

    Keri, Rangappa S; Patil, Siddappa A


    Tuberculosis (TB) remains a global public health problem in recent years. TB originated mainly from various strains of Mycobacterium tuberculosis, is a highly infectious and chronic disease with high infection rate since ancient times. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Among hetrocyclic compounds, quinoline compounds are important privileged structure in medicinal chemistry, are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain, quinoline-based compounds, also show effective anti-TB activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. 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 this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment tuberculosis. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic quinoline-based anti-TB drugs. PMID:25458785

  11. Agent Chameleons: Virtual Agents Real Intelligence

    O'Hare, Gregory; Duffy, Brian; Schoen-Phelan, Bianca; Martin, Alan; Bradley, John


    Agent Chameleons provides virtual agents powered by real intelligence, delivering next generation autonomic entities that can seamlessly migrate, mutate and evolve on their journey between and within physical and digital information spaces.

  12. AgentChess : An Agent Chess Approach

    Fransson, Henric


    The game of chess has many times been discussed and used for test purpose by science departments of Artificial Intelligence (AI). Although the technique of agent and as well multi-agent systems is quite old, the use of these offspring of AI within chess is limited. This report describes the project performed applying the use of agents to a chess program. To measure the performance of the logic has tests between the developed program main parts been performed. Further tests against a tradition...

  13. Synthesis and In Vitro Evaluation of New Thiosemicarbazone Derivatives as Potential Antimicrobial Agents

    Zafer Asım Kaplancıklı


    Full Text Available In an effort to develop potent antimicrobial agents, new thiosemicarbazone derivatives were synthesized via the reaction of 4-[4-(trifluoromethylphenyl]thiosemicarbazide with aromatic aldehydes. The compounds were evaluated for their inhibitory effects on pathogenic bacteria and yeasts using the CLSI broth microdilution method. Microplate Alamar Blue Assay was also carried out to determine the antimycobacterial activities of the compounds against Mycobacterium tuberculosis H37Rv. Among these derivatives, compounds 5 and 11 were more effective against Enterococcus faecalis (ATCC 29212 than chloramphenicol, whereas compounds 1, 2, and 12 and chloramphenicol showed the same level of antibacterial activity against E. faecalis. Moreover, compound 2 and chloramphenicol exhibited the same level of antibacterial activity against Staphylococcus aureus. On the other hand, the most potent anticandidal derivatives were found as compounds 2 and 5. These derivatives and ketoconazole exhibited the same level of antifungal activity against Candida glabrata. According to the Microplate Alamar Blue Assay, the tested compounds showed weak to moderate antitubercular activity.

  14. Agents in domestic environments

    van Moergestel, Leo; Langerak, Wouter; Meerstra, Glenn; Nieuwenburg, Niels van; Pape, Franc; Telgen, Daniël; Puik, Erik; meyer, john-jules


    Athor supplied : "This paper describes an agent-based architecture for domotics. This architecture is based on requirements about expandability and hardware independence. The heart of the system is a multi-agent system. This system is distributed over several platforms to open the possibility to tie the agents directly to the actuators, sensors and devices involved. This way a level of abstraction is created and all intelligence of the system as a whole is related to the agents involved. A pr...

  15. Culturally Aware Agent Communication

    Rehm, Matthias; Nakano, Yukiko; Koda, Tomoko;


    Agent based interaction in the form of Embodied Conversational Agents (ECAs) has matured over the last decade and agents have become more and more sophisticated in terms of their verbal and nonverbal behavior like facial expressions or gestures. Having such “natural” communication channels...

  16. Riot Control Agents

    ... a person has been exposed to riot control agents. Long-term health effects of exposure to riot control agents Prolonged ... person is removed from exposure to riot control agents, long-term health effects are unlikely to occur. How you can ...

  17. Reasoning about emotional agents

    Meyer, J.-J.


    In this paper we discuss the role of emotions in artificial agent design, and the use of logic in reasoning about the emotional or affective states an agent can reside in. We do so by extending the KARO framework for reasoning about rational agents appropriately. In particular we formalize in this f

  18. Agents modeling agents in information economies

    Vidal, J.M.; Durfee, E.H. [Univ. of Michigan, Ann Arbor, MI (United States)


    Our goal is to design and build agents that act intelligently when placed in an agent-based information economy, where agents buy and sell services (e.g. thesaurus, search, task planning services, etc.). The economy we are working in is the University of Michigan Digital Library (UMDL), a large scale multidisciplinary effort to build an infrastructure for the delivery of library services. In contrast with a typical economy, an information economy deals in goods and services that are often derived from unique sources (authors, analysts, etc.), so that many goods and services are not interchangeable. Also, the cost of replicating and transporting goods is usually negligible, and the quality of goods and services is difficult to measure objectively: even two sources with essentially the same information might appeal to different audiences. Thus, each agent has its own assessment of the quality of goods and services delivered.

  19. Verapamil, and Its Metabolite Norverapamil, Inhibit Macrophage-induced, Bacterial Efflux Pump-mediated Tolerance to Multiple Anti-tubercular Drugs

    Adams, Kristin N.; Szumowski, John D.; Ramakrishnan, Lalita


    Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that tolerance developed to most antituberculosis drugs, including the newer agents moxifloxacin, PA-824,...

  20. Chemical crowd control agents.

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian


    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  1. Decontamination Data - Blister Agents

    U.S. Environmental Protection Agency — Decontamination efficacy data for blister agents on various building materials using various decontamination solutions This dataset is associated with the following...

  2. Agent Development Toolkits

    Singh, Aarti; Sharma, A K


    Development of agents as well as their wide usage requires good underlying infrastructure. Literature indicates scarcity of agent development tools in initial years of research which limited the exploitation of this beneficial technology. However, today a wide variety of tools are available, for developing robust infrastructure. This technical note provides a deep overview of such tools and contrasts features provided by them.

  3. Radiographic scintiscanning agent

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  4. Asimovian Adaptive Agents

    Gordon, D F


    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  5. How do agents represent?

    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.

  6. Hyperthermia and chemotherapy agent

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  7. Synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine-3-carboxamides.

    Pulipati, Lokesh; Sridevi, Jonnalagadda Padma; Yogeeswari, Perumal; Sriram, Dharmarajan; Kantevari, Srinivas


    A series of novel dibenzo[b,d]thiophene tethered imidazo[1,2-a]pyridine carboxamides 7a-s were designed and synthesized. The required building block, 2-dibenzo[b,d]thiophenyl imidazo[1,2-a]pyridine carboxylic acid (5) was synthesized from commercial dibenzo[b,d]thiophene in good yields following five-step reaction sequence. The desired carboxamides 7a-s was prepared through coupling of acid 5 with various benzyl amines. All the new analogues 7a-s was characterized by their NMR and mass spectral analysis. Among nineteen new compounds 7a-s screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, three compounds 7k (MIC: 0.78μg/mL); 7e and 7n (MIC: 1.56μg/mL) were identified as potent analogues with low cytotoxicity. The results reported here will help global efforts for identification of potential lead antimycobacterial agents. PMID:27184765

  8. Users, Bystanders and Agents

    Krummheuer, Antonia Lina


    Human-agent interaction (HAI), especially in the field of embodied conversational agents (ECA), is mainly construed as dyadic communication between a human user and a virtual agent. This is despite the fact that many application scenarios for future ECAs involve the presence of others. This paper...... the construction of the agent’s identity, and (3) how HAI, as a mediated interaction, is framed by an asymmetric participation framework. The paper concludes by suggesting various participation roles, which may inform development of ECAs....

  9. Agent-Based Optimization

    Jędrzejowicz, Piotr; Kacprzyk, Janusz


    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  10. Agent Standards Project

    National Aeronautics and Space Administration — The innovation of the work herein proposed is the development of standards for software autonomous agents. These standards are essential to achieve software...

  11. Programming Service Oriented Agents

    Hirsch, Benjamin; Konnerth, Thomas; Burkhardt, Michael; Albayrak, Sahin


    This paper introduces a programming language for service-oriented agents. JADL++ combines the ease of use of scripting-languages with a state-of-the-art service oriented approach which allows the seamless integration of web-services. Furthermore, the language includes OWL-based ontologies for semantic descriptions of data and services, thus allowing agents to make intelligent decisions about service calls.

