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Sample records for anti-hiv agents

  1. Potential Anti-HIV Agents from Marine Resources: An Overview

    OpenAIRE

    Thanh-Sang Vo; Se-Kwon Kim

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great de...

  2. Conjugates of Betulin Derivatives with AZT as Potent Anti-HIV Agents

    OpenAIRE

    Xiong, Juan; KASHIWADA, YOSHIKI; Chen, Chin-Ho; Qian, Keduo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung; Takaishi, Yoshihisa

    2010-01-01

    Fourteen novel conjugates of 3,28-di-O-acylbetulins with AZT were prepared as anti-HIV agents, based on our previously reported potent anti-HIV triterpene leads, including 3-O-acyl and 3,28-di-O-acylbetulins. Nine of the conjugates (49–53, 55, 56, 59, 60) exhibited potent anti-HIV activity at the submicromolar level, with EC50 values ranging from 0.040 to 0.098 µM in HIV-1NL4-3 infected MT-4 cells. These compounds were equipotent or more potent than 3-O-(3',3'-dimethylsuccinyl)betulinic acid ...

  3. Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Jing Li; Wen Long Huang; Hui Bin Zhang; Hai Qian; Yong Tang Zheng

    2011-01-01

    A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro. Compound 10 and 16b, of which TI were >10, had some anti-HTV-1 activity in vitro. Therein, compound 10 which was the best potent compound, could serve as a new lead for further development of anti-AIDS agents.

  4. Polyphenols: a diverse class of multi-target anti-HIV-1 agents.

    Science.gov (United States)

    Andrae-Marobela, Kerstin; Ghislain, Fotso Wabo; Okatch, Harriet; Majinda, Runner R T

    2013-05-01

    Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti- HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols - according to their respective compound classes - exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process. PMID:23330927

  5. Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids.

    Science.gov (United States)

    Kashiwada, Y; Wang, H K; Nagao, T; Kitanaka, S; Yasuda, I; Fujioka, T; Yamagishi, T; Cosentino, L M; Kozuka, M; Okabe, H; Ikeshiro, Y; Hu, C Q; Yeh, E; Lee, K H

    1998-09-01

    Oleanolic acid (1) was identified as an anti-HIV principle from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). It inhibited HIV-1 replication in acutely infected H9 cells with an EC50 value of 1.7 microg/mL, and inhibited H9 cell growth with an IC50 value of 21.8 microg/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also identified as an anti-HIV agent (EC50 1.4 microg/mL, T. I. 16.6). Although ursolic acid did show anti-HIV activity (EC50 2.0 microg/mL), it was slightly toxic (IC50 6.5 microg/mL, T. I. 3.3). A new triterpene (11) was also isolated from the CHCl3-soluble fraction of R. woodsii, though it showed no anti-HIV activity. The structure of 11 was determined to be 1beta-hydroxy-2-oxopomolic acid by spectral examination. Based on these results, we examined the anti-HIV activity of oleanolic acid- or pomolic acid-related triterpenes isolated from several plants. In addition, we previously demonstrated that derivatives of betulinic acid, isolated from the leaves of S. claviflorum as an anti-HIV principle, exhibited extremely potent anti-HIV activity. Accordingly, we prepared derivatives of oleanolic acid and evaluated their anti-HIV activity. Among the oleanolic acid derivatives, 18 demonstrated most potent anti-HIV activity, with an EC50 value of 0. 0005 microg/mL and a T. I. value of 22 400. PMID:9748372

  6. Synthesis and bioevaluation of substituted chalcones, coumaranones and other flavonoids as anti-HIV agents.

    Science.gov (United States)

    Cole, Amy L; Hossain, Sandra; Cole, Alex M; Phanstiel, Otto

    2016-06-15

    A series of chalcone, flavone, coumaranone and other flavonoid compounds were screened for their anti HIV-1 activity in two cell culture models using TZM-bl and PM1 cells. Within the systems evaluated, the most promising compounds contained either an α- or β-hydroxy-carbonyl motif within their structure (e.g., 8 and 9). Efficacious substituents were identified and used to design new HIV inhibitors with increased potency and lower cytotoxicity. Of the scaffolds evaluated, specific chalcones were found to provide the best balance between anti-HIV potency and low host cell toxicity. Chalcone 8l was shown to inhibit different clinical isolates of HIV in a dose-dependent manner (e.g., IC50 typically⩽5μM). Inhibition of HIV infection experiments using TZM-bl cells demonstrated that chalcone 8l and flavonol 9c had IC50 values of 4.7μM and 10.4μM, respectively. These insights were used to design new chalcones 8o and 8p. Rewardingly, chalcones 8o and 8p (at 10μM) each gave >92% inhibition of viral propagation without impacting PM1 host cell viability. Inhibition of viral propagation significantly increased (60-90%) when PM1 cells were pre-incubated with chalcone 8o, but not with the related flavonol 9c. These results suggested that chalcone 8o may be of value as both a HIV prophylactic and therapy. In summary, O-benzyl-substituted chalcones were identified as promising anti-HIV agents for future investigation. PMID:27161874

  7. Anti-AIDS Agents 69.1 Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents

    OpenAIRE

    Yu, Donglei; Sakurai, Yojiro; Chen, Chin-Ho; Chang, Fang-Rong; Huang, Li; Kashiwada, Yoshiki; Lee, Kuo-Hsiung

    2006-01-01

    In a continuing structure-activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20 and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4−3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analog 8...

  8. Abasic oligodeoxyribonucleoside phosphorothioates: synthesis and evaluation as anti-HIV-1 agents.

    OpenAIRE

    Iyer, R. P.; Uznanski, B; Boal, J; Storm, C; Egan, W; Matsukura, M; Broder, S; Zon, G; Wilk, A.; Koziolkiewicz, M

    1990-01-01

    The syntheses and anti-HIV-1 evaluations of two, abasic oligodeoxyribonucleotide phosphorothioate analogs, d[Cps(Eps)26C] and d[Cps(Vps)26C] (where E and V derive from 1,2-dideoxy-D-ribofuranose and (+/-)-butane 1, 3-diol, respectively), are described.

  9. Topological estimation of cytotoxic activity of some anti-HIV agents: HEPT analogues

    Indian Academy of Sciences (India)

    Vijay K Agrawal; Kamlesh Mishra; Ruchi Sharma; P V Khadikar

    2004-03-01

    QSAR studies on anti-HIV cytotoxic activities of a series of HEPT(1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)-thymine) analogues have been discussed. The molecular descriptors used being van der Waals volume () and equalized electronegativity (eq). The in vitro cytotoxicities (50) were modelled using these parameters. It was observed that upon introduction of indicator parameters statistically excellent models are obtained. The predictive power of the models was examined using a cross-validation method.

  10. Approaches of Novel drug delivery systems for Anti-HIV agents

    OpenAIRE

    Vedha Hari B. N; Devendharan K,; Narayanan N

    2013-01-01

    The Human Immunodeficiency Virus (HIV) is a pandemic disease spreading very rapidly all over the world, causing approximately 15,000 or more new infections every day and the community acquiring sexually transmitted infections (STIs) is prone to easily acquire this HIV infections. The objective of the current review is to describe the comprehensiveness of the various advanced anti-HIV drug delivery systems and compounds that have been developed for targeting drugs to the macrophages, gastric m...

  11. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains

    OpenAIRE

    Rui-Rui Wang; Yue-Dong Gao; Chun-Hui Ma; Xing-Jie Zhang; Cheng-Gang Huang; Jing-Fei Huang; Yong-Tang Zheng

    2011-01-01

    The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1ⅢB induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50) at 16.90 μM and a therapeutic index (TI) above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic prot...

  12. HIV Integrase Inhibitors with Nucleobase Scaffolds: Discovery of a Highly Potent anti-HIV Agent

    OpenAIRE

    Nair, Vasu; Chi, Guochen; Ptak, Roger; Neamati, Nouri

    2006-01-01

    HIV integrase is essential for HIV replication. However, there are currently no integrase inhibitors in clinical use for AIDS. We have discovered a conceptually new β-diketo acid that is a powerful inhibitor of both the 3′-processing and strand transfer steps of HIV-1 integrase. The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIVTEKI and HIV-1NL4-3 replication in PBMC (TI >4,000 and >10,000, respectively).

  13. Inhibition of visna virus replication and cytopathic effect in sheep choroid plexus cell cultures by selected anti-HIV agents.

    Science.gov (United States)

    Thormar, H; Balzarini, J; Debyser, Z; Witvrouw, M; Desmyter, J; De Clercq, E

    1995-05-01

    Several anti-HIV agents were tested against visna virus replication and cytopathic effect (CPE) in sheep choroid plexus cell cultures. Sulphated polysaccharides (i.e., dextran sulphate, pentosan polysulphate and heparin) and plant lectins, which inhibit viral adsorption and fusion, were found to be 10- to 40-fold less active against visna virus than against HIV. Bicyclam derivatives were at least 250-fold less active against visna virus and the highly HIV-1 specific TIBO derivatives were without a significant inhibitory effect on visna virus at subtoxic concentrations. In contrast, several 2',3'-dideoxynucleosides and acyclic nucleoside phosphonate analogues, which inhibit reverse transcription, were found to be very effective inhibitors of visna virus replication and viral CPE in cell culture. PMID:7486958

  14. Approaches of Novel drug delivery systems for Anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Vedha Hari B. N

    2013-12-01

    Full Text Available The Human Immunodeficiency Virus (HIV is a pandemic disease spreading very rapidly all over the world, causing approximately 15,000 or more new infections every day and the community acquiring sexually transmitted infections (STIs is prone to easily acquire this HIV infections. The objective of the current review is to describe the comprehensiveness of the various advanced anti-HIV drug delivery systems and compounds that have been developed for targeting drugs to the macrophages, gastric mucosa and brain. Novel drug delivery system gives an opportunity to bypass the shortcomings related to the anti-retroviral treatment. It helps in addressing towards the complexity of dosage form development such as instability, insolubility and limited entrapment of the drugs. Several optional routes have been identified for the management of the ARV therapy which includes transdermal, mucosal (vaginal, rectal, buccal, etc. and also lymphatic delivery, with the application of novel systems like nanoparticles, vesicular systems (liposomes, niosomes, ethosomes, emulsomes, micellar assemblies, etc. This review spotlights the prospectives of novel drug release systems used in preventing the transmission and treatment of retroviral infections.

  15. Mangiferin, an Anti-HIV-1 Agent Targeting Protease and Effective against Resistant Strains

    Directory of Open Access Journals (Sweden)

    Rui-Rui Wang

    2011-05-01

    Full Text Available The anti-HIV-1 activity of mangiferin was evaluated. Mangiferin can inhibit HIV-1ⅢB induced syncytium formation at non-cytotoxic concentrations, with a 50% effective concentration (EC50 at 16.90 μM and a therapeutic index (TI above 140. Mangiferin also showed good activities in other laboratory-derived strains, clinically isolated strains and resistant HIV-1 strains. Mechanism studies revealed that mangiferin might inhibit the HIV-1 protease, but is still effective against HIV peptidic protease inhibitor resistant strains. A combination of docking and pharmacophore methods clarified possible binding modes of mangiferin in the HIV-1 protease. The pharmacophore model of mangiferin consists of two hydrogen bond donors and two hydrogen bond acceptors. Compared to pharmacophore features found in commercially available drugs, three pharmacophoric elements matched well and one novel pharmacophore element was observed. Moreover, molecular docking analysis demonstrated that the pharmacophoric elements play important roles in binding HIV-1 protease. Mangiferin is a novel nonpeptidic protease inhibitor with an original structure that represents an effective drug development strategy for combating drug resistance.

  16. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2′,3′-seco-3′-nor DCP and DCK analogues

    Science.gov (United States)

    Chen, Ying; Cheng, Ming; Liu, Faqiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2011-01-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1′-O-, 1′-S-, 4′-O- and 4′-substituted-2′,3′-seco-3′-nor DCP and DCK analogues (8–37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1NL4-3 and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22–24, and 32) exhibited potent anti-HIV activity with EC50 values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1′-O-Isopropoxy-2′,3′-seco-3′-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC50 values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1NL4-3 and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates. PMID:21864952

  17. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2',3'-seco-3'-nor DCP and DCK analogues.

    Science.gov (United States)

    Chen, Ying; Cheng, Ming; Liu, Fa-Qiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1'-O-, 1'-S-, 4'-O- and 4'-substituted-2',3'-seco-3'-nor DCP and DCK analogues (8-37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1(NL4-3) and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22-24, and 32) exhibited potent anti-HIV activity with EC(50) values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1'-O-Isopropoxy-2',3'-seco-3'-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC(50) values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1(NL4-3) and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates. PMID:21864952

  18. Comparison of three quantification methods for the TZM-bl pseudovirus assay for screening of anti-HIV-1 agents.

    Science.gov (United States)

    Xing, Liying; Wang, Shunyi; Hu, Qin; Li, Jingtao; Zeng, Yi

    2016-07-01

    The TZM-bl pseudovirus assay is commonly used to evaluate the efficacy of neutralizing antibodies and small molecular inhibitors in HIV-1 research. Here, to determine the optimal measurement method for screening anti-HIV-1 inhibitors, we compared three measurement methods based on firefly luciferase and β-galactosidase activities. The 50% tissue culture infective doses (TCID50) of the pseudoviruses were determined using the luciferase, β-galactosidase colorimetric, and 5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside (X-gal) staining assays. Three commercial reverse-transcriptase inhibitors (azidothymidine, nevirapine, and lamivudine) were tested as reference drugs to compare the reproducibility, linear correlation, and half maximal inhibitory concentration (IC50) values determined using these methods. In the TCID50 assay, the sensitivity of β-galactosidase colorimetric assay was almost 562 times lower than that of the other two methods. Reproducible dose-response curves were obtained for the inhibitors with all methods; the IC50 values of the inhibitors were not significantly different. Linear regression analysis showed linear correlation between methods. Compared to the β-galactosidase colorimetric assay, the other two methods have the advantage of high sensitivity and are less affected by interference. In conclusion, the luciferase and X-gal staining assays, which can be applied either alone or combined, are recommended for anti-HIV-1 inhibitor screening. PMID:27016178

  19. Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2′,3′-seco-3′-nor DCP and DCK analogues

    OpenAIRE

    Chen, Ying; Cheng, Ming; Liu, Faqiang; Xia, Peng; Qian, Keduo; Yu, Donglei; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2011-01-01

    In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1′-O-, 1′-S-, 4′-O- and 4′-substituted-2′,3′-seco-3′-nor DCP and DCK analogues (8–37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1NL4-3 and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22–24, and 32) exhibited potent a...

  20. Testing anti-HIV activity of antiretroviral agents in vitro using flow cytometry analysis of CEM-GFP cells infected with transfection-derived HIV-1 NL4-3.

    Science.gov (United States)

    Frezza, Caterina; Grelli, Sandro; Federico, Maurizio; Marino-Merlo, Francesca; Mastino, Antonio; Macchi, Beatrice

    2016-06-01

    An assay, specifically optimized to evaluate the anti-HIV activity of antiretrovirals by flow cytometry analysis, is described. As widely used anti-HIV agents, zidovudine (AZT), abacavir (ABC), 2',3'-dideoxyinosine (DDI), lamivudine (3TC), nevirapine (NVP), and efavirenz (EFV), and as drugs of recent approval raltegravir (RAL), etravirine (ETR), and rilpivirine (RPV), were utilized as reference drugs. HIV-1 NL4-3 virus was prepared by transfection of HEK293T cells with purified plasmid DNA and quantified by p24 antigen-capture assay. For infection, CEM-GFP cells were exposed to vehicle or to several concentrations of the drugs for 2 hr at 37 °C before HIV-1 NL4-3 was added to each sample. The adsorption was prolonged for 3 hr at 37 °C. After 72 hr of incubation, HIV-induced GFP expression in infected CEM-GFP cells was assessed by flow cytometry analysis and expressed as % positive cells. For comparison, p24 production in supernatants was assessed by a commercial ELISA kit. On the basis of IC50 values, the anti-HIV activity, as assayed by this method, was EFV > 3TC > AZT > NVP > DDI > ABC and ETR > RPV > RAL. The comparison between the IC50 values calculated through flow cytometry and p24 production revealed overlapping results, showing that the optimized protocol of CEM-GFP infection with HIV NL4-3 is a suitable method to perform quantitative, rapid and low-expensive screening tests to evaluate the in vitro effect of new candidate anti-HIV drugs. PMID:26519867

  1. Metabolism of novel anti-HIV agent 3-cyanomethyl-4-methyl-DCK by human liver microsomes and recombinant CYP enzymes

    Institute of Scientific and Technical Information of China (English)

    Xiao-mei ZHUANG; Jing-ting DENG; Hua LI; Wei-li KONG; Jin-xiu RUAN; Lan XIE

    2011-01-01

    Aim:To investigate the metabolism of 3-cyanomethyl-4-methyl-DCK (CMDCK),a novel anti-HIV agent,by human liver microsomes (HLMs) and recombinant cytochrome P450 enzymes (CYPs).Methods:CMDCK was incubated with HLMs or a panel of recombinant cytochrome P450 enzymes including CYP1A2,2B6,2C8,2C9,2C19,2D6,3A4,and 3A5.LC-ion trap mass spectrometry was used to separate and identify CMDCK metabolites.In the experiments with recombinant cytochrome P450 enzymes,specific chemical inhibitors combined with CYP antibodies were used to identify the CYP isoforms involved in CMDCK metabolism.Results:CMDCK was rapidly and extensively metabolized by HLMs.Its intrinsic hepatic clearance estimated from the in vitro data was 19.4 mL.min-1·kg-1,which was comparable to the mean human hepatic blood flow rate (20.7 mL·min-1·kg-1).The major metabolic pathway of CMDCK was oxidation,and a total of 14 metabolites were detected.CYP3A4 and 3A5 were found to be the principal CYP enzymes responsible for CMDCK metabolism.Conclusion:CMDCK was metabolized rapidly and extensively in human hepatic microsomes to form a number of oxidative metabolites.CYP3A4 and 3A5 were the predominant enzymes responsible for the oxidation of CMDCK.

  2. Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.

    Science.gov (United States)

    Liu, Hong-Shan; Xu, Shi-Qing; Cheng, Ming; Chen, Ying; Xia, Peng; Qian, Keduo; Xia, Yi; Yang, Zheng-Yu; Chen, Chin-Ho; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2011-10-01

    Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9. PMID:21871800

  3. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-09-15

    In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 microM to 0.14 microM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 microM; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 microM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  4. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2′,2′-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-01-01

    In a continued study, 23 3′R,4′R-di-O-(−)-camphanoyl-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5–27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 μM to 0.14 μM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 μM; TI 310 and 200, respectively), and were two-fold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 μM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5–10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  5. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Science.gov (United States)

    Behbahani, Mandana

    2014-01-01

    Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs) used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR) assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50) values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies. PMID:25333699

  6. Anti-HIV-1 activity of eight monofloral Iranian honey types.

    Directory of Open Access Journals (Sweden)

    Mandana Behbahani

    Full Text Available Monofloral Iranian honeys from eight floral sources were analyzed to determine their anti-HIV-1 activities as well as their effects on lymphocyte proliferation. The Peripheral Blood Mononuclear Cells (PBMCs used in this study were prepared from five healthy volunteers who were seronegative for HIV, HCV, HBV and TB. The anti-HIV-1 activity of eight different honeys was performed by quantitative polymerase chain reaction (PCR assay and high pure viral nucleic acid kit. The results demonstrated that monofloral honeys from Petro selinum sativum, Nigella sativa, Citrus sinensis, Zataria multiflora, Citrus aurantium and Zizyphus mauritiana flowers had potent anti-HIV-1 activity with half maximal effective concentration (EC50 values of 37.5, 88, 70, 88, 105 and 5 µg/ml respectively. However, monofloral Iranian honeys from Astragalus gummifer and Chamaemelum nobile flowers had weak anti-HIV-1 activity. The frequency and intensity of CD4 expression on PBMCs increased in the presence of all honey types. CD19 marker were also increased after the treatment with monofloral honeys from Z. multiflora and N. sativa. The anti-HIV-1 agent in monofloral honeys from P. sativum, N. sativa, Z. multiflora and Z. mauritiana flowers was detected by spectroscopic analysis as methylglyoxal. Time of drug addition studies demonstrated that the inhibitory effect of methylglyoxal is higher on the late stage of HIV-1 infection. The result demonstrated that methylglyoxal isolated from monofloral honey types is a good candidate for preclinical evaluation of anti-HIV-1 therapies.

  7. A Review of Electroanalytical Techniques for Determination of Anti-HIV Drugs

    Directory of Open Access Journals (Sweden)

    Burçin Bozal

    2011-01-01

    Full Text Available Until now after the human immunodeficiency virus (HIV was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS, exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, lamivudine, abacavir, stavudine, and emtricitabine, nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir, nonnucleoside reverse transcriptase inhibitors (NNRTIs: efavirenz, nevirapine, delavirdine, and etravirine, protease inhibitors (PIs: ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir, fosamprenavir, atazanavir, tipranavir and darunavir, fusion inhibitors (FIs: enfuvirtide, coreceptor inhibitors (CRIs: maraviroc, and integrase inhibitors (INIs: raltegravir. The present paper submitted the use of various electroanalytical techniques for the determination of anti-HIV drugs. This paper covers the time period from 1990 to 2010 including voltammetric techniques that were reported. Presented application concerns analysis of anti-HIV drugs from pharmaceutical dosage forms and biological samples.

  8. In vitro anti-HIV-1 activity of fucoidan from Sargassum swartzii.

    Science.gov (United States)

    Dinesh, Subramaniam; Menon, Thangam; Hanna, Luke E; Suresh, V; Sathuvan, M; Manikannan, M

    2016-01-01

    Sargassum swartzii, a marine brown algae with wide range of biological properties belongs to the family Sargassaceae. Bioactive fucoidan fractions (CFF, FF1 and FF2) were isolated from S. swartzii and characterized by linear gradient anion-exchange chromatography and FT-IR. The characterized fucoidan fractions contained mainly sugars, sulfate and uronic acid. In the present study, anti-HIV-1 property of the fucoidan fractions was investigated. Fraction FF2 was found to exhibit significant anti-HIV-1 activity at concentrations of 1.56 and 6.25 μg/ml as observed by >50% reduction in HIV-1 p24 antigen levels and reverse transcriptase activity. Fucoidan fractions have no cytotoxic effects on PBMCs at the concentration range of 1.56-1000 μg/ml. These results suggest that fucoidan fractions could have inhibitory activity against HIV and has potential as an anti-HIV-1 agent. PMID:26472515

  9. Lectins with Anti-HIV Activity: A Review

    OpenAIRE

    Ouafae Akkouh; Tzi Bun Ng; Senjam Sunil Singh; Cuiming Yin; Xiuli Dan; Yau Sang Chan; Wenliang Pan; Randy Chi Fai Cheung

    2015-01-01

    Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV al...

  10. Anti - HIV-1 integrase activity of Thai Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Kingkan Bunluepuech

    2009-08-01

    Full Text Available For the purpose of discovering anti-HIV-1 agents from natural sources, the aqueous and EtOH extracts of eight Thaiplants including Clerodendron indicum (whole plant, Tiliacora triandra (stem, Capparis micracantha (wood, Harrissoniaperforata (wood, Ficus glomerata (wood, Diospyros decandra (wood, Dracaena loureiri (heartwood, and Tinospora crispa (stem were screened for their inhibitory activities against HIV-1 integrase (IN using the multiplate integration assay(MIA. Of the EtOH extracts, Ficus glomerata (wood was the most potent with an IC50 value of 7.8 g/ml; whereas the water extract of Harrisonia perforata (wood was the most potent aqueous extract with an IC50 value of 2.3 g/ml. The isolation of active principles against HIV-1 IN from Ficus glomerata is now actively pursued.

  11. [Anti-HIV drugs and drug delivery system].

    Science.gov (United States)

    Obaru, K; Mitsuya, H

    1998-03-01

    A number of candidate drugs for therapy of HIV-1 infection which show significant activity against the virus in vitro were reported; however, many of them have been dropped from drug development due to (i) insufficient intracellular activation in certain human target cells (particularly in case of nucleoside reverse transcriptase inhibitors), (ii) poor pharmacokinetic profiles, or (iii) intolerable in vitro and/or in vivo toxicities. To circumvent some of these problems, certain drug delivery systems have been applied and several candidate drugs including two novel nucleoside reverse transcriptase inhibitors, abacavir and adefovir, have acquired favorable properties in the clinical setting. This paper reviews several avenues for developing prodrugs of anti-HIV-1 agents to overcome their inherent limitations. PMID:9549371

  12. A Review of Electroanalytical Techniques for Determination of Anti-HIV Drugs

    OpenAIRE

    Burçin Bozal; Bengi Uslu; Özkan, Sibel A.

    2011-01-01

    Until now after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, lamivudine, abacavir, stavudine, and emtricitabine), nucleotide reverse transcriptase inhibitors (NtRTIs: t...

  13. Voltammetry Study of an Anti-HIV Compound by means of a Thin Organic Membrane

    OpenAIRE

    Achille Nassi; Thiery Christophe Ebelle; Dika Manga, Joseph M.; Jules-Blaise Mabou Leuna; Joel Donkeng Dazie; Emmanuel Ngameni

    2013-01-01

    Cyclic and square wave voltammetries have been used to study electrochemical behaviour of an anti-HIV agent (Guttiferone A) at the liquid-liquid interface. The thin organic membrane is formed by an organic solvent containing redox probe. Guttiferone A, a benzophenone (BP) with appropriate electrolyte. It is demonstrated that BP possesses three reduction systems due to the redox transformation of the three tautomeric forms that lead to the migration of proton between the hydroxyl group in posi...

  14. Pharmacokinetics and Dose-range Finding Toxicity of a Novel anti-HIV Active Integrase Inhibitor

    OpenAIRE

    Nair, Vasu; Okello, Maurice; Mishra, Sanjay; Mirsalis, Jon; O’Loughlin, Kathleen; Zhong, Yu

    2014-01-01

    Integration of viral DNA into human chromosomal DNA catalyzed by HIV integrase represents the “point of no return” in HIV infection. For this reason, HIV integrase is considered a crucial target in the development of new anti-HIV therapeutic agents. We have discovered a novel HIV integrase inhibitor 1, that exhibits potent antiviral activity and a favorable metabolism profile. This paper reports on the pharmacokinetics and toxicokinetics of compound 1 and the relevance of these findings with ...

  15. Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

    OpenAIRE

    Carolina Horta Andrade; Lenis Medeiros de Freitas; Valéria de Oliveira

    2011-01-01

    From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleo...

  16. Anti-HIV-1 Therapeutics: From FDA-approved Drugs to Hypothetical Future Targets

    OpenAIRE

    Adamson, Catherine S; Freed, Eric O.

    2009-01-01

    More than twenty-five years after its discovery, HIV-1 remains one of the world’s most formidable and destructive pathogens. Several classes of anti-HIV-1 agents are currently in widespread clinical use in developed nations; however, viral resistance to these drugs limits their effectiveness in a growing number of patients. It is therefore imperative that novel drugs be developed. Recent advances in the fields of HIV-1 molecular virology and cell biology have revealed possible new targets for...

  17. TARGETING OF ANTIVIRAL DRUGS TO LYMPHOCYTES-T4 - ANTI-HIV ACTIVITY OF NEOGLYCOPROTEIN AZTMP CONJUGATES INVITRO

    NARCIS (Netherlands)

    MOLEMA, G; JANSEN, RW; PAUWELS, R; DECLERCQ, E; MEIJER, DKF

    1990-01-01

    The delivery of the anti-HIV agent 3'-azido-3'-deoxythymidine (AZT), in its 5'-monophosphate form, (in)to human T-lymphocyte MT-4 cells in vitro through covalent coupling to neoglycoproteins was investigated. In vivo application of this drug targeting concept may lead to increased efficacy and/or di

  18. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    Directory of Open Access Journals (Sweden)

    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  19. Anti-HIV drug development on the fast track

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ An international cooperation deal was made recently in Shanghai on developing a new anti-HIV drug based on the research results of CAS scientists and their preclinical studies,marking a breakthrough progress for China's research in the field.

  20. Targeting anti-HIV drugs to the CNS

    OpenAIRE

    Rao, Kavitha S.; Ghorpade, Anuja; Labhasetwar, Vinod

    2009-01-01

    The development of antiretroviral drugs over the past couple of decades has been commendable due to the identification of several new targets within the overall Human Immunodeficiency Virus (HIV) replication cycle. However, complete control over HIV/Acquired Immune Deficiency Syndrome is yet to be achieved. This is because the current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. This occurs because most anti-HIV drugs...

  1. Anti-HIV Drug Development Through Computational Methods

    OpenAIRE

    Gu, Wan-Gang; Zhang, Xuan; Yuan, Jun-Fa

    2014-01-01

    Although highly active antiretroviral therapy (HAART) is effective in controlling the progression of AIDS, the emergence of drug-resistant strains increases the difficulty of successful treatment of patients with HIV infection. Increasing numbers of patients are facing the dilemma that comes with the running out of drug combinations for HAART. Computational methods play a key role in anti-HIV drug development. A substantial number of studies have been performed in anti-HIV drug development us...

  2. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

    OpenAIRE

    Arun K. Nalla; Trobridge, Grant D.

    2016-01-01

    Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a pote...

  3. Design, synthesis and anti-HIV-1 evaluation of hydrazide-based peptidomimetics as selective gelatinase inhibitors.

    Science.gov (United States)

    Yang, Liang; Wang, Ping; Wu, Ji-Feng; Yang, Liu-Meng; Wang, Rui-Rui; Pang, Wei; Li, Yong-Gang; Shen, Yue-Mao; Zheng, Yong-Tang; Li, Xun

    2016-05-01

    As our ongoing work on research of gelatinase inhibitors, an array of hydrazide-containing peptidomimetic derivatives bearing quinoxalinone as well as spiro-heterocyclic backbones were designed, synthesized, and assayed for their in vitro enzymatic inhibitory effects. The results demonstrated that both the quinoxalinone (series I and II) and 1,4-dithia-7-azaspiro[4,4]nonane-based hydrazide peptidomimetics (series III) displayed remarkably selectivity towards gelatinase A as compared to APN, with IC50 values in the micromole range. Structure-activity relationships were herein briefly discussed. Given evidences have validated that gelatinase inhibition may be contributable to the therapy of HIV-1 infection, all the target compounds were also submitted to the preliminary in vitro anti-HIV-1 evaluation. It resulted that gelatinase inhibition really has positive correlation with anti-HIV-1 activity, especially compounds 4m and 7h, which gave enhanced gelatinase inhibition in comparison with the positive control LY52, and also decent anti-HIV-1 potencies. The FlexX docking results provided a straightforward insight into the binding pattern between inhibitors and gelatinase, as well as the selective inhibition towards gelatinase over APN. Collectively, our research encouraged potent gelatinase inhibitors might be used in the development of anti-HIV-1 agents. And else, compounds 4m and 7h might be promising candidates to be considered for further chemical optimization. PMID:27039251

  4. Development and Preclinical Studies of Broad-spectrum Anti-HIV Agent (3′R,4′R)-3-Cyanomethyl-4-methyl-3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (3-Cyanomethyl-4-methyl-DCK)

    OpenAIRE

    Xie, Lan; Guo, Huan-Fang; LU, Hong; Zhuang, Xiao-Mei; Zhang, An-Ming; Wu, Gang; Ruan, Jin-xiu; Zhou, Ting; Yu, Donglei; Qian, Keduo; Lee, Kuo-Hsiung; Jiang, Shibo

    2008-01-01

    In prior investigation, we discovered that (3'R,4'R)-3-cyanomethyl-4-methyl-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (4, 3-cyanomethyl-4-methyl-DCK) showed promising anti-HIV activity. In these current studies, we developed and optimized successfully a practical ten-step synthesis for scale-up preparation to increase the overall yield of 4 from 7.8% to 32%. Furthermore, compound 4 exhibited broad-spectrum anti-HIV activity against wild-type and drug-resistant viral infection of CD4+ T ce...

  5. Design, synthesis and anti-HIV activity of novel quinoxaline derivatives.

    Science.gov (United States)

    Patel, Saloni B; Patel, Bhumika D; Pannecouque, Christophe; Bhatt, Hardik G

    2016-07-19

    In order to design novel anti-HIV agents, pharmacophore modelling, virtual screening, 3D-QSAR and molecular docking studies were performed. Pharmacophore model was generated using 17 structurally diverse molecules using DISCOtech followed by refinement with GASP module of Sybyl X. The best model containing four features; two donor sites, one acceptor atom and one hydrophobic region; was used as a query for virtual screening in NCI database and 6 compounds with Qfit value ≥98 were retrieved. The quinoxaline ring which is the bio-isostere of pteridine ring, retrieved as a hit in virtual screening, was selected as a core moiety. 3D-QSAR was carried on thirty five 5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested incorporation of hydrophobic, bulky and electronegative groups to increase potency of the designed compounds. 50 quinoxaline derivatives with different substitutions were designed on basis of both ligand based drug design approaches and were mapped on the best pharmacophore model. From this, best 32 quinoxaline derivatives were docked onto the active site of integrase enzyme and in-silico ADMET properties were also predicted. From this data, synthesis of top 7 quinoxaline derivatives was carried out and were characterized using Mass, (1)H-NMR and (13)C-NMR spectroscopy. Purity of compounds were checked using HPLC. These derivatives were evaluated for anti-HIV activity on III-B strain of HIV-1 and cytotoxicity studies were performed on VERO cell line. Two quinoxaline derivatives (7d and 7e) showed good results, which can be further explored to develop novel anti-HIV agents. PMID:27105027

  6. Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery

    OpenAIRE

    Zhou, Jiehua; Li, Haitang; Zhang, Jane; Piotr, Swiderski; Rossi, John

    2011-01-01

    The global epidemic of infection by HIV has created an urgent need for new classes of antiretroviral agents. The potent ability of small interfering (si)RNAs to inhibit the expression of complementary RNA transcripts is being exploited as a new class of therapeutics for a variety of diseases including HIV. Many previous reports have shown that novel RNAi-based anti-HIV/AIDS therapeutic strategies have considerable promise; however, a key obstacle to the successful therapeutic application and ...

  7. Twenty-six years of HIV science: an overview of anti-HIV drugs metabolism

    Directory of Open Access Journals (Sweden)

    Carolina Horta Andrade

    2011-06-01

    Full Text Available From the identification of HIV as the agent causing AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research over the past twenty-six years have been formidable. Currently, there are twenty-five anti-HIV compounds which have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs, protease inhibitors (PIs, cell entry inhibitors or fusion inhibitors (FIs, co-receptor inhibitors (CRIs, and integrase inhibitors (INIs. Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. Formation of active or toxic metabolites will also have an impact on the pharmacological and toxicological outcomes. Therefore, it is widely recognized that metabolism studies of a new chemical entity need to be addressed early in the drug discovery process. This paper describes an overview of the metabolism of currently available anti-HIV drugs.Da identificação do HIV como o agente causador da AIDS, ao desenvolvimento de fármacos antirretrovirais eficazes, os avanços científicos na pesquisa sobre o HIV nos últimos vinte e seis anos foram marcantes. Atualmente, existem vinte e cinco fármacos anti-HIV formalmente aprovados pelo FDA para utilização clínica no tratamento da AIDS. Estes compostos são divididos em seis classes: inibidores nucleosídeos de transcriptase reversa (INTR, inibidores nucleotídeos de transcriptase reversa (INtTR, inibidores não-nucleosídeos de transcriptase reversa (INNTR, inibidores de protease (IP, inibidores da entrada celular ou inibidores de fusão (IF, inibidores de co-receptores (ICR e inibidores de integrase (INI. O metabolismo consiste em um dos maiores determinantes do perfil farmacocinético de um fármaco. A forma

  8. Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

    OpenAIRE

    Nisachon Khunnawutmanotham; Nitirat Chimnoi; Arunee Thitithanyanont; Patchreenart Saparpakorn; Kiattawee Choowongkomon; Pornpan Pungpo; Supa Hannongbua; Supanna Techasakul

    2009-01-01

    Ten dipyridodiazepinone derivatives were synthesized and evaluated for their anti HIV-1 reverse transcriptase activity against wild-type and mutant type enzymes, K103N and Y181C. Two of them were found to be promising inhibitors for HIV-1 RT.

  9. Hydrogen bonds of anti-HIV active aminophenols

    Science.gov (United States)

    Belkov, M. V.; Ksendzova, G. A.; Skornyakov, I. V.; Sorokin, V. L.; Tolstorozhev, G. B.; Shadyro, O. I.

    2011-05-01

    Analysis of IR-Fourier spectra from solutions and crystals of antiviral sulfo-containing aminophenols has shown that various types of intramolecular and intermolecular interactions can occur in molecules of these compounds. Three types of intramolecular hydrogen bonds (O-HṡṡṡN, O-HṡṡṡO=S=O, and N-HṡṡṡO=S=O) are formed in CCl4 solutions of the sulfo-containing aminophenols. The formation of intermolecular H-bonds involving the NH- and OH-groups and the preservation of the intramolecular O-HṡṡṡO=S=O H-bond are characteristic of the anti-HIV active aminophenol crystals. Spectral attributes are determined in order to distinguish between the anti-HIV active and inactive sulfo-containing aminophenols.