  12. Adrenal imaging agents

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  13. Agent amplified communication

    Kautz, H.; Selman, B.; Milewski, A. [AT& T Laboratories, Murray Hill, NJ (United States)


    We propose an agent-based framework for assisting and simplifying person-to-person communication for information gathering tasks. As an example, we focus on locating experts for any specified topic. In our approach, the informal person-to-person networks that exist within an organization are used to {open_quotes}referral chain{close_quotes} requests for expertise. User-agents help automate this process. The agents generate referrals by analyzing records of e-mail communication patterns. Simulation results show that the higher responsiveness of an agent-based system can be effectively traded for the higher accuracy of a completely manual approach. Furthermore, preliminary experience with a group of users on a prototype system has shown that useful automatic referrals can be found in practice. Our experience with actual users has also shown that privacy concerns are central to the successful deployment of personal agents: an advanced agent-based system will therefore need to reason about issues involving trust and authority.

  14. Agent Oriented Programming进展%Advances in Agent Oriented Programming

    王一川; 石纯一


    Agent-oriented programming (AOP) is a framework to develop agents, and it aims to link the gap betweentheory and practical in agent research. The core of an AOP framework is its language and semantics. In this paper,we propose the necessary properties which agents should have, and then give a summary and analysis about differentAOP languages based on these properties.

  15. Agents unleashed a public domain look at agent technology

    Wayner, Peter


    Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

  16. El agente encubierto

    Anaya Marcos, María del Carmen


    [ES] El trabajo versa sobre la figura del agente encubierto. Debemos enmarcar tal medida de investigación dentro del ámbito de la criminalidad organizada. Actualmente, estamos asistiendo a una proliferación de la delincuencia organizada. La sociedad ha evolucionado, y con ella la delincuencia. Fruto de tal evolución fue necesario incluir en nuestra Ley de Enjuiciamiento Criminal medidas extraordinarias de investigación, y una de ellas es el agente encubierto. Se trata de una medida muy polémi...

  17. The PLS agent : agent behavior validation by partial least squares

    Lorscheid, Iris; Meyer, Matthias; Pakur, Sandra; Ringle, Christian


    Agent-based modeling is widely applied in the social sciences. However, the validation of agent behavior is challenging and identified as one of the shortcomings in the field. Methods are required to establish empirical links and support the implementation of valid agent models. This paper contributes to this, by introducing the PLS agent concept. This approach shows a way to transfer results about causalities and decision criteria from empirical surveys into an agent-based decision model, th...

  18. Trading Agents for Roaming Users

    Boman, Magnus; Bylund, Markus; Espinoza, Fredrik; Danielson, Mats; Lyback, David


    Some roaming users need services to manipulate autonomous processes. Trading agents running on agent trade servers are used as a case in point. We present a solution that provides the agent owners with means to upkeeping their desktop environment, and maintaining their agent trade server processes, via a briefcase service.

  19. Software Agent Techniques in Design

    Hartvig, Susanne C


    This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments.......This paper briefly presents studies of software agent techniques and outline aspects of these which can be applied in design agents in integrated civil engineering design environments....

  20. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.


    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 107.1620 Section 107.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance...

  1. Programming multi-agent systems

    Dastani, Mehdi


    With the significant advances in the area of autonomous agents and multi-agent systems in the last decade, promising technologies for the development and engineering of multi-agent systems have emerged. The result is a variety of agent-oriented programming languages, development frameworks, executio




    Last year the buying agent LOGITRADE started operations on the CERN site, processing purchasing requests for well-defined families of products up to a certain value. It was planned from the outset that a second buying agent would be brought in to handle the remaining product families. So, according to that plan, the company CHARLES KENDALL will be commencing operations at CERN on 8 May 2000 in Building 73, 1st floor, offices 31 and 35 (phone and fax numbers to be announced).Each buying agent will have its own specific list of product families and will handle purchasing requests up to 10'000 CHF.Whenever possible they will provide the requested supplies at a price (including the cost of their own services) which must be equivalent to or lower than the price mentioned on the purchasing request, changing the supplier if necessary. If a lower price cannot be obtained, agents will provide the necessary administrative support free of charge.To ensure that all orders are processed in the best possible conditions, us...

  3. Radioactive diagnostic agent

    A dispersion of denatured aggregates of serum albumin to which tin is attached is prepared and lyophilized. A mixture of polycarboxylic acid and a disaccharide or monosaccharide is included in the dispersion in sufficient amount to reduce degradation during lyophilization and aging. The dispersion is suitable for radioactive labelling and use as a diagnostic agent

  4. Developing Enculturated Agents

    Rehm, Matthias

    Embodied Conversational Agents (ECAs) are complex multimodal systems with rich verbal and nonverbal repertoires. There human-like appearance raises severe expectations regarding natural communicative behaviors on the side of the user. But what is regarded as “natural” is to a large degree dependent...

  5. Biomimetic Emotional Learning Agents

    Kenyon, Samuel H.


    This extended abstract proposes a type of AI agent comprised of: an autonomous real-time control system, low-level emotional learning (including a simple knowledge base that links homeostatic/innate drives to sensory perception states), and a novel sliding-priority drive motivation mechanism. Learning occurs in both phylogenetic and ontogenetic training.

  6. Agents of Change

    Hansen, Jens Aage; Lehmann, Martin


    at large, it emphasises universities as key change agents and providers in new learning, including tools such as project based and problem oriented learning (PBL) as well as information and communication technology (ICT); as providers of competent and motivated graduates to fill key positions in society...

  7. The need for agents

    Abolfazlian, Ali Reza Kian


    I denne artikel arbejder vi med begrebet Intelligent Software Agents (ISAs), som autonomous, social, reactive, proactive og subservient computer systemer. Baseret på socialt psykologiske argumenter viser jeg endvidere, hvordan både den menneskelige natur og det teknologiske stadium, som mennesket...

  8. Build Autonomic Agents with ABLE



    The IBM Agent Building and Learning Environment(ABLE) provides a lightweight Java~(TM) agent frame- work,a comprehensive JavaBeansTM library of intelligent software components,a set of development and test tools, and an agent platform.After the introduction to ABLE,classes and interfaces in the ABLE agent framework were put forward.At last an autonomic agent that is an ABLE-based architecture for incrementally building autonomic systems was discussed.

  9. Actions and Agents

    Alonso, E.


    In this chapter the notion of agency in AI is presented..It has been argued that in order to behave rationally in prevalent software applications artificial entities would have to be autonomous and adaptive. Besides, rather than working with single, isolated systems the new trend in AI would need to focus on inherently social entities in the form of multi-agent systems. The chapter begins by introducing the notion of action in traditional AI systems, deliberative and reactive. Next, the i...

  10. Towards Soft Computing Agents

    Neruda, Roman; Krušina, Pavel; Petrová, Zuzana


    Roč. 10, č. 5 (2000), s. 859-868. ISSN 1210-0552. [SOFSEM 2000 Workshop on Soft Computing. Milovy, 27.11.2000-28.11.2000] R&D Projects: GA ČR GA201/00/1489; GA ČR GA201/99/P057 Institutional research plan: AV0Z1030915 Keywords : hybrid systems * intelligent agents Subject RIV: BA - General Mathematics

  11. Sunscreening Agents: A Review

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


    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 an...

  12. Perioperative allergy: uncommon agents.

    Caimmi, S; Caimmi, D; Cardinale, F; Indinnimeo, L; Crisafulli, G; Peroni, D G; Marseglia, G L


    Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia. PMID:22014927

  13. Advanced scale conditioning agents

    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

  14. SAM : Semantic Agent Model for SWRL rule-based agents

    Subercaze, Julien; Maret, Pierre


    International audience SemanticWeb technologies are part of multi-agent engineering, especially regarding knowledge base support. Recent advances in the field of logic for the semantic web enable a new range of applications. Among them, programming agents based on semantic rules is a promising field. In this paper we present a semantic agent model that allows SWRL programming of agents. Our approach, based on the extended finite state machine concept, results in a three layers architecture...

  15. Peripheral Neuropathy and Agent Orange

    ... Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset peripheral neuropathy is related to their exposure to Agent Orange or other herbicides during service when the disease ...