  10. Natural antimicrobial peptides as promising anti-HIV candidates

    Science.gov (United States)

    Wang, Guangshun

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection remains to be one of the major global health problems. It is thus necessary to identify novel therapeutic molecules to combat HIV-1. Natural antimicrobial peptides (AMPs) have been recognized as promising templates for developing topical microbicides. This review systematically discusses over 80 anti-HIV peptides annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Such peptides have been discovered from bacteria, plants, and animals. Examples include gramicidin and bacteriocins from bacteria, cyclotides from plants, melittins and cecropins from insects, piscidins from fish, ascaphins, caerins, dermaseptins, esculentins, and maximins from amphibians, and cathelicidins and defensins from vertebrates. These peptides appear to work by different mechanisms and could block viral entry in multiple ways. As additional advantages, such anti-HIV peptides may possess other desired features such as antibacterial, antiparasital, spermicidal, and anticancer activity. With continued optimization of peptide stability, production, formulation and delivery methods, it is anticipated that some of these compounds may eventually become new anti-HIV drugs. PMID:26834391

  11. Self-delivery Multifunctional Anti-HIV Hydrogels for Sustained Release

    OpenAIRE

    Li, Jiayang; Li, Xinming; Kuang, Yi; Gao, Yuan; Du, Xuewen; Shi, Junfeng; Xu, Bing

    2013-01-01

    None of the clinical trials of anti-HIV gels based on conventional polymers or lipid emulsions is successful, suggesting the need of new molecular design of the anti-HIV gels. This paper reports the conversion of anti-HIV prodrugs into self-delivery supramolecular hydrogels. By covalently conjugating reverse transcriptase inhibitors to a versatile self-assembly motif, we obtained the hydrogelators that self-assemble to form supramolecular nanofibers as the matrices of hydrogels in a weak acid...

  12. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials.How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them.This article references the literature and the experience of reviewers,to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  13. Early-phase clinical trials of anti-HIV Drugs——understanding and discussion

    Institute of Scientific and Technical Information of China (English)

    LI YaJie; ZHAO Ming; ZHAO DeHeng

    2009-01-01

    Innovative anti-HIV drugs developed by local sponsors in China have come into the stage of early-phase clinical trials. How to systemically design the clinical trials of innovative anti-HIV drugs still remains a challenge for them. This article references the literature and the experience of reviewers, to introduce general considerations concerning early-phase clinical trials of innovative anti-HIV drugs.

  14. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Santos, Fernanda da Costa; Batalha, Pedro Netto; Brozeguini, Leonardo; Seidl, Peter R.; de Alencastro, Ricardo Bicca; Cunha, Anna Cláudia; de Souza, Maria Cecília B. V.; Ferreira, Vitor F.; Giongo, Viveca A.; Cirne-Santos, Cláudio; Paixão, Izabel C. P.

    2014-09-01

    Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.

  15. Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV.

    Science.gov (United States)

    De Clercq, Erik

    2009-04-01

    In 2008, 25 years after the human immunodeficiency virus (HIV) was discovered as the then tentative aetiological agent of acquired immune deficiency syndrome (AIDS), exactly 25 anti-HIV compounds have been formally approved for clinical use in the treatment of AIDS. These compounds fall into six categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine, efavirenz and etravirine); protease inhibitors (PIs: saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir); cell entry inhibitors [fusion inhibitors (FIs: enfuvirtide) and co-receptor inhibitors (CRIs: maraviroc)]; and integrase inhibitors (INIs: raltegravir). These compounds should be used in drug combination regimens to achieve the highest possible benefit, tolerability and compliance and to diminish the risk of resistance development. PMID:19108994

  16. Nanomedicine in the development of anti-HIV microbicides.

    Science.gov (United States)

    das Neves, José; Nunes, Rute; Rodrigues, Francisca; Sarmento, Bruno

    2016-08-01

    Prevention plays an invaluable role in the fight against HIV/AIDS. The use of microbicides is considered an interesting potential approach for topical pre-exposure prophylaxis of HIV sexual transmission. The prospects of having an effective product available are expected to be fulfilled in the near future as driven by recent and forthcoming results of clinical trials. Different dosage forms and delivery strategies have been proposed and tested for multiple microbicide drug candidates presently at different stages of the development pipeline. One particularly interesting approach comprises the application of nanomedicine principles to the development of novel anti-HIV microbicides, but its implications to efficacy and safety are not yet fully understood. Nanotechnology-based systems, either presenting inherent anti-HIV activity or acting as drug nanocarriers, may significantly influence features such as drug solubility, stability of active payloads, drug release, interactions between active moieties and virus/cells, intracellular drug delivery, drug targeting, safety, antiviral activity, mucoadhesive behavior, drug distribution and tissue penetration, and pharmacokinetics. The present manuscript provides a comprehensive and holistic overview of these topics as relevant to the development of vaginal and rectal microbicides. In particular, recent advances pertaining inherently active microbicide nanosystems and microbicide drug nanocarriers are discussed. PMID:26829288

  17. Evaluation of anti-HIV-1 activity of a new iridoid glycoside isolated from Avicenna marina, in vitro.

    Science.gov (United States)

    Behbahani, Mandana

    2014-11-01

    This study was carried out to check the efficacy of methanol seed extract of Avicenna marina and its column chromatographic fractions on Peripheral Blood Mono nuclear Cells (PBMCs) toxicity and HIV-1 replication. The anti-HIV-1 activities of crude methanol extract and its fractions were performed by use of real-time polymerase chain reaction (PCR) assay and HIV-1 p24 antigen kit. A time of drug addiction approach was also done to identify target of anti-HIV compound. The activity of the extracts on CD4, CD3, CD19 and CD45 expression in lymphocytes population was performed by use of flow cytometry. The most active anti-HIV agent was detected by spectroscopic analysis as 2'-O-(4-methoxycinnamoyl) mussaenosidic acid. The apparent effective concentrations for 50% virus replication (EC50) of methanol extract and iridoid glycoside were 45 and 0.1 μg/ml respectively. The iridoid glycoside also did not have any observable effect on the proportion of CD4, CD3, CD19 and CD45 cells or on the intensity of their expressions on PBMCs. In addition, the expression level of C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on CD4(+) T cells were decreased in cells treated with this iridoid glycoside. The reduction of these two HIV coreceptors and the result of time of addition study demonstrated that this iridoid glycoside restricts HIV-1 replication on the early stage of HIV infection. PMID:25239814

  18. The anti-HIV activities of photoactive terthiophenes

    International Nuclear Information System (INIS)

    Various synthetic analogues of naturally occurring terthiophene, α-terthienyl (αT), were evaluated for anti-human immunodeficiency virus (HIV) activity. The compounds were incubated individually with a known amount of virus, with or without UVA radiation (long-wavelength ultra violet) and residual virus was monitored for its ability to produce cytopathic effects in cell culture and the production of virus-specific protein. The basic terthiophene structure was essential for good anti-HIV activity, although various side chains, such as alcohols, bromo, methyl, thiomethyl and trimethylsilyl groups, permitted retention of maximum activity. Under optimum conditions, as little as 12 ng/mL of these compounds (i.e. approximately 3 x 10-8 M) could inactivate 103 infectious virions. None of the compounds however were more active than αT itself. In all cases, UVA radiation was essential. (Author)

  19. International award received recognizing anti-HIV spermicide.

    Science.gov (United States)

    1998-10-19

    Until recently, the only topical microbicide being considered for protection against sexually transmitted HIV infection contains nonoxynol-9 (N-9), a detergent ingredient widely used for more than 30 years in the form of gels, foams, aerosols, creams, sponges, suppositories, films, and foaming tablets. While N-9 has both spermicidal and antibacterial/antiviral properties against pathogens responsible for STDs, including HIV, recent clinical studies have found it to be ineffective in protecting against HIV and other STDs. Moreover, N-9 disrupts cell membranes, damages cervicovaginal epithelia, and causes an acute tissue inflammatory response, thus enhancing the likelihood of HIV infection. There is therefore an urgent need for new, effective, safe, and easy-to-use microbicides with anti-HIV activity lacking detergent-type membrane toxicity. Dr. Osmond D'Cruz et al. of the Hughes Institute in St. Paul, Minnesota, have developed an anti-HIV spermicide with the potential of becoming the active ingredient in many beneficial products. Its lead compound is 400 times more potent than N-9 against HIV and at least 10 times more potent than N-9 as a spermicide. These dual-function compounds are non-inflammatory by their nature. Hughes et al.'s discovery is expected to enter human clinical trials within 12 months. A clinical paper describing their achievement won the prestigious Prize Paper Award for the Plenary Session of the Conjoint 16th World Congress on Fertility and Sterility at the 54th Annual Meeting of the American Society of Reproductive Medicine, held in San Francisco, California, during October 4-9, 1998. PMID:12294481

  20. Estimation of Anti-HIV Activity of HEPT Analogues Using MLR, ANN, and SVM Techniques

    OpenAIRE

    Basheerulla Shaik; Tabassum Zafar; Vijay K. Agrawal

    2013-01-01

    The present study deals with the estimation of the anti-HIV activity (log1/C) of a large set of 107 HEPT analogues using molecular descriptors which are responsible for the anti-HIV activity. The study has been undertaken by three techniques MLR, ANN, and SVM. The MLR model fits the train set with R 2=0.856 while in ANN and SVM with higher values of R 2 = 0.850, 0.874, respectively. SVM model shows improvement to estimate the anti-HIV activity of trained data, while in test set ANN have highe...

  1. Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents†

    OpenAIRE

    Kuo, Reen-Yen; Qian, Keduo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2009-01-01

    This article reviews the antitumor and anti-HIV activities of naturally occurring triterpenoids, including the lupane, ursane, oleanane, lanostane, dammarane, and miscellaneous scaffolds. Structure–activity relationships of selected natural compounds and their synthetic derivatives are also discussed.

  2. Research Progression of Anti-HIV Chinese Medicines and Their Natural Active Ingredients

    OpenAIRE

    Jing Chen; Linchun Fu; Maoqing Li; Jiantao Chen

    2014-01-01

    Objective: To review the research progression of Chinese medicines for anti-human immunodeficiency virus (HIV) and their natural active ingredients at home and abroad so as to provide references for pharmaceutical research and clinical medication. Methods: Abundant representative literatures at home and abroad were classified to introduce the anti-HIV monomers, compounds and natural active ingredients of Chinese medicines. Results: The researches on anti-HIV natural medicines have obtained gr...

  3. Anti-HIV antibodies in the CSF of AIDS patients: a serological and immunoblotting study.

    OpenAIRE

    Bukasa, K S; Sindic, Christian; Bodéus, Monique; Burtonboy, Guy; Laterre, C; Sonnet, J.

    1988-01-01

    CSF and serum samples from 16 AIDS patients were tested for the presence of anti-HIV antibodies either by classical serological methods or by an immunoblot technique based on agarose gel isoelectric focusing and transfer of the specific IgG antibodies onto HIV antigens-loaded nitrocellulose sheets. This method enabled the demonstration of an intrathecal synthesis of anti-HIV oligoclonal IgG antibodies, often superimposed on diffuse polyclonal production, in 14 patients. The two negative cases...

  4. The highly specific carbohydrate-binding protein cyanovirin-N: structure, anti-HIV/Ebola activity and possibilities for therapy.

    Science.gov (United States)

    Barrientos, Laura G; Gronenborn, Angela M

    2005-01-01

    Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. CV-N was originally identified as a highly active anti-HIV agent and later, as a virucidal agent against other unrelated enveloped viruses such as Ebola, and possibly other viruses. CV-N's antiviral activity appears to involve unique recognition of N-linked high-mannose oligosaccharides, Man-8 and Man-9, on the viral surface glycoproteins. Due to its distinct mode of action and opportunities for harnessing the associated interaction for therapeutic intervention, a substantial body of research on CV-N has accumulated since its discovery in 1997. In this review we focus in particular on structural studies on CV-N and their relationship to biological activity. PMID:15638789

  5. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids

    Directory of Open Access Journals (Sweden)

    Vasu Nair

    2015-07-01

    Full Text Available HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibition data for the strand transfer (ST step are compared with in vitro anti-HIV data. The review also examines the issue of the lack of correlation between the ST enzymology data and anti-HIV assay results. Because this disconnect appeared to be a problem associated with permeability, prodrugs of these inhibitors were designed and synthesized. Prodrugs dramatically improved the anti-HIV activity data. For example, for compound, 96, the anti-HIV activity (EC50 improved from 500 nM for this diketo acid to 9 nM for its prodrug 116. In addition, there was excellent correlation between the IC50 and IC90 ST enzymology data for 96 (6 nM and 97 nM, respectively and the EC50 and EC90 anti-HIV data for its prodrug 116 (9 nM and 94 nM, respectively. Finally, it was confirmed that the prodrug 116 was rapidly hydrolyzed in cells to the active compound 96.

  6. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids.

    Science.gov (United States)

    Nair, Vasu; Okello, Maurice

    2015-01-01

    HIV integrase, encoded at the 3'-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of "no-return" in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibition data for the strand transfer (ST) step are compared with in vitro anti-HIV data. The review also examines the issue of the lack of correlation between the ST enzymology data and anti-HIV assay results. Because this disconnect appeared to be a problem associated with permeability, prodrugs of these inhibitors were designed and synthesized. Prodrugs dramatically improved the anti-HIV activity data. For example, for compound, 96, the anti-HIV activity (EC50) improved from 500 nM for this diketo acid to 9 nM for its prodrug 116. In addition, there was excellent correlation between the IC50 and IC90 ST enzymology data for 96 (6 nM and 97 nM, respectively) and the EC50 and EC90 anti-HIV data for its prodrug 116 (9 nM and 94 nM, respectively). Finally, it was confirmed that the prodrug 116 was rapidly hydrolyzed in cells to the active compound 96. PMID:26184144

  7. Notable Difference in anti-HIV Activity of Integrase Inhibitors as a Consequence of Geometric and Enantiomeric Configurations

    OpenAIRE

    Okello, Maurice; Mishra, Sanjay; Nishonov, Malik; Nair, Vasu

    2013-01-01

    While some examples are known of integrase inhibitors that exhibit potent anti-HIV activity, there are very few cases reported of integrase inhibitors that show significant differences in anti-HIV activity that result from distinctions in cis-and trans-configurations as well as enantiomeric stereostructure. We describe here the design and synthesis of two enantiomeric trans-hydroxycyclopentyl carboxamides which exhibit notable difference in anti-HIV activity. This difference is explained thro...

  8. Drogas anti-VIH: passado, presente e perspectivas futuras Drugs anti-HIV: past, present and future perspectives

    Directory of Open Access Journals (Sweden)

    Marcus Vinícius Nora de Souza

    2003-05-01

    Full Text Available Currently available anti-HIV drugs can be classified into three categories: nucleoside analogue reverse transcriptase inhibitors (NRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs and protease inhibitors (PIs. In addition to the reverse transcriptase (RT and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (1 viral adsorption, through binding to the viral envelope glycoprotein gp120; (2 viral entry, through blockage of the viral coreceptors CXCR4 and CCR5; (3 virus-cell fusion, through binding to the viral envelope glycoprotein gp 41; (4 viral assembly and disassembly through NCp7 zinc finger-targeted agents; (5 proviral DNA integration, through integrase inhibitors and (6 viral mRNA transcription, through inhibitors of the transcription (transactivation process. Also, various new NRTIs, NNRTIs and PIs have been developed, possessing different improved characteristics.

  9. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    International Nuclear Information System (INIS)

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

  10. Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV 5'TGGGAG3' Hotoda’s Sequence

    Directory of Open Access Journals (Sweden)

    Domenica Musumeci

    2012-10-01

    Full Text Available A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxycholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG3' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents.

  11. Estratégias farmacológicas para a terapia anti-AIDS Pharmacological strategies for anti-HIV therapy

    Directory of Open Access Journals (Sweden)

    Emerson Poley Peçanha

    2002-12-01

    Full Text Available The replicative cycle of HIV presents several events. The proteins involved in these events can be anticipated as pharmacological targets, aiming to the development of anti viral agents. Presently, there are fifteen commercially available anti-HIV drugs, which act at substrate binding site of reverse transcriptase (zidovudine, didanosine, zalcitabine, stavudine, lamivudine and abacavir, at a non-substrate binding site of reverse transcriptase (nevirapine, delavirdine and efavirenz, or by inhibiting HIV protease activity (saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. The present review focus both on these established classes of drugs and on new classes of compounds acting on other virus specific steps.

  12. Nevirapine Inhibits the Anti-HIV Activity of CD8+ Cells

    OpenAIRE

    Liu, Lianxing; Wang, Lin; Huang, Liusheng; Siu, Vincent; Teque, Fernando; Aweeka, Francesca T.; Levy, Jay A.

    2013-01-01

    Antiretroviral therapy (ART) significantly reduced the CD8+ cell non-cytotoxic anti-HIV response (CNAR) in twelve HIV-1-infected subjects (p < 0.0001). In separate experiments, CD8+ cells from long term survivors (LTS) were co-cultured with HIV-infected CD4+ cells using varying concentrations of anti-HIV drugs. The antiviral function of CD8+ cells from four of fourteen LTS was reduced with exposure to 10µM nevirapine (p < 0.05). The antiviral activity of CD8+ cells from two LTS was inhibited ...

  13. Abo and Rh Blood Groups Distribution in Hemophilia and Anti Hiv Positive Individuals

    Directory of Open Access Journals (Sweden)

    D.D. FARHUD

    1987-07-01

    Full Text Available A group of Iranian patients suffering from Factor VIII deficiency (Hemophilia A and treated with contaminated coagulation factor (imported, became seropositive as determined by ELISA method. Sixty of these individuals, which were available, were studied for ABO distribution. The B blood group in anti HIV pos. individuals (13.33% shows a significant decrease in comparison with the total (1504 of factor VIII hemophilia (21.87%. Statistical analysis of ABO distribution in anti HIV Pos. compared with hemophilia A and the control group showed x2 values of 6.86(0.10 > p>0.05 and 10.21(0.02> P >0.01 respectively.

  14. Synthesis and anti-HIV activity of new modified 1,2,3-triazole acyclonucleosides

    OpenAIRE

    Lazrek, H B; Taourirte, M; Oulih, T; Barascut, J L; Imbach, J L; Pannecouque, Christophe; Witvrouw, Myriam; De Clercq, Erik

    2001-01-01

    The synthesis of 1,2,3-triazole acyclonucleosides 7a-h via 1,3-dipolar cycloaddition of N-9/N-1-propargylpurine/pyrimidine 2a-h with azido-pseudo-sugar 4 is described and none of them had anti-HIV activity.

  15. New anti-HIV-1, antimalarial, and antifungal compounds from Terminalia bellerica

    DEFF Research Database (Denmark)

    Valsaraj, R; Pushpangadan, P; Smitt, U W;

    1997-01-01

    A bioactivity-guided fractionation of an extract of Terminalia bellerica fruit rind led to the isolation of two new lignans named termilignan (1) and thannilignan (2), together with 7-hydroxy-3',4'-(methylenedioxy)flavan (3) and anolignan B (4). All four compounds possessed demonstrable anti-HIV-......, antimalarial, and antifungal activity in vitro....

  16. Synthesis and anti-HIV Activity of New 3'-O-Phosphonomethyl Nucleosides

    Czech Academy of Sciences Publication Activity Database

    Česnek, Michal; Herdewijn, P.

    2010-01-01

    Roč. 82, č. 1 (2010), s. 663-687. ISSN 0385-5414 Institutional research plan: CEZ:AV0Z40550506 Keywords : anti-HIV * 4-(S)-ethynyl nucleotides * PMDTT Subject RIV: CC - Organic Chemistry Impact factor: 1.093, year: 2010

  17. 抗HIV巨噬细胞靶向给药系统的研究进展%Anti-HIV macrophage-targeted drug delivery systems:research advances

    Institute of Scientific and Technical Information of China (English)

    杜丽娜; 金义光

    2013-01-01

    巨噬细胞是人免疫缺陷病毒(HIV)的宿主,藏匿在巨噬细胞中的HIV能在适宜时机复制而导致艾滋病复发,因此,巨噬细胞可成为HIV的新传染源.目前大部分抗艾滋病药的细胞膜渗透性差、体内半衰期短,造成给药剂量大和次数频繁,并且难以在巨噬细胞内分布而清除残留HIV.因此抗HIV巨噬细胞靶向给药系统的研究很重要.本文综述了抗HIV药物的纳米给药系统及其巨噬细胞靶向作用,涉及纳米粒、脂质体、纳米混悬剂、自组装药物传递系统、纳米凝胶和纳米囊,为艾滋病治疗提供新思路.%Macrophages are the reservoir of human immunodeficiency virus (HIV). HIV hidden in the macrophages is replicated under appropriate conditions, leading to recurrence of AIDS. Macrophages are a new infection resource of HIV. Biomembrane penetration of current anti-HIV drugs is poor and the in vivo half life is short, resulting in high dose and frequent administration. Their distribution in macrophages is too little to eradicate the hidden HIV. Therefore, the development of anti-HIV macrophage-targeted delivery systems is very important. The review summarizes the nanoparticulate delivery systems of anti-HIV agents and their macrophage-targeted effects, involving nanoparticles, liposomes, nanosuspensions, self-assembled drug delivery systems, nanogels and nanocapsules, in order to provide a new strategy for the treatment of AIDS.

  18. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

    International Nuclear Information System (INIS)

    Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. In this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl) -1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)methyl]benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery

  19. Design and Synthesis of DiselenoBisBenzamides (DISeBAs) as Nucleocapsid Protein 7 (NCp7) Inhibitors with anti-HIV Activity.

    Science.gov (United States)

    Sancineto, Luca; Mariotti, Alice; Bagnoli, Luana; Marini, Francesca; Desantis, Jenny; Iraci, Nunzio; Santi, Claudio; Pannecouque, Christophe; Tabarrini, Oriana

    2015-12-24

    The interest in the synthesis of Se-containing compounds is growing with the discovery of derivatives exhibiting various biological activities. In this manuscript, we have identified a series of 2,2'-diselenobisbenzamides (DISeBAs) as novel HIV retroviral nucleocapsid protein 7 (NCp7) inhibitors. Because of its pleiotropic functions in the whole viral life cycle and its mutation intolerant nature, NCp7 represents a target of great interest which is not reached by any anti-HIV agent in clinical use. Using the diselenobisbenzoic scaffold, amino acid, and benzenesulfonamide derivatives were prepared and biologically profiled against different models of HIV infection. The incorporation of amino acids such as glycine and glutamate into DISeBAs 7 and 8 resulted in selective anti-HIV activity against both acutely and chronically infected cells as well as an interesting virucidal effect. DISeBAs demonstrated broad antiretroviral activity, encompassing HIV-1 drug-resistant strains including clinical isolates, as well as simian immunodeficiency virus (SIV). Time of addition experiments, along with the observed dose dependent inhibition of the Gag precursor proper processing, confirmed that their mechanism of action is based on NCp7 inhibition. PMID:26613134

  20. A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity

    OpenAIRE

    Chi, Guochen; Nair, Vasu; Semenova, Elena; Pommier, Yves

    2006-01-01

    We have synthesized novel phosphonic acid analogues of β-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of β-diketo phosphonic acids of structural, synthetic and antiviral interest.

  1. CADA, a novel CD4-targeted HIV inhibitor, is synergistic with various anti-HIV drugs in vitro

    OpenAIRE

    Vermeire, Kurt; Princen, Katrien; Hatse, Sigrid; De Clercq, Erik; Dey, Kaka; Bell, Thomas W.; Schols, Dominique

    2004-01-01

    OBJECTIVE: To evaluate the anti-HIV-1 activity of the cyclotriazadisulfonamide CADA against primary isolates in vitro and the combination of CADA with approved anti-HIV drugs for potential synergy. METHODS: Peripheral blood mononuclear cells (PBMC) were treated with CADA and infected with 16 different clinical isolates. After 8 days of infection, the median inhibitory concentration (IC50) was calculated from the p24 viral antigen content in the supernatant. MT-4 cells were infected with HIV-1...

  2. DNA Triplex-Based Complexes Display Anti-HIV-1-Cell Fusion Activity.

    Science.gov (United States)

    Xu, Liang; Zhang, Tao; Xu, Xiaoyu; Chong, Huihui; Lai, Wenqing; Jiang, Xifeng; Wang, Chao; He, Yuxian; Liu, Keliang

    2015-08-01

    DNA triplexes with hydrophobic modifications were designed and evaluated for their activity as inhibitors of the cell fusion of human immunodeficiency virus type 1 (HIV-1). Triplex inhibitors displayed low micromolar activities in the cell-cell fusion assay and nanomolar activities in the anti-HIV-1 pseudovirus test. Helix structure and the presence of sufficient numbers of hydrophobic regions were essential for the antifusion activity. Results from native polyacrylamide gel electrophoresis and a fluorescent resonance energy transfer-based inhibitory assay indicated that these triplexes may interact with the primary pocket at the glycoprotein 41 (gp41) N-heptad repeat, thereby inhibiting formation of the HIV-1 gp41 6-helical bundle. Triplex-based complexes may represent a novel category of HIV-1 inhibitors in anti-HIV-1 drug discovery. PMID:26192705

  3. Kan vericilerde HBsAg, anti-HCV, anti-HIV ve Sifilis seroprevalansı

    OpenAIRE

    Altındiş, Mustafa; Aslan, Savaş; Kalaycı, Raike

    2011-01-01

    Bu çalışmada Afyon Kocatepe Üniversitesi Tıp Fakültesi Kan Merkezi'ne başvuran donörlerde HBsAg, anti-HCV, anti-HIV 1/2 ve RPR seroprevalansının tespiti ve oranların yıllara ve cinsiyete göre dağılımının belirlenmesi amaçlanmıştır. Ocak'2001 ve Aralık'2010 tarihleri arasında Kan Merkezi'ne başvuran 37343 kan donörünün HBsAg, anti-HCV, anti-HIV ½ tarama testleri mikropartikül ELISA (Vitros, Ortho-Clinical Diagnostics) yöntemi ile Ortho-Clinical Diagnostics (HBsAg, HCV 3.jenerasyon, HIV 1/2) ki...

  4. 7,8-secolignans from Schisandra neglecta and their anti-HIV-1 activities

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei; Mu, Huaixue; Hu, Qiufen, E-mail: huqiufena@yahoo.com.cn [Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission and Ministry of Education, Yunnan University of Nationalities (China); Wang, Ruirui; Yang, Liumeng; Zheng, Yongtang [Kunming Institute of Zoology, Chinese Academy of Sciences (China); Sun, Handong; Xiao, Weilie, E-mail: xwl@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China)

    2012-10-15

    Four new 7,8-secolignans (neglectahenols A-D), together with two known 7,8-secolignans, were isolated from leaves and stems of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive one and two dimension NMR (nuclear magnetic resonance) techniques. 7,8-Secolignans and neglectahenols A-D were also tested for their anti-HIV-1 (human immunodeficiency virus type 1) activities, and all of them showed modest activities. (author)

  5. In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds.

    Science.gov (United States)

    Forthal, Donald N; Phan, Tran B; Slepenkin, Anatoly V; Landucci, Gary; Chu, Hencelyn; Elofsson, Mikael; Peterson, Ellena

    2012-10-01

    Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. In this study, the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides were determined. Inhibitory activity was assessed using TZM-bl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Antiviral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the antibacterial activity of salicylidene acylhydrazides is reversible by Fe(2+), the ability of Fe(2+) and other cations to reverse the anti-HIV-1 activity of the compounds was determined. Real-time PCR was also employed to determine the stage affected in the HIV-1 replication cycle. Four compounds with 50% inhibitory concentrations against HIV-1 of 1-7 μM were identified. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether the target for virus replication was TZM-bl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe(2+), but not other cations, reversed the anti-HIV-1 effect. Finally, the inhibitory effect of the compounds occurred at a post-integration step. In conclusion, salicylidene acylhydrazides were identified with in vitro anti-HIV-1 activity in the micromolar range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide. PMID:22819150

  6. Ab Initio Study on the Anti-HIV Activities of Hydroxyflavones

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu

    2005-01-01

    Flavone and 95 hydroxyflavones have been studied with ab initio method, and their total energies, atomic charges, dipole moments, multipole moments, molecular orbital compositions, orbital energies etc. were obtained. Among them the relationship between total atomic charges and activities against HIV is basically in accordance with the experimental results. The beneficial references are provided for the extraction and synthesis of strong active anti-HIV medicines.

  7. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma

    OpenAIRE

    Martellini, Julie A.; Amy L Cole; Venkataraman, Nitya; Quinn, Gerry A.; Svoboda, Pavel; Bhushan K Gangrade; Pohl, Jan; Sørensen, Ole E.; Cole, Alexander M.

    2009-01-01

    Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation ...

  8. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

    OpenAIRE

    Esteves, Ana I. S.; Joao Goncalves; Madalena Humanes; Marisa Nicolai

    2011-01-01

    The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition). Cliona celata pellets showed low polysacch...

  9. CD25 Preselective Anti-HIV Vectors for Improved HIV Gene Therapy

    OpenAIRE

    Kalomoiris, Stefanos; Lawson, Je'Tai; Chen, Rachel X.; Bauer, Gerhard; Nolta, Jan A.; Anderson, Joseph S.

    2012-01-01

    As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy ...

  10. 7,8-secolignans from Schisandra neglecta and their anti-HIV-1 activities

    International Nuclear Information System (INIS)

    Four new 7,8-secolignans (neglectahenols A-D), together with two known 7,8-secolignans, were isolated from leaves and stems of Schisandra neglecta. The structures were elucidated by spectroscopic methods, including extensive one and two dimension NMR (nuclear magnetic resonance) techniques. 7,8-Secolignans and neglectahenols A-D were also tested for their anti-HIV-1 (human immunodeficiency virus type 1) activities, and all of them showed modest activities. (author)

  11. CD8+ Cell Anti-HIV Activity Rapidly Increases Upon Discontinuation of Early Antiretroviral Therapy

    OpenAIRE

    Killian, M. Scott; Roop, Jeremy; Ng, Sharon; Frederick M Hecht; Levy, Jay A.

    2009-01-01

    CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. CD8+ lymphocytes from subjects with untreated primary HIV-1 in...

  12. In vitro screening of traditional medicines for anti-HIV activity: memorandum from a WHO meeting.

    OpenAIRE

    1989-01-01

    Many plant products are being used by patients with acquired immunodeficiency syndrome (AIDS) in some countries without any scientific proof that they possess anti-HIV (human immunodeficiency virus) activity. Traditional healers are now offering their remedies for scientific evaluation, and a few studies provide information on the inhibitory activity against HIV of plants such as Viola yedoensis, Arctium lappa, Epimedium grandiflorum, Glycyrrhiza uralensis and Castanospermum australe. Natural...

  13. Novel multi-component nanopharmaceuticals derived from poly(ethylene glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

    Directory of Open Access Journals (Sweden)

    Rabson Arnold B

    2006-04-01

    Full Text Available Abstract Background Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties. Results Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more potent than L-Tat9 while the addition of biotin resulted in a prodrug that was 2850 times more potent than L-Tat9. Flow cytometry and confocal microscopy studies suggest that variations in intracellular uptake and intracellular localization, as well as synergistic inhibitory effects of SQV and Tat peptides, contributed to the unexpected and substantial differences in antiviral activity. Conclusion Our results demonstrate that highly potent nanoscale multi-drug conjugates with low non-specific toxicity can be produced by combining moieties with anti-HIV agents for different targets onto macromolecules having improved delivery properties.

  14. Seropositivity of HBsAg, anti-HCV and anti-HIV in preoperative patients

    Directory of Open Access Journals (Sweden)

    Berrin Karaayak Uzun

    2014-12-01

    Full Text Available Objective: The infections caused by human immunodeficiency virus (HIV, hepatitis B (HBV and C (HCV viruses pose a serious occupational risk for the healthcare workers especially those in emergency services, laboratories and surgery wards. Vaccination and establishment of the strict biosafety procedures are the main principles to prevent blood-borne infections in healthcare workers. Additionally, serological screening of the preoperative patients could decrease the risk for exposure. In this study, we aimed to determine the seroprevalence of HBsAg, anti-HCV, anti-HIV 1/2 in preoperative patients. Methods: Hospital automation records were evaluated retrospectively for 4.367 patients who were scheduled for surgery and scanned for anti-HIV 1/2, HBsAg and anti-HCV as preoperative procedures in the preparation period of operation between January 2012 and December 2012. Results: HBsAg positivity rate was found in 7.7% (n=336, anti-HCV positivity rate was found in 2.3% (n=101. A two (0.05% of five patients were positive for anti-HIV 1/2 was found positive verification test and the other three samples were accepted as false positive test results. Conclusion: All healthcare workers must be trained about occupational diseases and vaccinated against Hepatitis B. Universal precautions must be strictly followed particularly in the operating room. In addition, all patients should be considered as potential carriers regarded as a carrier of the potential for infection. J Clin Exp Invest 2013; 4 (4: 449-452

  15. Structure and conformational analysis of the anti-HIV AZT 5'-aminocarbonylphosphonate prodrug using DFT methods

    International Nuclear Information System (INIS)

    Graphical abstract: The phosphonate prodrug studied offers an excellent potential as alternative to AZT. Display Omitted Highlights: → The phosphonate prodrug studied offers an excellent potential as alternative to AZT. → The 84 most energetically favourable conformers were identified by DFT methods. → The increment in the ring puckering produces a higher flexibility than in AZT. → The high charge on the oxygen's chain could explain the high activity of this prodrug. → The phosphonate chain has little influence in the charge distribution on the rings. - Abstract: A comprehensive theoretical conformational analysis of the anti-HIV AZT 5'-aminocarbonylphosphonate prodrug was carried out, due to this prodrug has noticeable advantage over approved drugs AZT and Nikavir. The whole conformational parameters (χ, γ, β, α, δ, ε, τ, P, νmax) were analysed as well as the NBO Natural atomic charges. The calculations were carried out by means of B3LYP/6-31G** and B3LYP/6-311++G(3df,pd) DFT levels of theory with full relaxation of all geometrical parameters. The search located at least 86 stable structures, 6 of which are within a 1 kcal/mol electronic energy range of the global minimum and 11 conformers are within a 1 kcal/mol Gibbs energy range. The global minimum with the 6-311++G(3df,pd) basis set corresponds to the calculated values of the exocyclic torsional angles χ = -121.6 deg., β = 153.0 deg., γ = -152.0 deg. and α = -74.1 deg. The results obtained are in accordance to those found in related anti-HIV nucleoside Analogs. Comparisons of the conformers with those determined in the common anti-HIV drug AZT were carried out. Several correlations and general conclusions were emphasized.

  16. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi

    Directory of Open Access Journals (Sweden)

    Wan-Fei Li

    2015-11-01

    Full Text Available Henrin A (1, a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D and two-dimensional (2D NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2.

  17. Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi.

    Science.gov (United States)

    Li, Wan-Fei; Wang, Juan; Zhang, Jing-Jie; Song, Xun; Ku, Chuen-Fai; Zou, Juan; Li, Ji-Xin; Rong, Li-Jun; Pan, Lu-Tai; Zhang, Hong-Jie

    2015-01-01

    Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2). PMID:26610490

  18. Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids

    OpenAIRE

    Vasu Nair; Maurice Okello

    2015-01-01

    HIV integrase, encoded at the 3′-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of “no-return” in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyridinone scaffolds. Methodologies for synthesis of these compounds are discussed. Integrase inhibiti...

  19. Asymmetric Total Synthesis of (+)- and (−)-Clusianone and (+)- and (−)Clusianone Methyl Enol Ether via ACC Alkylation and Evaluation of their Anti-HIV Activity

    OpenAIRE

    Garnsey, Michelle R.; Matous, James A.; Kwiek, Jesse J; Coltart, Don M.

    2011-01-01

    The total asymmetric synthesis of (+)- and (−)-clusianone and (+)- and (−)-clusianone methyl enol ether is reported. Asymmetric induction is achieved through the use of ACC alkylation, providing the key intermediates with an er of 99:1. The four synthetic compounds were evaluated for their anti-HIV activity. Both (+)- and (−)-clusianone displayed significant anti-HIV activity.

  20. Enhanced transdermal delivery of an anti-HIV agent via ethanolic liposomes.

    Science.gov (United States)

    Dubey, Vaibhav; Mishra, Dinesh; Nahar, Manoj; Jain, Vikas; Jain, Narendra Kumar

    2010-08-01

    Indinavir, as a protease inhibitor with a short biological half life, variable pH-dependent oral absorption, and extensive first-pass metabolism, presents a challenge with respect to its oral administration. The current work aims to formulate and characterize indinavir-bearing ethanolic liposomes (ethosomes), and to investigate their enhanced transdermal delivery potential. The prepared ethanolic liposomes were characterized to be spherical, unilamellar structures having low polydispersity, nanometric size range, and improved entrapment efficiency over other delivery formulations. Permeation studies of indinavir across human cadaver skin resulted in enhanced transdermal flux from ethanolic liposomes that was significantly (P ethosomes), and investigate their enhanced transdermal delivery potential, demonstrating a potentially a suitable approach for transdermal delivery of this protease inhibitor for HIV treatment, which typically has been associated with limited bioavailability via the oral route. PMID:20093197

  1. An investigation on ABO and Rh blood groups and HBsAg, anti-HIV, VDRL positivity

    OpenAIRE

    GENÇ, Dr. Metin; ASLAN, Dr. Turan

    1997-01-01

    Using records, we screened 2500 blood donors for blood groups, hepatitis-B surface antigen (HBsAg), anti-HIV, and VDRL. The results were analysed to assess the prevalence and the possible relation to sex and blood groups. Our present study was done at Regional Blood Center in Malatya province. The distribution of blood groups was compared with other studies. Our findings suggested that the prevalence of HBsAg was 5.16% in the donor population. VDRL and anti-HIV positivity were not found. HBsA...

  2. Coating flow of non-Newtonian anti-HIV microbicide vehicles

    Science.gov (United States)

    Park, Su Chan; Szeri, Andrew; Verguet, Stéphane; Katz, David; Weiss, Aaron

    2008-11-01

    Elastohydrodynamic lubrication over soft substrates is of importance for the drug delivery functions of vehicles for anti-HIV topical microbicides. These are intended to inhibit transmission into vulnerable mucosa, e.g. in the vagina. First generation prototype microbicides have gel vehicles, which spread after insertion and coat luminal surfaces. Effectiveness derives from potency of the active ingredients and completeness and durability of coating. Delivery vehicle rheology, luminal biomechanical properties and the force due to gravity influence the coating mechanics. We develop a framework for understanding the relative importance of boundary squeezing and body forces on the extent and speed of the coating that results. In the case of a shear-thinning fluid, the Carreau number also plays a role. Numerical solutions are developed for a range of conditions and materials. Results are interpreted with respect to tradeoffs between wall elasticity, longitudinal forces, bolus viscosity and bolus volume. These provide initial insights of practical value for formulators of non-Newtonian gel delivery vehicles for anti-HIV microbicidal formulations.

  3. Sulfated Polysaccharides in Marine Sponges: Extraction Methods and Anti-HIV Activity

    Directory of Open Access Journals (Sweden)

    Ana I. S. Esteves

    2011-01-01

    Full Text Available The extraction, fractionation and HIV-1 inhibition potential of polysaccharides extracted from three species of marine sponges, Erylus discophorus, Cliona celata and Stelletta sp., collected in the Northeastern Atlantic, is presented in this work. The anti-HIV activity of 23 polysaccharide pellets and three crude extracts was tested. Crude extracts prepared from Erylus discophorus specimens were all highly active against HIV-1 (90 to 95% inhibition. Cliona celata pellets showed low polysaccharide content (bellow 38.5% and almost no anti-HIV activity (<10% inhibition. Stelletta sp. pellets, although quite rich in polysaccharide (up to 97.3%, showed only modest bioactivity (<36% HIV-1 inhibition. Erylus discophorus pellets were among the richest in terms of polysaccharide content (up to 98% and the most active against HIV-1 (up to 95% inhibition. Chromatographic fractionation of the polysaccharide pellet obtained from a specimen of Erylus discophorus (B161 yielded only modestly active fractions. However, we could infer that the active molecule is most probably a high molecular weight sulfated polysaccharide (>2000 kDa, whose mechanism is possibly preventing viral attachment and entry (fusion inhibitor.

  4. Voluntariado e negociação de protocolos de vacinas anti-HIV no Brasil Volunteers and negotiation of anti-HIV vaccine protocols in Brazil

    Directory of Open Access Journals (Sweden)

    Gisela Cordeiro Pereira Cardoso

    2010-07-01

    Full Text Available O estudo acompanhou a rotina de um ensaio clínico de vacinas experimentais anti-HIV no Rio de Janeiro, Brasil, focalizando os processos de recrutamento, seleção e seguimento dos voluntários. Utilizaram-se técnicas de observação da rotina do centro de pesquisas e entrevistas a profissionais e voluntários. Os resultados evidenciaram que o ensaio é uma atividade coletiva, em que constantes negociações são necessárias entre o que é exigido pelo protocolo e o que precisa, pode ou deve ser adaptado para que ele funcione, em função de situações como: tempo prolongado de aprovação do estudo pelas instâncias regulatórias, dificuldades no recrutamento de voluntários, até problemas maiores como a descontinuidade das vacinações (ocorrida no protocolo estudado. Discute-se como a aplicação do protocolo transborda o script técnico-científico, transformando-se em um objeto fronteiriço entre mundos sociais diferentes. O protocolo é adaptado segundo uma ordem local, de acordo com a dinâmica das relações sociais, não podendo desconsiderar-se a constante inter-relação entre ciência, sociedade, técnica e política.This study monitored the protocol of a clinical trial for experimental anti-HIV vaccines in Rio de Janeiro, Brazil, focusing on the recruitment, selection, and follow-up of volunteers. The techniques included observation of the research center's routine and interviews with health professionals and volunteers. The results show that the trial is a collective activity, in which constant negotiations are needed between the protocol requirements and what can, should, or must be adapted in order for it to work, as a function of: prolonged time before the trial's approval by the regulatory bodies, difficulties in recruiting volunteers, and even larger problems like discontinuity in the vaccines (which occurred in a specific protocol. The article discusses how the protocol's application extends beyond the technical and

  5. Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket.

    Science.gov (United States)

    Yang, Jiapei; Chen, Wenmin; Kang, Dongwei; Lu, Xueyi; Li, Xiao; Liu, Zhaoqiang; Huang, Boshi; Daelemans, Dirk; Pannecouque, Christophe; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

    2016-02-15

    The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 μM to 1.99 μM. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), Ia (EC50 = 43 nM) and IIa (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib, IIb and IIh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of IIb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 μM), 50 times more than DLV (EC50 = 2.48 μM) and about 3 times more than EFV (EC50 = 0.12 μM), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. PMID:26802545

  6. Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery.

    Science.gov (United States)

    Mashingaidze, Felix; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Maharaj, Vinesh; Buchmann, Eckhart; Pillay, Viness

    2016-04-30

    This paper explores the potential of polyethylene glycol enclatherated pectin-mucin (PEG-encl-PEC:MUC) submicron matrices (SMMs) as an intravaginal drug delivery system capable of delivering an anti-HIV-1 agent (zidovudine; AZT) over a prolonged duration. A three factor and three level (3(3)) Box-Behnken statistical design was employed to optimize the SMMs. Optimized PEG-encl-PEC:MUC SMMs prepared as a stable W/O emulsion (determined by the degree of reversible colloidal phenomena) were spherical with a mean particle size of 270.6±5.533nm and mean zeta potential of -34.4±0.539mV. The microencapsulation of AZT and the hydrogen bonding mediated shielding of AZT by SMMs was confirmed by Fourier Transform Infrared (FTIR) analysis. The thermochemical (differential scanning calorimetry and thermogravimetric analysis) data proposed that Ca(2+)-based macromolecular ionic crosslinking as well as the intermolecular interactions may be responsible for the thermal stability of the delivery system. The partially amorphous nature of drug-loaded SMMs, as confirmed by X-ray diffraction patterns, further strengthened the matricization of AZT into the pectin-mucin matrix. In vitro drug release studies from the SMMs showed approximately 91% zidovudine release in simulated vaginal fluid (SVF) and 94% in phosphate buffered saline (PBS) in 24h. The mean dissolution time (MDT) of zidovudine from the SMMs was 5.974h. The attainment of required dimensional structure and drug release profiles from SMMs highlights the potential of their inclusion into a secondary carrier system for extended and controlled intravaginal stay. PMID:26943973

  7. Construction of Ru(II) Polypyridyl Based Macrocycles: Synthesis, Characterization, Electrochemical, Li+ Binding, Antitumour and Anti-HIV properties

    OpenAIRE

    Mishra, Lallan; Sinha, Ragini; Pandey, P. C.

    2001-01-01

    Some ruthenium (II) polypyridyl complexes with a bis-chalcone (obtained by the condensation of 3-methyl-thiophene-2-carboxaldehyde and 4-acetyl pyridine) have been synthesized and characterized spectroscopically (IR, NMR, UV/Vis), conductimetric, elemental analysis and FAB mass data. Their luminescent, redox and Li+ binding properties have been studied. The anti-HIV and antitumour activities have also been reported.

  8. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy

    Science.gov (United States)

    Lee, Sulggi A.; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R.; O’Doherty, Una; Palmer, Sarah; Richman, Douglas D.; Siliciano, Janet D.; Yukl, Steven A.; Deeks, Steven G.; Burbelo, Peter D.

    2016-01-01

    Background A major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the “reservoir”). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART). Methods We evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables. Results Among 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate models including age and duration of ART did not markedly alter results. Conclusions Our findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV

  9. Anti-HIV-1 activity of flavonoid myricetin on HIV-1 infection in a dual-chamber in vitro model.

    Directory of Open Access Journals (Sweden)

    Silvana Pasetto

    Full Text Available HIV infection by sexual transmission remains an enormous global health concern. More than 1 million new infections among women occur annually. Microbicides represent a promising prevention strategy that women can easily control. Among emerging therapies, natural small molecules such as flavonoids are an important source of new active substances. In this study we report the in vitro cytotoxicity and anti-HIV-1 and microbicide activity of the following flavonoids: Myricetin, Quercetin and Pinocembrin. Cytotoxicity tests were conducted on TZM-bl, HeLa, PBMC, and H9 cell cultures using 0.01-100 µM concentrations. Myricetin presented the lowest toxic effect, with Quercetin and Pinocembrin relatively more toxic. The anti-HIV-1 activity was tested with TZM-bl cell plus HIV-1 BaL (R5 tropic, H9 and PBMC cells plus HIV-1 MN (X4 tropic, and the dual tropic (X4R5 HIV-1 89.6. All flavonoids showed anti-HIV activity, although Myricetin was more effective than Quercetin or Pinocembrin. In TZM-bl cells, Myricetin inhibited ≥90% of HIV-1 BaL infection. The results were confirmed by quantification of HIV-1 p24 antigen in supernatant from H9 and PBMC cells following flavonoid treatment. In H9 and PBMC cells infected by HIV-1 MN and HIV-1 89.6, Myricetin showed more than 80% anti-HIV activity. Quercetin and Pinocembrin presented modest anti-HIV activity in all experiments. Myricetin activity was tested against HIV-RT and inhibited the enzyme by 49%. Microbicide activities were evaluated using a dual-chamber female genital tract model. In the in vitro microbicide activity model, Myricetin showed promising results against different strains of HIV-1 while also showing insignificant cytotoxic effects. Further studies of Myricetin should be performed to identify its molecular targets in order to provide a solid biological foundation for translational research.

  10. Differential gene expression in CD8+ cells exhibiting noncytotoxic anti-HIV activity

    International Nuclear Information System (INIS)

    Suppressive subtractive hybridization with polymerase chain reaction was used to identify the gene(s) associated with the CD8+ cell noncytotoxic anti-HIV response. The differences in gene expression profiles of CD8+ cells from a pair of discordant HIV-positive identical twins were studied. Forty-nine genes were identified as expressed at higher levels in the CD8+ cells from the infected twin that inhibited viral replication. The differential expression of these genes was then evaluated using Q-PCR to determine if this gene expression pattern is evident in CD8+ cells from other HIV-positive subjects showing this antiviral activity. Three genes, including one unknown, were found to have significantly increased expression in antiviral CD8+ cells

  11. Electronic structure and spectroscopic properties of anti-HIV active aminophenols

    Science.gov (United States)

    Bazyl', O. K.; Artyukhov, V. Ya.; Maier, G. V.; Tolstorozhev, G. B.; Raichenok, T. F.; Skornyakov, I. V.; Shadyro, O. I.; Sorokin, V. L.; Ksendzova, G. A.

    2012-02-01

    We have measured the absorption and fluorescence spectra and fluorescence quantum yields of sulphone-containing anti-HIV active o-aminophenol molecules in an inert solvent, hexane, and in a polar solvent, acetonitrile. We have studied IR Fourier-transform spectra and examined structural features of o-aminophenols with different substituents in solutions and crystals. Functional groups of molecules that are involved in the formation of hydrogen bonds have been revealed. Proton acceptor properties of o-aminophenol molecules have been theoretically evaluated using the method of molecular electrostatic potential. Using quantum chemistry methods, we have calculated and interpreted absorption and fluorescence spectra of o-aminophenols. Calculation data are compared with experimental results. We have determined the main channels and mechanisms of photophysical relaxation processes in o-aminophenols.

  12. Role of seminal plasma in the anti-HIV-1 activity of candidate microbicides

    Directory of Open Access Journals (Sweden)

    Li Yun-Yao

    2006-10-01

    Full Text Available Abstract Background Evaluation of microbicides for prevention of HIV-1 infection in macaque models for vaginal infection has indicated that the concentrations of active compounds needed for protection by far exceed levels sufficient for complete inhibition of infection in vitro. These experiments were done in the absence of seminal plasma (SP, a vehicle for sexual transmission of the virus. To gain insight into the possible effect of SP on the performance of selected microbicides, their anti-HIV-1 activity in the presence, and absence of SP, was determined. Methods The inhibitory activity of compounds against the X4 virus, HIV-1 IIIB, and the R5 virus, HIV-1 BaL was determined using TZM-bl indicator cells and quantitated by measuring β-galactosidase induced by infection. The virucidal properties of cellulose acetate 1,2-benzene-dicarboxylate (CAP, the only microbicide provided in water insoluble, micronized form, in the presence of SP was measured. Results The HIV-1 inhibitory activity of the polymeric microbicides, poly(naphthalene sulfonate, cellulose sulfate, carrageenan, CAP (in soluble form and polystyrene sulfonate, respectively, was considerably (range ≈ 4 to ≈ 73-fold diminished in the presence of SP (33.3%. Formulations of micronized CAP, providing an acidic buffering system even in the presence of an SP volume excess, effectively inactivated HIV-1 infectivity. Conclusion The data presented here suggest that the in vivo efficacy of polymeric microbicides, acting as HIV-1 entry inhibitors, might become at least partly compromised by the inevitable presence of SP. These possible disadvantages could be overcome by combining the respective polymers with acidic pH buffering systems (built-in for formulations of micronized CAP or with other anti-HIV-1 compounds, the activity of which is not affected by SP, e.g. reverse transcriptase and zinc finger inhibitors.

  13. Conditional Cytotoxic Anti-HIV Gene Therapy for Selectable Cell Modification.

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2016-05-01

    Gene therapy remains one of the potential strategies to achieve a cure for HIV infection. One of the major limitations of anti-HIV gene therapy concerns recovering an adequate number of modified cells to generate an HIV-proof immune system. Our study addresses this issue by developing a methodology that can mark conditional vector-transformed cells for selection and subsequently target HIV-infected cells for elimination by treatment with ganciclovir (GCV). We used the herpes simplex virus thymidine kinase (TK) mutant SR39, which is highly potent at killing cells at low GCV concentrations. This gene was cloned into a conditional HIV vector, pNL-GFPRRESA, which expresses the gene of interest as well as green fluorescent protein (GFP) in the presence of HIV Tat protein. We show here that TK-SR39 was more potent that wild-type TK (TK-WT) at eliminating infected cells at lower concentrations of GCV. As the vector expresses GFP in the presence of Tat, transient expression of Tat either by Tat RNA transfection or transduction by a nonintegrating lentiviral (NIL) vector marked the cells with GFP for selection. In cells selected by this strategy, TK-SR39 was more potent at limiting virus replication than TK-WT. Finally, in Jurkat cells modified and selected by this approach, infection with CXCR4-tropic Lai virus could be suppressed by treatment with GCV. GCV treatment limited the number of HIV-infected cells, virus production, as well as virus-induced cytopathic effects in this model. We provide proof of principle that TK-SR39 in a conditional HIV vector can provide a safe and effective anti-HIV strategy. PMID:26800572

  14. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges.

    Science.gov (United States)

    Gautam, Rajeev; Nishimura, Yoshiaki; Pegu, Amarendra; Nason, Martha C; Klein, Florian; Gazumyan, Anna; Golijanin, Jovana; Buckler-White, Alicia; Sadjadpour, Reza; Wang, Keyun; Mankoff, Zachary; Schmidt, Stephen D; Lifson, Jeffrey D; Mascola, John R; Nussenzweig, Michel C; Martin, Malcolm A

    2016-05-01

    Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission. PMID:27120156

  15. Flazinamide, a novel β-carboline compound with anti-HIV actions

    International Nuclear Information System (INIS)

    A β-carboline compound, flazin isolated from Suillus granulatus has been shown weak anti-HIV-1 activity. Based on the structure of flazin, flazinamide [1-(5'- hydromethyl-2'-furyl)-β-carboline-3-carboxamide] was synthesized and its anti-HIV activities were evaluated in the present study. The cytotoxicity of flazinamide was about 4.1-fold lower than that of flazin. Flazinamide potently reduced syncytium formation induced by HIV-1IIIB with EC50 value of 0.38 μM, the EC50 of flazinamide was about 6.2-fold lower than that of flazin. Flazinamide also inhibited HIV-2ROD and HIV-2CBL-20 infection with EC50 values of 0.57 and 0.89 μM, respectively. Flazinamide reduced p24 antigen expression in HIV-1IIIB acute infected C8166 and in clinical isolated strain HIV-1KM018 infected PBMC, with EC50 values of 1.45 and 0.77 μM, respectively. Flazinamide did not suppress HIV-1 replication in chronically infected H9 cells. Flazinamide blocked the fusion between normal cells and HIV-1 or HIV-2 chronically infected cells. It weakly inhibited activities of recombinant HIV-1 reverse transcriptase, protease or integrase at higher concentrations. In conclusion, the conversion of the carboxyl group in 3 position of flazin markedly enhanced the anti-viral activity (TI value increased from 12.1 to 312.2) and flazinamide might interfere in the early stage of HIV life cycle

  16. Inhibition of Anti-HIV MicroRNA Expression: A Mechanism for Opioid-Mediated Enhancement of HIV Infection of Monocytes

    OpenAIRE

    Wang, Xu; Ye, Li; Zhou, Yu; Liu, Man-Qing; Zhou, Dun-Jin; Ho, Wen-Zhe

    2011-01-01

    Several micro RNAs (miRNAs) have the ability to inhibit HIV replication in target cells. Thus, we investigated the impact of opioids (morphine and heroin), widely abused drugs among people infected with HIV, on the expression of cellular anti-HIV miRNAs in monocytes. We found that morphine-treated monocytes expressed lower levels of cellular anti-HIV miRNAs than untreated cells. In addition, morphine treatment of monocytes compromised type I interferon (IFN)–induced anti-HIV miRNA expression....

  17. Asymmetric Total Synthesis of (+)- and (−)-Clusianone and (+)- and (−)Clusianone Methyl Enol Ether via ACC Alkylation and Evaluation of their Anti-HIV Activity

    Science.gov (United States)

    Garnsey, Michelle R.; Matous, James A.; Kwiek, Jesse J.; Coltart, Don M.

    2011-01-01

    The total asymmetric synthesis of (+)- and (−)-clusianone and (+)- and (−)-clusianone methyl enol ether is reported. Asymmetric induction is achieved through the use of ACC alkylation, providing the key intermediates with an er of 99:1. The four synthetic compounds were evaluated for their anti-HIV activity. Both (+)- and (−)-clusianone displayed significant anti-HIV activity. PMID:21414776

  18. [HPLC enantioseparation, absolute configuration determination and anti-HIV-1 activity of (±)-F18 enantiomers].

    Science.gov (United States)

    Zhang, Lei-lei; Xue, Hai; Li, Li; Lu, Xiao-fan; Chen, Zhi-wei; Lu, Gang

    2015-06-01

    Racemic (±)-F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide A), an analog of nature product (+)-calanolide A, is a new anti-HIV-1 nonnucleoside reverse transcript inhibitor (NNRTI). A successful enantioseparation of (±)-F18 offering (R)-F18 and (S)-F18 was achieved by a chiral stationary phase prepared HPLC. Their absolute configurations were determined by measurement of their electronic circular dichroisms combined with modem quantum-chemical calculations. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses. PMID:26521445

  19. HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Olofsson, S; Nielsen, Jens Ole;

    1994-01-01

    To characterize the role of the humoral immune response on HIV-1 infection of monocytes and macrophages (M phi s) we examined the susceptibility of in vitro cultured monocyte/M phi s to various HIV-1 isolates and the influence of heterologous and particularly autologous anti HIV-1 sera on this...... infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately...... CD4 and that post binding events may be common to the infection of lymphocytes. Anti HIV-1 sera showed neutralizing activity against heterologous and even autologous escape virus. This finding, together with the observation that monocytes and M phi s are infected in vivo, suggests that protection...

  20. Aaptamine Derivatives with Antifungal and Anti-HIV-1 Activities from the South China Sea Sponge Aaptos aaptos

    Directory of Open Access Journals (Sweden)

    Hao-Bing Yu

    2014-12-01

    Full Text Available Five new alkaloids of aaptamine family, compounds (1–5 and three known derivatives (6–8, have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated by spectroscopic analyses, as well as by comparison with the literature data. Compounds 1–2 are characterized with triazapyrene lactam skeleton, whereas compounds 4–5 share an imidazole-fused aaptamine moiety. These compounds were evaluated in antifungal and anti-HIV-1 assays. Compounds 3, 7, and 8 showed antifungal activity against six fungi, with MIC values in the range of 4 to 64 μg/mL. Compounds 7–8 exhibited anti-HIV-1 activity, with inhibitory rates of 88.0% and 72.3%, respectively, at a concentration of 10 μM.

  1. Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study.

    Science.gov (United States)

    Chaniad, Prapaporn; Wattanapiromsakul, Chatchai; Pianwanit, Somsak; Tewtrakul, Supinya

    2016-06-01

    Context Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors. Objective The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN. Materials and methods The ethyl acetate and water fractions (1-100 μg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method. Results and discussions The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3',5'-tetrahydroxybibenzyl (2), and 5,7,4'-trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC50 value of 3.15 μM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC50 value= 14.20 μM), quercetin-3-O-β-d-glucopyranoside (6, IC50 value = 19.39 μM) and quercetin-3-O-β-d-galactopyranoside (7, IC50 value = 21.80 μM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3'-processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN. PMID:26864337

  2. The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

    OpenAIRE

    Nicholas C. Obitte; Rohan, Lisa C; Adeyeye, Christianah M; Parniak, Michael A; Esimone, Charles O

    2013-01-01

    Background CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability. Objective The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity. Methods CSIC self-emulsifying oil formulations (SEFs)...

  3. Evaluation of HBsAg, anti-HCV, anti-HIV and VDRL test results in blood donors

    OpenAIRE

    Deveci, Özcan; Tekin, Alicem; Günbay, Seda Sibel; Kılıç, Dilek; KAYGUSUZ, Sedat; Ağalar, Canan; Özer, Türkan Toka

    2011-01-01

    Objectives: The most frequently encountered complication in the transfusion of blood and blood products are transmitted infections from these products. Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) remain the leading most important health problems in the transfusion of blood and blood products worldwide. Therefore, screening tests such as HBsAg, anti-HCV, anti-HIV, and RPR or VDRL for Treponema pallidum are mandatory tests to loo...

  4. Synthesis, Antimicrobial, and Anti-HIV1 Activity of Quinazoline-4(3H)-one Derivatives

    OpenAIRE

    K. Vijayakumar; A. Jafar Ahamed; Thiruneelakandan, G.

    2013-01-01

    The present investigation aims to synthesize 11 compounds of quinazoline-1 derivatives and to test their antimicrobial and anti-HIV1 activities. A quick-witted method was developed for the synthesis of novel substituted quinazolinone derivatives by summarizing diverse diamines with benzoxazine reactions, and it demonstrated the benefits of typical reactions, handy operation, and outstanding product yields. These compounds were confirmed by elemental analysis, I R, 1H NMR, 13C NMR, and mass sp...

  5. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

    Science.gov (United States)

    Briz, Verónica; Sepúlveda-Crespo, Daniel; Diniz, Ana Rita; Borrego, Pedro; Rodes, Berta; de La Mata, Francisco Javier; Gómez, Rafael; Taveira, Nuno; Muñoz-Fernández, Mª Ángeles

    2015-08-01

    The development of topical microbicide formulations for vaginal delivery to prevent HIV-2 sexual transmission is urgently needed. Second- and third-generation polyanionic carbosilane dendrimers with a silicon atom core and 16 sulfonate (G2-S16), napthylsulfonate (G2-NS16) and sulphate (G3-Sh16) end-groups have shown potent and broad-spectrum anti-HIV-1 activity. However, their antiviral activity against HIV-2 and mode of action have not been probed. Cytotoxicity, anti-HIV-2, anti-sperm and antimicrobial activities of dendrimers were determined. Analysis of combined effects of triple combinations with tenofovir and raltegravir was performed by using CalcuSyn software. We also assessed the mode of antiviral action on the inhibition of HIV-2 infection through a panel of different in vitro antiviral assays: attachment, internalization in PBMCs, inactivation and cell-based fusion. Vaginal irritation and histological analysis in female BALB/c mice were evaluated. Our results suggest that G2-S16, G2-NS16 and G3-Sh16 exert anti-HIV-2 activity at an early stage of viral replication inactivating the virus, inhibiting cell-to-cell HIV-2 transmission, and blocking the binding of gp120 to CD4, and the HIV-2 entry. Triple combinations with tenofovir and raltegravir increased the anti-HIV-2 activity, consistent with synergistic interactions (CIwt: 0.33-0.66). No vaginal irritation was detected in BALB/c mice after two consecutive applications for 2 days with 3% G2-S16. Our results have clearly shown that G2-S16, G2-NS16 and G3-Sh16 have high potency against HIV-2 infection. The modes of action confirm their multifactorial and non-specific ability, suggesting that these dendrimers deserve further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

  6. Fluorine Substituted 1,2,4-Triazinones as Potential Anti-HIV-1 and CDK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Mohammed S. I. Makki

    2014-01-01

    Full Text Available Fluorine substituted 1,2,4-triazinones have been synthesized via alkylation, amination, and/or oxidation of 6-(2-amino-5-fluorophenyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H-one 1 and 4-fluoro-N-(4-fluoro-2-(5-oxo-3-thioxo-2,3,4,5-tetrahydro-1,2,4-triazin-6-ylphenylbenzamide 5 as possible anti-HIV-1 and CDK2 inhibitors. Alkylation on positions 2 and 4 in 1,2,4-triazinone gave compounds 6–8. Further modification was performed by selective alkylation and amination on position 3 to form compounds 9–15. However oxidation of 5 yielded compounds 16–18. Structures of the target compounds have been established by spectral analysis data. Five compounds (5, 11, 14, 16, and 17 have shown very good anti-HIV activity in MT-4 cells. Similarly, five compounds (1, 3, and 14–16 have exhibited very significant CDK2 inhibition activity. Compounds 14 and 16 were found to have dual anti-HIV and anticancer activities.

  7. Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

    DEFF Research Database (Denmark)

    Pedersen, Erik Bjerregaard; Nielsen, Jakob Toudahl; Nielsen, Claus; Filichev, Vyacheslav V

    2011-01-01

    Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1-pyrenylet......Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4......-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming...... of the 50-phosphate inhibits dimerisation of this G-quadruplex as a result of negative charge–charge repulsion. Contrary to that, we found that attachment of the 50-O-DMT-group produced a more active 17-mer sequence that showed signs of aggregation—forming multimeric G-quadruplex species in solution...

  8. Transgenic Production of an Anti HIV Antibody in the Barley Endosperm.

    Directory of Open Access Journals (Sweden)

    Goetz Hensel

    Full Text Available Barley is an attractive vehicle for producing recombinant protein, since it is a readily transformable diploid crop species in which doubled haploids can be routinely generated. High amounts of protein are naturally accumulated in the grain, but optimal endosperm-specific promoters have yet to be perfected. Here, the oat GLOBULIN1 promoter was combined with the legumin B4 (LeB4 signal peptide and the endoplasmic reticulum (ER retention signal (SEKDEL. Transgenic barley grain accumulated up to 1.2 g/kg dry weight of recombinant protein (GFP, deposited in small roundish compartments assumed to be ER-derived protein bodies. The molecular farming potential of the system was tested by generating doubled haploid transgenic lines engineered to synthesize the anti-HIV-1 monoclonal antibody 2G12 with up to 160 μg recombinant protein per g grain. The recombinant protein was deposited at the periphery of protein bodies in the form of a mixture of various N-glycans (notably those lacking terminal N-acetylglucosamine residues, consistent with their vacuolar localization. Inspection of protein-A purified antibodies using surface plasmon resonance spectroscopy showed that their equilibrium and kinetic rate constants were comparable to those associated with recombinant 2G12 synthesized in Chinese hamster ovary cells.

  9. Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

    Directory of Open Access Journals (Sweden)

    Fabrizio Chiodo

    2014-06-01

    Full Text Available The therapeutic approach for the treatment of HIV infection is based on the highly active antiretroviral therapy (HAART, a cocktail of antiretroviral drugs. Notwithstanding HAART has shown different drawbacks like toxic side effects and the emergence of viral multidrug resistance. Nanotechnology offers new tools to improve HIV drug treatment and prevention. In this scenario, gold nanoparticles are an interesting chemical tool to design and prepare smart and efficient drug-delivery systems. Here we describe the preparation and antiviral activity of carbohydrate-coated gold nanoparticles loaded with anti-HIV prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs-containing glyconanoparticles were characterized and the pH-mediated release of the drug from the nanoparticle has been determined. The antiviral activity was tested by evaluating the replication of NL4-3 HIV in TZM-bl infected cells. The proof-of-principle presented in this work aims to introduce gold glyconanoparticles as a new multifunctional drug-delivery system in the therapy against HIV.

  10. Novel anti-HIV therapeutics targeting chemokine receptors and actin regulatory pathways.

    Science.gov (United States)

    Spear, Mark; Guo, Jia; Wu, Yuntao

    2013-11-01

    The human immunodeficiency virus-1 (HIV-1) infects helper CD4(+) T cells, and causes CD4(+) T-cell depletion and immunodeficiency. In the past 30 years, significant progress has been made in antiretroviral therapy, and the disease has become manageable. Nevertheless, an effective vaccine is still nowhere in sight, and a cure or a functional cure awaits discovery. Among possible curative therapies, traditional antiretroviral therapy, mostly targeting viral proteins, has been proven ineffective. It is possible that targeting HIV-dependent host cofactors may offer alternatives, both for preventing HIV transmission and for forestalling disease progression. Recently, the actin cytoskeleton and its regulators in blood CD4(+) T cells have emerged as major host cofactors that could be targeted. The novel concept that the cortical actin is a barrier to viral entry and early post-entry migration has led to the nascent model of virus-host interaction at the cortical actin layer. Deciphering the cellular regulatory pathways has manifested exciting prospects for future therapeutics. In this review, we describe the study of HIV interactions with actin cytoskeleton. We also examine potential pharmacological targets that emerge from this interaction. In addition, we briefly discuss several actin pathway-based anti-HIV drugs that are currently in development or testing. PMID:24117829

  11. Anti-HIV microRNA expression in a novel Indian cohort.

    Science.gov (United States)

    Dey, Rakesh; Soni, Kartik; Saravanan, Shanmugam; Balakrishnan, Pachamuthu; Kumar, Vikram; Boobalan, Jayaseelan; Solomon, Sunil Suhas; Scaria, Vinod; Solomon, Suniti; Brahmachari, Samir K; Pillai, Beena

    2016-01-01

    HIV-1 replication inside host cells is known to be regulated by various host factors. Host miRNAs, by virtue of its normal functioning, also regulate HIV-1 RNA expression by either directly targeting virus mRNAs or indirectly by regulating host proteins that HIV-1 uses for own replication. Therefore, it is highly possible that with differential miRNA expression, rate of disease progression will vary in HIV-1 infected individuals. In this study we have compared expression of a panel of 13 reported anti-HIV miRNAs in human PBMCs from long term non progressors (LTNPs), regular progressors and rapid progressors. We found that LTNPs have substantial lower expression of miR-382-5p that positively correlates with viral loads. Combinatorial regulation is highly probable in dictating differential disease progression as average expression of miR-382-5p and miR-155-5p can substantially distinguish LTNP individuals from regular progressors. PMID:27320691

  12. Coating flow of an anti-HIV microbicide gel: boundary dilution and yield stress

    Science.gov (United States)

    Szeri, Andrew J.; Tasoglu, Savas; Park, Su Chan; Katz, David F.

    2010-11-01

    A recent study has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [1]. However, the gel for this drug, and anti-HIV microbicide gels in general, have not been designed using an understanding of how gel spreading govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [2]. Here, we extend our initial analysis: we incorporate a yield stress, and we model the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our model developed in [2] is supplemented with a convective-diffusive transport equation to characterize dilution, and solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally. To model the common yield stress property of gels, we proceed by scaling analysis first. This establishes the conditions for validity of lubrication theory of a shear thinning yield stress fluid. This involves further development of the model in [2], incorporating a biviscosity model.[4pt] [1] Karim, et al., Science, 2010.[0pt] [2] Szeri, et al., Phy. of Fluids, 2008.

  13. Transient swelling behavior and drug delivery from a dissolving film deploying anti-HIV microbicide

    Science.gov (United States)

    Tasoglu, Savas; Katz, David F.; Szeri, Andrew J.

    2010-11-01

    Despite more than two decades of HIV vaccine research, there is still no efficacious HIV vaccine. Very recently, a research group has shown that a microbicide gel formulation of antiretroviral drug Tenofovir, significantly inhibits HIV transmission to women [1]. However, there is a widespread agreement that more effective and diverse drug delivery vehicles must be developed. In this setting, there is now great interest in developing different delivery vehicles such as vaginal rings, gels, and films. Here, we develop a model for transient fluid uptake and swelling behavior, and subsequent dissolution and drug deployment from a film containing anti-HIV microbicide. In the model, the polymer structural relaxation via water uptake is assumed to follow first order kinetics. In the case of a film loaded with an osmotically active solute, the kinetic equation is modified to account for the osmotic effect. The transport rate of solvent and solute within the matrix is characterized by a diffusion equation. After the matrix is relaxed to a specified concentration of solvent, lubrication theory and convective-diffusive transport are employed for flow of the liquefied matrix and drug dispersion respectively. [1] Karim, et al., Science, 2010.

  14. Effects of dilution on elastohydrodynamic coating flow of an anti-HIV microbicide vehicle

    Science.gov (United States)

    Szeri, Andrew; Park, Su Chan; Tasoglu, Savas; Katz, David F.

    2009-11-01

    Elastohydrodynamic lubrication over soft substrates characterizes the drug delivery of anti-HIV topical microbicides carried in gel vehicles. These gels are under development to prevent HIV transmission into vulnerable vaginal mucosa during intercourse. Their effectiveness depends on completeness and durability of coating, as well as on the active ingredients. Here we investigate the influence of dilution by vaginal fluid on the coating flows that serve to protect the user. The effects of dilution by vaginal fluid simulant are assessed through rheological experiments at variable dilution of the gel vehicle. This involves determination of the way parameters in a Carreau model of a shear-thinning gel are modified by dilution. The changes in coating are determined from a computational model, based on dilution rheology measured in the laboratory. The elastohydrodynamic lubrication model of Szeri, et al. Physics of Fluids (2008) is supplemented with a convective-diffusive transport equation to handle dilution, and solved using a multi-step scheme in a moving domain.

  15. The anti-HIV activity of ADS-J1 targets the HIV-1 gp120

    International Nuclear Information System (INIS)

    Recent data suggest that heparin sulfates may bind to a CD4 induced epitope in the HIV-1 gp120 that constitutes the coreceptor binding site. We have studied the mechanism of action of ADS-J1, a non-peptidic compound selected by docking analysis to interact with gp41 and to interfere with the formation of N-36/C-34 complexes in sandwich ELISA experiments. We show that ADS-J1 blocked the binding of wild-type HIV-1 NL4-3 strain to MT-4 cells but not virus-cell binding of a polyanion-resistant virus. However, ADS-J1 blocked the replication of polyanion-resistant, T-20- and C34-resistant HIV-1, suggesting a second mechanism of action. Development of resistance to ADS-J1 on the polyanion-resistant HIV-1 led to mutations in gp120 coreceptor binding site and not in gp41. Time of addition experiments confirmed that ADS-J1, but not polyanions such as dextran sulfate or AR177, worked at a step that mimics the activity of an HIV coreceptor antagonist but prior to gp41-dependent fusion. We conclude that ADS-J1 may bind to the HIV coreceptor binding site as its mechanism of anti-HIV activity

  16. Voltammetric determination of wedelolactone, an anti-HIV herbal drug, at boron-doped diamond electrode

    Indian Academy of Sciences (India)

    Sachin Saxena; Ratnanjali Shrivastava; Soami P Satsangee

    2015-05-01

    Boron-doped diamond electrode has been utilized for the study of electrochemical behaviour of an anti-HIV herbal drug wedelolactone in Britton-Robinson buffer (pH-2.5) by square-wave and cyclic voltammetry techniques. The response characteristics of cyclic voltammetry and square wave voltammetry showed a remarkable increase in the anodic peak current and electrochemical impedance spectroscopy revealed a lowering in charge transfer resistance at the boron-doped diamond electrode as compared to the glassy carbon electrode that can be attributed to the higher sensitivity of boron-doped diamond sensor. Cyclic voltammetry at the boron-doped diamond surface revealed the oxidation of wedelolactone with two oxidation peaks (P1 and P2) with Ep1 = 0.4V and Ep2 =1.00 V with scan rate varying from 10 - 220 mV/s and exhibits diffusion-controlled process. Based on the electrochemical measurements, a probable oxidation mechanism has been deduced and the electrode dynamics parameters have been evaluated. The effect of concentration on the peak currents of wedelolactone was found to have a linear relationship within the concentration range of 50–700 ng/mL. The LOD and LOQ were found to be 43.87 and 132.93 ng/mL respectively. The applicability of the proposed method was further scrutinized by the successful determination of wedelolactone in real plant samples.