  16. Agents Play Mix-game

    Gou, C


    In mix-game which is an extension of minority game, there are two groups of agents; group1 plays the majority game, but the group2 plays the minority game. This paper studies the change of the average winnings of agents and volatilities vs. the change of mixture of agents in mix-game model. It finds that the correlations between the average winnings of agents and the mean of local volatilities are different with different combinations of agent memory length when the proportion of agents in group 1 increases. This study result suggests that memory length of agents in group1 be smaller than that of agent in group2 when mix-game model is used to simulate the financial markets.

  17. The Power Trading Agent Competition

    Ketter, W.; Collins, J.; REDDY, P; Flath, C.


    This is the specification for the Power Trading Agent Competition for 2011 (Power TAC 2011). Agents are simulations of electrical power brokers, who must compete with each other for both power production and consumption, and manage their portfolios.

  18. Mediating Performance Through Virtual Agents

    Giannachi, Gabriella; Gillies, Marco; Kaye, Nick; Swapp, David


    This paper presents the process of creation of virtual agents used in a virtual reality performance. The performance aimed to investigate how drama and performance could inform the creation of virtual agents and also how virtual reality could raise questions for drama and performance. The virtual agents were based on the performance of 2 actors. This paper describes the process of preparing the actors, capturing their performances and transferring them to the virtual agents. A second set of a...

  19. Erythropoietic Agents and the Elderly

    Agarwal, Neeraj; Prchal, Josef T.


    Erythropoietin is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development, which either act as ligands for the cell surface receptors of erythropoietin or promote erythropoietin production that stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents stimulating erythropoiesis (such as continuous erythropoietin receptor activator (C...

  20. Cultural Differentiation of Negotiating Agents

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.


    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  1. Cultural differentiation of negotiating agents

    Hofstede, G.J.; Jonker, C.M.; Verwaart, T.


    Negotiations proceed differently across cultures. For realistic modeling of agents in multicultural negotiations, the agents must display culturally differentiated behavior. This paper presents an agent-based simulation model that tackles these challenges, based on Hofstede’s model of national cultu

  2. Collaborating with Autonomous Agents

    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


    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.

  3. Agentes de información Information Agents

    Alfonso López Yepes


    Full Text Available Este artículo realiza un repaso sobre las tipologías de agentes de información y describe aspectos como movilidad, racionalidad y adaptatividad, y el ajuste final de estos conceptos a entornos distribuidos como Internet, donde este tipo de agentes tienen un amplio grado de aplicación. Asimismo, se propone una arquitectura de agentes para un sistema multiagente de recuperación de información donde se aplica un paradigma documental basado en el concepto de ciclo documental.This article summarizes the main information agent types reflecting on issues such as mobility, rationality, adaptability and the final adjustment of this concepts to distributed environments such as the Internet, where this kind of agents has wide range application. Likewise, an information agent architecture is proposed to create a multi-agent information retrieval system in which a documentary paradigm based on the documentary cycle is developed.

  4. Secure Mobile Trade Agent

    Musbah M. Aqe


    Full Text Available E-commerce on the internet has the ability to produce millions of transactions and a great number of merchants whose supply merchandise over the internet. As a result, it is difficult for entities to roam over every site on the internet and choose the best merchandise to trade. So, in this paper we introduced a mobile trade agent that visit the sites to gather and evaluate the information from merchant servers and decide to trade goods on behalf of the user. We observed that the combination of public key cryptosystem with distributed object technology make this proposed scheme more secure and efficient than the already existed schemes.

  5. Configuring Computational Agents

    Beuster, G.; Neruda, Roman

    Halifax : Saint Mary's University, 2004 - (Zhuge, H.; Cheung, W.; Liu, J.), s. 57-62 ISBN 0-9734039-8-5. [International Workshop on Knowledge Grid and Grid Intelligence /2./. Beijing (CN), 20.09.2004] R&D Projects: GA AV ČR 1ET100300419 Grant ostatní: CZ-DE project(XX) CZE-03/023 Institutional research plan: CEZ:AV0Z1030915 Keywords : Bang 3 * multi-agent systems * computational intelligence models Subject RIV: BA - General Mathematics

  6. Holograms as Teaching Agents

    Walker, Robin A.


    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.

  7. Amphoteric surface active agents

    Eissa, A.M. F.


    Full Text Available 2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR and nuclear magnetic resonance (NMR. Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height and critical micelle concentration (cmc were determined and a comparative study was made between their chemical structure and surface active properties. Antimicrobial activity of these surfactants was also determined.

    Se prepararon cuatro series de agentes tensioactivos del tipo 2-[trimetil amonio, trietil amonio, piridinio y 2-amino piridinio] alcanoatos, que contienen cadenas carbonadas con C12, C14, C16 y C18 átomos de carbono.
    Se determinaron la tensión superficial e interfacial, el punto de Krafft, el tiempo humectante, el poder de emulsionamiento, la altura espumante y la concentración critica de miscela (cmc y se hizo un estudio comparativo entre la estructura química y sus propiedades tensioactivas. Se determinó también la actividad antimicrobiana de estos tensioactivos. Estas estructuras se caracterizaron por microanálisis, infrarrojo (IR y resonancia magnética nuclear (RMN.

  8. Contrast agents for MRI

    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. - Highlights: • This paper studies the contrast agents for MRI. • Fe―Co alloys and Mn-ferrites exhibit suitable contrast enhancement. • Nonhydrolytic thermal-decomposition synthetic method is suitable to produce MNPs. • This method allows controlling the size, magnetic dopants, magneto-crystalline anisotropy. • The increase in the superparamagnetic size leads to the contrast-enhancement

  9. Agent-oriented Software Engineering

    GUAN Xu; CHENG Ming; LIU Bao


    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to design and build complex systems. Yet. todate, little effort had been devoted to discuss the advantages of agent-oriented approach as a mainstreamsoftware engineering paradigm. Here both of this issues and the relation between object-oriented and agent-oriented will be argued. we describe an agent-oriented methodology and provide a quote for designing anauction system.

  10. Learning models of intelligent agents

    Carmel, D.; Markovitch, S. [Computer Science Dept., Haifa (Israel)


    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

    Goldsmith; Steven Y.


    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. Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents.

    Keri, Rangappa S; Sasidhar, B S; Nagaraja, Bhari Mallanna; Santos, M Amélia


    Tuberculosis (TB) is still a challenging worldwide health problem and mycobacterium tuberculosis (MTB) remains one of the most deadly human pathogens. TB is the second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of antituberculosis drugs comes from the emergence of multi-drug resistant (MDR) strains. The development of MDR strains to commonly used drugs is due to, longer durations of therapy as results of resistance, and the resurgence of the disease in immune compromised patients. Therefore, there is an urgent need to explore new antitubercular (anti-TB) agents. Ironically, the low number of potentially new chemical entities which can act as anti-TB candidates is of great importance at present situation. Considering the severity of the problem, WHO has prepared a strategic plan in Berlin declaration 2007 to stop TB, globally. Among the oxygen heterocycles, coumarin derivatives are important motifs, which can be widely found in many natural products, and many of them displaying diverse biological activities. This spectacular spectrum of applications has intrigued organic and medicinal chemists for decades to explore the natural coumarins or their synthetic analogs for their applicability as anti-TB drugs. To pave the way for the future research, there is a need to collect the latest information in this promising area. In the present review, we collated published reports on coumarin derivatives to shed light on the insights on different types of methods reported for their preparations, characterizations and anti-TB applications, so that its full therapeutic potential class of compounds can be utilized for the treatment of tuberculosis. Therefore, the objective of this review is to focus on important coumarin analogs with anti-TB activities, and structure-activity relationships (SAR) for designing the better anti-TB agents. It is hoped that, this review will be helpful for new thoughts in the

  13. UTBot: A Virtual Agent Platform for Teaching Agent System Design

    In-Cheol Kim


    Full Text Available We introduce UTBot, a virtual agent platform for teaching agent system design. UTBot implements a client for the Unreal Tournament game server and Gamebots system. It provides students with the basic functionality required to start developing their own intelligent virtual agents to play autonomously UT games. UTBot includes a generic agent architecture, CAA (Context-sensitive Agent Architecture, a domain-specific world model, a visualization tool, several basic strategies (represented by internal modes and internal behaviors, and skills (represented by external behaviors. The CAA architecture can support complex long-term behaviors as well as reactive short-term behaviors. It also realizes high context-sensitivity of behaviors. We also discuss our experience using UTBot as a pedagogical tool for teaching agent system design in undergraduate Artificial Intelligence course.