  17. L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.

    Science.gov (United States)

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo; Zhang, Xiaoyan; Yan, Huimin

    2012-06-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens. PMID:22391529

  18. Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein.

    Science.gov (United States)

    Moghadam, Ali; Niazi, Ali; Afsharifar, Alireza; Taghavi, Seyed Mohsen

    2016-01-01

    In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents. PMID:27459300

  19. Anti-HIV Drug-Combination Nanoparticles Enhance Plasma Drug Exposure Duration as Well as Triple-Drug Combination Levels in Cells Within Lymph Nodes and Blood in Primates

    OpenAIRE

    Freeling, Jennifer P.; Koehn, Josefin; Shu, Cuiling; Sun, Jianguo; Ho, Rodney J. Y.

    2015-01-01

    HIV patients on combination oral drug therapy experience insufficient drug levels in lymph nodes, which is linked to viral persistence. Following success in enhancing lymph node drug levels and extending plasma residence time of indinavir formulated in lipid nanoparticles, we developed multidrug anti-HIV lipid nanoparticles (anti-HIV LNPs) containing lopinavir (LPV), ritonavir (RTV), and tenofovir (PMPA). These anti-HIV LNPs were prepared, characterized, scaled up, and evaluated in primates w...

  20. HIV testing among pregnant women in Brazil: rates and predictors Prueba anti-HIV en mujeres embarazadas en Brasil: tasas y predictivos Testagem anti-HIV em mulheres grávidas no Brasil: taxas e preditores

    Directory of Open Access Journals (Sweden)

    Valdiléa G Veloso

    2008-10-01

    Full Text Available OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234 who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance.OBJETIVO: Estimar las tasas de oferta y realización de la prueba anti-HIV y sus predictivos entre mujeres que recibieron atención prenatal. MÉTODOS: Se realizó un estudio transversal, de base poblacional, con 2.234 puérperas en 12 ciudades de Brasil. Las muestras probabilísticas fueron seleccionadas independientemente por ciudad, entre puérperas que asistieron a por lo menos una visita prenatal. Se colectaron datos sociodemográficos, informaciones sobre cuidado prenatal y acceso a

  1. Avaliação da testagem anti-HIV no pré-natal e na assistência ao parto no Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Daniela Marcondes Gomes

    2015-12-01

    Full Text Available Resumo Objetivos: avaliar a testagem anti-HIV durante a assistência pré-natal e ao parto no Sistema Único de Saúde. Métodos: estudo transversal conduzido em 2009 em 15 maternidades no Rio de Janeiro, sendo entrevistada amostra representativa de 835 parturientes e observados prontuários. Para avaliação da adequação da testagem anti-HIV foi elaborado um modelo lógico. Resultados: segundo informação das parturientes, 86,7% dispunham de sorologia não reagente do pré-natal e 55,7% foram submetidas ao teste rápido anti-HIV no hospital; em 49,9% dos casos o procedimento relativo ao teste rápido anti-HIV no hospital foi considerado adequado: mães com status ignorado de HIV do pré-natal submetidas ao teste rápido e mães com status conhecido não submetidas ao mesmo. Segundo dados do prontuário, 68,0% dispunham de sorologia não reagente e 79,6% foram submetidas ao teste rápido anti-HIV; em 50,9% dos casos o procedimento relativo ao teste rápido anti- HIV no hospital foi adequado. Conclusões: o protocolo de exames anti-HIV no pré-natal e na maternidade, vigentes em 2009, não foram cumpridos a contento, tanto por gerar procedimentos desnecessários quanto falhas na testagem da população alvo, ameaçando a instituição oportuna de medidas profiláticas de controle da transmissão vertical.

  2. In vitro and ex vivo inhibition of human telomerase by anti-HIV nucleoside reverse transcriptase inhibitors (NRTIs but not by non-NRTIs.

    Directory of Open Access Journals (Sweden)

    Kyle R Hukezalie

    Full Text Available Telomerase is a specialized reverse transcriptase responsible for the de novo synthesis of telomeric DNA repeats. In addition to its established reverse transcriptase and terminal transferase activities, recent reports have revealed unexpected cellular activities of telomerase, including RNA-dependent RNA polymerization. This telomerase characteristic, distinct from other reverse transcriptases, indicates that clinically relevant reverse transcriptase inhibitors might have unexpected telomerase inhibition profiles. This is particularly important for the newer generation of RT inhibitors designed for anti-HIV therapy, which have reported higher safety margins than older agents. Using an in vitro primer extension assay, we tested the effects of clinically relevant HIV reverse transcriptase inhibitors on cellular telomerase activity. We observed that all commonly used nucleoside reverse transcriptase inhibitors (NRTIs, including zidovudine, stavudine, tenofovir, didanosine and abacavir, inhibit telomerase effectively in vitro. Truncated telomere synthesis was consistent with the expected mode of inhibition by all tested NRTIs. Through dose-response experiments, we established relative inhibitory potencies of NRTIs on in vitro telomerase activity as compared to the inhibitory potencies of the corresponding dideoxynucleotide triphosphates. In contrast to NRTIs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs nevirapine and efavirenz did not inhibit the primer extension activity of telomerase, even at millimolar concentrations. Long-term, continuous treatment of human HT29 cells with select NRTIs resulted in an accelerated loss of telomere repeats. All tested NRTIs exhibited the same rank order of inhibitory potencies on telomerase and HIV RT, which, according to published data, were orders-of-magnitude more sensitive than other DNA polymerases, including the susceptible mitochondria-specific DNA polymerase gamma. We concluded that

  3. Molecular Modeling, Synthesis, and Anti-HIV Activity of Novel Isoindolinedione Analogues as Potent Non-nucleoside Reverse Transcriptase Inhibitors.

    Science.gov (United States)

    Kumari, Garima; Singh, Ramendra K

    2016-02-01

    Different isoindolinedione derivatives bearing imine, amide, thioamide, and sulfonamide linkages have been designed in silico using discovery studio software (BIOVIA, San Diego, CA, USA), synthesized, and evaluated for their anti-HIV activity. SAR studies revealed that the linkages in these molecules did affect their anti-HIV activity and the molecules having sulfonamide linkages were the most potent HIV-RT inhibitors as the S=O bonds of the sulfonamide moiety interacted with Lys103 (NH or carbonyl or both) and Pro236; the NH part of the sulfonamide linkage formed bond with carbonyl of Lys101. blood-brain barrier (BBB) plots were also studied, and it was found that all the designed molecules have potential to cross BBB, a very vital criteria for anti-HIV drugs. In vitro screening was performed using HIV-1 strain IIIB in MT-4 cells using the MTT assay, and it was seen that some of these molecules were effective inhibitors of HIV-1 replication at nanomolar concentration with selectivity indices ranging from 33.75 to 73.33 under in vitro conditions. Some of these molecules have shown good anti-HIV activity at 3-4 nm concentrations. These derivatives have potential to be developed as lead molecules effective against HIV-1. Novel isoindolinedione derivatives as probable NNRTIs have been synthesized and characterized. Some of these molecules have shown good anti-HIV activity at 3-4 nm concentrations. PMID:26212217

  4. A Rapid, Self-confirming Assay for HIV: Simultaneous Detection of Anti-HIV Antibodies and Viral RNA

    Science.gov (United States)

    Chen, Zongyuan; Zhu, Hui; Malamud, Daniel; Barber, Cheryl; Ongagna, Yhombi Yvon Serge; Yasmin, Rubina; Modak, Sayli; Janal, Malvin N.; Abrams, William R.; Montagna, Richard A.

    2016-01-01

    Objective We developed a microfluidic system to simultaneously detect host anti-HIV antibodies and viral RNA in the same specimen in order to satisfy two important diagnostic criteria, especially within resource-limited settings. First, the system can detect acute HIV infection and allow immediate confirmation of a seropositive screening result by detection of HIV RNA. It also addresses the well-known "seroconversion window" during early HIV infection when antibodies are not yet detectable and viral loads are at their highest. Methods We first developed and optimized two separate manual assays for the detection of host anti-HIV antibodies and viral RNA and then converted them to the microfluidic system. We optimized a commercially available serologic assay to run within the microfluidic device while we incorporated the isothermal LAMP assay to detect the presence of viral RNA. The microfluidic device and instrumentation were developed to simultaneously perform both assays without any user intervention. Results The finalized system consists of a disposable injection molded and film-laminated microfluidic CARD disposable device and a portable, software controlled instrument, which together can automatically perform all steps of both assays without any user intervention after the initial loading of samples and reagents. The microfluidic CARD cartridge has multiple microchannels, valves, pumps and reservoirs, which perform the immunoassay, isolates viral RNA for detection by magnetic bead based purification, and Reverse Transcriptase loop-mediated isothermal amplification (RT-LAMP). The microfluidic system was able to detect host anti-HIV antibodies and viral RNA in either a blood or saliva sample. Conclusion The ability to detect antibodies and simultaneously confirm a seropositive HIV-RNA result provides healthcare workers with a complete and accurate appraisal of a patient's infection status in the earliest stages of the disease and represents an important tool for

  5. Structure and conformational analysis of the anti-HIV AZT 5'-aminocarbonylphosphonate prodrug using DFT methods

    Energy Technology Data Exchange (ETDEWEB)

    Tamara Molina, A. [Departamento de Quimica-Fisica I, Facultad de Ciencias Quimicas, Universidad Complutense, Ciudad Universitaria, Madrid 28040 (Spain); Alcolea Palafox, M., E-mail: alcolea@quim.ucm.es [Departamento de Quimica-Fisica I, Facultad de Ciencias Quimicas, Universidad Complutense, Ciudad Universitaria, Madrid 28040 (Spain)

    2011-08-25

    Graphical abstract: The phosphonate prodrug studied offers an excellent potential as alternative to AZT. Display Omitted Highlights: {yields} The phosphonate prodrug studied offers an excellent potential as alternative to AZT. {yields} The 84 most energetically favourable conformers were identified by DFT methods. {yields} The increment in the ring puckering produces a higher flexibility than in AZT. {yields} The high charge on the oxygen's chain could explain the high activity of this prodrug. {yields} The phosphonate chain has little influence in the charge distribution on the rings. - Abstract: A comprehensive theoretical conformational analysis of the anti-HIV AZT 5'-aminocarbonylphosphonate prodrug was carried out, due to this prodrug has noticeable advantage over approved drugs AZT and Nikavir. The whole conformational parameters ({chi}, {gamma}, {beta}, {alpha}, {delta}, {epsilon}, {tau}, P, {nu}{sub max}) were analysed as well as the NBO Natural atomic charges. The calculations were carried out by means of B3LYP/6-31G** and B3LYP/6-311++G(3df,pd) DFT levels of theory with full relaxation of all geometrical parameters. The search located at least 86 stable structures, 6 of which are within a 1 kcal/mol electronic energy range of the global minimum and 11 conformers are within a 1 kcal/mol Gibbs energy range. The global minimum with the 6-311++G(3df,pd) basis set corresponds to the calculated values of the exocyclic torsional angles {chi} = -121.6 deg., {beta} = 153.0 deg., {gamma} = -152.0 deg. and {alpha} = -74.1 deg. The results obtained are in accordance to those found in related anti-HIV nucleoside Analogs. Comparisons of the conformers with those determined in the common anti-HIV drug AZT were carried out. Several correlations and general conclusions were emphasized.

  6. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity.

    Science.gov (United States)

    Dezzutti, Charlene S; Brown, Elizabeth R; Moncla, Bernard; Russo, Julie; Cost, Marilyn; Wang, Lin; Uranker, Kevin; Kunjara Na Ayudhya, Ratiya P; Pryke, Kara; Pickett, Jim; Leblanc, Marc-André; Rohan, Lisa C

    2012-01-01

    Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm. PMID:23144863

  7. Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity.

    Directory of Open Access Journals (Sweden)

    Charlene S Dezzutti

    Full Text Available Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC aqueous- (n = 10, lipid- (n = 2, and silicone-based (n = 2 products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9, KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.

  8. Is Wetter Better? An Evaluation of Over-the-Counter Personal Lubricants for Safety and Anti-HIV-1 Activity

    OpenAIRE

    Dezzutti, Charlene S.; Brown, Elizabeth R.; Bernard Moncla; Julie Russo; Marilyn Cost; Lin Wang; Kevin Uranker; Kunjara Na Ayudhya, Ratiya P.; Kara Pryke; Jim Pickett; Marc-André Leblanc; Rohan, Lisa C.

    2012-01-01

    Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmo...

  9. Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi

    OpenAIRE

    Bashyal, Bharat P.; Wellensiek, Brian P.; Ramakrishnan, Rajesh; Faeth, Stanley H.; Ahmad, Nafees; Leslie Gunatilaka, A. A.

    2014-01-01

    Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, alterto...

  10. HIV-1 infection of in vitro cultured human monocytes: early events and influence of anti HIV-1 antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Olofsson, S; Nielsen, Jens Ole; Hansen, J E

    To characterize the role of the humoral immune response on HIV-1 infection of monocytes and macrophages (M phi s) we examined the susceptibility of in vitro cultured monocyte/M phi s to various HIV-1 isolates and the influence of heterologous and particularly autologous anti HIV-1 sera on this...... infection. Depending on the period of in vitro cultivation and the virus isolate used different patterns of susceptibility were detected. One week old monocyte/M phi s were highly susceptible to HIV-1 infection, in contrast to monocyte/M phi s cultured 4 weeks. The infection by virus isolated immediately...

  11. In vitro anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca

    OpenAIRE

    Behbahani, M.; Sayedipour, S.; Pourazar, A.; Shanehsazzadeh, M.

    2014-01-01

    Previously, we reported that the kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca showed potent anti-HSV activity. In the present study the anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside are investigated at different concentrations (100, 50, 25 and 10 μg/ml) using HIV-1 p24 Antigen kit. Real-time Polymerase chain reaction (RT-PCR) assay was also used for quantification of full range of virus load observed in treated and untreated cells. According t...

  12. Avaliação da testagem anti-HIV no pré-natal e na assistência ao parto no Rio de Janeiro, Brasil

    OpenAIRE

    Daniela Marcondes Gomes; Maria Inês Couto de Oliveira; Sandra Costa Fonseca

    2015-01-01

    Resumo Objetivos: avaliar a testagem anti-HIV durante a assistência pré-natal e ao parto no Sistema Único de Saúde. Métodos: estudo transversal conduzido em 2009 em 15 maternidades no Rio de Janeiro, sendo entrevistada amostra representativa de 835 parturientes e observados prontuários. Para avaliação da adequação da testagem anti-HIV foi elaborado um modelo lógico. Resultados: segundo informação das parturientes, 86,7% dispunham de sorologia não reagente do pré-natal e 55,7% foram submeti...

  13. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina)

    Science.gov (United States)

    ZHANG, Xiao-Liang; SONG, Jia-Hao; PANG, Wei; ZHENG, Yong-Tang

    2016-01-01

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  14. Molecular cloning and anti-HIV-1 activities of APOBEC3s from northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Zhang, Xiao-Liang; Song, Jia-Hao; Pang, Wei; Zheng, Yong-Tang

    2016-07-18

    Northern pig-tailed macaques (NPMs, Macaca leonina) are susceptible to HIV-1 infection largely due to the loss of HIV-1-restricting factor TRIM5α. However, great impediments still exist in the persistent replication of HIV-1 in vivo, suggesting some viral restriction factors are reserved in this host. The APOBEC3 proteins have demonstrated a capacity to restrict HIV-1 replication, but their inhibitory effects in NPMs remain elusive. In this study, we cloned the NPM A3A-A3H genes, and determined by BLAST searching that their coding sequences (CDSs) showed 99% identity to the corresponding counterparts from rhesus and southern pig-tailed macaques. We further analyzed the anti-HIV-1 activities of the A3A-A3H genes, and found that A3G and A3F had the greatest anti-HIV-1 activity compared with that of other members. The results of this study indicate that A3G and A3F might play critical roles in limiting HIV-1 replication in NPMs in vivo. Furthermore, this research provides valuable information for the optimization of monkey models of HIV-1 infection. PMID:27469256

  15. Altertoxins with potent anti-HIV activity from Alternaria tenuissima QUE1Se, a fungal endophyte of Quercus emoryi.

    Science.gov (United States)

    Bashyal, Bharat P; Wellensiek, Brian P; Ramakrishnan, Rajesh; Faeth, Stanley H; Ahmad, Nafees; Gunatilaka, A A Leslie

    2014-11-01

    Screening of a small library of natural product extracts derived from endophytic fungi of the Sonoran desert plants in a cell-based anti-HIV assay involving T-cells infected with the HIV-1 virus identified the EtOAc extract of a fermentation broth of Alternaria tenuissima QUE1Se inhabiting the stem tissue of Quercus emoryi as a promising candidate for further investigation. Bioactivity-guided fractionation of this extract led to the isolation and identification of two new metabolites, altertoxins V (1) and VI (2) together with the known compounds, altertoxins I (3), II (4), and III (5). The structures of 1 and 2 were determined by detailed spectroscopic analysis and those of 3-5 were established by comparison with reported data. When tested in our cell-based assay at concentrations insignificantly toxic to T-cells, altertoxins V (1), I (3), II (4), and III (5) completely inhibited replication of the HIV-1 virus at concentrations of 0.50, 2.20, 0.30, and 1.50 μM, respectively. Our findings suggest that the epoxyperylene structural scaffold in altertoxins may be manipulated to produce potent anti-HIV therapeutics. PMID:25260957

  16. In vitro anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca.

    Science.gov (United States)

    Behbahani, M; Sayedipour, S; Pourazar, A; Shanehsazzadeh, M

    2014-01-01

    Previously, we reported that the kaempferol and kaempferol-7-O-glucoside isolated from Securigera securidaca showed potent anti-HSV activity. In the present study the anti-HIV-1 activities of kaempferol and kaempferol-7-O-glucoside are investigated at different concentrations (100, 50, 25 and 10 μg/ml) using HIV-1 p24 Antigen kit. Real-time Polymerase chain reaction (RT-PCR) assay was also used for quantification of full range of virus load observed in treated and untreated cells. According to the results of RT- PCR, tested compounds at a concentration of 100 μg/ml exerted potent inhibitory effect. Time of drug addition experiments demonstrated that these compounds exerted their inhibitory effects on the early stage of HIV infection. The results also showed potent anti-HIV-1 reverse transcriptase activity. Antiviral activity of kaempferol-7-O-glucoside was more pronounced than that of kaempferol. These findings demonstrate that kaempferol-7-O-glucoside could be considered as a new potential drug candidate for the treatment of HIV infection which requires further assessments. PMID:26339261

  17. "Who's to Blame?": An Activity to Stimulate Reflection about Anti-HIV Stigma in an Undergraduate Course on the HIV Epidemic

    Science.gov (United States)

    Beshers, Sarah C.

    2007-01-01

    A classroom-based activity was created to help undergraduate students in a course about the HIV epidemic explore and better understand the nature and scope of anti-HIV stigma. The activity asks students to assess the extent of their sympathy for several people living with HIV disease when given only a brief statement about how each person became…

  18. Synthesis and Anti-HIV Activity of Trisubstituted (3'R, 4'R)-3',4'- Di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) Analogs

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives (4-13)were designed, synthesized, and evaluated against HIV replication in MT4 cells and H9 lymphocytes.

  19. Safety and anti-HIV assessments of natural vaginal cleansing products in an established topical microbicides in vitro testing algorithm

    Directory of Open Access Journals (Sweden)

    Jones Maureen

    2010-07-01

    Full Text Available Abstract Background At present, there is no effective vaccine or other approved product for the prevention of sexually transmitted human immunodeficiency virus type 1 (HIV-1 infection. It has been reported that women in resource-poor communities use vaginally applied citrus juices as topical microbicides. These easily accessible food products have historically been applied to prevent pregnancy and sexually transmitted diseases. The aim of this study was to evaluate the efficacy and cytotoxicity of these substances using an established topical microbicide testing algorithm. Freshly squeezed lemon and lime juice and household vinegar were tested in their original state or in pH neutralized form for efficacy and cytotoxicity in the CCR5-tropic cell-free entry and cell-associated transmission assays, CXCR4-tropic entry and fusion assays, and in a human PBMC-based anti-HIV-1 assay. These products were also tested for their effect on viability of cervico-vaginal cell lines, human cervical explant tissues, and beneficial Lactobacillus species. Results Natural lime and lemon juice and household vinegar demonstrated anti-HIV-1 activity and cytotoxicity in transformed cell lines. Neutralization of the products reduced both anti-HIV-1 activity and cytotoxicity, resulting in a low therapeutic window for both acidic and neutralized formulations. For the natural juices and vinegar, the IC50 was ≤ 3.5 (0.8-3.5% and the TC50 ≤ 6.3 (1.0-6.3%. All three liquid products inhibited viability of beneficial Lactobacillus species associated with vaginal health. Comparison of three different toxicity endpoints in the cervical HeLa cell line revealed that all three products affected membrane integrity, cytosolic enzyme release, and dehydrogenase enzyme activity in living cells. The juices and vinegar also exerted strong cytotoxicity in cervico-vaginal cell lines, mainly due to their acidic pH. In human cervical explant tissues, treatment with 5% lemon or lime juice

  20. A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition. METHODS: 30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood. RESULTS: A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators. CONCLUSIONS: Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and

  1. The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research.

    Science.gov (United States)

    Varatharajan, Lavanya; Thomas, Sarah A

    2009-05-01

    The advent of highly active antiretroviral therapy (HAART), which constitutes HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors, has dramatically reduced the morbidity and mortality associated with human immunodeficiency virus (HIV) infection in resource-rich countries. However, this disease still kills several million people each year. Though the reason for therapeutic failure is multi-factorial, an important concern is the treatment and control of HIV within the central nervous system (CNS). Due to the restricted entry of anti-HIV drugs, the brain is thought to form a viral sanctuary site. This not only results in virological resistance, but also is often associated with the development of complications such as HIV-associated dementia. The CNS delivery of anti-HIV drugs is limited by the blood-brain and blood-CSF interfaces due to a combination of restricted paracellular movement, powerful metabolic enzymes and numerous transporters including members of the ATP binding cassette (ABC) and solute carrier (SLC) superfamilies. A better appreciation of the transporters present at the brain barriers will prove a valuable milestone in understanding the limited brain penetration of anti-HIV drugs in HIV and also aid the development of new anti-HIV drugs and drug combinations, with enhanced efficacy in the CNS. This review aims to summarise current knowledge on the transport of anti-HIV drugs across the blood-brain barrier and the choroid plexus, as well as provide recommendations for future research. PMID:19176219

  2. Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Mimi Ghosh

    Full Text Available We investigated the impact of antimicrobials in cervicovaginal lavage (CVL from HIV(+ and HIV(- women on target cell infection with HIV. Since female reproductive tract (FRT secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+ and (- women inhibit HIV infection.CVL from 32 HIV(+ healthy women with high CD4 counts and 15 healthy HIV(- women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+ women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(- controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3alpha indicated that each was present in CVL from HIV(+ and HIV(- women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+ women.These findings indicate that CVL from healthy HIV(+ and HIV(- women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

  3. Discovery of non-peptide small molecular CXCR4 antagonists as anti-HIV agents: Recent advances and future opportunities.

    Science.gov (United States)

    Zhang, Heng; Kang, Dongwei; Huang, Boshi; Liu, Na; Zhao, Fabao; Zhan, Peng; Liu, Xinyong

    2016-05-23

    CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced. PMID:26974376

  4. Inculcating safe sex attitudes in South African adolescents: a directive for the government's anti-HIV/AIDS policy.

    Science.gov (United States)

    D'Souza, Jayesh

    2010-01-01

    South Africa has one of the highest rates of HIV/AIDS in the world. Much blame for this has been laid on the apathy of the South African government and the cultural traits of South Africans. AIDS prevention research calls for early childhood education to raise awareness of the causes, dangers, and prevention of HIV/AIDS. This study involved surveys among a select sample of South African adolescents to determine their sexual attitudes before and after a cognitive-behavioral intervention. Overall, the results did not make a significant difference in their attitudes, suggesting pre-adolescent sex education might prove to be a more useful tool in anti-HIV/AIDS education. Risky sexual behavior, under the influence of alcohol, also serves as a warning to educate young consumers of alcohol. PMID:22192941

  5. Synthesis and in vitro anti-HIV-1 activity of a series of N-arylsulfonyl-3-propionylindoles.

    Science.gov (United States)

    Che, Zhiping; Tian, Yuee; Hu, Zhenjie; Chen, Yingwu; Liu, Shengming; Chen, Genqiang

    2016-05-01

    Fifteen N-arylsulfonyl-3-propionylindoles (3a-o) were prepared and preliminarily evaluated as in vitro inhibitors of human immunodeficiency virus type-1 (HIV-1). Three compounds 3c, 3g and 3i exhibited potent anti-HIV-1 activity with effective concentration (EC50) values of 0.8, 4.0 and 1.2 μg/mL, and therapeutic index (TI) values of 11.7, 16.6 and 84.1, respectively. N-(m-Nitro)phenylsulfonyl-3-propionyl-6-methylindole (3i) exhibited the most promising and best activity against HIV-1 replication. The cytotoxicity of these compounds was assessed as well. PMID:27124676

  6. An anti-HIV-1 gp120 antibody expressed as an endocytotic transmembrane protein mediates internalization of HIV-1

    International Nuclear Information System (INIS)

    In this study, we used HIV-1 as a model to demonstrate a novel approach for receptor-independent cell entry of virus. The heavy chain of an anti-HIV-1 gp120 antibody was engineered with endocytotic and transmembrane motifs from either the cation-independent mannose 6-phospate receptor or the low-density lipoprotein receptor. Flow cytometry and immunofluorescence studies showed that the chimeric antibodies were expressed on the cell surface and can undergo rapid internalization. Furthermore, one of the chimeric antibodies was able to bind and internalize HIV-1. Using a luciferase reporter HIV-1, we further showed that internalized viruses could undergo replication. Therefore, we have demonstrated a proof-of-principle of a novel method that can be used to internalize virus into cells, without prior knowledge of the cellular receptor for the virus. We propose that this approach would be particularly useful for studying viruses whose cellular receptor(s) is not known

  7. A New Neolignan, and the Cytotoxic and Anti-HIV-1 Activities of Constituents from the Roots of Dasymaschalon sootepense.

    Science.gov (United States)

    Hongthong, Sakchai; Kuhakarn, Chutima; Jaipetch, Thaworn; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Limthongkul, Jitra; Nuntasaen, Narong; Reutrakul, Vichai

    2016-06-01

    Bioassay-guided isolation from the ethyl acetate extract of Dasymaschalon sootepense roots led to the isolation of twelve compounds including a new dihydrobenzo-furan neolignan, (+)-(2S,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-methylbenzofuran-5-carbaldehyde (5), and eleven known compounds (1-4, and 6-12). The chemical structures and stereochemistry of all the isolated compounds were established by spectroscopic techniques. The known compounds 4 and 6 have been fully characterized spectroscopically, including their absolute configurations. Cytotoxic and anti-HIV-1 reverse transcriptase (RT) activities of compounds 1-3, 5 and 8-12 were determined. Among compounds screened, compounds 2, 3 and 10 displayed weak cytotoxic activity with ED50 values ranging from 9.6-47.5 μM and only compound 2 was found weakly active against HIV-1 RT with an IC50 value of 323.2 μM. PMID:27534123

  8. Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz.

    Science.gov (United States)

    Wanke, Riccardo; Novais, David A; Harjivan, Shrika G; Marques, M Matilde; Antunes, Alexandra M M

    2012-06-21

    We report the oxidation of the first line anti-HIV drug efavirenz (EFV), mediated by a bio-inspired nonheme Fe-complex. Depending upon the experimental conditions this system can be tuned either to yield the major EFV metabolite, 8-hydroxy-EFV, in enantiomerically pure form or to mimic cytochrome P450 (CYP) activity, yielding 8-hydroxy-EFV and 7-hydroxy-EFV, the two phenolic EFV metabolites reported to be formed in vivo. The successful oxidation of the anti-estrogen tamoxifen and the equine estrogen equilin into their CYP-mediated metabolites supports the general application of bio-inspired nonheme Fe-complexes in mirroring CYP activity. PMID:22569890

  9. Mapping the Vif-A3G interaction using peptide arrays: a basis for anti-HIV lead peptides.

    Science.gov (United States)

    Reingewertz, Tali H; Britan-Rosich, Elena; Rotem-Bamberger, Shahar; Viard, Mathias; Jacobs, Amy; Miller, Abigail; Lee, Ji Youn; Hwang, Jeeseong; Blumenthal, Robert; Kotler, Moshe; Friedler, Assaf

    2013-06-15

    Human apolipoprotein-B mRNA-editing catalytic polypeptide-like 3G (A3G) is a cytidine deaminase that restricts retroviruses, endogenous retro-elements and DNA viruses. A3G plays a key role in the anti-HIV-1 innate cellular immunity. The HIV-1 Vif protein counteracts A3G mainly by leading A3G towards the proteosomal machinery and by direct inhibition of its enzymatic activity. Both activities involve direct interaction between Vif and A3G. Disrupting the interaction between A3G and Vif may rescue A3G antiviral activity and inhibit HIV-1 propagation. Here, mapping the interaction sites between A3G and Vif by peptide array screening revealed distinct regions in Vif important for A3G binding, including the N-terminal domain (NTD), C-terminal domain (CTD) and residues 83-99. The Vif-binding sites in A3G included 12 different peptides that showed strong binding to either full-length Vif, Vif CTD or both. Sequence similarity was found between Vif-binding peptides from the A3G CTD and NTD. A3G peptides were synthesized and tested for their ability to counteract Vif action. A3G 211-225 inhibited HIV-1 replication in cell culture and impaired Vif dependent A3G degradation. In vivo co-localization of full-length Vif with A3G 211-225 was demonstrated by use of FRET. This peptide has the potential to serve as an anti-HIV-1 lead compound. Our results suggest a complex interaction between Vif and A3G that is mediated by discontinuous binding regions with different affinities. PMID:23545135

  10. Symmetrical 1-pyrrolidineacetamide showing anti-HIV activity through a new binding site on HIV-1 integrase

    Institute of Scientific and Technical Information of China (English)

    Li DU; Ya-xue ZHAO; Liu-meng YANG; Yong-tang ZHENG; Yun TANG; Xu SHEN; Hua-liang JIANG

    2008-01-01

    Aim:To characterize the functional and pharmacological features of a symmetrical 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide,as a new anti-HIV compound which could competitively inhibit HIV-1 integrase (IN) binding to viral DNA.Methods:A surface plasma resonance (SPR)-based competitive assay was employed to determine the compound's inhibitory activity,and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell assay was used to qualify the antiviral activity.The potential binding sites were predicted by molecular modeling and determined by site-directed mutagenesis and a SPR binding assay.Results:l-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene) bis-1-pyrrolidineacetamide could competitively inhibit IN binding to viral DNA with a 50% inhibitory concentration (IC50) value of 7.29±0.68 μmol/L as investigated by SPR-based investigation.Another antiretroviral activity assay showed that this compound exhibited inhibition against HⅣ-Ⅰ(ⅢB) replication with a 50% effective concentration (EC50) value of 40.54 μmol/L in C8166 cells,and cytotoxicity with a cytotoxic concentration value of 173.84 μmol/L in mock-infected C8166 cells.Molecular docking predicted 3 potential residues as 1-pyrrolidineacetamide,N,N'-(methylene-di-4,1-phenylene)bis-1-pyrrolidineacetamide binding sites.The importance of 3 key amino acid residues (Lys103,Lys173,and Thr174) involved in the binding was further identified by site-directed mutagenesis and a SPR binding assay.Conclusion:This present work identified a new anti-HIV compound through a new IN-binding site which is expected to supply new potential drug-binding site information for HIV-1 integrase inhibitor discovery and development.

  11. A model of transluminal flow of an anti-HIV microbicide vehicle: Combined elastic squeezing and gravitational sliding

    Science.gov (United States)

    Szeri, Andrew J.; Park, Su Chan; Verguet, Stéphane; Weiss, Aaron; Katz, David F.

    2008-08-01

    Elastohydrodynamic lubrication over soft substrates is of importance in a number of biomedical problems: From lubrication of the eye surface by the tear film, to lubrication of joints by synovial fluid, to lubrication between the pleural surfaces that protect the lungs and other organs. Such flows are also important for the drug delivery functions of vehicles for anti-HIV topical microbicides. These are intended to inhibit transmission into vulnerable mucosa, e.g., in the vagina. First generation prototype microbicides have gel vehicles, which spread after insertion and coat luminal surfaces. Effectiveness derives from potency of the active ingredients and completeness and durability of coating. Delivery vehicle rheology, luminal biomechanical properties, and the force due to gravity influence the coating mechanics. We develop a framework for understanding the relative importance of boundary squeezing and body forces on the extent and speed of the coating that results. A single dimensionless number, independent of viscosity, characterizes the relative influences of squeezing and gravitational acceleration on the shape of spreading in the Newtonian case. A second scale, involving viscosity, determines the spreading rate. In the case of a shear-thinning fluid, the Carreau number also plays a role. Numerical solutions were developed for a range of the dimensionless parameter and compared well with asymptotic theory in the limited case where such results can be obtained. Results were interpreted with respect to trade-offs between wall elasticity, longitudinal forces, bolus viscosity, and bolus volume. These provide initial insights of practical value for formulators of gel delivery vehicles for anti-HIV microbicidal formulations.

  12. Studies on the Compounds of d4T Combined with Nitric Oxide Donors and Nitric Oxide Synthase Inhibitors and their Anti-HIV and AIDS Activity

    Institute of Scientific and Technical Information of China (English)

    KWALE MOLIME GUITREMBI Blaise(Central African); YAO Qi-zheng

    2004-01-01

    Stavudine, a potent anti-HIV and AiDS-related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5'-position on the sugar is an interesting template for the elaboration of new potent anti-HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.

  13. Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes.

    OpenAIRE

    Vandendriessche, T.; Chuah, M. K.; L. Chiang; Chang, H K; Ensoli, B; Morgan, R A

    1995-01-01

    Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vect...

  14. Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

    OpenAIRE

    Chen Xi; Zhang Xiujuan; Lu Hong; Tan Suiyi; Lu Lu; Yang Jie; Qiao Pengyuan; Li Lin; Wu Shuguang; Jiang Shibo; Liu Shuwen

    2010-01-01

    Abstract Background Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbi...

  15. L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

    OpenAIRE

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo

    2012-01-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1...

  16. Frequency of HBsAg, anti-HCV, and anti-HIV in pregnant women and/or patients with gynecologic diseases in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    Tülay Özlü

    2013-06-01

    Full Text Available Objective: Hepatitis B virus (HBV, hepatitis C virus (HCV and human immunodeficiency virus (HIV are viruses that can be transmitted to the health care workers by infected body fluids and from mother to the baby before, during or after delivery. In the present study, we aimed to investigate the frequency of hepatitis B surface antigens (HBsAg, hepatitis C antibodies (anti-HCV, and HIV antibodies (anti-HIV in pregnant women and/or patients with gynecologic diseases that admit to a university hospital in Bolu.Methods: HBsAg, anti-HCV, and anti-HIV results of the pregnant women and/or patients with gynecologic diseases that admitted to the obstetrics and gynecology clinics between January 2006 and June 2012 were retrospectively investigated. All markers were tested in the microbiology laboratory of our hospital by using macro ELISA method (Axsyme and Architect i2000SR systems, Abbott Diagnostics, Chicago, IL, USA.Results: The frequency of HBsAg, anti-HCV, and antiHIV positivity were 1.8%, 0.5%, and 0% in pregnant women and 1.9%, 1.1%, and 0% in patients with gynecologic diseases, respectively.Conclusion: The frequencies detected in our hospital are at low levels as seen in developed countries. Since there is no effective method of prevention especially from HCV, awareness of this serologic result before high risk procedures will enable the doctors and the health care workers to take extensive measures to prevent the transmission of the disease. J Clin Exp Invest 2013; 4 (2: 166-170Key words: anti-HCV, anti-HIV, HBsAg, pregnant women, gynecology

  17. 抗HIV活性木脂素类化合物研究进展%Advances in the Study on Anti-HIV Lignan Compounds

    Institute of Scientific and Technical Information of China (English)

    秦浩; 高丽; 郭军

    2012-01-01

    Lignan compounds have a variety of pharmacological activities. The mechanism of anti-HIV lig-nans is through affecting a particular aspect of HIV replication cycle, thus inhibiting viral replication and infection. Lignan is divided into four categories based on different anti-HIV detection methods. In this paper, we summarize the advance in the study on anti-HIV lignan compounds in last two decades.%木脂素类化合物具有多种药理活性,其抗HIV机制是通过影响HIV复制周期的某个环节,从而抑制病毒的复制和感染.按其抗HIV检测方法不同,将木脂素类化合物分成4类,本文对1990~2011年有关抗HIV活性木脂素类化合物研究文献进行综述.

  18. Array-in-well platform-based multiplex assay for the simultaneous detection of anti-HIV- and treponemal-antibodies, and Hepatitis B surface antigen.