  14. Mushrooms as therapeutic agents

    Sushila Rathee


    Full Text Available Mushrooms have been known for their nutritional and culinary values and used as medicines and tonics by humans for ages. In modern terms, they can be considered as functional foods which can provide health benefits beyond the traditional nutrients. There are monographs that cover the medicinal and healing properties of some individual traditional mushrooms. There has been a recent upsurge of interest in mushrooms not only as a health food which is rich in protein but also as a source of biologically active compounds of medicinal value which include complementary medicine/dietary supplements for anticancer, antiviral, hepatoprotective, immunopotentiating and hypocholesterolemic agents. However the mechanisms of the various health benefits of mushrooms to humans still require intensive investigation, especially given the emergence of new evidence of their health benefits. In the present paper the medicinal potential of mushrooms is being discussed.

  15. Microencapsulation of chemotherapeutic agents

    Mixing various amounts of chemotherapeutic agents such as cisplatinum, 5-fluorouracil, mitomycin-C, and adriamycin with polymers such as poly-d, 1-lactide, ethylhydroxyethylcellulose, and polycaprolactone, several kinds of microcapsules were made. Among them, microcapsule made from ethylhydroxyethylcellulose showed best yield. Under light microscopy, the capsules were observed as particles with refractive properties. For the basic toxicity test, intraarterial administration of cisplatinum was done in 6 adult mongrel dogs. Follow-up angiography was accomplished in 2 wk intervals for 6 wks. Despite no significant difference in the histopathological examination between the embolized and normal kidneys, follow-up angiogram showed atrophy of renal cortex and diminished numbers of arterial branches in the embolized kidneys. In order to identify the structural properties of microcapsules, and to determine the drug content and the rate of release, further experiment is thought to be necessary. (Author)

  16. Hepatocytes as Immunological Agents.

    Crispe, Ian N


    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314


    Shrivastava Neelesh


    Full Text Available This paper discuss on clinical representation of morbid jealousy which often termed delusional jealousy or ‘Othello Syndrome’ is a psychiatric condition where a lover believes against all reason and their beloved is being sexually unfaithful. Patients will be preoccupied with their partner’s perceived lack of sexual fidelity and will often behave in an unacceptable or extreme way as they endeavor to prove their ideas. Misuse of any psychomotor is an important association cause morbidity jealousy agents, like CNS stimulants that release the catecholamine, particularly dopamine, from pre synaptic terminals substance should be treated as a priority. Where higher levels of violence are reported Sildenafil may be useful as a diagnostic as well as therapeutic test in such cases .Many studies have shown an association between high alcohol consumption and developing morbid jealousy. Amphetamine-induced psychosis has been extensively studied because of its close resemblance to schizophrenia.

  18. Agent Assignment for Process Management: Pattern Based Agent Performance Evaluation

    Jablonski, Stefan; Talib, Ramzan

    In almost all workflow management system the role concept is determined once at the introduction of workflow application and is not reevaluated to observe how successfully certain processes are performed by the authorized agents. This paper describes an approach which evaluates how agents are working successfully and feed this information back for future agent assignment to achieve maximum business benefit for the enterprise. The approach is called Pattern based Agent Performance Evaluation (PAPE) and is based on machine learning technique combined with post processing technique. We report on the result of our experiments and discuss issues and improvement of our approach.

  19. Odor Classification using Agent Technology

    Sigeru OMATU


    Full Text Available In order to measure and classify odors, Quartz Crystal Microbalance (QCM can be used. In the present study, seven QCM sensors and three different odors are used. The system has been developed as a virtual organization of agents using an agent platform called PANGEA (Platform for Automatic coNstruction of orGanizations of intElligent Agents. This is a platform for developing open multi-agent systems, specifically those including organizational aspects. The main reason for the use of agents is the scalability of the platform, i.e. the way in which it models the services. The system models functionalities as services inside the agents, or as Service Oriented Approach (SOA architecture compliant services using Web Services. This way the adaptation of the odor classification systems with new algorithms, tools and classification techniques is allowed.

  20. Stability of Evolving Agent Populations

    Briscoe, G


    Stability is perhaps the most desired feature in the systems that we design. It is important for us to be able to predict the response of a Multi-Agent System (MAS) to various environmental conditions prior to its actual deployment. The Chli-DeWilde agent stability measure views a MAS as a discrete time Markov chain with a potentially unknown transition probabilities. A MAS is considered to be stable when its state, a stochastic process, has converged to an equilibrium distribution. We investigate an extension of their agent stability definition to include MASs with evolutionary dynamics, focusing on evolving agent populations. Additionally, using our extended agent stability measure, we construct an entropy-based definition for the degree of instability. An example system, the Digital Ecosystem, is considered in detail to investigate the stability of an evolving agent population through simulations. The results are consistent with the original Chli-DeWilde measure.

  1. Agent-based enterprise integration

    N. M. Berry; C. M. Pancerella


    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.

  2. Mobile Agents for Digital Signage

    SATOH, Ichiro


    International audience This paper presents an agent-based framework for building and operating context-aware multimedia content on digital signage in public/private spaces. It enables active and multimedia content to be composed from mobile agents, which can travel from computer to computer and provide multimedia content for advertising or user-assistant services to users. The framework automatically deploys their agents at computers near to their current positions to provide advertising o...

  3. An agent for ecological deliberation

    Debenham, John; Sierra, Carles


    An agent architecture supports the two forms of deliberation used by human agents. Cartesian, constructivist rationalism leads to game theory, decision theory and logical models. Ecological rationalism leads to deliberative actions that are derived from agents’ prior interactions and are not designed; i.e., they are strictly emergent. This paper aims to address the scant attention paid by the agent community to the predominant form of deliberation used by mankind.

  4. Agent factory: towards social robots

    O'Hare, G. M. P.; Duffy, Brian R.; Collier, Rem; Rooney, Colm, (Thesis); O'Donoghue, Ruadhan


    This paper advocates the application of multi-agent techniques in the realisation of social robotic behaviour. We present the Social Robot Architecture, which integrates the key elements of agent-hood and robotics in a coherent and systematic manner. This architecture seamlessly integrates, real world robots, multi-agent development tools, and VRML visualisation tools into a coherent whole. Using these elements, we deliver a development environment, which facilitates rapid prototyping of soci...

  5. Agent Systems in Software Engineering

    Lazarou, Vasilios S.; Gardikiotis, Spyridon K.; Malevris, Nicos


    In this chapter, the application of multi-agent systems to tackle the software engineering task was outlined. The concentration was on the employment of agent technology in order to deal with distributed software systems and mainly distributed database applications and web applications. The rationale behind utilizing agent technology has to do with the multi-tier architecture and the associated inherent complication of distributed applications and the required interoperability of software res...

  6. Research on Negotiating Agent Development

    WEI Ding-guo; PENG Hong


    The paper presents a flexible and effective method of development of negotiating agents.A strategy specification, which is specified by a state chart and defeasible rules, can be dynamically inserted into an agent shell incorporating a state chart interpreter and a defeasible logic inference engine, in order to yield a desirable agent.The set of desirable criteria and rules is required to be justified with different context of the application.

  7. Extending Agent Languages for Autonomy

    Meneguzzi, Felipe Rech


    BDI agent languages provide a useful abstraction for complex systems comprised of interactive autonomous entities, but they have been used mostly in the context of single agents with a static plan library of behaviours invoked reactively. These languages provide a theoretically sound basis for agent design but are very limited in providing direct support for autonomy and societal cooperation needed for large scale systems. Some techniques for autonomy and cooperation have been explored in the...