    Science.gov (United States)

    Talha, Sheikh M; Saviranta, Petri; Hattara, Liisa; Vuorinen, Tytti; Hytönen, Jukka; Khanna, Navin; Pettersson, Kim

    2016-02-01

    Multiplex assays detecting sets of related clinical analytes simultaneously can save considerable amount of time and resources. Array-in-well (AIW) is a powerful platform for the multiplex detection of different analytes where microarrays can be printed at the bottom of microtiter wells, thus combining the potential of microarrays with the ease of handling microtiter wells. We have developed a single-step AIW assay for the simultaneous screening of HIV, Treponema pallidum subspecies pallidum (causing syphilis) and Hepatitis B virus infections targeting the specific detection of anti-HIV- and treponemal-antibodies and Hepatitis B surface antigen (HBsAg), respectively, using two different fluorescent label technologies i.e. DyLight 633 and europium nanoparticle. Double-antigen assay formats were used for anti-HIV- and treponemal-antibody detection that can simultaneously detect both IgG and IgM, and thus reduce the window period of detection. AIW assay was evaluated with well characterized serum/plasma samples (n=111), and the qualitative results were in near complete agreement with those of the reference assays. The AIW assay exhibited 100% sensitivities for all three analytes, and 100% specificities for anti-HIV antibodies and HBsAg, and 98.6% specificity for treponemal antibodies. The limit of detection of HBsAg in AIW assay was 0.18 ng/ml. This high performing AIW assay has the potential to be used as a multiplex screening test for these three infections. PMID:26711310

  19. MULTIPLE WAYS OF TARGETING APOBEC3/VIF INTERACTIONS FOR ANTI-HIV-1 DRUG DEVELOPMENT

    OpenAIRE

    Smith, Jessica L.; Bu, Wei; Burdick, Ryan C.; Pathak, Vinay K.

    2009-01-01

    Human immunodeficiency virus type 1 (HIV-1) infections and the resulting acquired immunodeficiency syndrome (AIDS) pandemic remain a global challenge in the absence of a protective vaccine and because of rapid selection of drug-resistant viral variants in response to all currently available antiviral therapies. Development of new and highly active antiviral agents would greatly facilitate effective clinical management of HIV-1 infections and delay the onset of AIDS. Recent advances in our und...

  20. Electrochemical studies of nevirapine, an anti-HIV drug, and its assay in tablets and biological samples

    Directory of Open Access Journals (Sweden)

    JALDAPPAGARI SEETHARAMAPPA

    2012-06-01

    Full Text Available The electrochemical oxidation of nevirapine, an anti-HIV drug, at a glassy carbon electrode has been studied by voltammetric techniques. Nevirapine showed one well defined irreversible oxidation peak with a potential of 0.749 V in phosphate buffer at pH 10. The effects of different electrolytes, pH and scan rate on the electrochemical behaviour of nevira¬pine were examined to determine the optimum reaction conditions. The oxidation peak current was found to vary linearly with the concentration of nevirapine in the range of 5.0 – 350 µM. The limit of detection and limit of quantification values were calculated and found to be 1.026 µM and 3.420 µM, respectively. The low relative standard deviation values of inter-day and intra-day assays highlighted the good reproducibility of the proposed m¬ethod for assay of nevirapine. Further, a sensitive and accurate differential pulse voltammetric method was developed for the determination of nevirapine concentrations in pharma¬ceutical formulations.

  1. Activation of the human nuclear xenobiotic receptor PXR by the reverse transcriptase-targeted anti-HIV drug PNU-142721

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yuan; Redinbo, Matthew R. (UNC)

    2012-10-09

    The human pregnane X receptor (PXR) is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. PXR responds to a structurally diverse variety of endogenous and xenobiotic compounds, and coordinates the expression of genes central to the metabolism and excretion of potentially harmful chemicals, including human therapeutics. The reverse transcriptase inhibitor PNU-142721 has been designed to treat human immunodeficiency virus (HIV) infection. Although this compound has anti-HIV activity, it was established using cell-based assays that PNU-142721 is an efficacious PXR agonist. We present here the 2.8 {angstrom} resolution crystal structure of the human PXR ligand-binding domain in complex with PNU-142721. PXR employs one hydrogen bond and fourteen van der Waals contacts to interact with the ligand, but allows two loops adjacent to the ligand-binding pocket to remain disordered in the structure. These observations highlight the role structural flexibility plays in PXR's promiscuous responses to xenobiotics. The crystal structure also explains why PNU-173575, a thiomethyl metabolite of PNU-142721, exhibits enhanced PXR activation relative to the unmodified compound and why PNU-142721 can also activate rat PXR. Taken together, the results presented here elucidate the structural basis for PXR activation by PNU-142721 and related chemicals.

  2. Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Rafati, Amir Abbas, E-mail: aa_rafati@basu.ac.ir; Afraz, Ahmadreza

    2014-06-01

    The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus infection. The detection and determination of this drug are very importance in human serum because of its undesirable effects. A new ZDV sensor was fabricated on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the electrodeposited silver has a nanofilm structure and further electrochemical studies showed that the prepared nanocomposite has high electrocatalytic activity and is appropriate for using in sensors. The amperometric technique under optimal conditions is used for the determination of ZDV ranging from 0.1 to 400 ppm (0.37 μM–1.5 mM) with a low detection limit of 0.04 ppm (0.15 μM) (S/N = 3) and good sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and shows an average recovery of 98.6% in real samples. - Highlights: • New anti-HIV drug sensor was fabricated on the basis of nanomaterials composite. • The GCE modified by prepared hydrophilic MWCNT silver nanoparticles. • Silver nanofilm electrodeposited on MWCNT/GCE and characterized by SEM, EDX, CV and LSV • Response of electrode to ZDV was thoroughly investigated by electrochemical techniques.

  3. Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

    Directory of Open Access Journals (Sweden)

    Min-Hsuan Lin

    Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

  4. Amperometric sensing of anti-HIV drug zidovudine on Ag nanofilm-multiwalled carbon nanotubes modified glassy carbon electrode

    International Nuclear Information System (INIS)

    The zidovudine (ZDV) is the first drug approved for the treatment of HIV virus infection. The detection and determination of this drug are very importance in human serum because of its undesirable effects. A new ZDV sensor was fabricated on the basis of nanocomposite of silver nanofilm (Ag-NF) and multiwalled carbon nanotubes (MWCNTs) immobilized on glassy carbon electrode (GCE). The modified electrodes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV), and linear sweep voltammetry (LSV) techniques. Results showed that the electrodeposited silver has a nanofilm structure and further electrochemical studies showed that the prepared nanocomposite has high electrocatalytic activity and is appropriate for using in sensors. The amperometric technique under optimal conditions is used for the determination of ZDV ranging from 0.1 to 400 ppm (0.37 μM–1.5 mM) with a low detection limit of 0.04 ppm (0.15 μM) (S/N = 3) and good sensitivity. The prepared sensor possessed accurate and rapid response to ZDV and shows an average recovery of 98.6% in real samples. - Highlights: • New anti-HIV drug sensor was fabricated on the basis of nanomaterials composite. • The GCE modified by prepared hydrophilic MWCNT silver nanoparticles. • Silver nanofilm electrodeposited on MWCNT/GCE and characterized by SEM, EDX, CV and LSV • Response of electrode to ZDV was thoroughly investigated by electrochemical techniques

  5. Combined molecular docking, molecular dynamics simulation and quantitative structure-activity relationship study of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives as potent anti-HIV drugs

    Science.gov (United States)

    Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun; Li, Peizhen; Tian, Yueli; Zhai, Honglin; Li, Yang

    2014-06-01

    3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine is an antiretroviral agent, which can act against human immunodeficiency virus (HIV) infection, but the mechanism of action of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives remained ambiguous. In this study, multiple linear regression (MLR) was applied to establish a quite reliable model with the squared correlation coefficient (R2) of 0.8079. We also used chemical information descriptors based on the simplified molecular input line entry system (SMILES) to get a better model with R2 of 0.9086 for the training set, and R2 of 0.8031 for the test set. Molecular docking was utilized to provide more useful information between pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives and HIV-1 protease, such as active site, binding mode and important residues. Molecular dynamics simulation was employed to further validate the docking results. This work may lead to a better understanding of the mechanism of action and aid to design novel and more potent anti-HIV drugs.

  6. Synthesis of highly anti-HIV active sulfated poly- and oligo-saccharides and analysis of their action mechanisms by NMR [nuclear magnetic resonance] spectroscopy

    International Nuclear Information System (INIS)

    We have been synthesizing sulfated polysaccharides and oligosaccharides with highly anti-HIV (human immunodeficiency virus) activities. It has been known that sulfated polysaccharides such as dextran sulfate and pentosan polysulfate have biological activities such as anticoagulant activity and recently anti-HIV activity. Curdlan sulfate having 1,3-β-linked glucan backbone had high anti-HIV activity but low anticoagulant activity. Phase I/II test for the curdlan sulfate as an AIDS (acquired immunodeficiency syndrome) drug was carried out in the United States. In this study, regioselectivity sulfatec curdlan sulfates were prepared in order to study effects of sulfate groups and conformation of curdlan sulfates. In addition, action mechanisms of curdlan sulfate as anti-AIDS drug and of heparin as an anticoagulant were examined by means of NMR spectroscopy. 1. Structure dependence of anti-HIV and anticoagulant activities of sulfated polysaccharides. Curdlan with M n 9000 was regioselectively sulfated on its hydroxyl groups at 6, 4, and 2 positions. Those were a curdlan sulfate 62S in which 100% of 6-OH, and about 50% of 2-OH was sulfated, a curdlan sulfate 42S in which 4- and 2-OH's were sulfated, and a curdlan sulfate in which 6, 4, and 2-OH's were partially sulfated. All curdlan sulfates had very high anti-HIV activities exhibited by the drug concentration of 50% inhibition of infection, i.e., EC50 of 0.04 - 0.25 μg/mL. However, there was almost no difference in the activity among the samples. Therefore, it was revealed that the degree of sulfation and putative conformation of the curdlan sulfates but not the position of sulfate groups have large effects on the anti-HIV activity. On the other hand, the anticoagulant activity increased with increasing molecular weight of the curdlan sulfates. As a result, it is assumed that the size of reaction sites of the virus protein reacting with curdlan sulfate is different from that of the proteins related to anticoagulant. 2

  7. Anti-HIV Drug Discovery and Development: Current Innovations and Future Trends.

    Science.gov (United States)

    Zhan, Peng; Pannecouque, Christophe; De Clercq, Erik; Liu, Xinyong

    2016-04-14

    The early effectiveness of combinatorial antiretroviral therapy (cART) in the treatment of HIV infection has been compromised to some extent by rapid development of multidrug-resistant HIV strains, poor bioavailability, and cumulative toxicities, and so there is a need for alternative strategies of antiretroviral drug discovery and additional therapeutic agents with novel action modes or targets. From this perspective, we first review current strategies of antiretroviral drug discovery and optimization, with the aid of selected examples from the recent literature. We highlight the development of phosphate ester-based prodrugs as a means to improve the aqueous solubility of HIV inhibitors, and the introduction of the substrate envelope hypothesis as a new approach for overcoming HIV drug resistance. Finally, we discuss future directions for research, including opportunities for exploitation of novel antiretroviral targets, and the strategy of activation of latent HIV reservoirs as a means to eradicate the virus. PMID:26509831

  8. A simplified and less expensive strategy for confirming anti HIV-1 screening results in a diagnostic laboratory in Lubumbashi, Zaire.

    Science.gov (United States)

    Laleman, G; Kambale, M; Van Kerckhoven, I; Kapila, N; Konde, M; Selemani, U; Piot, P; van der Groen, G

    1991-12-01

    The conventional algorithm for HIV testing based on the confirmation of all positive anti-HIV screening reactions by Western blot (WB) is too expensive for developing countries. We investigated the validity of confirming positive screening assay reactions by a second screening test, limiting the use of the supplemental assay to the discrepant test results (algorithm 3), or screening all sera with 2 different assays and retesting all discrepant results by a supplemental assay (algorithm 4) on a panel of 519 sera in a regional reference laboratory in Lubumbashi, Zaire. Combining the Vironostika anti-HTLV-III ELISA with HIV Chek 1 + 2 or Clonatec Rapid HIV 1/2 Ab on all samples and retesting the discrepant results in WB or a line immunoassay (INNO-LIA) (algorithm 4), yielded a sensitivity of 100% and specificities of 98.4% and 99.0% respectively, at costs of 7.3 US $ and 9.3 US $ per test, respectively, for a 40% prevalence of HIV antibody positive samples. The conventional algorithm scored a sensitivity of 97.1% and a specificity of 100% for 11.3 US $ per test. The testing strategy of combining HIV Chek 1 + 2 and Clonatec Rapid HIV 1/2 Ab, an interesting option for small isolated centra, had a 96.6% sensitivity, but yielded only a slightly better specificity of 99.0%, as compared to 97.8% for HIV Chek alone. The price of combining the two simple assays using algorithm 3 was 6.8 US $ per test, using algorithm 4 was 10.6 US $. HIV testing strategies based on ELISA and a simple HIV test are a valuable alternative for reference laboratories faced with a high prevalence of HIV positive samples. PMID:1789703

  9. Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

    Science.gov (United States)

    Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

    2015-01-01

    The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target. PMID:26355431

  10. The effects of inhomogeneous boundary dilution on the coating flow of an anti-HIV microbicide vehicle

    Science.gov (United States)

    Tasoglu, Savas; Peters, Jennifer J.; Park, Su Chan; Verguet, Stéphane; Katz, David F.; Szeri, Andrew J.

    2011-09-01

    A recent study in South Africa has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [Karim et al., Science 329, 1168 (2010)]. However, the gel for this drug and anti-HIV microbicide gels in general have not been designed using an understanding of how gel spreading and retention in the vagina govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [Szeri et al., Phys. Fluids 20, 083101 (2008)]. This should incorporate the full rheological behavior of a gel, including how rheological properties change due to contact with, and dilution by, ambient vaginal fluids. Here, we extend our initial analysis, incorporating the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our original model is supplemented with a convective-diffusive transport equation to characterize water transport into the gel and, thus, local gel dilution. The problem is solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally, delineating the way constitutive parameters of a shear-thinning gel are modified by dilution. Results show that dilution accelerates the coating flow by creating a slippery region near the vaginal wall akin to a dilution boundary layer, especially if the boundary flux exceeds a certain value. On the other hand, if the diffusion coefficient of boundary fluid is increased, the slippery region diminishes in extent and the overall rate of gel spreading decreases.

  11. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody.

    Directory of Open Access Journals (Sweden)

    Frank Sainsbury

    Full Text Available The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product.To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER. Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO cell-produced 2G12.Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for

  12. Identification of a Small Molecular Anti - HIV - 1 Compound that Interferes with Formation of the Fusion - active gp41 Core

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The human immunodeficiency virus type 1 (HIV - 1 ) envelope glycoprotein gp41 plays a critical role in the fusion of viral and target cell membranes. The gp41 extracellular domain, which contains fusion peptide (FP), N - and C - terminal hydrophobic heptad repeats (NHR and CHR, respectively). Peptides derived from NHR and CHR regions,designated N- and C- peptides, respectively, can interact with each other to form a six - stranded coiled - coil domain, representing the fusion-active gp41 core. Our previous studies demonstrated that the C- peptides have potent inhibitory activity against HIV- 1 infection.These peptides inhibit HIV- 1 -mediated membrane fusion by binding to NHR regions for preventing the formation of fusion- active gp41 core. One of the C - peptides, T - 20, which is in the phase Ⅲ clinical trails, is expected to become the first peptide HIV fusion inhibitory drug in the near future. However, this peptide HIV fusion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Therefore, it is essential to develop small molecular non -peptide HIV fusion inhibitors having similar mechanism of action as the C- peptides. We have established an ELISA- based screening assay using a unique monoclonal antibody, NC- 1, which can specifically bind to a conformational epitope on the gp41 core domain. Using this screening assay, we have identified a small molecular anti- HIV- 1 compound,named ADS-Jl, which inhibits HIV- 1- mediated membrane fusion by blocking the interaction between the NHR and CHR regions to form the fusion - active gp41 core. This compound will be used as a lead to design and develop novel HIV fusion inhibitors as new drugs for the treatment of HIV infection and/or AIDS.

  13. PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo.

    Science.gov (United States)

    Aravantinou, Meropi; Frank, Ines; Hallor, Magnus; Singer, Rachel; Tharinger, Hugo; Kenney, Jessica; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Salazar, Andres; Piatak, Michael; Lifson, Jeffrey D; Robbiani, Melissa; Derby, Nina

    2016-01-01

    Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity. PMID:27603520

  14. Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2010-04-01

    Full Text Available Abstract Background Previous studies have shown that 3-hydroxyphthalic anhydride (HP-modified bovine milk protein, β-lactoglobulin (β-LG, is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission. Results Maleic anhydride (ML, succinic anhydride (SU and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low in vitro cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells. Conclusion ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.

  15. Regioselective synthesis and anti-HIV activity of the novel 2- and 4- substituted pyrazolo [4,5-e] [ 1,2,4]thiadiazines

    Institute of Scientific and Technical Information of China (English)

    Xin Yong Liu; Ren Zhang Yan; Nian Gen Chen; Wen Fang Xu

    2007-01-01

    The new regioisomer 7-methyl-pyrazolo[4,5-e] [1,2,4]thiadiazine nucleus (5) was synthesized, and its novel mono-N2- or N4-substituted pyrazolo[4,5-e][1,2,4]thiadiazines (6, 7) were regioselectively prepared by deprotonation of N2 or/and N4 atoms with different molar ratio of NaH and alkyl halides. Anti-HIV-1 screening tests showed some compounds to be potent as HIV-1 nonnucleoside reverse transcriptase inhibitors (HIV-1 NNRTIs).(C) 2006 Xin Yong Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  16. Synthesis of novel PETT analogues: 3,4-dimethoxy phenyl ethyl 1,3,5-triazinyl thiourea derivatives and their antibacterial and anti-HIV studies

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Rakesh B. [Veer Narmad South Gujarat University, Udhna, Gujarat (India). Dept. of Chemistry; Chikhalia, Kishor H.; Pannecouque, Christophe [Gujarat University, Navrangpura, Gujarat (India). School of Science. Dept. of Chemistry]. E-mail: chikhalia_kh@yahoo.com; Clercq, Erik de [K.U.Leuven, Leuven (Belgium)). Rega Institute for Medical Research

    2007-03-15

    3,4-Dimethoxy phenyl ethyl-1,3,5-triazinyl thiourea derivatives (8a-o and 9a-o) were prepared by condensation of 2,4,6-trichloro-1,3,5-s-triazine (1) with 4-hydroxy coumarin (2), 3,4-dimethoxy phenyl ethyl thiourea (4) and various substituted phenyl urea/thiourea (6a-o/7a-o) and tested for their antibacterial and anti-HIV activities against different microorganisms. The structures of novel synthesized compounds have been established on the basis of {sup 1}H NMR, IR and Elemental Analysis. (author)

  17. Synthesis of novel PETT analogues: 3,4-dimethoxy phenyl ethyl 1,3,5-triazinyl thiourea derivatives and their antibacterial and anti-HIV studies

    International Nuclear Information System (INIS)

    3,4-Dimethoxy phenyl ethyl-1,3,5-triazinyl thiourea derivatives (8a-o and 9a-o) were prepared by condensation of 2,4,6-trichloro-1,3,5-s-triazine (1) with 4-hydroxy coumarin (2), 3,4-dimethoxy phenyl ethyl thiourea (4) and various substituted phenyl urea/thiourea (6a-o/7a-o) and tested for their antibacterial and anti-HIV activities against different microorganisms. The structures of novel synthesized compounds have been established on the basis of 1H NMR, IR and Elemental Analysis. (author)

  18. 抗 HIV 药物的研发现状及发展趋势分析%Research Status Quo and Development Trend of Anti - HIV Drugs

    Institute of Scientific and Technical Information of China (English)

    张婷; 贾晓峰; 安嘉璐

    2014-01-01

    近年来,艾滋病感染人数急剧增加,已成为威胁人类健康的重大疾病。为了解抗人类免疫缺陷病毒(HIV)药物的研究现状和发展趋势,对 Thomson Reuters Integrity 数据库中收录的抗 HIV 药物信息进行统计,从药物发展阶段、药物类型、作用靶点和天然来源类型等方面进行分析。研究发现,抗 HIV 药物大多处于生物测定阶段,生物制品在药物类型中占绝对优势,作用靶点大多数是针对 HIV 复制周期中的关键酶,抗 HIV 药物的天然来源以植物为主,天然产物是未来重要的发展方向。%( Research Institute of Medical Information . Medical Library,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China 100020) In recent years,the number of HIV infections increases sharply,which has become a major disease threatening the human health. In order to understand the research status quo and the development trend of anti - HIV drugs,the anti - HIV drugs information included in the Thomson Reuters Integrity database was performed the statistics for conducting the analysis on the aspects of the devel-opment stage of drugs,drug types,effect targets and natural source type. The study finds that most of the anti - HIV drugs are in the stage of biological testing;the biological products occupies the absolute superiority;the most effect targets aim at the key enzymes in the HIV replication cycle;natural sources of anti - HIV drugs are dominated by plants. The natural products are the important development direction in future.

  19. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer;

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients...

  20. A testagem anti-HIV nos serviços de ginecologia do município do Rio de Janeiro

    Directory of Open Access Journals (Sweden)

    Carla Luzia França Araújo

    2014-03-01

    Full Text Available Esta pesquisa propõe um estudo sobre a oferta do teste anti-HIV em serviços da Atenção Básica de Saúde do município do Rio de Janeiro, na clínica de ginecologia. O objetivo desse estudo foi analisar os aspectos que envolvem a ampliação do acesso ao diagnóstico do HIV/AIDS nos serviços de Ginecologia da Atenção Básica no município do Rio de Janeiro. Métodos: Estudo qualitativo descritivo. Os dados foram obtidos por meio de entrevista semiestruturada, e, para a análise dos dados qualitativos, optamos por utilizar o Discurso do Sujeito Coletivo. Como resultados, pudemos perceber que,na área de ginecologia, a oferta de testes anti-HIV ainda é muito baixa, acontecendo na maior parte dos casos devido ao pré-natal. Conclusão: De forma geral, as pessoas não se sentem vulneráveis ao HIV, e julgam não apresentar comportamentos de risco por muitas vezes desconhecerem a forma de transmissão da doença.

  1. Novel Synthesis and Anti-HIV-1 Activity of 2-Arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (Aryl S-DABOs)

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo;

    2007-01-01

    The synthesis and the anti-HIV-1 activity of a series of 2-arylthio-6-benzyl-2,3-dihydro-1H-pyrimidin-4-ones (aryl S-DABOs) are reported. These compounds were synthesized via a coupling reaction of the corresponding 6-benzyl-2-thiouracils with aryl iodides in the presence of neocuproine hydrate, ...

  2. Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study)

    DEFF Research Database (Denmark)

    Worm, Signe W; De Wit, Stephane; Weber, Rainer;

    2009-01-01

    DM and preexisting CHD on the development of a new CHD episode among 33,347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). METHODS AND RESULTS: Over 159,971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV...

  3. A testagem anti-HIV nos serviços de ginecologia do município do Rio de Janeiro

    OpenAIRE

    Carla Luzia França Araújo; Priscila da Silva Aguiar; Gleice Kelly Araújo dos Santos; Maíra Guimarães Ponce de Oliveira; Lívia de Souza Câmara

    2014-01-01

    Esta pesquisa propõe um estudo sobre a oferta do teste anti-HIV em serviços da Atenção Básica de Saúde do município do Rio de Janeiro, na clínica de ginecologia. O objetivo desse estudo foi analisar os aspectos que envolvem a ampliação do acesso ao diagnóstico do HIV/AIDS nos serviços de Ginecologia da Atenção Básica no município do Rio de Janeiro. Métodos: Estudo qualitativo descritivo. Os dados foram obtidos por meio de entrevista semiestruturada, e, para a análise dos dados qualitativos, ...

  4. Studies of the quantitative structure activity relationship for phenylethylthiazolylthiourea of anti-HIV drug using new three-dimensional structure descriptors

    International Nuclear Information System (INIS)

    A newly developed three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) was used to describe the chemical structures of 61 anti-HIV drugs as phenylethylthiazolylthiourea derivatives. Here one quantitative structure activity relationship (QSAR) model was built by partial least square regression (PLS). The estimation stability and generalization ability of the model were strictly analyzed by both internal and external validations. The correlation coefficient of established PLS model (Rcum), leave-one-out cross-validation (QVV) , predicted values versus experimental ones of external samples (Qext) were 0.907, 0.878, 0.913, respectively. The results indicated that QSAR model had both favorable estimation stability and good prediction capabilities. Satisfactory results showed that 3D-HoVAIF can preferably express information related to biological activity of phenylethylthiazolylthiourea derivatives. (authors)

  5. A New Activity of Anti-HIV and Anti-tumor Protein GAP31: DNA Adenosine Glycosidase – Structural and Modeling Insight into its Functions

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Huang, P; Zhang, D; Sun, Y; Chen, H; Zhang, J; Huang, P; Kong, X; Lee-Huang, S

    2010-01-01

    We report here the high-resolution atomic structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third, GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA.

  6. A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui-Guang [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Huang, Philip L. [American Biosciences, Boston, MA 02114 (United States); Zhang, Dawei; Sun, Yongtao [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Chen, Hao-Chia [Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892 (United States); Zhang, John [Department of Chemistry, New York University, New York, NY 10003 (United States); Huang, Paul L. [Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114 (United States); Kong, Xiang-Peng, E-mail: xiangpeng.kong@med.nyu.edu [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States); Lee-Huang, Sylvia, E-mail: sylvia.lee-huang@med.nyu.edu [Department of Biochemistry, New York University School of Medicine, New York, NY 10016 (United States)

    2010-01-01

    We report here the high-resolution atomic structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third, GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA.

  7. A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase - Structural and modeling insight into its functions

    International Nuclear Information System (INIS)

    We report here the high-resolution atomic structures of GAP31 crystallized in the presence of HIV-LTR DNA oligonucleotides systematically designed to examine the adenosine glycosidase activity of this anti-HIV and anti-tumor plant protein. Structural analysis and molecular modeling lead to several novel findings. First, adenine is bound at the active site in the crystal structures of GAP31 to HIV-LTR duplex DNA with 5' overhanging adenosine ends, such as the 3'-processed HIV-LTR DNA but not to DNA duplex with blunt ends. Second, the active site pocket of GAP31 is ideally suited to accommodate the 5' overhanging adenosine of the 3'-processed HIV-LTR DNA and the active site residues are positioned to perform the adenosine glycosidase activity. Third, GAP31 also removes the 5'-end adenine from single-stranded HIV-LTR DNA oligonucleotide as well as any exposed adenosine, including that of single nucleotide dAMP but not from AMP. Fourth, GAP31 does not de-purinate guanosine from di-nucleotide GT. These results suggest that GAP31 has DNA adenosine glycosidase activity against accessible adenosine. This activity is distinct from the generally known RNA N-glycosidase activity toward the 28S rRNA. It may be an alternative function that contributes to the antiviral and anti-tumor activities of GAP31. These results provide molecular insights consistent with the anti-HIV mechanisms of GAP31 in its inhibition on the integration of viral DNA into the host genome by HIV-integrase as well as irreversible topological relaxation of the supercoiled viral DNA.

  8. Synthesis and biological evaluation of 1,3,3,4-tetrasubstituted pyrrolidine CCR5 receptor antagonists. Discovery of a potent and orally bioavailable anti-HIV agent.

    Science.gov (United States)

    Ma, Dawei; Yu, Shanghai; Li, Ben; Chen, Li; Chen, Renhai; Yu, Kunqian; Zhang, Linqi; Chen, Zhiwei; Zhong, Dafang; Gong, Zheng; Wang, Renxiao; Jiang, Hualiang; Pei, Gang

    2007-02-01

    A series of 1,3,3,4-tetrasubstituted pyrrolidine containing CCR5 receptor antagonists were designed, which were elaborated either by condensation of a lithium salt of 3-(N,N-dibenzyl)aminopropionic acid methyl ester with ethyl benzoformate or by Baylis-Hillman reaction of ethyl acrylate with ethyl benzoformate and subsequent 1,4-addition of benzylamine, in the key steps. These compounds bearing 4-(N,N-disubstituted)amino piperidine units showed low nanomolar potency against the CCR5 receptor, whereas molecules with a 4-phenylpiperidine moiety displayed poor activity. Asymmetric synthesis of the most potent compound 23 a gave rise to the (3R,4S)-enantiomer 30 and the (3S,4R)-enantiomer 31, which showed IC(50) values of 2.9 and 385.9 nM, respectively. These results indicated that (3R,4S)-configuration in the series of compounds is favored for their interaction with the CCR5 receptor. The possible binding mode of these antagonists with the CCR5 receptor was discussed using a computer-modeling method. Compound 30 displayed excellent replication inhibition of seven genetically diverse R5 HIV-1 strains in the PBMC model, in a concentration-dependent manner with EC(50) values ranging from 0.3 nM to 30 nM. This molecule showed oral bioavailabilities of 41.2 % and 21.6 % in rats and dogs, respectively. Thus, compound 30 is a promising candidate for the treatment of HIV-1 infection. PMID:17163560

  9. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding mechanism of the FDA-approved HIV PIs binding to human Hsp90. Information gained from this study should also provide a route map toward the design, optimization, and further experimental investigation of potential derivatives of PIs to treat HER2+ breast cancer.Keywords: binding free energy, loop docking, molecular dynamics, HIV-1 protease inhibitors, anticancer

  10. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents.

    Science.gov (United States)

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published "target-bound pharmacophore modeling approach". The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  11. A Simplifed and Efficient Synthesis of 7-Hydroxymethyl-6,7- Dihydropyrro- [ 1,2- c ]-Pyrimidine-1,3-Dione as a Potent Anti- HIV-1 Agent

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-Wei; ZHANG Zhi-Li; HAN Peng; MA Xiao-Yan; LIU Jun-Yi

    2003-01-01

    @@ The reverse transcriptase of HIV provides a key target for the development of anti-AIDS drugs. The discovery of 1-[ 2-hydroxyethoxymethyl]-6-phenylthio-thymine (HEPT) as a compound with potent and selective in vivo activity against HIV-1[1] has led to the synthesis many new non-nucleoside reverse transcriptase inhibitors.[2

  12. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Science.gov (United States)

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud ES

    2016-01-01

    A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD) simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621) showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  13. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    OpenAIRE

    Cele FN; Ramesh M; Soliman ME

    2016-01-01

    Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacop...

  14. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from this work confirm that this new approach is favorable in the future of the drug design industry. Keywords: HIV-1, reverse transcriptase, GSK952, molecular dynamic simulations, pharmacophore model, molecular docking

  15. Synthesis of tritium-labelled 5-chloro-2',3'-dideoxy-3'-fluorouridine (935U83) - a selective anti-HIV agent

    International Nuclear Information System (INIS)

    [5'-3H]-5-Chloro-2',3'-dideoxy-3'-fluorouridine (1; R=[3H]) was prepared at a specific activity of 10.2 Ci/mmol suitable for development of a radioimmunoassay procedure. The synthetic sequence employed controlled oxidation of unlabelled 1 to the 5'-aldehyde (2), isolation as the imidazolidine adduct (3), regeneration of the free aldehyde, reduction with [3H]NaBH4, and purification by preparative TLC. The radiochemical purity was 98.0%. (Author)

  16. Synthesis and anti-HIV evaluation of hybrid-type prodrugs conjugating HIV integrase inhibitors with d4t by self-cleavable spacers containing an amino acid residue.

    Science.gov (United States)

    Fossey, Christine; Huynh, Ngoc-Trinh; Vu, Anh-Hoang; Vidu, Anamaria; Zarafu, Irina; Laduree, Daniel; Schmidt, Sylvie; Laumond, Geraldine; Aubertin, Anne-Marie

    2007-10-01

    In an attempt to combine the anti-HIV inhibitory capacity of reverse transcriptase (RT) inhibitors (NRTIs) and integrase (IN) inhibitors (INIs), several heterodimer analogues of the previously reported [d4T]-PABC-[INI] and [d4T]-OABC-[INI] prototypes have been prepared. In these novel series, we wished to extend our results to conjugates which incorporated an enzymatically labile aminoacid unit (L-alanine) connected to d4T through a self-immolative para- or ortho-aminobenzyl carbonate (PABC or OABC) spacer. Among the novel heterodimers, several derivatives show a potent anti-HIV-1 activity, which proved comparable to that of the [L-708,906]-PABC-[d4T] Heterodimer A prototype. However, although the compounds proved inhibitory to HIV-1, they were less potent than the parent compounds from which they were derived. PMID:18035829

  17. Anti-HIV-1 activities of the extracts from the medicinal plant Linum grandiflorum Desf

    DEFF Research Database (Denmark)

    Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.;

    2009-01-01

    As part of our screening of anti-AIDS agents from natural sources e.g. Ixora undulata, Paulownia tomentosa, Fortunella margarita, Aegle marmelos and Erythrina abyssinica, the different organic and aqueous extracts of Linum grandiflorum leaves and seeds were evaluated in vitro by the microculture ...

  18. Synthesis and Anti-HIV-1 Activity of New MKC-442 Analogues with an Alkynyl-Substituted 6-Benzyl Group

    DEFF Research Database (Denmark)

    Aly, Youssef L.; Pedersen, Erik Bjerreg.; La Colla, Paolo;

    2007-01-01

    Synthesis and antiviral activities are reported of a series of 6-(3-alkynyl benzyl)-substituted analogues of MKC-442 (6-benzyl-1-(ethoxymethyl)-5-isopropyluracil), a highly potent agent against HIV. The 3-alkynyl group is assumed to give a better stacking of the substituted benzyl group to revers...

  19. Synthesis and Anti-HIV-1 Evaluation of New Sonogashira-Modified Emivirine (MKC-442) Analogues

    DEFF Research Database (Denmark)

    Danel, Krzystof; Jørgensen, Per Trolle; La Colla, Paolo;

    2009-01-01

    The MKC-442 analogue 6-(3,5-dimethylbenzyl)-5-ethyluracil substituted with a (propargyloxo)methyl group at N(1) has previously been found highly active against HIV-1. The C C bond in the substituent at N(1) is here utilized in a series of chemical reactions in order to develop new agents with hig...

  20. Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120

    Energy Technology Data Exchange (ETDEWEB)

    Hoque, M. Mominul [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Rajshahi University, Rajshahi (Bangladesh); Suzuki, Kaoru [Iwaki Meisei University, Iwaki, Fukushima 970-8551 (Japan); Tsunoda, Masaru; Jiang, Jiandong; Zhang, Fang; Takahashi, Atsushi; Ohbayashi, Naomi; Zhang, Xiaoxue [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tanaka, Haruo [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); KIIM Pharmaceutical Laboratories Inc., Fukushima 970-8551 (Japan); Ōmura, Satoshi [Kitasato University, Tokyo 108-8641 (Japan); Takénaka, Akio, E-mail: atakenak@sakura.email.ne.jp [Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Iwaki Meisei University, 5-5-1 Chuodai-Iino, Iwaki, Fukushima 970-8551 (Japan); Tokyo Institute of Technology, Yokohama 226-8501 (Japan)

    2012-12-01

    X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P2{sub 1}2{sub 1}2{sub 1} symmetry to exhibit an apparent space group P2{sub 1}3 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O{sup 3} and O{sup 4} atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O{sup 1} atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features

  1. Differences in the mannose oligomer specificities of the closely related lectins from Galanthus nivalis and Zea mays strongly determine their eventual anti-HIV activity

    Directory of Open Access Journals (Sweden)

    Fouquaert Elke

    2011-02-01

    Full Text Available Abstract Background In a recent report, the carbohydrate-binding specificities of the plant lectins Galanthus nivalis (GNA and the closely related lectin from Zea mays (GNAmaize were determined by glycan array analysis and indicated that GNAmaize recognizes complex-type N-glycans whereas GNA has specificity towards high-mannose-type glycans. Both lectins are tetrameric proteins sharing 64% sequence similarity. Results GNAmaize appeared to be ~20- to 100-fold less inhibitory than GNA against HIV infection, syncytia formation between persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T-lymphocyte SupT1 cells, HIV-1 capture by DC-SIGN and subsequent transmission of DC-SIGN-captured virions to uninfected CD4+ T-lymphocyte cells. In contrast to GNA, which preferentially selects for virus strains with deleted high-mannose-type glycans on gp120, prolonged exposure of HIV-1 to dose-escalating concentrations of GNAmaize selected for mutant virus strains in which one complex-type glycan of gp120 was deleted. Surface Plasmon Resonance (SPR analysis revealed that GNA and GNAmaize interact with HIV IIIB gp120 with affinity constants (KD of 0.33 nM and 34 nM, respectively. Whereas immobilized GNA specifically binds mannose oligomers, GNAmaize selectively binds complex-type GlcNAcβ1,2Man oligomers. Also, epitope mapping experiments revealed that GNA and the mannose-specific mAb 2G12 can independently bind from GNAmaize to gp120, whereas GNAmaize cannot efficiently bind to gp120 that contained prebound PHA-E (GlcNAcβ1,2man specific or SNA (NeuAcα2,6X specific. Conclusion The markedly reduced anti-HIV activity of GNAmaize compared to GNA can be explained by the profound shift in glycan recognition and the disappearance of carbohydrate-binding sites in GNAmaize that have high affinity for mannose oligomers. These findings underscore the need for mannose oligomer recognition of therapeutics to be endowed with anti-HIV activity and that mannose, but

  2. Structural insights into the specific anti-HIV property of actinohivin: structure of its complex with the α(1–2)mannobiose moiety of gp120

    International Nuclear Information System (INIS)

    X-ray analysis of anti-HIV actinohivin in complex with the target α(1-2)mannobiose moiety of high-mannose type glycans attached to HIV-1 gp120 reveals that the three rotamers generated with 120 rotations around the molecular pseudo-rotation axis are packed randomly in the unit cell according to the P212121 symmetry to exhibit an apparent space group P213 as the statistical structure. However, the high-resolution X-ray structure shows the detailed interaction geometry for specific binding. Actinohivin (AH) is an actinomycete lectin with a potent specific anti-HIV activity. In order to clarify the structural evidence for its specific binding to the α(1–2)mannobiose (MB) moiety of the D1 chains of high-mannose-type glycans (HMTGs) attached to HIV-1 gp120, the crystal structure of AH in complex with MB has been determined. The AH molecule is composed of three identical structural modules, each of which has a pocket in which an MB molecule is bound adopting a bracket-shaped conformation. This conformation is stabilized through two weak C—H⋯O hydrogen bonds facilitated by the α(1–2) linkage. The binding features in the three pockets are quite similar to each other, in accordance with the molecular pseudo-threefold symmetry generated from the three tandem repeats in the amino-acid sequence. The shape of the pocket can accept two neighbouring hydroxyl groups of the O3 and O4 atoms of the equatorial configuration of the second mannose residue. To recognize these atoms through hydrogen bonds, an Asp residue is located at the bottom of each pocket. Tyr and Leu residues seem to block the movement of the MB molecules. Furthermore, the O1 atom of the axial configuration of the second mannose residue protrudes from each pocket into an open space surrounded by the conserved hydrophobic residues, suggesting an additional binding site for the third mannose residue of the branched D1 chain of HMTGs. These structural features provide strong evidence indicating that AH is

  3. A broad spectrum anti-HIV inhibitor significantly disturbs V1/V2 domain rearrangements of HIV-1 gp120 and inhibits virus entry.