  8. Radioactive scanning agents with stabilizer

    Stable compositions useful as technetium 99-based scintigraphic agents comprise gentisyl alcohol or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

  9. Technetium diagnostic agent and carrier

    A stable sup(99m)Tc-labelled radioactive diagnostic agent is produced by contacting sup(99m)Tc-containing pertechnetate with a non-radioactive carrier comprising a chelating agent, a water-soluble reducing agent and a stabilizer. The stabilizer is chosen from ascorbic acid and erythorbic acid and their pharmaceutically acceptable salts and esters. A mole ratio of more than 100 moles ascorbic or erythorbic acid to 1 mole of reducing agent provides a stable composition at high levels of radioactivity

  10. Relational agents: A critical review

    Campbell, Robert H.; Grimshaw, Mark Nicholas; Green, Gill


    and non-player characters that can actively participate in such relationships. The focus of this review is relational agents, agents that can build long term socioemotional relationships with users. In virtual worlds, such agents are just starting to emerge; they are more common in other environments...... but remain few and far between. This review critically assesses the progress of relational agent development and research since their inception in 2005, proposes new areas of research and considers the potential for their exploitation in virtual worlds....

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

    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.

  12. Plasmids encoding therapeutic agents

    Keener, William K.


    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.

  13. Gastrointestinal scanning agent

    An easily prepared radiolabeled gastrointestinal scanning agent is described. Technetium-99m has ideal characteristics for imaging the upper and lower GI tract and determining stomach emptying and intestinal transit time when used with an insoluble particulate material. For example, crystalline and amorphous calcium phosphate particles can be effectively labeled in a one-step process using sup(99m)TcO4 and SnCl2. These labeled particles have insignificant mass and when administered orally pass through the GI tract unchanged, without affecting the handling and density of the intestinal contents. Visualization of the esophageal entry into the stomach, the greater and lesser curvatures of the stomach, ejection into the duodenum, and rates of passage through the upper and lower GI tract are obtained. The slurry of sup(99m)TC particulate can be given rectally by enema. Good images of the cecum and the ascending, transverse, and descending colon are obtained. Mucosal folds and the splenic and hepatic flexures are visualized. The resilience of the large intestine is also readily visualized by pneumocolonographic techniques. (author)

  14. 2012 Survey of clothing agents


    Clothing agents take part in China International Clothing and Accessories Fairs ( CHIC ) year by year. In order to attracting investment, they compared with each other at improving their originality and service levels. At the exhibition brands manufacturers and agents had a face-to-face communication,

  15. Topical agents in burn care

    Momčilović Dragan


    Full Text Available Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injured. It was not until the XX century, after the discovery of antibiotics, when this condition was fulfilled. In 1968, combining silver and sulfadiazine, fox made silver-sulfadiazine, which is a 1% hydro-soluble cream and a superior agent in topical treatment of burns today. Current topical agents None of the topical antimicrobial agents available today, alone or combined, have the characteristics of ideal prophylactic agents, but they eliminate colonization of burn wound, and invasive infections are infrequent. With an excellent spectrum of activity, low toxicity, and ease of application with minimal pain, silver-sulfadiazine is still the most frequently used topical agent. Conclusion The incidence of invasive infections and overall mortality have been significantly reduced after introduction of topical burn wound antimicrobial agents into practice. In most burn patients the drug of choice for prophylaxis is silver sulfadiazine. Other agents may be useful in certain clinical situations.

  16. Agent Roles in Human Teams

    Lewis, M.; Sycara, K.; Payne, T.R.


    In this paper, we describe results of a series of experiments investigating the effects of agent aiding on human teams. The role an agent played, its task, and the ease with which it communicated with its human teammates all influenced team behavior. Team supporting tasks such as relaying and reminding seemed particularly effective.

  17. Intelligent Agents in Physics Education

    Sánchez-Guzmán, D.; Mora, César


    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.

  18. Markov Tracking for Agent Coordination

    Washington, Richard; Lau, Sonie (Technical Monitor)


    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.

  19. Agent Communications using Distributed Metaobjects

    Goldsmith, Steven Y.; Spires, Shannon V.


    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.

  20. Mobile agent driven by aspect

    Youssef Hannad


    Full Text Available Domain application of mobile agents is quite large. They are used for network management and the monitoring of complex architecture. Mobile agent is also essential into specific software architecture such that adaptable grid architecture. Even if the concept of mobile agent seems to be obvious, the development is always complex because it needs to understand network features but also security features and negotiation algorithms. We present a work about an application of aspects dedicated to mobile agent development over a local network. At this level, the underlying protocol is called jini and allows managing several essential concepts such that short transaction and permission management. Three subsets of aspects are defined in this work. A part is for the description of agent host and its security level, accessible resource, etc. A second part is about mobile agent and their collaboration. This means how they can operate on an agent host with the respect of the execution context. All the results are illustrated through a distributed monitoring application called DMA. Its main objective is the observation of component servers.

  1. Intelligent Farmer Agent for Multi-Agent Ecological Simulations Optimization

    Filipe Cruz; António Pereira; Pedro Valente; Pedro Duarte; Luis Paulo Reis


    This paper presents the development of a bivalve farmer agent interacting with a realistic ecological simulation system. The purpose of the farmer agent is to determine the best combinations of bivalve seeding areas in a large region, maximizing the production without exceeding the total allowed seeding area. A system based on simulated annealing, tabu search, genetic algorithms and reinforcement learning, was developed to minimize the number of iterations required to unravel a semi-optimum s...

  2. MDE and Mobile Agents : another reflexion on the agent migration

    Gherbi, Tahar; Borne, Isabelle; Meslati, Djamel


    International audience Model Driven Engineering (MDE) is a software development approach family based on the use of models in the software construction. It allows the exploitation of models to simulate, estimate, understand, communicate and produce code. Mobile agents are a very interesting technology to develop applications for mobile and distributed environments. A mobile agent is essentially a computer program that acts autonomously on behalf of a user and travels through a network of h...

  3. Knowledge mining using intelligent agents

    Dehuri, Satchidananda


    ""Knowledge Mining Using Intelligent Agents"" explores the concept of knowledge discovery processes and enhances decision-making capability through the use of intelligent agents like ants, termites and honey bees. In order to provide readers with an integrated set of concepts and techniques for understanding knowledge discovery and its practical utility, this book blends two distinct disciplines - data mining and knowledge discovery process, and intelligent agents-based computing (swarm intelligence and computational intelligence). For the more advanced reader, researchers, and decision/policy

  4. Agent-oriented Software Engineering

    MingCheng; XuGuan; BaoLiu


    An increasing number of computer systems are being viewed in terms of autonomous agents.Most people believe that agent-oriented approach is well suited to designing and building complex systems. Yet, to date, little effort had been devoted to discussing the advantages of agent-oriented approach as a mainstream software engineering paradiam.Here both of this issues and the relation between object-oriented and agentoriented will be argued.We describe an agent-oriented methodology and provide a quote for designing a auction system.

  5. Optimistic Agents are Asymptotically Optimal

    Sunehag, Peter; Hutter, Marcus


    We use optimism to introduce generic asymptotically optimal reinforcement learning agents. They achieve, with an arbitrary finite or compact class of environments, asymptotically optimal behavior. Furthermore, in the finite deterministic case we provide finite error bounds.

  6. Agents containing chlorhexidine in dentistry

    Lebedeva S.N.; Zemlyanichenko М.К.


    Aclinical definition of the efficacy of chlorhexidine-containing means for reducing the risk of dental caries and gingivitis with plastic caps. Chlorhexidine is an effective antimicrobial agent for the formation of individual programs for the prevention of dental caries

  7. Chemical Agents: Facts about Evacuation

    ... Health Emergency Response Guide Reaching At-Risk Populations Chemical Agents: Facts About Evacuation Format: Select one PDF [ ... on Facebook Tweet Share Compartir Some kinds of chemical accidents or attacks, such as a train derailment ...


    Sharma Ganesh N.; Sanadya Jyotsana; Kaushik Avinash; Dwivedi Abha


    Many current therapeutic agents like antibiotics, ionizable and peptide drugs are impermeable or do not possess the requisite physicochemical properties for efficient transport through outer tissue barrier to attain therapeutic blood level. For this reason the delivery of such drugs through barriers is currently one of the major interests in pharmaceutical research. Penetration enhancers or promoters are agents that have no therapeutic properties of their own but can transport the sorption of...

  9. Agents in E-learning

    S. Mencke; Dumke, R


    This paper presents a framework to describe thecrossover domain of e-learning and agent technology.Furthermore it is used to classify existing work and possiblestarting points for the future development of agenttechniques and technologies order to enhance theperformance and the effectiveness of several aspects of elearningsystems. Agents are not a new concept but their usein the field of e-learning constitutes a basis for consequentialadvances.

  10. Handling of injectable antineoplastic agents.

    Knowles, R S; Virden, J E


    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.

  11. Biocontrol agents in signalling resistance

    Loon, L C; Pieterse, C.M.J.


    The mechanisms by which biological control agents suppress disease comprise competition for nutrients, notably iron, production of antibiotics, and secretion of lytic enzymes, as well as inducing resistance in the plant. The former three mechanisms act primarily on the pathogen by decreasing its activity, growth, and/or survival and require the biocontrol agent and the pathogen to be in close proximity. Because microorganisms with biocontrol properties and soilborne pathogens are both attract...

  12. Epidemic Spreading with External Agents

    Banerjee, Siddhartha; Gopalan, Aditya; Das, Abhik Kumar; Shakkottai, Sanjay


    We study epidemic spreading processes in large networks, when the spread is assisted by a small number of external agents: infection sources with bounded spreading power, but whose movement is unrestricted vis-\\`a-vis the underlying network topology. For networks which are `spatially constrained', we show that the spread of infection can be significantly speeded up even by a few such external agents infecting randomly. Moreover, for general networks, we derive upper-bounds on the order of the...

  13. Locating Agents in RFID Architectures

    Abdel-Naby, Sameh; Giorgini, Paolo


    The use of software agents can create an “intelligent” interface between users’ preferences and the back‐end systems. Agents are now able to interact and communicate with each other, forming a virtual community and feeding back the user with suggestions. Innovative systems related to Asset Tracking, Inventory and Shelving architectures are more often involving advanced communication techniques (e.g., RFID); these systems are responsible for user authentication and objects verification. RFID s...

  14. Towards Building Computational Agent Schemes

    Beuster, Gerd; Krušina, Pavel; Neruda, Roman; Rydvan, Pavel

    Wien : SpringerVerlag, 2003 - (Pearson, D.; Steele, N.; Albrecht, R.), s. 210-215 ISBN 3-211-00743-1. [ICANNGA'2003 /6./. Roanne (FR), 23.04.2003-25.04.2003] R&D Projects: GA ČR GA201/02/0428 Institutional research plan: AV0Z1030915 Keywords : multi agent system s * intelligent agent s * hybrid models Subject RIV: BA - General Mathematics

  15. Cooperation of Computational Intelligence Agents

    Neruda, Roman

    Los Alamitos : IEEE Computer Society, 2006 - (Smari, W.; McQuay, W.), s. 256-263 ISBN 0-9785699-0-3. [International Symposium on Collaborative Technologies and System s. Las Vegas (US), 14.05.2006-17.05.2006] R&D Projects: GA AV ČR(CZ) 1ET100300419 Institutional research plan: CEZ:AV0Z10300504 Keywords : multi - agent system s * cooperative agent s * computational intelligence * ontologies Subject RIV: IN - Informatics, Computer Science

  16. Bacteriocins as potential anticancer agents

    Sukhraj eKaur; Sumanpreet eKaur


    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 nonspecific toxicity towards 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 therapeu...

  17. Bacteriocins as Potential Anticancer Agents

    Kaur, Sumanpreet; Kaur, Sukhraj


    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 therapeu...

  18. Business Intelligence using Software Agents

    Ana-Ramona BOLOGA; Razvan BOLOGA


    This paper presents some ideas about business intelligence today and the importance of developing real time business solutions. The authors make an exploration of links between business intelligence and artificial intelligence and focuses specifically on the implementation of software agents-based systems in business intelligence. There are briefly presented some of the few solutions proposed so far that use software agents properties for the benefit of business intelligence. The authors then...

  19. What makes virtual agents believable?

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon


    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.

  20. 46 CFR Sec. 2 - General Agents' authority.


    ... 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...

  1. Interactions of ionic and nonionic contrast agents with thrombolytic agents

    Both the ionic and nonionic intravascular contrast media have been used before and after the administration of thrombolytic agents to evaluate clot lysis during angioplasty and the treatment of myocardial infarction. In experimental animal models, the authors found that the clot lytic efficacy of streptokinase, streptokinase-plasminogen complex, and tissue plasminogen activator (t-PA) is markedly augmented if these agents are administered within 1 hour after the angiographic producers. Furthermore, contrast agents injected after the administration of t-Pa exhibit a synergistic action. In stimulated models administration of one ionic contrast medium (Angiovist, Berlex, Wayne, NJ) and two nonionic contrast agents (Isovue-370, Squibb Diagnostics, New Brunswick, NJ; Omnipaque-350, Winthrop, NY) 15 minutes before the administration of t-PA resulted in marked enhancement of the lytic activity. Although the mechanism of this interaction is unknown at this time, it should be taken into consideration in the treatment of patients with myocardial infarction, in whom contrast agents are continually used to evaluate the therapeutic lysis. Furthermore, this interaction may be partly related to the therapeutic efficacy and/or hemorrhagic actions observed

  2. Geo-Agents: Design and Implement


    Geo-Agents, a multi-agent system that processes distr ib utedgeospatial information and geospatial service was presented. Firstly, the requirement for distributed geographical information process was discussed, and the architecture of Geo-Agents was introduced. Then in-depth discussions were r aised on agent system implementation, such as the basic agent, agent advertising , message passing, and collaborating. An example was also given to explain the p roblem solving process.

  3. Special issue about advances in Physical Agents

    Cazorla Quevedo, Miguel Ángel; Matellán Olivera, Vicente


    Nowadays, there are a lot of Spanish groups which are doing research in areas related with physical agents: they use agent-based technologies concepts, especially industrial applications, robotics and domotics (physical agents) and applications related to the information society, (software agents) highlighting the similarities and synergies among physical and software agents. In this special issue we will show several works from those groups, focusing on the recent advances in Physical Agents.

  4. Learning by Observation of Agent Software Images

    Costa, Paulo Roberto; Botelho, Luís Miguel


    Learning by observation can be of key importance whenever agents sharing similar features want to learn from each other. This paper presents an agent architecture that enables software agents to learn by direct observation of the actions executed by expert agents while they are performing a task. This is possible because the proposed architecture displays information that is essential for observation, making it possible for software agents to observe each other. The agent architecture support...

  5. Colitis associated with biological agents

    Hugh James Freeman


    Full Text Available In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn’s disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody, bevacizumab (a monoclonal antibody against the vascular endothelial growth factor and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.

  6. A multi-agent architecture for geosimulation of moving agents

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem


    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  7. Sensors for detecting biological agents

    Kim E. Sapsford


    Full Text Available Biological agents including viruses, bacteria, and other naturally occurring pathogenic organisms, along with the toxins they produce, are considered far harder to detect and defend against than chemical agents. Here we provide an overview of the predominant molecular sensing technologies for the detection of these agents. This includes biosensing strategies based upon use of antibodies, genomic analysis, biochemical testing, other recognition interactions, and cellular-based responses. We survey some popular sensing approaches, illustrate them with current examples showing how they have been applied, and discuss their intrinsic benefits and potential liabilities. Lastly, within the context of security applications, some approaches for integrating sensing technologies into field-portable devices are discussed.

  8. Agent review phase one report.

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


    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. Dopamine agents for hepatic encephalopathy

    Junker, Anders Ellekær; Als-Nielsen, Bodil; Gluud, Christian;


    BACKGROUND: Patients with hepatic encephalopathy may present with extrapyramidal symptoms and changes in basal ganglia. These changes are similar to those seen in patients with Parkinson's disease. Dopamine agents (such as bromocriptine and levodopa, used for patients with Parkinson's disease) have...... therefore been assessed as a potential treatment for patients with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of dopamine agents versus placebo or no intervention for patients with hepatic encephalopathy. SEARCH METHODS: Trials were identified through the Cochrane...... the trials followed participants after the end of treatment. Only one trial reported adequate bias control; the remaining four trials were considered to have high risk of bias. Random-effects model meta-analyses showed that dopamine agents had no beneficial or detrimental effect on hepatic...