    Science.gov (United States)

    Berinyuy, Emiliene; Soliman, Mahmoud E S

    2016-01-01

    Inhibition of human immunodeficiency virus (HIV) entry into target human cells is considered as a critical strategy for preventing HIV infection. Conformational shifts of the HIV-1 envelope glycoprotein (gp120) facilitates the attachment of the virus to target cells, therefore gp120 remains an attractive target for antiretroviral therapy development. Compound 18A has been recently identified as a broad-spectrum anti-HIV inhibitor. It was proposed that 18A disrupts rearrangements of V1/V2 region in gp120; however, the precise mechanism by which 18A interferes with the inherent motion of V1/V2 domain remains obscure. In this report, we elaborate on the binding mode of compound 18A to the closed conformation of a soluble cleaved gp120 and further examine the dynamic motion of V1/V2 region in both gp120 and the gp120-18A complex via all-atom molecular dynamics simulations. In this work, comparative molecular dynamic analyses revealed that 18A makes contact with Leu179, Ile194, Ile424, Met426 W427, E370 and Met475 in the main hydrophobic cavity of the unliganded gp120 and disrupts the restructuring of V1/V2 domain observed in apo gp120. The unwinding of α1 and slight inversion of β2 in gp120 leads to the shift of VI/V2 domain away from the V3 N-terminal regions and toward the outer domain. Stronger contacts between Trp425 and Trp112 rings may contribute to the reduced flexibility of α1 observed upon 18A binding thereby inhibiting the shifts of the V1/V2 region. Binding of 18A to gp120: (1) decreases the overall flexibility of the protein and (2) inhibits the formation a gp120 conformation that closely ressembles a CD4-bound-like conformation. Information gained from this report not only elaborates on important dynamic features of gp120, but will also assist with the future designs of potent gp120 inhibitors as anti-HIV. PMID:26446906

  4. Plasmids encoding therapeutic agents

    Science.gov (United States)

    Keener, William K.

    2007-08-07

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

  5. Study on Anti-HIV of Quercetin Derivants in Natural Products%天然产物中槲皮素类化合物的抗HIV作用研究

    Institute of Scientific and Technical Information of China (English)

    王晓建; 王珊; 黄胜阳

    2011-01-01

    Objective:To review the research about anti-HIV activity of quercetin derivants from natural products, and provide reference for clinical and further research. Method:Retrieve and inspect the literatures and monographs over the past decade about anti-HIV of quercetin derivants from natural products, and analyze and summary these paper by the different function of quercetin derivants. Result: Quercetin derivants have strong anti-HIV activity, and they are mainly inhibit HIV viral replication through the three key enzymes; protease, reverse transcriptase, integrase. Conclusion: Natural products in the anti-HIV compounds quercetin play an important role, there is great significance in-depth study of these compounds%目的:综述天然产物中槲皮素类化合物的抗HIV作用方面的研究进展,为进一步临床应用和研究提供参考.方法:全面检索、查阅国内外近10年来有关天然产物中槲皮素类化合物抗HIV作用的文献与著作,并按照槲皮素类化合物的不同作用对其进行分析总结.结果:槲皮素类化合物是天然产物中具有较强抗HIV活性的一类化合物,主要作用于HIV复制所需的三个关键酶——蛋白酶、逆转录酶、整合酶,从而抑制HIV在体内的复制.结论:天然产物中的槲皮素类化合物在抗HIV方面中有着重要的作用,深入研究该类化合物具有重大意义.

  6. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    OpenAIRE

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; D'Arminio Monforte, Antonella; Smith, Colette; De Wit, Stephane; Kirk, Ole; Lundgren, Jens D.; Weber, Rainer

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as fol...

  7. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIVSF162P4. Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  8. A realização do teste anti-hiv no pré-natal: os significados para a gestante El establecimiento de la lucha contra la prueba del vih en pre-navidad: significados para el embarazo The establishment of anti-hiv test in pre-natal: meanings for pregnancy

    Directory of Open Access Journals (Sweden)

    Roberta Maria de Oliveira Silva

    2008-12-01

    Full Text Available O estudo teve por objetivo conhecer e analisar o significado da realização do teste anti-HIV no pré-natal para as gestantes. Trata-se de uma pesquisa com abordagem qualitativa e foi realizada em um Hospital Escola e em uma Maternidade do município do Rio de Janeiro. Como recurso técnico-metodológico utilizou-se o discurso do sujeito coletivo (DSC. Após a análise dos discursos verificamos que para as gestantes a realização do teste significa a possibilidade de prevenir a transmissão vertical do HIV e como parte da assistência pré-natal. O pré-natal foi considerado pelas gestantes uma excelente oportunidade para a realização do teste anti HIV, para o conhecimento da condição sorológica e início precoce do tratamento. Conclui-se que o teste, para a maioria das gestantes, representa a possibilidade de proteger o filho do HIV, além de fazer parte da construção do papel materno a partir de um cuidado concreto com a saúde do bebê.El estudio que tenía para que el objetivo sepa y analice el significado de la realización del anti-VIH de la prueba en el prenatal para las mujeres embarazadas. Uno está sobre una investigación con acercamiento cualitativo y fue ejecutado en una escuela del hospital y una maternidad de la ciudad de Rio de Janeiro. Como recurso técnico-metodológico el discurso del ciudadano colectivo fue utilizado (DSC. Después de que el análisis de los discursos, nosotros verificamos que para las mujeres embarazadas la realización de la prueba significa la posibilidad para prevenir la transmisión vertical del VIH y como parte de la ayuda prenatal. El prenatal era considerado por las mujeres embarazadas una ocasión excelente para la realización del anti VIH de la prueba, para el conocimiento de la condición sorological y del principio precoz del tratamiento. Se concluye que la prueba, para la mayoría de las mujeres embarazadas, representa la posibilidad para proteger al hijo del VIH, más allá de ser

  9. Superiority of the S,S conformation in diverse pharmacological processes: Intestinal transport and entry inhibition activity of novel anti-HIV drug lead.

    Science.gov (United States)

    Fanous, Joseph; Swed, Avi; Joubran, Salim; Hurevich, Mattan; Britan-Rosich, Elena; Kotler, Moshe; Gilon, Chaim; Hoffman, Amnon

    2015-11-30

    Chirality is an important aspect in many pharmacological processes including drug transport and metabolism. The current investigation examined the stereospecific transport and entry inhibitory activity of four diastereomers derived from a small (macrocyclic) molecule that has two chiral centers. These molecules were designed to mimic the interaction between CD4 and gp120 site of HIV-1 and thereby to function as entry inhibitor(s). Intestinal permeability was assessed by ex-vivo model using excised rat intestine mounted in side-by-side diffusion chambers. The entry inhibitory activity was monitored using indicator HeLa-CD4-LTR-beta-gal cells (MAGI assay). The (S/S) diastereomer, named CG-1, exhibited superiority in both unrelated tested biological processes: (I) high transport through the intestine and (II) entry inhibition activity (in the low μM range). The permeability screening revealed a unique transporter-mediated absorption pathway of CG-1, suggesting a significant role of the molecule's conformation on the mechanism of intestinal absorption. Here we highlight that only the S,S enantiomer (CG-1) has both (I) promising anti HIV-1 entry inhibitory properties and (II) high transporter mediated intestinal permeability. Hence we suggest preference in pharmacological processes to the S,S conformation. This report augments the knowledge regarding stereoselectivity in receptor mediated and protein-protein interaction processes. PMID:26392249

  10. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations.

    Science.gov (United States)

    Benjelloun, Fahd; Oruc, Zeliha; Thielens, Nicole; Verrier, Bernard; Champier, Gael; Vincent, Nadine; Rochereau, Nicolas; Girard, Alexandre; Jospin, Fabienne; Chanut, Blandine; Genin, Christian; Cogné, Michel; Paul, Stephane

    2016-09-01

    Mucosal HIV-1-specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir. PMID:27481846

  11. Formação, práticas e trajetórias de aconselhadores de centros de testagem anti-HIV do Rio de Janeiro, Brasil

    Directory of Open Access Journals (Sweden)

    Claudia Mora

    2015-12-01

    Full Text Available Perante a importância do aconselhamento na testagem anti-HIV, analisamos as diretrizes institucionais, as competências privilegiadas no treinamento profissional e os saberes/práticas de aconselhadores. Trata-se de estudo qualitativo centrado na análise documental, observação e entrevista com aconselhadores de Centros de Testagem e Aconselhamento (CTA do estado do Rio de Janeiro. A análise foi orientada pela teoria de Pierre Bourdieu. Foi evidenciado que o habitus profissional dos aconselhadores resulta da articulação dos treinamentos, da graduação e de experiências e interesses pessoais. A operacionalização de competências, como a escuta ativa, é limitada pela rotina dos serviços e escassez de espaços de reflexão. Para incrementar a prática do aconselhamento, é importante desenvolver competências no treinamento, manter a educação continuada e fazer adequações na rotina do serviço. Tais ajustes podem fortalecer a passagem das diretrizes à ação e o aprimoramento da organização e gestão dos CTA.

  12. Anti-HIV drug development: structural features and limitations of present day drugs and future challenges in the successful HIV/AIDS treatment.

    Science.gov (United States)

    Kumari, Garima; Singh, Ramendra K

    2013-01-01

    Acquired Immune Deficiency Syndrome (AIDS), an immuno-compromized condition, a sequel to untreated human immunodeficiency virus (HIV) infection, inviting several life-threatening diseases, has become one of the most fatal disorders in the recent past because of HIV strain variance due to mutations, passive latency and reservoirs helping in replenishing and reviving the HIV-1 proviral DNA. Scientific efforts have led to the discovery of several effective drugs against HIV and lowered the morbidity and mortality all over the world. However, despite availability of a good number of anti-HIV drugs, the problem, for the foreseeable reasons, stands out as the most chronic disease due to the less tolerability and low accessibility of drugs, life-long expensive treatment, and above all, the emergence of drug resistant viral strains. This review dwells upon HIV infection and its proliferation inside the host system, drug targets, different types of drugs, their structural features and mode of interaction with viral targets and drug regimens. It further focuses on topics of latest interest regarding drug development, fixed dose combinations (FDCs), the limitations of present day drugs with their structural features along with their pharmacodynamics, pharmacokinetics and pharmacogenomics and the challenges in finding a permanent cure for HIV/AIDS. PMID:23092282

  13. 天然药物抗HIV机制的研究进展%Research Progress of the Mechanism of Anti-HIV Natural Medicines

    Institute of Scientific and Technical Information of China (English)

    赵梅; 周淑琴; 杨莉娅

    2012-01-01

    Acquired immunodeficiency syndrome (AIDS) is one of the most serious infectious diseases that severely threats the human health. Till now there are still no satisfactory therapeutic strategy against AIDS. Recent studies have shown that natural medicines possess various anti-AIDS pharmacological activities including immuno-regulation, inhibition of the enzymes in the process of HIV replication, and antioxidant function, etc. In this article, we overview the advances in the mechanism research of anti-HIV natural medicines.%艾滋病是威胁人类健康的重大传染性疾病,目前仍未有令人满意的治疗方法.近年来的研究发现,天然药物具有广泛的抗HIV药理学活性,如免疫调节、抑制HIV复制中相关功能酶、抗氧化等.本文就天然药物抗HIV的相关作用机制展开综述.

  14. Aconselhamento pós-teste anti-HIV: análise à luz de uma teoria humanística de Enfermagem Consejería pós test Anti-HIV: análisis a luz de una teoría humanistica de enfermería Anti-HIV after-test counselling: analysis at a light of a Nursing humanistic theory

    Directory of Open Access Journals (Sweden)

    Maria Alix Leite Araújo

    2006-12-01

    Full Text Available Este trabalho analisa o aconselhamento pós-teste anti-HIV em Unidades Básicas de Saúde. Trata-se de um estudo qualitativo desenvolvido em Unidades Básicas de Saúde da Família de Fortaleza (UBASF. O trabalho de campo ocorreu pela observação do atendimento de 12 enfermeiros em consultas de pré-natal. O referencial teórico de análise foi a Teoria Humanística de Enfermagem de Paterson e Zderad visto que a Enfermagem, segundo a teoria, implica um tipo especial de encontro entre seres humanos. A análise baseou-se no conceito de diálogo, tendo como variáveis seus elementos estruturais: o encontro, o relacionamento, a presença e o chamado, e a resposta. Observou-se que a assistência às gestantes não atingiu o relacionamento EU-TU, ou seja, o relacionamento sujeito-sujeito, com a presença do diálogo genuíno. Prevaleceu o relacionamento EU-ISSO, sujeito-objeto. As consultas eram rápidas e puramente mecânicas, levando esses profissionais, em certos momentos, a fugirem de uma assistência humanizada.Este trabajo analiza el pos test de consejería anti-HIV en las Unidades Básicas de Salud. Es un estudio cualitativo desarrollado en las Unidades Básicas de Salud de la Familia en la ciudad de Fortaleza (UBASF. El trabajo de campo sucedió por la observación de la asistencia de 12 enfermeros en las consultas de pré-natal. El referencial teórico de análisis fué la Teoría Humanistica de Paterson y Zderad de Enfermería, visto en la enfermería, según la teoría, implica en un tipo especial de encuentro entre los seres humanos. El análisis era basado en el concepto de diálogo, teniendo como las variables sus elementos estructurales: el encuentro, la relación, la presencia y el llamamiento y la respuesta. Fue observado que la ayuda a la embarazada no alcanzó la relación YO-USTED, en otros términos, el sujeto-sujeto de la relación, con la presencia del diálogo auténtico. La relación que prevaleció era el YO-AQUEL, sujeto

  15. Evaluation of Cynanchum otophyllum glucan sulfate against human immunodeficiency virus and herpes simplex virus as a microbicide agent

    Directory of Open Access Journals (Sweden)

    Jian Tao

    2011-01-01

    Full Text Available Objective : The root ofCynanchum otophyllum -also known as Qing Yang Sheng-is a traditional ethnical Chinese medicine. The objective of this study was to evaluate in vitro activities and safety of C. otophyllum glucan sulfate (PS20 against Human Immunodeficiency Virus (HIV and Herpes Simplex Virus (HSV. Materials and Methods : Anti-HIV activity was detected with syncytial formation assay and quantitative P24 Enzyme-Linked Immunosorbent Assay (ELISA. Anti-HSV activity was detected with plaque reduction assay; cytotoxicity was tested with MTT colorimetric assay; and anti-bacterial activity was tested with microdilution method. Anti-HIV mechanism was investigated with fusion inhibition, time of addition, and pretreatment. Results : The 50% Inhibition Concentration (IC 50 of PS20 for HIV-1 IIIB , HIV- Ada-M , HIV-1 Bal , HSV-I, and -II were 0.26 ± 0.02 mM, 0.46 ± 0.02 mM, 0.90 ± 0.04 mM, 3.45 ± 0.85 mM, and 0.70 ± 0.22 mM, respectively. Selectivity Indices (SI were 653, 50, 39, 85, and 362, respectively. Studies on anti-HIV mechanism of PS20 showed that the target molecule should be the envelope protein. The 50% Cytotoxicity Concentrations (CC 50 of PS20 for HeLa and ME-180 cell lines and human foreskin fibroblast cells was more than 70 mM. The Minimum Inhibitory Concentration (MIC for vaginal lactobacilli was more than 1000 mM. Conclusion : PS20 possesses anti-HIV and HSV effect and low cytotoxicity to epithelium cells and vaginal lactobacilli. It may be considered as a potential microbicide agent for further investigation.

  16. Controlling drug efficiency by encapsulation into carbon nanotubes: A theoretical study of the antitumor Cisplatin and the anti-HIV TIBO molecules

    Science.gov (United States)

    Bessrour, R.; Belmiloud, Y.; Hosni, Z.; Tangour, B.

    2012-06-01

    From the beginning of last century, Paul Ehrlich, a specialist in the immune system and the Nobel Prize (1908) had raised the possibility of "magic bullets" can directly address, in an organism, drugs in a particular area of the body, sparing all other parts of side effects. Carbon nanotubes (CNTs) have particular property to cross cell membranes easily. In an effort to optimize the use of CNT as drug nanocarriers, we divided our study into two parts. In the first, our concern was to find the minimum diameter of a single wall CNT can encapsulate an anticancer drug that iscisplatin without altering its geometry in order conserve its therapeutic power. Behavior of one and two Cisplatin(Cp) molecules confined in capped and opened single-walled carbon nanotubes (CNTs) is studied by means of ab-initio calculations. Single molecule binding energies clearly exhibit encapsulation dependence on tube diameters that range from 6.26 Å to 12.04 Å. A weak stabilization energy of the Cp@(11,0) equal to -70 kcal.mol-1 has been obtained corresponding to a CNT's diameter of 8.5Å. We noticed that Cisplatin molecule changes shape when encapsulated into CNTs' whose diameters are less than 7.6 Å. In the presence of a second Cisplatin molecule in the (10,0) CNT, preferred position stays parallel to CNT's axis leading to a linear density of roughly 1588 molecules/μm of CNT's length corresponding to a linear density of 7.9 10-19 g/μm. The 195Pt chemical shift tensors are calculated using GIAO method. NMR calculations reveal that Platinum chemical shift is sensitive to CNT's diameter and is linearly correlated to confinement energy. 195Pt chemical shift measurement may be a direct method to access to the diameter of the encapsulating CNT's and to control the amount of drug molecule transported by this CNT. In the second part, the opposite has been sought is to say how the use of nanotubes with different diameters can control the change in a geometry of an anti-HIV drug that is TIBO

  17. Desenvolvimento de formulações e tecnologia de obtenção de comprimidos revestidos de efavirenz: terapia anti-HIV Development of formulations and technology of efavirenz coated tablets obtention: anti-HIV therapy

    Directory of Open Access Journals (Sweden)

    Osnir de Sá Viana

    2006-12-01

    Full Text Available O efavirenz é uma das mais recentes classes de agentes anti-retrovirais aplicados no tratamento de infecções por HIV. Está entre os medicamentos de primeira escolha no tratamento da AIDS. Como o efavirenz possui característica hidrofóbica, baixa densidade e oferece grande resistência ao escoamento, a escolha de uma formulação adequada deste fármaco é essencial no desenvolvimento dos comprimidos e para garantir melhor disponibilização no trato gastrointestinal, de forma a alcançar a biodisponibilidade e o efeito terapêutico desejados. Neste trabalho, apresentamos, de forma lógica, o desenvolvimento tecnológico de comprimidos revestidos de efavirenz, levando em consideração suas características físicas e físico-químicas. Os núcleos (comprimidos de efavirenz foram obtidos utilizando-se a técnica de granulação por via úmida. No revestimento por película utilizou-se Opadry® Y-1-7000 em sistema aquoso. Os parâmetros adotados para avaliação física dos comprimidos seguiram as especificações farmacopéicas oficiais e a determinação quantitativa foi realizada mediante método analítico desenvolvido e validado.Efavirenz is one of the most recent classes of anti-retroviral drugs used in the treatment of HIV infections. It is the first choice therapy for AIDS treatment. As efavirenz detains hydrofobic characteristic, low density and offers great resistance to draining, it has been essential to choose an adequated formulation for it, in order to guarantee drug's availability in gastro-intestinal tract, achieving bioavailability and expected therapeutical effects. This work presents efavirez coated tablets thecnological development, considering the physics and physico-chemical characteristics of this drug. The efavirez nucleus (tablets has been obtained employing granulation technics by humid via. In the coating by film, Opadry Y-1-7000 in aquous system was used. The adopted parameters to tablet phisics evaluation

  18. Anti-HIV Ⅰ/Ⅱ Activity and Molecular Cloning of a Novel Mannose/Sialic Acid-binding Lectin from Rhizome of Polygonatum cyrtonema Hua

    Institute of Scientific and Technical Information of China (English)

    Jie AN; Jin-Ku BAO; Jin-Zhi LIU; Chuan-Fang WU; Jian LI; Lei DAI; Els Van DAMME; Jan BALZARINI; Erik De CLERCQ; Fang CHEN

    2006-01-01

    The anti-human immunodeficiency virus (HIV) Ⅰ/Ⅱ activity of a mannose and sialic acid binding lectin isolated from rhizomes of Polygonatum cyrtonema Hua was elucidated by comparing its HIV infection inhibitory activity in MT-4 and CEM cells with that of other mannose-binding lectins (MBLs). The anti-HIV activity of Polygonatum cyrtonema Hua lectin (PCL) was 10- to 100-fold more potent than other tested MBLs, but without significant cytotoxicity towards MT-4 or CEM cells. To amplify cDNA of PCL by 3'/5'-rapid amplification of cDNA ends (RACE), the 30 amino acids of N-terminal were determined by sequencing and the degenerate oligonucleotide primers were designed. The full-length cDNA of PCL contained 693 bp with an open reading frame encoding a precursor protein of 160 amino acid residues, consisting of a 28-residue signal peptide, a 22-residue C-terminal cleavage peptide and a 110-residue mature polypeptide which contained three tandemly arranged subdomains with an obvious sequence homology to the monocot MBL. However, only one active mannose-binding site (QDNVY) was found in subdomain Ⅰ of PCL, that of subdomain Ⅱ and Ⅲ changed to HNNVY and PDNVY, respectively. There was no intron in PCL, which was in good agreement with other monocot MBLs. Molecular modeling of PCL indicated that its three-dimen-sional structure resembles that of the snowdrop agglutinin. By docking, an active sialic acid-binding site was found in PCL. The instabilization of translation initiation region (TIR) in mRNA of PCL benefits its high expression in rhizomes.

  19. Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review.

    Science.gov (United States)

    Jing, Wanghui; Liu, Ruilin; Du, Wei; Luo, Zhimin; Guo, Pengqi; Zhang, Ting; Zeng, Aiguo; Chang, Chun; Fu, Qiang

    2016-01-01

    A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A), as well as UDP-glucuronosyltransferases (UGTs) primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs' metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs) induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3' and C-4' positions, the configuration of C-3' and C-4', and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs. PMID:27005602

  20. Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review

    Directory of Open Access Journals (Sweden)

    Wanghui Jing

    2016-03-01

    Full Text Available A vast number of structural modifications have been performed for khellactone derivatives (KDs that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A, as well as UDP-glucuronosyltransferases (UGTs primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs’ metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3′ and C-4′ positions, the configuration of C-3′ and C-4′, and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs.

  1. An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rγnull mice allows HIV replication and development of anti-HIV immune responses.

    Directory of Open Access Journals (Sweden)

    Maneesh Singh

    Full Text Available Cord blood hematopoietic progenitor cells (CB-HPCs transplanted immunodeficient NOD/LtsZ-scidIL2Rγ(null (NSG and NOD/SCID/IL2Rγ(null (NOG mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

  2. Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of HBV or HCV co-infection. The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study

    OpenAIRE

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno; Ryom, Lene; Worm, Signe W; Smith, Colette; Phillips, Andrew; Reiss, Peter; Fontas, Eric; Petoumenos, Kathy; De Wit, Stéphane; Morlat, Philippe; Lundgren, Jens D.; Weber, Rainer

    2013-01-01

    Background. Liver diseases are leading causes of death in HIV-positive persons since the widespread use of combination antiretroviral treatment (ART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus co-infections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality.Methods. All patients of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study without HCV or HBV co-infection were prospectively f...

  3. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

    DEFF Research Database (Denmark)

    De Wit, Stephane; Sabin, Caroline A; Weber, Rainer;

    2008-01-01

    OBJECTIVE: The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with...... the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS: D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes...

  4. Assimetria nas relações internacionais, propriedade industrial e medicamentos anti-aids Asymmetry in international relations, industrial property rights and anti-HIV medication

    Directory of Open Access Journals (Sweden)

    Maria Helena Costa-Couto

    2008-12-01

    Full Text Available Este artigo analisa a assimetria nas relações internacionais entre países no que diz respeito ao reconhecimento da propriedade industrial no setor específico da indústria farmacêutica. O foco é o impacto destas relações no acesso a medicamentos anti-retrovirais (ARV, questão de interesse mundial em face da sua relação com o desenvolvimento das nações. A disputa de interesses no campo e o posicionamento de alguns países frente às leis patentárias, ao longo do tempo, apontam um cenário pouco favorável para acesso aos medicamentos anti-aids pelos países que não pertencem ao núcleo do sistema mundial. O sucesso do programa brasileiro de Doenças Sexualmente Transmissíveis (DSTs e Aids nas negociações dos preços dos ARV, ao contrário, aponta para novas possibilidades de enfrentamento desta realidade. A saída parece ser o fortalecimento interno dos Estados Nacionais e um papel ativo das Agências do Sistema das Nações Unidas na defesa dos interesses humanos coletivos.This paper analyzes the asymmetry in the international relations as refers to the recognition of industrial property rights in the pharmaceutical industry. It focuses on the impact of such relations upon the access to ARV medication, an issue of worldwide interest due to its connection with the development of the nations. Clashing interests and the position taken by some countries in their patent laws point to a scenario less favorable for the access of peripheral countries to anti-HIV/AIDS medication. On the other hand, it seems that the success of the Brazilian STD/AIDS program in negotiating ARV prices will open new possibilities. The solution may be the internal strengthening of the National States and the active role played by the Agencies of the United Nations System in defense of the collective human interests.

  5. Induction of a Soluble Anti-HIV-1 factor (s with IFN-γ, IL-10, and β-Chemokine Modulating Activity by an Influenza-Bacterial Polyantigenic Mixture

    Directory of Open Access Journals (Sweden)

    José W. Rodríguez

    2007-01-01

    Full Text Available Partial immune restoration may be obtained with highly active antiretroviral therapy (HAART, but specific anti-HIV-1 immune responses do not appear to improve substantially. We have demonstrated that a soluble factor(s induced by a mixture of inactivated influenza and bacterial vaccines called polyantigenic immunomodulator (PAI, possesses strong immunoregulatory and anti-HIV-1 activities. In the present study, we show that culture fluids from both PAI-stimulated peripheral blood mononuclear cells (PBMC and CD8+ T-cells of HIV-1 infected patients were able to suppress HIV-1 replication in an MHC-unrestricted fashion. The PAI-induced antiviral activity was eliminated when culture fluids were pre-heated at 100oC for 10 min. and it is associated with induction of IFN-Γ, MIP-1α, MIP-1β, and RANTES production, but inhibition of IL-10. Furthermore, this induction is dependent on the immunological status (CD4:CD8 ratio of the HIV-1 infected patient. Taken together, our results suggest that the MHC-unrestricted HIV-1 suppression that is induced by culture fluids from PAI-stimulated PBMC may result from the stimulation of immune cell subpopulations to produce a heat-labile antiviral soluble factor(s, which in turn modulate cytokine and β-chemokine production. The identification of this PAI-induced soluble factor(s may have major therapeutic potential.

  6. Progress in clinical and basic researches on anti-HIV drug resistance%HIV耐药的临床和基础研究进展

    Institute of Scientific and Technical Information of China (English)

    孙丽君; 刘安

    2011-01-01

    The review focuses on the following topics: strategic study on sustaining survival ,storage and eradication of HIV-1 virus; study on resistance of HIV-1 entering anti-HIV drugs (including the determination of HIV-1 core acceptor sites by comparing the genotype and phenotype before using CCR5 inhibitors); study on resistance of reverse transcriptase inhibitor in polymerase ( including the resistance of hepatitis B and HIV-1 viruses to 3TC, and the mutation of HIV-1 B and C sub-types at K65Rw site); study on the resistance of reverse transcriptase inhibitor linking with RNase H( including role of mutation in response to EFV and etravirine ); study on resistance of hepatitis C virus and HIV-1 protease inhibitors; study of resistance of raltegravir, an integrase inhibitor; global resistance prevalence( including model of prediting resistance to second line ARV drugs in resource-limited areas); roles of a number of resistant mutation strains( including roles of mutation strains in PMTCT)%文章主要关注以下方面内容:艾滋病病毒Ⅰ型(HIV-1)持续存在、储存和消除等方面的策略研究;HIV-1侵入抑制剂的耐药研究(包括通过对比使用CCR5拈抗剂治疗前的基因型和表现型来确定HIV-1的核心接受位点);反转录酶抑制剂在聚合酶领域的耐药研究(包括乙型肝炎病毒和HIV-1对拉米夫定的耐药,HIV-1B和C亚型在K65Rw位点突变);反转录酶抑制剂在联结和RNase H领域的耐药研究[包括突变在对依非韦仑和etravirine(一种新药)应答方面的作用];对丙型肝炎病毒和HIV-1蛋白酶抑制剂的耐药研究;对整合酶抑制剂雷特格韦(Raltegravir)的耐药研究;全球耐药流行情况(包括对资源匮乏地区二线抗病毒药物耐药反应的预测模型);少数耐药变异株的作用(包括这些变异株在预防艾滋病母婴传播中的作用).

  7. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kamata, Masakazu, E-mail: masa3k@ucla.edu [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Kim, Patrick Y. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ng, Hwee L. [Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ringpis, Gene-Errol E.; Kranz, Emiko; Chan, Joshua; O' Connor, Sean [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Yang, Otto O. [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States); AIDS Healthcare Foundation, Los Angeles, CA (United States); Chen, Irvin S.Y. [Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); UCLA AIDS Institute, Los Angeles, CA (United States)

    2015-07-31

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.

  8. Ectopic expression of anti-HIV-1 shRNAs protects CD8+ T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

    International Nuclear Information System (INIS)

    Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8+ T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To test this possibility, highly purified CD8+ T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8+ T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24Gag in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8+ T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8+ T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8+ T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8+ T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8+ T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8+ T cells from HIV-1 infection suppresses its cytopathic effect

  9. Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents.

    Science.gov (United States)

    Mfuh, A M; Larionov, O V

    2015-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  10. Disponibilidade de sorologia anti-HIV como um teste voluntário na rotina do atendimento pré-natal em unidades básicas de saúde

    OpenAIRE

    Fátima RAL Neves; Afonso DC Passos; Wagner L Gueleri

    1999-01-01

    São apresentadas, de forma sucinta, as principais etapas cumpridas para a implementação da sorologia anti-HIV no atendimento às gestantes em unidades básicas de saúde. A partir de agosto de 1996, a realização de testes sorológicos para detecção do HIV passou a ser ofertada às gestantes atendidas em unidades básicas de saúde de Ribeirão Preto, SP, integrada a um conjunto de atividades rotineiramente executadas no atendimento pré-natal. Até o final de 1998, o teste sorológico foi aplicado em 68...

  11. Anti-HIV-1 activity and structure-activity relationship of pyranocoumarin analogs%吡喃香豆素衍生物对HIV-1的抑制作用及其构效关系

    Institute of Scientific and Technical Information of China (English)

    董飚; 马涛; 章天; 周春梅; 刘刚; 王琳; 陶佩珍; 张兴权

    2011-01-01

    The purpose of this study is to find out anti-HIV-1 reverse transcriptase (RT)/protease (PR) activity and inhibition of virus replication in cell cultures of novel coumarin analogs and determine their structure-activity relationship. Coumarin derivatives have been demonstrated to inhibit the activity of HIV-1 RT/PR in cell free system. It also shows inhibition effects to HIV-1 replication in cell culture. Based on the Chinese traditional pharmacological characteristics and protein three dimension computer aided design, analogs of tetracyclic dipyranocoumarin were synthesized from natural leading compounds. We studied the relationship of antiviral effects and chemical structures via HIV-1 PR/RT enzyme models and cell culture model system. Seven compounds were designed and tested. Several compounds showed anti-HIV-1 activity in varying degrees, especially V0201 showed much higher anti-HIV-1 activity with 3.56 and 0.78 μmol·L-1 of IC50 against HIV-1 PR/RT and 0.036 μmol·L-1 against HIV-1 replication in PBMC cultures. V0201 with a novel structure may be a new leading compound. These new compounds are valuable for development of new anti-HIV drugs in the future.%研究香豆素衍生物对人类免疫缺陷病毒l型逆转录酶(HIV-1 RT)、蛋白酶(HIV-1 PR)和细胞内复制的抑制作用及其构效关系.不同香豆素衍生物具有抑制HIV-1 RT、HIV-1 PR活性,且在细胞内显示出抑制HIV-1复制的作用已见报道.本课题根据国内传统药学的特点,考察以天然产物为先导化合物、结合HIV-1蛋白酶三维结构计算机辅助药物设计、合成的四环双吡喃香豆素及其类似物.以HIV-1 RT及HIV-1 PR以及细胞内病毒复制为靶点,利用酶学模型和细胞培养模型进行药物筛选及其构效关系研究,设计合成的7个化合物的药效学实验结果显示.部分化合物显示了不同程度的抗HIV-1活性.其中V0201作用最强,它对HIV-1 PR和HIV-1 RT的IC50分别为3.56和0.78 μmol·L-1;

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

    Science.gov (United States)

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

    2016-01-01

    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

  13. In vitro anti-HIV-1 activities of resveratrol derivatives%白藜芦醇衍生物体外抗HIV-1活性的初步研究

    Institute of Scientific and Technical Information of China (English)

    黄宁; 杨柳萌; 王睿睿; 朱海亮; 郑永唐

    2012-01-01

    Objective; To study the in vitro anti-HIV-1 activities of resveratrol derivatives and the mechanisms. Methods; The cytotoxicities of compounds were tested by MTT assay. The anti-HIV activities of compounds in acute infection were evaluated by cytopathogenic effect (CPE) assay. The inhibition of HIV-lKm018 replication in PBMC was evaluated by p24 antigen expression. The fusion between of HIV-1 infected and uninfected cells was e-valuated by CPE. The inhibition of HIV-1 recombinant reverse transcriptase activity, HIV-1 recombinant protease activity and direct HIV-1 virus killing were used to determine the mechanism. Results; IFB-1 and IFB-9 from resveratrol derivatives markedly inhibited syncytium formation with selective indexes of 16. 16 and 230.27 , respectively. IFB-1 and IFB-9 suppressed HIV-1 p24 antigen production in acutely HIV-111IB-infected C8166 cells with EC50, of 14.57 and 0.23 μg·mL-1 , respectively. They also inhibited HIV-lKM018 replication in PBMC. IFB-1 and IFB-9 blocked the fusion between normal cells and chronically HIV-1-infected cells, but did not inhibit recombinant RT, PR activities and did not directly kill HIV-1. Conclusions; IFB-1 and IFB-9 show potential anti-HIV-1 activities and the mechanism might be associated with inhibition virus entry.%目的:检测白藜芦醇衍生物IFB-1和IFB-9的体外抗HIV-1活性,并对其进行抗HIV-1作用机制的初步研究.方法:采用MTT比色法检测白藜芦醇衍生物IFB-1和IFB-9的细胞毒性;细胞病变法检测化合物对HIV-1急性感染的抑制活性;采用HIV-1 p24抗原ELISA方法检测临床分离株HIV-1KM018在PBMC中复制的抑制实验;采用细胞病变法检测HIV-1感染和未感染细胞之间的融合;采用HIV-1重组逆转录酶活性抑制实验,HIV-1重组蛋白酶活性抑制实验以及直接杀病毒实验来研究化合物体外抗HIV-1机制.结果:白藜芦醇衍生物IFB-1和IFB-9对HIV-1 ⅢB诱导的合胞体形成抑制的选择指数分别为16

  14. Migration of CD8+ T Cells into the Central Nervous System Gives Rise to Highly Potent Anti-HIV CD4dimCD8bright T Cells in a Wnt Signaling-Dependent Manner.