  10. Multi-Agent Software Engineering

    This paper proposed an alarm-monitoring system for people based on multi-agent using maps. The system monitors the users physical context using their mobile phone. The agents on the mobile phones are responsible for collecting, processing and sending data to the server. They can determine the parameters of their environment by sensors. The data are processed and sent to the server. On the other side, a set of agents on server can store this data and check the preconditions of the restrictions associated with the user, in order to trigger the appropriate alarms. These alarms are sent not only to the user who is alarmed to avoid the appeared restriction, but also to his supervisor. The proposed system is a general purpose alarm system that can be used in different critical application areas. It has been applied for monitoring the workers of radiation sites. However, these workers can do their activity tasks in the radiation environments safely

  11. Monitoring presence of chemical agents

    The specification describes a case for use with a hand-portable chemical agent detector for continuously monitoring an atmosphere for the presence of predetermined chemical agents. The detector having means for ionizing air samples and providing at an output terminal electrical signals representative of the mobility spectrum of ionized chemical vapours produced by the ionizing means. The case comprises means for defining a chamber in the case for supporting and removably enclosing the detector, means for communicating ambient atmosphere to the chamber, electrical circuit means in the case, the circuit means being adapted to be detachably connected to the detector output terminal when the detector is positioned in the chamber and being responsive to the electrical signals for producing an alarm signal when the signals detect a chemical agent concentration in the atmosphere exceeding a predetermined concentration level, and alarm means responsive to the alarm signal. (author)

  12. Erythropoietic agents and the elderly.

    Agarwal, Neeraj; Prchal, Josef T


    Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development that either act as ligands for the cell surface receptors of Epo or promote Epo production, which stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under active investigation include continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF-1), thereby stimulating Epo production and iron availability and supply. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of Epo levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as "neocytolysis." The relative decrease in the serum Epo level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  13. Autonomous sensor manager agents (ASMA)

    Osadciw, Lisa A.


    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.

  14. An overview of inotropic agents.

    Vroom, Margreeth B


    The use of inotropic agents has been surrounded by many controversies. Recent guidelines for the treatment of patients with chronic and acute heart failure have elucidated some of the issues, but many remain. As a result, a substantial variability in the use of agents between institutions and caregivers remains, which mainly results from the lack of uniform data in the literature. Prospective randomized trials with a long-term follow-up and sufficient power are clearly needed, and a number of trials are currently in progress. PMID:16959760

  15. Building Multi-Agent Systems Using Jason

    Boss, Niklas Skamriis; Jensen, Andreas Schmidt; Villadsen, Jørgen


    Technical University of Denmark (DTU). A part of this course was a short introduction to the multi-agent framework Jason, which is an interpreter for AgentSpeak, an agent-oriented programming language. As the final project in this course a solution to the Multi-Agent Programming Contest from 2007, the Gold...

  16. Using Agent to Coordinate Web Services

    Liu, C H; Chen, Jason J Y


    Traditionally, agent and web service are two separate research areas. We figure that, through agent communication, agent is suitable to coordinate web services. However, there exist agent communication problems due to the lack of uniform, cross-platform vocabulary. Fortunately, ontology defines a vocabulary. We thus propose a new agent communication layer and present the web ontology language (OWL)-based operational ontologies that provides a declarative description. It can be accessed by various engines to facilitate agent communication. Further, in our operational ontologies, we define the mental attitudes of agents that can be shared among other agents. Our architecture enhanced the 3APL agent platform, and it is implemented as an agent communication framework. Finally, we extended the framework to be compatible with the web ontology language for service (OWL-S), and then develop a movie recommendation system with four OWL-S semantic web services on the framework. The benefits of this work are: 1) dynamic ...

  17. Tc-99m imaging agents

    A wide range of pharmaceuticals for labeling with Tc-99m, developed by the Soreq Radiopharmaceuticals Department, is described. Details of the production and quality control of 13 kits are given, as well as the range of results required for consistently high quality imaging agents

  18. Antibacterial activities of antineoplastic agents.

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


    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.

  19. Raspberry Pi for secret agents

    Sjogelid, Stefan


    This book is an easy-to-follow guide with practical examples in each chapter. Suitable for the novice and expert alike, each topic provides a fast and easy way to get started with exciting applications and also guides you through setting up the Raspberry Pi as a secret agent toolbox.

  20. Identity Management in Agent Systems

    Brazier, F.M.T.; Groot, de D.R.A.


    If agent-based applications are to be used in large scale, open environments, security is a main issue; digital identity management (DIDM) an essential element. DIDM is needed to be able to determine the rights and obligations of the four main

  1. Kriitikute lemmikfilm on "Agent Sinikael"


    Eesti Filmiajakirjanike Ühing andis kümnendat korda välja auhinda Aasta film 2002. Parimaks filmiks tunnistati mängufilm "Agent Sinikael" : režissöör Marko Raat. Viimane sai preemiaks Neitsi Maali kuju ja 12 000 krooni

  2. Improving agents using reliable communication

    Zheng, Jinbin


    Recent advances in introspective modalities and linear time symmetries do not necessarily obviate the need for web browsers [1]. In our research, we disprove the exploration of agents, which embodies the appropriate principles of electrical engineering. Here we demonstrate that even though semaphores and XML [1] are mostly incompatible, randomized algorithms and write-back caches are mostly incompatible.

  3. Foodborne illness and microbial agents

    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...

  4. Bridging humans via agent networks

    Recent drastic advance in telecommunication networks enabled the human organization of new class, teleorganization, which differ from any existing organization in that the organization which is easy to create by using telecommunication networks is virtual and remote, that people can join multiple organizations simultaneously, and that the organization can involve people who may not know each other. In order to enjoy the recent advance in telecommunication, the agent networks to help people organize themselves are needed. In this paper, an architecture of agent networks, in which each agent learns the preference or the utility functioin of the owner, and acts on behalf of the owner in maintaining the organization, is proposed. When an agent networks supports a human organization, the conventional human interface is divided into personal and social interfaces. The functionalities of the social interface in teleconferencing and telelearning were investigated. In both cases, the existence of B-ISDN is assumed, and the extension to the business meeting scheduling using personal handy phone (PHS) networks with personal digital assistant (PDA) terminals is expected. These circumstances are described. Mutual selection protocols (MSP) and their dynamic properties are explained. (K.I.)

  5. Anchor Toolkit - a secure mobile agent system

    Mudumbai, Srilekha S.; Johnston, William; Essiari, Abdelilah


    Mobile agent technology facilitates intelligent operation in software systems with less human interaction. Major challenge to deployment of mobile agents include secure transmission of agents and preventing unauthorized access to resources between interacting systems, as either hosts, or agents, or both can act maliciously. The Anchor toolkit, designed by LBNL, handles the transmission and secure management of mobile agents in a heterogeneous distributed computing environment. It provide...

  6. Providing Reliable Agents for Electronic Commerce

    Straßer, Markus; Rothermel, Kurt; Maihöfer, Christian


    It is widely agreed that mobile agents in conjunction with WWW technology will provide the technical foundation for future electronic commerce. A prerequisite for the use of mobile agents in a commercial environment is, that agents have to be executed reliable, independent of communication and node failure. In this paper, we first present a recently proposed fault-tolerant protocol to ensure the exactly-once execution of an agent by monitoring the agents execut...

  7. Halide test agent replacement study

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


    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.

  8. Biologic agents in juvenile spondyloarthropathies.

    Katsicas, María Martha; Russo, Ricardo


    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  9. Migration Dynamics in Artificial Agent Societies

    Harjot Kaur


    Full Text Available An Artificial Agent Society can be defined as a collection of agents interacting with each other for some purpose and/or inhabiting a specific locality, possibly in accordance to some common norms/rules. These societies are analogous to human and ecological societies, and are an expanding and emerging field in research about social systems. Social networks, electronic markets and disaster management organizations can be viewed as such artificial (open agent societies and can be best understood as computational societies. Members of such artificial agent societies are heterogeneous intelligent software agents which are operating locally and cooperating and coordinating with each other in order to achieve goals of an agent society. These artificial agent societies have some kind of dynamics existing in them in terms of dynamics of Agent Migration, Role-Assignment, Norm- Emergence, Security and Agent-Interaction. In this paper, we have described the dynamics of agent migration process, starting from the various types of agent migration, causes or reasons for agent migration, consequences of agent migration, and an agent migration framework to model the its behavior for migration of agents between societies.