    Science.gov (United States)

    Richards, Maureen H; Narasipura, Srinivas D; Seaton, Melanie S; Lutgen, Victoria; Al-Harthi, Lena

    2016-01-01

    The role of CD8(+) T cells in HIV control in the brain and the consequences of such control are unclear. Approximately 3% of peripheral CD8(+) T cells dimly express CD4 on their surface. This population is known as CD4(dim)CD8(bright) T cells. We evaluated the role of CD4(dim)CD8(bright) and CD8 single positive T cells in HIV-infected brain using NOD/SCID/IL-2rcγ(-/-) mice reconstituted with human PBMCs (NSG-huPBMC). All three T cell populations (CD4 single positive, CD8 single positive, and CD4(dim)CD8(bright)) were found in NSG-huPBMC mouse brain within 2 wk of infection. Wnts secreted from astrocytes induced CD4(dim)CD8(bright) T cells by 2-fold in vitro. Injection of highly purified CD8 single positive T cells into mouse brain induced CD4(dim)CD8(bright) T cells by 10-fold, which were proliferative and exhibited a terminally differentiated effector memory phenotype. Brain CD4(dim)CD8(bright) T cells from HIV-infected mice exhibited anti-HIV-specific responses, as demonstrated by induction of CD107ab post exposure to HIV peptide-loaded targets. Further, higher frequency of CD4(dim)CD8(bright) T cells (R = -0.62; p ≤ 0.001), but not CD8 single positive T cells (R = -0.24; p ≤ 0.27), negatively correlated with HIV gag mRNA transcripts in HIV-infected NSG-huPBMC brain. Together, these studies indicate that single positive CD8(+) T cells entering the CNS during HIV infection can give rise to CD4(dim)CD8(bright) T cells, likely through a Wnt signaling-dependent manner, and that these cells are associated with potent anti-HIV control in the CNS. Thus, CD4(dim)CD8(bright) T cells are capable of HIV control in the CNS and may offer protection against HIV-associated neurocognitive disorders. PMID:26582945

  15. Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

    OpenAIRE

    Rabson Arnold B; Leibowitz Michael J; Debrah Olivia; Pooyan Shahriar; Gunaseelan Simi; Zhang Xiaoping; Wan Li; Stein Stanley; Sinko Patrick J

    2006-01-01

    Abstract Background Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug del...

  16. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study.

    Science.gov (United States)

    Kovari, Helen; Sabin, Caroline A; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; d'Arminio Monforte, Antonella; Smith, Colette; de Wit, Stephane; Kirk, Ole; Lundgren, Jens D; Weber, Rainer

    2016-01-01

    Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (2 years RR = 1.26, 95% CI, 1.13-1.41); stavudine (2 years RR = 1.17, 95% CI, 1.03-1.32), and tenofovir disoproxil fumarate (2 years RR = 1.18, 95% CI, 1.05-1.32), but only short-term exposure to nevirapine (abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions.  Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated. PMID:26925429

  17. Emerging drugs for the treatment of Human Immunodeficiency virus.

    Science.gov (United States)

    Bhopale, Girish M

    2012-04-01

    Rapid emergence of drug resistant Human Immunodeficiency virus (HIV) variants and severe side effects of anti-HIV drugs limit the efficacy of existing anti-HIV therapies. Efforts are being made to develop newer anti-HIV agents. Few newer anti-HIV agents reached the different clinical phases of development and appear promising for future therapy. The present article highlights the current status of available anti-HIV drugs, emerging anti-HIV drug agents and recent anti-HIV drugs patents information. PMID:22353003

  18. In vitro anti-HIV-1 activities of Qishile, a Chinese medicine effective fraction formula%中药有效部位复方奇士乐体外抗HIV-1活性研究

    Institute of Scientific and Technical Information of China (English)

    杨柳萌; 王睿睿; 张高红; 张兴杰; 陈纪军; 郑永唐

    2011-01-01

    目的 评价有效部位复方奇士乐(QSL)的体外抗HIV-1药效学.方法 通过合胞体抑制、HIV-1感染细胞保护、HIV-1 p24抗原测定等方法检测急性感染中QSL对HIV-1实验株、临床分离株、耐药株的抑制作用和对慢性感染细胞中病毒复制的影响;通过ELISA方法和荧光法分别检测了QSL体外抑制HIV-1逆转录酶和蛋白酶活性作用.结果 有效部位复方制剂QSL能有效地抑制HIV-1ⅢB诱导淋巴细胞病变、保护HIV-1ⅢB感染MT-4细胞死亡、阻断HIV-1ⅢB慢性感染H9细胞与C8166细胞间融合的作用.QSL对HIV-1实验株HIV-1ⅢB、临床分离株HIV-1KM018、耐药株HIV-174V的病毒复制也有较好的抑制作用.QSL抑制HIV活性的作用机制可能为多靶点,主要是抑制HIV逆转录酶、蛋白酶和病毒进入细胞.结论 QSL是具有较好体外抗HIV-1活性的中药有效部位复方.%Aim To evaluate the anti-HIV-1 activities of Qishile ( QSL) in vitro , a Chinese medicine effective fraction formula. Methods The inhibition of syncytia formation induced by HIV -1 was determined under microscopy. The protection of HIV-1 induced MT-4 cell lytic effects was measured by MTT assay . The level of HIV-1 p24 antigen in acute and chronic HIV-1 infection was assayed by ELISA. HIV-1 reverse transcriptase and protease activites in vitro were tested by ELISA and FRET, respectively. Results QSL markedly inhibited syncytium formation induced by HIV-1 ⅢB , protected HIV-1 ⅢB induced MT-4 cell lytic effects and blocked cell-to-cell fusion. It also showed obviously inhibitory effect on the clinical strain HIV-1KM018 ancl drug resistant strain HIV-174V replication.QSL maybe inhibited HIV-I replication through multiple targets, including reverse transcriptase , protease and virus entry. Conclusion QSL is a Chinese medicine effective fraction formula with potent anti-HIV-1 activities.

  19. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

    Science.gov (United States)

    Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.; Sarma, R. H.

    1997-01-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex

  20. Development and identification of a novel anti-HIV-1 peptide derived by modification of the N-terminal domain of HIV-1 integrase

    Directory of Open Access Journals (Sweden)

    Marina eSala

    2016-06-01

    Full Text Available The viral enzyme integrase (IN is essential for the replication of human immunodeficiency virus type 1 (HIV-1 and represents an important target for the development of new antiretroviral drugs. In this study, we focused on the N-terminal domain (NTD, which is mainly involved into protein oligomerization process, for the development and synthesis of a library of overlapping peptide sequences, with specific length and specific offset covering the entire native protein sequence NTD IN 1-50. The most potent fragment, VVAKEIVAH (peptide 18, which includes a His residue instead of the natural Ser at position 39, inhibits the HIV-1 IN activity with an IC50 value of 4.5 M. Amino acid substitution analysis on this peptide revealed essential residues for activity and allowed us to identify two nonapeptides (peptides 24 and 25, that show a potency of inhibition similar to the one of peptide 18. Interestingly, peptide 18 does not interfere with the dynamic interplay between IN subunits, while peptides 24 and 25 modulated these interactions in different manners. In fact, peptide 24 inhibited the IN-IN dimerization, while peptide 25 promoted IN multimerization, with IC50 values of 32 and 4.8 µM, respectively. In addition, peptide 25 has shown to have selective anti-infective cell activity for HIV-1. These results confirmed peptide 25 as a hit for further development of new chemotherapeutic agents against HIV-1.

  1. Systematic evaluation of methyl ester bioisosteres in the context of developing alkenyldiarylmethanes (ADAMs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) for anti-HIV-1 chemotherapy.

    Science.gov (United States)

    Hoshi, Ayako; Sakamoto, Takeshi; Takayama, Jun; Xuan, Meiyan; Okazaki, Mari; Hartman, Tracy L; Buckheit, Robert W; Pannecouque, Christophe; Cushman, Mark

    2016-07-01

    The alkenyldiarylmethanes (ADAMs) are a class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting HIV-1. Four chemically and metabolically stabilized ADAMs incorporating N-methoxyimidoyl halide replacements of the methyl esters of the lead compound were previously reported. In this study, twenty-five new ADAMs were synthesized in order to investigate the biological consequences of installing nine different methyl ester bioisosteres at three different locations. Attempts to define a universal rank order of methyl ester bioisosteres and discover the 'best' one in terms of inhibitory activity versus HIV-1 reverse transcriptase (RT) led to the realization that the potencies are critically dependent on the surrounding structure at each location, and therefore the definition of universal rank order is impossible. This investigation produced several new non-nucleoside reverse transcriptase inhibitors in which all three of the three methyl esters of the lead compound were replaced by methyl ester bioisosteres, resulting in compounds that are more potent as HIV-1 RT inhibitors and antiviral agents than the lead compound itself and are expected to also be more metabolically stable than the lead compound. PMID:27234889

  2. Development and Identification of a Novel Anti-HIV-1 Peptide Derived by Modification of the N-Terminal Domain of HIV-1 Integrase

    Science.gov (United States)

    Sala, Marina; Spensiero, Antonia; Esposito, Francesca; Scala, Maria C.; Vernieri, Ermelinda; Bertamino, Alessia; Manfra, Michele; Carotenuto, Alfonso; Grieco, Paolo; Novellino, Ettore; Cadeddu, Marta; Tramontano, Enzo; Schols, Dominique; Campiglia, Pietro; Gomez-Monterrey, Isabel M.

    2016-01-01

    The viral enzyme integrase (IN) is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents an important target for the development of new antiretroviral drugs. In this study, we focused on the N-terminal domain (NTD), which is mainly involved into protein oligomerization process, for the development and synthesis of a library of overlapping peptide sequences, with specific length and specific offset covering the entire native protein sequence NTD IN 1–50. The most potent fragment, VVAKEIVAH (peptide 18), which includes a His residue instead of the natural Ser at position 39, inhibits the HIV-1 IN activity with an IC50 value of 4.5 μM. Amino acid substitution analysis on this peptide revealed essential residues for activity and allowed us to identify two nonapeptides (peptides 24 and 25), that show a potency of inhibition similar to the one of peptide 18. Interestingly, peptide 18 does not interfere with the dynamic interplay between IN subunits, while peptides 24 and 25 modulated these interactions in different manners. In fact, peptide 24 inhibited the IN-IN dimerization, while peptide 25 promoted IN multimerization, with IC50 values of 32 and 4.8 μM, respectively. In addition, peptide 25 has shown to have selective anti-infective cell activity for HIV-1. These results confirmed peptide 25 as a hit for further development of new chemotherapeutic agents against HIV-1. PMID:27375570

  3. Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

    Science.gov (United States)

    Kovari, Helen; Sabin, Caroline A.; Ledergerber, Bruno; Ryom, Lene; Reiss, Peter; Law, Matthew; Pradier, Christian; Dabis, Francois; d'Arminio Monforte, Antonella; Smith, Colette; de Wit, Stephane; Kirk, Ole; Lundgren, Jens D.; Weber, Rainer

    2016-01-01

    Background. Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (2 years RR = 1.26, 95% CI, 1.13–1.41); stavudine (2 years RR = 1.17, 95% CI, 1.03–1.32), and tenofovir disoproxil fumarate (2 years RR = 1.18, 95% CI, 1.05–1.32), but only short-term exposure to nevirapine (<2 years RR = 1.44, 95% CI, 1.29–1.61), efavirenz (<2 years RR = 1.14, 95% CI, 1.03–1.26), emtricitabine (<2 years RR = 1.18, 95% CI, 1.04–1.33), and atazanavir (<2 years RR = 1.20, 95% CI, 1.04–1.38). Chronic liver enzyme elevation was not associated with use of lamivudine, abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions. Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated. PMID:26925429

  4. Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D study

    Directory of Open Access Journals (Sweden)

    Kathy Petoumenos

    2012-10-01

    Full Text Available Introduction: HIV-positive patients receiving combination antiretroviral therapy (cART frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD and diabetes mellitus (DM. Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods: All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC curve and predicted DM events were determined. Results: Of 33,308 patients, 16,632 (50% patients were included, with 376 cases of new onset DM during 89,469 person-years (PY. Factors predictive of DM included higher glucose, body mass index (BMI and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940 and 0.877 (95% CI: 0.823, 0.932, respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower

  5. Agent engineering

    CERN Document Server

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

    2001-01-01

    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

  6. Dual anti-HIV mechanism of clofarabine

    OpenAIRE

    Daly, Michele B.; Roth, Megan E.; Bonnac, Laurent; Maldonado, José O.; Xie, Jiashu; Clouser, Christine L; Patterson, Steven E.; Kim, Baek; Louis M. Mansky

    2016-01-01

    Background HIV-1 replication kinetics inherently depends on the availability of cellular dNTPs for viral DNA synthesis. In activated CD4+ T cells and other rapidly dividing cells, the concentrations of dNTPs are high and HIV-1 reverse transcription occurs in an efficient manner. In contrast, nondividing cells such as macrophages have lower dNTP pools, which restricts efficient reverse transcription. Clofarabine is an FDA approved ribonucleotide reductase inhibitor, which has shown potent anti...

  7. An important role for type Ⅲ interferon(IFN-lambda) in anti-HIV activity%新型干扰素——IFN-λ抗HIV-1感染

    Institute of Scientific and Technical Information of China (English)

    赵颖岚; 孙黎; 王旭; 侯炜; 霍文哲

    2009-01-01

    Objective To examine whether IFN-λ has the ability to inhibit HIV-1 infection of blood monocyte-derived macrophages and its mechanism(s). Methods Macrophages were pretreated with IFN-λ/ IFN-λ2 for 24 h before infected by HIV-1 R5 strains (Bal, Jago, and JRFL). And then the culture supernatants were detected HIV-1 reverse transcription (RT) activity and p24 protein expression by HIV-1 BT assay and ELISA. The expressions of IFN-λ receptor, CD4, CCRS, CXCR4 were evaluated by real-time PCR. Results Both IFN-λ1 and IFN-λ2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-λ-mediated anti-HIV-I activity is broad, as IFN-λ could inhibit infection by both laboratory-adapted and clinical strains of HIV-1. Investigations of mechanism(s) responsible for the IFN-λ action showed that although IFN-λ had little effect on HIV-1 entry receptor CD4 and co-receptor CCR5 and CXCR4 expression, IFN-λ inhibited HIV-I infection of macrophages through connecting with IFN-λ recep-tor. Conclusion IFN-λ could inhibit HIV-I replication in macrophages. These findings indicate that IFN-λ may have a therapeutic value in the treatment of HIV-1 infection.%目的 研究干扰素λ(IFN-λ)是否对HIV-1感染人臣噬细胞有抑制作用,并对可能介导IFN-λ抗HIV-1作用的受体和辅助受体表达水平进行研究,初步探讨其抗HIV-1感染的机制.方法 HIV-1毒株感染人巨噬细胞前用IFN-λ处理细胞24 h,感染后第4天、第8天以及第12天分别检测感染细胞上清中HIV-1逆转录酶(RT)活性和p24蛋白水平,并用实时定量PCR检测细胞上IFN-λ受体、CD4、CCR5、CXCR4的表达.结果 IFN-λ对HIV-1感染人巨噬细胞具有明显抑制作用,且此作用与其剂量及作用时间呈正相关.但IFN-λ对CD4、CCR5、CXCR4的表达影响无统计学意义.结论 IFN-λ能有效抑制HIV-1感染人口噬细胞,并证实这一作用是通过其受体发挥功能的.但IFN-λ介导的抗HIV-1

  8. Antibiotic Agents

    Science.gov (United States)

    ... 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 ...

  9. 蕨麻提取物的体外抗HIV-1活性及毒性研究%Study on the anti-HIV-1 activity and toxicity of the potentilla anserine L.extract

    Institute of Scientific and Technical Information of China (English)

    刘铁军; 黄洋; 徐维四; 孙坚萍; 刘玉磊; 李灵芝; 马丽英

    2012-01-01

    Objective To study the anti-HIV-1 activity and toxicity of the potenlilla anserine L. extract. Methods TZM-bl and MT-4 cell lines were infected with HIV-1 laboratory-adapted strain(SF33), two H1V-1 clinical i-solates(XJDC257,020100968)and four HIV-1 pseudotype viruses(9-14;18-36,74-2 and Z20-11). The activity of inhibiting replication of HIV-1 was observed respectively by using Luciferase assay system based on TZM bl cell line and P24 antigen expression detection based on MT-4 cell line.. The TZM-bl, MT-4 and PBMCs were co-cultured with polentilla anserine L. extract of different concentrations, then CCK-8 kit was used to detect the number of the living cells for evaluating the cytotoxicity of the extract. Results The IC50 and SI of the potentill anserine L. extract against SF33 was 6. 2 μg/mL. 26. 4 by using MT-4 cell line and 4. 7 μg/mL. 73. 5 by using TZM-bl cell line. The IC50 and TI of the extract against HIV-1 clinical isolates XJDC257 and 020100968 was 2.1 μg/mL. 70. 6 and 1. 9 μg/mL, 77. 6, respectively. The IC50 of the extract against the HIV-1 pseudotype viruses 9-14,18-36,74-2 and Z20-11 was 1. 8 μg/mL, 1. 0 μg/mL, 3. 4 μg/mL and 3. 5 μg/mL,respectively and therapeutic index(TI) was 81. 9, 147. 5,43. 4 and 42. 1, respectively. Conclusion: The potentilla anserine L. extract could inhibit the replication of HIV-1 in vitro.%目的 研究蕨麻提取物的抗艾滋病病毒Ⅰ型( HIV-1)活性及毒性.方法 用HIV-1实验室适应株SF33、临床分离株XJDC257和020100968、假病毒颗粒9-14,18-36,74-2和Z20-11分别感染TZM-b1、MT-4,利用基于TZM-b1细胞的荧光素酶检测体系和基于MT-4细胞的P24抗原检测方法,观察蕨麻提取物抑制HIV-1病毒复制的活性;用不同稀释度的蕨麻提取物与TZM-b1.MT-4.PBMCs共培养,使用Cell Counting Kit-8检测活细胞的数量,观察蕨麻提取物对相应细胞的毒性作用.结果 利用MT-4细胞和TZM-b1细胞测得蕨麻提取物对SF33的半数抑制浓度( IC50)

  10. Agent, autonomous

    OpenAIRE

    Luciani, Annie

    2007-01-01

    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.

  11. Antifungal agents.

    Science.gov (United States)

    Ryder, N S

    1999-12-01

    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

  12. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    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

  13. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    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.

  14. Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents.

    Science.gov (United States)

    Dar, Bilal Ahmad; Lone, Ali Mohd; Shah, Wajaht Amin; Qurishi, Mushtaq Ahmad

    2016-03-23

    Ursolic acid present abundantly in plant kingdom is a well-known compound with various promising biological activities including, anti-cancer, anti-inflammatory, hepatoprotective, antiallergic and anti-HIV properties. Herein, a library of ursolic acid-benzylidine derivatives have been designed and synthesized using Claisen Schmidt condensation of ursolic acid with various aromatic aldehydes in an attempt to develop potent antitumor agents. The compounds were evaluated against a panel of four human carcinoma cell lines including, A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2). The results from MTT assay revealed that all the compounds displayed high level of antitumor activities compared with the triazole analogs (previously reported) and the parent ursolic acid. However, compound 3b, the most active derivative was subjected to mechanistic studies to understand the underlying mechanism. The results revealed that compound 3b induced apoptosis in HCT-116 cell lines, arrest cell cycle in the G1 phase, caused accumulation of cytochrome c in the cytosol and increased the expression levels of caspase-9 and caspase-3 proteins. Therefore, compound 3b induces apoptosis in HCT-116 cells through mitochondrial pathway. PMID:26854375

  15. In Vitro Drug Combination Studies of Letermovir (AIC246, MK-8228) with Approved Anti-Human Cytomegalovirus (HCMV) and Anti-HIV Compounds in Inhibition of HCMV and HIV Replication

    OpenAIRE

    Wildum, Steffen; Zimmermann, Holger; Lischka, Peter

    2015-01-01

    Despite modern prevention and treatment strategies, human cytomegalovirus (HCMV) remains a common opportunistic pathogen associated with serious morbidity and mortality in immunocompromised individuals, such as transplant recipients and AIDS patients. All drugs currently licensed for the treatment of HCMV infection target the viral DNA polymerase and are associated with severe toxicity issues and the emergence of drug resistance. Letermovir (AIC246, MK-8228) is a new anti-HCMV agent in clinic...

  16. Anti-HIV-1 activities of the extracts from the medicinal plant Linum grandiflorum Desf.:In Proceedings of 4th Conference on Research and Development of Pharmaceutical Industries (Current Challenges)

    OpenAIRE

    Mohammed, Magdy M. D.; Christensen, Lars Porskjær; Ibrahim, Nabaweya A.; Awad, Nagwa E.; Zeid, Ibrahim F.; Pedersen, Erik Bjerregaard; Jensen, Kenneth Bendix; Colla, Paolo L.

    2009-01-01

    As part of our screening of anti-AIDS agents from natural sources e.g. Ixora undulata, Paulownia tomentosa, Fortunella margarita, Aegle marmelos and Erythrina abyssinica, the different organic and aqueous extracts of Linum grandiflorum leaves and seeds were evaluated in vitro by the microculture tetrazolium (MTT) assay. The activity of the tested extracts against multiplication of HIV-1 wild type IIIB, N119, A17, and EFVR in acutely infected cells was based on inhibition of virus-induced cyto...

  17. HIV-1逆转录酶抑制剂的合成及活性评价%Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

    Institute of Scientific and Technical Information of China (English)

    闫寒; 王孝伟; 郭盈; 张志丽; 刘俊义

    2011-01-01

    N-1-alkyl-5-halogeno-6-alkylamino uracils, which are novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)analogues, were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(HIV)-1 reverse transcriptase inhibitors. Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase. For instance, compounds ld, lm and In exhibited potent anti-HIV-1 activity with the ICso values of 13.3, 11.7 and 3.15 gM, respectively,which are comparable to that of nevirapinc(IC5O 8.38 μM).%本研究以HIV-1逆转录酶为靶点,设计了一类具有HEPT类结构的化合物:1-乙氧基甲基/苄氧基甲基-5-卤代-6-脂肪胺尿嘧啶作为抑制剂,并对合成的目标化合物进行了生物活性测定,一些化合物显示出较强的抗HIV生物活性,与对照物奈韦拉平相比(IC50 8.30μM)化合物1d,1m和1n的IC50 值分别达到了13.3,11.7和3.15 μM.

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

    OpenAIRE

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

    2004-01-01

    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...

  19. Agent Chameleons: Virtual Agents Real Intelligence

    OpenAIRE

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

    2003-01-01

    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.

  20. Synthesis and Conformation of Novel 4'-Fluorinated 5'-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

    International Nuclear Information System (INIS)

    Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to 100 μM

  1. AgentChess : An Agent Chess Approach

    OpenAIRE

    Fransson, Henric

    2003-01-01

    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...

  2. Agents in domestic environments

    OpenAIRE

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

    2013-01-01

    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...

  3. Culturally Aware Agent Communication

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  4. Riot Control Agents

    Science.gov (United States)

    ... 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 ...

  5. Reasoning about emotional agents

    NARCIS (Netherlands)

    Meyer, J.-J.

    2008-01-01

    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

  6. Agents modeling agents in information economies

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

    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.

  7. Evaluation Of Algorithms Of Anti- HIV Antibody Tests

    Directory of Open Access Journals (Sweden)

    Paranjape R.S

    1997-01-01

    Full Text Available Research question: Can alternate algorithms be used in place of conventional algorithm for epidemiological studies of HIV infection with less expenses? Objective: To compare the results of HIV sero- prevalence as determined by test algorithms combining three kits with conventional test algorithm. Study design: Cross â€" sectional. Participants: 282 truck drivers. Statistical analysis: Sensitivity and specificity analysis and predictive values. Results: Three different algorithms that do not include Western Blot (WB were compared with the conventional algorithm, in a truck driver population with 5.6% prevalence of HIV â€"I infection. Algorithms with one EIA (Genetic Systems or Biotest and a rapid test (immunocomb or with two EIAs showed 100% positive predictive value in relation to the conventional algorithm. Using an algorithm with EIA as screening test and a rapid test as a confirmatory test was 50 to 70% less expensive than the conventional algorithm per positive scrum sample. These algorithms obviate the interpretation of indeterminate results and also give differential diagnosis of HIV-2 infection. Alternate algorithms are ideally suited for community based control programme in developing countries. Application of these algorithms in population with low prevalence should also be studied in order to evaluate universal applicability.

  8. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton; Lundgren, Jens Dilling

    2007-01-01

    Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding and...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...

  9. Recent advances on anti-HIV vaginal delivery systems development.

    Science.gov (United States)

    Antimisiaris, Sophia G; Mourtas, Spyridon

    2015-09-15

    A review of the recent outcomes regarding technologies to prevent vaginal transmission of HIV, mainly by using antiretroviral (ARV) drugs formulated as microbicides. An introduction about the HIV transmission mechanisms by the vaginal route is included, together with the recent challenges faced for development of successful microbicide products. The outcomes of clinical evaluations are mentioned, and the different formulation strategies studied to-date, with the requirements, advantages, disadvantages and limitations of each dosage-form type, are presented. Finally, the recent attempts to apply various types of nanotechnologies in order to develop advanced microbicide-products and overcome existing limitations, are discussed. PMID:25858666

  10. Criticality of timing for anti-HIV therapy initiation.

    Directory of Open Access Journals (Sweden)

    Filippo Castiglione

    Full Text Available The time of initiation of antiretroviral therapy in HIV-1 infected patients has a determinant effect on the viral dynamics. The question is, how far can the therapy be delayed? Is sooner always better? We resort to clinical data and to microsimulations to forecast the dynamics of the viral load at therapy interruption after prolonged antiretroviral treatment. A computational model previously evaluated, produces results that are statistically adherent to clinical data. In addition, it allows a finer grain analysis of the impact of the therapy initiation point to the disease course. We find a swift increase of the viral density as a function of the time of initiation of the therapy measured when the therapy is stopped. In particular there is a critical time delay with respect to the infection instant beyond which the therapy does not affect the viral rebound. Initiation of the treatment is beneficial because it can down-regulate the immune activation, hence limiting viral replication and spread.

  11. Clinical outcomes in clinical trials of anti-HIV treatment

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; J, Neaton;

    2007-01-01

    Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding and k...

  12. Investigation of the anti-HIV properties of oxihumate

    Energy Technology Data Exchange (ETDEWEB)

    van Rensburg, C.E.J.; Dekker, J.; Weis, R.; Smith, T.L.; van Rensburg, E.J.; Schneider, J. [University of Pretoria, Pretoria (South Africa). Dept. of Pharmacology, Faculty of Health Science

    2002-07-01

    The paper describes a process for converting bituminous coal by controlled wet oxidation followed by base treatment to a water-soluble humate called oxihumate. Oxihumate inhibited HIV-1 infection of MT-2 cells with an IC50 of 12.5 {mu}g/ml. Treatment of free and cell-attached HIV with oxihumate irreversibly reduced infectivity, while the susceptibility of target cells to the virus was not impaired by treatment prior to infection. The infectivity of the HIV particles was inhibited by interference with CD4 binding and the V3 loop-mediated step of virus entry. No viral resistance to oxihumate developed over a 12-week period in vitro. Oxihumate therefore holds promise for the treatment of HIV-infected patients.

  13. The anti-HIV-1 effect of scutellarin

    International Nuclear Information System (INIS)

    Scutellarin was purified from the plant Erigeron breviscapus (Vant.) Hand.-Mazz. The activity against 3 strains of human immunodeficiency virus (HIV) was determined in vitro in this study. These were laboratory-derived virus (HIV-1IIIB), drug-resistant virus (HIV-174V), and low-passage clinical isolated virus (HIV-1KM018). From syncytia inhibition study, the EC50 of scutellarin against HIV-1IIIB direct infection in C8166 cells was 26 μM with a therapeutic index of 36. When the mode of infection changed from acute infection to cell-to-cell infection, this compound became even more potent and the EC50 reduced to 15 μM. This suggested that cell fusion might be affected by this compound. By comparing the inhibitory effects on p24 antigen, scutellarin was also found to be active against HIV-174V (EC50 253 μM) and HIV-1KM018 (EC50 136 μM) infection with significant difference in potency. The mechanism of its action was also explored in this study. At a concentration of 433 μM, scutellarin inhibited 48% of the cell free recombinant HIV-1 RT activity. It also caused 82% inhibition of HIV-1 particle attachment and 45% inhibition of fusion at the concentrations of 54 μM. In summary, scutellarin was found to inhibit several strains of HIV-1 replication with different potencies. It appeared to inhibit HIV-1 RT activity, HIV-1 particle attachment and cell fusion. These are essential activities for viral transmission and replication

  14. Development of HIV vectors for anti-HIV gene therapy.

    OpenAIRE

    Poeschla, E; Corbeau, P; Wong-Staal, F

    1996-01-01

    Current gene therapy protocols for HIV infection use transfection or murine retrovirus mediated transfer of antiviral genes into CD4+ T cells or CD34+ progenitor cells ex vivo, followed by infusion of the gene altered cells into autologous or syngeneic/allogeneic recipients. While these studies are essential for safety and feasibility testing, several limitations remain: long-term reconstitution of the immune system is not effected for lack of access to the macrophage reservoir or the pluripo...

  15. Chemical crowd control agents.

    Science.gov (United States)

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

    2016-03-01

    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

  16. Decontamination Data - Blister Agents

    Data.gov (United States)

    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...

  17. O aconselhamento e a testagem anti-HIV como estratégia preventiva: uma revisão da literatura internacional, 1999-2011 Counseling and testing for HIV as a prevention strategy: an international review of published research, 1999-2011

    Directory of Open Access Journals (Sweden)

    Priscilla da Silva Soares

    2012-12-01

    Full Text Available Com base em revisão bibliográfica discute-se a literatura produzida nos anos de 1999 a 2011, no campo da saúde coletiva, sobre uma importante estratégia de prevenção da transmissão do HIV: o aconselhamento e testagem anti-HIV. O artigo realiza um balanço da literatura internacional, analisando criticamente os aspectos mais assinalados pela comunidade científica, apontando divergências e convergências entre os estudos e identificando lacunas que possam estimular o desenvolvimento de novas pesquisas neste campo temático. Como resultado, evidenciou-se que os processos de decisão de realizar um teste e a experiência da testagem são discutidos na literatura com abordagens fragmentadas, sejam de ordem individual ou institucional. Para compreender diversas dimensões implicadas na adoção de uma prática preventiva como o teste HIV, é preciso contemplar indicadores sociais tais como gênero, religião, identidade sexual, raça/cor, e relacioná-los às políticas públicas e à operacionalização dos serviços de saúde. O uso expressivo do conceito de risco (aliado às categorias de grupo, comportamento, percepção e de escalas quantitativas para aferir a percepção individual do risco como uma barreira para a realização do teste ilustra o foco excessivo sobre uma dimensão individual e parcial do problema.Based in a bibliographical review, this paper discusses the literature produced between 1999 and 2011 in the field of Public Health over an important strategy of prevention of the transmission of HIV virus: the counseling and testing for HIV. The article critically analyzes the aspects highlighted by the literature, indicating divergences and convergences among the studies and identifying possible gaps that can stimulate new researches in this thematic field. The results of this work indicate a tendency of the literature in treating the processes of decision and the experience of taking a test under fragmented approaches at an

  18. Agent Development Toolkits

    CERN Document Server

    Singh, Aarti; Sharma, A K

    2011-01-01

    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.

  19. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    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.)

  20. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    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: ...

  1. How do agents represent?

    Science.gov (United States)

    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.

  2. Hyperthermia and chemotherapy agent

    International Nuclear Information System (INIS)

    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

  3. Synthesis and Conformation of Novel 4'-Fluorinated 5'-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Lien; Kim, Eunae; Choi, Eun Joo; Yoo, Jin Cheol; Lee, Wonjae; Hong, Joon Hee [Chosun Univ., Kwangju (Korea, Republic of)

    2012-12-15

    Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to 100 μM.

  4. Potential use of rapamycin in HIV infection

    OpenAIRE

    Donia, Marco; McCubrey, James A.; Bendtzen, Klaus; Nicoletti, Ferdinando

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of pu...

  5. Users, Bystanders and Agents

    DEFF Research Database (Denmark)

    Krummheuer, Antonia Lina

    2015-01-01

    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....

  6. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    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.

  7. Agent Standards Project

    Data.gov (United States)

    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...

  8. Programming Service Oriented Agents

    OpenAIRE

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

    2010-01-01

    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.

  9. Adrenal imaging agents

    International Nuclear Information System (INIS)

    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

  10. Agent amplified communication

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

    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.

  11. Demandas e expectativas de usuários de centro de testagem e aconselhamento anti-HIV Demandas y expectativas de usuarios de centros de examen y consejo anti-VIH Demands and expectations of users of HIV testing and counseling centers

    Directory of Open Access Journals (Sweden)

    Vânia de Souza Souza

    2010-06-01

    Full Text Available OBJETIVO: Analisar características, demandas e expectativas de usuários de um centro de testagem e aconselhamento anti-HIV. PROCEDIMENTOS METODOLÓGICOS: Pesquisa qualitativa realizada com 32 usuários de centro de testagem e aconselhamento do estado de Minas Gerais, de novembro de 2005 a março de 2006. Utilizou-se a técnica de entrevista aberta semi-estruturada e uma adaptação do método de análise de conteúdo, empregando-se a modalidade temática. ANÁLISE DOS RESULTADOS: A falta de conhecimento do serviço, a dificuldade de se perceber vulnerável à infecção, as justificativas por não pertencer aos grupos de risco, o receio do constrangimento e de um atendimento precário surgiram como importantes limitações de acesso aos centros de testagem e aconselhamento. CONCLUSÕES: No discurso dos usuários, foi identificado um paradoxo entre o aspecto participativo na superação da vulnerabilidade e a busca de soluções pragmáticas de exclusão do risco. Suas demandas sinalizaram estratégias que contenham: qualidade da informação prestada, acesso ao serviço e aos discursos de prevenção e promoção da saúde.OBJETIVO: Analizar características, demandas y expectativas de usuarios de centro de examen y consejo anti-VIH. PROCEDIMIENTOS METODOLÓGICOS: Investigación cualitativa realizada con 32 usuarios de centro de examen y consejo del estado de Minas Gerais, en sureste de Brasil, de noviembre de 2005 a marzo de 2006. Se utilizó técnica de entrevista abierta semi-estructurada y una adaptación del método de análisis de contenido, empleándose la modalidad temática. ANÁLISIS DE LOS RESULTADOS: La falta de conocimiento del servicio, la dificultad de percibirse vulnerable a la infección, las justificaciones por no pertenecer a los grupos de riesgo, el recelo del constreñimiento y de una atención precaria surgieron como importantes limitaciones de acceso a los centros de examen y consejo. CONCLUSIONES: En el discurso de los

  12. TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus

    OpenAIRE

    Uckun, Fatih M.; Chelstrom, Lisa M.; Tuel-Ahlgren, Lisa; Dibirdik, Ilker; Irvin, James D.; Langlie, Mridula-Chandan; Myers, Dorothea E.

    1998-01-01

    We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TX...

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

    Institute of Scientific and Technical Information of China (English)

    王一川; 石纯一

    2002-01-01

    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.

  14. Agents unleashed a public domain look at agent technology

    CERN Document Server

    Wayner, Peter

    1995-01-01

    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

  15. El agente encubierto

    OpenAIRE

    Anaya Marcos, María del Carmen

    2015-01-01

    [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...

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

    OpenAIRE

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

    2014-01-01

    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...

  17. Trading Agents for Roaming Users

    OpenAIRE

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

    2002-01-01

    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.

  18. Software Agent Techniques in Design

    DEFF Research Database (Denmark)

    Hartvig, Susanne C

    1998-01-01

    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....

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

    Science.gov (United States)

    2010-01-01

    ... 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...

  20. Programming multi-agent systems

    NARCIS (Netherlands)

    Dastani, Mehdi

    2015-01-01

    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

  1. SECOND BUYING AGENT

    CERN Multimedia

    SPL - SERVICES ACHATS

    2000-01-01

    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...

  2. Radioactive diagnostic agent

    International Nuclear Information System (INIS)

    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

  3. Developing Enculturated Agents

    DEFF Research Database (Denmark)

    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...

  4. Biomimetic Emotional Learning Agents

    OpenAIRE

    Kenyon, Samuel H.

    2005-01-01

    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.

  5. Agents of Change

    DEFF Research Database (Denmark)

    Hansen, Jens Aage; Lehmann, Martin

    2004-01-01

    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...

  6. The need for agents

    DEFF Research Database (Denmark)

    Abolfazlian, Ali Reza Kian

    1996-01-01

    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...

  7. Build Autonomic Agents with ABLE

    Institute of Scientific and Technical Information of China (English)

    吴吉义

    2007-01-01

    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.

  8. Synthesis of carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases

    Science.gov (United States)

    Cho, Jong hyun; Coats, Steven J.; Schinazi, Raymond F.

    2015-01-01

    New carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases were synthesized and evaluated as potential anti-HIV and anti-HCV agents. Among the synthesized carbocyclic nucleoside analogs, the pyrazole amide 15f exhibited modest selective anti-HIV-1 activity (EC50 = 24 µM). PMID:26028788

  9. Actions and Agents

    OpenAIRE

    Alonso, E.

    2014-01-01

    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

    Czech Academy of Sciences Publication Activity Database

    Neruda, Roman; Krušina, Pavel; Petrová, Zuzana

    2000-01-01

    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

    OpenAIRE

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

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food an...

  12. Perioperative allergy: uncommon agents.

    Science.gov (United States)

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

    2011-01-01

    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

    International Nuclear Information System (INIS)

    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. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    OpenAIRE

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2015-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action,...

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

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2010-01-01

    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...

  16. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... 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 ...

  17. Agents Play Mix-game

    CERN Document Server

    Gou, C

    2005-01-01

    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.

  18. The Power Trading Agent Competition

    OpenAIRE

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

    2011-01-01

    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.

  19. Mediating Performance Through Virtual Agents

    OpenAIRE

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

    2009-01-01

    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...

  20. Erythropoietic Agents and the Elderly

    OpenAIRE

    Agarwal, Neeraj; Prchal, Josef T.

    2008-01-01

    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...

  1. Cultural Differentiation of Negotiating Agents

    NARCIS (Netherlands)

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

    2012-01-01

    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. Cultural differentiation of negotiating agents

    NARCIS (Netherlands)

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

    2010-01-01

    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

  3. Collaborating with Autonomous Agents

    Science.gov (United States)

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

    2015-01-01

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

  4. Agentes de información Information Agents

    Directory of Open Access Journals (Sweden)

    Alfonso López Yepes

    2005-12-01

    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.

  5. Secure Mobile Trade Agent

    Directory of Open Access Journals (Sweden)

    Musbah M. Aqe

    2007-01-01

    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.

  6. Configuring Computational Agents

    Czech Academy of Sciences Publication Activity Database

    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

  7. Holograms as Teaching Agents

    Science.gov (United States)

    Walker, Robin A.

    2013-02-01

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

  8. Amphoteric surface active agents

    Directory of Open Access Journals (Sweden)

    Eissa, A.M. F.

    1995-10-01

    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.

  9. Contrast agents for MRI

    International Nuclear Information System (INIS)

    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

  10. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    GUAN Xu; CHENG Ming; LIU Bao

    2001-01-01

    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.

  11. Learning models of intelligent agents

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-12-31

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

  12. Flexible, secure agent development framework

    Science.gov (United States)

    Goldsmith; Steven Y.

    2009-04-07

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

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

    Directory of Open Access Journals (Sweden)

    In-Cheol Kim

    2007-02-01

    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

    Directory of Open Access Journals (Sweden)

    Sushila Rathee

    2012-04-01

    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

    International Nuclear Information System (INIS)

    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.

    Science.gov (United States)

    Crispe, Ian N

    2016-01-01

    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

  17. MORBIDITY AGENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Shrivastava Neelesh

    2011-09-01

    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

    Science.gov (United States)

    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. Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol

    Directory of Open Access Journals (Sweden)

    Meng Y

    2012-06-01

    virus-1. Furthermore, both PEGylated proteins showed about 60%–70% antitumor and antivirus activities, and at the same time decreased 50%–70% immunogenicity when compared with their unmodified counterparts.Conclusion/significance: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.Keywords: ribosome-inactivating proteins, alpha-momorcharin, momordica anti-HIV protein, antitumor, antivirus, (mPEG2-Lys-NHS (20 kDa, immunogenicity

  20. Odor Classification using Agent Technology

    Directory of Open Access Journals (Sweden)

    Sigeru OMATU

    2014-03-01

    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.

  1. Stability of Evolving Agent Populations

    CERN Document Server

    Briscoe, G

    2007-01-01

    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.

  2. Agent-based enterprise integration

    Energy Technology Data Exchange (ETDEWEB)

    N. M. Berry; C. M. Pancerella

    1998-12-01

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

  3. Mobile Agents for Digital Signage

    OpenAIRE

    SATOH, Ichiro

    2010-01-01

    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...

  4. An agent for ecological deliberation

    OpenAIRE

    Debenham, John; Sierra, Carles

    2010-01-01

    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.

  5. Agent factory: towards social robots

    OpenAIRE

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

    1999-01-01

    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...

  6. Agent Systems in Software Engineering

    OpenAIRE

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

    2008-01-01

    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...

  7. Research on Negotiating Agent Development

    Institute of Scientific and Technical Information of China (English)

    WEI Ding-guo; PENG Hong

    2004-01-01

    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.

  8. Extending Agent Languages for Autonomy

    OpenAIRE

    Meneguzzi, Felipe Rech

    2008-01-01

    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...

  9. Radioactive scanning agents with stabilizer

    International Nuclear Information System (INIS)

    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

  10. Technetium diagnostic agent and carrier

    International Nuclear Information System (INIS)

    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

  11. Relational agents: A critical review

    DEFF Research Database (Denmark)

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

    2009-01-01

    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....

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

    Science.gov (United States)

    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.

  13. Gastrointestinal scanning agent

    International Nuclear Information System (INIS)

    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

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    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

    Directory of Open Access Journals (Sweden)

    Momčilović Dragan

    2002-01-01

    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

    OpenAIRE

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

    2003-01-01

    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

    Science.gov (United States)

    Sánchez-Guzmán, D.; Mora, César

    2010-07-01

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

  18. Markov Tracking for Agent Coordination

    Science.gov (United States)

    Washington, Richard; Lau, Sonie (Technical Monitor)

    1998-01-01

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

  19. The Continuing Evolution of HIV-1 Therapy: Identification and Development of Novel Antiretroviral Agents Targeting Viral and Cellular Targets

    OpenAIRE

    Hartman, Tracy L.; Buckheit, Robert W.

    2012-01-01

    During the past three decades, over thirty-five anti-HIV-1 therapies have been developed for use in humans and the progression from monotherapeutic treatment regimens to today's highly active combination antiretroviral therapies has had a dramatic impact on disease progression in HIV-1-infected individuals. In spite of the success of AIDS therapies and the existence of inhibitors of HIV-1 reverse transcriptase, protease, entry and fusion, and integrase, HIV-1 therapies still have a variety of...

  20. Agent Communications using Distributed Metaobjects

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

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

  1. Mobile agent driven by aspect

    Directory of Open Access Journals (Sweden)

    Youssef Hannad

    2010-11-01

    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.

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

    OpenAIRE

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

    2007-01-01

    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...

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

    OpenAIRE

    Gherbi, Tahar; Borne, Isabelle; Meslati, Djamel

    2009-01-01

    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...

  4. Knowledge mining using intelligent agents

    CERN Document Server

    Dehuri, Satchidananda

    2010-01-01

    ""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

  5. Agent-oriented Software Engineering

    Institute of Scientific and Technical Information of China (English)

    MingCheng; XuGuan; BaoLiu

    2004-01-01

    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.

  6. Optimistic Agents are Asymptotically Optimal

    OpenAIRE

    Sunehag, Peter; Hutter, Marcus

    2012-01-01

    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.

  7. Agents containing chlorhexidine in dentistry

    OpenAIRE

    Lebedeva S.N.; Zemlyanichenko М.К.

    2011-01-01

    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

  8. Chemical Agents: Facts about Evacuation

    Science.gov (United States)

    ... 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 ...

  9. PENETRATION ENHANCEMENT OF MEDICINAL AGENTS

    OpenAIRE

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

    2012-01-01

    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...

  10. Agents in E-learning

    OpenAIRE

    S. Mencke; Dumke, R

    2007-01-01

    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.

  11. Handling of injectable antineoplastic agents.

    OpenAIRE

    Knowles, R S; Virden, J E

    1980-01-01

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

  12. Biocontrol agents in signalling resistance

    OpenAIRE

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

    2002-01-01

    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...

  13. Epidemic Spreading with External Agents

    OpenAIRE

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

    2012-01-01

    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...

  14. Locating Agents in RFID Architectures

    OpenAIRE

    Abdel-Naby, Sameh; Giorgini, Paolo

    2006-01-01

    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...

  15. Towards Building Computational Agent Schemes

    Czech Academy of Sciences Publication Activity Database

    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

  16. Cooperation of Computational Intelligence Agents

    Czech Academy of Sciences Publication Activity Database

    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

  17. Bacteriocins as potential anticancer agents

    OpenAIRE

    Sukhraj eKaur; Sumanpreet eKaur

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have 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...

  18. Bacteriocins as Potential Anticancer Agents

    OpenAIRE

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeu...

  19. Business Intelligence using Software Agents

    OpenAIRE

    Ana-Ramona BOLOGA; Razvan BOLOGA

    2011-01-01

    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...

  20. What makes virtual agents believable?

    Science.gov (United States)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

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

  1. 46 CFR Sec. 2 - General Agents' authority.

    Science.gov (United States)

    2010-10-01

    ... 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...

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

    International Nuclear Information System (INIS)

    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

  3. Geo-Agents: Design and Implement

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    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.

  4. Special issue about advances in Physical Agents

    OpenAIRE

    Cazorla Quevedo, Miguel Ángel; Matellán Olivera, Vicente

    2011-01-01

    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.

  5. Learning by Observation of Agent Software Images

    OpenAIRE

    Costa, Paulo Roberto; Botelho, Luís Miguel

    2014-01-01

    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...

  6. Colitis associated with biological agents

    Directory of Open Access Journals (Sweden)

    Hugh James Freeman

    2012-01-01

    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.

  7. Drug: D02499 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02499 Drug Enfuvirtide (USAN/INN); Fuzeon (TN) C204H301N51O64 4489.1866 4491.876 Ac-Tyr Thr Ser ... on] [DS:H00406] ATC code: J05AX07 fusion inhibitor HIV ... glycoprotein 41 (gp41) map07053 Anti-HIV ... agents An ... P drug classification [BR:br08302] Antivirals Anti-HIV ... Agents, Other Enfuvirtide D02499 Enfuvirtide (USAN ...

  8. Drug: D10066 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10066 Drug Dolutegravir (USAN) C20H19F2N3O5 419.1293 419.3788 D10066.gif Treatment of HIV ... infec ... tion [DS:H00406] ATC code: J05AX12 HIV -1 integrase inhibitor map07053 Anti-HIV ... agents Ana ... P drug classification [BR:br08302] Antivirals Anti-HIV ... Agents, Integrase Inhibitors (INSTI) Dolutegravir ...

  9. エイズおよび抗HIV薬開発研究について

    OpenAIRE

    中島, 秀喜; ナカシマ, ヒデキ; Nakashima, Hideki

    1998-01-01

    The unprecedented speed with which the etiologic agent of AIDS, human immunodeficiency virus (HIV) , was isolated and characterized, and then effective drugs were discovered remarkably. Discovery of some anti-HIV compounds suggested that the antiviral chemotherapy of AIDS was fesible, and opened the search for more potent and more selective anti-HIV agents. In the past two years, HIV-infected patients have been treated with combinations of drugs which inhibit enzymes present in HIV but not in...

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

    Science.gov (United States)

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

    2015-10-01

    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.

  11. Sensors for detecting biological agents

    Directory of Open Access Journals (Sweden)

    Kim E. Sapsford

    2008-03-01

    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.

  12. Agent review phase one report.

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-12-01

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

  13. Dopamine agents for hepatic encephalopathy

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  14. Multi-Agent Software Engineering

    International Nuclear Information System (INIS)

    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

  15. Monitoring presence of chemical agents

    International Nuclear Information System (INIS)

    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)

  16. Erythropoietic agents and the elderly.

    Science.gov (United States)

    Agarwal, Neeraj; Prchal, Josef T

    2008-10-01

    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

  17. Autonomous sensor manager agents (ASMA)

    Science.gov (United States)

    Osadciw, Lisa A.

    2004-04-01

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

  18. An overview of inotropic agents.

    Science.gov (United States)

    Vroom, Margreeth B

    2006-09-01

    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

  19. Building Multi-Agent Systems Using Jason

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...

  20. Using Agent to Coordinate Web Services

    CERN Document Server

    Liu, C H; Chen, Jason J Y

    2009-01-01

    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 ...

  1. Tc-99m imaging agents

    International Nuclear Information System (INIS)

    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

  2. Antibacterial activities of antineoplastic agents.

    OpenAIRE

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

    1985-01-01

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

  3. Raspberry Pi for secret agents

    CERN Document Server

    Sjogelid, Stefan

    2015-01-01

    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.

  4. Identity Management in Agent Systems

    NARCIS (Netherlands)

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

    2006-01-01

    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

  5. Kriitikute lemmikfilm on "Agent Sinikael"

    Index Scriptorium Estoniae

    2003-01-01

    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

  6. Improving agents using reliable communication

    Science.gov (United States)

    Zheng, Jinbin

    2013-10-01

    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.

  7. Foodborne illness and microbial agents

    Science.gov (United States)

    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...

  8. Bridging humans via agent networks

    International Nuclear Information System (INIS)

    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.)

  9. Synthesis and conformation of novel 3'-branched threo syl-5'-deoxy phosphonic acid nucleoside analogues

    International Nuclear Information System (INIS)

    The discovery that threo syl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) is a potent anti-HIV agent has led to the synthesis and biological evaluation of 5'-deoxy versions of threo syl phosphonate nucleosides. In the present study, (E)-3'-phosphono alkenyl and 3'-phosphono alkyl nucleoside analogues 13, 16, 20 and 23 were synthesized from acetol and tested for anti-HIV activity and cytotoxicity. The adenine analogue 16 was found to exhibit moderate in vitro anti-HIV-1 activity (EC50 = 22.2 μM)

  10. Synthesis and conformation of novel 3'-branched threo syl-5'-deoxy phosphonic acid nucleoside analogues

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Guang Huan; Kang, Li En; Kim, Eun Ae; Lee, Won Jae; Hong, Joon Hee [Chosun Univ., Kwangju (Korea, Republic of)

    2012-04-15

    The discovery that threo syl phosphonate nucleoside (PMDTA, EC{sub 50} = 2.53 μM) is a potent anti-HIV agent has led to the synthesis and biological evaluation of 5'-deoxy versions of threo syl phosphonate nucleosides. In the present study, (E)-3'-phosphono alkenyl and 3'-phosphono alkyl nucleoside analogues 13, 16, 20 and 23 were synthesized from acetol and tested for anti-HIV activity and cytotoxicity. The adenine analogue 16 was found to exhibit moderate in vitro anti-HIV-1 activity (EC{sub 50} = 22.2 μM)

  11. Anchor Toolkit - a secure mobile agent system

    OpenAIRE

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

    2008-01-01

    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...

  12. Providing Reliable Agents for Electronic Commerce

    OpenAIRE

    Straßer, Markus; Rothermel, Kurt; Maihöfer, Christian

    1998-01-01

    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...

  13. Halide test agent replacement study

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-02-01

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

  14. Biologic agents in juvenile spondyloarthropathies.

    Science.gov (United States)

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    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

  15. Migration Dynamics in Artificial Agent Societies

    Directory of Open Access Journals (Sweden)

    Harjot Kaur

    2014-02-01

    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.

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

    Science.gov (United States)

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

    2002-06-01

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

  17. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’

    Directory of Open Access Journals (Sweden)

    Haque Rosenani A

    2012-07-01

    Full Text Available Abstract Background Benzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are now interested to explore their potential as anti-cancer agents. In the present study, an effort was made to further explore this area of research. Furthermore, in order to increase the solubility and efficacy of these heterocycles, the interest is now shifted to the salts of these compounds. With this background, we planned to synthesize a series of meta-xylyl linked bis-benzimidazolium salts to assess their anti-proliferation efficacy on human colon cancer cell line (HCT 116. Results A number of N-alkylbenzimidazoles were synthesized by reactions of benzimidazole with alkyl halides (i-PrBr, PrBr, EthBr, Pent-2-ylBr, BuBr, BenzCl, HeptBr. The subsequent treatment of the resulting N-alkylbenzimidazoles with 1,3-(bromomethylenebenzene afforded corresponding bis-benzimidazolium salts. All synthesized compounds were characterized by spectroscopic techniques (Additional file 1: NMR & FT-IR and microanalysis. Molecular structures of selected compounds were established through single crystal x-ray diffraction studies. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116. Results showed that the compounds exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 0.1 to 17.6 μM. The anti-proliferation activity of all compounds was more pronounced than that of standard reference drug 5-flourouracil (IC50 =19.2 μM. Conclusions All the synthesized bis-benzimidazolium salts

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

    Science.gov (United States)

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  19. CATS-based Agents That Err

    Science.gov (United States)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  20. Biological effects of mutagenic agents

    International Nuclear Information System (INIS)

    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

  1. Extension agents and conflict narratives

    DEFF Research Database (Denmark)

    Bond, Jennifer Lauren

    2016-01-01

    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...

  2. Agent Based Individual Traffic Guidance

    DEFF Research Database (Denmark)

    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...

  3. [Infectious agents and autoimmune diseases].

    Science.gov (United States)

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

    1992-01-01

    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

  4. Oral agents in multiple sclerosis.

    Science.gov (United States)

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

    2015-01-01

    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

  5. Logical Theories for Agent Introspection

    DEFF Research Database (Denmark)

    Bolander, Thomas

    2004-01-01

    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...

  6. Injectable agents affecting subcutaneous fats.

    Science.gov (United States)

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

    2015-09-01

    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

  7. Topical agents in burn care

    OpenAIRE

    Momčilović Dragan

    2002-01-01

    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...

  8. Building Hybrid Soft Computing Agents

    Czech Academy of Sciences Publication Activity Database

    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

  9. MSA AGENT FOR MULTIMEDIA APPLICATIONS

    OpenAIRE

    Aruna Rani; A. K. Gautam

    2011-01-01

    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...

  10. Provably Bounded-Optimal Agents

    OpenAIRE

    Russell, S J; Subramanian, D.

    1995-01-01

    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...

  11. Autonomous Behavior of Computational Agents

    Czech Academy of Sciences Publication Activity Database

    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

  12. Agent Simulation of Chain Bankruptcy

    OpenAIRE

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

    2007-01-01

    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...

  13. Crimen organizado y agente encubierto

    OpenAIRE

    Herrero Reus, Ignacio

    2014-01-01

    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.

  14. Dimensions and Issues of Mobile Agent Technology

    Directory of Open Access Journals (Sweden)

    Yashpal Singh

    2012-09-01

    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.

  15. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    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.

  16. Agent planning in AgScala

    Science.gov (United States)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  17. A++: An Agent Oriented Programming Language

    Directory of Open Access Journals (Sweden)

    Deyi Xue

    2004-08-01

    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.

  18. Pharmacologic Agents for Chronic Diarrhea.

    Science.gov (United States)

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  19. Multi-agent autonomous system

    Science.gov (United States)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  20. An Agent Based Classification Model

    CERN Document Server

    Gu, Feng; Greensmith, Julie

    2009-01-01

    The major function of this model is to access the UCI Wisconsin Breast Can- cer data-set[1] and classify the data items into two categories, which are normal and anomalous. This kind of classifi cation can be referred as anomaly detection, which discriminates anomalous behaviour from normal behaviour in computer systems. One popular solution for anomaly detection is Artifi cial Immune Sys- tems (AIS). AIS are adaptive systems inspired by theoretical immunology and observed immune functions, principles and models which are applied to prob- lem solving. The Dendritic Cell Algorithm (DCA)[2] is an AIS algorithm that is developed specifi cally for anomaly detection. It has been successfully applied to intrusion detection in computer security. It is believed that agent-based mod- elling is an ideal approach for implementing AIS, as intelligent agents could be the perfect representations of immune entities in AIS. This model evaluates the feasibility of re-implementing the DCA in an agent-based simulation environ- ...

  1. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’

    OpenAIRE

    Haque Rosenani A; Iqbal Muhammad; Khadeer Ahamed Mohamed B; Majid AMS; Abdul Hameed Zena A

    2012-01-01

    Abstract Background Benzimidazole derivatives are structurally bioisosteres of naturally occurring nucleotides, which makes them compatible with biopolymers of living systems. This property gives benzimidazole a biological and clinical importance. In the last decade, this class of compounds has been reported to possess anti-allergic, anti-diabatic, anti-HIV, anti-hypertensive, anti-inflammatory, anti-mycobacterial, anti-oxidant, anti-protozoal, and anti-viral properties. The researchers are n...

  2. 14th International Conference on Practical Applications of Agents and Multi-Agent Systems : Special Sessions

    CERN Document Server

    Escalona, María; Corchuelo, Rafael; Mathieu, Philippe; Vale, Zita; Campbell, Andrew; Rossi, Silvia; Adam, Emmanuel; Jiménez-López, María; Navarro, Elena; Moreno, María

    2016-01-01

    PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest developments and the most important outcomes related to real-world applications. It provides a unique opportunity to bring multi-disciplinary experts, academics and practitioners together to exchange their experience in the development of Agents and Multi-Agent Systems. This volume presents the papers that have been accepted for the 2016 in the special sessions: Agents Behaviours and Artificial Markets (ABAM); Advances on Demand Response and Renewable Energy Sources in Agent Based Smart Grids (ADRESS); Agents and Mobile Devices (AM); Agent Methodologies for Intelligent Robotics Applications (AMIRA); Learning, Agents and Formal Languages (LAFLang); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and ...

  3. Borrelioses, agentes e vetores Borrelioses, agents and vectors: a review

    Directory of Open Access Journals (Sweden)

    Cleber O. Soares

    2000-03-01

    Full Text Available As borrelioses são enfermidades infecciosas determinadas por espiroquetas do gênero Borrelia, agentes transmissíveis, principalmente, por carrapatos aos animais e/ou ao homem. Nesta revisão são apresentadas e discutidas as enfermidades determinadas por borrélias, bem como as características gerais das espiroquetas, os aspectos relacionados a transmissão por artrópodes, as enfermidades nos animais domésticos e silvestres, quanto aos aspectos biológicos e patológicos, a doença de Lyme como principal zoonose do grupo, a associação de borrélia com outros agentes hematozoários e os métodos diagnósticos e a epidemiologia comparativa entre dados obtidos no Brasil com os de outros países. Estas borrelioses possuem características patológicas, clínicas e epidemiológicas variadas de acordo à região fisiográfica, devido à existência de distintas espécies, genoespécies e cepas; estes aspectos variam ainda em função dos artrópodes vetores, da interação vetor-patógeno e dos ecossistemas distintos.Borrelioses are infectous diseases caused by spirochaetes of the genus Borrelia. They are born mainly through ticks at animals and/or human beings. In this review are shown and discussed five groups of diseases determined by borrelia, general characteristics of the spirochaetes, aspects related to transmission by arthropods, biological and pathological aspects of the diseases in domestic and wild animals, Lyme disease as an important zoonosis, the association of borrelia with other hematozoa agents, the diagnostic methods and the comparative epidemiology with data obtained from Brazil and other countries. The borrelioses have pathological, clinical and epidemiological characteristics which vary according to physiographic regions due to the existence of different species, genospecies and strains of borrelia, of arthropod vectors, vector-agent relationship and of different ecocystems.

  4. Learning other agents` preferences in multiagent negotiation

    Energy Technology Data Exchange (ETDEWEB)

    Bui, H.H.; Kieronska, D.; Venkatesh, S. [Curtin Univ. of Technology, Perth, WA (Australia)

    1996-12-31

    In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complement knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).

  5. Agent Communication Channel Based on BACnet

    Institute of Scientific and Technical Information of China (English)

    Jiang Wen-bin; Zhou Man-li

    2004-01-01

    We analyze the common shortcoming in the existing agent MTPs (message transport protocols). With employing the File object and related service AtomicWriteFile of BACnet (a data communication protocol building automation and control networks), a new method of agent message transport is proposed and implemented. Every agent platform (AP) has one specified File object and agents in another AP can communicate with agents in the AP by using AtomicWriteFile service. Agent messages can be in a variety of formats. In implementation, BACnet/IP and Ethernet are applied as the BACnet data link layers respectively. The experiment results show that the BACnet can provide perfect support for agent communication like other conventional protocols such as hypertext transfer protocol(HTTP), remote method invocation (RMI) etc. and has broken through the restriction of TCP/IP. By this approach, the agent technology is introduced into the building automation control network system.

  6. Analysis and Optimization for Mobile Agent Communication

    Institute of Scientific and Technical Information of China (English)

    YANGBo; LIUDayou

    2005-01-01

    Communication performance is one of the most important factors affecting the efficiency of mobile agent system. Only traditional optimization techniques for communication performance are not enough, especially in large-scale intelligent mobile agent system, so more intelligent optimization techniques are needed. In the background, the paper studies communication of mobile agent system from the viewpoint of performance. The paper makes qualitative and quantitative analysis of four important factors that will affect the communication performance of mobile agent system and presents the communication performance optimization model. The model hasthree primary functions. First, the model provides a formalism method to describe the communication task and process of mobile agent. Second, the model provides a means to make quantitative analysis of the performance of mobile agent system. Third, the model can plan out an optimal communication scheme for mobile agent to minimize the cost of whole communication. The model could thus be a building block for the optimization of the communication behavior of mobile agent.

  7. Comparison of Communication Models for Mobile Agents

    Directory of Open Access Journals (Sweden)

    Xining Li

    2003-04-01

    Full Text Available An agent is a self-contained process being acting on behalf of a user. A Mobile Agent is an agent roaming the internet to access data and services, and carry out its assigned task remotely. This paper will focus on the communication models for Mobile Agents. Generally speaking, communication models concern with problems of how to name Mobile Agents, how to establish communication relationships, how to trace moving agents, and how to guarantee reliable communication. Some existing MA systems are purely based on RPC-style communication, whereas some adopts asynchronous message passing, or event registration/handling. Different communication concepts suitable for Mobile Agents are well discussed in [1]. However, we will investigate these concepts and existing models from a different point view: how to track down agents and deliver messages in a dynamic, changing world.

  8. A Framework for Multi-Agent Planning

    OpenAIRE

    Bos, A; Tonino, J.F.M.; De Weerdt, M.M.; Witteveen, C.

    2000-01-01

    We introduce a computational framework, consisting of resources, skills, goals and services to represent the plans of individual agents and to develop models and algorithms for cooperation processes between a collection of agents.

  9. Porphyria Cutanea Tarda and Agent Orange

    Science.gov (United States)

    ... ZIP code here Porphyria Cutanea Tarda and Agent Orange VA presumes porphyria cutanea tarda (PCT) is related to Veterans' exposure to Agent Orange or other herbicides during military service when the ...

  10. Soft Tissue Sarcomas and Agent Orange

    Science.gov (United States)

    ... ZIP code here Soft Tissue Sarcomas and Agent Orange VA presumes some soft tissue sarcomas in Veterans are related to their exposure to Agent Orange or other herbicides during military service. The soft ...

  11. Structure-Activity Relationships of Synthetic Coumarins as HIV-1 Inhibitors

    OpenAIRE

    I. Kostova; S. Raleva; Genova, P.; R. Argirova

    2006-01-01

    HIV/AIDS pandemics is a serious threat to health and development of mankind, and searching for effective anti-HIV agents remains actual. Considerable progress has been made in recent years in the field of drug development against HIV. A lot of structurally different coumarins were found to display potent anti-HIV activity. The current review demonstrates the variety of synthetic coumarins having unique mechanism of action referring to the different stages of HIV replication. Recent studies ba...

  12. Mobile agents for distributed decision support systems

    OpenAIRE

    Blaz Rodič

    2011-01-01

    This article focuses on the performance of Java based mobile agents using format translation via an intermediary XML based format. Our goal was to develop and verify the performance of a lightweight, mobile agent based solution that would allow strong security, portability and access to heterogeneous data resources from a mobile platform to facilitate exchange of data between simulation models and data resources. We have developed two types of agents: a mobile agent that functions as a server...

  13. Security Issues in Mobile Agent Paradigm

    OpenAIRE

    Nitin Jain; Neeraj Singla

    2011-01-01

    A mobile Agent is a Software program that migrates from node tonode of a heterogeneous network. They are goal-oriented i.e. workautonomously towards a goal, capable of suspending their executionon one platform and moving to other where they can resumeexecution using resources of these nodes and they meet and interactwith other agents. Agents may be stationary, always resident at asingle platform or mobile, capable of moving among differentplatforms at different time. The mobile agent paradigm...

  14. Explaining Simulations Through Self Explaining Agents

    OpenAIRE

    Maaike Harbers; John-Jules Meyer; Karel Van den Bosch

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is more variable and harder to predict than reactive behavior, and therefore it might be harder to explain. However, the approach presented in this paper tries to make advantage of the agents' pro-active...

  15. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    HuayuQiu; ChuanfuLiu; XiaokeMa; YingjuanFu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-15 30%, were better than that of the imported product.

  16. ENZYMATIC DEINKING AGENTS FOR MIXED OFFICE WASTEPAPER

    Institute of Scientific and Technical Information of China (English)

    Huayu Qiu; Chuanfu Liu; Xiaoke Ma; Yingjuan Fu

    2004-01-01

    This article focused on deinking agents for enzymatic deinking of MOW (mixed office wastepaper). The deinking performances of many series of surfactants were discussed at the experimental conditions, and finally, some surfactants, which had good deinking effect, were selected. Then two-composed deinking agents were discussed. The deinkability of the deinking agents, e.g. deinking agents containing T-123 50% and P-10 50%, T-123 70% and O-1530%, were better than that of the imported product.

  17. Virtual Knowledge Communities for Semantic Agents

    OpenAIRE

    Subercaze, Julien; Maret, Pierre

    2011-01-01

    International audience Virtual Knowledge Communities are a well suited paradigm for decentralized knowldege exchanges and they have been applied in several domains. In this paper we investigate the implementation of virtual knowledge communities with se- mantic agents. Using the SAM (Semantic Agent Modeling) approach, we show that agents can exchange community re- lated concepts (in OWL) and behavior (in SWRL). Agents can then learn and adapt new community-related behavior, which is useful...

  18. On Programming Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt

    Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives that the......-aware, thus removing the middleware and letting the agents directly reason about the organization. In this paper, we discuss the results so far, and describe the future goals and research direction for the project....

  19. Sports Agent Industry Emerges in China

    Institute of Scientific and Technical Information of China (English)

    HeiZiand; YiYou

    2003-01-01

    The agent profession is not new to Chinese. First appearing in the Western Zhou Dynasty, agents were called "Zhi Ren" then and "Ya Ren" from the Tang Dynasty onwards. In the Ming Dynasty, a certain amount of property and a license were required if one wanted to become an agent. In the late Qing Dynasty, Mai Ban (Chinese executives working in foreign firms), also a sort of agents, began to emerge in major cities of China.

  20. Integration of Agent System with Legacy Software

    Institute of Scientific and Technical Information of China (English)

    SHEN Qi; ZHAO Yan-hong; YIN Zhao-lin

    2003-01-01

    Agent technique is a new method that can analyze, design and realize a distributed open system. It has been used in almost every field. But if act for the real practical words in technique, it must integrate with legacy software, such as database system etc, and control them. This paper introduces the specification of agent software integration, ontology, instances database as implementing agent software integration with CORBA technique and takes XML, ACL as language communicating among agents.

  1. Topology and Social Behaviour of Agents

    OpenAIRE

    O. Hudak

    2003-01-01

    In a social group its members are caled here agents. Any two agents from the group may interact. The interaction consists of the exchange of information and it costs some energy. There exist subgroups of interacting agents which are nonreducibile. The structure, configuration of interactions between agents in the group, forms a macroscopic structure. The statistical equilibrium due to microreversibility is characterised by the maximum of entropy and by the minimum of energy, costs of informat...

  2. Self-Adapting Reactive Autonomous Agents

    Science.gov (United States)

    Andrecut, M.; Ali, M. K.

    This paper describes a new self-adapting control algorithm for reactive autonomous agents. The architecture of the autonomous agents integrates the reactive behavior with reinforcement learning. We show how these components perform on-line adaptation of the autonomous agents to various complex navigation situations by constructing an internal model of the environment. Also, a discussion on cooperation and coordination of teams of agents is presented.

  3. Properties of Ettringite Type Expansive Agent

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    By employing different forms and amounts of materials,many kinds of ettringite type expansive agents had been prepared.The relationship between the compositions and properties of expansive agents was analyzed.The design methods of expansive agent have been put forward according to the property requirement of expansive concrete.

  4. Agent for roentgenocontrast examination of cavities

    International Nuclear Information System (INIS)

    The water-soluble agent, additionaly containing starch, agar, water, is suggested to increase accuracy of injured cavity diagnostics. The method for roentgenocontrast agent preparation on the base of starch-agar gel is described. Advantages of the agent suggested in comparison with those of roentgenologic cavity investigation used are shown

  5. Cooperative heuristic multi-agent planning

    NARCIS (Netherlands)

    De Weerdt, M.M.; Tonino, J.F.M.; Witteveen, C.

    2001-01-01

    In this paper we will use the framework to study cooperative heuristic multi-agent planning. During the construction of their plans, the agents use a heuristic function inspired by the FF planner (l3l). At any time in the process of planning the agents may exchange available resources, or they may r

  6. Stability of Evolving Multi-Agent Systems

    CERN Document Server

    De Wilde, Philippe; 10.1109/TSMCB.2011.2110642

    2011-01-01

    A Multi-Agent System is a distributed system where the agents or nodes perform complex functions that cannot be written down in analytic form. Multi-Agent Systems are highly connected, and the information they contain is mostly stored in the connections. When agents update their state, they take into account the state of the other agents, and they have access to those states via the connections. There is also external, user-generated input into the Multi-Agent System. As so much information is stored in the connections, agents are often memory-less. This memory-less property, together with the randomness of the external input, has allowed us to model Multi-Agent Systems using Markov chains. In this paper, we look at Multi-Agent Systems that evolve, i.e. the number of agents varies according to the fitness of the individual agents. We extend our Markov chain model, and define stability. This is the start of a methodology to control Multi-Agent Systems. We then build upon this to construct an entropy-based defi...

  7. The Ontogenesis of Agent: Linguistic Expression.

    Science.gov (United States)

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  8. Embedded Automation in Human-Agent Environment

    CERN Document Server

    Tweedale, Jeffrey W

    2012-01-01

    This research book proposes a general conceptual framework for the development of automation in human-agents environments that will allow human- agent teams to work effectively and efficiently. We examine various schemes to implement artificial intelligence techniques in agents.  The text is directed to the scientists, application engineers, professors and students of all disciplines, interested in the agency methodology and applications.

  9. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    Science.gov (United States)

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  10. A theoretical framework for explaining agent behavior

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2011-01-01

    To understand emergent processes in multi-agent-based simulations it is important to study the global processes in a simulation as well as the processes on the agent level. The behavior of individual agents is easier to understand when they are able to explain their own behavior. In this paper, a th

  11. Stigmergy in multi-agent reinforcement learning

    OpenAIRE

    Aras, Raghav; Dutech, Alain; Charpillet, François

    2004-01-01

    http://www.computer.org In this paper, we describe how certain aspects of the biological phenomena of stigmergy can be imported into multi-agent reinforcement learning (MARL), with the purpose of better enabling coordination of agent actions and speeding up learning. In particular, we detail how these stigmergic aspects can be used to define an inter-agent communication framework.

  12. Explaining simulations through self explaining agents

    NARCIS (Netherlands)

    Harbers, M.; Bosch, K. van den; Meyer, J.J.C.

    2010-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  13. Explaining Simulations through Self Explaining Agents

    NARCIS (Netherlands)

    Harbers, M.; Dignum, F.; Bosch, K. van den; Meyer, J.J.C.

    2008-01-01

    Several strategies are used to explain emergent interaction patterns in agent-based simulations. A distinction can be made between simulations in which the agents just behave in a reactive way, and simulations involving agents with also pro-active (goal-directed) behavior. Pro-active behavior is mor

  14. Mobile Agents in Networking and Distributed Computing

    CERN Document Server

    Cao, Jiannong

    2012-01-01

    The book focuses on mobile agents, which are computer programs that can autonomously migrate between network sites. This text introduces the concepts and principles of mobile agents, provides an overview of mobile agent technology, and focuses on applications in networking and distributed computing.

  15. On Programming Organization-Aware Agents

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt

    2013-01-01

    Since it is difficult (or even impossible) to assume anything about the agents’ behavior and goals in an open multi-agent system, it is often suggested that an organization is imposed upon the agents, whichhich, by abstracting away from the agents, specifies boundaries and objectives that the age...

  16. Radioactive scanning agents with hydroquinone stabilizer

    International Nuclear Information System (INIS)

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise hydroquinone 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 which carries the radionuclide to bone, thus providing a skeletal imaging agent

  17. Honey - A Novel Antidiabetic Agent

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa, Siti A. Sulaiman, Mohd S. Ab Wahab

    2012-01-01

    Full Text Available Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT, on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise of these experimental data in diabetic human subjects.

  18. Anticancer agents from marine sponges.

    Science.gov (United States)

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  19. Social Robots as Persuasive Agents

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2014-01-01

    Robots are more and more used in a social context, and in this paper we try to formulate a research agenda concerning ethical issues around social HRI in order to be prepared for future scenarios where robots may be a naturally integrated part of human society. We outline different paradigms to d...... describe the role of social robots in communication processes with humans, and connect HRI with the topic of persuasive technology in health care, to critically reflect the potential benefits of using social robots as persuasive agents....

  20. A Multi-targeted Drug Candidate with Dual Anti-HIV and Anti-HSV Activity

    Czech Academy of Sciences Publication Activity Database

    Balzarini, J.; Andrei, G.; Balestra, E.; Huskens, D.; Vanpouille, C.; Introini, A.; Zicari, S.; Liekens, S.; Snoeck, R.; Holý, Antonín; Perno, C. F.; Margolis, L.; Schols, D.

    2013-01-01

    Roč. 9, č. 7 (2013), e1003456. E-ISSN 1553-7374 Institutional support: RVO:61388963 Keywords : herpes simplex virus * phosphonylmethoxyalkyl derivatives * nucleoside phosphonates * antiviral activity Subject RIV: EE - Microbiology, Virology Impact factor: 8.057, year: 2013 http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003456