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

    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


    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.

  11. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    Baker, Lauri M.; Hadley, Gregg


    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…

  12. CATS-based Agents That Err

    Callantine, Todd J.


    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.

  13. Biological effects of mutagenic agents

    There is an increasing body of evidence that mutagenic agents (biological, chemical and physical) play an important role in the etiology of human diseases. Mutations may occur in the germinal as well as in the somatic cells. Mutations of the germ cells may result on infertility or fertilization of damaged cells, the later leading to abortion or birth of a malformed fetus. Somatic-cells mutations may have various biological effects, depending on the period of the human life at which the mutation occurs. If it occurs during the prenatal life, a teratogenic or carcinogenic effect will be observed. If the somatic cell is damaged during the postnatal life, this will lead to neoplastic transformation. Therefore it is extremely important to know the mutagenic, teratogenic and carcinogenic effects of various biological, chemical and physical agents in order to eliminate them from our environment. (author). 13 refs, 4 figs, 1 tab

  14. Extension agents and conflict narratives

    Bond, Jennifer Lauren


    Purpose: This work investigated the narratives of development extensionists in relation to natural resource conflict, in order to understand the competing discourses surrounding the wicked problems of natural resource management in Laikipia County, Kenya. Methodology: Q methodology was used to...... professionals from government, non-government, faith-based and private organizations. Findings: Four factors were elicited from the data, labelled—A: ‘Improved Leadership’; B: ‘Resource-centred conflict’; C: ‘Improved Governance’; and D: ‘Improved Management’. Practical Implications: Narratives of neo...... resource conflict. Originality: This work contributes to a growing body of literature interested in the role of extension agents in conflict management. By applying Q methodology, this work has shown that while extension agents are involved in conflict management, their perceptions of these conflicts are...

  15. Agent Based Individual Traffic Guidance

    Wanscher, Jørgen

    This thesis investigates the possibilities in applying Operations Research (OR) to autonomous vehicular traffic. The explicit difference to most other research today is that we presume that an agent is present in every vehicle - hence Agent Based Individual Traffic guidance (ABIT). The next...... that the system can be divided into two separate constituents. The immediate dispersion, which is used for small areas and quick response, and the individual alleviation, which considers the longer distance decision support. Both of these require intrinsicate models and cost functions which at the...... beginning of the project were not previously considered. We define a special inseparable cost function and develop a solution complex capable of using this cost function. In relation to calibration and estimation of statistical models used for dynamic route guidance we worked with generating random number...

  16. [Infectious agents and autoimmune diseases].

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R


    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  17. Oral agents in multiple sclerosis.

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E


    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  18. Logical Theories for Agent Introspection

    Bolander, Thomas


    Artificial intelligence systems (agents) generally have models of the environments they inhabit which they use for representing facts, for reasoning about these facts and for planning actions. Much intelligent behaviour seems to involve an ability to model not only one's external environment but...... self-reference. In the standard approach taken in artificial intelligence, the model that an agent has of its environment is represented as a set of beliefs. These beliefs are expressed as logical formulas within a formal, logical theory. When the logical theory is expressive enough to allow...... introspective reasoning, the presence of self-reference causes the theory to be prone to inconsistency. The challenge therefore becomes to construct logical theories supporting introspective reasoning while at the same time ensuring that consistency is retained. In the thesis, we meet this challenge by devising...

  19. Injectable agents affecting subcutaneous fats.

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B


    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. PMID:26566569

  20. Topical agents in burn care

    Momčilović Dragan


    Introduction Understanding of fluid shifts and recognition of the importance of early and appropriate fluid replacement therapy have significantly reduced mortality in the early post burn period. After the bum patient successfully passes the resuscitation period, the burn wound represents the greatest threat to survival. History Since the dawn of civilization, man has been trying to find an agent which would help burn wounds heal, and at the same time, not harm general condition of the injure...

  1. Building Hybrid Soft Computing Agents

    Neruda, Roman

    Anheim : ACTA Press, 2003 - (Castillo, O.), s. 7-11 ISBN 0-88986-347-4. [IASTED International Conference on Neural Networks and Computational Intelligence. Cancun (MX), 19.05.2003-21.05.2003] R&D Projects: GA ČR(CZ) GP201/03/P163 Institutional research plan: CEZ:AV0Z1030915 Keywords : evolutionary algorithms * multi - agent system s * hybrid methods Subject RIV: BA - General Mathematics


    Aruna Rani; A. K. Gautam


    The MSA Agent is the software developed to design rectangular and U slotted micro strip antenna.It is applied for the various applications such as satellite communications, UHF applications. Within the multimedia frequency range the developed software is tested and analyzed for various results. The software is developed using genetic algorithm. This provides extra flexibility and new capability to design rectangular and U slotted micro strip antenna for multimedia application also. The result...

  3. Provably Bounded-Optimal Agents

    Russell, S J; Subramanian, D.


    Since its inception, artificial intelligence has relied upon a theoretical foundation centered around perfect rationality as the desired property of intelligent systems. We argue, as others have done, that this foundation is inadequate because it imposes fundamentally unsatisfiable requirements. As a result, there has arisen a wide gap between theory and practice in AI, hindering progress in the field. We propose instead a property called bounded optimality. Roughly speaking, an agent is boun...

  4. Autonomous Behavior of Computational Agents

    Vaculín, Roman; Neruda, Roman

    Wien : Springer-Verlag, 2005 - (Ribiero, B.; Albrecht, R.; Dobnikar, A.; Pearson, D.; Steele, N.), s. 514-517 ISBN 3-211-24934-6. [ICANNGA'2005 /7./. Coimbra (PT), 21.03.2005-23.03.2005] R&D Projects: GA AV ČR 1ET100300419 Institutional research plan: CEZ:AV0Z10300504 Keywords : computational agents * autonomous behavior * reasoning Subject RIV: BA - General Mathematics

  5. Agent Simulation of Chain Bankruptcy

    Yuichi Ikeda; Yoshi Fujiwara; Wataru Souma; Hideaki Aoyama; Hiroshi Iyetomi


    We have conducted an agent-based simulation of chain bankruptcy. The propagation of credit risk on a network, i.e., chain bankruptcy, is the key to nderstanding largesized bankruptcies. In our model, decrease of revenue by the loss of accounts payable is modeled by an interaction term, and bankruptcy is defined as a capital deficit. Model parameters were estimated using financial data for 1,077 listed Japanese firms. Simulations of chain bankruptcy on the real transaction network consisting o...

  6. Crimen organizado y agente encubierto

    Herrero Reus, Ignacio


    Uno de los objetivos de la justicia penal actual es la lucha contra la criminalidad organizada, bien por su propia naturaleza de “crimen organizado”, bien porque presenta elementos trasnacionales que impiden su investigación a fondo. Todo ello exige la creación de recursos que permitan la investigación de dichos delitos, recursos como el de infiltración de los agentes policiales, objeto del trabajo.

  7. Dimensions and Issues of Mobile Agent Technology

    Yashpal Singh


    Full Text Available Mobile Agent is a type of software system which acts “intelligently” on one’s behalf with the feature of autonomy, learning ability and most importantly mobility. Now mobile agents are gaining interest in the research community. In this article mobile agents will be addressed as tools for mobile computing. Mobile agents have been used in applications ranging from network management to information management. We present mobile agent concept, characteristics, classification, need, applications and technical constraints in the mobile technology. We also provide a brief case study about how mobile agent is used for information retrieval.

  8. Antagonistic formation motion of cooperative agents

    卢婉婷; 代明香; 薛方正


    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  9. Agent planning in AgScala

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana


    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.

  10. A++: An Agent Oriented Programming Language

    Deyi Xue


    Full Text Available A new Agent-Oriented Programming (AOP language called A++ is introduced in this research for developing agent-based distributed systems. In this work, agent-oriented programming is defined as a programming method with characteristics of distribution, autonomy, concurrency, and mobility. Both agents and objects can be modeled in A++. In addition to data and methods that can be defined in objects including classes and instances, each agent is also associated with an independent computing process in agent-oriented programming.